The many faces and mimics of papillary thyroid carcinoma.

PubMed

Albores-Saavedra, Jorge; Wu, Jianhua

2006-01-01

This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto's thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.

Diffuse lipomatosis of the thyroid gland with papillary microcarcinoma: Report of a rare entity.

PubMed

Nandyala, Hariharanadha Sarma; Madapuram, Srinivasulu; Yadav, Megha; Katamala, Sudheer Kumar

2015-01-01

Presence of lobules of adipose tissue either focally or diffusely is very rare in the thyroid gland. Fat accumulation can be macroscopic or microscopic. Focal infiltrates of fat have been reported in conditions such as adenolipoma, intrathyroid lipoma, and encapsulated papillary carcinoma. Diffuse lipomatosis has been reported in conditions such as amyloid goitre, heterotopic fat nests, thyrolipoma and liposarcoma. The exact mechanism of fat accumulation is not known although there are many theories postulated. Investigations such as ultrasound, computed tomography scan, and magnetic resonance imaging can detect the presence of macroscopic fat in the thyroid gland. Accurate diagnosis of the type of fat accumulation is necessary because tumorous and nontumorous conditions fall into the differential diagnosis. Only nine cases of papillary carcinoma associated with lipomatosis of thyroid are reported so far. We report possibly the first case of diffuse lipomatosis of the thyroid gland with a focus of papillary microcarcinoma.

Loss of c-KIT expression in thyroid cancer cells.

PubMed

Franceschi, Sara; Lessi, Francesca; Panebianco, Federica; Tantillo, Elena; La Ferla, Marco; Menicagli, Michele; Aretini, Paolo; Apollo, Alessandro; Naccarato, Antonio Giuseppe; Marchetti, Ivo; Mazzanti, Chiara Maria

2017-01-01

Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression.

Loss of c-KIT expression in thyroid cancer cells

PubMed Central

Panebianco, Federica; Tantillo, Elena; La Ferla, Marco; Menicagli, Michele; Aretini, Paolo; Apollo, Alessandro; Naccarato, Antonio Giuseppe; Marchetti, Ivo; Mazzanti, Chiara Maria

2017-01-01

Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression. PMID:28301608

Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients.

PubMed

Gambardella, Claudio; Tartaglia, Ernesto; Nunziata, Anna; Izzo, Graziella; Siciliano, Giuseppe; Cavallo, Fabio; Mauriello, Claudio; Napolitano, Salvatore; Thomas, Guglielmo; Testa, Domenico; Rossetti, Gianluca; Sanguinetti, Alessandro; Avenia, Nicola; Conzo, Giovanni

2016-09-19

Lymph nodal involvement is very common in differentiated thyroid cancer, and in addition, cervical lymph node micrometastases are observed in up to 80 % of papillary thyroid cancers. During the last decades, the role of routine central lymph node dissection (RCLD) in the treatment of papillary thyroid cancer (PTC) has been an object of research, and it is now still controversial. Nevertheless, many scientific societies and referral authors have definitely stated that even if in expert hands, RCLD is not associated to higher morbidity; it should be indicated only in selected cases. In order to better analyze the current role of prophylactic neck dissection in the surgical treatment of papillary thyroid cancers, an analysis of the most recent literature data was performed. Prophylactic or therapeutic lymph node dissection, selective, lateral or central lymph node dissection, modified radical neck dissection, and papillary thyroid cancer were used by the authors as keywords performing a PubMed database research. Literature reviews, PTCs large clinical series and the most recent guidelines of different referral endocrine societies, inhering neck dissection for papillary thyroid cancers, were also specifically evaluated. A higher PTC incidence was nowadays reported in differentiated thyroid cancer (DTC) clinical series. In addition, ultrasound guided fine-needle aspiration citology allowed a more precocious diagnosis in the early phases of disease. The role of prophylactic neck dissection in papillary thyroid cancer management remains controversial especially regarding indications, approach, and surgical extension. Even if morbidity rates seem to be similar to those reported after total thyroidectomy alone, RCLD impact on local recurrence and long-term survival is still a matter of research. Nevertheless, only a selective use in high-risk cases is supported by more and more scientific data. In the last years, higher papillary thyroid cancer incidence and more precocious diagnoses were worldwide reported. Among endocrine and neck surgeons, there is agreement about indications to prophylactic treatment of node-negative "high-risk" patients. A recent trend toward RCLD avoiding radioactive treatment is still debated, but nevertheless, prophylactic dissections in low-risk cases should be avoided. Prospective randomized trials are needed to evaluate the benefits of different approaches and allow to drawn definitive conclusions.

Cytological features of warthin-like papillary thyroid carcinoma: A case report with review of previous cytology cases.

PubMed

Vallonthaiel, Archana George; Agarwal, Shipra; Jain, Deepali; Yadav, Rajni; Damle, Nishikant A

2017-09-01

Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC. © 2017 Wiley Periodicals, Inc.

Differentiated thyroid cancer in children and adolescents.

PubMed

Farahati, J; Parlowsky, T; Mäder, U; Reiners, C; Bucsky, P

1998-08-01

There have been only a few studies on differentiated childhood thyroid cancer (DTC) in children and adolescents. We analyzed the characteristics of DTC with respect to age, gender and histology in 114 patients under 18 years of age. In a questionnaire-based survey, data of 114 patients, aged between 3 years and 18 years, was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated, and the prognostic effect of age, gender, histology, multicentric growth, tumor stage and N-status on distant metastases was tested using multivariate discriminant analysis. Between-group comparison was performed using student t-test and chi-squared test. The incidence of DTC in females was higher than in males with a peak of female:male ratio at puberty, which was more pronounced in children with papillary thyroid cancer, but not with follicular thyroid cancer. Papillary thyroid cancer was associated with more advanced disease (P=0.009), more lymph-node involvement (P=0.007) and more distant metastases (P=0.02) compared with follicular thyroid cancer. Multivariate analysis showed advanced tumor stage as the only significant factor (P=0.02) associating with distant metastasis. It can be concluded that in children and adolescents: 1. The incidence of papillary thyroid cancer is higher in females than males, with a peak at puberty. 2. The only significant factor associated with distant metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently associated with lymph-node involvement, distant metastases and advanced tumor stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular type.

A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

PubMed

Kiatpanabhikul, Phatharaporn; Shuangshoti, Shanop; Chantra, Kraisri; Navicharern, Patpong; Kingpetch, Kanaungnit; Houngngam, Natnicha; Snabboon, Thiti

2017-07-01

Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

[[Is it necessary to perform a central lymphodissection in highly differentiated iviicrocarcinoiva of thyroid gland?].

PubMed

Zavgorodniy, S N; Danilyuk, M B; Rylov, A I; Dolya, O S

2016-08-01

The rate of the highly differentiated thyroid microcarcinoma methastasizing in central (6th) group of cervical lymph nodes was studied. In the clinic in 2013 - 2015 yrs 62 patients were operated for primary thyroid microcarcinoma. In accordance to TNM (UICC, AJCC, 2009) classification, papillary cancer in stage TlaNOMO was diagnosed in 35 (56.5%) patients, T1aN1MO - in 22 (35.5%); follicular cancer stage T1aNOMO - in 2 (3.2%); papillary cancer, follicular variant in stage T1aN1 MO - in 2 (3.2%); follicu- lar cancer, papillary variant in stage T1aNOMO - in 1 (1.6%). In 8 (12.9%) patients intraorgan multifocal metastasizing into contralateral thyroid lobe was revealed. In accordance to morphological investigation date of the excised samples, in 24 (38.7%) patients the metastases into the 6th group lymph nodes were revealed. In 4 (16.7%) patients, to whom lateral cervical lymphodissection was done, metastases in 2 - 5th groups of lymph nodes on the thyroid affection side were revealed.

Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement.

PubMed

Basolo, Fulvio; Giannini, Riccardo; Toniolo, Antonio; Casalone, Rosario; Nikiforova, Marina; Pacini, Furio; Elisei, Rossella; Miccoli, Paolo; Berti, Piero; Faviana, Pinuccia; Fiore, Lisa; Monaco, Carmen; Pierantoni, Giovanna Maria; Fedele, Monica; Nikiforov, Yuri E; Santoro, Massimo; Fusco, Alfredo

2002-02-10

A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8. Copyright 2001 Wiley-Liss, Inc.

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

ClinicalTrials.gov

2016-12-02

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

Role of Dicer1 in thyroid cell proliferation and differentiation.

PubMed

Penha, Ricardo Cortez Cardoso; Sepe, Romina; De Martino, Marco; Esposito, Francesco; Pellecchia, Simona; Raia, Maddalena; Del Vecchio, Luigi; Decaussin-Petrucci, Myriam; De Vita, Gabriella; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

2017-01-01

DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

ClinicalTrials.gov

2018-05-23

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma AJCC v7; Stage I Thyroid Gland Papillary Carcinoma AJCC v7; Stage II Thyroid Gland Follicular Carcinoma AJCC v7; Stage II Thyroid Gland Papillary Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

ClinicalTrials.gov

2014-08-20

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Can Cytology Face the Challenge of Diagnosis in the Light of the New Classification?

PubMed

Díaz Del Arco, Cristina; Fernández Aceñero, M Jesús

2018-06-01

To assess the cytological findings of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), conventional papillary thyroid carcinomas (C-PTC), and invasive follicular variants of papillary thyroid carcinomas (IFV-PTC) to determine if there are cytological differences between groups. We have reviewed all thyroid fine-needle aspiration cytology samples diagnosed between 2000 and 2017. We have included all NIFTP cases (n = 6) and randomly selected cases of C-PTC (n = 14) and IFV-PTC (n = 8). Comparing NIFTP and C-PTC cases, NIFTP cases showed significantly less papillary or pseudopapillary architecture, more bidimensional groups and microfollicles, and less tridimensionality, giant cells, and nuclear folds. We observed a trend towards significance for smear cellularity and amount of cytoplasm. Presence of nuclear folds was the only significant difference between NIFTP and IFV-PTC cases. The differences between groups in percent papillary or pseudopapillary architecture, cellularity, and tridimensionality showed a trend towards significance. Amount of colloid, dirty background, pleomorphism or atypia, nuclear pseudoinclusions, type of chromatin, and nucleolus were not significant. No cytopathological feature can differentiate between invasive and encapsulated IFV-PTC. In accordance with the recently accepted category, PTC smears with cells arranged in a predominantly follicular architecture should be reported as Bethesda IV category with descriptive terms to avoid false-positive cases. © 2018 S. Karger AG, Basel.

Thyroid cancer: what to do after fine needle aspiration.

PubMed

Rometo, David A; Baranski, Thomas J

2011-01-01

The incidence of differentiated thyroid cancer (including papillary, follicular, and Hurthle cell carcinoma) has nearly tripled in the past 20 years. Diagnosis, treatment, and long-term management are evolving with advances in radiology, surgical techniques, nuclear medicine, genetics, and targeted therapeutics. Here we detail the current recommended course of action for differentiated thyroid cancer and options on the horizon.

Histogram analysis of greyscale sonograms to differentiate between the subtypes of follicular variant of papillary thyroid cancer.

PubMed

Kwon, M-R; Shin, J H; Hahn, S Y; Oh, Y L; Kwak, J Y; Lee, E; Lim, Y

2018-06-01

To evaluate the diagnostic value of histogram analysis using ultrasound (US) to differentiate between the subtypes of follicular variant of papillary thyroid carcinoma (FVPTC). The present study included 151 patients with surgically confirmed FVPTC diagnosed between January 2014 and May 2016. Their preoperative US features were reviewed retrospectively. Histogram parameters (mean, maximum, minimum, range, root mean square, skewness, kurtosis, energy, entropy, and correlation) were obtained for each nodule. The 152 nodules in 151 patients comprised 48 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs; 31.6%), 60 invasive encapsulated FVPTCs (EFVPTCs; 39.5%), and 44 infiltrative FVPTCs (28.9%). The US features differed significantly between the subtypes of FVPTC. Discrimination was achieved between NIFTPs and infiltrative FVPTC, and between invasive EFVPTC and infiltrative FVPTC using histogram parameters; however, the parameters were not significantly different between NIFTP and invasive EFVPTC. It is feasible to use greyscale histogram analysis to differentiate between NIFTP and infiltrative FVPTC, but not between NIFTP and invasive EFVPTC. Histograms can be used as a supplementary tool to differentiate the subtypes of FVPTC. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Discrepant serum and urine β-hCG results due to production of β-hCG by a cribriform-morular variant of thyroid papillary carcinoma.

PubMed

Alikhan, Mir; Koshy, Anoopa; Hyjek, Elizabeth; Stenson, Kerstin; Cohen, Ronald N; Yeo, Kiang-Teck J

2015-01-01

Although patients with medullary thyroid cancer are known to present with paraneoplastic hormone production, this is much less common with papillary thyroid cancer. We present a patient with the cribriform morular variant of papillary thyroid cancer in association with familial adenomatous polyposis who developed a positive pregnancy test in the absence of known pregnancy. The patient had developed vaginal bleeding, and her laboratory testing was characterized by elevated serum human chorionic gonadotropin (β-hCG) concentrations, but negative qualitative urine results. After a thorough gynecological evaluation to exclude unexpected normal, ectopic, or molar pregnancy, we pursued an evaluation for other sources of β-hCG production. We showed that the elevated serum β-hCG concentrations were not the result of heterophile antibody interferences, and ultimately we proved that her recurrent tumor produced the ectopic β-hCG. This is the first report of β-hCG production by papillary thyroid cancer. Thus, the possibility of ectopic production of β-hCG by papillary thyroid cancer needs to be included in the differential diagnosis of elevated hCG concentration in the absence of pregnancy. This study of an unusual paraneoplastic syndrome highlights the importance of investigating discrepancies in the clinical laboratory. Copyright © 2014 Elsevier B.V. All rights reserved.

NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

PubMed Central

Schneider, David F.; Chen, Herbert

2013-01-01

Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834

[The significance of lymph node status in papillary and follicular thyroid gland carcinoma for the nuclear medicine physician].

PubMed

Farahati, J; Mörtl, M; Reiners, C

2000-01-01

The impact of lymph node metastases on prognosis of differentiated thyroid cancer is discussed controversially. Therefore the data of 596 patients with papillary or follicular thyroid cancer are analysed retrospectively, which have been treated between 1980 and 1995 at the Clinic and Policlinic for Nuclear Medicine of the University of Würzburg. The influence of lymph node metastases on prognosis with respect to survival is analysed with the univariate Kaplan-Meier-method and with the multivariate discriminant analysis. In addition, the influence of the prognostic factor "lymph node involvement" on distant metastases is analysed by a stratified comparison and an univariate test. In papillary thyroid cancer, the 15 year-survival-rate for stage pN1 is significantly lower (p < 0.001) with 88.7% as compared to stage pN0 (99.4%). In patients with follicular thyroid cancer this difference is even more pronounced (64.7% versus 97.2%, p < 0.001). However, the multivariate discriminant analysis shows that the only prognostic factors are tumour stage and distant metastases, and--in papillary thyroid cancer--patient's age. So lymph node metastases are not an independent prognostic factor concerning survival. However, lymph node metastases have a prognostic unfavourable influence with respect to distant metastases especially in papillary thyroid cancer stage pT4 (distant metastases in patients with negative lymph nodes 0% and in patients with positive lymph nodes 35.3% [p < 0.001]).

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1.

PubMed

Casey, Mary B; Lohse, Christine M; Lloyd, Ricardo V

2003-01-01

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.

Mapping fundamental life elements in papillary thyroid carcinoma tissue

NASA Astrophysics Data System (ADS)

Merolle, L.; Ragazzi, M.; Gianoncelli, A.; Altissimo, M.; Ciarrocchi, A.; Bedolla, D. E.; Marraccini, C.; Baricchi, R.; Pertinhez, T. A.

2018-05-01

Well-differentiated papillary thyroid carcinomas (PTCs) are the most common type of thyroid cancer. Thyroid function depends on the presence of certain trace elements necessary for both the synthesis and the metabolism of thyroid hormones. We conducted an observational translational study on formalin fixed paraffin embedded thyroid tissue slices collected from five patients who underwent surgical resection of thyroid gland after thyroid cancer diagnosis. A synchrotron-based XRF set up was used to map the distribution of oxygen, sodium, aluminum, selenium and magnesium in PTC sections. These experiments were performed at the TwinMic beamline (Elettra—Sincrotrone Trieste, Trieste, Italy). Our results show that Mg levels in PTC tissues are significantly higher than in the control ones. The results seem to provide highly valuable information suggesting that Mg may play a role in the development and metabolic process of PTC.

Typical thyroid-type carcinoma arising in struma ovarii: a report of 4 cases and review of the literature.

PubMed

Roth, Lawrence M; Miller, Alexander W; Talerman, Aleksander

2008-10-01

Struma ovarii has elicited considerable interest because of its many unique features since Ludwig Pick first elucidated its relationship to teratoma in the early part of the 20th century. In this article, we report 3 cases of papillary and 1 of follicular thyroid carcinoma; 2 of these cases were associated with mature cystic teratoma. Metastases occurred in 2 patients, and 1 died of neoplasm. In regard to the occurrence of thyroid-type carcinoma in struma ovarii, precise terminology should be used, and the expression malignant struma ovarii was avoided as a diagnostic term. Upon review of the literature, papillary carcinoma and follicular carcinoma are the most frequent types of malignancy to occur in ovarian struma; other forms of thyroid carcinoma occur only rarely. The diagnostic criteria for cases of papillary carcinoma are similar to those described in the cervical thyroid gland and are based primarily on nuclear and architectural features. In reference to follicular carcinoma, invasion into the surrounding ovarian tissue, vascular invasion, or metastasis is evidence of malignancy. Histological malignancy in a struma does not necessarily equate with biological malignancy, and the majority of thyroid-type carcinomas do not spread beyond the ovary. Occasionally, metastases of ovarian struma have an innocuous histological appearance, and such cases are referred to as highly differentiated follicular carcinoma of ovarian origin (HDFCO). Because its histological appearance resembles that of nonneoplastic thyroid, HDFCO characteristically cannot be diagnosed until the neoplasm spreads beyond the ovary. In this article, we apply the term typical thyroid carcinoma to those forms of thyroid malignancy arising in ovarian struma that closely resemble the types described in the cervical thyroid gland to distinguish them from HDFCO. Typical follicular carcinoma is more aggressive than the somewhat more common papillary carcinoma, and HDFCO is the least aggressive of these tumor types. Cases of thyroid-type carcinoma arising in the ovary sometimes lack evidence of preexisting struma. The more aggressive thyroid-type neoplasms can arise in thyroid tissue within a mature cystic teratoma, or they may overgrow and replace the struma. Primary thyroid-type carcinoma must be distinguished from rare instances of ovarian metastases that originate in the cervical thyroid gland and the less differentiated forms from other ovarian neoplasms such as clear cell adenocarcinoma and tumors with an oxyphilic appearance. In the differential diagnosis with other ovarian neoplasms, cases of thyroid-type carcinoma associated with strumal carcinoid should not be diagnosed as malignant strumal carcinoid because the latter diagnosis might lead to suboptimal therapy.

Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma.

PubMed

Kaushal, Seema; Sharma, Mehar Chand; Mathur, Sandeep R; Rastogi, Shishir; Bal, Chander Shekhar; Chumber, Sunil

2011-01-01

A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131) ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

Impact of Reclassification on Thyroid Nodules with Architectural Atypia: From Non-Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinomas to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

PubMed Central

Jeon, Min Ji; Song, Dong Eun; Jung, Chan Kwon; Kim, Won Gu; Kwon, Hyemi; Lee, Yu-Mi; Sung, Tae-Yon; Yoon, Jong Ho; Chung, Ki-Wook; Hong, Suck Joon; Baek, Jung Hwan; Lee, Jeong Hyun; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background The follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)’ for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia. Methods We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%). Results In total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7–35% in AUS-A nodules and 28–49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5–24% in AUS-A nodules, and 23–39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies. Conclusions After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs. PMID:27936121

Hyperfunctioning papillary thyroid carcinoma: A case report with literature review.

PubMed

Salih, Abdulwahid M; Kakamad, F H; Nihad, Han

2016-01-01

Thyroid malignant tumors are rarely associated with hyperfunctioning thyroid. The incidence of this co-incidence is highly variable. Here we report a rare case of papillary thyroid cancer associated with hyperthyroidism with brief literature review. A 40-year-old male, presented with palpitation, excess sweating and weight loss for one month duration. There was asymmetrical swelling of the neck, more on right side, mobile. Free T3: 11.09pmol/L, free T4: 34.41pmol/L, TFT: less than 0.005mIU/ml, Neck ultrasound showed features of background thyroiditis. Left lobe contained 9×7×5mm nodule with irregular outline and multiple dots of calcification, other nodules are of the same features. Under ultrasound guide, fine needle aspiration cytology showed features of papillary carcinoma. After preparation, total thyrodectomy done and the result of histopathological examination confirmed papillary thyroid carcinoma. The patient was put on 0.2mg thyroxine daily. Literature review has showed an increasing number of papers reporting the association of high level of thyroid function tests and thyroid malignancy. The cause of high level of TH in thyroid malignancy is thought to be due to an active mutation of the gene of TH receptor. Niepomniszcze and colleagues found that a combination of TSH receptor mutations and Ki-RAS was the main etiological factor for hyperfunction of the thyroid malignancy. Although the coexistence of them is rare, thyroid malignancy should be put in the differential diagnosis of hyperthyroid goiter. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area.

PubMed

Huszno, B; Szybiński, Z; Przybylik-Mazurek, E; Stachura, J; Trofimiuk, M; Buziak-Bereza, M; Gołkowski, F; Pantoflinski, J

2003-01-01

The aim of the study was to evaluate the correlation between thyroid cancer histotype and incidence rate (IR) and iodine nutrition level in two endemic goiter areas: the districts of Krakow and Nowy Sacz. The suspension of iodine prophylaxis in Poland in 1980 resulted in increased goiter prevalence in schoolchildren and adults and elevated TSH levels in newborns in the early 1990s. Since 1992 a rise in thyroid cancer IR was observed. Thyroid cancer IR in the Krakow population was 2.22 in 1986; 3.62 in 1995 and 6.02 in 2001; in Nowy Sacz: 1.52; 2.59 and 3.88 respectively. In 1986 papillary/follicular cancer ratio in both areas was about 1.0--the value typical of iodine deficient areas. After restoring the obligatory iodine prophylaxis in 1997, a significant decrease in elevated TSH concentration in newborns and urinary iodine concentration increase in schoolchildren were observed. A relative rise in the incidence of papillary thyroid cancer and decrease in follicular cancer, resulting in rise in papillary/follicular thyroid cancer ratio up to 5.9 in 2001 was also observed. Since 1999 no further thyroid cancer IR increase was noted. In conclusion, a significant increase in differentiated thyroid cancer IR was observed in association with the iodine prophylaxis suspension. Changes in thyroid cancer histotypes in 1986-2001 and a significant decrease in incremental rate of differentiated thyroid cancer probably reflect the influence of effective iodine prophylaxis. The significant difference between IR of thyroid cancer incidence in the districts of Krakow and Nowy Sacz may be related to differences in the exposure to radiation after the Chernobyl accident.

Differentiated thyroid carcinoma with functional autonomy.

PubMed

Yaturu, Subhashini; Fowler, Marjorie R

2002-01-01

To present a case of papillary carcinoma in an autonomously hyperfunctioning thyroid nodule. We chronicle the clinical and laboratory findings in a patient with a painless neck mass, with a particular focus on the pathologic findings after surgical removal of the right thyroid lobe. A 39-year-old woman had an enlarging nodule of the right thyroid lobe. Results of thyroid function tests suggested subclinical hyperthyroidism. Two months later, the patient complained of increasing swelling in the neck (but still had no symptoms suggestive of hyperthyroidism). Thus, resection of the right thyroid lobe was performed. Pathologic analysis disclosed low-grade papillary thyroid carcinoma within the nodule, with a small rim of compressed inactive-appearing thyroid tissue surrounding the nodule. Subsequently, she underwent total thyroidectomy and follow-up care for thyroid carcinoma. Although solitary hyperfunctioning nodules of the thyroid gland are usually considered benign, the current case suggests that the diagnosis of autonomous thyroid nodules does not preclude thyroid carcinoma in a functioning nodule.

Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon.

PubMed

Xu, Bin; Scognamiglio, Theresa; Cohen, Perry R; Prasad, Manju L; Hasanovic, Adnan; Tuttle, Robert Michael; Katabi, Nora; Ghossein, Ronald A

2017-07-01

Metastatic papillary thyroid carcinoma (PTC) without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon.We retrieved 7 of such cases and described in detail the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was PTC (n=5), poorly differentiated thyroid carcinoma in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma in association with a PTC tall cell variant (n=1). Fibrosis was present in the thyroid of 5 patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with poorly differentiated thyroid carcinoma did not recur and died of unknown causes. Finally, the patient with anaplastic thyroid carcinoma was alive with distant metastasis at last follow-up. The median follow-up for this cohort was 2.2years (range, 0.8-17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAF V600E -positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Skin metastasis on the neck: an unusual presentation of recurrence of papillary thyroid carcinoma

PubMed Central

Soylu, Selen; Teksoz, Serkan; Ozcan, Murat; Bukey, Yusuf

2017-01-01

Skin metastasis of papillary thyroid carcinoma (PTC) is rare. Here, two cases of skin metastases of PTC are presented. Both of the patients were females, one is 83 and the other is 65 years old. The patients were admitted to the hospital with a movable skin lesion on anterior neck region. Free T3 and T4 levels were in normal levels and TSH levels were low in both patients. The 83-year-old patient underwent total thyroidectomy due to papillary thyroid cancer and received 131I ablation therapy and then thyroid suppression therapy. After the surgery, the patient lived without evidence of disease for 3 years and then skin metastasis occurred. The 65-year-old patient had a total thyroidectomy 5 years ago due to PTC then neck dissection due to metastasis 3 years later and then received 131I ablation therapy. Thyroid ultrasonography of both patients showed hypoechoic nodules with central vascularization. In the histological examination of both patients, cystic lesions filled with papillary structures were seen. Fine needle aspiration biopsy (FNAB) taken from both patients were papillary carcinoma with solid trabecular pattern. PTC tends to metastasize to regional lymph nodes but distant metastasis is rare. When distant metastasis develops, prognosis of the disease is poor. Therefore, skin metastasis of papillary thyroid cancer is a poor prognostic factor. If the patient does not have a thyroid malignancy history, diagnosis of PTC metastatic to the skin may be difficult since primary skin tumors such as apocrine tumors have similar histopathological features. However, in the presented cases since there was a PTC history, the diagnosis was easier with the help of histopathological examination. Skin metastasis of PTC should be kept in mind when differential diagnosis of atypical skin lesions are made especially in the patients with thyroid malignancy history. PMID:29142854

[Differential diagnosis of papillary carcinomas of the thyroid, using image analysis and three dimensional reconstruction from serial sections].

PubMed

Holschbach, A; Kriete, A; Schäffer, R

1990-01-01

Papillae with fibrovascular cores are characteristic of papillary carcinoma of the thyroid. Papillae may be found in diffuse hyperplasia, nodular hyperplasia, Hashimoto's disease and follicular adenoma. Tissues from ten benign hyperplasias and ten papillary carcinomas were reconstructed from serial sections with three dimensional reconstruction programs. Significant qualitative and quantitative differences were found between the hyperplasia and the carcinoma. The principal differences between papillae of papillary carcinoma and hyperplasia were more clearly seen in the three dimensional reconstruction, than by means of morphometric methods. Certain criteria, e.g. the volume of papillae, were useful only with regard to the third dimension. Nevertheless, three dimensional reconstruction of biological tissue is a time consuming procedure which is not yet suitable for routine examination.

Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-08-18

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

PubMed Central

Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

ClinicalTrials.gov

2015-11-04

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

[GST genes expression as prognostic factor in papillary thyroid cancer].

PubMed

Gonçalves, Antonio Jose; Monte, Osmar; Morari, Eliane Cristina; Ward, Laura Sterian; Nakasako, Diana Shimoda; Nieto, Juliana; Nakai, Marianne Yumi

2009-01-01

Analyze the relationship between the AMES classification and molecular factors from Glutation-S-Transferase System, specifically the GSTT1 and GSTM1 in patients with well differentiated thyroid cancer. Samples of thyroid tissue of 66 patients with papillary thyroid carcinoma were obtained (53 women and 13 men). Patients were divided in two groups (high and low risk) according to the AMES classification. In each group, presence of the null genotype of both GST enzymes system was studied. These results were compared with the AMES classification. Samples were obtained in the operating room immediately after thyroidectomy, placed in cryotubes, immersed in liquid nitrogen and stored in a freezer at -80 masculineC. DNA of this enzymes was extracted by the fenol-cloroformium method. There were 17 high risk patients and 49 low risk patients. The null genotype of the high risk group was 5.8% and in the other group was 6.1%. There was no relationship between absence of genes GSTT1 and GSTM1 and prognosis of the papillary thyroid carcinoma when compared to the AMES classifications.

Thyroid nodules and thyroid autoimmunity in the context of environmental pollution.

PubMed

Benvenga, Salvatore; Antonelli, Alessandro; Vita, Roberto

2015-12-01

Evidence suggests that in most industrialized countries autoimmune disorders, including chronic lymphocytic thyroiditis, are increasing. This increase parallels the one regarding differentiated thyroid cancer, the increment of which is mainly due to the papillary histotype. A number of studies have pointed to an association between chronic lymphocytic thyroiditis and differentiated thyroid cancer. The upward trend of these two thyroid diseases is sustained by certain environmental factors, such as polluting substances acting as endocrine disrupting chemicals. Herein we will review the experimental and clinical literature that highlights the effects of environmental and occupational exposure to polluting chemicals in the development of autoimmune thyroid disease or differentiated thyroid cancer. Stakeholders, starting from policymarkers, should become more sensitive to the consequences for the thyroid resulting from exposure to EDC. Indeed, the economic burden resulting from such consequences has not been quantified thus far.

Coexistence of papillary thyroid cancer and Hashimoto thyroiditis in children: report of 3 cases.

PubMed

Koibuchi, Harumi; Omoto, Kiyoka; Fukushima, Noriyoshi; Toyotsuji, Tomonori; Taniguchi, Nobuyuki; Kawano, Mikihiko

2014-07-01

This report documents 3 pediatric papillary thyroid carcinoma cases with associated Hashimoto thyroiditis. In all 3 cases, hypoechoic nodules accompanied by multiple echogenic spots were noted on sonography of the thyroid. Hashimoto thyroiditis was suspected on the basis of positive thyroid autoantibody test results and pathologic examinations of thyroidectomy specimens, which revealed chronic thyroiditis with lymphocytic infiltration as the background of papillary thyroid carcinoma development. The potential for papillary carcinoma development warrants close follow-up, and meticulous sonographic examinations must be performed in children with Hashimoto thyroiditis. © 2014 by the American Institute of Ultrasound in Medicine.

Hyperfunctioning thyroid cancer: a five-year follow-up.

PubMed

Azevedo, Monalisa Ferreira; Casulari, Luiz Augusto

2010-02-01

Differentiated thyroid cancer rarely occurs in association with hyperfunctioning nodules. We describe a case of a 47-year-old woman who developed symptoms of hyperthyroidism associated with a palpable thyroid nodule. Thyroid scintigraphy showed an autonomous nodule, and fine-needle aspiration biopsy was suggestive of papillary carcinoma. Laboratorial findings were consistent with the diagnosis of hyperthyroidism. The patient underwent thyroidectomy and a papillary carcinoma of 3.0 x 3.0 x 2.0 cm, follicular variant, was described by histological examination. The surrounding thyroid tissue was normal. Postoperatively, the patient received 100 mCi of (131)I, and whole body scans detected only residual uptake. No evidence of metastasis was detected during five years of follow-up. Hot thyroid nodules rarely harbor malignancies, and this case illustrated that, when a carcinoma occurs the prognosis seems to be very good with no evidence of metastatic dissemination during a long-term follow-up.

Methylation Markers for Early Detection and Differentiation of Follicular Thyroid Cancer Subtypes

PubMed Central

Stephen, Josena K.; Chen, Kang Mei; Merritt, Jason; Chitale, Dhananjay; Divine, George; Worsham, Maria J.

2016-01-01

Thyroid cancer has the fastest rising incidence rates and is the fifth most common cancer in women. There are four main types of which the papillary and follicular types together account for >90%, followed by medullary cancers (3%−5%) and anaplastic carcinomas (<3%). For individuals who present with early stage disease of papillary and follicular cancers, there are no accurate markers to predict whether they will develop metastatic or recurrent disease. Our immediate goal is to molecularly differentiate follicular cancer subtypes for enhanced classification. Promoter methylation status of genes with reported associations in thyroid cancer (CASP8, CDKN2A, DAPK1, ESR1, NIS, RASSF1 and TIMP3) were examined in a cohort of follicular thyroid cancers comprising of 26 Hurthle and 27 Classic subtypes utilizing quantitative methylation-specific PCR. RASSF1 was differentially methylated in Classic tumor tissue compared to Hurthle (p<0.001). Methylation of RASSF1 pointed to racial group differences between African Americans and Caucasian Americans (p=0.05). Extra thyroidal extension was found to be associated with DAPK1 (p=0.014) and ESR1 (p=0.036) methylation. Late stage disease was associated with older age (p<0.001) and methylation of DAPK1 (p=0.034) and ESR1 (p=0.035). The methylation status of RASSF1, DAPK1 and ESR1 suggests the utility of methylation markers to molecularly differentiate thyroid cancer subtypes for enhanced classification and early detection of thyroid cancer. PMID:27158284

Warthin tumor-like papillary thyroid carcinoma with a minor dedifferentiated component: report of a case with clinicopathologic considerations.

PubMed

Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano

2010-01-01

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course.

Warthin Tumor-Like Papillary Thyroid Carcinoma with a Minor Dedifferentiated Component: Report of a Case with Clinicopathologic Considerations

PubMed Central

Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano

2010-01-01

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course. PMID:20593036

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

PubMed Central

McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

2015-01-01

Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

[Poorly differentiated thyroid carcinomas: new therapeutic considerations].

PubMed

Graf, Hans

2005-10-01

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.

Cytopathology of non-invasive follicular thyroid neoplasm with papillary-like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants.

PubMed

Mahajan, S; Agarwal, S; Kocheri, N; Jain, D; Mathur, S R; Iyer, V K

2018-06-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well-defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features. Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC-FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared. There were 23 NIFTP cases, 18 FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003). NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC-FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology. © 2018 John Wiley & Sons Ltd.

[Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

PubMed

Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

2017-02-01

Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry.

PubMed

Cooper, D S; Specker, B; Ho, M; Sperling, M; Ladenson, P W; Ross, D S; Ain, K B; Bigos, S T; Brierley, J D; Haugen, B R; Klein, I; Robbins, J; Sherman, S I; Taylor, T; Maxon, H R

1998-09-01

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.

Evaluation of the presence of Epstein-Barr virus (EBV) in Iranian patients with thyroid papillary carcinoma.

PubMed

Homayouni, Maryam; Mohammad Arabzadeh, Seyed Ali; Nili, Fatemeh; Razi, Farideh; Amoli, Mahsa Mohammad

2017-07-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma. In this study the presence of Epstein-Barr Nuclear Antigen 1 (EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N=41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene. In 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages. The significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important. Copyright © 2017 Elsevier GmbH. All rights reserved.

Thyroid cancer - papillary carcinoma

MedlinePlus

... this page: //medlineplus.gov/ency/article/000331.htm Thyroid cancer - papillary carcinoma To use the sharing features on ... the lower neck. Causes About 80% of all thyroid cancers diagnosed in the United States are the papillary ...

Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

PubMed

Iliadou, Paschalia K; Effraimidis, Grigoris; Konstantinos, Michalakis; Grigorios, Panagiotou; Mitsakis, Periklis; Patakiouta, Frideriki; Pazaitou-Panayiotou, Kalliopi

2015-12-01

The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. The medical records of children and adolescents (≤21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. © 2015 European Society of Endocrinology.

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors.

PubMed

Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Beltrami, Caroline Moraes; Kuasne, Hellen; Pinto, Clóvis Antônio Lopes; Ambatipudi, Srikant; Herceg, Zdenko; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

2017-11-01

Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. To identify a prognostic epigenetic signature in thyroid cancer. Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC. Copyright © 2017 Endocrine Society

Differentiation between malignant and benign thyroid nodules and stratification of papillary thyroid cancer with aggressive histological features: Whole-lesion diffusion-weighted imaging histogram analysis.

PubMed

Hao, Yonghong; Pan, Chu; Chen, WeiWei; Li, Tao; Zhu, WenZhen; Qi, JianPin

2016-12-01

To explore the usefulness of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) derived from reduced field-of-view (r-FOV) diffusion-weighted imaging (DWI) in differentiating malignant and benign thyroid nodules and stratifying papillary thyroid cancer (PTC) with aggressive histological features. This Institutional Review Board-approved, retrospective study included 93 patients with 101 pathologically proven thyroid nodules. All patients underwent preoperative r-FOV DWI at 3T. The whole-lesion ADC assessments were performed for each patient. Histogram-derived ADC parameters between different subgroups (pathologic type, extrathyroidal extension, lymph node metastasis) were compared. Receiver operating characteristic curve analysis was used to determine optimal histogram parameters in differentiating benign and malignant nodules and predicting aggressiveness of PTC. Mean ADC, median ADC, 5 th percentile ADC, 25 th percentile ADC, 75 th percentile ADC, 95 th percentile ADC (all P < 0.001), and kurtosis (P = 0.001) were significantly lower in malignant thyroid nodules, and mean ADC achieved the highest AUC (0.919) with a cutoff value of 1842.78 × 10 -6 mm 2 /s in differentiating malignant and benign nodules. Compared to the PTCs without extrathyroidal extension, PTCs with extrathyroidal extension showed significantly lower median ADC, 5 th percentile ADC, and 25 th percentile ADC. The 5 th percentile ADC achieved the highest AUC (0.757) with cutoff value of 911.5 × 10 -6 mm 2 /s for differentiating between PTCs with and without extrathyroidal extension. Whole-lesion ADC histogram analysis might help to differentiate malignant nodules from benign ones and show the PTCs with extrathyroidal extension. J. Magn. Reson. Imaging 2016;44:1546-1555. © 2016 International Society for Magnetic Resonance in Medicine.

Anti-cancer activity of myricetin against human papillary thyroid cancer cells involves mitochondrial dysfunction-mediated apoptosis.

PubMed

Ha, Tae Kwun; Jung, Inae; Kim, Mi Eun; Bae, Sung Kwon; Lee, Jun Sik

2017-07-01

Thyroid cancer is the most common endocrine malignancy and can range in severity from relatively slow-growing occult differentiated thyroid cancer to uniformly aggressive and fatal anaplastic thyroid cancer. A subset of patients with papillary thyroid cancer present with aggressive disease that is refractory to conventional treatment. Myricetin is a flavonol compound found in a variety of berries as well as walnuts and herbs. Previous studies have demonstrated that myricetin exhibits anti-cancer activity against several tumor types. However, an anti-cancer effect of myricetin against human papillary thyroid cancer (HPTC) cells has not been established. The present investigation was undertaken to gain insights into the molecular mechanism of the anti-cancer activity of myricetin against HPTC cells. We examined the cytotoxicity, DNA damaging, and cell cycle arresting activities of myricetin using SNU-790 HPTC cells. We found that myricetin exhibited cytotoxicity and induced DNA condensation in SNU-790 HPTC cells in a dose-dependent manner. Moreover, myricetin up-regulated the activation of caspase cascades and the Bax:Bcl-2 expression ratio. In addition, myricetin induced the release of apoptosis-inducing factor (AIF) and altered the mitochondrial membrane potential. Our results suggest that myricetin induces the death of SNU-790 HPTC cells and thus may prove useful in the development of therapeutic agents for human thyroid cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michigishi, T.; Mizukami, Y.; Mura, T.

1991-05-01

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma.

PubMed

Yu, Marc Gregory; Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma

PubMed Central

Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines. PMID:27746818

Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

PubMed

Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

1999-01-15

Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage to transformed thyroid cells.

Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.

PubMed Central

Saito, T; Endo, T; Kawaguchi, A; Ikeda, M; Katoh, R; Kawaoi, A; Muramatsu, A; Onaya, T

1998-01-01

Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue. PMID:9525971

Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors.

PubMed

Arnaldi, L A T; Borra, R C; Maciel, R M B; Cerutti, J M

2005-03-01

To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tumors, we compared the gene expression profiles of three thyroid carcinoma cell lines, which represent major tumor subtypes of thyroid cancer and normal thyroid tissue. Using cDNA array methodology, we investigated the expression of 1807 open reading frame expressed sequence tags (ORESTES), selected from head and neck tumor libraries generated through the Brazilian Human Cancer Project-LICR/FAPESP. We found that 505 transcripts were differentially expressed in the thyroid carcinoma cell lines. Using a more stringent criterion, transcripts underexpressed or overexpressed more than fivefold in 1 of 3 or 3 of 3 carcinoma cell lines, a list of 55 ESTs were detected. Five candidate genes were further validated by quantitative polymerase chain reaction (qPCR) in an independent set of 52 thyroid tumors and 22 matched normal thyroid tissues. DCN was found underexpressed in a high percentage of the follicular thyroid adenomas, follicular thyroid carcinomas, and follicular variant of papillary thyroid carcinomas. DIO1 and DIO2 were underexpressed in nearly all papillary thyroid carcinomas. These genes not only could help to better define a tumor signature for thyroid tumors, but may, in part, also become useful as potential targets for thyroid tumor treatment.

Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

ClinicalTrials.gov

2017-01-24

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

Thyroid Cancer—Health Professional Version

Cancer.gov

There are four types of thyroid cancer. These are papillary, follicular, medullary, and anaplastic thyroid cancer. Papillary is the most common type of thyroid cancer. Find evidence-based information on thyroid cancer treatment, screening, research, genetics, and statistics.

GNAq mutations are not identified in papillary thyroid carcinomas and hyperfunctioning thyroid nodules.

PubMed

Cassol, Clarissa A; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

2010-12-01

Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.

[Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 2)].

PubMed

Dietlein, M; Dressler, J; Farahati, J; Grünwald, F; Leisner, B; Moser, E; Reiners, C; Schicha, H; Schober, O

2004-08-01

The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counter-part to the procedure guidelines for (131)I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft für Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

PubMed

Machairas, Nikolaos; Kostakis, Ioannis D; Prodromidou, Anastasia; Stamopoulos, Paraskevas; Feretis, Themistoklis; Garoufalia, Zoe; Damaskos, Christos; Tsourouflis, Gerasimos; Kouraklis, Gregory

2017-11-01

Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].

PubMed

Liu, Yan; Miao, Yuhua; Li, Xiaoming

2015-06-01

To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K.

PubMed

Han, Fei; Zhang, Long; Zhang, Suxia; Zhou, Hong; Yi, Xianghua

2015-01-01

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAF(V600K) mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations.

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K

PubMed Central

Han, Fei; Zhang, Long; Zhang, Suxia; Zhou, Hong; Yi, Xianghua

2015-01-01

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAFV600K mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations. PMID:26191315

RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma

NASA Astrophysics Data System (ADS)

Rau, Julietta V.; Graziani, Valerio; Fosca, Marco; Taffon, Chiara; Rocchia, Massimiliano; Crucitti, Pierfilippo; Pozzilli, Paolo; Onetti Muda, Andrea; Caricato, Marco; Crescenzi, Anna

2016-10-01

Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.

Warthin-like papillary carcinoma of the thyroid: a case series and review of the literature.

PubMed

Erşen, Ayça; Durak, Merih Güray; Canda, Tülay; Sevınç, Ali Ibrahim; Saydam, Serdar; Koçdor, Mehmet Ali

2013-01-01

Warthin-like tumor of the thyroid is a recently described rare variant of thyroid papillary carcinoma. The distinguishing histological feature of this variant is papillary foldings lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. Its prognosis has been reported to be almost similar to conventional papillary carcinoma. In this case series, we report four cases with Warthin-like papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul University Faculty of Medicine Department of Pathology in 2008 and 2009. Three patients were female. The mean patient age was 39 years (range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). All of the cases had lymphocytic thyroiditis in the background. None of the tumors showed lymphovascular invasion. The patients are free of any recurrence and/or distant metastasis with a mean follow-up of 25 months. This rare variant of thyroid papillary carcinoma with distinct histopathological features should be indicated in pathology reports. Further studies and long-term follow-up of patients are needed to highlight the biological behavior of this variant.

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

A study of Galactin-3 on fine needle aspiration as a diagnostic marker differentiating benign from malignant thyroid neoplasm

PubMed Central

Muzafar, Alliya; Bukhari, Mulazim Hussain; Qureshi, Ihtesham uddin

2017-01-01

Background & Objective: Thyroid nodules are very common in our setup and their diagnosis on fine needle aspiration is not easy and is a taxing affair. It is a challenge to differentiate between follicular adenoma and follicular carcinoma without histology. Our objective was to investigate the role of Galectin-3 in fine needle aspirates of thyroid nodules as a prospective diagnostic marker and consequently its ability to differentiate benign from malignant neoplasms. Methods: The research was conducted at the department of Pathology, King Edward Medical University, in association with other teaching institutions of Lahore from June 2012 to July 2014.. Sixty cases of solitary thyroid nodules were included in the study. Haematoxylin and eosin staining of the fixed smears and Galectin-3 immunohistochemical staining of the sections prepared from the cell block was performed. Results: There were 60 patients in our study with a mean age of 33.35 years. The Bethesda system for reporting thyroid cytopathology was used to classify the smears and only categories IV, V and VI were included. On histological examination of the resected nodules there were 38.3% (23/60) cases of follicular adenoma, 46.6% (28/60) were of papillary carcinoma and follicular carcinoma made up to 15% (9/60) of all cases. Galectin-3 was negative in 100% (23/23) cases of follicular adenomas. Out of 37 malignant cases 65% lesions showed positivity, while 35% showed negativity for this immunomarker. Considering the malignant lesions, 75% cases of papillary carcinomas showed a positive reaction while only 33% of follicular carcinomas were positive for the immunomarker. This showed that the positive expression was more common in papillary as compared to follicular carcinomas. Conclusion: Galectin-3immunomarker is considerably expressed in malignant tumors, but it is not expressed in benign follicular lesions. PMID:28811803

Diffuse skeletal metastasis and low thyroglobulin level in a pediatric patient with papillary thyroid carcinoma.

PubMed

Zakavi, Seyed Rasoul; Ayati, Narjess; Farahati, Jamshid; Davachi, Behrooz

2015-01-01

Thyroglobulin (Tg) is frequently measured in follow-up of patients with differentiated thyroid carcinoma. A low stimulated Tg level (<1 ng/ml) associated with normal neck ultrasonography is considered as the most reliable criteria for complete remission in low risk patients. We are reporting a case of pediatric thyroid cancer with diffuse skeletal metastasis associated with low serum Tg level bringing a point of caution in evaluation of patients with low Tg.

Diagnosis and management of differentiated thyroid cancer using molecular biology.

PubMed

Witt, Robert L; Ferris, Robert L; Pribitkin, Edmund A; Sherman, Steven I; Steward, David L; Nikiforov, Yuri E

2013-04-01

To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer. Ovid Medline 2006-2012 Manuscripts with clinical correlates. Papillary thyroid carcinomas harbor point mutations of the BRAF and RAS genes or RET/PTC rearrangements, all of which activate the mitogen-activated protein kinase pathway. These mutually exclusive mutations are found in 70% of PTC. BRAF mutation is found in 45% of papillary thyroid cancer and is highly specific. Follicular carcinomas are known to harbor RAS mutation or PAX8/PPARγ rearrangement. These mutations are also mutually exclusive and identified in 70% of follicular carcinomas. Molecular classifiers measure the expression of a large number of genes on a microarray chip providing a substantial negative predictive value pending further validation. 1) 20% to 30% of cytologically classified Follicular Neoplasms and Follicular Lesion of Undetermined Significance collectively are malignant on final pathology. Approximately 70% to 80% of thyroid lobectomies performed solely for diagnostic purposes are benign. Molecular alteration testing may reduce the number of unnecessary thyroid procedures, 2) may reduce the number of completion thyroidectomies, and 3) may lead to more individualized operative and postoperative management. Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ for follicular lesion of undetermined significance and follicular neoplasm improve specificity, whereas molecular classifiers may add negative predictive value to fine needle aspiration diagnosis. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

Synchronous papillary thyroid carcinoma and primary hyperparathyroidism: diagnosis and management issues.

PubMed

Vysetti, Suneetha; Sridhar, Preethi; Theckedath, Boby; Gilden, Janice L; Morawiecki, Peter

2012-10-01

The occurrence of a papillary thyroid carcinoma in a patient with primary hyperparathyroidism is rare. Awareness of this condition will enable clinicians to evaluate for possible thyroid pathology in patients with primary hyperparathyroidism. Both of these endocrine conditions could then be managed with a single surgery involving concomitant resection of the thyroid and parathyroid glands. We report a case of a 53-year-old woman with a parathyroid adenoma and a unilateral papillary thyroid carcinoma, and detail the clinical features, diagnosis, and management.

Characteristics of young adults of Belarus with post-Chernobyl papillary thyroid carcinoma: a long-term follow-up of patients with early exposure to radiation at the 30th anniversary of the accident.

PubMed

Fridman, Mikhail; Lam, Alfred King-Yin; Krasko, Olga

2016-12-01

Studies of thyroid cancer related to the Chernobyl accident have focused on children as they are the most vulnerable group with the highest risk of developing radiation-associated cancer. In contrast, our research aimed to look at the clinical and pathological features of patients with post-Chernobyl papillary thyroid carcinoma that were 2 years old or less at the time of the Chernobyl accident. The study subjects were patients (n = 359) aged 0 to 2 at the time of the Chernobyl accident and aged ≥19 years at presentation/surgery who were treated in Belarus for papillary thyroid carcinoma during the period 2003-2013. In conventional or oncocytic variant of papillary thyroid carcinoma, the prevalence of extra-thyroidal extension, nodal disease, infiltrative growth or lymphatic vessel invasion was above 50%. These features were less pronounced when compared to tall cell or diffuse sclerosing variants of papillary thyroid carcinoma. The highest frequency of central lymph node metastases was found in patients aged 1-2 years at exposure (P = 0·004). Subjects exposed in utero were characterized by absent/insignificant lymphocytic infiltration around the carcinoma (P = 0·025), predominance of conventional papillary architecture and an association with lymphocytic thyroiditis. A number of features were associated with this group of patients that were very young at the time of radiation exposure. In addition, the incidence and basic characteristics of adult papillary thyroid carcinoma varied depending on the types of exposure conditions. © 2016 John Wiley & Sons Ltd.

Lack of HER-2 gene amplification and association with pathological and clinical characteristics of differentiated thyroid cancer.

PubMed

Mdah, Wahid; Mzalbat, Raneen; Gilbey, Peter; Stein, Moshe; Sharabi, Adi; Zidan, Jamal

2014-11-01

Human epidermal growth factor receptor 2 (HER-2) is a well recognized prognostic and predictive factor in breast cancer. However, the role of HER-2 in thyroid cancer remains controversial. The aim of this study was to evaluate HER-2 expression in differentiated thyroid cancer (DTC) and determine whether there is an association with other clinical and pathological characteristics. A total of 69 patients with DTC were investigated, 58 of whom had papillary and 11 follicular carcinomas. HER-2 was detected by immunohistochemical examination on sections from formalin-fixed, paraffin-embedded tumor tissues. Tumors with HER-2 expression classed as +1 and +2 were retested with chromogenic in situ hybridization. Clinicopathological data were retrieved from the hospital records of the patients. HER-2 overexpression was found in 4 (6.9%) of the 58 patients with papillary carcinoma, whereas there was no HER-2 overexpression in any of the 11 cases of follicular carcinoma. There was no association of HER-2 expression with tumor size, pathological grade and cervical lymph node metastasis. In conclusion, there were no HER-2 positive cases of follicular carcinoma and the incidence of HER-2 overexpression in papillary carcinoma was very low. Thus, HER-2 cannot be used routinely as a prognostic or predictive factor in DTC. The expression of other epidermal growth factor receptors in DTC merits further investigation.

Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.

PubMed

Yu, Yang; Yu, Xiaohui; Fan, Chenling; Wang, Hong; Wang, Renee; Feng, Chen; Guan, Haixia

2018-06-25

Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT 2 -PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells. These results were later confirmed via real-time PCR, Western blots, and immunohistochemical staining. We found that the levels of glutaminase were significantly correlated with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. The proliferative, viable, migratory, and invasive abilities of papillary thyroid cancer cells were impaired by both the pharmacological inhibition and the genetic knockdown of glutaminase. Additionally, the inhibition of glutaminase deactivated the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and apoptosis. Collectively, these findings show that glutaminase-mediated glutamine dependence may be a potential therapeutic target for papillary thyroid cancer. PTC cells are glutamine-dependent, and GLS is aberrantly overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells. GLS blockade causes deactivation of mTORC1 and induction of autophagy and apoptosis. GLS may be a potential therapeutic target for PTC.

Painless thyroiditis associated to thyroid carcinoma: role of initial ultrasonography evaluation.

PubMed

Valentini, Raisa Bressan; Macedo, Bruno Mussoi de; Izquierdo, Rogério Friedrich; Meyer, Erika Laurini Souza

2016-04-01

Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus.

An unusual metastasis of a papillary thyroidian carcinoma with follicular pattern.

PubMed

Coconu, M; Berdan, G; Roşculescu, I; Herlea, V

1998-01-01

The case of a 67-year-old man is presented. He was admitted for the presence of a left parietal tumour with progressive growing, without any other objective or subjective symptomatology. CT-scan detects a left parietal osteolytic area. The histopathological aspect suggested an adenocarcinomatous metastasis with papillary pattern, moderately differentiated. With the purpose of diagnosing the original tumour, immunnohistochemical techniques were performed, which led to a diagnosis of a thyroidian carcinoma. At the histological examination of the surgical extirpated thyroid, it was proved to be a papillary carcinoma (Chan, 1990, Hay, 1990), the follicular pattern.

The Increasing Incidence of Thyroid Cancer: The Influence of Access to Care

PubMed Central

Sikora, Andrew G.; Tosteson, Tor D.

2013-01-01

Background The rapidly rising incidence of papillary thyroid cancer may be due to overdiagnosis of a reservoir of subclinical disease. To conclude that overdiagnosis is occurring, evidence for an association between access to health care and the incidence of cancer is necessary. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to examine U.S. papillary thyroid cancer incidence trends in Medicare-age and non–Medicare-age cohorts over three decades. We performed an ecologic analysis across 497 U.S. counties, examining the association of nine county-level socioeconomic markers of health care access and the incidence of papillary thyroid cancer. Results Papillary thyroid cancer incidence is rising most rapidly in Americans over age 65 years (annual percentage change, 8.8%), who have broad health insurance coverage through Medicare. Among those under 65, in whom health insurance coverage is not universal, the rate of increase has been slower (annual percentage change, 6.4%). Over three decades, the mortality rate from thyroid cancer has not changed. Across U.S. counties, incidence ranged widely, from 0 to 29.7 per 100,000. County papillary thyroid cancer incidence was significantly correlated with all nine sociodemographic markers of health care access: it was positively correlated with rates of college education, white-collar employment, and family income; and negatively correlated with the percentage of residents who were uninsured, in poverty, unemployed, of nonwhite ethnicity, non-English speaking, and lacking high school education. Conclusion Markers for higher levels of health care access, both sociodemographic and age-based, are associated with higher papillary thyroid cancer incidence rates. More papillary thyroid cancers are diagnosed among populations with wider access to healthcare. Despite the threefold increase in incidence over three decades, the mortality rate remains unchanged. Together with the large subclinical reservoir of occult papillary thyroid cancers, these data provide supportive evidence for the widespread overdiagnosis of this entity. PMID:23517343

p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma.

PubMed

Erickson, L A; Yousef, O M; Jin, L; Lohse, C M; Pankratz, V S; Lloyd, R V

2000-09-01

In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.

Positive Surgical Margins in Favorable-Stage Differentiated Thyroid Cancer.

PubMed

Mercado, Catherine E; Drew, Peter A; Morris, Christopher G; Dziegielewski, Peter T; Mendenhall, William M; Amdur, Robert J

2018-04-16

The significance of positive margin in favorable-stage well-differentiated thyroid cancer is controversial. We report outcomes of positive-margin patients with a matched-pair comparison to a negative-margin group. A total of 25 patients with classic-histology papillary or follicular carcinoma, total thyroidectomy +/- node dissection, stage T1-3N0-1bM0, positive surgical margin at primary site, adjuvant radioactive iodine (I-131), and age older than 18 years were treated between 2003 and 2013. Endpoints were clinical and biochemical (thyroglobulin-only) recurrence-free survival. Matched-pair analysis involved a 1:1 match with negative-margin cases matched for overall stage and I-131 dose. Recurrence-free survival in positive-margin patients was 71% at 10 years. No patient was successfully salvaged with additional treatment. Only 1 patient died of thyroid cancer. Recurrence-free survival at 10 years was worse with a positive (71%) versus negative (90%) margin (P=0.140). Cure with a microscopically positive margin was suboptimal (71%) despite patients having classic-histology papillary and follicular carcinoma, favorable stage, and moderate-dose I-131 therapy.

Marine-Lenhart syndrome with papillary thyroid carcinoma.

PubMed

Atmaca, Hulusi; Çolak, Ramis; Yazici, Zihni Acar; Kefeli, Mehmet; Tosun, Fevziye Canbaz

2015-04-01

Graves' disease with accompanying functioning nodules is known as Marine-Lenhart syndrome. Autonomously functioning thyroid nodules (AFTNs) also within Graves' thyroid tissue are almost always bening in nature. A 45-year-old man developed hyperthyroidism due to the coexistence of Graves' disease and AFTN. Total thyroidectomy was performed. The hyperfunctioning nodule with centrally hypoactive foci detected by technetium-99m thyroid scanning was histologically diagnosed as papillary thyroid carcinoma that was 2.5 cm in diameter. We report the presence of papillary thyroid carcinoma within AFTN in patients with Marine-Lenhart syndrome, which has not been reported so far.

The follicular variant of papillary thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PubMed

Scharpf, Joseph; Kamani, Dipti; Sadow, Peter M; Randolph, Gregory W

2017-01-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new terminology proposed for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Recently, thyroid cancer incidence has increased dramatically, without affecting related mortality rate. This increase is widely attributed to the intensified surveillance leading to a substantial increase in the diagnosis of small classic papillary thyroid cancers and EFVPTCs. Recent studies emphasize the indolent behavior of the EFVPTC. Recently, there has been a reclassification of EFVPTC as NIFTP, a benign entity. The financial and emotional burden of 'cancer' diagnosis and treatment can be significant. This review recapitulates the literature supporting the reclassification of EFVPTC as NIFTP, a benign entity, and reviews standardized diagnostic criteria for EFVPTC. The information highlighted in this review will affect surgical decision making and may promote the offering of hemithyroidectomy over a total thyroidectomy to some patients with 'indeterminate' cytopathological category; postoperative radioiodine ablation will not be required for NIFTP patients.

Incidental nodal metastasis of differentiated thyroid carcinoma in neck dissection specimens from head and neck cancer patients.

PubMed

Lenzi, R; Marchetti, M; Muscatello, L

2017-04-01

Occult differentiated thyroid carcinomas are not uncommon. The initial presentation of a thyroid carcinoma is often detection of a metastatic cervical lymph node. A retrospective review was performed of the medical records of 304 patients who underwent neck dissection between 1996 and 2008 for squamous cell carcinoma of the head and neck. Ten patients (3.3 per cent) had nodal metastasis originating from papillary thyroid cancer. All of these patients underwent thyroidectomy and post-operative 131iodine radiometabolic therapy. No patient developed a thyroid tumour after surgery. Despite its metastatic spread, thyroid cancer does not affect the overall prognosis of patients who are already being treated for a more aggressive malignancy. However, in otherwise healthy patients, it is worth treating this second malignancy to avoid potential complications related to local disease or metastatic thyroid cancer.

Diffuse skeletal metastasis and low thyroglobulin level in a pediatric patient with papillary thyroid carcinoma

PubMed Central

Zakavi, Seyed Rasoul; Ayati, Narjess; Farahati, Jamshid; Davachi, Behrooz

2015-01-01

Thyroglobulin (Tg) is frequently measured in follow-up of patients with differentiated thyroid carcinoma. A low stimulated Tg level (<1 ng/ml) associated with normal neck ultrasonography is considered as the most reliable criteria for complete remission in low risk patients. We are reporting a case of pediatric thyroid cancer with diffuse skeletal metastasis associated with low serum Tg level bringing a point of caution in evaluation of patients with low Tg. PMID:26170580

Molecular markers in well-differentiated thyroid cancer.

PubMed

D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

2018-06-01

Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma Cells Surface in Comparison to Normal Cells.

PubMed

Bertoni, Ana Paula Santin; de Campos, Rafael Paschoal; Tsao, Marisa; Braganhol, Elizandra; Furlanetto, Tania Weber; Wink, Márcia Rosângela

2018-02-17

The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated the ability of thyroid cancer cells to hydrolyze extracellular ATP generating adenosine, and the expression of ecto-enzymes, as compared to normal cells. We found that normal thyroid derived cells presented a higher ability to hydrolyze ATP and higher mRNA levels for ENTDP1-2, when compared to papillary thyroid carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced an increase in proliferation and migration in PTC derived cells, whose effect was blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73. Taken together, these results showed that thyroid follicular cells have a functional purinergic signaling. The higher expression of CD73 in PTC derived cells might favor the accumulation of extracellular adenosine in the tumor microenvironment, which could promote tumor progression. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for thyroid cancer management and treatment.

Identification of differential pathways in papillary thyroid carcinoma utilizing pathway co-expression analysis.

PubMed

Qiu, Wei-Hai; Chen, Gui-Yan; Cui, Lu; Zhang, Ting-Ming; Wei, Feng; Yang, Yong

2016-01-01

To identify differential pathways between papillary thyroid carcinoma (PTC) patients and normal controls utilizing a novel method which combined pathway with co-expression network. The proposed method included three steps. In the first step, we conducted pretreatments for background pathways and gained representative pathways in PTC. Subsequently, a co-expression network for representative pathways was constructed using empirical Bayes (EB) approach to assign a weight value for each pathway. Finally, random model was extracted to set the thresholds of identifying differential pathways. We obtained 1267 representative pathways and their weight values based on the co-expressed pathway network, and then by meeting the criterion (Weight > 0.0296), 87 differential pathways in total across PTC patients and normal controls were identified. The top three ranked differential pathways were CREB phosphorylation, attachment of GPI anchor to urokinase plasminogen activator receptor (uPAR) and loss of function of SMAD2/3 in cancer. In conclusion, we successfully identified differential pathways (such as CREB phosphorylation, attachment of GPI anchor to uPAR and post-translational modification: synthesis of GPI-anchored proteins) for PTC using the proposed pathway co-expression method, and these pathways might be potential biomarkers for target therapy and detection of PTC.

Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.

PubMed

Vukasović, Anamarija; Kuna, Sanja Kusacić; Ostović, Karmen Trutin; Prgomet, Drago; Banek, Tomislav

2012-11-01

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.

Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy

NASA Astrophysics Data System (ADS)

Zhou, Chao; Wang, Yihong; Aguirre, Aaron D.; Tsai, Tsung-Han; Cohen, David W.; Connolly, James L.; Fujimoto, James G.

2010-01-01

We evaluate the feasibility of optical coherence tomography (OCT) and optical coherence microscopy (OCM) for imaging of benign and malignant thyroid lesions ex vivo using intrinsic optical contrast. 34 thyroid gland specimens are imaged from 17 patients, covering a spectrum of pathology ranging from normal thyroid to benign disease/neoplasms (multinodular colloid goiter, Hashimoto's thyroiditis, and follicular adenoma) and malignant thyroid tumors (papillary carcinoma and medullary carcinoma). Imaging is performed using an integrated OCT and OCM system, with <4 μm axial resolution (OCT and OCM), and 14 μm (OCT) and <2 μm (OCM) transverse resolution. The system allows seamless switching between low and high magnifications in a way similar to traditional microscopy. Good correspondence is observed between optical images and histological sections. Characteristic features that suggest malignant lesions, such as complex papillary architecture, microfollicules, psammomatous calcifications, or replacement of normal follicular architecture with sheets/nests of tumor cells, can be identified from OCT and OCM images and are clearly differentiable from normal or benign thyroid tissues. With further development of needle-based imaging probes, OCT and OCM could be promising techniques to use for the screening of thyroid nodules and to improve the diagnostic specificity of fine needle aspiration evaluation.

The value of the repeated examination of BRAF V600E mutation status in diagnostics of papillary thyroid cancer.

PubMed

Beiša, Augustas; Beiša, Virgilijus; Stoškus, Mindaugas; Ostanevičiūtė, Elvyra; Griškevičius, Laimonas; Strupas, Kęstutis

2016-01-01

Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics.

Papillary Thyroid Microcarcinoma Arising Within a Mature Ovarian Teratoma: Case Report and Review of the Literature

PubMed Central

Pineyro, Maria M; Pereda, Jimena; Schou, Pamela; de los Santos, Karina; de la Peña, Soledad; Caserta, Benedicta; Pisabarro, Raul

2017-01-01

Mature cystic teratoma is the most common kind of ovarian germ cell tumor. Malignant transformation is uncommon, with thyroid cancer rarely found. Papillary thyroid microcarcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-year-old woman who presented with abdominal pain and an ovarian mass. After surgery, the patient was diagnosed with a follicular variant papillary thyroid microcarcinoma that arose within a mature cystic ovarian teratoma. Based on the small size of the primary lesion and patient preferences, no further treatment was performed. To our knowledge, this is the third reported case of papillary thyroid microcarcinoma arising within a mature ovarian teratoma without struma ovarii. There is no consensus on the surgical approach and postoperative management of this condition. Whether further therapy with total thyroidectomy and radioiodine ablation may be beneficial is unknown. In conclusion, papillary thyroid microcarcinoma can also arise within mature ovarian teratomas. Although a favorable prognosis is anticipated, there is limited information about its history or prognosis. PMID:28615984

Papillary Thyroid Microcarcinoma Arising Within a Mature Ovarian Teratoma: Case Report and Review of the Literature.

PubMed

Pineyro, Maria M; Pereda, Jimena; Schou, Pamela; de Los Santos, Karina; de la Peña, Soledad; Caserta, Benedicta; Pisabarro, Raul

2017-01-01

Mature cystic teratoma is the most common kind of ovarian germ cell tumor. Malignant transformation is uncommon, with thyroid cancer rarely found. Papillary thyroid microcarcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-year-old woman who presented with abdominal pain and an ovarian mass. After surgery, the patient was diagnosed with a follicular variant papillary thyroid microcarcinoma that arose within a mature cystic ovarian teratoma. Based on the small size of the primary lesion and patient preferences, no further treatment was performed. To our knowledge, this is the third reported case of papillary thyroid microcarcinoma arising within a mature ovarian teratoma without struma ovarii. There is no consensus on the surgical approach and postoperative management of this condition. Whether further therapy with total thyroidectomy and radioiodine ablation may be beneficial is unknown. In conclusion, papillary thyroid microcarcinoma can also arise within mature ovarian teratomas. Although a favorable prognosis is anticipated, there is limited information about its history or prognosis.

Co-occurrence of papillary thyroid carcinoma and mucosa-associated lymphoid tissue lymphoma in a patient with long-standing hashimoto thyroiditis.

PubMed

Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-12-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies.

Co-Occurrence of Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Long-Standing Hashimoto Thyroiditis

PubMed Central

Nam, Yoon Jeong; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-01-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

PubMed

Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua

2017-05-01

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

Suggesting the cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): A retrospective analysis of atypical and suspicious nodules.

PubMed

Strickland, Kyle C; Howitt, Brooke E; Barletta, Justine A; Cibas, Edmund S; Krane, Jeffrey F

2018-02-01

The term "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) has replaced a subset of follicular variant of papillary thyroid carcinoma due to the indolent behavior of such tumors. NIFTPs are most often classified in an "indeterminate" diagnostic category. In the current study, the authors sought to identify cytologic features helpful in distinguishing NIFTP from other entities in these categories, particularly benign nodules. The authors retrospectively evaluated a consecutive cohort of 130 thyroid fine-needle aspiration (FNA) specimens with an indeterminate diagnosis and available histopathologic follow-up. All FNA specimens were evaluated using the ThinPrep method. Each FNA was blindly reviewed by 2 board-certified cytopathologists, who assessed overall cellularity; architectural parameters; and nuclear features, including nuclear pallor and fine chromatin, distinct nucleoli, and irregular nuclear membranes. Each case received a score of 0 to 3, based on the presence or absence of these 3 nuclear features. Nuclear but not architectural features appeared to distinguish NIFTP from benign nodules. Ninety-one percent of the NIFTPs (32 of 35 NIFTPs) received a score of ≥2, compared with 35% of benign nodules (23 of 66 benign nodules) (P<.0001). In contrast, NIFTP could not be differentiated from the invasive/infiltrative follicular variant of papillary thyroid carcinoma using these criteria (P = 1.000). Nuclear scoring was found to be especially useful in atypia of undetermined significance/follicular lesion of undetermined significance (AUS); a score ≥2 enriched for NIFTP (39% vs 3% of AUS cases with a score <2), whereas a score <2 was more likely benign (85% vs 50% of AUS cases with a score ≥2). In indeterminate FNA specimens, the distinction of a possible NIFTP from a benign thyroid nodule can be suggested using a simple nuclear scoring system that is most valuable in AUS aspirates. Cancer Cytopathol 2018;126:86-93. © 2017 American Cancer Society. © 2017 American Cancer Society.

Characterization of the major histopathological components of thyroid nodules using sonographic textural features for clinical diagnosis and management.

PubMed

Chen, Shao-Jer; Yu, Sung-Nien; Tzeng, Jeh-En; Chen, Yen-Ting; Chang, Ku-Yaw; Cheng, Kuo-Sheng; Hsiao, Fu-Tsung; Wei, Chang-Kuo

2009-02-01

In this study, the characteristic sonographic textural feature that represents the major histopathologic components of the thyroid nodules was objectively quantified to facilitate clinical diagnosis and management. A total of 157 regions-of-interest thyroid ultrasound image was recruited in the study. The sonographic system used was the GE LOGIQ 700), (General Electric Healthcare, Chalfant St. Giles, UK). The parameters affecting image acquisition were kept in the same condition for all lesions. Commonly used texture analysis methods were applied to characterize thyroid ultrasound images. Image features were classified according to the corresponding pathologic findings. To estimate their relevance and performance to classification, ReliefF was used as a feature selector. Among the various textural features, the sum average value derived from co-occurrence matrix can well reflect echogenicity and can effectively differentiate between follicles and fibrosis base thyroid nodules. Fibrosis shows lowest echogenicity and lowest difference sum average value. Enlarged follicles show highest echogenicity and difference sum average values. Papillary cancer or follicular tumors show the difference sum average values and echogenicity between. The rule of thumb for the echogenicity is that the more follicles are mixed in, the higher the echo of the follicular tumor and papillary cancer will be and vice versa for fibrosis mixed. Areas with intermediate and lower echo should address the possibility of follicular or papillary neoplasm mixed with either follicles or fibrosis. These areas provide more cellular information for ultrasound guided aspiration

Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

PubMed Central

Gier, Belinda; Butler, Peter C.; Lai, Chi K.; Kirakossian, David; DeNicola, Matthew M.

2012-01-01

Background: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Methods: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Results: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. Conclusions: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted. PMID:22031513

[Study on the relationship between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis].

PubMed

Wang, X Q; Wei, W; Wei, X; Xu, Y; Wang, H L; Xing, X J; Zhang, S

2018-03-23

Objective: To investigate the correlation between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis. Methods: We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC), pathologically confirmed after surgery in Tianjin Medical University Cancer Institute & Hospital. All patients were divided into central cervical lymph node metastasis group and non-metastasis group. No lateral cervical lymph node metastasis was found in preoperative ultrasonography and postoperative pathology. The characteristics of the ultrasound was observed and analyzed. Results: 297 out of 486 patients with papillary thyroid carcinomahad central metastasis, and the other 189 cases did not. Take pathology results as a standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of preoperative ultrasound diagnosis in PTC patients with central cervical lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively. Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm, located in the lower pole, ill-defined margin, hypoechogenicity, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma were significantly associated with central cervical lymph node metastasis (all P <0.05). Multivariate analysis showed that diameter>1 cm, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma became independent risk factors of central cervical neck lymph node metastasis (all P <0.05). Conclusions: Preoperative description of ultrasonographical features has important value to assess central cervical lymph node metastasis in patients with papillary thyroid carcinoma. More information could be provided for clinical treatment. When the papillary thyroid carcinoma presented as diameter>1 cm, micro-calcification, and capsule invasion more than 1/4 perimeter of, there will be a greater risk of central cervical lymph node metastasis, and we shall suggest prophylactic central lymph cervical node dissection.

Struma Ovarii with Papillary Thyroid Carcinoma

PubMed Central

Alvarez, Daniel M.; Lee, Victor; Bhatt, Shweta; Dogra, Vikram S.

2011-01-01

Struma ovarii is an uncommon condition, in which thyroid tissue is the predominant or exclusive element in an ovarian teratoma. Thyroid tissue may demonstrate the same spectrum of pathological features as in the normal thyroid including benign and malignant changes. We present a case of papillary thyroid carcinoma arising in a struma ovarii of the left ovary in a 21-year-old female. PMID:22315711

[Confronting the practice of surgery on differentiated thyroid cancer with current guidelines in Germany. A multicenter trial].

PubMed

Schwab, R; Wieler, H; Birtel, S; Ostwald-Lenz, E; Kaiser, K P; Becker, H P

2005-01-01

For the surgical therapy of differentiated thyroid cancer precise guidelines are applied by the German medical societies. In a retrospective multicenter study, we investigated the following issues: Are the current guidelines respected? Is there a difference concerning the surgical radicalism and the outcome? Does the perioperative morbidity increase with the higher radicalism of the procedure? Data gained from 102 patients from 17 regional referral hospitals who underwent surgery for thyroid cancer and a following rodioiodine treatment (mean follow up: 42.7 [24-79] months) were analyzed. At least 71 criterias were analyzed in a SPSS file. 46.1% of carcinomas were incidentally detected during goiter surgery. The thyroid cancer (papillary n = 78; follicular n = 24) occurred in 87% unilateral and in 13% bilateral. Papillary carcinomas < 1 cm were detected in 25 cases; in five of these cases (20%) contralateral carcinomas < 1 cm were found. There were significant differences concerning the surgical radicalism: a range from hemithyroidectomy to radical thyroidectomy with lateral neck dissection. Analysis of the histopathologic reports revealed that lymph node dissection was not performed according to guidelines in 55% of all patients. The perioperative morbidity was lower in departments with a high case load. The postoperative dysfunction of the recurrent laryngeal nerve (mean: 7.9% total / 4.9% nerves at risk) variated highly, depending on differences in radicalism and hospitals. Up to now these variations in surgical treatment have shown no differences in their outcome and survival rates, when followed by radioiodine therapy. Current surgical regimes did not follow the guidelines in more than 50% of all cases. This low acceptance has to be discussed. The actual discussion about principles of treatment regarding, the so-called papillary microcarcinomas (old term) has to be respected within the current guidelines.

A putative OTU domain-containing protein 1 deubiquitinating enzyme is differentially expressed in thyroid cancer and identifies less-aggressive tumours

PubMed Central

Carneiro, A P; Reis, C F; Morari, E C; Maia, Y C P; Nascimento, R; Bonatto, J M C; de Souza, M A; Goulart, L R; Ward, L S

2014-01-01

Background: This study aimed to identify novel biomarkers for thyroid carcinoma diagnosis and prognosis. Methods: We have constructed a human single-chain variable fragment (scFv) antibody library that was selected against tumour thyroid cells using the BRASIL method (biopanning and rapid analysis of selective interactive ligands) and phage display technology. Results: One highly reactive clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was confirmed by ELISA, which was further tested against a tissue microarray that comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18 normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Conclusions: The strategy of screening and identifying a cell-surface-binding antibody against thyroid tissues was highly effective and resulted in a useful biomarker that recognises malignancy among thyroid nodules and may help identify lower-risk cases that can benefit from less-aggressive management. PMID:24937664

Dual malignancy in adolescence: A rare case report of metachronous papillary carcinoma of thyroid following dysgerminoma of ovary

PubMed Central

Chakrabarti, Suvadip; Desai, Sanjay M.; Mehta, Dharmendra Y.; Somanath, Shreyas

2016-01-01

Dual malignancy is rare in adolescents. Dual malignancy with the second malignancy of thyroid is rare. No association has been reported between dysgerminoma of ovary and carcinoma thyroid in medical literature. Despite a thorough PubMed search (key words — Papillary carcinoma of thyroid, metachronous, dysgerminoma ovary), we were unable to find a previous reported case of metachronous papillary carcinoma of thyroid (PTC) following dysgerminoma of the ovary. After surgery, the patient is being regularly followed up for recurrence/development of new primary. We report this unusual and rare case in a 17-year-old female patient. PMID:27904567

[Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

PubMed

Schmid, K W

2015-11-01

The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma

PubMed Central

Miftari, Rame; Topçiu, Valdete; Nura, Adem; Haxhibeqiri, Valdete

2016-01-01

Purpose: Papillary carcinoma is the most frequent type of thyroid cancer and was considered the most benign of all thyroid carcinomas, with a low risk of distant metastases. However, there are some variants of papillary thyroid carcinoma that have affinity to spread in many organs, such as: lymph nodes, lungs and bones. Aim: The aim of this study was presentation of a case with papillary carcinoma of the thyroid gland, very persistent and resistant in treatment with I 131. Material and results: A man 56 years old were diagnosed with papillary carcinoma of thyroid gland. He underwent a surgical removal of the tumor and right lobe of thyroid gland. With histopathology examination, were confirmed follicular variant of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin was found elevated above upper measured limits (more than 500 ng/ml). Patient underwent surgical removal of 10 metastatic lymph nodes in the left side of the neck and has been treated with 145 mCi of radioiodine I 131. The examination after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and focally uptake of J 131 in the left lung. Patient was treated once again with 150 mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of radioiodine in the middle of the left collarbone. After a month, patient refers the enlargement of the lymph node in the right side of the neck. Currently patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We have identified first positive response in treatment. Enlarged lymph node in the neck was reduced and the patient began feeling better. Conclusion: This study suggests that some subtypes of papillary thyroid carcinoma appear to have more aggressive biological course. Subtypes of papillary thyroid carcinoma such as diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants, appears to have more aggressive biological course and need early detection and other kind of treatment. PMID:27703298

Optimizing treatment for children and adolescents with papillary thyroid carcinoma in post-Chernobyl exposed region: The roles of lymph node dissections in the central and lateral neck compartments.

PubMed

Fridman, Mikhail; Krasko, Olga; Lam, Alfred King-Yin

2018-06-01

There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991-2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg].

PubMed

Körber, C; Geling, M; Werner, E; Mörtl, M; Mäder, U; Reiners, C; Farahati, J

2000-01-01

In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

PubMed

Agrawal, Nidhi; Abbott, Collette E; Liu, Cheng; Kang, Stella; Tipton, Laura; Patel, Kepal; Persky, Mark; King, Lizabeth; Deng, Fang-Ming; Bannan, Michael; Ogilvie, Jennifer B; Heller, Keith; Hodak, Steven P

2017-04-02

Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

Mean platelet volume could be a possible biomarker for papillary thyroid carcinomas.

PubMed

Baldane, Suleyman; Ipekci, Suleyman H; Sozen, Mehmet; Kebapcilar, Levent

2015-01-01

Thyroid cancer is the most prevalent endocrine cancer and is evident in nearly 5% of thyroid nodules. The correlation between mean platelet volume (MPV) and many other cancer types has been investigated previously. However, the correlation between papillary thyroid carcinoma (PTC) and MPV has not yet been studied in detail. The aim of this study was to examine whether MPV would be a useful inflammatory marker to differentiate PTC patients from cases of benign goiter and healthy controls. Preoperative MPV levels in patients with PTC were found to be significantly higher when compared with benign goiter patients and healthy controls ((respectively, 8.05 femtoliter (fl), 7.57 fl, 7.36 fl, p=0.001). After surgical treatment of PTC patients, a significant decrease in MPV levels was seen (8.05 fl versus 7.60 fl, p=0.005). ROC analysis suggested 7.81 as the cut-off value for MPV (AUC=0.729, sensitivity 60%, specificity 80%). In conclusion, maybe changes in MPV levels can be used as an easily available biomarker for monitoring the risk of PTC in patients with thyroid nodules, enabling early diagnosis of PTC.

Changing trends of incidence and prognosis of thyroid carcinoma in lower Franconia, Germany, from 1981-1995.

PubMed

Farahati, Jamshid; Geling, Markus; Mäder, Uwe; Mörtl, Markus; Luster, Markus; Müller, Justus G; Flentje, Michael; Reiners, Christoph

2004-02-01

A population-based registry (PBR) in Lower Frankonia in southern Germany was conducted to evaluate the changes of incidence and prognosis of thyroid carcinoma (TC) in this area. The study comprised 476 patients with differentiated thyroid carcinoma (DTC) from Lower Franconia (1.3 x 10(6) inhabitants) registered between 1981 and 1995 at the Regional Tumor Center. The incidence was assessed with respect to gender, age, histology, tumor stage, lymph node involvement and distant metastases in 5-year intervals (1981-1985, 1986-1990, and 1991-1995). An increasing rate of papillary thyroid carcinoma PTC and a decreasing rate of follicular thyroid carcinoma (FTC) were observed over the three time periods (1981-1985, 1986-1990, and 1991-1995). The overall incidence revealed no significant change with time for both females from 3.22 to 3.25 and 3.73 and males (1.07 to 1.54 and 1.69) between the three time periods. There was a significant improvement in outcome of patients with DTC with respect to life expectancy. Iodine prophylaxis does influence the distribution of the histologic types of thyroid cancer and leads to an increase in the ratio of papillary versus follicular carcinoma. Our study supports the hypothesis that the benefits of correcting iodine deficency outweigh the risks of iodine supplementation.

On-line transmission electron microscopic image analysis of chromatin texture for differentiation of thyroid gland tumors.

PubMed

Kriete, A; Schäffer, R; Harms, H; Aus, H M

1987-06-01

Nuclei of the cells from the thyroid gland were analyzed in a transmission electron microscope by direct TV scanning and on-line image processing. The method uses the advantages of a visual-perception model to detect structures in noisy and low-contrast images. The features analyzed include area, a form factor and texture parameters from the second derivative stage. Three tumor-free thyroid tissues, three follicular adenomas, three follicular carcinomas and three papillary carcinomas were studied. The computer-aided cytophotometric method showed that the most significant differences were the statistics of the chromatin texture features of homogeneity and regularity. These findings document the possibility of an automated differentiation of tumors at the ultrastructural level.

Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples.

PubMed

Mazeh, Haggi; Mizrahi, Ido; Halle, David; Ilyayev, Nadia; Stojadinovic, Alexander; Trink, Barry; Mitrani-Rosenbaum, Stella; Roistacher, Marina; Ariel, Ilana; Eid, Ahmed; Freund, Herbert R; Nissan, Aviram

2011-02-01

Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms. The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection. Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively. miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Pheochromocytoma, papillary thyroid carcinoma.

PubMed

Nasser, Tariq; Qari, Faiza

2009-08-01

A 53-year-old woman presented with labile and difficult to control hypertension on 3 different anti-hypertensive medications. Abdominal computed tomography and ultrasonography of the thyroid gland showed a 1.8 cm thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum thyroid stimulating hormone and free thyroxine, calcitonin, carcinoembryonic antigen, intact parathyroid hormone, and calcium levels were within normal limits. A 24-hour urine metanephrine showed significant elevation in urine metanephrine of approximately 3 times the upper limit of normal, and the result of 131I-metaiodobenzyleguanjdjne (131I-MIBG) scintigraphy confirmed that the adrenal mass was pheochromocytoma. Right adrenalectomy and total thyroidectomy were performed. The final pathology was pheochromocytoma and papillary thyroid carcinoma. An analysis of c-ret porto-oncogene mutation yielded a negative result. This unusual association of 2 tumors represents a new entity.

Biochemical and molecular characterization of thyroid tissue by micro-Raman spectroscopy and gene expression analysis

NASA Astrophysics Data System (ADS)

Neto, Lázaro P. M.; Martin, Aírton A.; Soto, Claudio A. T.; Santos, André B. O.; Mello, Evandro S.; Pereira, Marina A.; Cernea, Cláudio R.; Brandão, Lenine G.; Canevari, Renata A.

2016-02-01

Thyroid carcinomas represent the main endocrine malignancy and their diagnosis may produce inconclusive results. Raman spectroscopy and gene expression analysis have shown excellent results on the differentiation of carcinomas. This study aimed to improve the discrimination between different thyroid pathologies combining of both analyses. A total of 35 thyroid tissues samples including normal tissue (n=10), goiter (n=10), papillary (n=10) and follicular carcinomas (n=5) were analyzed. Confocal Raman spectra was obtain by using a Rivers Diagnostic System, 785 nm laser excitation and CCD detector. The data was processed by the software Labspec5 and Origin 8.5 and analyzed by Minitab® program. The gene expression analysis was performed by qRT-PCR technique for TG, TPO, PDGFB, SERPINA1, LGALS3 and TFF3 genes and statistically analyzed by Mann-Whitney test. The confocal Raman spectroscopy allowed a maximum discrimination of 91.1% between normal and tumor tissues, 84.8% between benign and malignant pathologies and 84.6% among carcinomas analyzed. Significant differences was observed for TG, LGALS3, SERPINA1 and TFF3 genes between benign lesions and carcinomas, and SERPINA1 and TFF3 genes between papillary and follicular carcinomas. Principal component analysis was performed using PC1 and PC2 in the papillary carcinoma samples that showed over gene expression when compared with normal sample, where 90% of discrimination was observed at the Amide 1 (1655 cm-1), and at the tyrosine spectra region (856 cm-1). The discrimination of tissues thyroid carried out by confocal Raman spectroscopy and gene expression analysis indicate that these techniques are promising tools to be used in the diagnosis of thyroid lesions.

Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

PubMed

Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

2016-10-01

Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.

Thyroid cancer characteristics in the population surrounding Three Mile Island.

PubMed

Goyal, Neerav; Camacho, Fabian; Mangano, Joseph; Goldenberg, David

2012-06-01

To determine differences in disease characteristics between the thyroid cancer populations in the area around the Three Mile Island (TMI) nuclear power plant and the rest of the state of Pennsylvania. Retrospective cross-sectional study. Data from the Pennsylvania Cancer Registry from 1985 to 2008 were reviewed and information regarding age at diagnosis, sex, race, residential status, county of residence, thyroid pathology, thyroid surgery, and staging was recorded. Dauphin, Lancaster, and York counties were defined as the TMI area. Records of 26,357 thyroid cancer patients were reviewed, with 2,611 patients within the TMI area. A higher proportion of papillary thyroid cancer (P < .001) and lower proportion of follicular thyroid cancer (P < .001) were noted in the TMI area population. Thyroid cancer cases from the TMI area were found to be more likely to be diagnosed before the age of 65 years (P < .001), be Pennsylvania born (P < .001), be well differentiated (P < .001), be <10 mm in size (P < .001), and be localized without spread (P < .001). Although the TMI area shows a higher incidence of thyroid cancer as compared to the rest of the state, this was not statistically significant. The TMI population showed a higher proportion of papillary thyroid cancer and less aggressive pathology and earlier diagnosis compared to the rest of Pennsylvania. No statistically significant difference in thyroid cancer incidence was noted. Overall, the study does not show a clear link with more advanced thyroid cancer and proximity to the TMI nuclear reactors. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Autonomously hyperfunctioning cystic nodule harbouring thyroid carcinoma - Case report and literature review.

PubMed

Lima, Maria João; Soares, Virgínia; Koch, Pedro; Silva, Artur; Taveira-Gomes, António

2018-01-01

Hyperthyroidism is rarely associated with malignancy, but it cannot rule out thyroid cancer. Although there is published data describing this coexistence, thyroid carcinomas inside autonomously functioning nodules are uncommon. A 49-year-old woman presented with a cervical mass, unexplained weight loss and anxiousness, sweating and insomnia. On physical examination, she had a palpable left thyroid nodule. Thyroid function tests showed suppressed TSH (<0,1 uUI/mL), thyroxine 1,44 ng/dL (normal range 0,70-1,48) and triiodothyronine 4,33 pg/mL (normal range 1,71-3,71). Ultrasound imaging revealed a left lobe, 4 cm partial cystic nodule. 99mTC thyroid scintigraphy showed a hyperfunctioning nodule with suppression of the remainder parenchyma. Fine-needle aspiration cytology was nondiagnostic (cystic fluid). The patient was started on thiamazole 5 mg daily with subsequent normalization of thyroid function, but she developed cervical foreign body sensation and a left hemithyroidectomy was performed. Histology showed a 4 cm cystic nodule with a follicular variant papillary carcinoma and the patient underwent completion thyroidectomy, followed by radio-iodine ablation. Published literature showed an increased prevalence of autonomously functioning nodules, harbouring thyroid carcinomas in adults. Papillary carcinoma is the most frequently described but the follicular variant is rare. Although rare, thyroid cancer is not definitively excluded in hyperthyroid patients and it should always be considered as differential diagnosis. Copyright © 2018. Published by Elsevier Ltd.

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors.

PubMed

Dralle, Henning; Musholt, Thomas J; Schabram, Jochen; Steinmüller, Thomas; Frilling, Andreja; Simon, Dietmar; Goretzki, Peter E; Niederle, Bruno; Scheuba, Christian; Clerici, Thomas; Hermann, Michael; Kußmann, Jochen; Lorenz, Kerstin; Nies, Christoph; Schabram, Peter; Trupka, Arnold; Zielke, Andreas; Karges, Wolfram; Luster, Markus; Schmid, Kurt W; Vordermark, Dirk; Schmoll, Hans-Joachim; Mühlenberg, Reinhard; Schober, Otmar; Rimmele, Harald; Machens, Andreas

2013-03-01

Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.

Papillary Microcarcinoma of the Thyroid among Atomic Bomb Survivors: Tumor Characteristics and Radiation Risk

PubMed Central

Hayashi, Yuzo; Lagarde, Frederic; Tsuda, Nobuo; Funamoto, Sachiyo; Preston, Dale L.; Koyama, Kojiro; Mabuchi, Kiyohiko; Ron, Elaine; Kodama, Kazunori; Tokuoka, Shoji

2009-01-01

Background Radiation exposure is an established cause of clinical thyroid cancer, but little is known about radiation effects on papillary microcarcinoma (PMC) of the thyroid, a relatively common subclinical thyroid malignancy. Because the incidence of these small thyroid cancers has been increasing, it is important to better understand them and their relationship to radiation. Methods PMCs were identified in a subset of 7659 members of the Life Span Study of atomic-bomb survivors who had archived autopsy or surgical materials. We conducted a pathology review of these specimens and evaluated the histological features of the tumors and the association between PMCs and thyroid radiation dose. Results From 1958 to1995, 458 PMCs were detected among 313 study subjects. The majority of cancers exhibited pathologic features of papillary thyroid cancers. Overall, 81% of the PMCs were of the sclerosing variant and 91% were nonencapsulated, psammoma bodies occurred in 13% and calcification was observed in 23%. Over 95% had papillary or papillary-follicular architecture and most displayed nuclear overlap, clear nuclei, and nuclear grooves. Several of these features increased with increasing tumor size, but no association was found with radiation dose. A significant radiation-dose response was found for the prevalence of PMCs (estimated excess odds ratio/Gy=0.57; 95% CI: 0.01-1.55), with the excess risk observed primarily among females. Conclusion Low-to-moderate doses of ionizing radiation appears to increase the risk of thyroid PMCs, even when exposure occurs during adulthood. PMID:20120034

Papillary thyroid carcinoma in an autonomous hyperfunctioning thyroid nodule: case report and review of the literature.

PubMed

Tfayli, Hala M; Teot, Lisa A; Indyk, Justin A; Witchel, Selma Feldman

2010-09-01

Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy.

Papillary Thyroid Carcinoma in an Autonomous Hyperfunctioning Thyroid Nodule: Case Report and Review of the Literature

PubMed Central

Tfayli, Hala M.; Teot, Lisa A.; Indyk, Justin A.

2010-01-01

Background Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. Summary An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. Conclusions We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy. PMID:20718686

Papillary thyroid carcinoma formation in a thyroglossal cyst. A case report.

PubMed

Ali, Ma; Abussa, A; Hashmi, H

2007-09-01

Thyroglossal cyst rarely presents with carcinoma formation in the remnants of the thyroid gland. We report a 40 year old male with papillary thyroid carcinoma formation in a thyroglossal cyst. The patient underwent surgical intervention for the cyst. His pathology was positive for thyroid carcinoma and he underwent complete thyroidectomy with postoperative radioactive iodine treatment. His follow up revealed no evidence of recurrence.

Papillary Thyroid Cancer: The Good and Bad of the "Good Cancer".

PubMed

Randle, Reese W; Bushman, Norah M; Orne, Jason; Balentine, Courtney J; Wendt, Elizabeth; Saucke, Megan; Pitt, Susan C; Macdonald, Cameron L; Connor, Nadine P; Sippel, Rebecca S

2017-07-01

Papillary thyroid cancer is often described as the "good cancer" because of its treatability and relatively favorable survival rates. This study sought to characterize the thoughts of papillary thyroid cancer patients as they relate to having the "good cancer." This qualitative study included 31 papillary thyroid cancer patients enrolled in an ongoing randomized trial. Semi-structured interviews were conducted with participants at the preoperative visit and two weeks, six weeks, six months, and one year after thyroidectomy. Grounded theory was used, inductively coding the first 113 interview transcripts with NVivo 11. The concept of thyroid cancer as "good cancer" emerged unprompted from 94% (n = 29) of participants, mostly concentrated around the time of diagnosis. Patients encountered this perception from healthcare providers, Internet research, friends, and preconceived ideas about other cancers. While patients generally appreciated optimism, this perspective also generated negative feelings. It eased the diagnosis of cancer but created confusion when individual experiences varied from expectations. Despite initially feeling reassured, participants described feeling the "good cancer" characterization invalidated their fears of having cancer. Thyroid cancer patients expressed that they did not want to hear that it's "only thyroid cancer" and that it's "no big deal," because "cancer is cancer," and it is significant. Patients with papillary thyroid cancer commonly confront the perception that their malignancy is "good," but the favorable prognosis and treatability of the disease do not comprehensively represent their cancer fight. The "good cancer" perception is at the root of many mixed and confusing emotions. Clinicians emphasize optimistic outcomes, hoping to comfort, but they might inadvertently invalidate the impact thyroid cancer has on patients' lives.

Bilateral pheochromocytoma associated with paraganglioma and papillary thyroid carcinoma: report of an unusual case.

PubMed

Yang, Jeong Hoon; Bae, Sung Jin; Park, Sanghui; Park, Hyun-Kyung; Jung, Hye Seung; Chung, Jae Hoon; Min, Yong-Ki; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

2007-04-01

A 42-year old woman presented with headache, palpitation and facial flushing. Ultrasonograms and computed tomograms revealed tumors in both of the adrenal glands, anterior aspect of the inferior vena cava, and the right lobe of the thyroid gland. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum calcitonin, CEA, intact PTH and calcium levels were within normal limits. Markedly elevated levels of urinary normetanephrine and vanillylmandelic acid, and the result of 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy indicated that both adrenal masses were pheochromocytoma. Bilateral adrenalectomy, paracaval mass removal and total thyroidectomy together with central lymph node dissection were performed. The final pathological diagnosis was bilateral adrenal pheochromocytoma, paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia. Analysis of the RET proto-oncogene mutation, von Hippel Lindau mutation, succinate dehydrogenase subunit B mutation, and succinate dehydrogenase subunit D mutation yielded negative results. The relationship of these lesions could not be determined. This is the first report of a combination of bilateral pheochromocytoma, abdominal paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia without hyperparathyroidism.

Perigastric lymph node metastasis from papillary thyroid carcinoma in a patient with early gastric cancer: the first case report.

PubMed

Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok

2014-09-01

Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.

SPECT/CT demonstrating 131I retention in Warthin tumor on thyroid cancer survey scan.

PubMed

Zhang, Yuyang; Minoshima, Satoshi

2013-09-01

A 48-year-old male patient of papillary thyroid cancer, status post-thyroidectomy and node dissection, was referred to (131)I scan prior to radioiodine treatment. The images showed 1 additional focus of (131)I uptake in the right upper neck outside of the thyroid bed. SPECT/CT demonstrated 2 separate foci of radioiodine uptake in the right parotid gland, instead of neck lymph nodes. Diagnostic CT showed 2 corresponding soft tissue nodules in the right parotid gland which were confirmed latter by fine-needle aspiration to be Warthin tumors. This case illustrates a pivotal role of SPECT/CT in differential diagnosis of abnormal neck uptake on (131)I thyroid cancer scan.

Patterns of differentiated thyroid cancer in Baluchistan Province of Pakistan: some initial observations.

PubMed

Iftikhar, A; Naseeb, A Khush; Khwaja, A; Mati, H; Karim, K; Hameeda, N

2011-10-01

The incidence of thyroid cancer is increasing in several countries. The main objective of this retrospective study was to find and describe province-specific estimates of incidence in males and females by age groups for differentiated thyroid cancer (DTC). This study reports on 87 cases of DTC from Baluchistan province of Pakistan treated with post operative radioiodine at the Center for Nuclear Medicine and Radiotherapy (CENAR) Quetta from January 2003 to December 2009. The patient data has been collected from CENAR Quetta. Patients with DTC were confirmed by clinical examination, thyroid scintigraphy (Thyroid scan), blood tests (T3, T4, TSH) and histopathalogy tests and then treated with radioiodine. The Median age of the patients was 35.5 years (Range 12-70 years). The final histological diagnosis was papillary carcinoma in 71 (81.6 %) cases, follicular carcinoma in 6 (6.9%) cases while 10 (11.5%) cases presented with mixed papillary and follicular carcinoma. About 53 % cases were found in females with age 21-40 years. No strike predominance was observed in any age group for males. Four patients presented with recurrence while six patients showed metastasis in cervical lymph nodes. The small annual incidence did not follow any definite pattern. DTC has a small incidence in Baluchistan due to lack of education and health care facilities. The incidence of DTC is higher in females when compared with males as per this study. This preliminary study will provide an insight to incidence of DTC, its treatment facilities and future planning strategies in Baluchistan, Pakistan.

Hyperthyroidism, hyperfunctioning thyroid nodule, and thyroid cancer in a young female: a rare and unusual coexistence.

PubMed

Hernán-Martínez, José; Uzcategui, María; Corder, Eric; Castillo, Manuel; Sostre, Samuel; Alicea, Luz

2010-03-01

The prevalence of concomitant thyroid carcinoma with Grave's disease has been reported to range from 0 to 10%. Many controversies exist in the literature regarding the diagnostic workup and management in these types of patients. We are reporting a case of a 31 year old woman who had Graves' disease, a palpable thyroid nodule, and results from a thyroid scan revealed a "hot" nodule. Interestingly, an ultrasound guided FNA of the "hot" nodule showed papillary thyroid microcarcinoma. Finally, a total thyroidectomy showed multilobar tumor involvement. The diagnostic tools employed to establish the proper management strategy for this patient were based on data in the literature that is full of discrepancies. The fact that Grave's disease occurs concomitantly with thyroid cancer, specifically the papillary type, is an indisputably rare combination. One rare feature on our clinical case was the reported malignancy of a papillary carcinoma within a "hot" nodule which usually is much less that 1%. Many studies describe an increasing incidence of Grave's disease patients with concomitant papillary thyroid carcinoma. One possible explanation for these findings could be improvements in medical technology of screening tools. We propose that, thyroid ultrasonography should be integrated in the diagnostic workup in patients presenting with Graves' disease, especially in those presenting with palpable nodules. Fine needle biopsy should not be restricted to cold nodules.

Occupation and thyroid cancer: a population-based case-control study in Connecticut

PubMed Central

Ba, Yue; Huang, Huang; Lerro, Catherine C.; Li, Shuzhen; Zhao, Nan; Li, Anqi; Ma, Shuangge; Udelsman, Robert; Zhang, Yawei

2016-01-01

Objective The study aims to explore the associations between various occupations and thyroid cancer risk. Methods A population-based case-control study involving 462 histologically confirmed incident cases and 498 controls was conducted in Connecticut in 2010–2011. Results A significantly increased risk of thyroid cancer, particularly papillary microcarcinoma, was observed for those working as the healthcare practitioners and technical workers, health diagnosing and treating practitioners and registered nurses. Those working in building and grounds cleaning, maintenance occupations, pest control, retail sales, and customer service also had increased risk for papillary thyroid cancer. Subjects who worked as cooks, janitors, cleaners, and customer service representatives were at an increased risk of papillary thyroid cancer with tumor size >1 cm. Conclusions Certain occupations were associated with an increased risk of thyroid cancer, with some tumor size and subtype specificity. PMID:26949881

[Intracellular signaling mechanisms in thyroid cancer].

PubMed

Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

2016-01-01

Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Cytological features of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" and their correlation with tumor histology.

PubMed

Maletta, Francesca; Massa, Federica; Torregrossa, Liborio; Duregon, Eleonora; Casadei, Gian Piero; Basolo, Fulvio; Tallini, Giovanni; Volante, Marco; Nikiforov, Yuri E; Papotti, Mauro

2016-08-01

Among thyroid papillary carcinomas (PTCs), the follicular variant is the most common and includes encapsulated forms (EFVPTCs). Noninvasive EFVPTCs have very low risk of recurrence or other adverse events and have been recently proposed to be designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features or NIFTP, thus eliminating the term carcinoma. This proposal is expected to significantly impact the risk of malignancy associated with the currently used diagnostic categories of thyroid cytology. In this study, we analyzed the fine needle aspiration biopsy (FNAB) cytology features of 96 histologically proven NIFTPs and determined how the main nuclear features of NIFTP correlate between cytological and histological samples. Blind review of FNAB cytology from NIFTP nodules yielded the diagnosis of "follicular neoplasm" (Bethesda category IV) in 56% of cases, "suspicious for malignancy" (category V) in 27%, "atypia of undetermined significance/follicular lesion of undetermined significance" (category III) in 15%, and "malignant" (category VI) in 2%. We found good correlation (κ=0.62) of nuclear features between histological and cytological specimens. NIFTP nuclear features (size, irregularities of contours, and chromatin clearing) were significantly different from those of benign nodules but not from those of invasive EFVPTC. Our data indicate that most of the NIFTP nodules yield an indeterminate cytological diagnosis in FNAB cytology and nuclear features found in cytology samples are reproducibly identified in corresponding histology samples. Because of the overlapping nuclear features with invasive EFVPTC, NIFTP cannot be reliably diagnosed preoperatively but should be listed in differential diagnosis of all indeterminate categories of thyroid cytology. Copyright © 2016 Elsevier Inc. All rights reserved.

Significance of expression of suppressor of cytokine signaling proteins: Suppressor of cytokine signaling-1, suppressor of cytokine signaling-2, and suppressor of cytokine signaling-3 in papillary thyroid cancer.

PubMed

Kobawala, Toral Pundrik; Trivedi, Trupti I; Gajjar, Kinjal Kevin; Patel, Girish H; Ghosh, Nandita R

2017-01-01

Uncontrolled cytokine signal transduction largely associated with oncogene activation, can have disastrous biological consequences. The suppressor of cytokine signaling (SOCS) proteins represent one of the mechanisms by which this rampant signaling can be dissipated. Thus, we aimed to study the expression of SOCS-1, SOCS-2, and SOCS-3 in patients having benign thyroid disease and papillary thyroid cancer. SOCS protein expression was studied in 45 patients with benign thyroid disease and in 83 papillary thyroid cancer patients by immunohistochemistry and their association with clinicopathological characteristics and overall survival in cancer patients were analyzed using SPSS software. Expressions of SOCS proteins were significantly higher in papillary thyroid cancer than in patients having benign disease. SOCS-1 expression was predominantly higher in males (P = 0.004), unilateral tumors (P = 0.030), and noninflammatory conditions (P = 0.028). SOCS-1 expression was also able to predict poor overall survival in subgroup of papillary thyroid cancer patients having larger tumor size (P = 0.013) and advanced stage disease (P = 0.033). Expression of SOCS-2 significantly correlated with tumor size (P = 0.017), extrathyroidal extension (P = 0.000), residual disease (P = 0.043), and treatment (P = 0.007), while preponderance of SOCS-3 expression was observed in males (P = 0.030) and in patients having extrathyroidal extension (P = 0.011) and absence of metastasis (P = 0.032). Expression of the studied SOCS proteins may be a consequence of activation of Janus kinase-signal transducers and activators of transcription and other pathways supporting growth and survival of cancer cells that are sustained by several cytokines. Thus, SOCS-1, SOCS-2, and SOCS-3 proteins may directly or indirectly, have important roles in development and pathogenesis of papillary thyroid cancer.

Molecular changes in thyroid neoplasia.

PubMed

Jarzab, B; Włoch, J; Wiench, M

2001-01-01

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.

Novel insights in ultrasound evaluation of thyroid gland in children with papillary thyroid carcinoma.

PubMed

Janus, Dominika; Wojcik, Malgorzata; Kalicka-Kasperczyk, Anna; Drabik, Grazyna; Wyrobek, Lukasz; Wedrychowicz, Anna; Starzyk, Jerzy B

2017-10-01

The coincidence of autoimmune thyroiditis (AIT) in patients with papillary thyroid carcinoma (PTC) is ranging between 10 and 58% in the general population. In the present study retrospective ultrasound, clinical and autoimmune assessment of 24 patients diagnosed with papillary thyroid carcinoma between 2000-2016 was performed. The coexistence of PTC and AIT was found in 50% of patients with PTC. Patients were divided into two groups. PTC AIT (+) group involved 12 children at the mean age 14.9 years (range 11-20 years, 9 girls) and PTC AIT (-) 12 children at the mean age 12.9 years (range 7-18 years, 5 girls). Papillary thyroid microcarcinoma (PTMC) was diagnosed in 6 patients (in 5 with AIT). US characteristics of PTC was heterogenous: hypoechogenic with/without increased vascularisation, normoechogenic with halo, with/without microcalcifications. In 70% PTC AIT (+) and in all PTC AIT (-) patients ultrasound analysis revealed that the thyroid tissue of the whole gland was normoechogenic. Local metastases in lymph nodes were found in 40% of PTMC AIT (+). Lack of increased vascularization and microcalcifications and presence of``halo`in the nodule does not exclude malignancy. Due to the presence of lymph node involvement in PTMC in all children with PTC total thyroidectomy should be performed with lymph nodes verification.

Overview of Genetically Engineered Mouse Models of Papillary and Anaplastic Thyroid Cancers: Enabling Translational Biology for Patient Care Improvement.

PubMed

Charles, Roch-Philippe

2015-06-01

The prognosis from thyroid cancer subtypes in humans covers a spectrum from "cured at almost 90%" to "100% lethal." Invasive and poorly differentiated forms of thyroid cancer are among the most aggressive human cancers, and there are few effective therapeutic options. Genetically engineered mice, based on mutations observed in patients, can accurately recapitulate the human disease and its progression, providing invaluable tools for the preclinical evaluation of novel therapeutic approaches. This overview details models developed to date as well as their uses for identifying novel anticancer agents. Copyright © 2013 John Wiley & Sons, Inc. All rights reserved.

[A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].

PubMed

Tajima, Yusuke; Kumamoto, Kensuke; Yamamoto, Azusa; Chika, Noriyasu; Watanabe, Yuichiro; Matsuzawa, Takeaki; Ishibashi, Keiichiro; Mochiki, Erito; Iwama, Takeo; Akagi, Kiwamu; Ishida, Hideyuki

2015-11-01

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.

Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study

PubMed Central

Cash, Stephanie Whisnant; Ma, Huiyan; Horn-Ross, Pamela L.; Reynolds, Peggy; Canchola, Alison J.; Sullivan-Halley, Jane; Beresford, Shirley A.A.; Neuhouser, Marian L.; Vaughan, Thomas L.; Heagerty, Patrick J.; Bernstein, Leslie

2012-01-01

Purpose Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women. Methods 116,939 women in the California Teachers Study, aged 22 to 79 years with no history of thyroid cancer at cohort entry, were followed from 1995-1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort). Results Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR=0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI<25.0 kg/m2, trend p=0.03) than among overweight or obese women (trend p=0.35; homogeneity-of-trends p=0.03). A similar pattern of risk was observed for recent activity (BMI<25 kg/m2, trend p=0.11; BMI≥25 kg/m2, trend p=0.16; homogeneity-of-trends p=0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood). Conclusions Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women. PMID:23116823

Follicular thyroid cancer and Hürthle cell carcinoma: challenges in diagnosis, treatment, and clinical management.

PubMed

Grani, Giorgio; Lamartina, Livia; Durante, Cosimo; Filetti, Sebastiano; Cooper, David S

2018-06-01

Follicular thyroid cancer is the second most common differentiated thyroid cancer histological type and has been overshadowed by its more common counterpart-papillary thyroid cancer-despite its unique biological behaviour and less favourable outcomes. In this Review, we comprehensively review the literature on follicular thyroid cancer to provide an evidence-based guide to the management of these tumours, to highlight the lack of evidence behind guideline recommendations, and to identify changes and challenges over the past decades in diagnosis, prognosis, and treatment. We highlight that correct identification of cancer in indeterminate cytological samples is challenging and ultrasonographic features can be misleading. Despite certain unique aspects of follicular thyroid cancer presentation and prognosis, no specific recommendations exist for follicular thyroid cancer and Hürthle cell carcinoma in evidence-based guidelines. Efforts should be made to stimulate additional research in this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Primary carcinoma of the thyroid growing in thyroglossal duct cyst: presentation of two cases].

PubMed

Godlewska, Paulina; Bruszewska, Elzbieta; Kozłowicz-Gudzińska, Izabella; Prokurat, Andrzej I; Chrupek, Małgorzata; Zegadło-Mylik, Maria A; Kluge, Przemysław

2007-01-01

Thyroglossal duct remnants (TGDR), most often cysts, are the most common type of developmental abnormalities of the thyroid gland. In about 1 to 2% of TGDR neoplastic transformation occurs. Papillary carcinoma of the thyroid may be encountered in over 90% of such cases. Two cases of primary papillary carcinoma of the thyroid in TGDR in young girls are presented. The diagnostic and therapeutic problems are shared, and up-to-date management guidelines in similar cases are discussed.

The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma.

PubMed

Taşli, Funda; Ozkök, Güliz; Argon, Asuman; Ersöz, Didem; Yağci, Ayşe; Uslu, Adam; Erkan, Nazif; Salman, Tarik; Vardar, Enver

2014-12-01

Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p < 0.004). Multifocality was found to be at a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4 (+) plasma cells with adverse prognostic parameters such as multifocality and extrathyroidal extension is attention-grabbing. To render these possibilities evaluable, studies to be carried out with larger case series are needed. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis.

PubMed

Yi, Jin Wook; Park, Ji Yeon; Sung, Ji-Youn; Kwak, Sang Hyuk; Yu, Jihan; Chang, Ji Hyun; Kim, Jo-Heon; Ha, Sang Yun; Paik, Eun Kyung; Lee, Woo Seung; Kim, Su-Jin; Lee, Kyu Eun; Kim, Ju Han

2015-01-01

Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT. We prepared 402 ROS-related genes from three gene sets by genomic database searching. We also analyzed a public microarray data to validate our results. Thirty-three ROS related genes were up-regulated in PTC with HT, whereas there were only nine genes in PTC without HT (Chi-square p-value < 0.001). Mean log2 fold changes of up-regulated genes was 0.562 in HT group and 0.252 in PTC without HT group (t-test p-value = 0.001). In microarray data analysis, 12 of 32 ROS-related genes showed the same differential expression pattern with statistical significance. In gene ontology analysis, up-regulated ROS-related genes were related with ROS metabolism and apoptosis. Immune function-related and carcinogenesis-related gene sets were enriched only in HT group in Gene Set Enrichment Analysis. Our results suggested that ROS levels may be increased in PTC with HT. Increased levels of ROS may contribute to PTC development in patients with HT.

First description of papillary carcinoma in the thyroid gland of a red-eared slider (Trachemys scripta elegans ).

PubMed

Gál, János; Csikó, György; Pásztor, István; Bölcskey-Molnár, Antal; Albert, Mihály

2010-03-01

Postmortem examination of the carcass of an approximately 10-year-old male Red-eared slider ( Trachemys scripta elegans ) was performed. The thyroid gland was enlarged, showed follicular structure, and shifted the base of the heart caudally. Histology revealed differently shaped and sized follicles in the thyroid gland. Based on the macroscopic appearance and histopathological changes of the thyroid gland, the pathological process was established as a papillary-cystic carcinoma. Neoplasia of the endocrine organs, especially of the thyroid gland, is rare in reptiles. The current case seems to be the first report of thyroid carcinoma in a Red-eared slider.

[Autonomy and malignancy of thyroid glad tumors. A critical analysis of the literature on the existence of hyperfunctioning follicular and papillary thyroid gland carcinomas].

PubMed

Schröder, S; Marthaler, B

1996-09-01

Data in the literature communicated in 63 publications were evaluated in which scintigraphically warm or hot nodules were described as identical to a follicular or papillary carcinoma diagnosed based on histology of the resection specimen, thus suggesting autonomous hyperfunction of a malignant thyroid neoplasia. In the majority of cases, this assumption could not be accepted, or only within strict limits. In these patients, it appeared more likely that the carcinoma was located adjacent to or within a benign hyperfunctioning thyroid area or that large masses of a thyroid carcinoma had only simulated the picture of a hyperfunctioning nodule by suppression of endogenous TSH and thus of the residual parenchyma's function. In other cases, the diagnosis of a hyperfunctioning thyroid carcinoma had to be doubted or rejected owing to the lack of plausibility of the documented morphological findings. At the end of the literature survey, only 10 case descriptions unequivocally verified that, though very rarely, a papillary or follicular thyroid carcinoma may manifest itself as a solitary warm or hot thyroid nodule. Such a scintigraphical finding thus cannot be regarded as proof of benignancy of a given thyroid tumour.

Thyroid consequences of the Chernobyl nuclear accident.

PubMed

Pacini, F; Vorontsova, T; Molinaro, E; Shavrova, E; Agate, L; Kuchinskaya, E; Elisei, R; Demidchik, E P; Pinchera, A

1999-12-01

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid antibodies not associated with significant thyroid dysfunction. This finding is consistent with the short period of follow-up, but it is highly likely that these children will develop clinical thyroid autoimmune diseases in the future. Therefore, screening programmes for this at-risk population should focus, not only on the detection of thyroid nodules and cancer, but also on the development of thyroid autoimmune diseases.

Absence of the BRAF mutation in HBME1+ and CK19+ atypical cell clusters in Hashimoto thyroiditis: supportive evidence against preneoplastic change.

PubMed

Nasr, Michel R; Mukhopadhyay, Sanjay; Zhang, Shengle; Katzenstein, Anna-Luise A

2009-12-01

An association between Hashimoto thyroiditis and papillary thyroid carcinoma has been postulated for decades. We undertook this study to identify potential precursors of papillary thyroid carcinoma in Hashimoto thyroiditis using a combination of morphologic, immunohistochemical, and molecular techniques. For the study, samples from 59 cases of Hashimoto thyroiditis were stained with antibodies to HBME1 and cytokeratin (CK)19. Tiny HBME1+ and CK19+ atypical cell clusters were identified and analyzed for the BRAF mutation by the colorimetric Mutector assay and allele-specific polymerase chain reaction. HBME1+ and CK19+ atypical cell clusters were identified in 12 (20%) of 59 cases. The minute size (<1 mm) of the clusters and the incomplete nuclear changes precluded a diagnosis of papillary microcarcinoma. The atypical cell clusters from all 12 cases were negative for BRAF. The absence of the BRAF mutation in these atypical cell clusters suggests that they may not be preneoplastic. Caution should be exercised in interpreting positive HBME1 or CK19 staining in Hashimoto thyroiditis.

The value of quantitative shear wave elastography in differentiating the cervical lymph nodes in patients with thyroid nodules.

PubMed

You, Jun; Chen, Juan; Xiang, Feixiang; Song, Yue; Khamis, Simai; Lu, Chengfa; Lv, Qing; Zhang, Yanrong; Xie, Mingxing

2018-04-01

This study aimed at evaluating the diagnostic performance of quantitative shear wave elastography (SWE) in differentiating metastatic cervical lymph nodes from benign nodes in patients with thyroid nodules. One hundred and forty-one cervical lymph nodes from 39 patients with thyroid nodules that were diagnosed as papillary thyroid cancer had been imaged with SWE. The shear elasticity modulus, which indicates the stiffness of the lymph nodes, was measured in terms of maximum shear elasticity modulus (maxSM), minimum shear elasticity modulus (minSM), mean shear elasticity modulus (meanSM), and standard deviation (SD) of the shear elasticity modulus. All the patients underwent thyroid surgery, 50 of the suspicious lymph nodes were resected, and 91 lymph nodes were followed up for 6 months. The maxSM value, minSM value, meanSM value, and SD value of the metastatic lymph nodes were significantly higher than those of the benign nodes. The area under the curve of the maxSM value, minSM value, meanSM value, and SD value were 0.918, 0.606, 0.865, and 0.915, respectively. SWE can differentiate metastasis from benign cervical lymph nodes in patients with thyroid nodules, and the maxSM, meanSM, and SD may be valuable quantitative indicators for characterizing cervical lymph nodes.

Total thyroidectomy: safe and adequate treatment for papillary microcarcinoma of the thyroid gland.

PubMed

Uhliarova, B; Hajtman, A

2016-08-01

Total thyroidectomy: safe and adequate treatment for papillary microcarcinoma of the thyroid gland. The purpose of this study was to evaluate the incidence of and surgical approach in patients with papillary thyroid microcarcinoma (PTMC; thyroid cancer s10 mm) when these patients underwent surgery for presumed benign thyroid conditions. Between January 2006 and December 2013, 1460 adult patients underwent partial or total thyroidectomy for presumed benign thyroid conditions in the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, University Hospital in Martin, Slovakia. Of this population, 78 patients with incidental PTMC were further studied. Incidental papillary microcarcinoma was more frequently detected in patients with multinodular goitre (P = 0.034) or Hashimoto's thyroiditis (P=0.00 13) than in patients with other thyroid diseases. Multifocal and bilateral occurance of PTMC was identified in 26% and 18% of patients, respectively. The initial surgical procedure was -hemithyroidectomy in 23% of patients. All patients initially treated with hemithyroidectomy underwent completion thyroidectomy 10-32 days (median 19 ±7 days) after initial surgery. There were no significant differences in postoperative complications (recurrent laryngeal nerve injury, hypoparathyroidism) between patients with hemithyroidectomy and patients with total thyroidectomy at the first operation (P = 0.647). Completion surgery in patients with hemithyroidectomy was not followed by a significant increase in the incidence of complications (P=0.228). Incidental PTMC is more often detected in patients that undergo surgery for multinodular goitre and Hashimoto's thyroiditis. Total thyroidectomy constitutes a safe and adequate surgical approach in patients with PTMC.

IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

PubMed

Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

2012-01-01

Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

Pediatric Thyroid Cancer

MedlinePlus

... Marketplace Find an ENT Doctor Near You Pediatric Thyroid Cancer Pediatric Thyroid Cancer Patient Health Information News media ... and neck issues, should be consulted. Types of thyroid cancer in children: Papillary : This form of thyroid cancer ...

Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis.

PubMed

González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René

2015-01-01

Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis.

Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis

PubMed Central

González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René

2015-01-01

Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis. PMID:25821606

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

PubMed Central

McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

2014-01-01

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

Subcentimeter noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PubMed

Rosario, Pedro Weslley

2018-05-23

Recently, it was proposed that the noninvasive encapsulated follicular variant of papillary thyroid carcinoma (noninvasive E-FVPTC) start to be called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). 1 As the original cohort of 109 patients with NIFTP studied by the consensus conference included only tumors which were equal or more than 1 cm in size, the consensus diagnostic criteria of NIFTP did not explicitly address subcentimeter lesions. 1,2 In fact, in a recent review published in this journal, Hung & Barletta recognize that there are a few published subcentimetre NIFTP in the literature. 3 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Thyroid Fine-Needle Aspiration Cytology:Causes of false-positive results.

PubMed

Malheiros, Daniela C; Canberk, Sule; Poller, David N; Schmitt, Fernando

2018-05-16

In this paper, we aim to focus on false positive results in the evaluation of thyroid aspirations, covering cystic, inflammatory, follicular and oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid. The recently described entity, "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP), is also discussed detailing the impact of its introduction on the sensitivity and specificity of thyroid FNA, as well as the use of molecular tests for diagnostics. Medicolegal issues in relation to current practice in English law are also described. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Hormonally Active Malignant Struma Ovarii

PubMed Central

Lara, Carolina; Salame, Latife; Padilla-Longoria, Rafael

2016-01-01

Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii. PMID:27882257

Diagnostic value of TROP-2 expression in papillary thyroid carcinoma and comparison with HBME-1, galectin-3 and cytokeratin 19.

PubMed

Murtezaoglu, Afsin Rahman; Gucer, Hasan

In this study, we compared the diagnostic value of TROP-2 expression in distinguishing between benign and malignant thyroid lesions to those of HBME-1, CK19 and galectin-3. We selected 102 cases from our archive including 20 normal thyroid tissues, 23 follicular nodular diseases, 17 follicular adenomas, 20 follicular variant papillary carcinomas and 22 classical variant papillary carcinomas. Tissue microarrays constructed from these cases were immunohistochemically analyzed with HBME-1, CK19, galectin-3 and TROP-2. Respectively 73.8%, 83.3%, 69% and 50% of all papillary carcinomas were positive with HBME-1, CK19, galectin-3 and TROP-2. CK19 was positive respectively by 100%, 43.5% and 35.3% in cases of normal thyroid, follicular nodular diseases and follicular adenoma, while the other markers were negative. In distinguishing benign and malignant lesions, which constitutes this study, HBME-1, CK19, galectin-3 and TROP-2 were statistically significant (p < 0.001). In distinguishing cases of follicular variant papillary carcinoma from follicular nodular diseases and follicular adenoma, HBME-1 and galectin-3 were statistically significant (p < 0.001). Consequently, in this study, we found that all immunohistochemical markers were effective in distinguishing benign and malignant thyroid lesions. In determining malignancy, HBME-1 had the highest diagnostic accuracy, while CK19 was the most sensitive marker. The sensitivity increased when the markers were used together.

Correlation of cytoplasmic beta-catenin and cyclin D1 overexpression during thyroid carcinogenesis around Semipalatinsk nuclear test site.

PubMed

Meirmanov, Serik; Nakashima, Masahiro; Kondo, Hisayoshi; Matsufuji, Reiko; Takamura, Noboru; Ishigaki, Katsu; Ito, Masahiro; Prouglo, Yuri; Yamashita, Shunichi; Sekine, Ichiro

2003-06-01

The Semipalatinsk nuclear test site (SNTS), the Republic of Kazakhstan, has been contaminated by radioactive fallout. The alteration of oncogenic molecules in thyroid cancer around the SNTS was considered worthy of analysis because it presented the potential to elucidate the relationship between radiation exposure and thyroid cancer. This study aimed to analyze both beta-catenin and cyclin D1 expressions in thyroid carcinomas around the SNTS. We examined nine cases of chronic thyroiditis, eight cases of follicular adenomas, and 23 cases of papillary carcinomas. Immunohistochemically, all carcinomas displayed a strong cytosolic beta-catenin expression, while both chronic thyroiditis and follicular adenomas showed a significantly lower cytoplasmic beta-catenin (22.2% and 37.5%, respectively). No cyclin D1 immunoreactivity was evident in chronic thyroiditis. In contrast, 62.5% of follicular adenomas and 87.0% of papillary carcinoma showed cyclin D1 overexpression. Additionally, a strong correlation between cytoplasmic beta-catenin and cyclin D1 expression was suggested in thyroid tumors. This study revealed a higher prevalence of both aberrant beta-catenin expression and cyclin D1 overexpression in papillary thyroid cancers around the SNTS than sporadic cases. The analysis of the alteration of the Wnt signaling-related molecules in thyroid cancer around the SNTS may be important to gain an insight into radiation-induced thyroid tumorigenesis.

Unusual thyroid carcinoma with excessive extracellular hyaline globules: a case of "hyalinizing papillary carcinoma".

PubMed

Kondo, Tetsuo; Nakazawa, Tadao; Terada, Nobuo; Nakazawa, Kumiko; Kawasaki, Tomonori; Mochizuki, Kunio; Yamane, Tetsu; Ohno, Shinichi; Katoh, Ryohei

2012-06-01

We present an unusual case of papillary thyroid carcinoma in a 47-year-old Japanese woman. The tumor, 0.8 cm in diameter, was located in the upper left lobe of the thyroid. Histologically, we observed a microfollicular-like and trabecular arrangement of the tumor cells with marked hyalinized stroma and hyaline globules. Immunohistochemically, tumor cells were positive for thyroglobulin and thyroid transcription factor 1. Hyaline stroma and globular bodies were immunopositive for laminin and type IV collagen. MIB-1 index was approximately 1% without membranous immunoreactivity. Under the electron microscope, hyaline stroma and globules showed electron-dense, complex meshwork structures composed of granular and fibrous elements similar to the structure of the lamina densa. Genetic analysis demonstrated a BRAF(V600E) mutation. Based on these findings, we diagnosed the present tumor as a rare morphological variation of papillary thyroid carcinoma with excessive hyaline globules consisting of basal membrane materials. Copyright © 2012 Elsevier Inc. All rights reserved.

Synchronous papillary carcinoma in thyroglossal duct cyst and thyroid gland: case report and review of literature.

PubMed

Cherian, Mathew Pynumootil; Nair, Balakrishnan; Thomas, Shaji; Somanathan, Thara; Sebastian, Paul

2009-10-01

We report a rare case of synchronous occurrence of thyroglossal duct cyst carcinoma and thyroid carcinoma and discuss its management in detail. A 59-year-old woman was clinically diagnosed to have a thyroglossal duct cyst and a solitary nodule. Fine-needle aspiration cytology revealed a papillary carcinoma in the thyroglossal duct cyst and a colloid in the thyroid nodule. Sistrunk's procedure along with a total thyroidectomy was performed followed by postoperative radioiodine ablation. Histopathologic examination revealed thyroglossal duct cyst carcinoma and bilateral foci of papillary carcinoma in the thyroid gland. She has remained free of disease on follow-up. Most cancers arising in thyroglossal duct cysts are of low risk, and Sistrunk's procedure is an adequate treatment for such cancers. However, for synchronously occurring cancers of the thyroglossal duct cyst and thyroid gland, or high-risk thyroglossal duct cyst cancers, more aggressive treatment comprising total thyroidectomy, Sistrunk's procedure, and radioiodine therapy is indicated. (c) 2009 Wiley Periodicals, Inc.

Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

PubMed

Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter

2016-01-01

The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.

ROLE OF MOLECULAR MARKERS IN THYROID NODULE MANAGEMENT: THEN AND NOW.

PubMed

Nikiforov, Yuri E

2017-08-01

To describe the evolution and clinical utility of molecular testing for thyroid nodules and cancer achieved over the last 2 decades. Scientific reports on thyroid cancer genetics and molecular diagnostics in thyroid nodules. Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded, such that most thyroid cancers now have known gene driver events. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer and for the introduction of new entities such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The progress with molecular tests for thyroid nodules started in the 1990s from demonstrating feasibility of detecting various molecular alterations in fine-needle aspiration (FNA) material collected from thyroid nodules. It was followed by the introduction of the first single-gene mutational markers, such as BRAF, and a small mutational panel into clinical practice in the mid 2000s. Currently, several more advanced molecular tests are available for clinical use. They are based on multiple molecular markers and have increasing impact on the clinical management of patients with thyroid nodules. The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA samples to inform more individualized management of these patients. FNA = fine-needle aspiration miRNA = micro RNA NGS = next-generation sequencing NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features NPV = negative predictive value PPV = positive predictive value PTC = papillary thyroid carcinoma RAI = radioactive iodine.

The reliability of fine-needle aspiration biopsy in terms of malignancy in patients with Hashimoto thyroiditis.

PubMed

Kapan, Murat; Onder, Akin; Girgin, Sadullah; Ulger, Burak Veli; Firat, Ugur; Uslukaya, Omer; Oguz, Abdullah

2015-02-01

The aim of this study was to analyze the presence of malignancy in patients with Hashimoto's thyroiditis and to investigate the reliability of preoperative fine-needle aspiration biopsy (FNAB). The retrospective study included 44 patients who were operated on for nodular goiter between December 2010 and October 2011. The patients underwent thyroidectomy following a cytologic analysis plus FNAB. Hashimoto's thyroiditis was confirmed on histopathology in all patients. FNAB results were defined as benign in 14 (31.8%), suspicion for malignancy in 17 (38.6%), malignant in 9 (20.5%), and inadequate in 4 (9.1%). Following the thyroidectomy, presence of papillary thyroid carcinoma and follicular variant of papillary thyroid carcinoma were detected in 10 patients (22.7%) and 1 (2.3%) patient, respectively. The FNAB results were interpreted in terms of malignancy, which revealed the sensitivity as 80%; specificity, 40%; false positives, 69.2%; false negatives, 14.3%; positive predictive value, 31.8%; negative predictive value, 85.7%; and diagnostic accuracy, 50%. The coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma is quite common. The FNAB results for such cases are hard to evaluate, and they are likely to increase the number of false positives.

[Solitary hyperfunctioning thyroid gland carcinomas].

PubMed

Zivaljevic, V; Zivic, R; Diklic, A; Krgovic, K; Kalezic, N; Vekic, B; Stevanovic, D; Paunovic, I

2011-08-01

Thyroid gland carcinomas usually appear as afunctional and hypofunctional lesions on thyroid scintigrams, but some rare cases of thyroid carcinoma with scintigraphic hyperfunctional lesions have also been reported. The aim of our retrospective study was to elucidate the frequency of carcinomas in patients operated for solitary hyperfunctional thyroid nodules and to represent their demographic and clinical features. During one decade (1997/2006), 308 patients were operated for solitary hyperfunctional thyroid nodules in the Centre for Endocrine Surgery in Belgrade. Malignancy was revealed in 9 cases (about 3 %) by histopathological examination. In 6 cases papillary microcarcinomas were found adjacent to dominant hyperfunctional adenomas, while in 3 cases (about 1 %) real hyperfunctional carcinomas were confirmed. Follicular carcinoma was diagnosed in 2 cases and papillary carcinoma in one. All 3 patients were preoperatively hyperthyroid. In both patients with follicular carcinoma we performed lobectomies. In the third case we carried out a total thyroidectomy considering the intraoperative frozen section finding of a papillary carcinoma. According to our results the frequency of solitary hyperfunctioning thyroid carcinomas is about 1 %, so that the possibility that a hyperfunctional nodule is malignant should be considered in the treatment of such lesions. © Georg Thieme Verlag KG Stuttgart ˙ New York.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

PubMed

Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario

2014-01-01

The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Encapsulated papillary oncocytic neoplasms of the thyroid: morphologic, immunohistochemical, and molecular analysis of 18 cases.

PubMed

Woodford, Randall Lyndon; Nikiforov, Yuri E; Hunt, Jennifer L; Bellizzi, Andrew M; Zhang, Xiaotang; Mills, Stacey E; Stelow, Edward B

2010-11-01

Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms.

Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT.

PubMed

Thanseer, N T K; Bhadada, Sanjay Kumar; Sood, Ashwani; Parihar, Ashwin Singh; Dahiya, Divya; Singh, Priyanka; Basher, Rajender Kumar; Das, Ashim; Mittal, Bhagwant R

2018-04-01

18 F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for the preoperative imaging of abnormal parathyroid tissue(s) helping to localize eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH PET/CT may show incidental uptake in various thyroid lesions necessitating further evaluation, whereas the role of 18 F-fluorodeoxyglucose (FDG) PET/CT in the detection of incidental thyroid nodules is well documented. The case of a middle-aged woman with dual pathology of parathyroid adenoma and papillary thyroid cancer detected on FCH and FDG PET/CT is presented.

Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse.

PubMed

Charles, Roch-Philippe; Iezza, Gioia; Amendola, Elena; Dankort, David; McMahon, Martin

2011-06-01

Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC). To model PTC, we bred mice with adult-onset, thyrocyte-specific expression of BRAF(V600E). One month following BRAF(V600E) expression, mice displayed increased thyroid size, widespread alterations in thyroid architecture, and dramatic hypothyroidism. Over 1 year, without any deliberate manipulation of tumor suppressor genes, all mice developed PTC displaying nuclear atypia and marker expression characteristic of the human disease. Pharmacologic inhibition of MEK1/2 led to decreased thyroid size, restoration of thyroid form and function, and inhibition of tumorigenesis. Mice with BRAF(V600E)-induced PTC will provide an excellent system to study thyroid tumor initiation and progression and the evaluation of inhibitors of oncogenic BRAF signaling.

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

PubMed Central

Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

2014-01-01

Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system. PMID:24295207

Not all occult papillary carcinomas are minimal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allo, M.D.; Christianson, W.; Koivunen, D.

1988-12-01

Occult papillary carcinomas are characterized as small papillary tumors of less than 1.5 cm in maximum diameter, with or without bulky metastatic deposits in cervical nodes. The primary lesion is usually not palpable, and although the clinical behavior usually follows a benign course, tumors with unfavorable histologic features (invasiveness, multifocality) or extrathyroidal disease or a combination of both may not do so. In this report six cases are presented to illustrate this entity. No patient had a history of irradiation to the head or neck. All had primary lesions smaller than 1.5 cm. None had a palpable nodule or abnormalmore » thyroid scan results, and the diagnosis of thyroid cancer was based on cervical lymph node or lung biopsy specimens, which revealed papillary thyroid cancer. All of the patients underwent total or near-total thyroidectomies and were found to have small, invasive papillary lesions with additional metastases to cervical nodes noted at the time of thyroidectomy. Adjunctive treatment consisted of a 5 mCi iodine-131 scan, ablative iodine-131 therapy, and suppression with L-thyroxine. Although distant metastasis to lung or other organs is uncommon and the mortality rate is low (as in larger papillary cancers), these invasive lesions--despite their small size--have a high propensity for recurrence and should be considered to behave more like encapsulated papillary tumors with extrathyroidal extension than like their small, unencapsulated intrathyroidal counterparts.« less

(99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

PubMed

Basu, Sandip; Joshi, Amit

2014-07-01

The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto's Thyroiditis.

PubMed

Yeo, Min-Kyung; Bae, Ja Seong; Lee, Sohee; Kim, Min-Hee; Lim, Dong-Jun; Lee, Youn Soo; Jung, Chan Kwon

2015-01-01

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto's thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto's thyroiditis.

The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto's Thyroiditis

PubMed Central

Yeo, Min-kyung; Bae, Ja Seong; Lim, Dong-Jun; Lee, Youn Soo

2015-01-01

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto's thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto's thyroiditis. PMID:25983754

[Papillary thyroid carcinoma in a child with congenital dyshormonogenetic hypothyroidism. Case report].

PubMed

Orellana, María José; Fulle, Angelo; Carrillo, Diego; Escobar, Lucía; Ebensperger, Alicia; Martínez, Raúl; Rumié Carmi, Hana

Papillary thyroid carcinoma (PTC) is a rare childhood disease. The development of PTC in dyshormonogenetic congenital hypothyroidism (CH) is infrequent, with very few case reports in literature. To report a case of PTC in a boy with dyshormonogenetic CH without goitre and exposed to ionising radiation. To evaluate relationships between these factors and development of PTC. We present a boy with dyshormonogenetic CH since birth. Early hormonal substitution was initiated, with subsequent normal levels of thyrotropin and thyroid hormones. He has also congenital cardiomyopathy, exposed to interventional treatment with 10 heart catheterisations, and approximately 26 chest X-rays at paediatric doses. A thyroid nodule was found in thyroid echography at the age of 6 years old. Fine needle aspiration biopsy confirmed high probability of thyroid carcinoma (Bethesda 5). The pre-surgical thorax and cerebral scan showed no evidence of metastasis. The patient underwent total thyroidectomy. Pathological examination revealed a 0.5cm papillary thyroid micro-carcinoma in the right lobe, with no evidence of dissemination. Genetic mutations and radiation exposure may play an important role in the development of PTC. There may be common pathways between dyshormonogenetic CH and thyroid carcinoma that need further investigation. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Hormonal and reproductive risk factors of papillary thyroid cancer: A population-based case-control study in France.

PubMed

Cordina-Duverger, Emilie; Leux, Christophe; Neri, Monica; Tcheandjieu, Catherine; Guizard, Anne-Valérie; Schvartz, Claire; Truong, Thérèse; Guénel, Pascal

2017-06-01

The three times higher incidence of thyroid cancer in women compared to men points to a role of female sex hormones in its etiology. However the effects of these factors are poorly understood. We analyzed the association between thyroid cancer and hormonal and reproductive factors among women enrolled in CATHY, a population-based case-control study conducted in France. The study included 430 cases of papillary thyroid cancer and 505 controls frequency-matched on age and area of residence. The odds ratios for thyroid cancer increased with age at menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared to premenopausal women, particularly if menopause followed an ovariectomy, and for women with age at menopause <55years. In addition, use of oral contraceptives and menopausal hormone therapy reduced the association with thyroid cancer by about one third, and breastfeeding by 27%. Overall, these findings provide evidence that the risk of thyroid cancer increases with later age at menarche and after menopause, and decreases with use of oral contraceptives and menopausal hormone therapy. These findings confirm an implication of hormonal factors in papillary thyroid cancer risk, whose mechanisms need to be elucidated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

PubMed Central

Yeh, Michael W; Rougier, Jean-Philippe; Park, Jin-Woo; Duh, Quan-Yang; Wong, Mariwil; Werb, Zena; Clark, Orlo H

2008-01-01

Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P<0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64– to 8.89-fold, P<0.0001) and membrane type-1 MMP (MT1-MMP, 1.97- to 2.67-fold, P<0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas. PMID:17158762

[Usefulness of galectin-3 expression in the clinical behavior of differentiated thyroid carcinoma].

PubMed

López Mondéjar, Pedro; Picó, Antonio; Seguí, Javier; López Maciá, Alicia

2008-02-16

Our objective was to quantify the galectin-3 (gal-3) expression in differentiated thyroid carcinoma and study its relation with the clinical behavior of these tumors. We investigated the immunohistochemical reaction of gal-3 in patients with papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) and performed a retrospective study in order to find correlations with clinical features. Gal-3 expression was studied in 53 differentiated tyroid carcinomas (42 PTC and 11 FTC), and was related with clinical features: metastases, extrathyroid invasion and initial stage in the diagnosis and persistence disease and relapses in the follow up. Gal-3 expression positivity in PTC had a median of 60% (percentil 25 [p25], 17.5%; percentil 75 [p75], 100%), and was significantly higher (p < 0.0001) than in FTC (median, 0%; p25, 0%; p75, 15%). In PTC, gal-3 expression was significantly higher in advanced stages at the time of initial diagnosis (p = 0.014), persistent disease (p = 0.012) and relapses (p = 0.012) during the follow up. We did not find any significant association between gal-3 expression and clinical features of FTC. Gal-3 is a negative prognosis marker in PTC but not in FTC.

Thyroid Cancer—Patient Version

Cancer.gov

Thyroid cancer can be of four main types. Anaplastic thyroid cancer is hard to cure with current treatments, whereas papillary (the most common), follicular, and medullary thyroid cancer can usually be cured. Start here to find information on thyroid cancer treatment, screening, research, and statistics.

Up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis in human papillary thyroid cancer cells.

PubMed

Mo, Xiao-Mei; Li, Li; Zhu, Ping; Dai, Yu-Jie; Zhao, Ting-Ting; Liao, Ling-Yao; Chen, George G; Liu, Zhi-Min

2016-08-15

17β-estradiol (E2) has been suggested to play a role in the development and progression of papillary thyroid cancer. Heat shock protein 27 (Hsp27) is a member of the Hsp family that is responsible for cell survival under stressful conditions. Previous studies have shown that the 5'-promoter region of Hsp27 gene contains a specificity protein-1 (Spl) and estrogen response element half-site (ERE-half), which contributes to Hsp27 induction by E2 in breast cancer cells. However, it is unclear whether Hsp27 can be up-regulated by E2 and which estrogen receptor (ER) isoform and tethered transcription factor are involved in this regulation in papillary thyroid cancer cells. In the present study, we demonstrated that Hsp27 can be effectively up-regulated by E2 at mRNA and protein levels in human K1 and BCPAP papillary thyroid cancer cells which have more than two times higher level of ERα than that of ERβ. The up-regulation of Hsp27 by E2 is mediated by ERα/Sp1 and ERβ has repressive effect on this ERα/Sp1-mediated up-regulation of Hsp27. Moreover, we showed that the up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis through interaction with procaspase-3. Targeting this pathway may be a potential strategy for therapy of papillary thyroid cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rising incidence of thyroid cancer in Singapore not solely due to micropapillary subtype.

PubMed

Shulin, J H; Aizhen, J; Kuo, S M; Tan, W B; Ngiam, K Y; Parameswaran, R

2018-04-01

Introduction The annual incidence of thyroid cancer is known to vary with geographic area, age and gender. The increasing incidence of thyroid cancer has been attributed to increase in detection of micropapillary subtype, among other factors. The aim of the study was to investigate time trends in the incidence of thyroid cancer in Singapore, an iodine-sufficient area. Materials and methods Data retrieved from the Singapore National Cancer Registry on all thyroid cancers that were diagnosed from 1974 to 2013 were reviewed. We studied the time trends of thyroid cancer based on gender, race, pathology and treatment modalities where available. Results The age-standardised incidence rate of thyroid cancer increased to 5.6/100,000 in 2013 from 2.5/100,000 in 1974. Thyroid cancer appeared to be more common in women, with a higher incidence in Chinese and Malays compared with Indians. Papillary carcinoma is the most common subtype. The percentage of papillary microcarcinoma has remained relatively stable at around 38% of all papillary cancers between 2007 and 2013. Although the incidence of thyroid cancer has increased since 1974, the mortality rate has remained stable. Conclusion This trend of increase in incidence of thyroid cancer in Singapore compares with other published series; however, the rise seen was not solely due to micropapillary type. Thyroid cancer was also more common in Chinese and Malays compared with Indians for reasons that needs to be studied further.

Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.

PubMed

Wreesmann, Volkert B; Ghossein, Ronald A; Hezel, Michael; Banerjee, Debenranrath; Shaha, Ashok R; Tuttle, R Michael; Shah, Jatin P; Rao, Pulivarthi H; Singh, Bhuvanesh

2004-08-01

The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms. Copyright 2004 Wiley-Liss, Inc.

Cytological Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma before and after the Bethesda System for Reporting Thyroid Cytopathology.

PubMed

Fazeli, Roghayeh; VandenBussche, Christopher J; Bishop, Justin A; Ali, Syed Z

2016-01-01

The follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common subtype of papillary carcinoma after the classical variant. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been introduced to standardize the practice of thyroid fine needle aspiration (FNA) reporting. We evaluated the impact of TBSRTC on the FNA interpretation of histologically proven FVPTCs. Cytology reports of 455 histologically proven FVPTCs were reviewed. The rate of each TBSRTC category was compared between pre- and post-TBSRTC eras. The distribution of FNA diagnoses for pre-TBSRTC cases included suspicious for follicular neoplasm (SFN; n = 51, 28.7%), papillary thyroid carcinoma (PTC; n = 47, 26.4%), suspicious for malignancy (SFM; n = 32, 18%), atypia of undetermined significance (AUS; n = 23, 13%), benign (n = 18, 10.1%), and nondiagnostic (ND; n = 7, 4%). Post-TBSRTC diagnoses were: AUS (n = 68, 24.6%), PTC (n = 64, 23.1%), SFM (n = 50, 18%), SFN and benign (n = 42, 15.2%) and ND (n = 11, 4%). SFN rate decreased significantly from 28.7 to 15.2% (p = 0.001) and AUS increased from 12.9 to 24.5% (p = 0.003). Following implementation of TBSRTC, the frequency of AUS diagnoses on FNA prior to surgical resection increased. Given that the rate of FVPTC diagnoses on thyroidectomy increased over the same period, this suggests that the use of AUS has resulted in greater surgical resection of FVPTC. © 2016 S. Karger AG, Basel.

TSH Compensates Thyroid-Specific IGF-I Receptor Knockout and Causes Papillary Thyroid Hyperplasia

PubMed Central

Müller, Kathrin; Führer, Dagmar; Mittag, Jens; Klöting, Nora; Blüher, Matthias; Weiss, Roy E.; Many, Marie-Christine; Schmid, Kurt Werner

2011-01-01

Although TSH stimulates all aspects of thyroid physiology IGF-I signaling through a tyrosine kinase-containing transmembrane receptor exhibits a permissive impact on TSH action. To better understand the importance of the IGF-I receptor in the thyroid in vivo, we inactivated the Igf1r with a Tg promoter-driven Cre-lox system in mice. We studied male and female mice with thyroidal wild-type, Igf1r+/−, and Igf1r−/− genotypes. Targeted Igf1r inactivation did transiently reduce thyroid hormone levels and significantly increased TSH levels in both heterozygous and homozygous mice without affecting thyroid weight. Histological analysis of thyroid tissue with Igf1r inactivation revealed hyperplasia and heterogeneous follicle structure. From 4 months of age, we detected papillary thyroid architecture in heterozygous and homozygous mice. We also noted increased body weight of male mice with a homozygous thyroidal null mutation in the Igf1r locus, compared with wild-type mice, respectively. A decrease of mRNA and protein for thyroid peroxidase and increased mRNA and protein for IGF-II receptor but no significant mRNA changes for the insulin receptor, the TSH receptor, and the sodium-iodide-symporter in both Igf1r+/− and Igf1r−/− mice were detected. Our results suggest that the strong increase of TSH benefits papillary thyroid hyperplasia and completely compensates the loss of IGF-I receptor signaling at the level of thyroid hormones without significant increase in thyroid weight. This could indicate that the IGF-I receptor signaling is less essential for thyroid hormone synthesis but maintains homeostasis and normal thyroid morphogenesis. PMID:21980075

Thyroid abnormalities after therapeutic external radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, S.L.; McDougall, I.R.; Constine, L.S.

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benignmore » adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.« less

A rare cause of hyperthyroidism: functioning thyroid metastases.

PubMed

Gardner, Daphne; Ho, Su Chin

2014-10-09

Hyperthyroidism is a common medical problem that is readily treated with antithyroid medications. However, attributing the correct aetiology of hyperthyroidism alters management and outcome. We present a case of a 66-year-old woman with a seemingly common problem of hyperthyroidism associated with a goitre, which was initially attributed to a toxic nodule. However, Tc-99m pertechnetate uptake scan and thyroid-stimulating hormone receptor antibody were negative, inconsistent with a toxic nodule or Grave's disease. Her thyroid function tests proved difficult to control over the next few months. She eventually proceeded to a total thyroidectomy and histology revealed follicular variant papillary thyroid carcinoma. She was started on levothyroxine postoperatively but developed severe hyperthyroidism, revealing the cause of hyperthyroidism to be autonomously functioning thyroid metastases. Although functioning thyroid metastases are very rare, they need to be considered among the differential diagnoses of hyperthyroidism, as there are nuances in management that could alter the eventual outcome. 2014 BMJ Publishing Group Ltd.

Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells.

PubMed

Schwertheim, Suzan; Wein, Frederik; Lennartz, Klaus; Worm, Karl; Schmid, Kurt Werner; Sheu-Grabellus, Sien-Yi

2017-07-01

The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer. Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits. Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase. Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

Role of ultrasonography in the differential diagnosis of thyrotoxicosis: a noninvasive, cost-effective, and widely available but underutilized diagnostic tool.

PubMed

Alzahrani, Ali S; Ceresini, Graziano; Aldasouqi, Saleh A

2012-01-01

To explore the use of ultrasonography as a diagnostic alternative to the traditional "gold standard" imaging study of nuclear scintigraphy in the evaluation of thyrotoxicosis. We review the relevant literature and share our own experience to highlight the promising role of ultrasonography in thyrotoxicosis. In addition, we present a diagnostic algorithm suggesting liberal use of ultrasonography in the evaluation of thyrotoxicosis. Ultrasonography has proved effective not only in the differentiation of Graves disease from other types and causes of thyrotoxicosis but also in the detection of subtle thyroid nodules. The latter role is emphasized in light of the recent observation of an increased risk of occurrence of papillary thyroid carcinoma in patients with Graves disease. Ultrasonography is a cost-effective, noninvasive, portable, and safe imaging modality in the evaluation of thyrotoxicosis, both for physiologic assessment and for detection of nonpalpable thyroid cancers that may elude identification on physical examination and nuclear imaging studies. Although thyroid scintigraphy remains a standard radiologic study, thyroid ultrasonography can be a practical alternative in many cases and the primary imaging modality in some situations such as during pregnancy and lactation and for evaluation and management of amiodarone-induced thyrotoxicosis.

BRAF mutation is unusual in chronic lymphocytic thyroiditis-associated papillary thyroid carcinomas and absent in non-neoplastic nuclear atypia of thyroiditis.

PubMed

Sargent, Rachel; LiVolsi, Virginia; Murphy, Justin; Mantha, Geeta; Hunt, Jennifer L

2006-01-01

Chronic lymphocytic thyroiditis (CLT) has an epidemiological relationship to papillary thyroid carcinoma (PTC). The follicular epithelium in CLT can be markedly atypical, with cytologic changes ranging from oncocytic morphology to clearing and overlapping. At the molecular level, the association between CLT and PTC is more controversial. In order to further characterize the molecular changes in CLT, this study examined the BRAF gene in 27 patient samples with CLT and without carcinoma and 28 samples with CLT and carcinoma (12 conventional papillary carcinomas, 13 follicular variants, and 3 tall cell variants). Microdissection, PCR, and sequencing of exon 15 of the BRAF gene were performed. BRAF mutations were uncommon in the cases studied with only two microscopic and two clinically sized PTCs had BRAF mutations (14%). There was no evidence of BRAF mutation in any of the areas with atypical follicular epithelium in CLT. These data suggest that BRAF is a less frequent mechanism of tumorigenesis in a background of CLT and that BRAF mutation is not present in the atypical follicular epithelium of CLT.

Fine-needle aspiration study of cystic papillary thyroid carcinoma: Rare cytological findings

PubMed Central

Mokhtari, Maral; Kumar, Perikala Vijayananda; Hayati, Kamran

2016-01-01

Background: Cystic papillary thyroid carcinoma (CPTC) is a variant of papillary carcinoma that has many mimickers in cytological grounds. Aim: To study the cytomorphologic features of CPTC and compare them to those of other cystic thyroid lesions using fine-needle aspiration cytology (FNAC). We also aimed to identify the cytomorphologic features that distinguish CPTC from other cystic thyroid lesions. Materials and Methods: Seventy-three cases of CPTC were included in the study. The cytomorphologic features of these cases were analyzed. The FNA smears of other thyroid lesions with cystic changes (300 colloid goiters, 290 adenomatoid nodules, 11 follicular neoplasms, and 9 hurtle cell neoplasm) were also studied. Results: The smears in CPTC revealed isolated follicular cells, small groups of cells with scalloped margins, cell swirls, small clusters with a cartwheel pattern, papillary clusters, intranuclear inclusions, nuclear grooves, sticky colloid, intracellular colloids, psammoma bodies, multinucleated giant cells, and foamy and hemosiderin laden macrophages. Small groups of cells with scalloped borders, cellular swirls, and small clusters with a cartwheel pattern were seen in CPTC, but not in other cystic lesions. Interestingly, mesothelial-like cells and hemophagocytic cells were seen in five and three cases of CPTC, respectively, but not in other cystic lesions. Conclusion: Mesothelial-like cells and hemophagocytic cells were observed in five and three cases of CPTC, respectively. Similar finding have not been previously reported in the literature. PMID:27756982

Thyroid carcinoma in Graves' disease: A meta-analysis.

PubMed

Staniforth, Joy U L; Erdirimanne, Senarath; Eslick, Guy D

2016-03-01

The incidence of thyroid carcinoma is increasing worldwide. Graves' disease is the most common hyperthyroid disease. Studies have suggested an increased risk of thyroid malignancy in Graves' disease: there has not yet been a meta-analysis to allow quantitative comparison. The purpose of this study was to determine the risk of thyroid carcinoma in Graves' disease, and to gather information on the histological subtypes of carcinoma and the co-existence of thyroid nodules. Several databases and article reference lists were searched. Inclusion criteria included appropriate diagnostic criteria for thyroid conditions and a diagnoses of carcinoma based on histology. 33 studies were selected, all reporting on surgically-resected specimens. The event rate of thyroid carcinoma in Graves' disease was 0.07 (95% CI 0.04 to 0.12). There was no data to allow comparison with patients without hyperthyroid diseases. There was no increase in the odds of developing carcinoma in Graves' disease compared to toxic multinodular goitre and toxic uninodular goitre. 88% of thyroid carcinomas in Graves' disease were papillary, with solitary papillary micro-carcinoma (diameter 10 mm or less) comprising 23% of all detected thyroid carcinomas. Patients with Graves' disease and co-existing thyroid nodules were almost 5 times more likely to be diagnosed with thyroid carcinoma than those without nodules. Thyroid malignancy in Graves' disease requiring surgical treatment should be considered as likely as in other hyperthyroid diseases needing surgical treatment. Clinicians should consider screening selected patients with Graves' disease for nodules whilst being aware of potentially over-diagnosing papillary micro-carcinoma. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Dual malignancy in a thyroid; papillary thyroid carcinoma and small lymphocytic lymphoma; a report of a case with a cyto-histologic correlation.

PubMed

Ahmed, Omar I; Salih, Ziyan T

2017-09-01

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Simultaneous involvement of the thyroid gland by multiple malignancies, is a rare occurrence. Similarly, primary thyroid lymphomas are also rare. We are reporting a rare case of a dual thyroid malignancy; PTC with secondary thyroid involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diagnosed on cytology and confirmed with flow cytometry, histology and immunohistochemistry. Imaging showed two hypermetabolic nodules, one in left parotid gland, and the other in the thyroid isthmus. Cytology smears showed features of PTC along with an atypical lymphocytic infiltrate, which co-expressed CD5, CD19, and CD23 on flowcytometry analysis. Subsequent thyroidectomy showed the atypical lymphocytic infiltrate involving the PTC papillae themselves. The diagnosis of dual malignancies on thyroid FNA is extremely rare and often unexpected, but is possible using appropriate ancillary studies. © 2017 Wiley Periodicals, Inc.

Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, M.; Maynard, S.; Sheldon, S.

This is the first reported case of an unbalanced chromosome rearrangement resulting in trisomy 5q35.5{r_arrow}qter and monosomy 16p 13.3{r_arrow}pter, in a boy with mental and growth retardation, minor anomalies, and a history of bilateral papillary thyroid carcinoma. This was the result of a familial balanced translocation. The clinical and cytogenetic manifestations of the case are presented and the possible role of the chromosomal rearrangement in the etiology of the thyroid carcinoma is discussed. 25 refs., 5 figs., 1 tab.

Hyalinizing Trabecular Tumor of the Thyroid Gland, a Diagnostic Challenge in Fine-Needle Aspiration Cytology: Case Report.

PubMed

Rhee, Ye-Young; Jung, Hong Kyu; Kim, Se Hoon; Kim, Soo Hee

2018-06-11

Hyalinizing trabecular tumor (HTT) is a rare thyroid tumor with low to minimal malignant potential. HTT is often misinterpreted as other thyroid tumors, including papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC), on fine-needle aspiration (FNA) cytology, because of its overlapping cytologic features, such as nuclear grooves and intranulcear pseudoinclusions. Although cytopathologists cannot definitely conclude HTT by FNA cytology, suspicion of HTT is necessary to avoid misdiagnosing HTT as PTC or MTC and to avoid unnecessary aggressive treatment. Here, we report a case of HTT with novel cytologic features in CellPrep liquid based cytology that was diagnosed as suspicious for papillary carcinoma by FNA and finally diagnosed as HTT in the surgical specimen.

External quality assurance in nongynecologic cytology: The Australasian experience.

PubMed

Shield, Paul W; Frost, Felicity; Finnimore, Jo L; Wright, R Gordon; Cummings, Margaret C

2017-05-01

The Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program has operated an external quality assurance program in nongynecologic cytopathology since 1993. Glass slide preparations of a wide range of nongynecologic cases were circulated to approximately 200 cytopathology laboratories in 16 countries. General nongynecologic cytology cases were manufactured from residual specimens after routine diagnosis. Fine-needle aspiration (FNA) cases were made by sampling fresh tissue and making direct specimens. The majority of cases consisted of both air-dried and fixed preparations. Results returned to laboratories included illustrated case discussions highlighting diagnostic features, key differential diagnoses, and useful adjunctive tests. The current study reviewed >22,000 results for 123 nongynecologic cases. Cases found to cause the most diagnostic difficulties included serous effusion cases with metastatic carcinoma in a dispersed pattern, well-differentiated carcinoma, and cellular reactive cases; urine specimens with sparse malignant cells; reactive pneumocytes in a bronchoalveolar lavage; breast FNA cases with papillary lesions; gestational specimens; and fibroadenoma. FNA specimens from the lung and thyroid, particularly papillary thyroid carcinoma, generally were well reported. The use of multiple preparations of the same specimen has allowed interlaboratory comparison, and the quality assurance program has played an educational role as well as informing the laboratory accreditation process. Cancer Cytopathol 2017;125:349-361. © 2017 American Cancer Society. © 2017 American Cancer Society.

INDUCTION OF NEOPLASMS IN THYROID GLANDS OF RATS BY SUBTOTAL THYROIDECTOMY AND BY THE INJECTION OF ONE MICROCURIE OF I$sup 13$$sup 1$

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldberg, R.C.; Lindsay, S.; Nichols, C.W. Jr.

1964-01-01

Female Long-Evans rats were subjected to subtotal thyroidectomy, subtotal thyroidectomy plus injection of 1 mu e of I/sup 131/, subtotal thyroidectomy plus injection of 1 mu c of I/sup 131/ plus feeding of a diet containing desiccated thyroid, subtotal thyroidectomy plus feeding of a diet containing desiccated thyroid, injection of 1 mu c of I/sup 131/, feeding of a diet containing desiccated thyroid, and injection of 1 mu c of I/sup 131/ plus feeding of a diet containing desiccated thyroid. Single and multiple adenomas were found in rats subjected to subtotal thyroidectomy and in those subtotally thyroidectomized and given injectionsmore » of 1 mu c of I/sup 131/. In rats subjected to these same treatments but, in addition, fed the thyroid-containing diet, significantly fewer adenomas were encountered. Four papillary carcinomas and one follicular carcinoma were found in rats subjected to subtotal thyroidectomy and/or given injections of 1 mu c I/sup 131/. No carcinoma was observed in control rats. Two papillary carcinomas were found in glands following subtotal thyroidectomy alone, a finding suggesting that thyrotropic hormone stimulation may cause the development of both benign and malignant thyroid neoplasms. One papillary and one follicular carcinoma developed in the intact thyroid glands of rats that received only 1 mu c of I/sup 131/. These malignant neoplasms were possibly induced solely by the I/sup 131/ irradiation. One papillary carcinoma developed in a rat that had been subjected to subtotal thyroidectomy, given an injection of 1 mu c of I/sup 131/, and fed the desiccated thyroid-containing diet. This neoplasm appeared to be the result of either prolonged thyrotropic hormone stimulation or I/sup 131/ irradiation. (auth)« less

Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.

PubMed

Demeure, Michael J; Aziz, Meraj; Rosenberg, Richard; Gurley, Steven D; Bussey, Kimberly J; Carpten, John D

2014-06-01

Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In radioiodine resistant aggressive papillary thyroid cancers, there remain few effective therapeutic options. A 62-year-old man who underwent multiple operations for papillary thyroid cancer and whose metastases progressed despite standard treatments provided tumor tissue. We analyzed tumor and whole blood DNA by whole genome sequencing, achieving 80× or greater coverage over 94 % of the exome and 90 % of the genome. We determined somatic mutations and structural alterations. We found a total of 57 somatic mutations in 55 genes of the cancer genome. There was notably a lack of mutations in NRAS and BRAF, and no RET/PTC rearrangement. There was a mutation in the TRAPP oncogene and a loss of heterozygosity of the p16, p18, and RB1 tumor suppressor genes. The oncogenic driver for this tumor is a translocation involving the genes for anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4). The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib. This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4-ALK translocation of a TRAPP oncogene mutation. These findings suggest that this tumor has a more distinct oncogenesis than BRAF mutant papillary thyroid cancer. Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.

Solitary liver metastasis from follicular variant papillary thyroid carcinoma: A case report and literature review

PubMed Central

Djenic, Brano; Duick, Daniel; Newell, James O.; Demeure, Michael J.

2014-01-01

Introduction Papillary (PTC) and follicular (FTC) thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Sites of metastases from FTC are usually osseous and those from PTC are in regional nodal basins and the lungs. Visceral metastases are rare and when they do occur, they tend do so in multiple sites. We present the case of a patient with a follicular variant of PTC and a solitary metastasis to the liver then review the relevant literature. Presentation of case An otherwise healthy 68-year-old woman was diagnosed with follicular variant papillary thyroid cancer in 2003 and subsequently underwent thyroidectomy. The patient’s endocrinologist conducted surveillance of her thyroid cancer. In 2012, due to rise in thyroglobulin, a whole body radioiodine scan was obtained which revealed an iodine-avid left liver lobe mass. Three cycles of radioiodine ablation therapy were unsuccessful and eventually the patient was referred for surgical resection. Metastatic evaluation including a PET scan was negative with the exception of an isolated enhancing 4 cm mass in segment 4B of the liver. Anatomic segmental resection of liver was performed without complications. Intraoperative ultrasonography was used to guide resection of the liver mass. Pathology reports confirmed metastatic follicular variant of PTC. Surgical margins were free of tumor. Patient was discharged home and is doing well one year after surgery. The latest thyroglobulin level was undetectable. Discussion Post-operative surveillance by PCP, endocrinologist or surgeon for patients with thyroid carcinoma should be performed routinely. If identified, a solitary liver metastasis from primary thyroid carcinoma should be considered for surgical resection. Due to sparse data available in literature, collecting more data to establish algorithms for treatment of such rare metastatic cancers may be able to aid physicians to achieve better outcomes. Conclusion Rare distant sites of metastases from DTC include eyes, pharynx, skin, muscle, ovaries, adrenal glands, kidneys, esophagus, pancreas and liver. Isolated, resectable liver metastases from PTC are exceedingly rare. Literature review revealed only 10 reported cases of liver metastases from DTC. As in our patient, solitary liver metastasis from PTC should be considered for surgical resection which offers the best chance for prolonged survival. PMID:25536153

Effects of different extracts of curcumin on TPC1 papillary thyroid cancer cell line.

PubMed

Perna, Angelica; De Luca, Antonio; Adelfi, Laura; Pasquale, Tammaro; Varriale, Bruno; Esposito, Teresa

2018-02-15

The thyroid gland is one of the largest endocrine glands in the body. The vast majority of TCs (> 90%) originate from follicular cells and are defined as differentiated thyroid cancers (DTC) and the two histological subtypes are the papillary TC with its variants and the follicular TC. Curcumin possesses a wide variety of biological functions, and thanks to its properties, it has gained considerable attention due to its profound medicinal values (Prasad, Gupta, Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014). We have undertaken the present work in order to define the possible role of curcumin in modulating the genetic expression of cell markers and to understand the effectiveness of this nutraceutical in modulating the regression of cancer phenotype. As a template we used the TPC-1 cells treated with the different extracts of turmeric, and examined the levels of expression of different markers (proliferative, inflammatory, antioxidant, apoptotic). Treatment with the three different curcumin extracts displays anti-inflammatory, antioxidant properties and it is able to influence cell cycle with slightly different effects upon the extracts. Furthermore curcumin is able to influence cell metabolic activity vitality. In conclusion curcumin has the potential to be developed as a safe therapeutic but further studies are needed to verify its antitumor ability in vivo.

Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1.

PubMed

Fanfone, Deborah; Despretz, Nadège; Stanicki, Dimitri; Rubio-Magnieto, Jenifer; Fossépré, Mathieu; Surin, Mathieu; Rorive, Sandrine; Salmon, Isabelle; Vander Elst, Luce; Laurent, Sophie; Muller, Robert N; Saussez, Sven; Burtea, Carmen

2017-10-06

The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.

Simultaneous Primary Hodgkin's Lymphoma of the Sigmoid Colon and Papillary Thyroid Carcinoma in an HIV-Positive Patient.

PubMed

Liszewski, Walter; Sittig, Mark; Kandil, Emad; Van Sickels, Nicholas; Safah, Hana

2015-01-01

Primary Hodgkin's lymphoma of the colon is a rare phenomenon previously only reported in patients with chronic diverticulitis or inflammatory bowel disease. Herein we report a case of primary Hodgkin's lymphoma of the sigmoid colon in an HIV-positive patient without a history of inflammatory bowel disease or chronic diverticulitis that was later complicated by the discovery of concurrent papillary thyroid carcinoma.

Accounting for tissue heterogeneity in infrared spectroscopic imaging for accurate diagnosis of thyroid carcinoma subtypes.

PubMed

Martinez-Marin, David; Sreedhar, Hari; Varma, Vishal K; Eloy, Catarina; Sobrinho-Simões, Manuel; Kajdacsy-Balla, André; Walsh, Michael J

2017-07-01

Fourier transform infrared (FT-IR) microscopy was used to image tissue samples from twenty patients diagnosed with thyroid carcinoma. The spectral data were then used to differentiate between follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma using principle component analysis coupled with linear discriminant analysis and a Naïve Bayesian classifier operating on a set of computed spectral metrics. Classification of patients' disease type was accomplished by using average spectra from a wide region containing follicular cells, colloid, and fibrosis; however, classification of disease state at the pixel level was only possible when the extracted spectra were limited to follicular epithelial cells in the samples, excluding the relatively uninformative areas of fibrosis. The results demonstrate the potential of FT-IR microscopy as a tool to assist in the difficult diagnosis of these subtypes of thyroid cancer, and also highlights the importance of selectively and separately analyzing spectral information from different features of a tissue of interest.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

[Prediction of occult carcinoma in contralateral nodules based on the ultrasonic features of unilateral papillary thyroid carcinoma].

PubMed

Yang, L M; Li, Q; Zhao, B W; Lyu, J G; Xu, H S; Xu, L L; Li, S Y; Gao, L; Zhu, J

2017-04-07

Objective: To investigate the occurrence of occult carcinoma in contralateral lobes based on the ultrasonic features of unilateral papillary thyroid carcinoma. Methods: The study included 202 consecutives cases of unilateral papillary thyroid carcinoma with benign nodules in the contralateral lobe identified by preoperative ultrasound or fine-needle aspiration from June 2014 to December 2015. All patients received total thyroidectomies, and with postoperative pathological examination they were divided into two groups, one including 60 cases with positive occult cancer and another one consisting of 142 cases with negative occult cancer. Univariate and multivariate analyses were performed to analyze the sonographic features of unilateral papillary thyroid carcinoma relevant to the occurrence of occult carcinoma in the contralateral nodules. Results: Univariate analysis indicated occult carcinoma in the contralateral lobes was associated with Hashimoto's thyroiditis(χ(2)=3.955, P =0.047), unclear border (χ(2)=4.375, P =0.036)and multifocality in the ipsilateral(χ(2)=7.375, P =0.007), but not with tumors maximum size, location, A/T, shape, internal structure, internal echo, acoustic halo, calcification, capsular invasion and blood flow signal in the lobe with carcinoma on another side. Multivariate analysis showed unclear border ( OR =2.727, P =0.010) and multifocality in the ipsilateral( OR =2.807, P =0.005)of carcinoma were independent predictive factor for contralateral occult PTC. Conclusions: Unclear border and multifocality of PTC in the ipsilateral were closely relevant to the occurrence of occult carcinoma in the contralateral nodules.

Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study.

PubMed

Michikawa, Takehiro; Inoue, Manami; Shimazu, Taichi; Sawada, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Yamaji, Taiki; Tsugane, Shoichiro

2012-05-01

Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about 80% of Japanese people's iodine intake. We examined the association between seaweed consumption and the risk of thyroid cancer in Japanese women. Women participating in the Japan Public Health Center-based Prospective Study (n=52 679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed consumption was assessed using a food-frequency questionnaire and divided into three categories: 2 days/week or less (reference); 3-4 days/week; and almost daily. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly associated with an increased risk of papillary carcinoma (HR for almost daily consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend P=0.04). After stratification for menopausal status, an increased risk was observed in postmenopausal women (papillary carcinoma HR for almost daily consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend P=0.76). This study identified a positive association between seaweed consumption and the risk of thyroid cancer (especially for papillary carcinoma) in postmenopausal women.

Follicular variant of papillary carcinoma presenting as a hyperfunctioning thyroid nodule.

PubMed

Gabalec, Filip; Svilias, Ioannis; Plasilova, Ivana; Hovorkova, Eva; Ryska, Aler; Horacek, Jiri

2014-03-01

In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism.

PubMed

Badziong, Julia; Ting, Saskia; Synoracki, Sarah; Tiedje, Vera; Brix, Klaudia; Brabant, Georg; Moeller, Lars Christian; Schmid, Kurt Werner; Fuhrer, Dagmar; Zwanziger, Denise

2017-09-01

Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n  = 19), follicular adenoma (FA, n  = 44), follicular thyroid carcinoma (FTC, n  = 45), papillary thyroid carcinoma (PTC, n  = 40), anaplastic thyroid carcinoma (ATC, n  = 40) and Graves' disease (GD, n  = 50) by calculating the 'hybrid' (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions. MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation. Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8. © 2017 European Society of Endocrinology.

Evaluation of thyroid tissue by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Teixeira, C. S. B.; Bitar, R. A.; Santos, A. B. O.; Kulcsar, M. A. V.; Friguglietti, C. U. M.; Martinho, H. S.; da Costa, R. B.; Martin, A. A.

2010-02-01

Thyroid gland is a small gland in the neck consisting of two lobes connected by an isthmus. Thyroid's main function is to produce the hormones thyroxine (T4), triiodothyronine (T3) and calcitonin. Thyroid disorders can disturb the production of these hormones, which will affect numerous processes within the body such as: regulating metabolism and increasing utilization of cholesterol, fats, proteins, and carbohydrates. The gland itself can also be injured; for example, neoplasias, which have been considered the most important, causing damage of to the gland and are difficult to diagnose. There are several types of thyroid cancer: Papillary, Follicular, Medullary, and Anaplastic. The occurrence rate, in general is between 4 and 7%; which is on the increase (30%), probably due to new technology that is able to find small thyroid cancers that may not have been found previously. The most common method used for thyroid diagnoses are: anamnesis, ultrasonography, and laboratory exams (Fine Needle Aspiration Biopsy- FNAB). However, the sensitivity of those test are rather poor, with a high rate of false-negative results, therefore there is an urgent need to develop new diagnostic techniques. Raman spectroscopy has been presented as a valuable tool for cancer diagnosis in many different tissues. In this work, 27 fragments of the thyroid were collected from 18 patients, comprising the following histologic groups: goitre adjacent tissue, goitre nodular tissue, follicular adenoma, follicular carcinoma, and papillary carcinoma. Spectral collection was done with a commercial FTRaman Spectrometer (Bruker RFS100/S) using a 1064 nm laser excitation and Ge detector. Principal Component Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. Comparing the goitre adjacent tissue with the goitre nodular region, an index of 58.3% of correct classification was obtained. Between goitre (nodular region and adjacent tissue) and papillary carcinoma, the index of correct classification was 64.9%, and the classification between benign tissues (goitre and follicular adenoma) and malignant tissues (papillary and follicular carcinomas), the index was 72.5%.

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior

PubMed Central

Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Pereira Gimba, Etel Rodrigues; Soares, Paula

2016-01-01

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches. PMID:27409830

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior.

PubMed

Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Gimba, Etel Rodrigues Pereira; Soares, Paula

2016-08-09

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches.

RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA.

PubMed

Chen, Pan; Feng, Hui-Juan; Ouyang, Wei; Wu, Ju-Qing; Wang, Jing; Sun, Yun-Gang; Xian, Jia-Lang; Huang, Liu-Hua

2016-09-01

Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 ((131)I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of (131)I therapy on pulmonary function and peripheral blood counts in the same cohort of patients. The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria. Multivariate Cox regression analysis indicated that age ≥45 years and (131)I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and (131)I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative (131)I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts. Similar to earlier studies, our results confirm that (131)I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression. CI = confidence interval DTC = differentiated thyroid cancer (18)F-FDG = fluoro-18 fluorodeoxyglucose FEF = forced expiratory flow FTC = follicular thyroid cancer FVC = forced vital capacity GR = granulocytes Hb = hemoglobin HR = hazard ratio (131)I = iodine-131 LN = lymph node OR = odds ratio OS = overall survival PET/CT = positive positron emission tomography/computed tomography PFS = progression-free survival PT = partial thyroidectomy PTC = papillary thyroid cancer RAI = radioactive iodine RBC = red blood cell Tg = thyroglobulin TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TT = total thyroidectomy WBC = white blood cells WBS = whole body scan.

The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population.

PubMed

Kaczmarek-Ryś, Marta; Ziemnicka, Katarzyna; Hryhorowicz, Szymon T; Górczak, Katarzyna; Hoppe-Gołębiewska, Justyna; Skrzypczak-Zielińska, Marzena; Tomys, Michalina; Gołąb, Monika; Szkudlarek, Malgorzata; Budny, Bartłomiej; Siatkowski, Idzi; Gut, Paweł; Ruchała, Marek; Słomski, Ryszard; Pławski, Andrzej

2015-01-01

Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible. The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene. The aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer. 602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher's exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software. The results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019). Identification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered.

Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality.

PubMed

Ahn, Hyeong Sik; Kim, Hyun Jung; Kim, Kyoung Hoon; Lee, Young Sung; Han, Seung Jin; Kim, Yuri; Ko, Min Ji; Brito, Juan P

2016-11-01

The incidence of thyroid cancer has increased worldwide. The country where the incidence has increased most is South Korea. The goal of this study is to understand the magnitude of association between opportunistic thyroid cancer screening and thyroid cancer incidence, thyroid cancer subtype, and disease-specific mortality. We used the 2010 Korea Community Health Survey, which queried 226,873 individuals if they had been screened for thyroid cancer in the last two years. Thyroid cancer incidence data from 2008 to 2010 were obtained from the Korea Cancer registry data, and mortality data from 2007-2010 were obtained from the Statistics Korea database. The ecological association between thyroid screening and thyroid cancer incidence and mortality by age and sex were examined across Korea's 16 administrative regions by general linear regression models. Between 2008 and 2010, the incidence of thyroid cancer was 64.1 per 100,000 individuals: the incidence in females was 107.3 and in males was 21.1. There was a strong positive correlation between regional thyroid cancer screening and regional thyroid cancer incidence (r = 0.77, [95% confidence interval 0.70-0.82]). The magnitude of correlation was higher for females (r = 0.88 [CI 0.83-0.92]) than in males (r = 0.76 [CI 0.67-0.84]) in any age group. Thyroid screening was only associated with increased detection of papillary thyroid cancer (r = 0.74 [CI 0.59-0.88]); and not associated with mortality (r = -0.08 [CI -0.59-0.63]) due to thyroid cancer. The magnitude of association between thyroid cancer screening in South Korea and the incidence of thyroid cancer strongly suggests that screening is the most important driver of the epidemic of thyroid cancer, particularly among females. Thyroid cancer screening, however, was only associated with the increase of one tumor histology, papillary thyroid cancer, and it did not have any association with thyroid cancer mortality. The extent to which opportunistic thyroid cancer screening is converting thousands of asymptomatic persons to cancer patients without any known benefit to them needs to be examined carefully.

Epidemiology of thyroid cancer: a review with special reference to Gulf Cooperation Council (GCC) states.

PubMed

Al-Zahrani, A S; Ravichandran, K

2007-07-01

A wide variation in incidence of thyroid cancer according to age, sex, ethnicity and geographic region was observed. In general, it occurs more frequently in women than men and a substantially higher rate was observed particularly during fertile period of women compared with men of the same age. Papillary carcinoma is the most prevalent histological type, irrespective of gender and conditions like iodine level. Over the years the incidence of thyroid cancer, especially papillary type, increases around the world. Ionizing radiation, in particular radiotherapy to head and neck region was the most established risk factor for thyroid cancer. Goiter, miscarriage or abortion (particularly in the first pregnancy) may also predispose to thyroid cancer risk. Cigarette smoking and use of contraceptives may be modifier of thyroid cancer risk. In all the GCC states thyroid cancer is the second most common cancer except in Babrain and Kuwait (where it stands third). During the five year peribd (1998-2002) 549 male and 1898 female thyroid caneers were diagnosed in all the GCC states. Papillary carcinoma is the predominant histological type followed by follicular carcinoma in both genders. Among females, Qatar has the highest incidence with an age standardized incidence rate of 13.5 per 100,000 followed by Kuwait (7.7), Bahrain (7.6), Emirates (6.0), Oman (5.9), and Saudi Arabia (5.0). There were at least 2.6 female thyroid cancer cases (in Kuwait) for each male thyroid cancer case and this goes up to 6.6 in Babrain. Incidence of thyroid cancer in the GCC states is closer or higher than that of some of the developed countries.

[Thyroid cancer in patients with Grave's Disease].

PubMed

Mssrouri, R; Benamr, S; Essadel, A; Mdaghri, J; Mohammadine, El H; Lahlou, M-K; Taghy, A; Belmahi, A; Chad, B

2008-01-01

To evaluate the incidence of thyroid carcinoma in patients operated on for Graves' disease, to identify criteria which may predict malignancy, and to develop a practical approach to determine the extensiveness of thyroidectomy. Retrospective study of all patients who underwent thyroidectomy for Graves' disease between 1995 and 2005. 547 patients underwent subtotal thyroidectomy for Graves' disease during this period. Post-operative pathology examination revealed six cases of thyroid cancer (1.1%). All six cases had differentiated thyroid carcinoma (papillary carcinoma in 3 cases, follicular carcinoma in 2 cases and papillo-follicular carcinoma in 1 case). The indication for initial thyroidectomy was a palpable thyroid nodule in 3 cases (50%), failure of medical treatment for Grave's disease in 2 cases (33%), and signs of goiter compression in 1 case (17%). Five patients underwent re-operative total thyroidectomy. This study shows that while malignancy in Grave's disease is uncommon, the presence of thyroid nodule(s) in patients with Grave's disease may be considered as an indication for radical surgery. The most adequate radical surgery in this situation is to perform a total thyroidectomy.

Papillary carcinoma occurring within an adenomatous goiter of the thyroid gland in Cowden's disease.

PubMed

Kameyama, K; Takami, H; Miyajima, K; Mimura, T; Hosoda, Y; Ito, K; Ito, K

2001-01-01

Cowden's disease is an autosomal dominant disorder characterized by multiple benign and malignant neoplastic lesions involving many organs. The presence of characteristic cutaneous lesions is crucial for the diagnosis. Thyroid disease is a major extracutaneous manifestation of this disease; however, the histologic characteristics have not been described in detail. We report a case of thyroid tumor associated with Cowden's disease. Grossly, the tumor showed a multinodular appearance, like an adenomatous goiter. Microscopically, it consisted of follicular adenomas with a trabecular pattern. Some of the nodules had a second component resembling papillary carcinoma. This was thought to be a unique histological feature not described previously, and might be specific to thyroid tumor associated with Cowden's disease.

Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

ClinicalTrials.gov

2015-05-14

Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

Thyroid neoplasms after radiation therapy for adolescent acne vulgaris. [X radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paloyan, E.; Lawrence, A.M.

There is a potential hazard of thyroid cancer after exposure to external irradiation for the treatment of adolescent acne vulgaris. We noted a 60% incidence of thyroid carcinoma among 20 patients with such a history, who were operated on for thyroid nodules during a five-year period. Eighty-three percent of the patients with carcinoma had either a follicular or a mixed papillary-follicular carcinoma; 17% had a papillary carcinoma; 33% had regional node metastases; none had evidence of distant metastases. The interval between radiation exposure and thyroidectomy ranged from nine to 41 years. This association of thyroid neoplasms and a prior historymore » of radiation for acne vulgaris may be coincidental and therefore remains to be proved by retrospective surveys of large numbers of treated patients with appropriate controls.« less

Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy

NASA Astrophysics Data System (ADS)

Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

2016-09-01

Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis.

PubMed

Hinson, Andrew M; Massoll, Nicole A; Jolly, Lee Ann; Stack, Brendan C; Bodenner, Donald L; Franco, Aime T

2017-08-01

The purpose of this study was to define and characterize the thyroid tumor-draining lymph nodes in genetically engineered mice harboring thyroid-specific expression of oncogenic Braf V600E with and without Pten insufficiency. After intratumoral injection of methylene blue, the lymphatic drainage of the thyroid gland was visualized in real time. The thyroid gland/tumor was resected en bloc with the respiratory system for histological analysis. Although mice harboring Braf V600E mutations were smaller in body size compared with their wild-type (WT) littermates, the size of their thyroid glands and deep cervical lymph nodes were significantly larger. Additionally, the tumor-draining lymph nodes showed increased and enlarged lymphatic sinuses that were distributed throughout the cortex and medulla. Tumor-reactive lymphadenopathy and histiocytosis, but no frank metastases, were observed in all mice harboring Braf V600E mutations. The tumor-draining lymph nodes undergo significant structural alterations in immunocompetent mice, and this may represent a primer for papillary thyroid carcinoma (PTC) metastasis. © 2017 Wiley Periodicals, Inc.

CHEK2 mutations and the risk of papillary thyroid cancer.

PubMed

Siołek, Monika; Cybulski, Cezary; Gąsior-Perczak, Danuta; Kowalik, Artur; Kozak-Klonowska, Beata; Kowalska, Aldona; Chłopek, Małgorzata; Kluźniak, Wojciech; Wokołorczyk, Dominika; Pałyga, Iwona; Walczyk, Agnieszka; Lizis-Kolus, Katarzyna; Sun, Ping; Lubiński, Jan; Narod, Steven A; Góźdż, Stanisław

2015-08-01

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid. © 2015 UICC.

Cyclin D1 in well differentiated thyroid tumour of uncertain malignant potential.

PubMed

Lamba Saini, Monika; Weynand, Birgit; Rahier, Jacques; Mourad, Michel; Hamoir, Marc; Marbaix, Etienne

2015-04-18

Encapsulated follicular tumours with equivocal papillary thyroid carcinoma (PTC) type nuclear features continue to remain a challenge despite the recent attempts to classify these borderline lesions. The term 'well differentiated tumour of uncertain malignant potential (WDT-UMP)' was introduced to classify these tumours. The present study aimed to evaluate the role of a cell cycle regulator like cyclin D1 in these tumours along with assessment of other well established PTC markers like galectin-3, HBME-1, CK19. Thirteen cases of metastatic PTC, papillary microcarcinoma and follicular variant of PTC (FVPTC) were identified from a histological review of 510 cases. In addition, 13 cases of a subset of follicular adenomatoid nodules with focal areas showing nuclear features characteristic of PTC, identified as WDT-UMP, were also analyzed. Immunohistochemical analysis of galectin-3, HBME-1, CK19 and the proliferation markers Ki67 and cyclin D1 was performed. Lesions were analyzed for cyclin D1 gene amplification by fluorescent in-situ hybridization. All WDT-UMP lesions showed immunolabelling of cyclin D1, Ki67; 11/ 13 cases showed immunolabelling of CK19; 10/13 cases showed immunolabelling of HBME-1 and 4/13 cases showed immunolabelling of galectin-3. Surrounding benign adenomatoid areas showed no to faint focal staining in all thirteen cases of cyclin D1, HBME-1 and galectin-3. A low rate of cyclin D1 gene amplification was identified in a significant proportion of cells in the WDT-UMP lesions as compared to surrounding benign adenomatoid areas. Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP lesions showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. Overexpression of cyclin D1, associated with the amplification of the gene suggests that these WDT-UMP lesions are an intermediate between the benign and malignant groups making this group of lesions a reliable precursor of FVPTC. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1851820807142117.

Roles of phosphatidylinositol 3-kinase regulatory subunit alpha, activator protein-1, and programmed cell death 4 in diagnosis of papillary thyroid carcinoma.

PubMed

Chen, Xiaojun; Wu, Wenjun; Chen, Xiong; Gong, Xiaohua

2016-05-01

This study evaluated the diagnostic values of phosphatidylinositol 3-kinase regulatory subunit alpha (P85α), activator protein-1 (AP-1), and programmed cell death 4 (PDCD4) in papillary thyroid carcinoma (PTC). P85α, AP-1, and PDCD4 expressions were detected in PTC tissues (n = 116) and thyroid papillary hyperplasia (PTH) tissues (n = 90) by immunohistochemistry, western blot, and enzyme-linked immunosorbent assay (ELISA). Associations of P85α, AP-1, and PDCD4 expressions with clinicopathological features in PTC were analyzed. Diagnostic values of P85α, AP-1, and PDCD4 in PTC were evaluated by receiver operating characteristic (ROC) curve. P85α, AP-1, and PDCD4 expression levels in PTC tissues were statistically different from those in PTH tissues (all P < 0.05). In PTC tissues, AP-1 expression was positively associated with P85α expression (r = 0.841, P < 0.01), while negatively associated with PDCD4 expression (r = -0.755, P < 0.01). P85α expression was associated with lymph node metastasis (LNM) and the degree of differentiation (both P < 0.05); AP-1 and PDCD4 expressions were associated with the degree of differentiation (both P < 0.05). The diagnostic sensitivity and specificity of P85α were 92.2 and 91.1 %, respectively, with a cutoff value of 2.100 and an area under curve (AUC) of 0.966. The diagnostic sensitivity and specificity of AP-1 reached 94.4 and 93.3 % with a cutoff value of 1.655 and an AUC of 0.987. The diagnostic sensitivity and specificity of PDCD4 were 54.4 and 85.6 % with a cutoff value of 2.025 and an AUC of 0.754. P85α, AP-1, and PDCD4 proteins may be related to the tumorigenesis and progression of PTC. Moreover, P85α, AP-1, and PDCD4 proteins may serve as potential diagnostic markers to the biological behavior of PTC.

Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer.

PubMed

Zeng, Rui-Chao; Jin, Lang-Ping; Chen, En-Dong; Dong, Si-Yang; Cai, Ye-Feng; Huang, Guan-Li; Li, Quan; Jin, Chun; Zhang, Xiao-Hua; Wang, Ou-Chen

2016-04-01

The purpose of this study was to evaluate the potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid carcinoma (PTC). A total of 619 patients with PTC who underwent total thyroidectomy with lymph node dissection were enrolled in this study. Univariable and multivariate analyses were used. Hashimoto's thyroiditis was present in 35.9% (222 of 619) of PTCs. Multivariate logistic regressions showed that BRAF(V600E) mutation, sex, extrathyroidal extension, and lymph node metastasis were independent factors for Hashimoto's thyroiditis. Female sex, more frequent extrathyroidal extension, and a higher incidence of lymph node metastasis were significantly associated with PTCs accompanied by BRAF(V600E) mutation without Hashimoto's thyroiditis compared with PTCs accompanied by BRAF(V600E) mutation with Hashimoto's thyroiditis. Hashimoto's thyroiditis was negatively associated with BRAF(V600E) mutation, extrathyroidal extension, and lymph node metastasis. In addition, Hashimoto's thyroiditis was related to less lymph node metastasis and extrathyroidal extension in PTCs with BRAF(V600E) mutation. Therefore, Hashimoto's thyroiditis is a potentially protective factor in PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1019-E1025, 2016. © 2015 Wiley Periodicals, Inc.

Utility of shear wave elastography to detect papillary thyroid carcinoma in thyroid nodules: efficacy of the standard deviation elasticity.

PubMed

Kim, Hye Jeong; Kwak, Mi Kyung; Choi, In Ho; Jin, So-Young; Park, Hyeong Kyu; Byun, Dong Won; Suh, Kyoil; Yoo, Myung Hi

2018-02-23

The aim of this study was to address the role of the elasticity index as a possible predictive marker for detecting papillary thyroid carcinoma (PTC) and quantitatively assess shear wave elastography (SWE) as a tool for differentiating PTC from benign thyroid nodules. One hundred and nineteen patients with thyroid nodules undergoing SWE before ultrasound-guided fine needle aspiration and core needle biopsy were analyzed. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity indices were measured. Among 105 nodules, 14 were PTC and 91 were benign. The EMean, EMin, and EMax values were significantly higher in PTCs than benign nodules (EMean 37.4 in PTC vs. 23.7 in benign nodules, p = 0.005; EMin 27.9 vs. 17.8, p = 0.034; EMax 46.7 vs. 31.5, p < 0.001). The EMean, EMin, and EMax were significantly associated with PTC with diagnostic odds ratios varying from 6.74 to 9.91, high specificities (86.4%, 86.4%, and 88.1%, respectively), and positive likelihood ratios (4.21, 3.69, and 4.82, respectively). The ESD values were significantly higher in PTC than in benign nodules (6.3 vs. 2.6, p < 0.001). ESD had the highest specificity (96.6%) when applied with a cut-off value of 6.5 kPa. It had a positive likelihood ratio of 14.75 and a diagnostic odds ratio of 28.50. The shear elasticity index of ESD, with higher likelihood ratios for PTC, will probably identify nodules that have a high potential for malignancy. It may help to identify and select malignant nodules, while reducing unnecessary fine needle aspiration and core needle biopsies of benign nodules.

A Greek family with a follicular variant of familial papillary thyroid carcinoma: TCO, MNG1, fPTC/PRN, and NMTC1 excluded as susceptibility loci.

PubMed

Tsilchorozidou, Tasoula; Vafiadou, Eleni; Yovos, John G; Romeo, Giovani; McKay, James; Lesueur, Fabienne; Bonora, Elena

2005-12-01

The familial form of nonmedullary thyroid carcinoma (FNMTC) has been recognized as a distinct clinical entity and is characterized by multifocality and a more severe phenotype than its sporadic counterpart. The majority of FNMTC pedigrees are small in size, show variable modes of inheritance, and may present with a variety of additional benign thyroid disorders. The existence of marked phenotypic differences between FNMTC families suggests that there is genetic heterogeneity. Recent studies have mapped a susceptibility locus for FNMTC at 2q21. This locus appears particular relevant to families with at least one case of the follicular variant of papillary thyroid cancer (fvPTC). We describe the clinical and pathologic characteristics of a large three-generation fPTC kindred, with two of the four PTC patients presented with the follicular variant of PTC. It is of interest the occurrence of PTC in three siblings within a period of 3 years. In addition, multinodular goiter (MNG) was diagnosed in seven individuals, lymphocytic thyroiditis in four, while one diagnosed with a benign adenoma. From the PTC patients, one had MNG and fvPTC, one MNG, lymphocytic thyroiditis and papillary pattern of PTC, one lymphocytic thyroiditis and fvPTC, and one MNG and papillary pattern of PTC. The inheritance pattern was autosomal dominant with incomplete penetrance and women were affected more frequently than men. Considering all PTC-affected individuals, the limit of detection (LOD) score we got for this family on 2q21 was 0.5. The low LOD score is caused by a PTC patient who does not share the affected haplotype, suggesting that maybe a new locus for PTC predisposition is present in this kindred. Linkage analysis also excluded TCO, MNG, and fPTC/PRN as susceptibility loci to FNMTC in this family.

RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease

PubMed Central

Su, Xuan; He, Caiyun; Ma, Jiangjun; Tang, Tao; Zhang, Xiao; Ye, Zulu; Long, Yakang; Shao, Qiong

2016-01-01

RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39–22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto's thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer. PMID:27802347

Expression of Simple Mucin Type Antigens and Lewis Type 1 and Type 2 Chain Antigens in the Thyroid Gland: An Immunohistochemical Study of Normal Thyroid Tissues, Benign Lesions, and Malignant Tumors.

PubMed

Fonseca, Elsa; Castanhas, Salome; Sobrinho-Simoes, Manuel

1996-01-01

In order to characterize the pattern of expression of carbohydrate structures in several types of thyroid tissues and to evaluate the putative usefulness of the detection of such antigens in diagnostic surgical pathology, we undertook the immunohistochemical study of simple mucin type antigens (T, Tn, and sialyl Tn), Lewis type I antigens (Lewis a, sialyl Lewis a, and Lewis b), and Lewis type 2 related antigens (precursor type 2, H type 2, Lewis x, sialyl Lewis x, and Lewis y) in thyroid samples obtained from 65 patients. The material consisted on paraffin sections of normal thyroid (n = 43), benign lesions (13 goiters/hyperplastic lesions and 15 adenomas), and malignant tumors (12 follicular carcinomas and 27 papillary carcinomas, 5 of which had lymph node metastases) of the thyroid follicular epithelium. Tn, T, and precursor type 2 antigens were the only antigens that were detected and very rarely in normal thyroid. Benign lesions were similar to normal thyroid despite displaying a higher prevalence of immunoreactivity for several antigens of the three groups. Thyroid carcinomas presented a significantly higher level of expression of all types of simple mucin, Lewis type 1, and Lewis type 2 antigens than the normal thyroid and benign lesions. The expression of sialyl Tn was restricted to malignant tumors, and the expression of sialyl Lewis x was closely associated, though not exclusively, to papillary carcinomas. The immunoreactivity was stronger and the number of positive cases was higher in papillary than in follicular carcinomas. No differences were found between primary tumors and the respective metastases. The existence of distinct patterns of expression of carbohydrate antigens in different types of thyroid lesions points to the usefulness of the detection of some of these antigens in thyroid surgical pathology. The putative role of such antigens in the peculiar metastatic properties of thyroid carcinomas remains unsettled.

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

PubMed

Lee, Young Chan; Na, Se Young; Park, Gi Cheol; Han, Ju Hyun; Kim, Seung Woo; Eun, Young Gyu

2017-02-01

The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Copyright © 2016 Elsevier Inc. All rights reserved.

Family history of cancer and risk of sporadic differentiated thyroid carcinoma.

PubMed

Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K; Sturgis, Erich M

2012-03-01

Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since the 1980s. Although the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid carcinoma (DTC). Therefore, the authors explored the association between sporadic DTC and family history of cancer. In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR, 4.1; 95% CI, 1.7-9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR, 4.6; 95% CI, 1.9-11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR, 7.4; 95% CI, 1.8-30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs 35.5%, P = .01). The study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. Copyright © 2011 American Cancer Society.

Family History of Cancer and Risk of Sporadic Differentiated Thyroid Carcinoma

PubMed Central

Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K.; Sturgis, Erich M.

2011-01-01

BACKGROUND Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since 1980s. While the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid cancer (DTC). Therefore, we explored the association between sporadic DTC and family history of cancer. METHODS In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. RESULTS The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR = 4.1, 95% CI: 1.7–9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR = 4.6, 95 CI%: 1.9–11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR = 7.4, 95% CI: 1.8–30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs. 35.5%, p = 0.01). CONCLUSIONS Our study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. PMID:21800288

[Hyperfunctioning thyroid carcinoma. Description of a case].

PubMed

Pandolfi, C; Colecchia, M; Gianini, A

1997-09-01

Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3% of thyroid nodules. A particular condition is represented by the association with hyperthyroidism, which is found in about 7% of cases. Even more rarely may be themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year old male patient, bearing a recently appeared goiter, referred to us for suspicion of lung cancer and hyperthyroid symptoms, is reported. Among appropriate investigations, the finding of high titer of thyroglobulin in the aspiration needle and cytology examination suggested that thyroid lesion was primary and not metastatic, while scintiscan with J-131 isotope showed that excess of thyroid hormones was just due to it; histological diagnosis was of papillary carcinoma. As to the pathogenesis of the neoplasma during hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been suggested in the cases associated with Graves' disease, absent in our patient, which could elicitate cancer progression in the mean time. Interestingly, activating mutation of thyroid hormone receptor (TSH-r) gene has been demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the unexpected clinical behaviour may appear very rare, molecular biology studies on aspiration biopsies (FNAB) will allow, in the future, to better define the neoplastic nature of some hot nodules. In personal opinion, this particular pathology must be attently searched both for its implications in the prognosis and therapeutic strategy and because it could be less rare than generally considered up to now.

The Treatment of Differentiated Thyroid Cancer in Children: Emphasis on Surgical Approach and Radioactive Iodine Therapy

PubMed Central

Mazzaferri, Ernest L.; Verburg, Frederik A.; Reiners, Christoph; Luster, Markus; Breuer, Christopher K.; Dinauer, Catherine A.; Udelsman, Robert

2011-01-01

Pediatric thyroid cancer is a rare disease with an excellent prognosis. Compared with adults, epithelial-derived differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancer, presents at more advanced stages in children and is associated with higher rates of recurrence. Because of its uncommon occurrence, randomized trials have not been applied to test best-care options in children. Even in adults that have a 10-fold or higher incidence of thyroid cancer than children, few prospective trials have been executed to compare treatment approaches. We recognize that treatment recommendations have changed over the past few decades and will continue to do so. Respecting the aggressiveness of pediatric thyroid cancer, high recurrence rates, and the problems associated with decades of long-term follow-up, a premium should be placed on treatments that minimize risk of recurrence and the adverse effects of treatments and facilitate follow-up. We recommend that total thyroidectomy and central compartment lymph node dissection is the surgical procedure of choice for children with DTC if it can be performed by a high-volume thyroid surgeon. We recommend radioactive iodine therapy for remnant ablation or residual disease for most children with DTC. We recommend long-term follow-up because disease can recur decades after initial diagnosis and therapy. Considering the complexity of DTC management and the potential complications associated with therapy, it is essential that pediatric DTC be managed by physicians with expertise in this area. PMID:21880704

American Thyroid Association consensus review and statement regarding the anatomy, terminology, and rationale for lateral neck dissection in differentiated thyroid cancer.

PubMed

Stack, Brendan C; Ferris, Robert L; Goldenberg, David; Haymart, Megan; Shaha, Ashok; Sheth, Sheila; Sosa, Julie Ann; Tufano, Ralph P

2012-05-01

Cervical lymph node metastases from differentiated thyroid cancer (DTC) are common. Thirty to eighty percent of patients with papillary thyroid cancer harbor lymph node metastases, with the central neck being the most common compartment involved. The goals of this study were to: (1) identify appropriate methods for determining metastatic DTC in the lateral neck and (2) address the extent of lymph node dissection for the lateral neck necessary to control nodal disease balanced against known risks of surgery. A literature review followed by formulation of a consensus statement was performed. Four proposals regarding management of the lateral neck are made for consideration by organizations developing management guidelines for patients with thyroid nodules and DTC including the next iteration of management guidelines developed by the American Thyroid Association (ATA). Metastases to lateral neck nodes must be considered in the evaluation of the newly diagnosed thyroid cancer patient and for surveillance of the previously treated DTC patient. Lateral neck lymph nodes are a significant consideration in the surgical management of patients with DTC. When current guidelines formulated by the ATA and by other international medical societies are followed, initial evaluation of the DTC patient with ultrasound (or other modalities when indicated) will help to identify lateral neck lymph nodes of concern. These findings should be addressed using fine-needle aspiration biopsy. A comprehensive neck dissection of at least nodal levels IIa, III, IV, and Vb should be performed when indicated to optimize disease control.

A novel variation of the recurrent laryngeal nerve.

PubMed

Wu, Gaosong; Wang, Kun

2017-06-02

Injury to the recurrent laryngeal nerve is one of the most severe complications of thyroid surgery. Several anatomic variations of the nerve increase the likelihood of iatrogenic damage. A 50-year-old woman was presented to our department with a nodule in the right thyroid lobe, and she reported no voice changes. She had no history of surgery or radiation to the head or neck. Fine-needle aspiration was recorded as papillary thyroid carcinoma. The preoperative laryngoscopy revealed left vocal cord paralysis. Right thyroid lobectomy was performed. A scarce course of the left recurrent laryngeal nerve was found during the operation that ascended along the medial edge of the superior thyroid pole and finally disappeared beneath the superior cornu of the thyroid cartilage without any tracheal, esophageal, or laryngeal branches. The patient was discharged on the third postoperative day with the diagnoses of papillary thyroid carcinoma and congenital left vocal cord paralysis. The novel variation of the recurrent laryngeal nerve may challenge the current concept of the anatomy of the nerve. The vocal folds mobility should be examined routinely before surgery in patients undergoing thyroid operation.

miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers.

PubMed

Saiselet, Manuel; Pita, Jaime M; Augenlicht, Alice; Dom, Geneviève; Tarabichi, Maxime; Fimereli, Danai; Dumont, Jacques E; Detours, Vincent; Maenhaut, Carine

2016-08-09

As in many cancer types, miRNA expression profiles and functions have become an important field of research on non-medullary thyroid carcinomas, the most common endocrine cancers. This could lead to the establishment of new diagnostic tests and new cancer therapies. However, different studies showed important variations in their research strategies and results. In addition, the action of miRNAs is poorly considered as a whole because of the use of underlying dogmatic truncated concepts. These lead to discrepancies and limits rarely considered. Recently, this field has been enlarged by new miRNA functional and expression studies. Moreover, studies using next generation sequencing give a new view of general miRNA differential expression profiles of papillary thyroid carcinoma. We analyzed in detail this literature from both physiological and differential expression points of view. Based on explicit examples, we reviewed the progresses but also the discrepancies and limits trying to provide a critical approach of where this literature may lead. We also provide recommendations for future studies. The conclusions of this systematic analysis could be extended to other cancer types.

Chronic lymphocytic thyroiditis does not influence the risk of recurrence in patients with papillary thyroid carcinoma and excellent response to initial therapy.

PubMed

Carvalho, Marina S; Rosario, Pedro W; Mourão, Gabriela F; Calsolari, Maria R

2017-03-01

This study evaluated the recurrence in patients with papillary thyroid cancer and an excellent response to initial therapy, comparing those with and without chronic lymphocytic thyroiditis. This was a prospective study. Patients who met the following criteria were selected: diagnosis of papillary thyroid cancer; submitted to total thyroidectomy followed or not by ablation with 131 I; and neck ultrasonography without abnormalities, nonstimulated thyroglobulina (Tg) ≤0.2 ng/ml, and undetectable antithyroglobulin antibodies (TgAb) 12-18 months after initial therapy. The patients were divided into two groups: group A, with chronic lymphocytic thyroiditis on histology; group B, without chronic lymphocytic thyroiditis on histology. Groups A and B were similar in terms of sex and age of the patients, characteristics of the tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients with chronic lymphocytic thyroiditis were more likely to progress to persistently borderline TgAb. No patient had positive TgAb (above the reference value) during follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but that returned to undetectable spontaneously, and in 1/13 (7.7 %) with persistently borderline TgAb. These rates did not differ significantly (p = 0.25). The results of the present study showed the absence of an association between chronic lymphocytic thyroiditis and recurrence risk at least in patients with an excellent response to initial therapy.

[Oncogenes RET/PTC and mechanisms of their involvement in thyroid cancerogenesis].

PubMed

Voskoboĭnyk, L H

2009-01-01

Papillary thyroid carcinomas are the most common type of thyroid oncopathology, and are rather often associated with the expression of RET/PTC oncogens. The first oncogen RET/PTC1 was isolated more than 20 years ago. Now 13 different forms of RET/PTC are known, and 12 different partner-genes are described, that could be involved in formation of RET/PTC oncogenes. The most common of them are RET/PTC1 and RET/PTC3 forms. The great majority of oncogens RET/PTC, except for two--ELKS-RET and HOOK3-RET, have been founded in radioaction-induced thyroid tumors. There is an opinion that the key role in development of papillary thyroid carcinomas belongs to RET/PTC oncogens. The data about different types of RET/PTC oncogens, factors, that lead to their formation have been described in the present review. Also different mechanisms of activation of transduction pathways and gene's expression in thyroid cells after RET/PTC induction have been presented.

Latent childhood thyroid carcinoma in diffuse lymphocytic thyroiditis.

PubMed

Siegal, A; Mimouni, M; Kovalivker, M; Griffel, B

1983-07-01

Diffuse thyroid enlargement in a child is a rare presenting symptom of thyroid carcinoma. A papillary carcinoma may be hidden in a diffuse lymphocytic thyroiditis and should be carefully searched for during surgery. Furthermore, the finding, in frozen sections, of psammoma bodies in a lymphocytic thyroiditis should raise the suspicion of an occult malignant neoplasm. A case illustrating these diagnostic difficulties in a 5-year-old child is presented.

Transoral videolaryngoscopic surgery for papillary carcinoma arising in lingual thyroid.

PubMed

Mogi, Chisato; Shinomiya, Hirotaka; Fujii, Natsumi; Tsuruta, Tomoyuki; Morita, Naruhiko; Furukawa, Tatsuya; Teshima, Masanori; Kanzawa, Maki; Hirokawa, Mitsuyoshi; Otsuki, Naoki; Nibu, Ken-Ichi

2018-05-15

Carcinoma arising in lingual thyroid is an extremely rare entity accounting for only 1% of all reported ectopic thyroids. Here, we report a case of carcinoma arising in lingual thyroid, which has been successfully managed by transoral resection and bilateral neck dissections. A lingual mass 4-cm in diameter with calcification was incidentally detected by computed tomography at medical check-up. No thyroid tissue was observed in normal position. Ultrasound examination showed bilateral multiple lymphadenopathies. Fine needle aspiration biopsy from lymph node in his right neck was diagnosed as Class III and thyroglobulin level of the specimen was 459ng/ml. Due to the difficulty in performing FNA of the lingual masses, right neck dissection was performed in advance for diagnostic purpose. Pathological examination showed existence of large and small follicular thyroid tissues in several lymph nodes, suggesting lymph node metastasis from thyroid carcinoma. Two months after the initial surgery, video-assisted transoral resection of lingual thyroid with simultaneous left neck dissection was performed. Postoperative course was uneventful. Papillary carcinoma was found in the lingual thyroid and thyroid tissues were also found in left cervical lymph nodes. Video-assisted transoral resection was useful for the treatment of thyroid cancer arising in lingual thyroid. Copyright © 2018 Elsevier B.V. All rights reserved.

Surgical implications of B-RafV600E mutation in fine-needle aspiration of thyroid nodules

PubMed Central

Mekel, Michal; Nucera, Carmelo; Hodin, Richard A.; Parangi, Sareh

2013-01-01

BACKGROUND Management of patients with thyroid nodules is based on establishing an accurate diagnosis; however, differentiating benign from malignant lesions preoperatively is not always possible using current cytological techniques. Novel molecular testing on cytological material could lead to clearer treatment algorithms. B-RafV600E mutation is the most common genetic alteration in thyroid cancer, specifically found in papillary thyroid cancer (PTC), and usually reported to be associated with aggressive disease. DATA SOURCE A literature search using PubMed identified all the pertinent literature on the identification and utilization of the B-RafV600E mutation in thyroid cancer. CONCLUSIONS The utility of using B-Raf mutation testing for nodules with indeterminate cytology is limited since many of those nodules (benign and malignant) do not harbor B-Raf mutations. However, when the pathologist sees cytological features suspicious for PTC, B-RafV600E mutation analysis may enhance the assessment of preoperative risks for PTC, directing a more aggressive initial surgical management when appropriate. PMID:20637346

Influence of presence/absence of thyroid gland on the cutoff value for thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid carcinoma.

PubMed

Zhao, Huan; Wang, Yong; Wang, Min-Jie; Zhang, Zhi-Hui; Wang, Hai-Rui; Zhang, Bing; Guo, Hui-Qin

2017-04-28

Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a sensitive method for detecting metastatic papillary thyroid carcinoma (PTC). However, the diagnostic threshold is not well established and the influence of the thyroid gland on the cutoff value is also controversial. In this study, patients were classified into two groups according to the presence or absence of thyroid tissue, to determine an appropriate cutoff value for clinical practice. Patients with a history of thyroid nodules or surgery for PTC and with enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA detection. One hundred ninety-six lymph nodes (189 patients) were included: 100 from preoperative patients, 49 from patients treated with partial thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%). Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in patients without thyroids. The cutoff value for Tg-FNA is influenced by residual thyroid tissue, and a higher cutoff value is recommended for patients with thyroids than for patients without thyroids.

Application of a cervical low incision in the functional neck dissection of thyroid papillary carcinoma.

PubMed

Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Kejing; Shang, Jinbiao; Fang, Xianhua; Ge, Minghua; Tan, Zhuo

2016-04-01

The present study aimed to discuss the advantage of the application of a cervical low incision for functional neck dissection in patients with thyroid papillary carcinoma. The study was a retrospective analysis of 87 thyroid papillary carcinoma patients; cervical low incision in the functional neck dissection was applied for 47 cases and the classic 'L' incision was applied for 40 cases. The different integrity, surgical time, blood loss and the aesthetic property of the incision were compared between the cervical low incision and the classic 'L' incision for lateral neck dissection of thyroid cancer. The postoperative pathological diagnosis was that the average total amount and the region II lymph nodes of the unilateral neck dissection were 33 and 10 for the cervical low incision group, and 32 and 11 for the classic 'L' incision group, respectively (P>0.05). The average unilateral neck dissection times were 87 and 58 min for the cervical low incision group and the classic 'L' incision group, respectively (P<0.05). The blood loss of the cervical low incision group was 67 ml, while the loss for the classic 'L' incision group was 61 ml (P>0.05). The postoperative incision of the cervical low incision group was smaller and more concealing. Additionally, the cosmetic deformities were milder for an inconspicuous cervical scar, and the sensation was improved for the patients in comparison with the classic 'L' incision group. These results suggest that the application of cervical low incision for functional neck dissection in thyroid papillary carcinoma patients aids in reducing postoperative complications, without increasing recurrence rates. Therefore, the classic 'L' incision can be replaced by the cervical low incision.

Application of a cervical low incision in the functional neck dissection of thyroid papillary carcinoma

PubMed Central

XU, JIAJIE; CHEN, CHAO; ZHENG, CHUANMING; WANG, KEJING; SHANG, JINBIAO; FANG, XIANHUA; GE, MINGHUA; TAN, ZHUO

2016-01-01

The present study aimed to discuss the advantage of the application of a cervical low incision for functional neck dissection in patients with thyroid papillary carcinoma. The study was a retrospective analysis of 87 thyroid papillary carcinoma patients; cervical low incision in the functional neck dissection was applied for 47 cases and the classic ‘L’ incision was applied for 40 cases. The different integrity, surgical time, blood loss and the aesthetic property of the incision were compared between the cervical low incision and the classic ‘L’ incision for lateral neck dissection of thyroid cancer. The postoperative pathological diagnosis was that the average total amount and the region II lymph nodes of the unilateral neck dissection were 33 and 10 for the cervical low incision group, and 32 and 11 for the classic ‘L’ incision group, respectively (P>0.05). The average unilateral neck dissection times were 87 and 58 min for the cervical low incision group and the classic ‘L’ incision group, respectively (P<0.05). The blood loss of the cervical low incision group was 67 ml, while the loss for the classic ‘L’ incision group was 61 ml (P>0.05). The postoperative incision of the cervical low incision group was smaller and more concealing. Additionally, the cosmetic deformities were milder for an inconspicuous cervical scar, and the sensation was improved for the patients in comparison with the classic ‘L’ incision group. These results suggest that the application of cervical low incision for functional neck dissection in thyroid papillary carcinoma patients aids in reducing postoperative complications, without increasing recurrence rates. Therefore, the classic ‘L’ incision can be replaced by the cervical low incision. PMID:27073645

Multifocality and Bilaterality of Papillary Thyroid Microcarcinoma

PubMed Central

So, Yoon Kyoung; Kim, Myung Woo

2015-01-01

Objectives Papillary thyroid carcinomas frequently occur as two or more separate foci within the thyroid gland (18%-87%). However, those multifocal tumors are easy to be undetected by preoperative radiologic evaluations, which lead to remnant disease after initial surgery. We aimed to study the incidence of multifocal papillary thyroid microcarcinomas (PTMCs), diagnostic accuracy of preoperative radiologic evaluation, predictive factors, and the chance of bilateral tumors. Methods Two hundred and seventy-seven patients with PTMC were included in this study. All patients underwent total thyroidectomy as an initial treatment. Medical records, pathologic reports, and radiological reports were reviewed for analysis. Results Multifocal PTMCs were detected in 100 of 277 patients (36.1%). The mean number of tumors in each patient was 1.6±1.1, ranging from 1 to 10. The additional tumor foci were significantly smaller (0.32±0.18 cm) than the primary tumors (0.63±0.22 cm) (P<0.001). There was no significant relationship between primary tumor size and the presence of contralateral tumors. With more tumors detected in one lobe, there was greater chance of contralateral tumors; 18.8% with single tumor focus, 30.2% with 2 tumor foci, and 46.2% with 3 or more tumor foci in one lobe. Sensitivity of preoperative sonography was 42.7% for multifocal tumors and 49.0% for bilateral tumors. With multivariate analysis, nodular hyperplasia was the only significant factor for multifocal tumors. Conclusion In cases of PTMCs, the incidence of multifocal tumors is high. However, additional tumor foci are too small to be diagnosed preoperatively, especially under the recent guidelines on radiologic screening tests for papillary thyroid carcinoma. Multifocal PTMCs have high risk of bilateral tumors, necessitating more extensive surgery or more thorough follow-up. PMID:26045918

Incidence of thyroid cancer in the selected areas of iodine deficiency in Poland.

PubMed

Szybiński, Z; Huszno, B; Zemla, B; Bandurska-Stankiewicz, E; Przybylik-Mazurek, E; Nowak, W; Cichon, S; Buziak-Bereza, M; Trofimiuk, M; Szybiński, P

2003-01-01

The aim of the study was to evaluate the incidence rate (IR), trend and histotype of the differentiated thyroid cancer in the selected areas with varying iodine deficiency. The study was carried out in three areas: Krakow, (Carpathian endemic goiter area with 1.99 million mixed rural and urban population), Gliwice (Upper Silesia--moderate iodine deficiency area mostly industrial with 4.89 million inhabitants) and Olsztyn (slight iodine deficiency area, mainly rural with 0.77 million inhabitants). Between 1990 and 2001, in the study area 2691 newly diagnosed cases of malignant neoplasms of the thyroid gland were registered. In over 80% of patients it was differentiated thyroid cancer: mainly in women over 40 years, with F/M ratio 5.8. The highest percentage of papillary cancer 72.9% was observed in Olsztyn and lowest--50.0%--in Krakow and Nowy Sacz districts. In this period of time incidence rate of differentiated thyroid cancer in women increased in Kraków, Gliwice, and Olsztyn from 1.51 to 9.34 in 1998 1.27 to 5.74 in 1999 and from 2.52 to 11.35 in 2001 respectively. In the youngest (0-20 years) age group no significant increase of IR was observed. Between 1998 and 2001 the dynamics of increase of the thyroid cancer incidence markedly diminished. In conclusion it was hypothesised that an increase in IR of differentiated thyroid cancer in the study area was caused mainly by the suspension of iodine prophylaxis in 1980 and was diminished by the introduction of an obligatory model of iodine prophylaxis in 1996/1997. It was modified in terms of histotype and dynamics of increase by exposure to ionizing radiation. A very specific group at risk on the population level were women aged 20-40 years in the reproductive age exposed to iodine deficiency after suspension of iodine prophylaxis in 1980 and to radiation after the Chernobyl accident in 1986.

TCGA study improves understanding of thyroid cancer genetics - TCGA

Cancer.gov

A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development.

DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers.

PubMed

Javid, Mahsa; Sasanakietkul, Thanyawat; Nicolson, Norman G; Gibson, Courtney E; Callender, Glenda G; Korah, Reju; Carling, Tobias

2018-02-01

Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis. MMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples. The findings were validated by qRT-PCR, and in follicular thyroid cancers (FTC) and follicular thyroid adenomas (FTA) for comparison. FOXO transcription factor expression was also analyzed. Protein expression was assessed by immunohistochemistry. Genomic integrity was evaluated by whole-exome sequencing-derived read-depth analysis and Mann-Whitney U test. Clinical correlations were assessed using Fisher's exact and t tests. Microarray and qRT-PCR revealed reduced expression of all four MMR genes in PTC compared with PCNT and of PMS2 compared with NT. FTC and FTA showed upregulation in MLH1, MLH3 and PMS2. PMS2 protein expression correlated with the mRNA expression pattern. FOXO1 showed lower expression in PMS2-deficient PTCs (log2-fold change -1.72 vs. -0.55, U = 11, p < 0.05 two-tailed). Rate of LOH, a measure of genomic instability, was higher in PMS2-deficient PTCs (median 3 and 1, respectively; U = 26, p < 0.05 two-tailed). No correlation was noted between MMR deficiency and clinical characteristics. MMR deficiency, potentially promoted by FOXO1 suppression, may explain the etiology for PTC development in some patients. FTC and FTA retain MMR activity and are likely caused by a different tumorigenic pathway.

Computer assisted detection and analysis of tall cell variant papillary thyroid carcinoma in histological images

NASA Astrophysics Data System (ADS)

Kim, Edward; Baloch, Zubair; Kim, Caroline

2015-03-01

The number of new cases of thyroid cancer are dramatically increasing as incidences of this cancer have more than doubled since the early 1970s. Tall cell variant (TCV-PTC) papillary thyroid carcinoma is one type of thyroid cancer that is more aggressive and usually associated with higher local recurrence and distant metastasis. This variant can be identified through visual characteristics of cells in histological images. Thus, we created a fully automatic algorithm that is able to segment cells using a multi-stage approach. Our method learns the statistical characteristics of nuclei and cells during the segmentation process and utilizes this information for a more accurate result. Furthermore, we are able to analyze the detected regions and extract characteristic cell data that can be used to assist in clinical diagnosis.

Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival.

PubMed

Zidan, Jamal; Karen, Drumea; Stein, Moshe; Rosenblatt, Edward; Basher, Walid; Kuten, Abraham

2003-03-01

The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Copyright 2003 American Cancer Society.

Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases.

PubMed

Dettloff, Jennifer; Seethala, Raja R; Stevens, Todd M; Brandwein-Gensler, Margaret; Centeno, Barbara A; Otto, Kristen; Bridge, Julia A; Bishop, Justin A; Leon, Marino E

2017-06-01

Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a t(12;15)(p13;q25) resulting in an ETV6-NTRK3 fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland or breast primary; the clinico-pathologic characteristics are reviewed. Assessment for rearrangement of the ETV6 (12p13) locus was conducted by fluorescence in situ hybridization (FISH) on representative FFPE sections using an ETV6 break apart probe (Abbott Molecular, Des Plaines, IL, USA). The patients were two females (52 and 55 years-old) and 1 male (74 years-old). The tumors were poorly circumscribed solid white tan nodules involving the thyroid. Histologically, they were invasive and showed solid, microcystic, cribriform, and tubular growth patterns composed of variably bland polygonal eosinophilic cells with vesicular nuclear chromatin and conspicuous nucleoli. All three cases showed metastasis to lymph nodes; one case showed lateral neck involvement. The tumor cells were positive for S100 and mammaglobin. GATA-3 and PAX-8 were positive in 2 cases, one of which only focally so. All three cases were negative for TTF-1 and thyroglobulin. Rearrangement of the ETV6 locus was confirmed in all cases and a diagnosis of MASC rendered for each case. A site of origin distinct from the thyroid gland was not identified, with a median follow up of 24 months. MASC may rarely involve the thyroid gland. The origin of these lesions is unknown; while an origin from ectopic salivary gland-type cells is entertained, a metastatic origin from an occult primary cannot be definitively excluded at this time. Given the histologic (follicular-like microcystic pattern with colloid-like secretions and papillary pattern), immunophenotypic (PAX-8), and even molecular overlap, MASC can be mistaken for papillary thyroid carcinoma and should be considered in the differential diagnosis of a thyroid mass.

(131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

PubMed

Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

2016-01-01

Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4).

PubMed

Farahati, J; Reiners, C; Stuschke, M; Müller, S P; Stüben, G; Sauerwein, W; Sack, H

1996-01-01

The role of adjuvant external radiotherapy in the survival of patients with differentiated thyroid cancer (DTC) is controversial. To our knowledge, no attempt has been undertaken thus far to assess the impact of this therapy with respect to the papillary and follicular types of thyroid cancer as separate entities. Between 1979 and 1992, 238 patients with differentiated papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) with Stage pT4 have been treated and followed in our clinic. One hundred sixty-nine patients free of metastases at the final staging, which was performed after the second radioiodine therapy, were included in this study. The standard treatment comprised total thyroidectomy, ablative radioiodine therapy, and thyroid-stimulating hormone-suppressive therapy with levothyroxin. Ninety-nine patients free of disease after the final staging received additional external radiotherapy to the neck (with a dose of 50-60 Gy), whereas the remaining 70 patients were treated with the standard treatment protocol only. Distributions of age, sex, and follow-up time were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence of age, sex, histologic subtype, and lymph node status as well as of external radiotherapy on the time to first locoregional and distant failure (LDF), and the time to locoregional recurrence (LR), was accomplished using Cox's proportional hazard model. In patients with DTC, external radiotherapy was a predictive factor for improvement of both LR (P = 0.004) and locoregional and distant failure (P = 0.0003). When the time to first locoregional and distant failure was calculated separately for patients with PTC and FTC, there was a significant difference in the PTC group in favor of irradiated patients (P = 0.0001), whereas there was no effect of external radiotherapy in the FTC group (P = 0.38). Further analyses disclosed that this effect was significantly present only in patients with PTC and lymph node involvement (P = 0.002), whereas those without lymph node involvement did not benefit from an additional adjuvant radiotherapy (P = 0.27). Because none of the patients younger than age 40 years died due to the disease nor had progressive disease during follow-up, we reassessed our results in patients older than age 40 years. The effect of external radiotherapy could be confirmed in this subgroup of patients (P = 0.0009) and in the subgroup of lymph node positive patients older than age 40 years with invasive PTC (P = 0.01). In addition to total thyroidectomy, treatment with radioiodine, and TSH-suppressive therapy with thyroid hormone, adjuvant external radiotherapy improves the recurrence-free survival in patients older than age 40 years with invasive PTC and lymph node involvement.

Iodide transport: implications for health and disease

PubMed Central

2014-01-01

Disorders of the thyroid gland are among the most common conditions diagnosed and managed by pediatric endocrinologists. Thyroid hormone synthesis depends on normal iodide transport and knowledge of its regulation is fundamental to understand the etiology and management of congenital and acquired thyroid conditions such as hypothyroidism and hyperthyroidism. The ability of the thyroid to concentrate iodine is also widely used as a tool for the diagnosis of thyroid diseases and in the management and follow up of the most common type of endocrine cancers: papillary and follicular thyroid cancer. More recently, the regulation of iodide transport has also been the center of attention to improve the management of poorly differentiated thyroid cancer. Iodine deficiency disorders (goiter, impaired mental development) due to insufficient nutritional intake remain a universal public health problem. Thyroid function can also be influenced by medications that contain iodide or interfere with iodide metabolism such as iodinated contrast agents, povidone, lithium and amiodarone. In addition, some environmental pollutants such as perchlorate, thiocyanate and nitrates may affect iodide transport. Furthermore, nuclear accidents increase the risk of developing thyroid cancer and the therapy used to prevent exposure to these isotopes relies on the ability of the thyroid to concentrate iodine. The array of disorders involving iodide transport affect individuals during the whole life span and, if undiagnosed or improperly managed, they can have a profound impact on growth, metabolism, cognitive development and quality of life. PMID:25009573

Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

PubMed

Gunalp, Bengul; Okuyucu, Kursat; Ince, Semra; Ayan, Aslı; Alagoz, Engin

2017-01-01

There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology. A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients. In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients. Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.

Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa.

PubMed

Mulaudzi, T V; Ramdial, P K; Madiba, T E; Callaghan, R A

2001-05-01

Western literature depicts papillary carcinoma as the most common thyroid malignancy followed by follicular carcinoma. To assess the clinical pattern of thyroid carcinoma among African and Indian patients. King Edward VIII Hospital, Durban, South Africa. A retrospective study. One hundred patients with thyroid carcinoma treated at a tertiary teaching hospital between 1990 and 1997. Seventy seven patients were Africans and 23 were Indians. The male to female ratio was 1:6. Ninety eight patients presented with goitre with or without regional lymph node involvement or distant disease. The duration of symptoms ranged from one to 360 months. The mean age at presentation was 48.6 +/- 16.0 years. Follicular carcinoma was the most common malignancy among African patients (68%), followed by papillary carcinoma (16%), anaplastic carcinoma (13%) and medullary carcinoma (2.6%). Papillary carcinoma was the most common malignancy among Indian patients (57%) followed by follicular carcinoma and medullary carcinoma. There was no anaplastic carcinoma among Indian patients. Fifty five patients underwent lobectomy with 32 undergoing subsequent completion thyroidectomy. Nine patients had near total thyroidectomy, 27 were offered total thyroidectomy as primary surgery and eight had biopsy only. The in-hospital mortality was 8%. Recurrence rate was 8%. Most patients present long after the development of symptoms. Follicular carcinoma is the most common thyroid malignancy among Africans. Further studies are required to explain this phenomenon.

A distinct variant of papillary thyroid carcinoma indicating familial adenomatous polyposis (FAP): a case report and brief review.

PubMed

Liyanapathirana, Nishantha; Seneviratne, Sanjeewa Anuruddha; Samarasekera, Dharmabandhu Nandadeva

2015-12-17

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome with an incidence of about 1/8300 births and accounts for about 1% of all colorectal cancers. It has a spectrum of extra-intestinal manifestations including thyroid carcinoma which occur in 1-2% of affected. The cribriform morular variant (CMV) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with FAP. Most of the reported cases describe the above entity in the background of well-established FAP. We report a case where both entities presenting simultaneously in a previously undiagnosed patient with FAP without a family history of polyposis. A 24 year old Asian female presented to the surgical clinic with a goitre of eight months duration and recent onset of altered bowel habits with features of anaemia. She was previously healthy and there was no family history of adenomatous polyposis, colorectal carcinoma or thyroid neoplasms. Colonoscopy revealed large bowel polyposis and fine needle aspiration of thyroid revealed a smear suspicious for malignancy. She underwent total thyroidectomy which revealed CMV PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clusters arranged as morules along with papillary structures which are the key features of this subtype. Diagnosis of CMV warrants ruling out of underlying FAP, irrespective of family history or gastrointestinal symptoms.

Childhood Thyroid Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Childhood thyroid cancer usually presents as a thyroid mass with or without painless cervical adenopathy. It may occur as part of a tumor predisposition syndrome such as multiple endocrine neoplasia or DICER1 syndrome. Get detailed information about the risk factors, histopathology, molecular features, presentation, diagnostic evaluation, and treatment of papillary, follicular, and medullary thyroid cancer in this summary for clinicians.

Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer.

PubMed

Kim, Su-jin; Myong, Jun Pyo; Jee, Hyeon-Gun; Chai, Young Jun; Choi, June Young; Min, Hye Sook; Lee, Kyu Eun; Youn, Yeo-Kyu

2016-01-01

The purpose of this study was to evaluate the association between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid cancer (PTC) and to determine their combined association with tumor aggressiveness in PTC. A total of 1780 patients with PTC who underwent surgery were enrolled in this study. Simple and multiple analyses were performed to determine the association between Hashimoto's thyroiditis and the BRAF(V600E) mutation in PTC. Hashimoto's thyroiditis was present in 11.5% of patients (204/1780) with PTC. Multiple logistic regressions showed that BRAF(V600E) (odds ratio [OR] = 0.493; 95% confidence interval [CI] = 0.360-0.678) and the female sex (OR = 7.146; 95% CI = 3.408-18.347) were independent factors associated with Hashimoto's thyroiditis in PTC. BRAF(V600E) mutation and the Hashimoto's thyroiditis-negative PTC group were associated with aggressive disease (OR = 3.069; 95% CI = 1.654-5.916). Hashimoto's thyroiditis was associated less frequently with BRAF(V600E) , and frequently with the female sex in patients with PTC. Hashimoto's thyroiditis and BRAF(V600E) status may help to predict clinical outcome of PTC. © 2015 Wiley Periodicals, Inc.

Time trends for thyroid cancer in northwestern Spain: true rise in the incidence of micro and larger forms of papillary thyroid carcinoma.

PubMed

Rego-Iraeta, Antonia; Pérez-Méndez, Luisa F; Mantinan, Beatriz; Garcia-Mayor, Ricardo V

2009-04-01

Thyroid cancer incidence is increasing throughout the world. Most studies attribute this rise entirely to the increase in papillary carcinoma, the most common thyroid malignancy in iodine-sufficient areas. A variety of nonetiological factors such as changes in clinical practice may affect the incidence of thyroid cancer and some researchers have suggested that this rise is only apparent due to an increase in diagnostic activity. Since data on the epidemiology of thyroid cancer in Spain are scarce, the main goal of this study was to analyze changes in thyroid cancer presentation, incidence, and prevalence in Vigo (northwestern Spain) between 1978 and 2001, and to investigate the relationship between the incidence rates and trends in tumor size and thyroid surgery. In this descriptive epidemiologic study, an analysis was carried out on new thyroid cancer cases obtained from the Pathology Registry of the University Hospital of Vigo (500,000 inhabitants). Trends in age, sex, thyroid surgery, histological type, tumor size, and incidence rates were calculated. The prevalence of thyroid cancer was determined in three cross-sectional surveys. The rate of population undergoing thyroid surgery significantly increased over time. Out of 322 new primary thyroid cancers, papillary thyroid cancer (PTC) was the predominant type (76%). The age-standardized incidence rate shows a significant increase in females: 1.56 per 100,000 year (1978 to 1985) to 3.83 (1986 to 1993) and 8.23 (1994 to 2001); and in males: 0.33, 1.19, and 2.65, respectively. PTC was mainly responsible for this pattern and was the result of both the increase in micropapillary thyroid carcinoma (MPTC) incidence and in PTC measuring more than 1 cm. Besides MPTC cases, no significant variations were observed in tumor size over time. In northwestern Spain, the incidence of thyroid cancer is increasing. These data should be taken into account when planning health resources for these patients. Our results may reflect the contribution that other factors, besides increased diagnostic activity, have made to the rise in thyroid cancer incidence in our region. Additional studies are needed to explain the rise in PTC incidence throughout the world and to search for potential risk factors that are currently unrecognized.

TCGAthyroidNewsNote

Cancer.gov

A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas (PTC) – the most common form of thyroid cancer – has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive diseas

Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?

PubMed

Rusinek, Dagmara; Chmielik, Ewa; Krajewska, Jolanta; Jarzab, Michal; Oczko-Wojciechowska, Malgorzata; Czarniecka, Agnieszka; Jarzab, Barbara

2017-08-22

A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are some aggressive forms, which do not respond to standard treatment. There are still some questions, which have to be resolved to avoid dangerous simplifications in the clinical management. In this article, we focused on the current advantages in preoperative molecular diagnostic tests and histopathological examination including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We discussed the controversies regarding the extent of thyroid surgery and adjuvant radioiodine therapy, as well as new treatment modalities for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Considering medullary thyroid cancer (MTC), we analyzed a clinical management based on histopathology and RET (ret proto-oncogene) mutation genotype, disease follow-up with a special attention to serum calcitonin doubling time as an important prognostic marker, and targeted therapy applied in advanced MTC. In addition, we provided some data regarding anaplastic thyroid cancer (ATC), a highly lethal neoplasm, which lead to death in nearly 100% of patients due to the lack of effective treatment options.

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

PubMed

Can, Nuray; Celik, Mehmet; Sezer, Yavuz Atakan; Ozyilmaz, Filiz; Ayturk, Semra; Tastekin, Ebru; Sut, Necdet; Gurkan, Hakan; Ustun, Funda; Bulbul, Buket Yilmaz; Guldiken, Sibel; Puyan, Fulya Oz

2017-08-20

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.

PubMed

La Perle, K M; Jhiang, S M; Capen, C C

2000-08-01

Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53-/- mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53-/- mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53-/- mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/- mice

Natural history of thyroid cancer [Review].

PubMed

Takano, Toru

2017-03-31

Thyroid cancers have long been considered to arise in middle age and, after their repeated proliferation, resulting in further damage to the genome, they progress to more aggressive and lethal cancers. However, in 2014, some studies were reported that might lead to a marked change in our understanding of the natural history of thyroid cancer. A high prevalence of papillary carcinoma in the young suggested that the first initiation of thyroid cancer is likely to occur in the infantile period. Such a conclusion was also supported by a very slow growth rate of papillary microcarcinomas (PMCs) in an observation trial. The proliferation rate of PMCs was negatively correlated with the age, and surgery to remove PMCs did not contribute to reduce mortality from thyroid cancer. These findings strongly suggested the existence of self-limiting cancers, which are truly malignant but do not progress to lethal cancers, for the first time in human history. The early detection of self-limiting cancers results in overdiagnosis. Ultrasonographic screening of the thyroid in the young should be avoided. Lethal thyroid cancers, whose origin is still unknown, appear suddenly after middle age. In the elderly, thyroid cancers are a mixture of self-limiting and lethal cancers; thus, when thyroid cancer is detected, careful follow-up with examination of its growth rate is required.

Partial thyrocyte-specific Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.

PubMed

Patyra, Konrad; Jaeschke, Holger; Löf, Christoffer; Jännäri, Meeri; Ruohonen, Suvi T; Undeutsch, Henriette; Khalil, Moosa; Kero, Andreina; Poutanen, Matti; Toppari, Jorma; Chen, Min; Weinstein, Lee S; Paschke, Ralf; Kero, Jukka

2018-05-25

Thyroid function is controlled by thyroid-stimulating hormone (TSH), which binds to its G protein-coupled receptor [thyroid-stimulating hormone receptor (TSHR)] on thyrocytes. TSHR can potentially couple to all G protein families, but it mainly activates the G s - and G q/11 -mediated signaling cascades. To date, there is a knowledge gap concerning the role of the individual G protein cascades in thyroid pathophysiology. Here, we demonstrate that the thyrocyte-specific deletion of G s -protein α subunit (Gα s ) in adult mice [tamoxifen-inducible G s protein α subunit deficient (iTGα s KO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGα s KO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGα s KO mice. Unexpectedly, hyperplastic follicles and papillary thyroid cancer-like tumor lesions with increased proliferation and slightly increased phospho-ERK1/2 staining were found in iTGα s KO mice at an older age. These tumors developed from nonrecombined thyrocytes still expressing Gα s in the presence of highly elevated serum TSH. In summary, we report that partial thyrocyte-specific Gα s deletion leads to hypothyroidism but also to tumor development in thyrocytes with remaining Gα s expression. Thus, these mice are a novel model to elucidate the pathophysiological consequences of hypothyroidism and TSHR/G s /cAMP-mediated tumorigenesis.-Patyra, K., Jaeschke, H., Löf, C., Jännäri, M., Ruohonen, S. T., Undeutsch, H., Khalil, M., Kero, A., Poutanen, M., Toppari, J., Chen, M., Weinstein, L. S., Paschke, R., Kero, J. Partial thyrocyte-specific Gα s deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.

Follicular variant of papillary thyroid carcinoma presenting as toxic nodule in an adolescent: coexistent polymorphism of the TSHR and Gsα genes.

PubMed

Ruggeri, Rosaria Maddalena; Campennì, Alfredo; Giovinazzo, Salvatore; Saraceno, Giovanna; Vicchio, Teresa Manuela; Carlotta, Dario; Cucinotta, Maria Paola; Micali, Carmelo; Trimarchi, Francesco; Tuccari, Giovanni; Baldari, Sergio; Benvenga, Salvatore

2013-02-01

Autonomously functioning, "hot", thyroid nodules are not common in children and adolescents. Such nodules are not considered alarming because they are assumed to be benign adenomas. Herein, we present a 15-year-old girl with a papillary thyroid carcinoma of 3.5 cm in diameter, which was functionally autonomous and scintigraphically hot. The patient, initially referred to our Endocrine Unit because of a thyroid nodule, returned 6 months later for symptoms of hyperthyroidism. Hyperthyroidism was confirmed biochemically. Radioactive iodine ((131)I) thyroid scintigraphy was consistent with an autonomous thyroid nodule. As per guidelines, the patient underwent surgery and a pathological examination revealed papillary carcinoma, follicular variant. The excised nodule was examined for activating mutations of the thyrotropin receptor (TSHR), Gsα (GNAS1), H-RAS, N-RAS, K-RAS, and BRAF genes by direct sequencing. No mutations were found. Nevertheless, two combined nonfunctioning mutations were detected: a single-nucleotide polymorphism (SNP) of the TSHR gene, in exon 7, at codon 187 (AAT→AAC, both encoding asparagine), and a SNP within exon 8 of the Gsα gene at codon 185 (ATC→ATT, both encoding isoleucine). Both SNPs were also identified in the germline DNA of the patient. The same SNPs were sought in the parents and brother of our patient. Her father was heterozygous for the TSHR SNP, her mother heterozygous for the Gsα SNP, and her brother was wild type. This case demonstrates that the presence of hyperfunctioning thyroid nodule(s) does not rule out cancer and warrants careful evaluation, especially in childhood and adolescence to overlook malignancy.

The impact of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature terminology in the routine diagnosis of thyroid tumours.

PubMed

Jaconi, M; Manzoni, M; Pincelli, A I; Giardini, V; Scardilli, M; Smith, A; Fellegara, G; Pagni, F

2017-12-01

Due to the recent proposal of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice. A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically-treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III-IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC-like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1). In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC-like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low-risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations. © 2017 John Wiley & Sons Ltd.

Risk Stratification of Neck Lesions Detected Sonographically During the Follow-Up of Differentiated Thyroid Cancer.

PubMed

Lamartina, Livia; Grani, Giorgio; Biffoni, Marco; Giacomelli, Laura; Costante, Giuseppe; Lupo, Stefania; Maranghi, Marianna; Plasmati, Katia; Sponziello, Marialuisa; Trulli, Fabiana; Verrienti, Antonella; Filetti, Sebastiano; Durante, Cosimo

2016-08-01

The European Thyroid Association (ETA) has classified posttreatment cervical ultrasound findings in thyroid cancer patients based on their association with disease persistence/recurrence. The objective of the study was to assess this classification's ability to predict the growth and persistence of such lesions during active posttreatment surveillance of patients with differentiated thyroid cancer (DTC). This was a retrospective, observational study. The study was conducted at a thyroid cancer center in a large Italian teaching hospital. Center referrals (2005-2014) were reviewed and patients selected with pathologically-confirmed DTC; total thyroidectomy, with or without neck dissection and/or radioiodine remnant ablation; abnormal findings on two or more consecutive posttreatment neck sonograms; and subsequent follow-up consisting of active surveillance. Baseline ultrasound abnormalities (thyroid bed masses, lymph nodes) were classified according to the ETA system. Patients were divided into group S (those with one or more lesions classified as suspicious) and group I (indeterminate lesions only). We recorded baseline and follow-up clinical data through June 30, 2015. The main outcomes were patients with growth (>3 mm, largest diameter) of one or more lesions during follow-up and patients with one or more persistent lesions at the final visit. The cohort included 58 of the 637 DTC cases screened (9%). A total of 113 lesions were followed up (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 y), group I had significantly lower rates than group S of lesion growth (8% vs 36%, P = .01) and persistence (64% vs 97%, P = .014). The median time to scan normalization was 2.9 years. The ETA's evidence-based classification of sonographically detected neck abnormalities can help identify papillary thyroid cancer patients eligible for more relaxed follow-up.

Inhibition of the Growth of Papillary Thyroid Carcinoma Cells by CI-1040

PubMed Central

Henderson, Ying C.; Ahn, Soon-Hyun; Clayman, Gary L.

2015-01-01

Background Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, usually possesses mutations, either RET/PTC rearrangement or BRAF mutation. Both mutations can activate the mitogen-activated protein kinase kinase/extracellular signal–related kinase signaling transduction pathway, which results in activation of transcription factors that regulate cellular proliferation, differentiation, and apoptosis. Objective To test the effects of CI-1040 (PD184352), a specific MEK1/2 inhibitor, on PTC cells carrying either an RET/PTC1 rearrangement or a BRAF mutation. Design The effects of CI-1040 on PTC cells were evaluated in vitro and in vivo. Main Outcome Measures The effects of CI-1040 on PTC cells were evaluated in vitro using a cell proliferation assay, cell cycle analysis, and immunoblotting. The antitumor effects of CI-1040 in vivo were evaluated in an orthotopic mouse model. Results The concentrations of CI-1040 needed to inhibit 50% cell growth were 0.052μM for PTC cells with a BRAF mutation and 1.1μM for PTC cells with the RET/PTC1 rearrangement. After 3 weeks of oral administration of CI-1040 (300 mg/kg/d) to mice with orthotopic tumor implants of PTC cells, the mean tumor volume of implants bearing the RET/PTC1 rearrangement (n=5) was reduced 47.5% compared with untreated mice (from 701.9 to 368.5 mm3), and the mean volume of implants with a BRAF mutation (n=8) was reduced 31.3% (from 297.3 to 204.2 mm3). Conclusions CI-1040 inhibits PTC cell growth in vitro and in vivo. Because RET/PTC rearrangements are unique to thyroid carcinomas and a high percentage of PTCs possess either mutation, these findings support the clinical evaluation of CI-1040 for patients with PTC. PMID:19380355

A comparative study of cell cycle mediator protein expression patterns in anaplastic and papillary thyroid carcinoma.

PubMed

Evans, Juanita J; Crist, Henry S; Durvesh, Saima; Bruggeman, Richard D; Goldenberg, David

2012-07-01

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p < 0.05) in thyroglobulin expression and statistically significant increases (p < 0.05) in Ki-67 and p53 expression as compared with the PTC cohort. A trend toward loss of p16 and p21 expression was noted in the ATC cohort. A trend toward decreased survival was noted with p21 expression. These data indicate disruption of the normal cell cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

Correlation between serum lead and thyroid diseases: papillary thyroid carcinoma, nodular goiter, and thyroid adenoma.

PubMed

Li, Hui; Li, Xiang; Liu, Jie; Jin, Langping; Yang, Fan; Wang, Junbo; Wang, Ouchen; Gao, Ying

2017-10-01

Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p < 0.05). This difference remained significant in females when stratified by sex. Serum lead was negatively correlated with TSH (r s  =  - 0.27, p < 0.05) in PTC group. T3 was positively related to lead at quartile4 (r s  = 0.61, p < 0.05) in PTC group. No significant correlations were observed between lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.

Malignant pleural effusion from papillary thyroid carcinoma diagnosed by pleural effusion cytology: A case report.

PubMed

Kosmas, Konstantinos; Tsonou, Anna; Mitropoulou, Georgia; Salemi, Eufrosyni; Kazi, Danai; Theofanopoulou, Ageliki

2018-02-01

Papillary thyroid carcinoma (PTC) is by far the most common thyroid malignancy (over 85%) of all the thyroid cancers. It has excellent prognosis and 10-year survival rate in most of the cases (95%). Most of the tumors are indolent and do not recur or metastasize after removal. However, widespread metastases to lung, skeleton, central nervous system and, occasionally, other organs may be observed. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion (MPE) and portend poor prognosis. This article reports the cytomorphologic and immunocytochemical findings of a female patient with a symptomatic pleural effusion resulting from PTC metastatic to the pleura. Pleural fluid cytology revealed abundant papillary clusters with relatively nuclear pleomorphism, intranuclear cytoplasmic inclusions and nuclear grooves, small and distinct nucleoli as well as small discrete vacuoles. Psammoma bodies were not seen. Immunocytochemical staining was positive for TGB, EMA, Ber-EP4, CK19, and negative for TTF-1. Metastasis of PTC to pleural fluid is extremely rare and diagnosing the disease by cytology is challenging and requires medical expertise as well as knowledge of clinical context and immunocytochemical staining. Additionally, a cytologic diagnosis of MPE due to PTC provides important treatment information and plays an important role in prognosis. © 2017 Wiley Periodicals, Inc.

Association of allelic loss on 1q, 4p, 7q, 9p, 9q, and 16q with postoperative death in papillary thyroid carcinoma.

PubMed

Kitamura, Y; Shimizu, K; Tanaka, S; Ito, K; Emi, M

2000-05-01

Papillary thyroid carcinomas, most of which are characterized by slow growth and good prognosis, account for the majority of thyroid carcinomas. To provide appropriate postoperative management, it is important to classify them by prediction of their prognosis. To find genetic markers associated with poor prognosis, allelic loss at all 39 nonacrocentric chromosome arms was compared in 24 deceased cases and 45 age-, sex-, stage-, and type-matched survived cases. Allelic loss was examined in primary tumors from both groups using highly polymorphic microsatellite markers on 39 nonacrocentric autosomal arms. Age at diagnosis, sex, stage, and types of tumors were matched between the two groups. No recurrent tumor was used for DNA analysis. Mean fractional allelic loss in the deceased and survived cases was 0.10+/-0.08 and 0.03+/-0.05 (P < 0.001). The survived cases showed marginal frequencies of allelic loss throughout all chromosome arms except 22q. The deceased cases showed frequent allelic losses on chromosomes 1q (37%), 4p (21%), 7q (20%), 9p (36%), 9q (31%), and 16q (29%), with significant difference (P < 0.05). These chromosome regions may include tumor suppressor genes whose inactivation is associated with aggressive phenotypes of papillary thyroid carcinoma.

Establishment and validation of the scoring system for preoperative prediction of central lymph node metastasis in papillary thyroid carcinoma.

PubMed

Liu, Wen; Cheng, Ruochuan; Ma, Yunhai; Wang, Dan; Su, Yanjun; Diao, Chang; Zhang, Jianming; Qian, Jun; Liu, Jin

2018-05-03

Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.

Sonographic findings predictive of central lymph node metastasis in patients with papillary thyroid carcinoma: influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography.

PubMed

Yoo, Yeon Hwa; Kim, Jeong-Ah; Son, Eun Ju; Youk, Ji Hyun; Kwak, Jin Young; Kim, Eun-Kyung; Park, Cheong Soo

2013-12-01

To analyze sonographic findings suggesting central lymph node metastasis of papillary thyroid carcinoma and to evaluate the influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography for predicting central lymph node metastasis. A total of 124 patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years) underwent sonographically guided fine-needle aspiration in central lymph nodes from January 2008 to July 2011. Sonographic features of size, shape, margin, thickening of the cortex, cortical echogenicity, presence of a hilum, cystic changes, calcification, and vascularity of enlarged lymph nodes were analyzed before fine-needle aspiration and classified into 2 categories (probably benign and suspicious). Sonographic findings were correlated with the pathologic diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of sonography for predicting central lymph node metastasis according to the associated thyroiditis. Fifty-one lymph nodes (39.5%) were malignant, and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical thickening, cortical echogenicity, cystic changes, calcification, and vascularity were significantly different between the benign and metastatic nodes (P < .05). On multivariate analysis, eccentric cortical thickening (odds ratio, 26.59; 95% confidence interval [CI], 3.26-216.66) and hyper echogenicity of the cortex (odds ratio, 18.46; 95% CI, 2.44-139.64) were significantly associated with malignant nodes (P < .05). The area under the curve values for sonography for predicting metastasis were 0.756 (95% CI, 0.618-0.894) in chronic lymphocytic thyroiditis-positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients. Eccentric cortical thickening and cortical hyperechogenicity were the sonographic findings predictive of central lymph node metastasis from papillary thyroid carcinoma. The diagnostic performance of sonography for predicting metastasis was superior in chronic lymphocytic thyroiditis-negative patients than in positive patients.

The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly.

PubMed

Keskin, Fatma Ela; Ozkaya, Hande Mefkure; Ferahman, Sina; Haliloglu, Ozlem; Karatas, Adem; Aksoy, Figen; Kadioglu, Pinar

2018-06-11

Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients. © Georg Thieme Verlag KG Stuttgart · New York.

Nodular Graves' disease with medullary thyroid cancer.

PubMed

Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

2015-01-01

Co-existence of thyroid nodules with Graves' disease has been reported in various studies. 10-15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves' disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves' disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC.

Asymptomatic solitary cerebral metastasis from papillary carcinoma thyroid: 131I SPECT/CT for accurate staging.

PubMed

Jain, Tarun Kumar; Karunanithi, Sellam; Sharma, Punit; Vijay, Maneesh Kumar; Ballal, Sanjana; Bal, Chandrasekhar

2014-11-01

Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is extremely rare. We here present such a case of a 48-year-old woman with PCT. SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in this patient to the right posterior parietal cortex, suggesting brain metastasis. Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately restaged the patient by detecting asymptomatic isolated brain metastasis and correctly directed the management strategy.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

PubMed Central

Waguespack, Steven G.; Bauer, Andrew J.; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M.; Dinauer, Catherine A.; Hamilton, Jill; Hay, Ian D.; Luster, Markus; Parisi, Marguerite T.; Rachmiel, Marianna; Thompson, Geoffrey B.; Yamashita, Shunichi

2015-01-01

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions. PMID:25900731

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

PubMed

Francis, Gary L; Waguespack, Steven G; Bauer, Andrew J; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M; Dinauer, Catherine A; Hamilton, Jill; Hay, Ian D; Luster, Markus; Parisi, Marguerite T; Rachmiel, Marianna; Thompson, Geoffrey B; Yamashita, Shunichi

2015-07-01

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

Follicular adenoma in ectopic thyroid. A case-report.

PubMed

Consalvo, Vincenzo; Barbieri, Gerarda; Rossetti, Amalia Rosaria Rita; Romano, Mafalda; Contieri, Rosaria; Tramontano, Salvatore; Rescigno, Carmela; Infranzi, Massimo; Lombardi, Domenico

2017-01-01

The term ectopic thyroid refers to the presence of thyroid tissue located far from its usual anatomic placement and with no vascular connection to the main gland. The presence of swelling in atypical locations is diagnostically differentiated from other pathologies like pleomorphic adenoma or carcinoma, inflammatory lesions like sialadenitis, neurogenic tumors, paraganglioma, fibrolipoma and lymphadenopaties of diverse etiologies. Here we present the case of a submandibular ectopic thyroid in a 67year old woman. She came to our attention for a left submandibular swelling. The anamnesis did not show related pathologies, as well as blood tests. Diagnostic image studies and a FNAC were performed. The mass was surgically removed and histopatology showed a follicular adenoma in the contest of the capsulated lesion. It is important to not underestimate these types of lesions and procede with hematochemical, instrumental tests and above all surgery that can eliminate any diagnostic uncertainty and on the whole be therapeutic. It should not be forgotten that ectopic thyroid tissue can be a site for adenoma or papillary carcinoma and thus any watch and wait strategy should be avoided. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Changes in active cysteine cathepsins in lysosomes from tissues thyroid papillary carcinomas with various biological characteristics].

PubMed

Kalinichenko, O V; Myshunina, T M; Tron'ko, M D

2013-01-01

To clarify possible role of cysteine cathepsin H, B and L in the proteolytic processes that contribute to the progression of tumor growth in the thyroid, we studied their activity in lysosomes isolated from the tissue of papillary carcinomas. It was shown that for these enzymes there is a dependence of the changes in their activity on a number of biological characteristics of the tumors. Thus, the sharp increase in the activity ofcathepsin H observed in lysosomes of tissue carcinomas category T2 and T3, with intra-and ekstrathyroid and lymphatic invasion of tumor cells. An increase in the activity of cathepsin B is set in the lysosomes of tissue heterogeneous follicular structure, especially in the presence of solid areas, in comparison with typical papillary tumors and in the lysosomes of tissue carcinomas in intrathyroid and cathepsin L-at extrathyroid invasion. A common feature of the enzymes is to increase the activity of cathepsins in lysosomes of tissue nonencapsulated papillary carcinomas. These enzymes probably do not take part in the invasion of tumor cells into blood vessels and in the mechanisms of tumor metastasis to regional lymph nodes. The latter shows no changes in the activity of cathepsins in lysosomes of tissue carcinomas category N1. The results indicate the different role of cathepsin H, B and L in thyroid carcinogenesis, where each enzyme has its specific function.

[Clinical guideline for management of patients with low risk differentiated thyroid carcinoma].

PubMed

Díez, Juan José; Oleaga, Amelia; Álvarez-Escolá, Cristina; Martín, Tomás; Galofré, Juan Carlos

2015-01-01

Incidence of thyroid cancer is increasing in Spain and worldwide. Overall thyroid cancer survival is very high, and stratification systems to reliably identify patients with worse prognosis have been developed. However, marked differences exist between the different specialists in clinical management of low-risk patients with thyroid carcinoma. Almost half of all papillary thyroid carcinomas are microcarcinomas, and 90% are tumors < 2 cm that have a particularly good prognosis. However, they are usually treated more aggressively than needed, despite the lack of adequate scientific support. Surgery remains the gold standard treatment for these tumors. However, lobectomy may be adequate in most patients, without the need for total thyroidectomy. Similarly, prophylactic lymph node dissection of the central compartment is not required in most cases. This more conservative approach prevents postoperative complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Postoperative radioiodine remnant ablation and strict suppression of serum thyrotropin, although effective for the more aggressive forms of thyroid cancer, have not been shown to be beneficial for the treatment of low risk patients, and may impair their quality of life. This guideline provides recommendations from the task force on thyroid cancer of the Spanish Society of Endocrinology and Nutrition for adequate management of patients with low-risk thyroid cancer. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

[Screening of benign and malignant thyroid nodules in 5 196 physical examination population].

PubMed

Li, M H; Liu, J T

2018-02-23

Objective: To investigate the distribution characteristics of thyroid nodules and thyroid cancer in physical examination population in Tianjin, and report the outcome of ultrasonography in detection of thyroid nodules. Methods: Enrolled all of physical examination population in our hospital from Jan 1, 2014 to Dec 31, 2014 as our study subjects then the thyroid gland lesions were screened by ultrasound diagnostic technique. The risk assessment of benign and malignant thyroid nodules was assessed by ultrasonography and thyroid imaging reporting and data system (TI-RADS), and the individuals were followed up for 1 year. Results: Among the 5 196 cases, the patients with thyroid nodules was 2 068 cases (39.80%). The thyroid nodules was 35.04% in male and 44.78% in female subjects, lower in females than in male cases ( P <0.001). 18 cases of thyroid cancer patients were detected (0.35%). The thyroid cancer rate were 0.34% and 0.36% in male and female respectively ( P >0.05). Thyroid nodules increased with age, but the thyroid cancer patients were mainly concentrated in the 30 to 39 years old group and 50 to 59 years old group. All of the thyroid cancer patients underwent surgical treatment, better differentiation thyroid papillary carcinoma (17 cases) in major, most were early stage cancer and micro-cancer, possessing relatively low risk of recurrence. The sensitivity, specificity and accuracy of ultrasonography and TI-RADS diagnosis of thyroid cancer was 72.22%, 98.94% and 98.85%. Conclusions: The detection rate of thyroid nodules in our population is close to 40%, and there are differences between sexes and ages. Ultrasonography and TI-RADS association is an efficient method to detect the nodules in thyroid.

Metabolic changes associated with papillary thyroid carcinoma: A nuclear magnetic resonance-based metabolomics study.

PubMed

Li, Yanyun; Chen, Minjian; Liu, Cuiping; Xia, Yankai; Xu, Bo; Hu, Yanhui; Chen, Ting; Shen, Meiping; Tang, Wei

2018-05-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients. The results were further annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG), and Human Metabolome Database, and then were analyzed using modules of pathway analysis and enrichment analysis of MetaboAnalyst 3.0. Based on the analytical techniques, we established the models of principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS‑DA) which could discriminate PTC from normal thyroid tissue, and found 15 robust differentiated metabolites from two OPLS-DA models. We identified 8 KEGG pathways and 3 pathways of small molecular pathway database which were significantly related to PTC by using pathway analysis and enrichment analysis, respectively, through which we identified metabolisms related to PTC including branched chain amino acid metabolism (leucine and valine), other amino acid metabolism (glycine and taurine), glycolysis (lactate), tricarboxylic acid cycle (citrate), choline metabolism (choline, ethanolamine and glycerolphosphocholine) and lipid metabolism (very-low‑density lipoprotein and low-density lipoprotein). In conclusion, the PTC was characterized with increased glycolysis and inhibited tricarboxylic acid cycle, increased oncogenic amino acids as well as abnormal choline and lipid metabolism. The findings in this study provide new insights into detailed metabolic changes of PTC, and hold great potential in the treatment of PTC.

Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis?

PubMed Central

Urra, Soledad; Fischer, Martin C.; Martínez, José R.; Véliz, Loreto; Orellana, Paulina; Solar, Antonieta; Bohmwald, Karen; Kalergis, Alexis; Riedel, Claudia; Corvalán, Alejandro H.; Roa, Juan C.; Fuentealba, Rodrigo; Cáceres, C. Joaquin; López-Lastra, Marcelo; León, Augusto; Droppelmann, Nicolás; González, Hernán E.

2018-01-01

Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies. PMID:29416784

Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation

PubMed Central

Chakravarty, Debyani; Santos, Elmer; Ryder, Mabel; Knauf, Jeffrey A.; Liao, Xiao-Hui; West, Brian L.; Bollag, Gideon; Kolesnick, Richard; Thin, Tin Htwe; Rosen, Neal; Zanzonico, Pat; Larson, Steven M.; Refetoff, Samuel; Ghossein, Ronald; Fagin, James A.

2011-01-01

Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAFV600E) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAFV600E, the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAFV600E expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAFV600E rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAFV600E mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications. PMID:22105174

The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing.

PubMed

Lan, Xiabin; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Cao, Jun; Zhu, Xuhang; Ge, Minghua

2018-05-25

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776-, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895- being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047-, chr9: 16435553-16437522-, and chr22: 36006931-36007153- being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Adrenal malignant melanoma masquerading as a pheochromocytoma in a patient with a history of a multifocal papillary and medullary thyroid carcinoma.

PubMed

Barmpari, Maria E; Savvidis, Christos; Dede, Anastasia D; Markogiannakis, Haridimos; Dikoglou, Christina; Xekouki, Paraskevi; Stratakis, Constantine A; Manouras, Andreas; Malaktari-Skarantavou, Sofia

2016-04-01

Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management.

Diagnosis and Treatment of Patients with Thyroid Cancer

PubMed Central

Nguyen, Quang T.; Lee, Eun Joo; Huang, Melinda Gingman; Park, Young In; Khullar, Aashish; Plodkowski, Raymond A.

2015-01-01

Background Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease. Objective To review the current approach to the diagnosis and treatment of patients with thyroid cancer. Discussion Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored. Conclusion The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality. PMID:25964831

Computed Tomography Features of Benign and Malignant Calcified Thyroid Nodules: A Single-Center Study.

PubMed

Kim, Donghyun; Kim, Dong Wook; Heo, Young Jin; Baek, Jin Wook; Lee, Yoo Jin; Park, Young Mi; Baek, Hye Jin; Jung, Soo Jin

No previous studies have investigated thyroid calcification on computed tomography (CT) quantitatively by using Hounsfield unit (HU) values. This study aimed to analyze quantitative HU values of thyroid calcification on preoperative neck CT and to assess the characteristics of benign and malignant calcified thyroid nodules (CTNs). Two hundred twenty patients who underwent neck CT before thyroid surgery from January 2015 to June 2016 were included. On soft-tissue window CT images, CTNs with calcified components of 3 mm or larger in minimum diameter were included in this study. The HU values and types of CTNs were determined and analyzed. Of 61 CTNs in 49 patients, there were 42 malignant nodules and 19 benign nodules. The mean largest diameter of the calcified component was 5.3 (2.5) mm (range, 3.1-17.1 mm). A statistically significant difference was observed in the HU values of calcified portions between benign and malignant CTNs, whereas there was no significant difference in patient age or sex or in the size, location, or type of each CTN. Of the 8 CTNs with pure calcification, 3 exhibited a honeycomb pattern on bone window CT images, and these 3 CTNs were all diagnosed as papillary thyroid carcinoma on histopathological examination. Hounsfield unit values of CTNs may be helpful for differentiating malignancy from benignity.

CIRCULATING THYROID-STIMULATING HORMONE RECEPTOR MESSENGER RNA AS A MARKER OF TUMOR AGGRESSIVENESS IN PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA.

PubMed

Aliyev, Altay; Gupta, Manjula; Nasr, Christian; Hatipoglu, Betul; Milas, Mira; Siperstein, Allan; Berber, Eren

2015-07-01

We have previously shown that thyroid-stimulating hormone receptor messenger RNA (TSHR mRNA) is detectable in the peripheral blood of patients with papillary thyroid microcarcinoma (PTmC). The aim of this study was to analyze the utility of TSHR mRNA status as a marker of tumor aggressiveness in patients with PTmC. Preoperative TSHR mRNA values were obtained in 152 patients who underwent thyroidectomy and were found to have PTmC on final pathology. Clinical parameters were analyzed from an institutional review board-approved database using χ(2) and t tests. Preoperatively, TSHR mRNA was detected in the peripheral blood in 46% of patients, which was less than that for macroscopic papillary thyroid carcinoma (PTC) (80%) but higher than for benign thyroid disease (18%) (P<.001). The focus of cancer was larger in the TSHR mRNA-positive group compared to the negative group (0.41 vs. 0.30 cm, respectively, P = .015). The prevalence of tall-cell variant was higher in the TSHR mRNA positive group. The rates of lymph node (LN) metastasis (16% vs. 10%), multifocality (46% vs. 49%), and extra-thyroidal extension (10% vs. 5%) were similar between the TSHR mRNA-positive and-negative groups, respectively. In patients 45 years or older, rate of LN metastasis was higher in those who were TSHR mRNA positive (10%) versus negative (2%) (P = .039). TSHR mRNA positivity predicted a higher likelihood of radioactive iodine treatment (36% vs. 17%, P = .009) postoperatively. This study shows that TSHR mRNA, which is a marker of circulating thyroid cancer cells, is detectable in about half of patients with PTmC. The positivity of this marker predicts a higher likelihood of LN involvement in patients with PTmC who are 45 years or older.

Impact of non-invasive follicular thyroid neoplasm with papillary-like nuclear features on the Bethesda system for reporting thyroid cytopathology: a multi-institutional study in five Asian countries.

PubMed

Bychkov, Andrey; Keelawat, Somboon; Agarwal, Shipra; Jain, Deepali; Jung, Chan Kwon; Hong, SoonWon; Lai, Chiung-Ru; Satoh, Shinya; Kakudo, Kennichi

2018-06-01

Several Western studies showed that the recent introduction of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) significantly decreased risk of malignancy for cytological diagnostic categories. We aimed to determine the impact of NIFTP on risk of malignancy within a cohort of thyroid nodules from Asian countries, and to compare distribution of diagnostic categories between NIFTP and invasive encapsulated follicular variant of papillary thyroid carcinoma (eFV-PTC). Consecutive thyroid fine-needle aspirates from six institutions were retrospectively analysed. Histopathology slides with a diagnosis of eFV-PTC were reviewed and reclassified into invasive eFV-PTC and NIFTP. The risk of malignancy was calculated with and without NIFTP. Of 11,372 thyroid nodules, 2044 had available surgical follow-up. NIFTP was diagnosed in 59 cases, which constituted 2.9% of all excised nodules, and 5.3% of malignant nodules. Preoperative cytological diagnoses for NIFTP were non-diagnostic (10.2%), benign (18.6%), atypia of undetermined significance/follicular lesion of undetermined significance (22.0%), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) (32.2%), suspicious for malignancy (SM) (11.9%), and malignant (5.1%). The only category which showed a relative reduction in risk of malignancy after reclassification of more than 20%, was FN/SFN (24.4%). There was a significantly higher prevalence of benign cytology in NIFTP (p = 0.04) and SM/malignant in invasive eFV-PTC (p = 0.05). A majority of NIFTP cases were classified in indeterminate categories, which decreased the corresponding risk of malignancy. However, the magnitude of NIFTP impact was much lower than in the Western reports. Asian countries may not experience significant effects of NIFTP reclassification on the practice of thyroid cytopathology. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Immunohistochemical detection of the BRAF V600E mutation in papillary thyroid carcinoma. Evaluation against real-time polymerase chain reaction.

PubMed

Paja Fano, Miguel; Ugalde Olano, Aitziber; Fuertes Thomas, Elena; Oleaga Alday, Amelia

2017-02-01

The BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma and is associated with a poorer clinical course. Usual methods for its study (DNA sequencing or molecular test based on PCR) are expensive and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation has been introduced. To compare the results of IHC and real time PCR (RT-PCR) in the detection of BRAF V600E mutation in papillary thyroid carcinoma. Analysis of clinical and pathological differences depending on RT-PCR results is included. A prospective study was performed in 82 consecutive samples, 54 of them taken through a core needle biopsy. IHC was performed on tissue fixed for 24hours with 10% neutral formalin using the anti-BRAF V600E (VE-1) mouse monoclonal primary antibody and was rated as positive or negative. DNA was extracted from formalin-fixed, paraffin-embedded tissues by manual microdissection, and BRAF mutation was detected by RT-PCR using the Cobas® 4800 BRAF V600 mutation test (Roche). Both techniques were concordant in 81 cases, and BRAF was positive in 49. Discordance appeared in a follicular variant showing positive IHC and negative RT-PCR, attributed to histological heterogeneity. Cost of materials for IHC was less than half of the cost for RT-PCR. IHC appears to be a reliable, economical and easily available alternative to molecular biology techniques for routine detection of the BRAF V600E mutation in papillary thyroid carcinoma patients, provided optimal fixation conditions are used. It may be a useful technique in hospitals with no access to molecular biology techniques. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Pre-operative prediction of cervical nodal metastasis in papillary thyroid cancer by 99mTc-MIBI SPECT/CT; a pilot study.

PubMed

Tangjaturonrasme, Napadon; Vasavid, Pataramon; Sombuntham, Premsuda; Keelawat, Somboon

2013-06-01

Papillary thyroid cancer has a high prevalence of cervical nodal metastasis. There is no "gold standard" imaging for pre-operative diagnosis. The aim of the present study was to assess the accuracy of pre-operative 99mTc-MBI SPECT/CT in diagnosis of cervical nodal metastasis in patients with papillary thyroid cancer Fifteen patients were performed 99Tc-MlBI SPECT/CT pre-operatively. Either positive pathological report of neck dissection or positive post-treatment I-131 whole body scan with SPECT/CT of neck was concluded for definite neck metastasis. The PPV, NPV, and accuracy of 99mTc-MIBI SPECT/CT were analyzed. The PPV NPV and accuracy were 80%, 88.89%, and 85.71%, respectively. 99mTc-MIBI SPECT/CT could localize the abnormal lymph nodes groups correctly in most cases when compared with pathological results. However the authors found one false positive case with caseating granulomatous lymphadenitis and one false negative case with positive post-treatment 1-131 whole body scan with SPECT/CT of neck on cervical nodes zone II and IV CONCLUSION: 99mTc-MIBI SPECT/CTseem promising for pre-operative staging of cervical nodal involvement in patients with papillary thyroid cancer without the need of using iodinated contrast that may complicate subsequence 1-131 treatment. However, false positive result in granulomatous inflammatory nodes should be aware of especially in endemic areas. 99mTc-MIBI SPECT/CT scan shows a good result when compared with previous study of CT or MRI imaging. The comparative study between different imaging modality and the extension of neck dissection according to MIBI result seems interesting.

Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients.

PubMed

Fayek, Ihab Samy

2015-01-01

Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value<0.001), extrathyroidal extension (p-value<0.001), level VI positive ((p-value<0.001) and level VII positive ((p-value<0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

Loss of p53 Promotes Anaplasia and Local Invasion in ret/PTC1-Induced Thyroid Carcinomas

PubMed Central

La Perle, Krista M. D.; Jhiang, Sissy M.; Capen, Charles C.

2000-01-01

Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53−/− mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53−/− mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53−/− mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/− mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/− mice ≤28 weeks of age or p53−/− mice ≤ 17 weeks of age; however, an older (170-day-old) male p53−/− mouse used to maintain the colony developed anaplastic thyroid carcinoma with liver metastases. These findings demonstrate that the lack of functional p53 in ret/PTC1 mice promotes anaplasia and invasiveness of thyroid carcinomas. PMID:10934169

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review

PubMed Central

Xing, Wanjia; Liu, Xiaohong; He, Qingqing; Zhang, Zongjing; Jiang, Zhaoshun

2017-01-01

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAFV600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAFV600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm. PMID:28928829

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review.

PubMed

Xing, Wanjia; Liu, Xiaohong; He, Qingqing; Zhang, Zongjing; Jiang, Zhaoshun

2017-09-01

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAF V600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAF V600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm.

Comparison of T stage, N stage, multifocality, and bilaterality in papillary thyroid carcinoma patients according to the presence of coexisting lymphocytic thyroiditis.

PubMed

Park, Jin Young; Kim, Dong Wook; Park, Ha Kyung; Ha, Tae Kwun; Jung, Soo Jin; Kim, Do Hun; Bae, Sang Kyun

2015-01-01

This study aimed to assess the relationship between coexisting lymphocytic thyroiditis and T-N stages of papillary thyroid carcinoma (PTC) by histopathological analysis. The study included 653 patients who underwent thyroid surgery for PTC at our hospital. Each case was classified as either Hashimoto's thyroiditis (HT), non-Hashimoto type of lymphocytic thyroiditis (NHLT), or normal according to the histopathology of thyroid parenchyma. Patient age, gender, surgical modality, location, T stage, N stage, multifocality and bilaterality were compared according to the histopathology. The prevalence of coexisting lymphocytic thyroiditis was 25.8% (169/653); HT (7.5%, 49/653) and NHLT (18.3%, 120/653). There were no significant differences in T stage, N stage, multifocality and bilaterality with regard to coexisting lymphocytic thyroiditis, regardless of whether HT and NHLT were considered collectively or discretely. Primary tumor size (p < 0.0001), location (p = 0.0011), N stage (p < 0.0001), multifocality (p < 0.0001) and bilaterality (p < 0.0001) differed significantly according to T stage, and gender (p = 0.0193), primary tumor size (p < 0.0001), T stage (p < 0.0001), multifocality (p < 0.0001) and bilaterality (p < 0.0001) differed significantly according to N stage. PTC patients with coexisting lymphocytic thyroiditis did not differ from those with normal parenchyma in terms of T stage, N stage, multifocality and bilaterality.

Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

PubMed

Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

2015-08-06

Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

Tuberculosis cervical lymphadenopathy mimics lateral neck metastasis from papillary thyroid carcinoma.

PubMed

Kim, Seok-Mo; Jun, Hak Hoon; Chang, Ho-Jin; Chun, Ki Won; Kim, Bup-Woo; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

2016-06-01

Tuberculosis (TB) lymphadenitis is a frequent cause of lymphadenopathy in areas in which TB is endemic. Cervical lymphadenopathy in TB can mimic lateral neck metastasis (LNM) from papillary thyroid carcinoma (PTC). This study evaluated the clinicopathological features of patients with PTC and TB lateral neck lymphadenopathy. Of the 9098 thyroid cancer patients who underwent thyroid cancer surgery at the Thyroid Cancer Center of Gangnam Severance Hospital between January 2009 and April 2013, 28 had PTC and showed TB lymphadenopathy of the lateral neck node. The clinicopathological features of these 28 patients were evaluated. Preoperatively, all 28 patients were diagnosed with PTC and showed cervical lymphadenopathy. All had radiological characteristics suspicious of metastasis in lateral neck nodes. Based upon the results from intraoperative frozen sections, lymph node dissection (LND) was not performed on 19 patients. Seven of eight patients who underwent LND had metastasis combined with tuberculous lymphadenopathy, with the remaining patient negative for LNM. Intraoperative sampling and frozen sectioning of lymph nodes suspicious of metastasis can help avoid unnecessary LND for tuberculous lymphadenopathy. © 2014 Royal Australasian College of Surgeons.

Coexistence of chronic lymphocytic thyroiditis and papillary thyroid carcinoma. Impact on presentation, management, and outcome.

PubMed

Dobrinja, C; Makovac, P; Pastoricchio, M; Cipolat Mis, T; Bernardi, S; Fabris, B; Piscopello, L; de Manzini, N

2016-04-01

The association between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) has been investigated for several years from different perspectives. In spite of that, there were only few attempts to design a common frame of references to understand the complex mutual interactions between the various pathways of inflammatory response and of thyroid tumor induction and progression. This study compares two independent groups of patients aiming to determine the frequency and the prognostic significance of CLT in patients with PTC. From January 2005 to September 2013, we conducted a retrospective study on 160 patients with PTC who underwent thyroidectomy. CLT was diagnosed histopathologically. Age, sex, tumor features (dimensions, angioinvasion, capsular infiltration, mono/multifocality and lymph node metastases) pathologic findings and outcome were considered. Mean follow-up (metastasis, completeness-of-resection, serum thyroglobulin levels, tumor recurrence) period was 61 months (ranged from 18 to 132 months). A p < 0.05 was considered statistically significant. Patients were divided in 2 groups. In group A there were 90 patients affected by PTC alone, and in group B there were 70 patients affected with PTC associated with CLT. Our data showed that the presence of CLT correlate with a lower grade of PTC (p < 0.05). Considering the sex of the patients there were a statistically significant correlation (p < 0.02) and the presence of CLT associated with PTC was most representative in female patients. The presence of CLT in patients with PTC correlated with a lower grade of PTC, but it does not affect the overall survival of papillary thyroid cancers. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Nodular Graves’ disease with medullary thyroid cancer

PubMed Central

Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

2015-01-01

Co-existence of thyroid nodules with Graves’ disease has been reported in various studies. 10–15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves’ disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves’ disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC. PMID:26430321

Expression of decoy receptor 3 in diffuse sclerosing variant of papillary thyroid carcinoma: correlation with M2 macrophage differentiation and lymphatic invasion.

PubMed

Chang, Wei-Chin; Chen, Jui-Yu; Lee, Chen-Hsen; Yang, An-Hang

2013-06-01

The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a unique variant of PTC that is characterized by extensive lymphovascular invasion of tumor cells in a background of lymphocytic thyroiditis. The lymphatic emboli contain tumor cells as well as macrophages, but the recruitment of these macrophages is not well understood. The aim of this study was to determine the relationship between the expression of Decoy receptor 3 (DcR3), the recruitment of tumor-associated macrophages (TAMs), and lymphatic invasion in DSV-PTC. We retrospectively examined 14 cases of DSV-PTC using immunohistochemistry studies. The density of TAMs, lymphatic vessel density, lymphatic invasion, tumor emboli area, and DcR3 expression were assessed. Statistical analyses were performed using Fisher's exact test, unpaired t-test, and linear regression. The lymphatic tumor emboli contained a relatively higher density of TAMs than stroma and classical PTC (CPTC) areas. In addition, the number of lymphatic invasions and the size of the tumor emboli area were positively correlated with the number of M2 TAMs. A higher density of M2 TAMs was associated with older patients and larger tumor size. Moreover, DcR3 was expressed only in lymphatic tumor cells and squamous metaplastic tumor cells, but not in macrophages and CPTC. In addition, the preferential expression of DcR3 in tumors was associated with higher levels of M2 TAMs and lymphatic invasion. Despite the fact that the exact relationship between DcR3, M2 macrophages, and lymphatic invasion in DSV-PTC remains to be elucidated, our findings suggest that DcR3 expression in DSV-PTC tumor cells may promote the polarized macrophage differentiation toward the M2 phenotype. This phenomenon may further promote lymphatic invasion of DSV-PTC tumor cells.

Multifocal fibrosing thyroiditis and its association with papillary thyroid carcinoma using BRAF pyrosequencing.

PubMed

Frank, Renee; Baloch, Zubair W; Gentile, Caren; Watt, Christopher D; LiVolsi, Virginia A

2014-09-01

Multifocal fibrosing thyroiditis (MFT) is characterized by numerous foci of fibrosis in a stellate configuration with fibroelastotic and fibroblastic centers entrapping epithelial structures. MFT has been proposed as a risk factor for papillary thyroid carcinoma (PTC) development. We attempted to identify whether MFT showed such molecular changes and could possibly be related to PTC. We identified seven cases of PTC with MFT in our institutional pathology database and personal consult service of one of the authors (VAL) for the years 1999 to 2012. Areas of PTC, MFT, and normal tissue were selected for BRAF analysis. Macro-dissection, DNA extraction and PCR amplification, and pyrosequencing were performed to detect BRAF mutations in codon 600. All of the MFT lesions and normal thyroid tissue were negative for BRAF mutations. Of the seven PTCs analyzed, five (71 %) were negative for BRAF mutations, while two cases were positive. In our study, none of the MFT lesions harbored BRAF mutations, whereas 29 % (two of seven) PTCs in the same gland were positive. Hence, in this small study, we found no evidence that the MFT lesion is a direct precursor to PTC. It is likely an incidental bystander in the process and a reflection of the background thyroiditis.

Influence of thyroid gland status on the thyroglobulin cutoff level in washout fluid from cervical lymph nodes of patients with recurrent/metastatic papillary thyroid cancer.

PubMed

Lee, Jun Ho; Lee, Hyun Chul; Yi, Ha Woo; Kim, Bong Kyun; Bae, Soo Youn; Lee, Se Kyung; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

2016-04-01

The influence of serum thyroglobulin (Tg) and thyroidectomy status on Tg in fine-needle aspiration cytology (FNAC) washout fluid is unclear. A total of 282 lymph nodes were prospectively subjected to FNAC, fine-needle aspiration (FNA)-Tg measurement, and frozen and permanent biopsies. We evaluated the diagnostic performance of several predetermined FNA-Tg cutoff values for recurrence/metastasis in lymph nodes according to thyroidectomy status. The diagnostic performance of FNA-Tg varied according to thyroidectomy status. The optimized cutoff value of FNA-Tg was 2.2 ng/mL. However, among FNAC-negative lymph nodes, the FNA-Tg cutoff value of 0.9 ng/mL showed better diagnostic performance in patients with a thyroid gland. An FNA-Tg/serum-Tg cutoff ratio of 1 showed the best diagnostic performance in patients without a thyroid gland. Applying the optimal cutoff values of FNA-Tg according to thyroid gland status and serum Tg level facilitates the diagnostic evaluation of neck lymph node recurrences/metastases in patients with papillary thyroid carcinoma (PTC). © 2015 Wiley Periodicals, Inc. Head Neck 38: E1705-E1712, 2016. © 2015 Wiley Periodicals, Inc.

Differential effect of extracellular matrix derived from papillary and reticular fibroblasts on epidermal development in vitro.

PubMed

Janson, David; Rietveld, Marion; Mahé, Christian; Saintigny, Gaëlle; El Ghalbzouri, Abdoelwaheb

2017-06-01

Papillary and reticular fibroblasts have different effects on keratinocyte proliferation and differentiation. The aim of this study was to investigate whether these effects are caused by differential secretion of soluble factors or by differential generation of extracellular matrix from papillary and reticular fibroblasts. To study the effect of soluble factors, keratinocyte monolayer cultures were grown in papillary or reticular fibroblast-conditioned medium. To study the effect of extracellular matrix, keratinocytes were grown on papillary or reticular-derived matrix. Conditioned medium from papillary or reticular fibroblasts did not differentially affect keratinocyte viability or epidermal development. However, keratinocyte viability was increased when grown on matrix derived from papillary, compared with reticular, fibroblasts. In addition, the longevity of the epidermis was increased when cultured on papillary fibroblast-derived matrix skin equivalents compared with reticular-derived matrix skin equivalents. The findings indicate that the matrix secreted by papillary and reticular fibroblasts is the main causal factor to account for the differences in keratinocyte growth and viability observed in our study. Differences in response to soluble factors between both populations were less significant. Matrix components specific to the papillary dermis may account for the preferential growth of keratinocytes on papillary dermis.

Incidental finding of papillary thyroid carcinoma with BRAFV600E mutation in a patient with coexistent primary hyperparathyroidism and Graves’ hyperthyroidism

PubMed Central

He, Yayi; Liu, Shu; Guo, Hui; Shi, Bingyin

2014-01-01

The simultaneous occurrence of hyperthyroidism and hyperparathyroidism was previously reported to be rare, but it was recognised more and more clearly by effective evaluations. Recent studies also mentioned the coexistence of parathyroid adenoma and papillary thyroid carcinoma (PTC). The potential mechanism is still unknown. We report a case of a 46-year-old man coexisted with primary hyperparathyroidism, Graves’ hyperthyroidism and occult PTC. The patient had a 6-month history of polyphagia and irritability. Blood examinations showed elevated serum calcium and parathyroid hormone levels. Serum phosphate was lower. Thyroid function evaluation indicted Graves’ hyperthyroidism. Ultrasound showed a solitary hyperchoic thyroid nodule in the right gland. Parathyroid radioisotope scanning found a mild enhancement of 99mTc absorption in the lower part of the right parathyroid gland. A surgical exploration was carried out and the parathyroid adenoma resection was performed. An occult micro-PTC with BRAFV600E mutation was also detected. PMID:24879726

Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

PubMed Central

Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

2016-01-01

RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

In papillary thyroid carcinoma, expression by immunohistochemistry of BRAF V600E, PD-L1, and PD-1 is closely related.

PubMed

Bai, Yanhua; Guo, Ting; Huang, Xiaozheng; Wu, Qi; Niu, Dongfeng; Ji, Xinqiang; Feng, Qin; Li, Zhongwu; Kakudo, Kennichi

2018-05-01

Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be effective in treating several types of human cancer. In papillary thyroid carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor microenvironment or its potential correlation with BRAF V600E mutation status. In this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by immunohistochemistry and investigated the clinical significance of expression status. We studied the expression of PD-L1, PD-1, and BRAF V600E by immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as differentiating lymphocytes in the context of CLT from tumor-infiltrating lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1 (41%), PD-L1-/PD-1- as type 2 (17%), PD-L1+/PD-1- as type 3 (5%), and PD-L1-/PD-1+ as type 4 (37%). Significant correlations were found between expression of BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation, which are refractory to radioiodine therapy.

[Total thyroidectomy with lymph node dissection of the central compartment for node-positive, capsular invasive papillary thyroid cancer: video contribution].

PubMed

Dralle, H; Nguyen Thanh, P

2014-10-01

The aim of radical oncological surgery for nodal metastasized papillary thyroid cancer is, as for other oncological interventions in visceral surgery, the anatomy-related implementation of the concept of en bloc (no touch) resection of the organ bearing the primary tumor together with the first lymph node station, while the structures of the aerodigestive tract, the recurrent laryngeal nerves and parathyroid glands are preserved. The surgical technique is demonstrated in detail with the help of a video of the operation and which is available on-line, the advantages and disadvantages of the technique are discussed.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

PubMed

Januś, D; Wójcik, M; Drabik, G; Wyrobek, Ł; Starzyk, J B

2018-03-01

The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

Identification of metastatic papillary thyroid carcinoma in FNA specimens using thyroid peroxidase immunohistochemistry.

PubMed

Shield, P W; Crouch, S J; Papadimos, D J; Walsh, M D

2018-06-01

We evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining. Cell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non-thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma). Thyroid tumours were stained with TTF1 and Tg in addition to TPO. All cases of metastatic lung carcinoma also had TTF-1 staining results. TPO staining was negative in all non-thyroid malignancies. Ninety percent (26/29) of PTC were positive. All positive cases showed strong cytoplasmic staining, although 54% (14/26) showed positivity in less than half of the cells. By comparison, Tg staining of TPC cases was present in 62% and TTF-1 in 100%. In addition to showing higher sensitivity, interpretation of staining results with TPO was generally easier with than Tg. All metastatic lung adenocarcinomas were positive for TTF-1 and TPO negative. The six medullary cancers showed positivity in 17%, 0% and 83% with TPO, Tg and TTF-1, respectively. TPO (mAb EP159) may be a useful addition to immunohistochemical panels for FNA specimens where metastatic PTC is a consideration, particularly in cases where metastatic lung carcinoma features in the differential diagnosis. © 2018 John Wiley & Sons Ltd.

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

PubMed

Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant.

PubMed

Rossi, Esther D; Martini, Maurizio; Straccia, Patrizia; Cocomazzi, Alessandra; Pennacchia, Ilaria; Revelli, Luca; Rossi, Armando; Lombardi, Celestino Pio; Larocca, Luigi M; Fadda, Guido

2014-07-01

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.

Incidental cervical metastases from thyroid carcinoma during neck dissection.

PubMed

Périé, S; Torti, F; Lefevre, M; Chabbert-Buffet, N; Jafari, A; Lacau St Guily, J

2016-12-01

To quantify and discuss the prevalence of unsuspected thyroid lymph node metastases discovered in specimens from neck dissection for head and neck squamous cell carcinoma (HNSCC) and discuss the impact on patient management. Retrospective study between May 2004 and January 2007. University hospital. Pathological analysis of cervical lymph node dissection performed during surgery for HNSCC in a total of 349 neck dissections in 266 consecutive patients. Twenty-one patients showed metastatic lymph nodes from thyroid cancer (prevalence 7.9%): 13 cases were metastatic from a papillary thyroid carcinoma and 8 cases from a follicular carcinoma. In 5 of the 21 patients, classical dissection was associated to recurrent nerve dissection and unilateral lobectomy; no thyroid carcinoma was found. Thirteen patients received radiotherapy for HNSCC. Follow-up comprised annual ultrasonographic examination of the neck and thyroid in these 21 patients. Total thyroidectomy was decided on in 5, with discovery of 3 micro-papillary thyroid carcinomas, in a single patient (complementary 131 I treatment). No thyroid carcinomas were found for the other 4 patients. No patients died from thyroid carcinoma during follow-up (mean: 41 months). The prevalence of lymph node metastasis from thyroid carcinoma in cervical lymph node dissection during treatment of HNSCC seems higher (7.9%) than rates reported in the literature (0.3 to 1.6%). This may be due to the histopathological methods employed. Management of patients should be discussed in the light of thyroid ultrasonography and prognosis of HNSCC. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ultrasonographic Differentiation Between Nodular Hyperplasia and Neoplastic Follicular-Patterned Lesions of the Thyroid Gland.

PubMed

Song, Yong Sub; Kim, Ji-Hoon; Na, Dong Gyu; Min, Hye Sook; Won, Jae-Kyung; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho

2016-08-01

We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Optical biopsy of head and neck cancer using hyperspectral imaging and convolutional neural networks

NASA Astrophysics Data System (ADS)

Halicek, Martin; Little, James V.; Wang, Xu; Patel, Mihir; Griffith, Christopher C.; El-Deiry, Mark W.; Chen, Amy Y.; Fei, Baowei

2018-02-01

Successful outcomes of surgical cancer resection necessitate negative, cancer-free surgical margins. Currently, tissue samples are sent to pathology for diagnostic confirmation. Hyperspectral imaging (HSI) is an emerging, non-contact optical imaging technique. A reliable optical method could serve to diagnose and biopsy specimens in real-time. Using convolutional neural networks (CNNs) as a tissue classifier, we developed a method to use HSI to perform an optical biopsy of ex-vivo surgical specimens, collected from 21 patients undergoing surgical cancer resection. Training and testing on samples from different patients, the CNN can distinguish squamous cell carcinoma (SCCa) from normal aerodigestive tract tissues with an area under the curve (AUC) of 0.82, 81% accuracy, 81% sensitivity, and 80% specificity. Additionally, normal oral tissues can be sub-classified into epithelium, muscle, and glandular mucosa using a decision tree method, with an average AUC of 0.94, 90% accuracy, 93% sensitivity, and 89% specificity. After separately training on thyroid tissue, the CNN differentiates between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multi-nodular goiter (MNG) with an AUC of 0.93, 87% accuracy, 88% sensitivity, and 85% specificity. Classical-type papillary thyroid carcinoma is differentiated from benign MNG with an AUC of 0.91, 86% accuracy, 86% sensitivity, and 86% specificity. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multi-category diagnostic information for normal head-and-neck tissue, SCCa, and thyroid carcinomas. More patient data are needed in order to fully investigate the proposed technique to establish reliability and generalizability of the work.

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

PubMed

Borowczyk, M; Janicki, A; Dworacki, G; Szczepanek-Parulska, E; Danieluk, M; Barnett, J; Antonik, M; Kałużna, M; Bromińska, B; Czepczyński, R; Bączyk, M; Ziemnicka, K; Ruchała, M

2018-04-04

The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P < 0.0001; OR = 0.21, 95% CI 0.14-0.31) was more frequent in the studied group, unlike extracapsular invasion, which was significantly more often present in patients with DTC but without CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

PubMed Central

Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph

2015-01-01

Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

Human herpes simplex viruses in benign and malignant thyroid tumours.

PubMed

Jensen, Kirk; Patel, Aneeta; Larin, Alexander; Hoperia, Victoria; Saji, Motoyasu; Bauer, Andrew; Yim, Kevin; Hemming, Val; Vasko, Vasyl

2010-06-01

To test the hypothesis that herpes viruses may have a role in thyroid neoplasia, we analysed thyroid tissues from patients with benign (44) and malignant (65) lesions for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression, and activation of viral-inducible signalling pathways. Expression of viral entry receptor nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV. HSV DNA was detected in 43/109 (39.4%) examined samples. HSV capsid protein expression correlated with HSV DNA status. HSV-positive tumours were characterized by activation of virus-inducible signalling such as interferon-beta expression and nuclear NFkappaB expression. Lymphocyte infiltration and oncocytic cellular features were common in HSV-positive tumours. HSV1 was detected with the same frequency in benign and malignant thyroid tumours. HSV2 was significantly associated with papillary thyroid cancer and the presence of lymph node metastases. The expression of HSV entry receptor nectin-1 was increased in thyroid tumours compared to normal thyroid tissue and further increased in papillary thyroid cancer. Nectin-1 expression was detected in all examined thyroid cancer cell lines. Nectin-1 expression in cancer cells correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signalling did not affect the level of nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. These findings showed that HSV is frequently detected in thyroid cancer. During tumour progression, thyroid cells acquire increased susceptibility to HSV due to increased expression of viral entry mediator nectin-1 and activation of mitogenic signalling in cancer cells.

Thyroid Carcinoma Secondary to Radiation Cloud Exposure from the Chernobyl Incident of 1986: A Case Study

PubMed Central

Atkinson, Andrew L.; Rosenthal, Andrew

2010-01-01

The Chernobyl accident of 1986 exposed most if not all of Europe to a blanket of radiation, creating a melting pot of human exposure sequelae that is still showing up in our medical clinics today. In our particular clinic, a young woman of 29 years presented with most of her extended family in attendance. The young woman was born and raised in northern Italy until the age of seven when she left and immigrated to the United States leaving most of her family behind. Shortly after the Chernobyl accident, 5 members of her family, all woman including her own mother, were diagnosed with papillary thyroid carcinoma. Twenty-two years later, this same young woman came into the clinic with papillary thyroid carcinoma, making her the sixth member of her family. This case report illustrates the patient's history with her radiation exposure while talking in depth about the source, Chernobyl. PMID:20740164

The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma

PubMed Central

Dillon, Laura W.; Lehman, Christine E.; Wang, Yuh-Hwa

2012-01-01

The incidence of thyroid cancer is increasing, especially papillary thyroid carcinoma (PTC), making it currently the fastest-growing cancer among women. Reasons for this increase remain unclear, but several risk factors including radiation exposure and improved detection techniques have been suggested. Recently, the induction of chromosomal fragile site breakage was found to result in the formation of RET/PTC1 rearrangements, a common cause of PTC. Chromosomal fragile sites are regions of the genome with a high susceptibility to forming DNA breaks and are often associated with cancer. Exposure to a variety of external agents can induce fragile site breakage, which may account for some of the observed increase in PTC. This paper discusses the role of fragile site breakage in PTC development, external fragile site-inducing agents that may be potential risk factors for PTC, and how these factors are especially targeting women. PMID:22762011

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

Surface-modified gold nanorods for specific cell targeting

NASA Astrophysics Data System (ADS)

Wang, Chan-Ung; Arai, Yoshie; Kim, Insun; Jang, Wonhee; Lee, Seonghyun; Hafner, Jason H.; Jeoung, Eunhee; Jung, Deokho; Kwon, Youngeun

2012-05-01

Gold nanoparticles (GNPs) have unique properties that make them highly attractive materials for developing functional reagents for various biomedical applications including photothermal therapy, targeted drug delivery, and molecular imaging. For in vivo applications, GNPs need to be prepared with very little or negligible cytotoxicitiy. Most GNPs are, however, prepared using growth-directing surfactants such as cetyl trimethylammonium bromide (CTAB), which are known to have considerable cytotoxicity. In this paper, we describe an approach to remove CTAB to a non-toxic concentration. We optimized the conditions for surface modification with methoxypolyethylene glycol thiol (mPEG), which replaced CTAB and formed a protective layer on the surface of gold nanorods (GNRs). The cytotoxicities of pristine and surface-modified GNRs were measured in primary human umbilical vein endothelial cells and human cell lines derived from hepatic carcinoma cells, embryonic kidney cells, and thyroid papillary carcinoma cells. Cytotoxicity assays revealed that treating cells with GNRs did not significantly affect cell viability except for thyroid papillary carcinoma cells. Thyroid cancer cells were more susceptible to residual CTAB, so CTAB had to be further removed by dialysis in order to use GNRs for thyroid cell targeting. PEGylated GNRs are further modified to present monoclonal antibodies that recognize a specific surface marker, Na-I symporter, for thyroid cells. Antibody-conjugated GNRs specifically targeted human thyroid cells in vitro.

Estrogen receptor (ER)-beta, but not ER-alpha, is present in thyroid vessels: immunohistochemical evaluations in multinodular goiter and papillary thyroid carcinoma.

PubMed

Ceresini, Graziano; Morganti, Simonetta; Graiani, Virna; Saccani, Maria; Milli, Bruna; Usberti, Elisa; Valenti, Giorgio; Ceda, Gian Paolo; Corcione, Luigi

2006-12-01

Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. We immunohistochemically evaluated both ER-alpha and ER-beta immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). ER-alpha IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-beta IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-beta IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. This study demonstrated that ER-beta, but not ER-alpha, IR is present in the endothelium of thyroid vessels. Furthermore, although data need to be confirmed in larger observations, these results suggest the lack of differences in the pattern of vascular ER-beta IR between MNG and PTC.

Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy.

PubMed

Naddaf, Sleiman Y; Syed, Ghulam Mustafa Shah; Hadb, Abdulrahman; Al-Thaqfi, Saif

2016-09-01

We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs.

[F-18-fluordeoxyglucose positron emission tomography on patients with differentiated thyroid cancer who present elevated human serum thyroglobulin levels and negative I-131 whole body scan].

PubMed

Ruiz Franco-Baux, J V; Borrego Dorado, I; Gómez Camarero, P; Rodríguez Rodríguez, J R; Vázquez Albertino, R J; Navarro González, E; Astorga Jiménez, R

2005-01-01

This study aimed to evaluate the role of Fluorine-18-fluorodeoxyglucose positron emission tomography (PET-FDG) in patients with elevated serum thyroglobulin (hTg) levels where thyroid cancer tissue does not concentrate radioiodine, rendering false-negative results on I-131 scanning. Whole-body PET imaging using FDG was performed in 54 patients (37 female, 17 male) aged 17-88 years: 45 with papillary tumors and 9 with follicular tumors who were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels (hTg > 2 ng/ml) under thyroid-stimulating hormone (TSH > or = 30 microIU/ml) in whom the iodine scan was negative. All whole body scans were obtained with diagnostic doses (185 MBq). Whole body PET imaging was performed in fasting patients following i.v. administration of 370 MBq FDG while the patients were receiving full thyroid hormone replacement. Before PET, 99mTc methoxyisobutylisonitrile scintigraphy (99mTc-MIBI) was done in 14 patients and morphologic imaging in 26 by CT scan. Positive PET results confirmed the presence of hypermetabolic foci in 25/54 patients (46.29 %). Positive findings were found for PET-FDG in patients with hTg levels higher than 10 ng/ml receiving full thyroid hormone replacement. 99mTc-MIBI demonstrated lesions in 7/14 patients (50 %). PET-FDG and 99mTc-MIBI had congruent positive results in 4/7 patients. All the lesions found by CT were detected by PET-FDG, while recurrent disease was found in 12/21 patients with previous negative CT. These results suggest that PET-FDG seems to be a promising tool in the follow-up of thyroid cancer and should be considered in patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases by elevated thyroglobulin levels, and negative I-131 whole body scans. PET-FDG might be more useful at hTg levels > 10 ng/ml.

Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Luchuan; Lv, Bin; Chen, Bo

2015-07-10

Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, wasmore » picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.« less

[18F]fluorodeoxyglucose triple-head coincidence imaging as an adjunct to 131I scanning for follow-up of papillary thyroid carcinoma.

PubMed

Gonzalo, Irene T Gaw; Itti, Emmanuel; Mlikotic, Anton; Pham, Le H; Cesar, Romeo B; Meignan, Michel; Mishkin, Fred S

2003-01-01

To evaluate the feasibility of using [(18)F]fluorodeoxyglucose ((18)FDG) triple-head coincidence imaging as a potential cost-effective alternative to positron emission tomography in the setting of suspected recurrence of papillary thyroid carcinoma. We retrospectively studied 10 patients with suspected recurrence of papillary carcinoma of the thyroid, who underwent (18)FDG coincidence imaging,(131)I scanning, and a reference anatomic scan (computed tomography, magnetic resonance imaging, or both) within 1 year in most cases. The (131)I scan detected the recurrence in five patients (62.5%) and failed to reveal recurrent cancer in three patients (37.5%); in contrast,(18)FDG imaging detected the recurrence in eight patients (100%) and was true negative in two patients in whom the scans were performed more than 1 year after effective therapy for the recurrence. The sensitivity of detection was unrelated to lesion size. The (18)FDG imaging results led to additional radiotherapy in all (131)I-negative patients, two of whom had high thyroglobulin levels and one of whom had a low thyroglobulin concentration but the presence of antithy-roglobulin antibodies. We conclude that (18)FDG triple-head coincidence imaging is useful for routine management of patients with thyroid cancer who have no abnormalities detected on (131)I scans but have high serum thyroglobulin levels. This technique, however, may not be as sensitive as a dedicated positron emission tomographic device, particularly for the assessment of small tumors.

ACTIVE SURVEILLANCE FOR PAPILLARY THYROID MICROCARCINOMA: NEW CHALLENGES AND OPPORTUNITIES FOR THE HEALTH CARE SYSTEM

PubMed Central

Haser, Grace C.; Tuttle, R. Michael; Su, Henry K.; Alon, Eran E.; Bergman, Donald; Bernet, Victor; Brett, Elise; Cobin, Rhoda; Dewey, Eliza H.; Doherty, Gerard; Dos Reis, Laura L.; Harris, Jeffrey; Klopper, Joshua; Lee, Stephanie L.; Levine, Robert A.; Lepore, Stephen J.; Likhterov, Ilya; Lupo, Mark A.; Machac, Josef; Mechanick, Jeffrey I.; Mehra, Saral; Milas, Mira; Orloff, Lisa A.; Randolph, Gregory; Revenson, Tracey A.; Roberts, Katherine J.; Ross, Douglas S.; Rowe, Meghan E.; Smallridge, Robert C.; Terris, David; Tufano, Ralph P.; Urken, Mark L.

2017-01-01

Objective The dramatic increase in papillary thyroid carcinoma (PTC) is primarily a result of early diagnosis of small cancers. Active surveillance is a promising management strategy for papillary thyroid microcarcinomas (PTMCs). However, as this management strategy gains traction in the U.S., it is imperative that patients and clinicians be properly educated, patients be followed for life, and appropriate tools be identified to implement the strategy. Methods We review previous active surveillance studies and the parameters used to identify patients who are good candidates for active surveillance. We also review some of the challenges to implementing active surveillance protocols in the U.S. and discuss how these might be addressed. Results Trials of active surveillance support nonsurgical management as a viable and safe management strategy. However, numerous challenges exist, including the need for adherence to protocols, education of patients and physicians, and awareness of the impact of this strategy on patient psychology and quality of life. The Thyroid Cancer Care Collaborative (TCCC) is a portable record keeping system that can manage a mobile patient population undergoing active surveillance. Conclusion With proper patient selection, organization, and patient support, active surveillance has the potential to be a long-term management strategy for select patients with PTMC. In order to address the challenges and opportunities for this approach to be successfully implemented in the U.S., it will be necessary to consider psychological and quality of life, cultural differences, and the patient’s clinical status. PMID:26799628

BRAFV600E mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl

PubMed Central

Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

2015-01-01

After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0–18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAFV600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAFV600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAFV600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs. PMID:26584635

Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture.

PubMed

Janson, David; Saintigny, Gaëlle; Mahé, Christian; El Ghalbzouri, Abdoelwaheb

2013-01-01

The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high-passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high-passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti-skin-ageing strategies. © 2013 John Wiley & Sons A/S.

Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis.

PubMed

Kim, Woon Won; Ha, Tae Kwun; Bae, Sung Kwon

2018-01-09

The purpose of this study was to examine the possible prognostics and clinicopathologic characteristics underlying the BRAFV600E mutation and papillary thyroid carcinoma (PTC) coexisting or in absence of chronic lymphocytic thyroiditis (CLT). This study was conducted on 172 patients who had undergone total thyroidectomy or unilateral total thyroidectomy for PTC; the patients were then examined for the BRAFV600E mutation using specimens obtained after their surgery from January 2013 to August 2015. BRAF mutations were found in 130 of 172 patients (75.6%). CLT was present in 27.9% of patients (48/172). The incidence of the BRAFV600E mutation was significantly increased in the group with no CLT (P = 0.001). The findings of the multivariate analysis pertaining to the coexistence of CLT and PTC showed no significant correlation other than the BRAFV600E mutation. No significant difference was noted in the clinicopathologic factors between the two groups based on the coexistence of CLT in univariate and multivariate analyses. The BRAFV600E mutation is less frequent in PTC coexisting with CLT presumably because CLT and the BRAFV600E mutation operate independently in the formation and progression of thyroid cancer.

Shear wave elastography diagnosis of the diffuse sclerosing variant of papillary thyroid carcinoma: A case report.

PubMed

Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei

2016-08-01

The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC.

Shear wave elastography diagnosis of the diffuse sclerosing variant of papillary thyroid carcinoma: A case report

PubMed Central

Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei

2016-01-01

The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC. PMID:27446574

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

PubMed

Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph

2015-12-01

Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic Papillary Thyroid Carcinoma.

PubMed

Li, Xiucan; Wang, Yiguo; Zhao, Yongfei; Liu, Jianheng; Xiao, Songhua; Mao, Keya

2017-11-15

MINI: A 3D printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma. The personalized porous implant printed in Ti6AL4V provided excellent physicochemical properties and biological performance, including biocompatibility, osteogenic activity, and bone ingrowth effect. A unique case report. A three-dimensional (3D) printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma in a middle-age female patient. Papillary thyroid carcinoma is a malignant neoplasm with a relatively favorable prognosis. A metastatic lesion in multilevel cervical spine (C2-C4) destroys neurological functions and causes local instability. Radical excision of the metastasis and reconstruction of the cervical vertebrae sequence conforms with therapeutic principles, whereas the special-shaped multilevel upper-cervical spine requires personalized implants. 3D printing is an additive manufacturing technology that produces personalized products by accurately layering material under digital model control via a computer. Reporting of this recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in the literature. Anterior-posterior surgery was performed in one stage. Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with insertion of a personalized implant manufactured by 3D printing technology, were performed to rebuild the cervical spine sequences. The porous implant was printed in Ti6AL4V with perfect physicochemical properties and biological performance, such as biocompatibility and osteogenic activity. Finally, lateral mass screw fixation was performed via a posterior approach. Patient neurological function gradually improved after the surgery. The patient received 11/17 on the Japanese Orthopedic Association scale and ambulated with a personalized skull-neck-thorax orthosis on postoperative day 11. She received radioiodine I therapy. The plane x-rays and computed tomography revealed no implant displacement or subsidence at the 12-month follow-up mark. The presented case substantiates the use of 3D printing technology, which enables the personalization of products to solve unconventional problems in spinal surgery. 5.

Expression of the membrane mucins MUC4 and MUC15, potential markers of malignancy and prognosis, in papillary thyroid carcinoma.

PubMed

Nam, Kee-Hyun; Noh, Tae-Woong; Chung, So-Hyang; Lee, So Hee; Lee, Mi Kyung; Hong, Soon Won; Chung, Woong Youn; Lee, Eun Jig; Park, Cheong Soo

2011-07-01

Papillary thyroid carcinoma (PTC) is the most frequent carcinoma of the thyroid gland and has a relatively good prognosis. However, it is important to identify PTC characteristics that indicate high risk for recurrence and metastasis. To date, overexpression of the membrane mucin, MUC1, has been investigated as a key molecular event in the pathogenesis of aggressive PTC. However, other membrane-associated mucins, matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-13 (TIMP-3), have not been studied yet. The aim of this study was to evaluate the expression levels of MUC4, MUC15, MMP-13, and TIMP-3 and their prognostic significance in PTC. We analyzed MUC4, MUC15, MMP-13, and TIMP-3 expression in 10 PTC and 10 normal thyroid tissue samples using real-time reverse transcription-polymerase chain reaction. Tissue array blocks were obtained from 98 PTC cases. Tumor regions and nontumor regions were analyzed in tissue array blocks and immunohistochemistry studies were conducted using sectioned slides. Semiquantitative scores were correlated with clinicopathological factors of 98 PTC patients. MUC4- and MUC15-specific mRNA was increased by 78-fold and 4.75-fold, respectively, in PTC samples compared with normal thyroid tissues. MMP-13 and TIMP-3 gene expression levels were decreased by approximately 0.39-fold and 0.53-fold, respectively. By immunohistochemistry, MUC4 and MUC15 expression levels were increased in PTC samples compared with normal thyroid tissues (p < 0.001). MMP-13 and TIMP-3 expression levels were decreased in PTC samples compared with normal thyroid tissues (p < 0.001). High MUC4 scores were significantly correlated with small tumor size and papillary thyroid microcarcinoma subtype. High MUC15 scores were significantly correlated with age (≥45 years), distant metastasis, and multifocality. MUC4 and MUC15 were overexpressed in PTC, and high MUC15 expression was associated with high malignant potential. MUC15 may serve as a prognostic marker and potential novel therapeutic target in PTC.

ENHANCED BETA-CATENIN EXPRESSION IS ASSOCIATED WITH THE RECURRENCE OF PAPILLARY THYROID CARCINOMA.

PubMed

Kordestani, Zeinab; Sanjari, Mojgan; Safavi, Moeinadin; Mashrouteh, Mahdieh; Asadikaram, Gholamreza; FekriSoofiAbadi, Maryam; Mirzazadeh, Ali

2018-03-02

A direct role of Catenin beta-1(βcat) in the proliferation of human thyroid tumor cells has been identified. This study aimed to determine if there is an association between βcat gene expression and the staging, recurrence, metastasis, and disease free survival of papillary thyroid cancer. A retrospective cohort study was conducted using data from available information in the medical records and paraffin blocks of 81 of 400 patients referred to the endocrine clinic over a 10-year period. Real-time polymerase chain reaction (PCR) was used to evaluate βcat gene expression. Disease-free survival was assessed using Kaplan-Meier method. The ten-year survival rate in these patients was 98.25% and disease-free survival was 48.1%. Cumulative dose of radioactive iodine that patients received was significantly and positively correlated with βcat gene expression (r = -0.2, p value=0.03).Also, in patients with recurrence, βcat gene expression was higher and statistically significant (5 fold increase p=0.002). Patients in more advanced stage and those with recurrence /distant metastasis had higher βcat gene expression .We found that the patients had a better survival (lower recurrence) if they had a lower βcat gene expression. (SD = 0.142-0.052) (Mantel-Cox test, P =0.002). We concluded that βcat gene expression was positively correlated with recurrence, distant metastasis and TNM stage. PTC = Papillary thyroid carcinoma; βcat = Catenin beta-1; FTC = Follicular thyroid cancer; TCF/LEF-1 = T-cell factor / lymphoid enhancer factor1; IHC = immunohistochemical; TG = Thyroglobulin; AUC = Area under the ROC curve; APC = Adenomatosis polyposis coli.

PANCREAS METASTASES FROM PAPILLARY THYROID CARCINOMA: A REVIEW OF THE LITERATURE.

PubMed

Davidson, Maja; Olsen, Randall J; Ewton, April A; Robbins, Richard J

2017-12-01

Although locoregional metastases occur in 5 to 10% of patients with papillary thyroid cancer (PTC), distant metastases are rare, especially to the pancreas. Here we review the literature regarding metastases to the pancreas from PTC and present an illustrative patient. The literature search was performed through using the PubMed database. The information regarding our illustrative case was obtained from the medical records of our institution. Since 1991, 11 cases of pancreas metastases of PTC have been reported. The average age at diagnosis was 55.3 years. There were 8 males and 3 females. Three had classic PTC histology, 2 had tall cell variant, and 2 had follicular variant. Four had T4 tumors, and 2 had T3 tumors. Seven had thyroid cancer spread to regional lymph nodes. One had distant metastasis. Pancreas metastases were diagnosed from 1 month to 13 years after primary PTC was detected; the average was 7 years. Our patient was an 84-year-old female diagnosed with PTC with a BRAFV600E mutation following total thyroidectomy. A whole-body scan after radioactive iodine (RAI) remnant ablation was negative for metastases. A pancreatic tumor was identified 2 years later on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. A biopsy of the tumor was histologically similar to PTC and positive for thyroglobulin, thyroid transcription factor-1, and the BRAFV600E mutation. The biological reasons why PTCs metastasize to the pancreas remain to be elucidated. Older patients with non-RAI avid, FDG-PET-positive metastases, and symptoms of pancreatitis are at increased risk of this rare entity. FDG = fluorodeoxyglucose FNA = fine-need aspiration PTC = papillary thyroid cancer RAI = radioactive iodine Tg = thyroglobulin TgAb = antithyroglobulin antibodies TNM = tumor-node-metastasis.

Hyperactive ERK and persistent mTOR signaling characterize vemurafenib resistance in papillary thyroid cancer cells.

PubMed

Hanly, Elyse K; Tuli, Neha Y; Bednarczyk, Robert B; Suriano, Robert; Geliebter, Jan; Moscatello, Augustine L; Darzynkiewicz, Zbigniew; Tiwari, Raj K

2016-02-23

Clinical studies evaluating targeted BRAFV600E inhibitors in advanced thyroid cancer patients are currently underway. Vemurafenib (BRAFV600E inhibitor) monotherapy has shown promising results thus far, although development of resistance is a clinical challenge. The objective of this study was to characterize development of resistance to BRAFV600E inhibition and to identify targets for effective combination therapy. We created a line of BCPAP papillary thyroid cancer cells resistant to vemurafenib by treating with increasing concentrations of the drug. The resistant BCPAP line was characterized and compared to its sensitive counterpart with respect to signaling molecules thought to be directly related to resistance. Expression and phosphorylation of several critical proteins were analyzed by Western blotting and dimerization was evaluated by immunoprecipitation. Resistance to vemurafenib in BCPAP appeared to be mediated by constitutive overexpression of phospho-ERK and by resistance to inhibition of both phospho-mTOR and phospho-S6 ribosomal protein after vemurafenib treatment. Expression of potential alternative signaling molecule, CRAF, was not increased in the resistant line, although formation of CRAF dimers appeared increased. Expression of membrane receptors HER2 and HER3 was greatly amplified in the resistant cancer cells. Papillary thyroid cancer cells were capable of overcoming targeted BRAFV600E inhibition by rewiring of cell signal pathways in response to prolonged vemurafenib therapy. Our study suggests that in vitro culture of cancer cells may be useful in assessing molecular resistance pathways. Potential therapies in advanced thyroid cancer patients may combine vemurafenib with inhibitors of CRAF, HER2/HER3, ERK, and/or mTOR to delay or abort development of resistance.

CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasis.

PubMed

Yasuoka, Hironao; Kodama, Rieko; Hirokawa, Mitsuyoshi; Takamura, Yuuki; Miyauchi, Akira; Sanke, Tokio; Nakamura, Yasushi

2008-09-30

Metastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers. Nitrite/nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells after induction and/or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed. Production of nitrite/nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC. Our data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma.

CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasis

PubMed Central

Yasuoka, Hironao; Kodama, Rieko; Hirokawa, Mitsuyoshi; Takamura, Yuuki; Miyauchi, Akira; Sanke, Tokio; Nakamura, Yasushi

2008-01-01

Background Metastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers. Methods Nitrite/nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells after induction and/or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed. Results Production of nitrite/nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC. Conclusion Our data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma. PMID:18826577

[Draft of the best medical treatment in patients with low-risk thyroid cancer].

PubMed

Vlček, Petr; Nováková, Dagmar; Vejvalka, Jan; Zimák, Jaroslav; Křenek, Martin; Vošmiková, Květuše; Smutný, Svatopluk; Bavor, Petr; Astl, Jaromír; Lukáš, Jindřich

2015-09-01

The incidence of well-differentiated low-risk thyroid cancer have increased globally over the last three decades. Thyroid cancer treatment relates to a suitable surgical procedure and the use of adjuvant radio-iodine therapy in selected patients. Evaluation of prognostic factors and risk stratification are critical for determining appropriate treatment. Survival of patients with low-risk thyroid cancer is excellent. Appropriate choice of medical treatment resulted in full recovery in most patients. Relapse risk increases with the size of the primary tumor, along with the findings of the risk factors in men. Our study included a total of 1 980 patients in whom were diagnosed T1a and T1b tumors between the years 2003 to 2012. The population included 1 675 women (84.6 %) of average age of 45.22 years and 305 men (15.4 %) of average age of 50.0 years. The bulk of the file represented papillary carcinomas (1 868; 94.4 %), and smaller group of follicular carcinomas (112; 5.6 %). Patients were divided into four groups according to tumor size. Patients were evaluated according to risk factors: unifocality no other risk factors, multifocality - more bearings in thyroid tumor, metastases in regional lymph nodes, distant metastases or combination of risk factors. Group A: In the monitored set of 678 patients with papillary and follicular microcarcinoma up to 5 mm, during histological input, the findings revealed one bearing (unifocal type of cancer) in 566 patients. Multifocality was found in 112 patients, local nodal metastasis were demonstrated in 24 cases and pulmonary metastasis was discove-red in 1 case. Group B: In this group there were 576 study patients with papillary and follicular microcarcinoma size of 5-10 mm. Histological findings were captured input one bearing carcinoma in 434 patients, 142 patients with multifocality, in 53 cases of local nodal metastasis, and 1 case of bone metastases. Group C: In this group there were 467 study patients with papillary and follicular microcarcinoma size 10-15 mm. The histological initial finding captured unifocal type of cancer in 344 patients, multifocality in 123 patients, in 45 cases local metastases and in 3 cases of pulmonary metastases. Group D: 259 patients were monitored in this group with breast size 16-20 mm. At the initial finding was captured one bearing cancer in 188 patients, multifocality in 71 patients, in 24 cases evidence of local metastases and 2 patients had a case of distant lung metastases. In patients in whom risk factors were found, radioiodine treatment was indicated. This included 744 patients. In this group of patients after a year or more, relapse was observed in 74 patients (9.94 %). In 1 236 patients who did not undergo radioiodine treatment, there was a relapse in 49 patients (3.96 %). Based on our analysis, it is necessary to stratify the risk of relapse according to risk factors. In case of missed radioiodine therapy in patients with low-risk cancer without confirmed risk factors, it is also necessary to have regular clinical, laboratory and ultrasound examination. It is important to distinguish patients with risk factors that may contribute to disease recurrence. Only in this way, on one hand we prevent excessive treatment of patients with low-risk thyroid cancer which leads to increased cost of health care, and on the other hand prevent reduced level of care for patients with an increase in relapses.

Cytological diagnosis of thyroid nodules in Hashimoto thyroiditis in elderly patients

PubMed Central

2013-01-01

Background Long standing Hashimoto Thyroiditis (HT) causes shrinking and atrophy of the thyroid, but may also lead to diffuse enlargement of the gland and/or formation of nodules. These nodules should be differentiated from papillary thyroid carcinoma (PTC) and primary thyroidal non-Hodgkin lymphoma (PTL), which are possible complications of HT, and require pre-surgical diagnoses and different treatments. This study focuses on the role of fine-needle cytology (FNC) in the clinical surveillance and pre-surgical diagnosis of HT with diffuse and nodular enlargement of the gland in elderly patients. Methods Thirty-four elderly patients (≥ 65 yrs) with HT and diffuse or nodular enlargement of the thyroid underwent ultrasound (US)-guided FNC. Smears were routinely stained and evaluated; additional passes were used for flow cytometry (FC) assessment of lymphoid infiltrate in 6 cases. Results The cytological diagnosis was HT in 12 cases with prevalence of Hurtle cells in 2 cases, PTC in 1 case and PTL in 2 cases. FC assessed the reactive, non-lymphomatous nature of the lymphoid infiltrate in 5 cases and demonstrated light chain restriction, hence the lymphomatous nature of the lymphoid infiltrate in 2 cases of PTL. Conclusions FNC plays a key role in the clinical surveillance and pre-surgical diagnosis of diffuse enlargement and nodular presentation of HT in elderly patients. FNC can correctly diagnose HT, PTC and PTL indicating the need for surgery and its extension in suspicious or neoplastic cases, leaving other cases to the medical treatment and clinical surveillance. PMID:24266923

Drug-induced liver injury caused by iodine-131

PubMed Central

Kim, Chei Won; Park, Ji Sun; Oh, Se Hwan; Park, Jae-Hyung; Shim, Hyun-Ik; Yoon, Jae Woong; Park, Jin Seok; Hong, Seong Bin; Kim, Jun Mi; Le, Trong Binh; Lee, Jin Woo

2016-01-01

Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well. PMID:27209646

Drug-induced liver injury caused by iodine-131.

PubMed

Kim, Chei Won; Park, Ji Sun; Oh, Se Hwan; Park, Jae-Hyung; Shim, Hyun-Ik; Yoon, Jae Woong; Park, Jin Seok; Hong, Seong Bin; Kim, Jun Mi; Le, Trong Binh; Lee, Jin Woo

2016-06-01

Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well.

Adjuvant Radioactive iodine 131 ablation in papillary microcarcinoma of thyroid: Saudi Arabian experience [corrected].

PubMed

Al-Qahtani, Khalid Hussain; Al Asiri, Mushabbab; Tunio, Mutahir A; Aljohani, Naji J; Bayoumi, Yasser; Fatani, Hanadi; AlHadab, Abdulrehman

2015-12-01

Papillary Microcarcinoma (PMC) of thyroid is a rare type of differentiated thyroid cancer (DTC), which according to the World Health Organization measures 1.0 cm or less. The gold standard of treatment of PMC is still controversy. Our aim was to contribute in resolving the debate on the therapeutic choices of the surgical and adjuvant I-131 (RAI) treatment in PMC. From 2000 to 2012, 326 patients were found to have PMC and were retrospectively reviewed for clinicopathological characteristics, treatment outcomes and prognostic factors. Mean age of cohort was 42.6 years (range: 18-76) and the mean tumor size was 0.61 cm ± 0.24; lymph node involvement was seen in 12.9 % of cases. Median follow up period was 8.05 years (1.62-11.4). Total 23 all site recurrences (7.13 %) were observed; more observed in patients without I-131 ablation (p <0.0001). Ten year DFS rates were 89.6 %. Cox regression Model analysis revealed size, histopathologic variants, multifocality, extrathyroidal extension, lymphovascular space invasion, nodal status, and adjuvant RAI ablation the important prognostic factors affecting DFS. Despite excellent DFS rates, a small proportion of patients with PMC develop recurrences after treatment. Adjuvant RAI therapy improves DFS in PMC patients with aggressive histopathologic variants, multifocality, ETE, LVSI, tumor size (> 0.5 cm) and lymph node involvement. Failure of RAI ablation to decrease risk in N1a/b supports prophylactic central neck dissection during thyroidectomy, however more trials are warranted. Adjuvant I-131 ablation following thyroidectomy in PMC patients, particularly with poor prognostic factors improves DFS rates.

The Effect of Thyroiditis on the Yield of Central Compartment Lymph Nodes in Patients with Papillary Thyroid Cancer.

PubMed

Lai, Victoria; Yen, Tina W F; Rose, Brian T; Fareau, Gilbert G; Misustin, Sarah M; Evans, Douglas B; Wang, Tracy S

2015-12-01

In patients who have undergone thyroidectomy and central compartment neck dissection (CCND) for papillary thyroid cancer (PTC), visualization of enlarged lymph nodes may lead to more extensive CCND. This study sought to determine the effect of patient age and the presence of thyroiditis on the number of malignant and total lymph nodes resected in patients who underwent CCND for PTC. This retrospective review examined a prospective database of patients who underwent total thyroidectomy and CCND for PTC between April 2009 and June 2013 and had thyroiditis on the final pathology. The patients were categorized into age groups by decade (18-29, 30-39, 40-49, 50-59, and ≥60 years) and compared with a control group of patients matched by age, gender, and tumor size. Of 74 patients with thyroiditis, 64 (87 %) were women. The median age of the patients was 47.5 years (range 18.2-72.0 years). The patients with thyroiditis had more lymph nodes resected than those without thyroiditis (median 11 vs 7; p < 0.01). However, these patients had fewer malignant lymph nodes (median 0 vs 1.5; p = 0.06), resulting in a lower lymph node ratio (0 vs 0.18; p = 0.02) for the entire cohort, but particularly for the youngest (18-29 years) and oldest (≥60 years) age groups. Patients with thyroiditis and PTC who underwent CCND had more lymph nodes resected but a had lower proportion of metastatic lymph nodes than those without thyroiditis. Given the relatively low yield of malignant cervical lymphadenopathy, a more judicious approach to CCND might be considered, particularly for the youngest and oldest patients with PTC and thyroiditis.

[Hyperthyroidism and carcinoma of the thyroid gland].

PubMed

Ardito, G; Mantovani, M; Vincenzoni, C; Guidi, M L; Corsello, S; Rabitti, C; Fadda, G; Di Giovanni, V

1997-01-01

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.

A Clinical Framework to Facilitate Risk Stratification When Considering an Active Surveillance Alternative to Immediate Biopsy and Surgery in Papillary Microcarcinoma.

PubMed

Brito, Juan P; Ito, Yasuhiro; Miyauchi, Akira; Tuttle, R Michael

2016-01-01

The 2015 American Thyroid Association thyroid cancer management guidelines endorse an active surveillance management approach as an alternative to immediate biopsy and surgery in subcentimeter thyroid nodules with highly suspicious ultrasonographic characteristics and in cytologically confirmed very low risk papillary thyroid cancer (PTC). However, the guidelines provide no specific recommendations with regard to the optimal selection of patients for an active surveillance management approach. This article describes a risk-stratified clinical decision-making framework that was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma (PMC) who were being evaluated for an active surveillance management approach in the United States. A risk-stratified approach to the evaluation of patients with probable or proven PMC being considered for an active surveillance management approach requires an evaluation of three interrelated but distinct domains: (i) tumor/neck ultrasound characteristics (e.g., size of the primary tumor, the location of the tumor within the thyroid gland); (ii) patient characteristics (e.g., age, comorbidities, willingness to accept observation); and (iii) medical team characteristics (e.g., availability and experience of the multidisciplinary team). Based on an analysis of the critical factors within each of these domains, patients with probable or proven PTC can then be classified as ideal, appropriate, or inappropriate candidates for active surveillance. Risk stratification utilizing the proposed decision-making framework will improve the ability of clinicians to recognize individual patients with proven or probable PMC who are most likely to benefit from an active surveillance management option while at the same time identifying patients with proven or probable PMC that would be better served with an upfront biopsy and surgical management approach.

Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

PubMed Central

Palma, Giuseppe; Vitiello, Michela; Capiluongo, Anna; D’Andrea, Barbara; Vuttariello, Emilia; Luciano, Antonio; Cerchia, Laura; Chiappetta, Gennaro; Arra, Claudio; Fusco, Alfredo

2018-01-01

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1 expression in thyroid cancer cells reverted their malignant phenotype by inducing mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we investigated the consequences of the homozygous and heterozygous loss of PATZ1 in the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1 oncogene under the thyroid specific control of the thyroglobulin promoter RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of the Patz1 gene. However, both RET/PTC1TG;Patz1+/− and RET/PTC1TG;Patz1−/− mice developed a more aggressive thyroid cancer phenotype—characterized by higher Ki-67 expression, presence of ATCs, and increased incidence of solid variants of PTC—than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression. PMID:29584698

Radioiodine therapy for thyroid cancer depicted uterine leiomyoma.

PubMed

Hirata, Kenji; Shiga, Tohru; Kubota, Kanako C; Okamoto, Shozo; Kamibayashi, Tomohito; Tamaki, Nagara

2009-03-01

A 55-year-old woman underwent radioiodine therapy for papillary carcinoma of the thyroid. Post-therapeutic I-131 scan revealed radioiodine uptake in the pelvic region and in the thyroid bed. CT revealed a huge mass connected to the uterus. The tumor was operated on and histologically proven to be a leiomyoma of the uterus. Some physiological conditions or nonthyroidal diseases can cause false positives in patients with postoperative thyroid cancer. We suggest that uterine leiomyoma might be added to the pitfall list, although the mechanism of I-131 uptake remains unclear.

Multifocal hyperfunctioning thyroid carcinoma without metastases.

PubMed

Nishida, Akiko T; Hirano, Shigeru; Asato, Ryo; Tanaka, Shinzo; Kitani, Yoshiharu; Honda, Nobumitsu; Fujiki, Nobuya; Miyata, Kouji; Fukushima, Hideyuki; Ito, Juichi

2008-09-01

Hyperthyroidism due to thyroid carcinoma is rare, and most cases are caused by hyperfunctioning metastatic thyroid carcinoma rather than primary carcinoma. Among primary hyperfunctioning thyroid carcinoma, multifocal thyroid carcinoma is exceedingly rare, with the only one case being reported in the literature. Here, we describe the case of a 62-year-old woman with multifocal functioning thyroid carcinoma. Technetium-99m (99m Tc) scintigraphic imaging showed four hot areas in the thyroid gland. Histopathological examination of all four nodules revealed papillary carcinoma, corresponding to hot areas in the 99m Tc scintigram. DNA sequencing of the thyrotropin receptor (TSH-R) gene from all nodules revealed no mutation, indicating that activation of TSH-R was unlikely in the pathophysiogenesis of hyperfunctioning thyroid carcinoma in the present case.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simpson, W.J.; Panzarella, T.; Carruthers, J.S.

We report the experience from 13 Canadian radiotherapy centers concerning the treatment and outcome for 1074 papillary and 504 follicular thyroid cancer patients followed for 4-24 years. Surgical resection was carried out in almost all patients; there was no correlation between the type of operation and recurrence or survival. Treatment with external irradiation (201 patients) radioiodine (214 patients), or both (107 patients) was used more often in poor prognosis patients than in those with good prognostic factors, and was effective in reducing local recurrences and improving survival, especially in patients with microscopic residual disease postoperatively. Treatment complications were common butmore » rarely fatal. Thyroid cancer was the cause of death in over half of the papillary cancer deaths and in two-thirds of the follicular cancer deaths.« less

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma.

PubMed

Wu, Gang; Guo, Jing-Jing; Ma, Zhen-Yu; Wang, Jie; Zhou, Zhong-Wen; Wang, Yi

2015-01-01

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): impact on the reclassification of thyroid nodules.

PubMed

Amendoeira, Isabel; Maia, Tiago; Sobrinho-Simões, Manuel

2018-04-01

The 2017 edition of the WHO book on Classification of Tumours of Endocrine Organs includes a new section entitled 'Other encapsulated follicular-patterned thyroid tumours', in which the newly created NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) is identified and described in detail. Despite deleting the word 'carcinoma' from its name, NIFTP is not a benign tumor either and is best regarded as a neoplasm with 'very low malignant potential'. The main goal of the introduction of NIFTP category is to prevent overdiagnosis and overtreatment. Sampling constraints, especially when dealing with heterogeneous and/or large nodules, and difficulties in the invasiveness evaluation, are the major weaknesses of the histological characterization of NIFTP. At the cytological level, NIFTP can be separated from classic papillary carcinoma (cPTC) but not from encapsulated, invasive follicular variant PTC. The impact of NIFTP individualization for cytopathology is the drop of rates of malignancy for each Bethesda category in general and for indeterminate categories in particular. The biggest impact will be seen in institutions with a high frequency of FVPTC. The introduction of NIFTP has changed the utility of predictive values of molecular tests because RAS mutations and PAX8-PPARg rearrangements are frequently detected in NIFTP. This turns less promising the application of mutation detection panels as indicators of malignancy and will probably contribute to switch to a rule-out approach of molecular testing. Selection for surgery will go on being determined by a combined detection of clinical, cytological and ultrasound suspicious features. © 2018 Society for Endocrinology.

Identification and optimal postsurgical follow-up of patients with very low-risk papillary thyroid microcarcinomas.

PubMed

Durante, Cosimo; Attard, Marco; Torlontano, Massimo; Ronga, Giuseppe; Monzani, Fabio; Costante, Giuseppe; Ferdeghini, Marco; Tumino, Salvatore; Meringolo, Domenico; Bruno, Rocco; De Toma, Giorgio; Crocetti, Umberto; Montesano, Teresa; Dardano, Angela; Lamartina, Livia; Maniglia, Adele; Giacomelli, Laura; Filetti, Sebastiano

2010-11-01

Most papillary thyroid microcarcinomas (PTMCs; ≤ 1 cm diameter) are indolent low-risk tumors, but some cases behave more aggressively. Controversies have thus arisen over the optimum postoperative surveillance of PTMC patients. We tested the hypothesis that clinical criteria could be used to identify PTMC patients with very low mortality/recurrence risks and attempted to define the best strategy for their management and long-term surveillance. We retrospectively analyzed data from 312 consecutively diagnosed PTMC patients with T1N0M0 stage disease, no family history of thyroid cancer, no history of head-neck irradiation, unifocal PTMC, no extracapsular involvement, and classic papillary histotypes. Additional inclusion criteria were complete follow-up data from surgery to at least 5 yr after diagnosis. All 312 had undergone (near) total thyroidectomy [with radioactive iodine (RAI) remnant ablation in 137 (44%) - RAI group] and were followed up yearly with cervical ultrasonography and serum thyroglobulin, TSH, and thyroglobulin antibody assays. During follow-up (5-23 yr, median 6.7 yr), there were no deaths due to thyroid cancer or reoperations. The first (6-12 months after surgery) and last postoperative cervical sonograms were negative in all cases. Final serum thyroglobulin levels were undetectable (<1 ng/ml) in all RAI patients and almost all (93%) of non-RAI patients. Accurate risk stratification can allow safe follow-up of most PTMC patients with a less intensive, more cost-effective protocol. Cervical ultrasonography is the mainstay of this protocol, and negative findings at the first postoperative examination are highly predictive of positive outcomes.

Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects.

PubMed

Accordi, Elen Dias; Xekouki, Paraskevi; Azevedo, Bruna; de Alexandre, Rodrigo Bertollo; Frasson, Carla; Gantzel, Siliane Marie; Papadakis, Georgios Z; Angelousi, Anna; Stratakis, Constantine A; Sotomaior, Vanessa Santos; Faucz, Fabio R

2016-07-01

Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA, SDHB, SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA, SDHB, SDHC, and SDHD genes and familiar PTC in a large Brazilian family. Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing. Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST. Familiar PTC and a GIST were not associated with SDHx mutations; additional genetic defects, yet unknown, may be responsible for the development of tumor.

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Śliwka, Przemysław W; Puła, Bartosz; Karwowski, Bolesław; Merecz-Sadowska, Anna; Dedecjus, Marek; Lewiński, Andrzej

2017-06-15

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131 I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake-the phenomenon called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131 I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations ( p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131 I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Concurrent hyperthyroidism and papillary thyroid cancer: a fortuitous and ambiguous case report from a resource-poor setting.

PubMed

Kadia, Benjamin Momo; Dimala, Christian Akem; Bechem, Ndemazie Nkafu; Aroke, Desmond

2016-07-26

Concurrent thyroid cancer (TC) and hyperthyroidism (HT) is rare though increasingly being reported. HT due to TC is much rarer and more challenging especially in Africa where TC and HT have significant case fatality rates. We present a 37-year-old Cameroonian female who had been on irregular regimens of propranolol and digoxin as treatment for worsening palpitations for 12 months. She came to our district hospital for her propranolol medication refill. We fortuitously identified features of HT and found a left uninodular goiter with no cervical lymphadenopathy. She was referred for thyroid assessment which suggested primary HT and an enlarged heterogeneous left lobe with a well-defined homogenous solid mass. We restarted her on propranolol and referred her for a course of methimazole. At the referral hospital, she also underwent a left thyroid lobectomy. The resected lobe was sent for histopathology which revealed a neoplastic nodule with features suggestive of a papillary thyroid cancer (PTC) causing HT. The patient's clinical progress postoperatively was good and there was regression of hyperthyroid symptoms. The historical, clinical, and laboratory findings were suggestive of HT due to PTC. A high index of suspicion, prompt referral and counter-referral lead to a positive outcome of such a rare case in a resource poor setting. We advocate for systematic and careful evaluation of all thyroid nodules.

Programmed death-ligand 1 expression by digital image analysis advances thyroid cancer diagnosis among encapsulated follicular lesions.

PubMed

Hsieh, Anne M-Y; Polyakova, Olena; Fu, Guodong; Chazen, Ronald S; MacMillan, Christina; Witterick, Ian J; Ralhan, Ranju; Walfish, Paul G

2018-04-13

Recognition of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) that distinguishes them from invasive malignant encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) can prevent overtreatment of NIFTP patients. We and others have previously reported that programmed death-ligand 1 (PD-L1) is a useful biomarker in thyroid tumors; however, all reports to date have relied on manual scoring that is time consuming as well as subject to individual bias. Consequently, we developed a digital image analysis (DIA) protocol for cytoplasmic and membranous stain quantitation (ThyApp) and evaluated three tumor sampling methods [Systemic Uniform Random Sampling, hotspot nucleus, and hotspot nucleus/3,3'-Diaminobenzidine (DAB)]. A patient cohort of 153 cases consisting of 48 NIFTP, 44 EFVPTC, 26 benign nodules and 35 encapsulated follicular lesions/neoplasms with lymphocytic thyroiditis (LT) was studied. ThyApp quantitation of PD-L1 expression revealed a significant difference between invasive EFVPTC and NIFTP; but none between NIFTP and benign nodules. ThyApp integrated with hotspot nucleus tumor sampling method demonstrated to be most clinically relevant, consumed least processing time, and eliminated interobserver variance. In conclusion, the fully automatic DIA algorithm developed using a histomorphological approach objectively quantitated PD-L1 expression in encapsulated thyroid neoplasms and outperformed manual scoring in reproducibility and higher efficiency.

BRAF mutation status in papillary thyroid carcinoma: significance for surgical strategy.

PubMed

Miccoli, P; Basolo, F

2014-02-01

BRAF mutation is probably the only molecular marker acting as a risk factor that is available before surgery: for this reason, soon after it became quite widespread, it seemed an important tool as a guide towards an individualized surgical therapy in papillary thyroid carcinoma. Capsule invasion, multifocality, and lymph node involvement are the most important parameters influencing the choice of surgical strategy in front of small papillary cancers and, in more detail, of micro papillary carcinomas. The relationship between these parameters and the BRAF mutation are closely examined through the more recent literature. Capsular invasion seems to show the strongest correlation with the mutation and this has important correlations, thus suggesting that a more aggressive local surgery might be advisable, whereas the correlation between the mutation and lymph node involvement would be weaker, at least according to the most recent studies. The personalization of surgical therapy, today, seems easier to achieve thanks to molecular testing. In particular, an important result could be in the short term reduction in the number of completion thyroidectomies following simple lobectomies. Also, post operative radioactivated iodine therapies should be more carefully evaluated and tailored according to BRAF status. A possible flow chart for the decision of the therapeutic approach is proposed in accordance to the results of the literature.

Increased Pleiotrophin Concentrations in Papillary Thyroid Cancer.

PubMed

Jee, Youn Hee; Sadowski, Samira M; Celi, Francesco S; Xi, Liqiang; Raffeld, Mark; Sacks, David B; Remaley, Alan T; Wellstein, Anton; Kebebew, Electron; Baron, Jeffrey

2016-01-01

Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown. 74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In FNA samples, PTN concentration normalized to Tg was significantly higher in PTC than in benign nodules (16 ± 6 vs 0.3 ± 0.1 ng/mg, p < 0.001). In follicular variant of PTC (n = 6), the PTN/Tg ratio was also higher than in benign nodules (1.3 ± 0.6 vs 0.3 ± 0.1 ng/mg, P < 0.001, respectively). IHC showed cytoplasmic localization of PTN in PTC cells. In ex vivo FNA samples, the PTN to thyroglobulin ratio was higher in PTCs, including follicular variant PTC, than in benign thyroid nodules. The findings raise the possibility that measurement of the PTN to Tg ratio may provide useful diagnostic and/or prognostic information in the evaluation of thyroid nodules.

Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome.

PubMed

Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2012-08-01

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence.

Coexistence of Chronic Lymphocytic Thyroiditis with Papillary Thyroid Carcinoma: Clinical Manifestation and Prognostic Outcome

PubMed Central

Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2012-01-01

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence. PMID:22876054

Differential expression of mucins 1-6 in papillary thyroid carcinoma: evidence for transformation-dependent post-translational modifications of MUC1 in situ.

PubMed

Magro, Gaetano; Schiappacassi, Monica; Perissinotto, Daniela; Corsaro, Antonella; Borghese, Cinzia; Belfiore, Antonino; Colombatti, Alfonso; Grasso, Sebastiano; Botti, Carlo; Bombardieri, Emilio; Perris, Roberto

2003-07-01

Mucins are primary glycoproteins of epithelia that are known to undergo major changes in their post-translational processing during neoplastic transformation. This study has examined the expression pattern of seven primary mucins, ie mucin (MUC) 1, 2, 3, 4, 5AC, 5B and 6, in normal, hyperplastic, benign neoplastic, and papillary-type carcinoma (PTC) tissues of the thyroid. MUC1 and MUC5B were the only mucins to be widely transcribed in both benign and malignant tissues. In contrast, MUC4 transcripts were undetectable in normal thyroids, and were present in only 40% of the hyperplastic and malignant thyroid tissues. In PTC, MUC1 was identified as a single mRNA transcript, rejecting the idea that this mucin may undergo transformation-dependent alternative splicing in thyroid tumours. The tissue distribution of MUC1 and MUC4 proteins was highly heterogeneous: this largely paralleled their mRNA expression profiles and supported the conclusion that whereas MUC1 was ubiquitously expressed in PTC, MUC4 was detectable in less than 20% of the cases analysed. In order to determine whether post-translational modifications of MUC1, putatively associated with malignancy, also occurred in the mucin produced by PTC, immunohistochemistry was performed with a panel of well-characterized anti-MUC1 antibodies in conjunction with digestion of the tissue sections with deglycosylating enzymes. These experiments, which were supported by immunochemical analyses of the MUC1 and MUC4 glycoforms extracted from tissues, collectively demonstrated markedly divergent MUC1 glycosylation profiles in normal and benign thyroid tissues when compared with PTC. Characteristically, these latter neoplastic cells produced mucin molecules carrying complex poly-N-lactosamine-type glycans capped with fucose and neuraminic acid residues. The present study also found evidence in PTC for the potential presence of proteolytically processed MUC1 isoforms which differ in their post-translational traits depending on whether they are retained on the cell surface or secreted into the extracellular space. It is proposed that the observed differences in the glycosylation properties of normal and neoplastic MUC1 may be exploitable as an ancillary tool in the diagnosis of PTC. Copyright 2003 John Wiley & Sons, Ltd.

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

PubMed

Le Pennec, Soazig; Konopka, Tomasz; Gacquer, David; Fimereli, Danai; Tarabichi, Maxime; Tomás, Gil; Savagner, Frédérique; Decaussin-Petrucci, Myriam; Trésallet, Christophe; Andry, Guy; Larsimont, Denis; Detours, Vincent; Maenhaut, Carine

2015-04-01

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer. © 2015 Society for Endocrinology.

Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy

PubMed Central

Lee, Junguee; Yi, Shinae; Kang, Yea Eun; Chang, Joon Young; Kim, Jung Tae; Sul, Hae Joung; Kim, Jong Ok; Kim, Jin Man; Kim, Joon; Porcelli, Anna Maria; Kim, Koon Soon; Shong, Minho

2016-01-01

Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hürthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hürthle cell tumors, including Hürthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hürthle cell carcinoma cell line XTC.UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy. PMID:27816963

Shear-Wave Elastography for the Differential Diagnosis of Breast Papillary Lesions

PubMed Central

Chung, Jin; Lee, Won Kyung; Cha, Eun-Suk; Lee, Jee Eun; Kim, Jeoung Hyun; Ryu, Young Hoon

2016-01-01

Objective To evaluate the diagnostic performance of shear-wave elastography (SWE) for the differential diagnosis of breast papillary lesions. Methods This study was an institutional review board-approved retrospective study, with a waiver of informed consent. A total of 79 breast papillary lesions in 71 consecutive women underwent ultrasound and SWE prior to biopsy. Ultrasound features and quantitative SWE parameters were recorded for each lesion. All lesions were surgically excised or excised using an ultrasound-guided vacuum-assisted method. The diagnostic performances of the quantitative SWE parameters were compared using the area under the receiver operating characteristic curve (AUC). Results Of the 79 lesions, six (7.6%) were malignant and 12 (15.2%) were atypical. Orientation, margin, and the final BI-RADS ultrasound assessments were significantly different for the papillary lesions (p < 0.05). All qualitative SWE parameters were significantly different (p < 0.05). The AUC values for SWE parameters of benign and atypical or malignant papillary lesions ranged from 0.707 to 0.757 (sensitivity, 44.4–94.4%; specificity, 42.6–88.5%). The maximum elasticity and the mean elasticity showed the highest AUC (0.757) to differentiate papillary lesions. Conclusion SWE provides additional information for the differential diagnosis of breast papillary lesions. Quantitative SWE features were helpful to differentiate breast papillary lesions. PMID:27893857

Thyroid fine-needle aspiration cytology: performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data.

PubMed

Eilers, Stan G; LaPolice, Paula; Mukunyadzi, Perkins; Kapur, Umesh; Wendel Spiczka, Amy; Shah, Ajay; Saleh, Husain; Adeniran, Adebowale; Nunez, Amberly; Balachandran, Indra; Clark, Jennifer J; Lemon, Larry

2014-10-01

Fine-needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies. The study evaluated 1558 responses in the American Society for Clinical Pathology (ASCP) Non-GYN Assessment program of aspirates of thyroid neoplasms and malignancies and placed them into the following groups: group A (target or correct interpretation), group B (incorrect interpretation as a benign thyroid nodule), group C (incorrect interpretation malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with incorrect interpretation). In clinical practice, responses in groups A, C, and D would lead to surgical excision, whereas responses in group B would not. Of a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%, 5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hürthle cell neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C, and D respectively. Fine-needle aspiration was effective in diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules into surgical and nonsurgical categories. Data from a large group of cytology professionals showed good performance; however, there is room for improvement, especially in making specific diagnoses. In particular, follicular neoplasm and follicular variant of papillary thyroid carcinoma were challenging diagnoses for participants. © 2014 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl.

PubMed

Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

2015-11-20

After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0-18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF(V600E) in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF(V600E) was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF(V600E) may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.

Split sample comparison of a liquid-based method and conventional smears in thyroid fine needle aspiration.

PubMed

Jung, Chan-Kwon; Lee, Ahwon; Jung, Eun-Sun; Choi, Yeong-Jin; Jung, So-Lyung; Lee, Kyo-Young

2008-01-01

To compare the efficacy of the SurePath (SP) vs. conventional smears (CS) in fine needle aspiration (FNA) of thyroid gland lesions. A total of 193 FNA cases with thyroid nodules were studied. Samples from ultrasound-guided FNA were split to prepare CS and SP slides. The diagnostic categories of unsatisfactory, benign, atypical and malignant were compared. Galectin-3 immunostaining was performed on SP slides. Some differences were found between the cytomorphology of CS and SP. SP slides showed more increased cellularity and more clustered tissue fragments. On SP slides, nuclear detail and nucleoli were more easily detected and nuclear irregularity was very useful for the diagnosis of papillary carcinoma. SP showed a trend toward a lower proportion of atypical category. The overall sensitivity of FNA in diagnosing thyroid neoplasm was 90.9% for CS and 93.9% for SP. Most lesions (73%) diagnosed as papillary carcinoma after surgery showed positive staining of galectin-3. The SP method showed easy evaluation of cytomorphologic features and consistent specimen quality and appeared to be more useful in diagnosing the suspicious cases. Moreover, it offered the possibility of adjunctive immunocytochemistry on the same sample.

Concomitant sarcoidosis and papillary thyroid cancer with severe hypercalcaemia as the main symptom.

PubMed

Riis, Mikael Groth; Juhl, Kasper Svendsen; Bruun, Jens Meldgaard

2018-06-08

A 65-year-old Caucasian man was admitted to our hospital due to incidental finding of plasma ionised calcium=1.83 mmol/L. During the previous months, he had felt more tired and had experienced an unintended weight loss of 6-8 kg. A CT scan revealed an inhomogeneous thyroid gland and enlarged lymph nodes along the cervical vessels and in the mediastinum. The patient underwent total thyroidectomy and, at the same time, two lymph nodes were removed. Histological examination of the thyroid gland revealed papillary thyroid carcinoma (PTC), T1aN0M0, and histological examination of the lymph nodes showed non-caseating granulomatous inflammation. After further investigation, a diagnosis of sarcoidosis (SA) was made.Coexistence of SA and PTC may yield a diagnostic challenge as both diseases might involve the lymph nodes of the neck. Furthermore, the case illustrates the importance of close follow-up of even moderate hypercalcaemia, since it may evolve into a hypercalcaemic crisis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Effects of Hashimoto Thyroiditis on Lymph Node Metastases in Unifocal and Multifocal Papillary Thyroid Carcinoma

PubMed Central

Zhu, Feng; Shen, Yi Bin; Li, Fu Qiang; Fang, Yun; Hu, Liang; Wu, Yi Jun

2016-01-01

Abstract The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT). A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases. Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126–0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model. Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT. PMID:26871795

The Effects of Hashimoto Thyroiditis on Lymph Node Metastases in Unifocal and Multifocal Papillary Thyroid Carcinoma: A Retrospective Chinese Cohort Study.

PubMed

Zhu, Feng; Shen, Yi Bin; Li, Fu Qiang; Fang, Yun; Hu, Liang; Wu, Yi Jun

2016-02-01

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126-0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.

Relationship of body mass index with BRAF (V600E) mutation in papillary thyroid cancer.

PubMed

Shi, Rong-Liang; Qu, Ning; Liao, Tian; Wei, Wen-Jun; Lu, Zhong-Wu; Ma, Ben; Wang, Yu-Long; Ji, Qing-Hai

2016-06-01

Current evidences suggest an influence of overweight body mass index (BMI) on the carcinogenesis in malignancies. However, the role of BMI is unclear in papillary thyroid cancer (PTC). The aim of the present study is to investigate the relationship between BMI and BRAF (V600E) mutation status in PTC. BRAF (V600E) mutation in 108 patients with PTC was analyzed by Sanger sequencing. The cutoff point of BMI was identified by X-tile for predicting mutation by overweight. Odds ratios (OR) and 95 % confidence interval (CI) of BRAF (V600E) mutation according to BMI and clinicopathologic variables were calculated using logistic regression models. Fifty-one patients were positive for BRAF (V600E) mutation. A positive relationship existed between BRAF (V600E) mutation and BMI (p = 0.039). A 24.3 kg/m(2) was identified as cutoff point for differentiating greater than 52.0 % observed probability of mutation for BRAF (V600E) in entire cohort, which was similar to the midpoint between the upper limit of normal BMI and overweight defined by WHO (≥24 kg/m(2)). Multivariate analysis confirmed the association between BRAF (V600E) mutation with overweight BMI range (OR 7.645, 95 % CI 1.275-45.831, p = 0.026). This study suggests an influence of overweight BMI on the status of BRAF (V600E) in patients with PTC, whereas the underlying mechanism need to be further investigated.

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto's thyroiditis.

PubMed

Hirokawa, Mitsuyoshi; Nishihara, Eijun; Takada, Nami; Higuchi, Miyoko; Kotakemori, Masumi; Hayashi, Toshitetsu; Miyauchi, Akira

2018-02-26

Hashimoto's thyroiditis with heavy lymphoplasmacytic infiltration is a common comorbidity of immunoglobulin G4 (IgG4)-related thyroiditis and Warthin-like papillary thyroid carcinoma (WL-PTC). We hypothesized that WL-PTC may have a strong association with IgG4-related thyroiditis. To validate this hypothesis, we clinically and immunohistochemically studied 17 WL-PTC cases. Fourteen patients (82.4%) had anti-thyroglobulin antibody and were confirmed to have Hashimoto's thyroiditis through microscopic analysis. Among them, five (29.4%) had disease consistent with IgG4-related thyroiditis but did not exhibit a "storiform" pattern or obliterative phlebitis. IgG4-related diseases were not found in other organs. No cases with serum IgG4 level of >135 mg/dL were noted. A total of 94.1% of WL-PTC cases had IgG4-positive plasma cells ( + PCs) in the stroma, and cases with rich IgG4 + PCs were more frequently associated with Hashimoto's thyroiditis than those with poor IgG4 + PCs. In this study, all three cases without Hashimoto's thyroiditis had poor IgG4 + PCs, and one of them did not exhibit IgG4 + PCs in the stroma of WL-PTC and Hashimoto's thyroiditis. Nodal metastatic lesions were seen in eight cases, all of which were not WL-PTC. As such, we should consider that the Hashimoto's disease with rich IgG4 + PCs seen in our cases is representative of non-IgG4-related disease and not IgG4-related disease involving multiple organs. This study is the first to demonstrate the presence of IgG4 + PCs in the stroma of WL-PTC. We concluded that the appearance of IgG4 + PCs in the stroma of WL-PTC may be related to Hashimoto's thyroiditis with rich IgG4 + PC.

Thyroid cancer incidence patterns in Sao Paulo, Brazil, and the U.S. SEER program, 1997-2008.

PubMed

Veiga, Lene H S; Neta, Gila; Aschebrook-Kilfoy, Briseis; Ron, Elaine; Devesa, Susan S

2013-06-01

Thyroid cancer incidence has risen steadily over the last few decades in most of the developed world, but information on incidence trends in developing countries is limited. Sao Paulo, Brazil, has one of the highest rates of thyroid cancer worldwide, higher than in the United States. We examined thyroid cancer incidence patterns using data from the Sao Paulo Cancer Registry (SPCR) in Brazil and the National Cancer Institute's Surveillance Epidemiology End Results (SEER) program in the United States. Data on thyroid cancer cases diagnosed during 1997-2008 were obtained from SPCR (n=15,892) and SEER (n=42,717). Age-adjusted and age-specific rates were calculated by sex and histology and temporal patterns were compared between the two populations. Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the United States among females (SPCR/SEER incidence rate ratio [IRR]=1.65) and males (IRR=1.23). Papillary was the most common histology in both populations, followed by follicular and medullary carcinomas. Incidence rates by histology were consistently higher in Sao Paulo than in the United States, with the greatest differences for follicular (IRR=2.44) and medullary (IRR=3.29) carcinomas among females. The overall female/male IRR was higher in Sao Paulo (IRR=4.17) than in SEER (IRR=3.10) and did not change over time. Papillary rates rose over time more rapidly in Sao Paulo (annual percentage change=10.3% among females and 9.6% among males) than in the United States (6.9% and 5.7%, respectively). Regardless of sex, rates rose faster among younger people (<50 years) in Sao Paulo, but among older people (≥50 years) in the United States. The papillary to follicular carcinoma ratio rose from <3 to >8 among both Sao Paulo males and females, in contrast to increases from 9 to 12 and from 6 to 7 among U.S.males and females, respectively. Increased diagnostic activity may be contributing to the notable rise in incidence, mainly for papillary type, in both populations, but it is not likely to be the only reason. Differences in iodine nutrition status between Sao Paulo and the U.S. SEER population might have affected the observed incidence patterns.

Thyroid Cancer Incidence Patterns in Sao Paulo, Brazil, and the U.S. SEER Program, 1997–2008

PubMed Central

Neta, Gila; Aschebrook-Kilfoy, Briseis; Ron, Elaine; Devesa, Susan S.

2013-01-01

Background Thyroid cancer incidence has risen steadily over the last few decades in most of the developed world, but information on incidence trends in developing countries is limited. Sao Paulo, Brazil, has one of the highest rates of thyroid cancer worldwide, higher than in the United States. We examined thyroid cancer incidence patterns using data from the Sao Paulo Cancer Registry (SPCR) in Brazil and the National Cancer Institute's Surveillance Epidemiology End Results (SEER) program in the United States. Methods Data on thyroid cancer cases diagnosed during 1997–2008 were obtained from SPCR (n=15,892) and SEER (n=42,717). Age-adjusted and age-specific rates were calculated by sex and histology and temporal patterns were compared between the two populations. Results Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the United States among females (SPCR/SEER incidence rate ratio [IRR]=1.65) and males (IRR=1.23). Papillary was the most common histology in both populations, followed by follicular and medullary carcinomas. Incidence rates by histology were consistently higher in Sao Paulo than in the United States, with the greatest differences for follicular (IRR=2.44) and medullary (IRR=3.29) carcinomas among females. The overall female/male IRR was higher in Sao Paulo (IRR=4.17) than in SEER (IRR=3.10) and did not change over time. Papillary rates rose over time more rapidly in Sao Paulo (annual percentage change=10.3% among females and 9.6% among males) than in the United States (6.9% and 5.7%, respectively). Regardless of sex, rates rose faster among younger people (<50 years) in Sao Paulo, but among older people (≥50 years) in the United States. The papillary to follicular carcinoma ratio rose from <3 to >8 among both Sao Paulo males and females, in contrast to increases from 9 to 12 and from 6 to 7 among U.S.males and females, respectively. Conclusions Increased diagnostic activity may be contributing to the notable rise in incidence, mainly for papillary type, in both populations, but it is not likely to be the only reason. Differences in iodine nutrition status between Sao Paulo and the U.S. SEER population might have affected the observed incidence patterns. PMID:23410185

Rare Case of Intratracheal Metastasis Detected on 68Ga-Prostate-Specific Membrane Antigen PET/CT Scan in a Case of Thyroglobulin Elevated Negative Iodine Scan Syndrome.

PubMed

Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Oommen, Karuna Elza; Jayakumar, R

2018-04-01

A 64-year-old woman underwent completion thyroidectomy with upper tracheal ring resection and right-sided neck dissection for papillary carcinoma of the thyroid infiltrating the trachea and was given I radioiodine treatment. Three years later, she presented with hemoptysis. On evaluation, she had increased serum thyroglobulin and negative iodine scan (TENIS). F-FDG PET/CT scan did not identify any site of disease. One year later, Ga-PSMA scan done revealed a moderate focal tracer-avid intratracheal soft tissue; biopsy revealed it to be metastatic papillary carcinoma of the thyroid. This case kindles the possibility of using Ga-PSMA PET/CT to reveal occult disease in cases of TENIS.

RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma

PubMed Central

Romei, Cristina; Elisei, Rossella

2012-01-01

Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the expression level of the thyroid differentiation genes was observed. Recently, a diagnostic role of RET/PTC rearrangements has been proposed. It can be searched for in the mRNA extracted from cytological sample especially in case with indeterminate cytology. However, both the fact that it can be present in a not negligible percentage of benign cases and the technical challenge in extracting mRNA from cytological material makes this procedure not applicable at routine level, at least for the moment. PMID:22654872

Diagnostic Approach to Eosinophilic Renal Neoplasms

PubMed Central

Kryvenko, Oleksandr N.; Jorda, Merce; Argani, Pedram; Epstein, Jonathan I.

2015-01-01

Context Eosinophilic renal neoplasms include a spectrum of solid and papillary tumors ranging from indolent benign oncocytoma to highly aggressive malignancies. Recognition of the correct nature of the tumor, especially in biopsy specimens, is paramount for patient management. Objective To review the diagnostic approach to eosinophilic renal neoplasms with light microscopy and ancillary techniques. Data Sources Review of the published literature and personal experience. Conclusions The following tumors are in the differential diagnosis of oncocytic renal cell neoplasm: oncocytoma, chromophobe renal cell carcinoma (RCC), hybrid tumor, tubulocystic carcinoma, papillary RCC, clear cell RCC with predominant eosinophilic cell morphology, follicular thyroid-like RCC, hereditary leiomyomatosis–associated RCC, acquired cystic disease–associated RCC, rhabdoid RCC, microphthalmia transcription factor translocation RCC, epithelioid angiomyolipoma, and unclassified RCC. In low-grade nonpapillary eosinophilic neoplasms, distinction between oncocytoma and low-grade RCC mostly rests on histomorphology; however, cytokeratin 7 immunostain may be helpful. In high-grade nonpapillary lesions, there is more of a role for ancillary techniques, including immunohistochemistry for cytokeratin 7, CA9, CD10, racemase, HMB45, and Melan-A. In papillary eosinophilic neoplasms, it is important to distinguish sporadic type 2 papillary RCC from microphthalmia transcription factor translocation and hereditary leiomyomatosis–associated RCC. Histologic and cytologic features along with immunohistochemistry and fluorescence in situ hybridization tests for TFE3 (Xp11.2) and TFEB [t(6;11)] are reliable confirmatory tests. Eosinophilic epithelial neoplasms with architecture, cytology, and/or immunoprofile not qualifying for either of the established types of RCC should be classified as unclassified eosinophilic RCC and arbitrarily assigned a grade (low or high). PMID:25357116

Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer.

PubMed

Vecchio, Giancarlo; Parascandolo, Alessia; Allocca, Chiara; Ugolini, Clara; Basolo, Fulvio; Moracci, Marco; Strazzulli, Andrea; Cobucci-Ponzano, Beatrice; Laukkanen, Mikko O; Castellone, Maria Domenica; Tsuchida, Nobuo

2017-04-18

Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.

Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

PubMed Central

Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

2014-01-01

The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

Upregulation of the ESR1 Gene and ESR Ratio (ESR1/ESR2) is Associated with a Worse Prognosis in Papillary Thyroid Carcinoma: The Impact of the Estrogen Receptor α/β Expression on Clinical Outcomes in Papillary Thyroid Carcinoma Patients.

PubMed

Yi, Jin Wook; Kim, Su-Jin; Kim, Jong Kyu; Seong, Chan Yong; Yu, Hyeong Won; Chai, Young Jun; Choi, June Young; Lee, Kyu Eun

2017-11-01

A gender disparity exists with respect to the incidence of papillary thyroid cancer (PTC), suggesting that sex hormones such as estrogen play a role in PTC development and progression. In this study, we compared estrogen receptor gene expression patterns in PTCs to determine the clinical significance of estrogen gene expression in PTC. We analyzed ESR1 and ESR2 messenger RNA expression counts using data from The Cancer Genome Atlas (TCGA). To validate the results of TCGA analysis, we analyzed microarray data (GSE 54958) from the Gene Expression Omnibus. ESR1 gene expression and ESR ratio (ESR1/ESR2) were significantly higher in PTC tissues than in paired normal thyroid tissues (mean 659.427 vs. 264.045 for ESR1, 92.017 vs. 19.064 for ESR ratio). Among female patients, ESR1 expression and ESR ratio were negatively correlated with increased age. ESR1 expression and ESR ratio were higher in patients with classic PTC, lymphovascular invasion, BRAF V600E mutation, and radioiodine therapy. Classification analysis demonstrated that higher ESR1 expression and a higher ESR ratio faced a worse overall survival (hazard ratio 6.348 for ESR1, 4.031 for ESR ratio). Validation microarray analysis demonstrated that ESR1 expression and ESR ratio were higher in tumor tissues, classic PTC, and BRAF V600E . Higher ESR1 expression and a higher ESR ratio were associated with aggressive prognostic factors and worse overall survival in female PTC patients. Our results suggest that ESR1 and ESR ratio can be used as prognostic markers to predict female patient survival and have potential as a therapeutic target.

Role of chronic lymphocytic thyroiditis in central node metastasis of papillary thyroid carcinoma.

PubMed

Paulson, Lorien M; Shindo, Maisie L; Schuff, Kathryn G

2012-09-01

(1) To investigate the role of chronic lymphocytic thyroiditis (CLT) in central node metastasis of papillary thyroid carcinoma (PTC) and (2) to evaluate the presence of chronic lymphocytic thyroiditis according to PTC-specific molecular markers. Historical cohort study. Academic medical center. All patients who underwent total thyroidectomy with central neck dissection for PTC at Oregon Health & Science University between 2005 and 2010 were screened for the presence of CLT and reviewed for clinical prognostic factors. Patients with inadequate central neck dissections were excluded. Molecular markers for PTC were analyzed on archived tumor samples. A total of 139 patients met selection criteria. The rate of CLT was 43.8%. The rate of central node positivity was 63%. Presence of CLT was associated with a significantly lower proportion of central node metastases (49% vs 74%, P = .003) and angiolymphatic invasion (31% vs 15%, P = .03). There was no significant difference in mean age, tumor size, and extracapsular extension. Molecular genotyping did not reveal a significant difference in the types of mutations found in both groups. The data indicate a lower incidence of central compartment lymph node metastasis in those with CLT in this patient population, suggesting a potential protective role in tumor spread. The equal distribution of tumor mutations between the carcinomas with and without evidence of CLT argues against a mutation-specific antigen as the immunologic stimulus. Further research is needed to characterize the role of autoimmunity in thyroid cancer.

[Analysis of the patterns of cervical lymph node recurrence in patients with cN0 papillary thyroid carcinoma after central neck lymph node dissection].

PubMed

Huang, Hui; Xu, Zhengang; Wang, Xiaolei; Wu, Yuehuang; Liu, Shaoyan

2015-10-01

To retrospectively analyze the long-term results of prophylactic central lymph node dissection in cN0 papillary thyroid carcinoma (PTC), and investigate the treatment method of the cervical lymph nodes for cN0 PTC. One hundred and thirty-six patients with cN0 PTC were treated by surgery at the Cancer Hospital of Chinese Academy of Medical Sciences from 2000 to 2006. Their clinicopathological characteristics, surgical procedures and survival outcomes were collected and analyzed. The occult lymph node metastasis rate in central compartment was 61.0%. The average number of positive lymph nodes was 2.47 (1-13), in which 54 patients had 1-2 and 29 patients had ≥ 3 positive lymph nodes. Multiple logistic regression analysis showed that age less than 45 (P=0.001, OR 3.571, 95% CI 1.681-7.587)and extracapsular spread (ECS) (P=0.015, OR 2.99, 95% CI 1.241-7.202)were independent risk factors for lymph node metastasis in the central compartment. The ten-year cumulative overall survival rate was 98.3% and cumulative lateral neck metastasis rate was 25.2%. Multivariate analysis with Cox regression model showed that ECS (P=0.001, OR 5.211, 95% CI1.884-14.411) and positive lymph nodes in the central compartment ≥ 3 (P=0.009, OR 4.005, 95% CI 1.419-11.307) were independent risk factors for lymph node recurrence in the lateral neck region. The distribution of recurrent lymph nodes: level IV (82.4%), level III (64.7%), level II (29.4%) and level V (11.8%). Routine central lymph node dissection, at least unilateral, should be conducted for cN0 papillary thyroid carcinoma. Attention should be paid to the treatment of lateral neck region in patients with cN0 papillary thyroid carcinoma. Selective neck dissection is suggested for cN0 PTC with ECS or positive central lymph nodes ≥ 3, or both. The range of dissection should include level III and IV at least.

MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Yanfei; Qin, Huadong; Cui, Yunfu, E-mail: yfma77@126.com

Highlights: •MiR-34a is up- and GAS1 is down-regulated in papillary thyroid carcinoma. •GAS1 is a direct target for miR-34a. •MiR-34a promotes PTC cells proliferation and inhibits apoptosis through PI3K/Akt/Bad pathway. -- Abstract: MicroRNAs (miRNAs) are fundamental regulators of cell proliferation, differentiation, and apoptosis, and are implicated in tumorigenesis of many cancers. MiR-34a is best known as a tumor suppressor through repression of growth factors and oncogenes. Growth arrest specific1 (GAS1) protein is a tumor suppressor that inhibits cancer cell proliferation and induces apoptosis through inhibition of RET receptor tyrosine kinase. Both miR-34a and GAS1 are frequently down-regulated in various tumors.more » However, it has been reported that while GAS1 is down-regulated in papillary thyroid carcinoma (PTC), miR-34a is up-regulated in this specific type of cancer, although their potential roles in PTC tumorigenesis have not been examined to date. A computational search revealed that miR-34a putatively binds to the 3′-UTR of GAS1 gene. In the present study, we confirmed previous findings that miR-34a is up-regulated and GAS1 down-regulated in PTC tissues. Further studies indicated that GAS1 is directly targeted by miR-34a. Overexpression of miR-34a promoted PTC cell proliferation and colony formation and inhibited apoptosis, whereas knockdown of miR-34a showed the opposite effects. Silencing of GAS1 had similar growth-promoting effects as overexpression of miR-34a. Furthermore, miR-34a overexpression led to activation of PI3K/Akt/Bad signaling pathway in PTC cells, and depletion of Akt reversed the pro-growth, anti-apoptotic effects of miR-34a. Taken together, our results demonstrate that miR-34a regulates GAS1 expression to promote proliferation and suppress apoptosis in PTC cells via PI3K/Akt/Bad pathway. MiR-34a functions as an oncogene in PTC.« less

Thyroid cancer in Graves' disease: is surgery the best treatment for Graves' disease?

PubMed

Tamatea, Jade A U; Tu'akoi, Kelson; Conaglen, John V; Elston, Marianne S; Meyer-Rochow, Goswin Y

2014-04-01

Graves' disease is a common cause of thyrotoxicosis. Treatment options include anti-thyroid medications or definitive therapy: thyroidectomy or radioactive iodine (I(131) ). Traditionally, I(131) has been the preferred definitive treatment for Graves' disease in New Zealand. Reports of concomitant thyroid cancer occurring in up to 17% of Graves' patients suggest surgery, if performed with low morbidity, may be the preferred option. The aim of this study was to determine the rate of thyroid cancer and surgical outcomes in a New Zealand cohort of patients undergoing thyroidectomy for Graves' disease. This study is a retrospective review of Waikato region patients undergoing thyroid surgery for Graves' disease during the 10-year period prior to 1 December 2011. A total of 833 patients underwent thyroid surgery. Of these, 117 were for Graves' disease. Total thyroidectomy was performed in 82, near-total in 33 and subtotal in 2 patients. Recurrent thyrotoxicosis developed in one subtotal patient requiring I(131) therapy. There were two cases of permanent hypoparathyroidism and one of permanent recurrent laryngeal nerve palsy. Eight patients (6.8%) had thyroid cancer detected, none of whom had overt nodal disease. Five were papillary microcarcinomas (one of which was multifocal), two were papillary carcinomas (11 mm and 15 mm) and one was a minimally invasive follicular carcinoma. Thyroid cancer was identified in approximately 7% of patients undergoing surgery for Graves' disease. A low complication rate (<2%) of permanent hypoparathyroidism and nerve injury (<1%) supports surgery being a safe alternative to I(131) especially for patients with young children, ophthalmopathy or compressive symptoms. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

Nationwide cohort study on the epidemiology and survival outcomes of thyroid cancer

PubMed Central

Liu, Fu-Chao; Lin, Huan-Tang; Lin, Shu-Fu; Kuo, Chang-Fu; Chung, Ting-Ting; Yu, Huang-Ping

2017-01-01

In the past three decades, the thyroid cancer incidence has surged globally. Herein, the Taiwan National Health Insurance database was used to identify thyroid cancer patients and to estimate the prevalence and incidence of thyroid cancer during 1997-2012. The Taiwan Cancer Registry and the National Death Registry databases were crosslinked to obtain information on the histological subtypes and survival rates. Joinpoint regression analysis was used for estimating the average annual percentage changes (APCs) in prevalence, incidence, and survival. The age-standardized incidence of thyroid cancer increased from 5.66 per 100,000 person-years in 1997 to 12.30 per 100,000 person-years in 2012, with an average APC of 5.1 (6.9 in males, 4.6 in females). Thyroid cancer was more prevalent in patients with high socioeconomic status and in urban areas. Papillary carcinoma was the most abundant subtype, with a 2.9-fold increase of incident cases noted during 1998-2012 (from 80.6% to 89.8% of all cases). Among the different treatments, partial thyroidectomy increased the most (average APC, 17.3). The overall survival rates by sex and subtype remained stable over time, with 5-year survival rates of 90.2% in 1997 and 92.4% in 2010. In conclusion, 2.2- and 4.2-fold increases in the incidence and prevalence of thyroid cancer, respectively, were observed during 1997-2012 in Taiwan. The surging incidence of thyroid cancer but stable survival rates, and mainly increased in the papillary subtype, altogether imply enhanced detection of subclinical lesions. A true increase due to environmental carcinogens might also be responsible, but warrant further investigations. PMID:29108240

Preoperative Molecular Markers in Thyroid Nodules.

PubMed

Sahli, Zeyad T; Smith, Philip W; Umbricht, Christopher B; Zeiger, Martha A

2018-01-01

The need for distinguishing benign from malignant thyroid nodules has led to the pursuit of differentiating molecular markers. The most common molecular tests in clinical use are Afirma ® Gene Expression Classifier (GEC) and Thyroseq ® V2. Despite the rapidly developing field of molecular markers, several limitations exist. These challenges include the recent introduction of the histopathological diagnosis "Non-Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features", the correlation of genetic mutations within both benign and malignant pathologic diagnoses, the lack of follow-up of molecular marker negative nodules, and the cost-effectiveness of molecular markers. In this manuscript, we review the current published literature surrounding the diagnostic value of Afirma ® GEC and Thyroseq ® V2. Among Afirma ® GEC studies, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) ranged from 75 to 100%, 5 to 53%, 13 to 100%, and 20 to 100%, respectively. Among Thyroseq ® V2 studies, Se, Sp, PPV, and NPV ranged from 40 to 100%, 56 to 93%, 13 to 90%, and 48 to 97%, respectively. We also discuss current challenges to Afirma ® GEC and Thyroseq ® V2 utility and clinical application, and preview the future directions of these rapidly developing technologies.

BRAF Mutations in an Italian Regional Population: Implications for the Therapy of Thyroid Cancer

PubMed Central

Monti, Eleonora; Bovero, Michela; Mortara, Lorenzo; Pera, Giorgia; Zupo, Simonetta; Gugiatti, Elena; Dono, Mariella; Massa, Barbara; Ansaldo, Gian Luca; Massimo, Giusti

2015-01-01

Background. Molecular diagnostics has offered new techniques for searching for mutations in thyroid indeterminate lesions. The study's aim was to evaluate the BRAF mutations' incidence in an Italian regional population. Subjects and Methods. 70 Caucasian patients born in Liguria with indeterminate or suspicious cytological diagnoses. Results. A BRAF gene mutation was successfully analyzed in 56/70 patients. The mutation was BRAF V600E in 12/56 cases (21%) and BRAF K601E in 2/56 (4%). Of the BRAF mutated samples on cytological diagnosis (14/56 cases), 2/14 cases (14%) were benign on final histology and 12/14 (86%) were malignant. All BRAF-mutated cases on cytology that were found to be benign on histological examination carried the K601E mutation. Of the nonmutated BRAF cases (42/56, 75%) which were later found to be malignant on definitive histology, 5 cases were follicular carcinomas (36%), 3 cases were incidentally found to be papillary microcarcinomas (22%), 2 were cases papillary carcinomas (14%), 1 was case follicular variant of papillary carcinoma (7%), 1 was case medullary carcinoma (7%), 1 case was Hurtle cell tumor (7%), and 1 case was combined cell carcinoma and papillary oncocytic carcinoma (7%). Conclusions. The presence of the BRAF V600E mutation may suggest a more aggressive surgical approach. BRAF K601E mutation did not correlate with malignancy indexes. PMID:26693224

Determinants of papillary cancer of the thyroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wingren, G.; Hatschek, T.; Axelson, O.

1993-10-01

Determinants of papillary thyroid cancer were evaluated in a questionnaire-based case-control study from southeastern Sweden. A total of 104 cases, diagnosed from 1977 to 1987, and 387 randomly selected controls were included in the analyses. Female subjects with papillary cancer reported a work history as dentists/dental assistants, telephone operators, teachers, and day nursery personnel, and an occupational contact with chemicals and video display terminals more often than did controls. The 11 male cases more often reported working as mechanics and metal workers and having occupational contact with solvents. Other factors associated with increased risk for female papillary cancer were havingmore » private well water at the birth address; leisure time exposure to combustion smoke; low intake of cruciferous vegetables and seafood; and a family history of goiter, heart disease, biliary disorder, or female genital cancer. Diagnostic radiographic examinations, especially to the head, neck, or upper back/chest area, or repeated dental examinations, were also found to be associated with this form of cancer. With regard to the possible influence from hormonal factors among women less than age 50 years at time of diagnosis, an increased risk was found for a pregnancy soon after puberty. Tendencies toward a decreasing risk with increasing age at first pregnancy as well as an increasing risk with increasing number of pregnancies were found as well. Multiparity seemed to potentiate the effect from prior radiographic examinations.« less

A rare case of laryngotracheal chondrosarcoma in a patient with past history of radioiodine therapy for thyroid cancer.

PubMed

Mohajeri, Gholamreza; Hekmatnia, Ali; Ahrar, Hossein; Hekmatnia, Farzane; Nia, Reza Basirat; Afsharmoghadam, Nushin; Eftekhari, Mehdi; Jafarpishe, Saleh

2013-01-01

Tracheal chondrosarcoma is a rare malignant mesenchymal tumor and there are less than 15 reports in the literature. We report a rare case of laryngotracheal chondrosarcoma in a 74-year-old man. He gave a history of radioiodine therapy for thyroid papillary carcinoma about 24 years ago. Diagnostic steps, histological presentation, and therapy are described in detail.

The advantages of subtotal thyroidectomy and suppression of TSH in the primary treatment of papillary carcinoma of the thyroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crile, G. Jr.; Antunez, A.R.; Esselstyn, C.B. Jr.

1985-06-01

Patients between the ages of 6 and 45 years with distant metastases from papillary carcinoma of the thyroid can be treated as effectively by subtotal thyroidectomy and suppressive doses of thyroid hormone as by total thyroidectomy followed by treatment with iodine 131 (/sup 131/I). Moreover, distant metastases can be treated by either /sup 131/I or suppression as effectively after they are apparent on x-ray as they can be when treated in a subclinical stage. Therefore, in patients younger than 45 years old it is rarely necessary to perform a total thyroidectomy or to do frequent postoperative scans. In patients oldermore » than 44 or younger than 7 who have distant metastases or extensive involvement of both lobes, total or almost total thyroidectomy is justified if it can be done with minimal morbidity. In patients of this age group whose tumors fail to respond to suppressive doses of thyroid, /sup 131/I should be used. In view of the importance of diagnostic related groups (DRG) to the economy of hospitals, we note that the cost of total thyroidectomy, ablation by /sup 131/I, and intermittent body scans is at least three times that of less radical procedures which, in conjunction with suppression by thyroid feeding, give the same survival with less morbidity.« less

Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis.

PubMed

Zivancevic-Simonovic, Snezana; Mihaljevic, Olgica; Majstorovic, Ivana; Popovic, Suzana; Markovic, Slavica; Milosevic-Djordjevic, Olivera; Jovanovic, Zorica; Mijatovic-Teodorovic, Ljiljana; Mihajlovic, Dusan; Colic, Miodrag

2015-08-01

Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); Th9-interleukin 9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity.

ThinPrep versus conventional smear cytologic preparations in the analysis of thyroid fine-needle aspiration specimens.

PubMed

Biscotti, C V; Hollow, J A; Toddy, S M; Easley, K A

1995-08-01

Paired fine-needle aspiration specimens were analyzed from 41 surgically resected thyroid nodules, to compare diagnostic accuracy, amount (absent, mild, moderate, or marked) and pattern (diffuse, droplets, or both) of colloid, nuclear detail (poor, satisfactory, or excellent) and cytoplasmic detail (intact or disrupted) in ThinPrep (TP) (Cytyc, Marlborough, MA) versus conventional smear (CS) cytologic preparations. The 41 surgical specimens included 25 colloid nodules, 6 papillary carcinomas, 4 follicular adenomas, 2 minimally invasive (encapsulated) follicular carcinomas, 3 Hashimoto's thyroiditis, and 1 Grave's disease. Both techniques identified seven of the eight carcinomas with the minimally invasive follicular carcinomas categorized as hypercellular follicular nodule, possibly malignant (HCFN). One papillary carcinoma was classified as a HCFN by both TP and CS techniques. The four follicular adenomas were classified as HCFN based on the TP slides. One oxyphilic follicular adenoma, associated with focal lymphocytic thyroiditis, was misinterpreted as Hashimoto's thyroiditis on a conventional smear. Three colloid nodules were interpreted as HCFN based on the TP slides. Two of these were similarly classified based on the conventional smear. ThinPrep slides contained less colloid and the colloid occurred as droplets rather than a diffuse pattern. TP slides had better nuclear detail but more often disrupted cytoplasm. In conclusion, the TP process does alter some cellular features; however, we experienced similar diagnostic accuracy with the TP and conventional smear preparations.

[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses].

PubMed

Dalquen, P; Rashed, B; Hinsch, A; Issa, R; Clauditz, T; Luebke, A; Lüttges, J; Saeger, W; Bohuslavizki, K H

2016-09-01

Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. Investigation of causes and relevance of discrepant diagnoses. The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma.

PubMed

Brahma, Bayu; Yulian, Erwin Danil; Ramli, Muchlis; Setianingsih, Iswari; Gautama, Walta; Brahma, Putri; Sastroasmoro, Sudigdo; Harimurti, Kuntjoro

2013-01-01

Throughout Indonesia, thyroid cancer is one of the ten commonest malignancies, with papillary thyroid carcinoma (PTC) in our hospital accounting for about 60% of all thyroid nodules. Although fine needle aspiration biopsy (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as indeterminate and second surgery is common for PTC. The aim of this study was to establish the diagnostic value and feasibility of testing the BRAF T1799A mutation on FNA specimens for improving PTC diagnosis. This prospective study enrolled 95 patients with thyroid nodules and future surgery planned. Results of mutational status were compared with surgical pathology diagnosis. Of the 70 cases included in the final analysis, 62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for BRAF mutation analysis were 36%, 100%, 100% and 48%, respectively. With other data findings, nodules with "onset less than 5 year" and "hard consistency" were proven as diagnostic determinants for BRAF mutation with a probability of 62.5%. This mutation was also a significant risk factor for extra-capsular extension. Molecular analysis of the BRAF T1799A mutation in FNAB specimens has high specificity and positive predictive value for PTC. It could be used in the selective patients with clinical characteristics to facilitate PTC diagnosis and for guidance regarding extent of thyroidectomy.

Increased Pleiotrophin Concentrations in Papillary Thyroid Cancer

PubMed Central

Jee, Youn Hee; Sadowski, Samira M.; Celi, Francesco S.; Xi, Liqiang; Raffeld, Mark; Sacks, David B.; Remaley, Alan T.; Wellstein, Anton; Kebebew, Electron; Baron, Jeffrey

2016-01-01

Background Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown. Method and Findings 74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In FNA samples, PTN concentration normalized to Tg was significantly higher in PTC than in benign nodules (16 ± 6 vs 0.3 ± 0.1 ng/mg, p < 0.001). In follicular variant of PTC (n = 6), the PTN/Tg ratio was also higher than in benign nodules (1.3 ± 0.6 vs 0.3 ± 0.1 ng/mg, P < 0.001, respectively). IHC showed cytoplasmic localization of PTN in PTC cells. Conclusion In ex vivo FNA samples, the PTN to thyroglobulin ratio was higher in PTCs, including follicular variant PTC, than in benign thyroid nodules. The findings raise the possibility that measurement of the PTN to Tg ratio may provide useful diagnostic and/or prognostic information in the evaluation of thyroid nodules. PMID:26914549

One-third of an Archivial Series of Papillary Thyroid Cancer (Years 2007–2015) Has Coexistent Chronic Lymphocytic Thyroiditis, Which Is Associated with a More Favorable Tumor-Node-Metastasis Staging

PubMed Central

Ieni, Antonio; Vita, Roberto; Magliolo, Emilia; Santarpia, Mariacarmela; Di Bari, Flavia; Benvenga, Salvatore; Tuccari, Giovanni

2017-01-01

The significance and impact of the coexistence of chronic lymphocytic thyroiditis (CLT) with thyroid cancer is still debated. To verify the influence of CLT on papillary thyroid cancer (PTC), we retrospectively collected 505 PTC cases and analyzed age at diagnosis, sex, size, lymph node status, and staging. We found that CLT was present in 168 PTC (33.3%). Compared with the 337 patients without CLT (non-CLT), CLT patients were younger (44.42 ± 13.72 vs. 47.21 ± 13.76 years, P = 0.03), had smaller tumors (9.39 ± 6.10 vs. 12 ± 9.71 mm, P = 0.002), and lower rate of lymph node metastases (12.5 vs. 21.96%, P = 0.01, OR = 0.508). Tumor-node-metastasis (TNM) staging (T1a through T4) was more favorable for the CLT group compared to the non-CLT group (for instance, T1a = 65.5 vs. 49.8%, T3 = 4.8 vs. 23.4%). This study shows that one in three patients with PTC harbors CLT, which is associated with a more favorable TNM staging, consistently with a favorable outlook of PTC. PMID:29250033

One-third of an Archivial Series of Papillary Thyroid Cancer (Years 2007-2015) Has Coexistent Chronic Lymphocytic Thyroiditis, Which Is Associated with a More Favorable Tumor-Node-Metastasis Staging.

PubMed

Ieni, Antonio; Vita, Roberto; Magliolo, Emilia; Santarpia, Mariacarmela; Di Bari, Flavia; Benvenga, Salvatore; Tuccari, Giovanni

2017-01-01

The significance and impact of the coexistence of chronic lymphocytic thyroiditis (CLT) with thyroid cancer is still debated. To verify the influence of CLT on papillary thyroid cancer (PTC), we retrospectively collected 505 PTC cases and analyzed age at diagnosis, sex, size, lymph node status, and staging. We found that CLT was present in 168 PTC (33.3%). Compared with the 337 patients without CLT (non-CLT), CLT patients were younger (44.42 ± 13.72 vs. 47.21 ± 13.76 years, P  = 0.03), had smaller tumors (9.39 ± 6.10 vs. 12 ± 9.71 mm, P  = 0.002), and lower rate of lymph node metastases (12.5 vs. 21.96%, P  = 0.01, OR = 0.508). Tumor-node-metastasis (TNM) staging (T1a through T4) was more favorable for the CLT group compared to the non-CLT group (for instance, T1a = 65.5 vs. 49.8%, T3 = 4.8 vs. 23.4%). This study shows that one in three patients with PTC harbors CLT, which is associated with a more favorable TNM staging, consistently with a favorable outlook of PTC.

Follow-up of differentiated thyroid carcinoma.

PubMed

Pagano, L; Klain, M; Pulcrano, M; Angellotti, G; Pasano, F; Salvatore, M; Lombardi, G; Biondi, B

2004-12-01

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.

Microfollicular adenoma of ectopic thyroid gland masquerading as salivary gland tumor - a diagnostic and therapeutic challenge: a case report.

PubMed

Deshmukh, Sanjay D; Khandeparkar, Siddhi G Sinai; Gulati, Harveen K; Naik, Chetana S

2014-08-07

Ectopic thyroid tissue may appear in any location along the trajectory of the thyroglossal duct from the foramen cecum to the mediastinum. Rarely, there is incomplete descent of the gland where the final resting point may be high resulting in sublingual ectopic thyroid tissue. Ectopic thyroid tissue carries a low risk of malignancy. Most recently reported neoplasms in ectopic thyroid tissue have been papillary carcinoma of thyroid. Individual case reports of clear cell type of follicular adenoma within the ectopic thyroid tissue have been described in the literature. We present a rare case of microfollicular follicular adenoma in an ectopic sublingual thyroid tissue presenting as submental swelling in a euthyroid 24-year-old Dravidian woman. Findings in this case emphasize that when confronted with a submental/sublingual mass lesion, the evaluation of thyroid function tests and ultrasonography of the neck should be included in a pre-operative workup.

Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid

PubMed Central

El Demellawy, Dina; Nasr, Ahmed; Alowami, Salem

2008-01-01

Papillary carcinoma of the thyroid (PTC) is the commonest thyroid cancer. In the recent decades an obvious increase in the incidence of PTC has occurred. The pathological diagnosis of PTC is usually an easy diagnosis in the majority of cases. However since the introduction of follicular variant of PTC and the wide threshold range in interpretation of the clearly set pathological criteria for diagnosis of PTC, between pathologists including experts, the diagnosis in some cases became quite difficult. Unfortunately some cases are unjustifiably over-called as follicular variant of PTC as a result of the wide inter observable variability between pathologists, including thyroid pathologists. Ancillary studies such as immmunohistochemistry may be helpful, but till now there is no 100% consistent marker(s), that distinct between PTC and other follicular thyroid lesions and tumors. We assessed expression of antibodies against CD56, CK19, P63 and E-Cadherin in PTC and other follicular thyroid lesions and neoplasms. A total of 175 cases were studied. The neoplastic cases included 75 carcinomas (72 papillary, 2 follicular, 1 Hurthle cell) and 35 adenomas (32 follicular and 3 Hurthle cell). The non-neoplastic thyroids included 65 cases, (25 nodular hyperplasia, 5 thyrotoxic hyperplasia (Grave's disease), 19 lymphocytic thyroiditis and 6 Hashimoto's thyroiditis). All cases were evaluated by immunohistochemistry for the expression of the above mentioned markers. The markers' patterns and intensities of staining were scored. Positive expression of the markers equal or >10% of the follicular epithelium within the tumor or lesional cells was considered positive. An expression of <10% was considered to be negative. Our results showed CD56 positive in all the lesions and tumors except for PTC in all cases (100%). CD56 was negative in all PTC cases (100%). CK 19 showed positive expression in PTC accounting for 85% of cases and in 26% of non PTC lesions/tumors. P63 showed selective focal positivity in PTC cases, in contrast to other non PTC lesions/tumors. P63 expression was in 70% of cases of PTC and was consistently absent in all the non PTC cases. E-Cadherin showed consistent non discriminatory expression in all cases included in the study. We concluded that a panel consisted of CD56, CK19 and P63 is of value in distinction of PTC from other thyroid follicular lesion. P63 is a specific but less sensitive marker for PTC than CK19. CD56 is more specific and sensitive marker than CK19, however it is a negative rather than a positive marker for PTC. E-Cadherin is of no value in the diagnosis of thyroid follicular lesions/tumors. We recommend application of a panel composed of CK19, P63 and CD56 by a group of expert thyroid pathologists on a large series of follicular malignant thyroid neoplasms of uncertain malignant. PMID:18254952

[Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

PubMed

Itoh, Mitsuyasu

2012-11-01

Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

Thyroid carcinoma in children and adolescents resulting from the Chernobyl accident: possible causes of the incidence increase overestimation.

PubMed

Jargin, S V

2009-04-01

The Chernobyl accident in the nuclear power plant on 26th April 1986 was followed by numerous publications overestimating the medical consequences of the disaster. In the publications, interpretations of spontaneous diseases as radiation-induced, indication of radioactivity or dose levels without confrontation with the natural radiation background, or conclusions about incidence increase without comparison with the increase tendencies in larger regions or the whole country, can be found. Improved diagnostics after the Chernobyl accident is not always taken into account. The high figures could have been caused in some cases by non-random material selection or inadequate morphological assessment of biopsy specimens. The application of the linear-no-threshold theory to the inhabitants of contaminated areas contributed to an overestimation of medical consequences of the Chernobyl accident as well. The incidence increase of thyroid carcinoma in children and adolescents started in 1990, four years after the accident. High tumor expectancy after the accident, in the circumstances of limited technical possibilities and outdated equipment of histological laboratories, contributed to a higher number of registered cases. The quality of specimens necessary for the assessment of nuclear criteria of papillary carcinoma was not always achieved at that time. The incidence increase of thyroid carcinoma can, at least in part, be explained by improved detection of thyroid nodules with occasional false-positive conclusions about malignancy. Besides, latent carcinomas and well-differentiated thyroid tumors of uncertain malignant potential, diagnosed as malignancies, could have additionally contributed to the high figures.

A novel RET/PTC variant detected in a pediatric patient with papillary thyroid cancer without ionization history.

PubMed

Halkova, Tereza; Dvorakova, Sarka; Vaclavikova, Eliska; Sykorova, Vlasta; Vcelak, Josef; Sykorova, Pavla; Vlcek, Petr; Reboun, Martin; Katra, Rami; Kodetova, Daniela; Schrumpf, Melanie; van Wezel, Tom; Morreau, Hans; Bendlova, Bela

2015-12-01

Papillary thyroid carcinoma (PTC) is the most frequent type of thyroid cancer. Its development is often caused by the formation of RET/PTC fused genes. RET/PTC1 is the most prevalent form, where exon 1 of CCDC6 gene is fused with the intracellular portion of RET protooncogene starting with exon 12. We have discovered a novel RET/PTC1 variant which we have named RET/PTC1ex9 in metastatic PTC of 8-year-old boy. RET/PTC1ex9 detection was performed by real-time polymerase chain reaction with melting curve analysis and subsequent Sanger and next-generation sequencing. A fusion of exon 1 of CCDC6 with exon 9 of extracellular domain of RET followed by exon 12 of RET was revealed. This is the first RET/PTC variant among PTC cases that contain the extracellular part of RET. This observation could be probably explained by incorrect splicing of RET due to the somatic 32-bp deletion in exon-intron 11 boundary of RET. Copyright © 2015 Elsevier Inc. All rights reserved.

Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969-2013.

PubMed

Nash, Sarah H; Lanier, Anne P; Southworth, Molly B

2018-04-01

Nationwide, the incidence of thyroid cancer is lower among American Indian/Alaska Native (AI/AN) people than among U.S. whites (USW). However, little is known about the incidence of thyroid or other endocrine cancers specifically among Alaska Native (AN) people. Data were examined from the National Cancer Institute's Surveillance, Epidemiology, and End Results Alaska Native Tumor Registry on endocrine cancers diagnosed among AN people from 1969-2013, with a specific focus on thyroid cancers. Frequencies of endocrine cancers by site and also of thyroid cancers by histology, size, and stage at diagnosis were evaluated. Distributions were compared to USW (Surveillance, Epidemiology, and End Results 9 Registries) using the chi-square test. Five-year average annual age-adjusted incidence rates of thyroid cancers were calculated, stratified by histology, age, and five-year period of diagnosis, and compared to those observed among USW. Five-year cause-specific survival was evaluated using cause of death data from the National Death Index Plus from the National Center for Health Statistics. During the 45-year period (1969-2013), 224 endocrine cancers were diagnosed among AN people, of which 210 (94%) were thyroid cancers. Compared to USW, AN people were diagnosed at a slightly younger age, had a higher proportion of thyroid cancers diagnosed with a size of 20-40 mm, and a larger proportion of patients with regional metastases. More than 85% of AN thyroid cancers were of papillary histology. The incidence of thyroid cancers was similar between AN people and USW, and appeared to increase among AN people over the period of surveillance. Finally, five-year cause-specific survival rate was 100% for papillary carcinoma patients and 86.3% [confidence interval 54.7-96.5] for follicular thyroid cancer patients. This study is the first report of endocrine cancers and the first detailed examination of thyroid cancer among AN people. The incidence of thyroid cancer was similar among AN people and USW. However, compared to USW, AN people appear to be at risk for diagnosis at a younger age, larger size, and higher stage. Further research is needed to explore the causes of these differences.

Clinical Features of Early and Late Postoperative Hypothyroidism After Lobectomy.

PubMed

Park, Suyeon; Jeon, Min Ji; Song, Eyun; Oh, Hye-Seon; Kim, Mijin; Kwon, Hyemi; Kim, Tae Yong; Hong, Suck Joon; Shong, Young Kee; Kim, Won Bae; Sung, Tae-Yon; Kim, Won Gu

2017-04-01

Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur. We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC). This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up. Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001). Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery. Copyright © 2017 by the Endocrine Society

My approach to oncocytic tumours of the thyroid

PubMed Central

Asa, S L

2004-01-01

The traditional approach to oncocytic thyroid lesions classified these as a separate entity, and applied criteria that are somewhat similar to those used for follicular lesions of the thyroid. In general, the guidelines to distinguish hyperplasia from neoplasia, and benign from malignant were crude and unsubstantiated by scientific evidence. In fact, there is no basis to separate oncocytic lesions from other classifications of thyroid pathology. The factors that result in mitochondrial accumulation are largely unrelated to the genetic events that result in proliferation and neoplastic transformation of thyroid follicular epithelial cells. The concept of classifying oncocytic lesions, including follicular variant papillary carcinomas, based on nuclear morphology, immunohistochemical profiles, and molecular markers may pave the way for a better understanding of the biology of oncocytic lesions of the thyroid. PMID:14990587

Effects of Chronic Lymphocytic Thyroiditis on the Clinicopathological Features of Papillary Thyroid Cancer.

PubMed

Babli, Saleha; Payne, Richard J; Mitmaker, Elliot; Rivera, Juan

2018-03-01

The effects of chronic lymphocytic thyroiditis (CLT) on the presentation and outcome of papillary thyroid carcinoma (PTC) have long been a topic of controversy. To evaluate the effect of coexistent CLT on the clinicopathological features of PTC. Retrospective study. All patients with PTC who had been followed by the 2 co-investigators (Juan Rivera and Richard J. Payne) between 2006 and 2011 were included. CLT was present in 35% (166) of the included patients and was associated with a higher proportion of patients with TNM stage I ( p = 0.027) and fewer patients with persistent disease ( p = 0.014) in comparison with the PTC-only group. Analysis of the data based on age (<45 or >45 years) revealed that in the older group, the presence of CLT was associated with fewer patients with persistent disease ( p = 0.03) and capsular invasion ( p = 0.05). However, in patients <45 years of age, the presence of CLT was associated with more capsular invasion ( p = 0.003) and extrathyroidal extension ( p = 0.004) compared with the PTC-only group. CLT in patients with PTC was associated with lower-stage disease and less disease persistence in patients >45 years of age. In patients <45 years, the presence of CLT appeared to be associated with unfavorable pathological features.

An audit of management of differentiated thyroid cancer in specialist and non-specialist clinic settings.

PubMed

Kumar, H; Daykin, J; Holder, R; Watkinson, J C; Sheppard, M C; Franklyn, J A

2001-06-01

Thyroid cancer is the most common endocrine malignancy but is none the less rare. Some aspects of its management remain controversial. Previous audits of patient management in the United Kingdom have revealed deficiencies, especially in communication between specialists. We have audited patient management in a large university-associated teaching hospital, assessing points of good practice identified from published guidelines and reviews, and have compared findings in groups of patients managed jointly by specialists with an interest in thyroid cancer (including surgeon, endocrinologist and oncologist) with a group managed by other clinicians outside that setting. Retrospective case-note review of 205 patients with differentiated (papillary or follicular) cancer including group A (n = 134; managed in a specialist multi-disciplinary clinic setting) and group B (n = 71; managed in other clinic settings). Points of good practice investigated were adequacy of surgery, surgical complications, prescription and adequacy of T4 treatment, adequacy of monitoring by measurement of serum thyroglobulin and action taken and appropriate administration of ablative radioiodine. Deficiencies in management of the cohort as a whole were identified, including inadequate surgery and inadequate TSH suppression in approximately one-fifth of the cases. Monitoring with thyroglobulin measurements and action when serum thyroglobulin was high were also inadequate in some cases and ablative radioiodine was not given, despite being indicated in 11.7% of the cohort. Inadequate surgery and failure to administer radioiodine were less common in those managed in a specialist clinic setting than in those managed in other clinic settings. The findings highlight the need for locally agreed protocols in managing relatively rare endocrine disorders such as thyroid cancer and argue in favour of centralization of expertise and patient management in multi-disciplinary specialist clinic settings.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Nancy L., E-mail: nlcho@partners.org; Lin, Chi-Iou; Du, Jinyan

Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using amore » bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.« less

Hyperthyroidism in patients with thyroid cancer.

PubMed

Sharma, Sunil Dutt; Kumar, Gaurav; Guner, Karen; Kaddour, Hesham

2016-06-01

We present a retrospective case series of patients with hyperthyroidism and thyroid cancer. Our goal was to look at their clinical characteristics and outcomes to determine which patients would require further investigation. We reviewed the case notes of all patients with a histopathologic diagnosis of thyroid cancer and biochemical evidence of hyperthyroidism who had been treated at a thyroid cancer center from January 2006 through October 2013. During that time, 66 patients had been diagnosed with thyroid cancer. Of these, 8 patients (12%)-all women, aged 29 to 87 years (mean: 55.6; median: 50.5)-had biochemical evidence of hyperthyroidism. Among these 8 patients, 4 had an autonomously functioning toxic nodule (AFTN), 3 were diagnosed with Graves disease, and 1 had a toxic multinodular goiter. Five patients had suspicious features on preoperative ultrasonography. All 8 patients were diagnosed with the papillary type of thyroid carcinoma. The mean size of the tumor in the 4 patients with AFTN was significantly larger than it was in those with Graves disease (42.3 ± 23.8 mm vs. 3.8 ± 1.6; p = 0.04). The 3 patients with Graves disease all had incidentally found papillary microcarcinoma. Between these two groups, the patients with AFTN had a poorer prognosis; 2 of them had extracapsular invasion and lymph node metastasis, and another died of her disease. We found that the incidence of hyperthyroidism in thyroid cancer patients was relatively high (12%). In contrast to what has previously been reported in the literature, patients with AFTN seem to have more aggressive disease and poorer outcomes than do patients with Graves disease. Any suspicious nodule associated with hyperthyroidism should be evaluated carefully.

Ultrasonographic features and clinical characteristics of Warthin-like variant of papillary thyroid carcinoma.

PubMed

Kim, Ga Ram; Shin, Jung Hee; Hahn, Soo Yeon; Ko, Eun Young; Oh, Young Lyun

2016-04-25

Warthin-like variant of papillary thyroid carcinoma (WVPTC) is a rare entity recently characterized. We evaluated ultrasonographic (US) features and clinical characteristics of WVPTC. Nine patients were diagnosed with WVPTC through surgery in our institution from May 2005 to January 2015. Eight of nine patients had available preoperative US images. A retrospective review of the US and clinical characteristics was performed. WVPTC compromised of 0.06% of 14,071 PTCs surgically confirmed. A mean age of nine patients was 53.2 years (range, 32-75 years). The mean nodule size of nine WVPTCs was 0.9 cm (range, 0.5-1.5 cm). Two patients showed central nodal metastasis and one patient with conventional PTC as an index tumor underwent central and lateral neck dissection. No one showed recurrence or distant metastasis during the follow-up period (mean, 4.6 years; range, 0.6-10 years). The most common US features of WVPTCs were solid composition (62.5%), hypoechogenicity (75%), and wider-than-tall shape (100%), respectively. Four (50%) of eight nodules showed well-defined margin and three (37.5%) of them had cystic component. One of eight resembled focal thyroiditis. Three nodules were considered as probably benign with US. All nine cases demonstrated underlying heterogeneous parenchymal echogenicity and accompanied chronic lymphocytic thyroiditis in permanent sections. Thyroid function tests in all patients were normal except for one with subclinical hypothyroidism. WVPTC is an uncommon subtype of PTC and has favorable prognosis, which can be misdiagnosed as a probably benign nodule or focal thyroiditis with US. All cases are associated with heterogeneous parenchyma in the background.

Follicular neoplasms of the thyroid: importance of clinical and cytological correlation.

PubMed

Granados-García, Martín; Cortés-Flores, Ana Olivia; del Carmen González-Ramírez, Imelda; Cano-Valdez, Ana María; Flores-Hernández, Lorena; Aguilar-Ponce, José Luis

2010-01-01

Thyroid cancer presents as nodules. Thyroid nodules are frequent, but only 5-30% are malignant. Fine needle aspiration biopsy (FNAB) is useful for initial evaluation; nevertheless, malignancy is uncertain when follicular neoplasm is reported. Some factors can be associated with malignancy. Therefore, we analyzed our follicular neoplasms in order to identify those factors associated with a higher risk of malignancy. We analyzed the clinical files of consecutive patients with cytological diagnoses of follicular neoplasm. From 1,005 cases of thyroid nodules, 121 were follicular neoplasms according to cytology. Of these, 75 were surgically treated. Definitive report showed 45 benign (60%) and 30 malignant (40%) cases. Benign cases included 29 goiters, 11 follicular adenomas, and 5 cases of thyroiditis. Malignant cases were comprised of 12 papillary carcinomas, 4 follicular carcinomas, 3 papillary carcinomas-follicular variant, 1 lymphoma, 1 teratoma, 5 medullary carcinomas, 2 insular carcinomas, 1 anaplastic carcinoma and 1 metastatic breast carcinoma. Tumor size of benign lesions was 3.43 ± 2.04 cm, and 4.67 ± 2.78 (p = 0.049) for malignant lesions. Age was 46.95 ± 15.39 years for benign lesions and 48.67 ± 17.28 for malignant lesions (p = 0.66). Fifty percent of males showed malignancy vs. 37.7% of females (p < 0.005). Our results suggest that size and gender, but not age, are associated with cytological pattern. Ultrasonographic characteristics may be useful discriminating patients with a higher risk of malignancy. FNAB is a useful tool for initial evaluation of thyroid nodules, but clinical evaluation can enhance predictive value.

Our experience of treatment of cribriform morular variant of papillary thyroid carcinoma; difference in clinicopathological features of FAP-associated and sporadic patients.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Ishikawa, Hideki; Hirokawa, Mitsuhiro; Kudo, Takumi; Tomoda, Chisato; Miya, Akihiro

2011-01-01

Cribriform-morular variant (CMV) is a comparably rare histological subtype of papillary thyroid carcinoma (PTC). This can be associated with familial adenomatous polyposis (FAP) due to APC gene mutations. In this study, we investigated the difference in the biological characteristics between FAP-associated and sporadic CMV. Between 1991 and 2010, 32 patients with CMV were treated in Kuma Hospital. Thirty-one of these underwent initial surgery for CMV in Kuma Hospital. Twelve patients were FAP-associated and the remaining 19 were sporadic CMV. All patients were female. Tumors of FAP-associated CMV were more frequently multiple than those of sporadic CMV. Patient age and tumor size did not differ between the two groups. Of 12 FAP-associated CMV, 5 were detected by thyroid nodule (thyroid precedent group) and 7 were detected by FAP (polyposis precedent group) as an initial manifestation. Patient age was younger and tumor size was smaller in the polyposis group than in the thyroid nodule group. All patients lacked extrathyroid extension on intraoperative finding and were node-negative on pathological examination. To date, two patients with FAP-associated CMV who initially underwent hemithyroidectomy (one in Kuma Hospital and one in another hospital) showed recurrence to the remnant thyroid during follow-up. None of the patients showed recurrence to other regions or died of carcinoma. Taken together, CMV is considered an indolent disease in our series. FAP-associated CMV showed multiple tumors more frequently than sporadic CMV. Total thyroidectomy is recommended for FAP-associated CMV, but extensive lymph node dissection is not necessary.

Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women

PubMed Central

2013-01-01

Background Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC). Methods To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography–mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs. Results The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P < 0.025) than in the benign group. The metabolic ratios of 16α-OH-estrone/estrone and estriol/estradiol, which are responsible for 16α-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P < 0.02 each). The more than 6.2-fold decrease in the urinary 2-/16α-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01). Conclusions Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women. PMID:24156385

Tumor size measured by preoperative ultrasonography and postoperative pathologic examination in papillary thyroid carcinoma: relative differences according to size, calcification and coexisting thyroiditis.

PubMed

Yoon, Young Hoon; Kwon, Ki Ryun; Kwak, Seo Young; Ryu, Kyeung A; Choi, Bobae; Kim, Jin-Man; Koo, Bon Seok

2014-05-01

Ultrasonography (US) is a useful diagnostic modality for evaluation of the size and features of thyroid nodules. Tumor size is a key indicator of the surgical extent of thyroid cancer. We evaluated the difference in tumor sizes measured by preoperative US and postoperative pathologic examination in papillary thyroid carcinoma (PTC). We reviewed the medical records of 172 consecutive patients, who underwent thyroidectomy for PTC treatment. We compared tumor size, as measured by preoperative US, with that in postoperative specimens. And we analyzed a number of factors potentially influencing the size measurement, including cancer size, calcification and coexisting thyroiditis. The mean size of the tumor measured by preoperative US was 11.4, and 10.2 mm by postoperative pathologic examination. The mean percentage difference (US-pathology/US) of tumor sizes measured by preoperative US and postoperative pathologic examination was 9.9 ± 19.3%, which was statistically significant (p < 0.001). When the effect of tumor size (≤10.0 vs. 10.1-20.0 vs. >20.0 mm) and the presence of calcification or coexisting thyroiditis on the tumor size discrepancy between the two measurements was analyzed, the mean percentage differences according to tumor size (9.1 vs. 11.2% vs. 9.8%, p = 0.842), calcification (9.2 vs. 10.2%, p = 0.756) and coexisting thyroiditis (17.6 vs. 9.5%, p = 0.223) did not show statistical significance. Tumor sizes measured in postoperative pathology were ~90% of those measured by preoperative US in PTC; this was not affected by tumor size, the presence of calcification or coexisting thyroiditis. When the surgical extent of PTC treatment according to tumor size measured by US is determined, the relative difference between tumor sizes measured by preoperative US and postoperative pathologic examination should be considered.

Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-11

Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Parathyroid Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVA Papillary Thyroid Cancer; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVB Basal Cell Carcinoma of the Lip; Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Follicular Thyroid Cancer; Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Lymphoepithelioma of the Oropharynx; Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVB Papillary Thyroid Cancer; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVC Basal Cell Carcinoma of the Lip; Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Follicular Thyroid Cancer; Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Lymphoepithelioma of the Oropharynx; Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVC Papillary Thyroid Cancer; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Thryoid Gland Nonmedullary Carcinoma; Thyroid Gland Medullary Carcinoma; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Ultrasonographic Features of Papillary Thyroid Carcinoma in Patients with Graves' Disease

PubMed Central

Chung, Jin Ook; Cho, Dong Hyeok; Chung, Dong Jin

2010-01-01

Background/Aims To characterize ultrasonographic findings in papillary thyroid carcinoma (PTC) combined with Graves' disease. Methods Medical records and ultrasonographic findings of 1,013 patients with Graves' disease and 3,380 patients without Graves' disease were analyzed retrospectively. A diagnosis of PTC was based on a pathologic examination. Results The frequency of hypoechogenicity was lower in patients with PTC and Graves' disease than in patients with PTC alone (p < 0.05). The frequency of perinodular blood flow in patients with PTC and Graves' disease was significantly higher than in those with PTC alone (p < 0.05). PTC combined with Graves' disease was characterized by more ill-defined borders and less frequency of overall calcification, punctate calcification, and heterogeneous echogenicity, although the difference was not statistically significant. Conclusions Our results suggest that patients with Graves' disease more frequently have atypical PTC findings on ultrasonography. PMID:20195406

Verteporfin inhibits papillary thyroid cancer cells proliferation and cell cycle through ERK1/2 signaling pathway

PubMed Central

Liao, Tian; Wei, Wen-Jun; Wen, Duo; Hu, Jia-Qian; Wang, Yu; Ma, Ben; Cao, Yi-Min; Xiang, Jun; Guan, Qing; Chen, Jia-Ying; Sun, Guo-Hua; Zhu, Yong-Xue; Li, Duan-Shu; Ji, Qing-Hai

2018-01-01

Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC. PMID:29721041

[Biological characteristics and management of familial papillary thyroid carcinoma].

PubMed

Zhao, Jing; Yu, Yang; Xia, Ting-ting; Liu, You-zhong; Wei, Song-feng; Zheng, Xiang-qian; Gao, Ming

2011-11-01

To analyze the clinical biological characteristics and investigate the managements of familial papillary thyroid carcinoma (FPTC). Clinical data of 36 patients with PTC from 15 families were retrospectively analyzed compared with 95 control cases taken randomly from the patients with sporadic PTC diagnosed and treated in Tianjin Cancer Hospital between January 2010 and August 2011. Of the 36 patients with FPTC, 15 (41.7%) were ≥45 years old, 12 (33.3%) had bilateral carcinoma, 20 (55.6%) were multifocality, 27 (75.0%) had neck lymph node metastases, 17 (47.2%) coexisted thyroid benign tumors. Of the 95 patients with SPTC, 60 (63.2%) were ≥45 years old, 12(12.6%)had bilateral carcinomas, 21 (22.1%) were multifocality, 51 (53.7%) had neck lymph node metastases, and 26(27.4%)coexisted thyroid benign tumors. Of the 36 patients with FPTC, 22 (61.1%) underwent total thyroidectomy and 14 (38.9%) with unilateral thyroidectomy plus isthmusectomy, 3 (8.3%) received unilateral or bilateral lateral neck dissection and central compartment neck dissection (CND), 7 (19.4%) received unilateral or bilateral posterolateral neck dissection and CND, 6 (16.6%) received posterolateral neck dissection and bilateral CND, and 20 (55.6%) received unilateral or bilateral CND. Age at disease presentation of FPTC was younger than that of SPTC. FPTC has higher rates of multifocality and bilateral carcinoma coexisting with thyroid benign tumor than those of SPTC. It necessary to take family history in detail and to evaluate diseases before operation.

Neck circumference correlates with tumor size and lateral lymph node metastasis in men with small papillary thyroid carcinoma.

PubMed

Kim, Mi Ra; Kim, Sang Soo; Huh, Jung Eun; Lee, Byung Joo; Lee, Jin Choon; Jeon, Yun Kyung; Kim, Bo Hyun; Kim, Seong Jang; Wang, Soo Geun; Kim, Yong Ki; Kim, In Joo

2013-01-01

Obesity is correlated with numerous diseases, including thyroid cancer, but the clinical significance of obesity with regard to the clinical characteristics of thyroid cancer remains unclear. Neck circumference is an index of upper-body adipose tissue distribution. In total, 401 patients with papillary thyroid carcinoma (PTC) measuring ≤ 2 cm were included. Neck circumference was measured horizontally at the level just below the thyroid cartilage on preoperative neck computed tomographic images. Neck circumference correlated significantly with tumor size in men (p = 0.001) but not in women (p = 0.930). Body mass index (BMI) did not significantly correlate with tumor size in either sex. Neck circumference was significantly larger in men with lateral lymph node (LN) metastasis than in those without (p = 0.004). Neck circumference and BMI did not differ significantly in women according to other factors such as tumor size, multifocality, extrathyroid extension, and LN metastasis. Tumor size and the prevalence of lateral LN metastasis in men tended to increase in the middle/large neck circumference subgroup compared with those in the low neck circumference subgroup. Multivariate logistic regression analysis revealed that neck circumference (p = 0.009) was a predictor for the presence of lateral LN metastasis in men. BMI was not a predictive factor for lateral LN involvement in either sex. Neck circumference, an indicator of central or visceral obesity but not BMI, may be associated with some prognostic factors in men with small PTC.

The clinicopathologic differences in papillary thyroid carcinoma with or without co-existing chronic lymphocytic thyroiditis.

PubMed

Yoon, Yeo-Hoon; Kim, Hak Joon; Lee, Jin Woo; Kim, Jin Man; Koo, Bon Seok

2012-03-01

The goal of this study is to determine the clinicopathologic differences in patients with papillary thyroid carcinoma (PTC) with or without chronic lymphocytic thyroiditis (CLT). We reviewed the medical records of 195 consecutive PTC patients who underwent total thyroidectomy and bilateral central lymph node dissection from April 2008 to March 2010. The differences in clinicopathologic factors, such as age, gender, size of primary tumor, perithyroidal invasion, lymphovascular invasion, capsular invasion, and central lymph node (CLN) metastasis, were analyzed in PTC patients with or without CLT. Among 195 patients, 56 (28.7%) had co-existing CLT. Patients with CLT had the following characteristics as compared to patients without CLT: significantly younger, female predominance, smaller tumor size, and lower incidence of capsular invasion (p = 0.038, 0.006, 0.037, and 0.026, respectively). Also, patients with CLT (12.5%) had a significantly lower incidence of CLN metastases than patients without CLT (28.1%; p = 0.025) based on univariate analysis. Moreover, multivariate analysis showed that younger age (p = 0.042, odds ratio = 1.033) and female gender (p = 0.012, odds ratio = 6.865) are independent clinical factors in patients with CLT compared to patients without CLT. CLT was shown to be commonly associated with PTC. Compared to patients with PTC without CLT, patients with CLT were younger with a female predominance, which are the most important and well-known prognostic variables for thyroid cancer mortality.

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.

PubMed

Kim, Seo Ki; Woo, Jung-Woo; Lee, Jun Ho; Park, Inhye; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

2016-01-01

It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status. © 2016 Society for Endocrinology.

Multifocal fibrosing thyroiditis: report of 55 cases of a poorly recognized entity.

PubMed

Fellegara, Giovanni; Rosai, Juan

2015-03-01

During the course of our consultation activity, we have recognized a peculiar form of thyroiditis in which multiple foci of fibrosis, most of which were associated with reactive atypia of the surrounding follicles, are present. We have referred to this condition, both in our consultation reports and in the third series of A.F.I.P. Fascicle on Tumors of the Thyroid Gland, as "multifocal fibrosing thyroiditis" or (less frequently) "multifocal sclerosing thyroiditis," which are descriptive terms that highlight the benign/inflammatory nature of the process, its multiplicity, and its unknown pathogenesis. The aim of this study is to better define the morphologic features of this process and correlate it with some clinical data. With this purpose, the consultation files of one of the authors (J.R.) were searched for cases coded as multifocal fibrosing thyroiditis or multifocal sclerosing thyroiditis in a 20-year period ranging from January 1989 to December 2009. A total of 55 cases were identified that displayed the above-listed features. There were 51 (93%) female and 4 (7%) male patients (F/M=12.75), with ages ranging between 15 and 71 years (mean age, 47.03 y; median age, 44.5 y). Microscopically, multiple foci of fibrosis were identified in all cases, their number ranging from 2 to 51 per case (mean number, 16), with a mean diameter of 3 mm (range: 0.36 to 15.1 mm). Although heterogenous in shape and size, the individual foci were rather similar to each other in composition, being characterized by a fibrotic poorly cellular center that merged with a cellular peripheral zone. Some of the follicular structures present at the periphery of the scar and-to a lesser extent-those entrapped inside it underwent complex reactive and regenerative (atypical) changes that simulated malignancy. We discuss the differential diagnosis with other benign and malignant thyroid conditions and speculate about its pathogenesis and possible relationship with papillary thyroid microcarcinoma.

Association between rs12045440 Polymorphism in the CAPZB Intron and Serum TSH Concentrations in Chinese Thyroid Tumor Patients

PubMed Central

Feng, Shouhao; Lin, Shengli; Zou, Jidong; Wang, Yulong; Ji, Qinghai; Lv, Zhenghua

2015-01-01

The aim of this study was to investigate the possible influence of different genotypes of the lead single nucleotide polymorphisms (SNPs) rs10917468 and rs12045440 in the CAPZB gene on the thyroid function in papillary thyroid carcinoma (PTC) and benign thyroid neoplasm (BN) patients. In the study, a significant association was detected between rs12045440 and serum TSH concentrations in thyroid tumor patients (p = 0.001). After the adjustment of relevant covariates, the difference between the mean serum TSH levels in different genotypes of rs12045440 was still significant in the BN group (p = 0.003) but was not significant in the PTC cases (p = 0.115). No significant association of rs10917468 with TSH levels was found. The SNP rs12045440 was associated with the serum TSH concentrations in Chinese thyroid tumor patients, especially in benign thyroid tumor cases. PMID:26273293

Occult thyroid carcinoma in our experience -- should we reconsider total thyroidectomy for benign thyroid pathology?

PubMed

Alecu, L; Bărbulescu, M; Ursuţ, B; Enciu, O; Slavu, I; Braga, V

2014-01-01

The reported incidence rate of occult thyroid carcinoma in patients operated for benign thyroid pathology has been much higher than expected in the last years,especially for multinodular goitre, which raises the question about which should the proper surgical management for these cases be. To assess the incidence rate of OTC in a single medium volume surgical center and to establish the correct indication for initial surgical management, as well as to identify the benign thyroid pathology most frequently associated with OTC. We also reviewed the relevant scientific literature on this topic. We conducted a retrospective study in the General Surgery Clinic of "Prof. dr. Agrippa Ionescu" Clinical Emergency Hospital, Bucharest, on a series of 145 patients who underwent surgical interventions for preoperatively diagnosed benign thyroid pathology over a ten year period, between 1st January 2002 - 31st December 2012. All cases of known thyroid cancer were excluded. Incidence rate of occult thyroid carcinoma in our series was 6.9 % (10 out of 145 patients), 80 % of them being diagnosed with multinodular goitre and two cases (20 %) with Hashimoto's lymphocytic thyroiditis. 6.8 % of all patients with multinodular goitre were found to present occult carcinoma,but this association was without statistical significance(p 0.05). Incidence rate of occult cancer among patients with Hashimoto thyroiditis was proved to be as high as 28.6%,statistically significant (p=0.020). The mean size of postoperatively diagnosed occult microcarcinoma was 7 mm, ranging between 3 mm and 14 mm, 90% of them being smaller than 1cm. Histologically, papillary microcarcinoma was found in all cases. The mean age of the patients diagnosed with occult microcarcinoma was 47.8 years with majority of the female gender. The most frequent operation performed was total thyroidectomy (70.8%). Overall morbidity in our series was 6.9% with a 0.7 % mortality rate (1 case). In our opinion, primary total thyroidectomy should be performed as the procedure of choice for the most part of preoperatively diagnosed benign thyroid pathology and particularly for multinodular goitre and Hashimoto thyroiditis,in order to radically resect all possible foci of aggressive thyroid microcarcinomas.Abbreviations and Acronyms: OTC (Occult Thyroid Carcinoma), PTMC (Papillary Thyroid Microcarcinoma); TT(Total Thyroidectomy), MNG (Multinodular Goitre), GD(Graves' disease), TNG (Toxic Nodular Goitre), FNAB(fine-needle aspiration biopsy). Celsius.

Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classical papillary thyroid carcinoma?

PubMed

Song, Eyun; Jeon, Min Ji; Oh, Hye-Seon; Han, Minkyu; Lee, Yu-Mi; Kim, Tae Yong; Chung, Ki-Wook; Kim, Won Bae; Shong, Young-Kee; Song, Dong Eun; Kim, Won Gu

2018-06-06

Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes. Retrospective cohort study. This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV), and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis, and extrathyroidal extension. The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR=2.16, 95% CI 1.12-4.16, p=0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n=121) and matched cPTC. However, CCV group (n=18) had significantly poorer DFS than matched cPTC group (HR=12.19, 95% CI 2.11-70.33, p=0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (p=0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR, 4.28; 95% CI, 1.66-11.00, p=0.001). When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis.

PubMed

Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

2016-01-01

Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as "MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node." Total thyroidectomy specimen showed "MTC with coexisting HT." At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists.

c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules

PubMed Central

2012-01-01

Background A large amount of information has been collected on the molecular tumorigenesis of thyroid cancer. A low expression of c-KIT gene has been reported during the transformation of normal thyroid epithelium to papillary carcinoma suggesting a possible role of the gene in the differentiation of thyroid tissue rather than in the proliferation. The initial presentation of thyroid carcinoma is through a nodule and the best way nowadays to evaluate it is by fine-needle aspiration (FNA). However many thyroid FNAs are not definitively benign or malignant, yielding an indeterminate or suspicious diagnosis which ranges from 10 to 25% of FNAs. BRAF mutational analysis is commonly used to assess the malignancy of thyroid nodules but unfortunately it still leaves indeterminate diagnoses. The development of molecular initial diagnostic tests for evaluating a thyroid nodule is needed in order to define optimal surgical approach for patients with uncertain diagnosis pre- and intra-operatively. Methods In this study we extracted RNA from 82 FNA smears, 46 malignant and 36 benign at the histology, in order to evaluate by quantitative Real Time PCR the expression levels of c-KIT gene. Results We have found a highly preferential decrease rather than increase in transcript of c-KIT in malignant thyroid lesions compared to the benign ones. To explore the diagnostic utility of c-KIT expression in thyroid nodules, its expression values were divided in four arbitrarily defined classes, with class I characterized by the complete silencing of the gene. Class I and IV represented the two most informative groups, with 100% of the samples found malignant or benign respectively. The molecular analysis was proven by ROC (receiver operating characteristic) analysis to be highly specific and sensitive improving the cytological diagnostic accuracy of 15%. Conclusion We propose the use of BRAF test (after uncertain cytological diagnosis) to assess the malignancy of thyroid nodules at first, then the use of the c-KIT expression to ultimately assess the diagnosis of the nodules that otherwise would remain suspicious. The c-KIT expression-based classification is highly accurate and may provide a tool to overcome the difficulties in today's preoperative diagnosis of thyroid suspicious malignancies. PMID:22233760

Comprehensive Survey Results of Childhood Thyroid Ultrasound Examinations in Fukushima in the First Four Years After the Fukushima Daiichi Nuclear Power Plant Accident.

PubMed

Suzuki, Shinichi; Suzuki, Satoru; Fukushima, Toshihiko; Midorikawa, Sanae; Shimura, Hiroki; Matsuzuka, Takashi; Ishikawa, Tetsuo; Takahashi, Hideto; Ohtsuru, Akira; Sakai, Akira; Hosoya, Mitsuaki; Yasumura, Seiji; Nollet, Kenneth E; Ohira, Tetsuya; Ohto, Hitoshi; Abe, Masafumi; Kamiya, Kenji; Yamashita, Shunichi

2016-06-01

Thyroid nodules and cancers are rare in children compared with adults. However, after the 1986 Chernobyl Nuclear Power Plant accident, a rapid increase in childhood thyroid cancer was observed. To avoid any confusion and misunderstanding of data obtained in Fukushima after the 2011 nuclear accident, baseline prevalence of thyroid nodules and cancers should be carefully assessed with standardized criteria systematically, and comprehensively applied to the population perceived to be at risk. Under the official framework of the Fukushima Health Management Survey, the thyroids of children in Fukushima were examined using ultrasound, and the results collected in the first four years after the nuclear accident were analyzed in order to establish a baseline prevalence of childhood thyroid abnormalities, especially cancer. Of 367,685 people aged 18 years or younger as of April 1, 2011, who were living in Fukushima Prefecture at the time of the accident, 300,476 underwent thyroid ultrasound screening. Of those, 2108 subjects with thyroid nodules were further examined using an advanced ultrasound instrument, with standardized criteria applied to determine the need for fine-needle aspiration cytology (FNAC). FNAC results determined the need for surgery and histological confirmation of the cytological diagnosis. Of the 2108 rescreened subjects, 543 underwent FNAC, of whom 113 were diagnosed with malignancy or suspected malignancy. Subsequently, 99 patients underwent surgical resection, revealing 95 cases of papillary thyroid cancer, three poorly differentiated cancers, and one benign nodule. The overall prevalence of childhood thyroid cancer in Fukushima was determined to be 37.3 per 100,000 with no significant differences between evacuated and non-evacuated areas. Thyroid cancer patients had external exposure estimates of <2.2 mSv during the first four months. The high prevalence of childhood thyroid cancer detected in this four-year study in Fukushima can be attributed to mass screening. It clearly exceeds what is found incidentally anywhere else. Direct comparisons with any other results, even those from cancer registries, are not meaningful because of differences in methodology.

The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression.

PubMed

Heiden, Katherine B; Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Wang, Yimin; Liu, Dingxie; Xing, Mingzhao; Prinz, Richard A; Xu, Xiulong

2014-11-01

Cancer stem cells (CSCs) have been recently identified in thyroid neoplasm. Anaplastic thyroid cancer (ATC) contains a higher percentage of CSCs than well-differentiated thyroid cancer. The signaling pathways and the transcription factors that regulate thyroid CSC self-renewal remain poorly understood. The objective of this study is to use two ATC cell lines (KAT-18 and SW1736) as a model to study the role of the sonic hedgehog (Shh) pathway in maintaining thyroid CSC self-renewal and to understand its underlying molecular mechanisms. The expression and activity of aldehyde dehydrogenase (ALDH), a marker for thyroid CSCs, was analyzed by Western blot and ALDEFLUOR assay, respectively. The effect of three Shh pathway inhibitors (cyclopamine, HhAntag, GANT61), Shh, Gli1, Snail knockdown, and Gli1 overexpression on thyroid CSC self-renewal was analyzed by ALDEFLUOR assay and thyrosphere formation. The sensitivity of transfected KAT-18 cells to radiation was evaluated by a colony survival assay. Western blot analysis revealed that ALDH protein levels in five thyroid cancer cell lines (WRO82, a follicular thyroid cancer cell line; BCPAP and TPC1, two papillary thyroid cancer cell lines; KAT-18 and SW1736, two ATC cell lines) correlated with the percentage of the ALDH(High) cells as well as Gli1 and Snail expression. The Shh pathway inhibitors, Shh and Gli1 knockdown, in KAT-18 cells decreased thyroid CSC self-renewal and increased radiation sensitivity. In contrast, Gli1 overexpression led to increased thyrosphere formation, an increased percentage of ALDH(High) cells, and increased radiation resistance in KAT-18 cells. Inhibition of the Shh pathway by three specific inhibitors led to decreased Snail expression and a decreased number of ALDH(High) cells in KAT-18 and SW1736. Snail gene knockdown decreased the number of ALDH(High) cells in KAT-18 and SW1736 cells. The Shh pathway promotes the CSC self-renewal in ATC cell lines by Gli1-induced Snail expression.

Chinese Data of Efficacy of Low- and High-Dose Iodine-131 for the Ablation of Thyroid Remnant.

PubMed

Ma, Chao; Feng, Fang; Wang, Shaoyan; Fu, Hongliang; Wu, Shuqi; Ye, Zhiyi; Chen, Suyun; Wang, Hui

2017-06-01

Chinese data on the efficacy of low- and high-dose radioiodine for thyroid remnant are still absent. The aim of the study was to investigate whether a low dose of radioiodine is as effective as a high dose for remnant ablation in Chinese patients. Patients presenting for radioiodine ablation in the authors' department were included. Inclusion criteria were aged ≥16 years, total or near-total thyroidectomy, tumor-node-metastasis (TNM) stage of pT1-3, any N stage, and M0. All patients were randomly allocated to either the high-dose group of 3700 MBq or the low-dose group of 1850 MBq for remnant ablation. The response to treatment was defined as successful or unsuccessful after a six- to nine-month interval. Ablation was considered to be successful if patients fulfilled the following criteria: no tracer uptake in the thyroid bed on diagnosis whole-body scanning and a negative level of serum thyroglobulin. There were 327 patients enrolled between January 2013 and December 2014. More than 95% had papillary thyroid cancer. Data could be analyzed for 278 cases (M age  = 44 years; 71.6% women), 155 in the low-dose group and 123 in the high-dose group. The rate of initial successful ablation was 84.2% in all patients, 82.6% in the low-dose group, and 86.2% in the high-dose group. There was no difference between the two groups (p = 0.509). In Chinese patients with differentiated thyroid carcinoma, the low dose of 1850 MBq radioiodine activity is as effective as a high dose of 3700 MBq for thyroid remnant ablation.

Thyroid cancer incidence by histological type and related variants in a mildly iodine-deficient area of Northern Italy, 1998 to 2009.

PubMed

Ceresini, Graziano; Corcione, Luigi; Michiara, Maria; Sgargi, Paolo; Teresi, Giulio; Gilli, Annalisa; Usberti, Elisa; Silini, Enrico; Ceda, Gian Paolo

2012-11-15

The incidence of thyroid cancer is increasing in several countries. However, the issue of whether this applies to all different histological types and related variants is poorly addressed. All incident thyroid cancers diagnosed between 1998 and 2009 in a mildly iodine-deficient area in northern Italy were derived from a population-based tumor registry. Stage of disease, size of the tumor, focality, and histological variants were recorded from a review of pathology reports and slides. The mean annual increase (MAI) of the standardized incidence rate was calculated over the entire 12-year period of observation and a standardized rate ratio was evaluated to compare the mean standardized incidence between 2 periods of 6 years each (1998-2003 vs 2004-2009). In total, 980 cases were considered. An increase in the incidence trend for all thyroid tumors was demonstrated; the increase was found to be continuous from 1998 to 2002 but not afterward. The cancer incidence increased in both male and female subjects. Papillary thyroid carcinoma (PTC), the follicular variant of PTC, the tall cell variant of PTC (TCV-PTC), and Hurthle cell carcinoma (HC) showed the most relevant changes in incidence whereas follicular carcinoma was not found to be significantly affected. TCV-PTC was the only histological type to demonstrated a significant (P < .01) proportional increase in the second 6-year period of observation. Only TCV-PTC and HC were found to display a significant MAI after 2002. The incidence of thyroid cancer has increased within the last decade, an increase that is accounted for mostly by differentiated tumors. The most significant increases were documented for aggressive variants of basic histotypes. Copyright © 2012 American Cancer Society.

The influence of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) resection diagnosis on the false-positive thyroid cytology rate relates to quality assurance thresholds and the application of NIFTP criteria.

PubMed

Ohori, N Paul; Wolfe, Jenna; Carty, Sally E; Yip, Linwah; LeBeau, Shane O; Berg, Aaron N; Schoedel, Karen E; Nikiforov, Yuri E; Seethala, Raja R

2017-09-01

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly defined entity and recent studies have suggested a decrease of a few percentage points in the rate of malignancy (ROM) for the positive-for-malignancy (PFM) cytology category as a result of NIFTP implementation. However, the distinction between a diagnosis of PFM and one of suspicious for malignancy (SFM) may depend on a variety of factors. In the current study, the authors investigated the ROM for the PFM and SFM diagnoses before and after histologic NIFTP reclassification. Cytology cases with PFM and SFM diagnoses and subsequent surgical resection specimens were searched in the files of the study institution from September 2008 to September 2016. The surgical pathology cases of noninvasive encapsulated follicular variant of papillary thyroid carcinoma were reexamined to determine whether they qualified for NIFTP. The distinct ROMs for the PFM and SFM cases were calculated accordingly. The authors' search identified 338 cases of PFM and 139 cases of SFM with a resection outcome. Before NIFTP reclassification, the PFM cases had a ROM of 99.4%; after NIFTP reclassification, the ROM was 99.1% (P = .6861). The ROM of the SFM cases decreased from 75.5% to 66.9% with NIFTP reclassification (P = .1402). One case in the PFM group and 6 cases in the SFM group could not be verified due to insufficient sampling. In the current large series, NIFTP reclassification did not appear to significantly alter the high ROM for the PFM diagnosis. The authors attribute this finding to a strict quality assurance policy, an emphasis on key cytologic criteria, and systematic application of the NIFTP criteria to follicular-patterned lesions. Cancer Cytopathol 2017;125:692-700. © 2017 American Cancer Society. © 2017 American Cancer Society.

Functional Toll-like Receptor 4 Overexpression in Papillary Thyroid Cancer by MAPK/ERK-Induced ETS1 Transcriptional Activity.

PubMed

Peyret, Victoria; Nazar, Magalí; Martín, Mariano; Quintar, Amado A; Fernandez, Elmer A; Geysels, Romina C; Fuziwara, Cesar S; Montesinos, María M; Maldonado, Cristina A; Santisteban, Pilar; Kimura, Edna T; Pellizas, Claudia G; Nicola, Juan P; Masini-Repiso, Ana M

2018-05-01

Emerging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAF V600E mutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. In agreement, conditional BRAF V600E expression in normal rat thyroid cells and mouse thyroid tissue upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonist lipopolysaccharide. Of note, The Cancer Genome Atlas data analysis revealed that BRAF V600E -positive tumors with high TLR4 expression were associated with shorter disease-free survival. Transcriptomic data analysis indicated a positive correlation between TLR4 expression levels and MAPK/ERK signaling activation. Consistently, chemical blockade of MAPK/ERK signaling abrogated BRAF V600E -induced TLR4 expression. A detailed study of the TLR4 promoter revealed a critical MAPK/ERK-sensitive Ets-binding site involved in BRAF V600E responsiveness. Subsequent investigation revealed that the Ets-binding factor ETS1 is critical for BRAF V600E -induced MAPK/ERK signaling-dependent TLR4 gene expression. Together, these data indicate that functional TLR4 overexpression in PTCs is a consequence of thyroid tumor-oncogenic driver dysregulation of MAPK/ERK/ETS1 signaling. Implications: Considering the participation of aberrant NF-κB signaling activation in the promotion of thyroid tumor growth and the association of high TLR4 expression with more aggressive tumors, this study suggests a prooncogenic potential of TLR4 downstream signaling in thyroid tumorigenesis. Mol Cancer Res; 16(5); 833-45. ©2018 AACR . ©2018 American Association for Cancer Research.

[Factors associated with advanced thyroid cancer in pediatric patients in a high specialty medical unit in Northeast Mexico].

PubMed

García-Castillo, Lizbeth Ariana; Bahena-García, Ana Laura; Sánchez-Sánchez, Luz María; del Carmen Palacios-Saucedo, Gerardo

2015-01-01

Thyroid cancer represents 2% of all childhood malignances. Its incidence rises 1.1% per year. In comparison with adults, childhood thyroid cancer is detected in a more advanced stage, but with a survival rate above 95%. The objective of this study was to evaluate whether there are factors associated with advanced stages of thyroid cancer in pediatric patients. Nineteen patients were included, 13 (68.4%) were female and six male, all between 7-15 years, with a median of 11 years. Fifteen in advanced and four in early stage. The median age of patients in advanced stage at time of diagnosis was 10.6 years (7-15) and 13.2 (12-14) were in early stage (p=0.075). There was a delay of nine months to get a diagnosis in advanced stage, and 7.2 in early stage (p=0.931). Three of the patients with advanced stage and two with early stage were from Nuevo León (Mexico) and the rest were foreign (p=0.567). In the group with advanced stage, two had thyroid cancer familiar history, and none in the early stage group (p=0.452). Nine patients in advanced stage and three in early stage presented thyroid nodule as the first sign of illness. Six patients in advanced stage and one in early stage presented goiter (p=0.590). None of the studied patients had radiation history. Six patients in advanced stage and one in early stage suffered from Hashimoto's Thyroiditis (p=0.590). Eleven in advanced stage and one in early stage had papillary histologic variety. Four in advanced stage and three in early stage had papillary histologic variety with a follicular patter (p=0.083). Eight patients presented lung metastasis at time of diagnosis (p=0.061). There are no factors associated with advanced stage thyroid cancer in pediatric populations. Although half of studied patients presented lung metastasis, treatment response and survival is satisfactory.

Comparison of 800 and 3700 MBq iodine-131 for the postoperative ablation of thyroid remnant in patients with low-risk differentiated thyroid cancer.

PubMed

Caglar, Meltem; Bozkurt, Fani M; Akca, Ceren Kapulu; Vargol, Sezen Elhan; Bayraktar, Miyase; Ugur, Omer; Karaağaoğlu, Ergun

2012-03-01

The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. A total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg < 0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ≤ 0.2% RAIU, and (iii) Tg < 2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg < 0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg < 2 ng/ml. When three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). Our findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.

Warthin-like variant of papillary thyroid carcinoma: single institution experience.

PubMed

Jun, Hak Hoon; Kim, Seok-Mo; Hong, Soon Won; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

2016-06-01

Correct diagnosis of the variants of papillary thyroid carcinoma (PTC) is important because these variants differ in clinical course. The Warthin-like variant (WLV) is relatively uncommon and is recognized as not different from conventional PTC. We therefore assessed the clinicopathological features of patients with WLV of PTC who were diagnosed and treated at our institution. Of the 8179 patients treated for PTC at the Thyroid Cancer Center, Gangnam Severance Hospital, Yonsei University College of Medicine, between January 2007 and December 2012, 16 patients (0.2%) were pathologically diagnosed with WLV of PTC. Their clinicopathological features and post-operative follow-up for local recurrence and distant metastasis were retrospectively investigated. Mean patient age was 44.9 years (range: 23-61 years), with seven (44%) being younger than 45 years. Only one of the 16 patients was male (6%). Mean tumour size was 8.9 mm (range: 3-22 mm). Extrathyroidal extension was observed in seven patients (44%), associated thyroiditis in 11 (69%) and lymph node metastasis in six (38%). The mean follow-up period was 37 months (range: 13-78 months), during which none of the 16 patients experienced recurrence or metastasis. Fifteen patients (94%) had MACIS score <6, with the remaining patient having a MACIS score of 6.33. WLV of PTC is rare, with favourable prognosis. Nevertheless, it is important to determine the histopathological features of these tumours. © 2014 Royal Australasian College of Surgeons.

Back so soon? – Is early recurrence of Papillary Thyroid Cancer really just persistent disease?

PubMed Central

Bates, Maria F; Lamas, Marcos R; Randle, Reese W; Long, Kristin L; Pitt, Susan C; Schneider, David F; Sippel, Rebecca S

2017-01-01

Background Papillary thyroid carcinoma (PTC) has excellent survival, yet recurrence remains a challenge. We sought to determine the proportion of re-operations performed for persistent, rather than truly recurrent disease. Methods We conducted a retrospective review of a prospectively maintained database. Patients with PTC that had re-operation for disease from 2000–2016 were included. We defined recurrence as disease that developed after a patient had an undetectable thyroglobulin and negative ultrasound within one year of surgery. Results A total of 69 patients underwent 92 re-operations. On initial pathology: mean tumor size was 2.6cm; 50.7% were multifocal; and 42% had extra-thyroidal extension. Half (46%) of the patients underwent a central/lateral neck dissection at initial surgery and 76.8% were treated with post-operative radioactive iodine. The median time to first re-operation was 21 months (range, 1–292), and 41.8% occurred within 1 year. Only three operations met criteria for true “recurrence”, while 71 operations were categorized as persistence. Conclusion Many re-operations for PTC are for management of persistent disease. Over half of the patients required re-operation within the first two years, which strongly suggests that improvements in the pre-operative assessment and adequacy of initial surgery need to be made to improve the care of patients with thyroid cancer. PMID:29128176

Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study.

PubMed

Igci, Yusuf Ziya; Erkilic, Suna; Arslan, Ahmet

2014-07-01

Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers. The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this disease is present due to the resemblance of nuclear properties of the classical type (CVPTC). However, making use of ancillary molecular markers in the diagnosis of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC (FVPTC(e), n=25), and CVPTC (n=15), and benign hyperfunctioning thyroid nodules (HypN, n=15) were used in this study. Nuclear, cytoplasmic, and overall (total) SEPT7 protein expression levels were determined by using immunohistochemistry. Nuclear, cytoplasmic, and overall SEPT7 expressions (p=0.02, p=0.001, p=0.002, respectively) were significantly lower in FVPTC(e) tissues when compared to HypN. In CVPTC group, nuclear expression was significantly lower (p=0.004) while overall and cytoplasmic expressions were not changed (p>0.05). In HypN group, highest nuclear (mean=2.73), cytoplasmic (mean=2.86), and overall (mean=2.86) expression scores were detected. Significantly lower SEPT7 expression in all expressional categories in FVPTC(e) group may be a sign of different molecular signature in this type of tissue. Copyright © 2014 Elsevier GmbH. All rights reserved.

Reactivity of thyroid papillary carcinoma cells to thyroid stimulating hormone-dominated endocrine therapy

PubMed Central

Ma, Yuqin; Zhang, Xia; Wang, Yutao

2017-01-01

This study investigated the effect of thyroid stimulating hormone (TSH) on the proliferation of papillary thyroid carcinoma (PTC) cells and the therapeutic effect of levothyroxine sodium (TH). PTC cells (TPC-1) were cultured using 0.1, 1.0 and 10 U/l TSH and 10−2, 10−4 and 10−6 mol/l TH. After the appropriate concentration was screened, TPC-1 cells were further divided into control group, TSH group, TH group and TSH+TH group. The cell proliferation was detected via methyl thiazolyl tetrazolium (MTT) method, TPC-1 cell cycle was detected via flow cytometer, and the mRNA and protein expression of cyclin D1 were detected via real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Compared with control group, TSH significantly promoted the proliferation of TPC-1 cells (P<0.05 or P<0.01), obviously promoted the transition of TPC-1 cells from G1 phase to S phase (P<0.01) and remarkably increased the mRNA and protein expression of cyclin D1 (P<0.01); but TH had a significant inhibitory effect on these results of TSH (P<0.05 or P<0.01). TSH can promote the proliferation of PTC cells, and the appropriate complement of TH can inhibit its proliferation. PMID:29250166

Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model

PubMed Central

Danysh, Brian P.; Rieger, Erin Y.; Sinha, Deepankar K.; Evers, Caitlin V.; Cote, Gilbert J.; Cabanillas, Maria E.; Hofmann, Marie-Claude

2016-01-01

The BRAF V600E mutation is commonly observed in papillary thyroid cancer (PTC) and predominantly activates the MAPK pathway. Presence of BRAF V600E predicts increasing risk of recurrence and higher mortality rate, and treatment options for such patients are limited. Vemurafenib, a BRAF V600E inhibitor, is initially effective, but cells inevitably develop alternative mechanisms of pathway activation. Mechanisms of primary resistance have been described in short-term cultures of PTC cells; however, mechanisms of acquired resistance have not. In the present study, we investigated possible adaptive mechanisms of BRAF V600E inhibitor resistance in KTC1 thyroid cancer cells following long-term vemurafenib exposure. We found that a subpopulation of KTC1 cells acquired resistance to vemurafenib following 5 months of treatment with the inhibitor. Resistance coincided with the spontaneous acquisition of a KRAS G12D activating mutation. Increases in activated AKT, ERK1/2, and EGFR were observed in these cells. In addition, the resistant cells were less sensitive to combinations of vemurafenib and MEK1 inhibitor or AKT inhibitor. These results support the KRAS G12D mutation as a genetic mechanism of spontaneously acquired secondary BRAF inhibitor resistance in BRAF V600E thyroid cancer cells. PMID:27127178

Interleukin-10-1082 gene polymorphism is associated with papillary thyroid cancer.

PubMed

Çil, Esra; Kumral, Alkın; Kanmaz-Özer, Müge; Vural, Pervin; Doğru-Abbasoğlu, Semra; Altuntaş, Yüksel; Uysal, Müjdat

2014-05-01

The etiopathogenesis of thyroid cancer has not been clearly elucidated although the role of chronical inflammation and the imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with papillary thyroid cancer (PTC), and to evaluate the relationship between genotypes and clinical/laboratory manifestation of PTC. Tumor necrosis factorα (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 A-1082G (rs 1800896) single nucleotide polymorphisms in DNA from peripheral blood leukocytes of 190 patients with thyroid cancer and 216 healthy controls were investigated by real-time PCR combined with melting curve analysis. There was no notable risk for PTC afflicted by TNFα-308 and IL-6-174 alone. However, IL-10-1082 G allele frequency were higher among PTC patients than healthy controls (p=0.009). The patients with IL-10-1082 GG geotype have twofold increased risk of developing thyroid cancer according to AA genotype (OR 2.07, 95% CI 1.21-3.55). In addition, the concomitant presence of IL-10-1082 G allele (GG+AG genotypes) together with IL-6 -174 GG genotype has a nearly twofold increased risk for thyroid cancer (OR 1.75 with 95% CI 1.00-3.05, p=0.049). We suggest that IL-10-1082 G allele is associated with an increased risk of PTC. The polymorphism of IL-10 gene can improve our knowledge about the pathogenesis of PTC, and could provide to estimate people at the increased risk for PTC.

Hybrid-type endoscopic thyroidectomy (HET: Tori's method) for differentiated thyroid carcinoma including invasion to the trachea.

PubMed

Tori, Masayuki

2014-03-01

Endoscopic thyroidectomy (ET) or robotic thyroidectomy is yet to be applied to thyroid carcinoma invasive to the trachea and to wide lymph node node metastasis. On the other hand, small-incision thyroidectomy lacks sufficient working space and clear vision. The author has newly developed hybrid-type endoscopic thyroidectomy (HET) to overcome these problems. From March 2011 to February 2012, HET was performed for 85 patients. Clinicopathologic characteristics were analyzed. To evaluate the superiority of HET for malignancy representatively, conventional lobectomy with central compartment node dissection (CCND) performed 1 year previously was compared with HET. In lobectomy and node dissection, a single skin incision (1.5 cm) is made above the clavicle, with a port incision (5 mm) made 3 cm below the clavicle. Then CCND is performed directly through the incision by lifting up the isthmus. To obtain sufficient working space for the lobectomy, the strap muscles are taped and pulled toward the head, then hung by the cradle. The thyroid lobe is retracted to the midline with a retractor, followed by isolation of the inferior laryngeal nerve and transection of the inferior thyroid vessels with the monitor of the scope. Lateral lymph nodes dissection can be performed at the same time, if necessary. In total thyroidectomy, the same procedure is performed at the opposite side. The scalpel can be used to shave through each incision in case of tracheal invasion. Of the 85 cases, 62 were malignant, involving papillary thyroid carcinoma (PTC), and 23 were benign. Total thyroidectomy was performed for 22 of the PTC cases and CCND for 49 of the cases. Shaving for tracheal invasion was performed for eight patients. No mortality, complications, recurrence, or metastasis was found 1-2 years after the operation. Compared with conventional thyroidectomy, HET was superior in blood loss, visual analog scale, and postoperative hospital stay. The author's method (Tori's method) might be less invasive, cosmetically excellent, and moreover, safe and feasible for differentiated thyroid carcinoma including invasion to the trachea.

Characteristics of differentiated thyroid carcinoma in children and adolescents with respect to age, gender, and histology.

PubMed

Farahati, J; Bucsky, P; Parlowsky, T; Mäder, U; Reiners, C

1997-12-01

Because of its rarity there have been only a few detailed studies on differentiated thyroid carcinoma (DTC) in children. The current investigation was undertaken to assess the characteristics of DTC with respect to age, gender, and histology in children and adolescents. In a questionnaire-based survey, data from 114 children and adolescents with DTC (age range, 3-18 years) was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated and the influence of age, gender, histology, multicentric growth, tumor stage, and lymph node involvement on distant metastases was tested using multivariate discriminant analysis. Comparison between groups was performed using the Student's t test and chi-square test. Correlation between incidence and age was assessed by linear regression analysis. The overall incidence of thyroid carcinoma in females was higher than in males, with a peak of female/male ratio occurring at puberty. The incidence of DTC correlated with age in females < 16 years (correlation coefficient [r] = 0.84; P = 0.0006), which was more pronounced in children with papillary thyroid carcinoma (PTC) (r = 0.83; P = 0.006) but not in those with follicular thyroid carcinoma (FTC) (r = 0.20; P = 0.16). FTC was associated with less advanced disease (P = 0.009), fewer lymph nodes involved (P = 0.007), and fewer metastases (P = 0.02) compared with PTC. Males tended to have a higher risk for distant metastases. However, statistical analysis failed to reach a level of significance (P = 0.08). Multivariate analysis revealed tumor stage as the only powerful factor (P = 0.02) correlated with distant metastasis. The incidence of PTC shows a marked increase in females with the highest female/male ratio occurring at puberty. Childhood thyroid carcinoma frequently is associated with lymph node involvement, distant metastases, and extrathyroidal tumor infiltration. In children FTC appears to be less aggressive than PTC. Advanced local-regional extension stage appears to be the most powerful factor influencing the risk for distant metastases in children.

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mincione, Gabriella, E-mail: g.mincione@unich.it; Center of Excellence on Aging, Ce.S.I., ‘G. d'Annunzio’ University Foundation, Chieti; Tarantelli, Chiara

2014-09-10

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC andmore » FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.« less

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

PubMed Central

Schrock, Alexa B.; Anderson, Peter M.; Morris, John C.; Heilmann, Andreas M.; Holmes, Oliver; Wang, Kai; Johnson, Adrienne; Waguespack, Steven G.; Ou, Sai‐Hong Ignatius; Khan, Saad; Fung, Kar‐Ming; Stephens, Philip J.; Erlich, Rachel L.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.

2017-01-01

Background. Thyroid carcinoma, which is rare in pediatric patients (age 0–18 years) but more common in adolescent and young adult (AYA) patients (age 15–39 years), carries the potential for morbidity and mortality. Methods. Hybrid‐capture‐based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety‐three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. Implications for Practice. The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young patients with papillary, anaplastic, or medullary thyroid carcinoma, particularly for advanced or refractory cases for which clinical trials involving molecularly targeted therapies may be appropriate. PMID:28209747

BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

PubMed Central

Cabanillas, M.E.; Patel, A.; Danysh, B. P.; Dadu, R.; Kopetz, S.; Falchook, G.

2014-01-01

The U.S. Food and Drug Administration–approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine–refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30–40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use. PMID:25467940

Clinicopathologic risk factors for right paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma.

PubMed

Yu, Q A; Ma, D K; Liu, K P; Wang, P; Xie, C M; Wu, Y H; Dai, W J; Jiang, H C

2018-03-17

To investigate risk factors associated with right paraesophageal lymph node (RPELN) metastasis in patients with papillary thyroid carcinoma (PTC) and to determine the indications for right lymph node dissection. Clinicopathologic data from 829 patients (104 men and 725 women) with PTC, operated on by the same thyroid surgery team at the First Affiliated Hospital of Harbin Medical University from January 2013 to May 2017, were analyzed. Overall, 309 patients underwent total thyroidectomy with bilateral lymph node dissection, 488 underwent right thyroid lobe and isthmic resection with right central compartment lymph node dissection, and 32 underwent near-total thyroidectomy (ipsilateral thyroid lobectomy with contralateral near-total lobectomy) with bilateral lymph node dissection. The overall rate of central compartment lymph node metastasis was 43.5% (361/829), with right central compartment lymph node and RPELN metastasis rates of 35.5% (294/829) and 19.1% (158/829), respectively. Tumor size, number, invasion, and location, lymph node metastasis, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis were associated with RPELN in the univariate analysis, whereas age and sex were not. Multivariate analysis identified tumors with a diameter ≥ 1 cm, multiple tumors, tumors located in the right lobe, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis as independent risk factors for RPELN metastasis. Lymph node dissection, including RPELN dissection, should be performed for patients with PTC with a tumor diameter ≥ 1 cm, multiple tumors, right-lobe tumors, right central compartment lymph node metastasis, or suspected lateral compartment lymph node metastasis.

Identification of occult tumors by whole-specimen mapping in solitary papillary thyroid carcinoma.

PubMed

Park, Seog Yun; Jung, Yuh-S; Ryu, Chang Hwan; Lee, Chang Yoon; Lee, You Jin; Lee, Eun Kyung; Kim, Seok-Ki; Kim, Tae Sung; Kim, Tae Hyun; Jang, Jeyun; Park, Daeyoon; Dong, Seung Myung; Kang, Jae-Goo; Lee, Jin Soo; Ryu, Junsun

2015-08-01

We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study are 82 consecutive patients who underwent a total thyroidectomy under a preoperative diagnosis of solitary PTC. All thyroidectomy specimens were serially sectioned in 2 mm thickness and whole-thyroid mapping was carried out for additional foci of occult PTC. The frequencies of occult lesions detected in the whole and contralateral lobe were determined, and clinicopathologic factors associated with multifocality were assessed. Whole-thyroid mapping revealed 66 occult PTC lesions missed by preoperative ultrasound in 37 (45.1%) of the 82 patients. The great majority (92.5%) of the occult PTC was smaller than 3 mm in size and 25 patients (30.5%) had contralateral lesions. We found that the male sex was an independent predictor of multifocality (odds ratio (OR), 3.00; 95% CI, 1.11-8.14), adjusting for preoperative findings. Analysis with pathologic parameters showed that the male sex (OR, 5.03; 95% CI, 1.68-15.08) and extrathyroidal extensions (OR, 3.03; 95% CI, 1.03-8.95) were associated with multifocal PTC. However, none of the clinicopathologic factors evaluated predicted contralateral PTC. Our study demonstrates the diagnostic limitations of ultrasound for the detection of multifocal PTC and the need to consider the possibility of occult lesions in the management of solitary PTC, especially in male patients. © 2015 Society for Endocrinology.

Papillary thyroid cancer: time course of recurrences during postsurgery surveillance.

PubMed

Durante, Cosimo; Montesano, Teresa; Torlontano, Massimo; Attard, Marco; Monzani, Fabio; Tumino, Salvatore; Costante, Giuseppe; Meringolo, Domenico; Bruno, Rocco; Trulli, Fabiana; Massa, Michela; Maniglia, Adele; D'Apollo, Rosaria; Giacomelli, Laura; Ronga, Giuseppe; Filetti, Sebastiano

2013-02-01

The current use of life-long follow-up in patients with papillary thyroid cancer (PTC) is based largely on the study of individuals diagnosed and treated in the latter half of the 20th century when recurrence rates were approximately 20% and relapses detected up to 20-30 years after surgery. Since then, however, diagnosis, treatment, and postoperative monitoring of PTC patients have evolved significantly. The objective of the study was to identify times to PTC recurrence and rates by which these relapses occurred in a more recent patient cohort. We retrospectively analyzed follow-up data for 1020 PTC patients consecutively diagnosed in 1990-2008 in 8 Italian hospital centers for thyroid disease. Patients underwent thyroidectomy, with or without radioiodine ablation of residual thyroid tissue and were followed up with periodic serum thyroglobulin assays and neck sonography. At the initial posttreatment (≤ 12 months) examination, 948 patients had no structural/functional evidence of disease. During follow-up (5.1-20.4 years; median 10.4 years), recurrence (cervical lymph nodes, thyroid bed) was diagnosed in 13 (1.4%) of these patients. All relapses occurred 8 or fewer years after treatment (10 within the first 5 years, 6 within the first 3 years). Recurrence was unrelated to the use/omission of postoperative radioiodine ablation. In PTC patients whose initial treatment produces disease remission (no structural evidence of disease), recurrent disease is rare, and it usually occurs during the early postoperative period. The picture of recurrence timing during the follow-up provides a foundation for the design of more cost-effective surveillance protocols for PTC patients.

Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience.

PubMed

Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo

2016-06-28

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into "simple" or "complex" growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia).

Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience

PubMed Central

Park, Cheol Keun; Yoon, Gun; Cho, Yoon Ah; Kim, Hyun-Soo

2016-01-01

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into “simple” or “complex” growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia). PMID:27322430

Contribution of immunocytochemical stainings for galectin-3, CD44, and HBME1 to fine-needle aspiration cytology diagnosis of papillary thyroid carcinoma.

PubMed

Das, Dilip K; Al-Waheeb, Salah K M; George, Sara S; Haji, Bahiyah I; Mallik, Mrinmay K

2014-06-01

In cytology practice some papillary thyroid carcinoma (PTC) cases have indeterminate diagnoses and overlapping cytological features with benign lesions. This study was undertaken to find out if immunocytochemistry using Galectin-3, CD-44 and HBME-1 could be of help in such situations. Forty-six cases consisting of 22 malignancy (PTC) cases, 7 suspicious of (S/O) PTC, 1 follicular neoplasm, 5 follicular lesion of undetermined significance (FLUS), and 11 benign (colloid goiter) cases diagnosed by FNA were included in this study. Staining reactions were graded in a sliding scale of -, 1+, 2+, 3+, and 4+. In an assessment of 100 cells, each cell with weak, and moderate to strong positive reaction were assigned a score of 1 and 4, respectively. Staining reaction of ≥+2 and scores >100 were considered positive. Frequency of cases with ≥+2 reaction, and scores >100 for each of Galectin-3, CD-44, and HBME-1 were significantly higher in PTC or combined PTC and S/O PTC cases as compared with FLUS and benign cases taken together (P = 0.01744 to 0.00000). When the cases were compared according to histological malignant and benign diagnoses, the difference was also significant in respect of ≥+2 reaction, and scores >100 for Galectin-3 and CD44 (P = 0.04923 to 0.00947); however, there was no significant difference, when these parameters for HBME1 were compared. Galectin 3, CD 44, and to some extent HBME 1 are useful immunocytochemical parameters with potential to support FNAC diagnosis of PTC, especially in situations with difficult differential diagnoses. Copyright © 2013 Wiley Periodicals, Inc.

The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

2010-08-01

Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

A prospective comparison of patient body image after robotic thyroidectomy and conventional open thyroidectomy in patients with papillary thyroid carcinoma.

PubMed

Lee, Sohee; Kim, Ha Yan; Lee, Cho Rok; Park, Seulkee; Son, Haiyoung; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2014-07-01

Body image is associated with self-esteem and identity and has a close relationship with quality of life (QoL). We compared the impact of surgical scars on the patient's perception of body image between conventional open thyroidectomy (OT) and robotic thyroidectomy (RT) in female papillary thyroid carcinoma patients. From October 2009 to December 2010, we enrolled prospectively 116 papillary thyroid carcinoma patients who underwent total thyroidectomy at the Yonsei University Health System (Seoul, Korea). Of these 116 patients, 56 had OT and 60 RT. Their scars were assessed using the Vancouver Scar Scale (VSS), and psychometric properties were evaluated using the Body Image Scale (BIS) questionnaire postoperatively. Both groups were compared using cross-sectional and time-series methods. Mean age was significantly younger in the RT group. Regarding scar quality, the OT group showed superiority in scar pigmentation and the total VSS score during the early postoperative period, but the VSS score improved over time and was similar between both groups at 9 months. The RT group had better scores regarding most of the BIS items, a trend that remained relatively constant over time. In patients with noticeable scars (VSS ≥ 2) at 9 months, the RT group had better BIS scores regarding almost all items, including "self-conscious," "physical attractiveness," "feeling of less feminine," "sexual attractiveness," "dissatisfaction with body, scar and appearance when dressed," and "avoidance of people due to appearance." RT provides a better self-body image and improves QoL compared with conventional OT by avoiding a noticeable cervical scar. Copyright © 2014 Mosby, Inc. All rights reserved.

Changing clinical characteristics of thyroid carcinoma at a single center from Turkey: before and after the Chernobyl disaster.

PubMed

Ozdemir, D; Dagdelen, S; Kiratli, P; Tuncel, M; Erbas, B; Erbas, T

2012-09-01

The aim of the study was to determine the possible role of Chernobyl disaster on changing clinical features of thyroid carcinoma (TC) in a moderately iodine deficient region. We retrospectively reviewed demographical features, presenting symptoms, tumor size, histopathological diagnosis and distant metastates in 160 patients with TC diagnosed between 1990-2007. We compared our findings with the database of 118 TC patients diagnosed between 1970-1990 in the same center. There were 123 female (76.9%) and 37 (23.1%) male patients with a mean age of 44.89±14.84. Sex distribution and age at diagnosis were similar between 1970-1990 and 1990-2007 (P=0.77 and P=0.42, respectively). Histopathological diagnoses were papillary in 114 (73.1%), follicular in 22 (14.1%), medullary in 9 (5.8%), hurthle cell in 7 (4.5%) and anaplastic TC in 4 (2.6%) patients. We observed a marked increase in papillary TC (P<0.001) and marked decreases in follicular (P<0.001) and anaplastic TC (P=0.01) compared to the period between 1970-1990. Thyroid microcarcinomas accounted for 27.1% and 37.1% of carcinomas in 1970-1990 and 1990-2007, respectively (P<0.05). We showed that incidence of papillary TC increased and incidences of follicular and anaplastic TC decreased in a period that might be affected by Chernobyl fallout in a moderately iodine deficient area. Presenting symptoms of TC have changed and microcarcinomas are diagnosed more frequently compared to past. Further large scale trials are needed to find out whether Chernobyl disaster has role on changing characteristic of TC in countries that are not very near but also not very far from Chernobyl such as Turkey.

Molecular Profiling of Papillary Thyroid Carcinoma in Korea with a High Prevalence of BRAFV600E Mutation.

PubMed

Lee, Seung Eun; Hwang, Tae Sook; Choi, Yoon-La; Kim, Wook Youn; Han, Hye Seung; Lim, So Dug; Kim, Wan-Seop; Yoo, Young Bum; Kim, Suk Kyeong

2017-06-01

The BRAF V600E mutation in papillary thyroid carcinoma (PTC) is particularly prevalent in Korea, and a considerable number of wild-type BRAF PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC has prompted endocrine pathologists to reclassify this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). This study analyzed the genetic alterations among the histologic variants of PTC, including NIFTP. Mutations of the BRAF and RAS genes and rearrangement of the RET/PTC1, NTRK1, and ALK genes using 769 preoperative fine-needle aspiration specimens and resected PTCs were analyzed. Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAF V600E mutation (80.8%) was the most frequent alteration, followed by RAS mutation and RET/PTC1, NTRK1, and ALK rearrangements (5.6%, 2.1%, 0.4%, and 0%, respectively). The low prevalence of NTRK1 fusions and the absence of an ALK fusion detected in Korea may also be attributed to the higher prevalence of the BRAF V600E mutation. There were significant differences in the frequency of the genetic alterations among the histologic variants of PTC. The prevalence of NIFTP in PTC was 2.7%, and among the NIFTPs, 28.6% and 57.1% harbored BRAF and RAS mutations, respectively. Clinicopathologic factors and mutational profiles between NIFTP and encapsulated follicular variant PTC with capsular invasion group were not significantly different. Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group.

Thyroid malignancy among goitrous thyroid lesions: a review of hospital-based studies in Malaysia and Myanmar.

PubMed

Htwe, T T

2012-03-01

Endemic goitre is a major concern in many parts of the world, including Southeast Asia. Goitrous thyroid lesion is postulated as a precursor lesion to thyroid cancer (TC). This paper reviews the prevalence rates and characteristics of TC among cases of goitrous thyroid-swelling in different parts of Malaysia and Myanmar. Recorded data from hospital-based retrospective studies of thyroid cases, whose study periods ranged from three to 11 years, were analysed. These included research findings from the author's publications as well as other published review articles of retrospective analyses. The incidence of TC varies among gender, age, race/ethnicity and histological type. There appears to be a higher rate of occurrence among females aged 21-60 years. Papillary thyroid carcinoma is the more common histological type compared to follicular cancer. This review also presents a descriptive analysis and discussion on studies conducted in other countries. Further exploration is warranted in order to uncover the possible risk factors for the rising incidence of TC.

[Application of central lymph node dissection to surgical operation for clinical stage n0 papillary thyroid carcinoma].

PubMed

Hu, Wei; Shi, Jun-Yi; Sheng, Yuan; Ll, Li

2008-03-01

The treatment for papillary thyroid carcinoma (PTC) without cervical lymph node metastasis (cN0) is controversial. This study was to explore a suitable method to dissect cervical lymph nodes for stage cN0 PTC patients. Eighty-four stage cN0 PTC patients, diagnosed by B ultrasound or cervical MRI from 2005--2006, were randomly divided into two groups. Thyroidectomy and ipsilateral central lymph node dissection were performed in Group A, while only thyroidectomy was performed in Group B. Each group contained 42 patients. Both groups took thyroxin tablets after operation. An average of 3 lymph nodes were found in each case of Group A, and the lymph node metastasis rate was 47.62%. The occurrence rates of complications were not significantly different between the two groups (P<0.05). Thyroidectomy plus ipsilateral central lymph node dissection is recommended for the treatment of stage cN0 PTC. It can also avoid damage of recurrent laryngeal nerve in re-dissection.

Long-term survival in a patient with brain metastases of papillary thyroid carcinoma

PubMed Central

Guelho, Daniela; Ribeiro, Cristina; Melo, Miguel; Carrilho, Francisco

2016-01-01

We present the case of a 43-year-old woman who underwent total thyroidectomy with bilateral lymphadenectomy for a papillary thyroid carcinoma (PTC), solid variant (T4bN1bMx), with V600E BRAF mutation. After ablative therapy, she presented undetectable thyroglobulin (Tg) but progressively increasing anti-Tg antibodies (TgAbs). During follow-up, nodal, lung and brain metastases were identified. She was submitted to surgical excision of lung lesions, radiosurgery of brain metastases and five radioiodine treatments. The latest brain MRI showed no lesions, pulmonary CT showed stable micronodules and there was progressive reduction in TgAbs. This is a peculiar case of a PTC with lung and brain metastatic lesions detected through TgAbs. Initial histological and molecular study suggested a more aggressive clinical behaviour, which was eventually confirmed. Although PTC brain metastases are extremely rare and present poor prognosis, our patient presented a good response to treatment and longer survival than usually reported for similar cases. PMID:26961557

Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated p21 expression in papillary thyroid carcinoma.

PubMed

Gou, Qiheng; Gao, Linbo; Nie, Xinwen; Pu, Wenchen; Zhu, Jingqiang; Wang, Yichao; Liu, Xuesha; Tan, Shuangyan; Zhou, Jian-Kang; Gong, Yanqiu; He, Juan; Wu, Ke; Xie, Yuxin; Zhao, Wanjun; Dai, Lunzhi; Liu, Lunxu; Xiang, Rong; Wei, Yu-Quan; Zhang, Lin; Peng, Yong

2018-05-07

Long noncoding RNAs (lncRNAs) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. Copyright ©2018, American Association for Cancer Research.

Ciliated muconodular papillary tumour of the lung: a newly defined low-grade malignant tumour.

PubMed

Sato, Shuichi; Koike, Teruaki; Homma, Keiichi; Yokoyama, Akira

2010-11-01

We present two cases of ciliated muconodular papillary tumour (CMPT) in this report. CMPT is a newly defined low-grade malignant tumour with ciliated columnar epithelial cells, occurring in the peripheral lung. Both patients underwent pulmonary resection due to an enlarged solitary pulmonary nodule. Pathological findings in both cases confirmed a papillary tumour with a mixture of ciliated columnar and goblet cells. The tumours were rich in mucous and had spread along the alveolar walls, as observed in bronchioloalveolar carcinoma. Nuclear atypia was mild, and no mitotic activity was observed. Immunohistochemically, tumour cells stained positive for carcinoembryonic antigen, thyroid transcription factor-1 and cytokeratin 7 but not for cytokeratin 20. The immunohistochemical staining patterns were almost identical to those of pulmonary adenocarcinoma. We definitively diagnosed as CMPT. Both patients remained relapse-free.

MiR-221, a potential prognostic biomarker for recurrence in papillary thyroid cancer.

PubMed

Dai, Lei; Wang, Yaozong; Chen, Liangliang; Zheng, Jueru; Li, Jianjun; Wu, Xianjiang

2017-01-07

Many studies have reported several transcriptionally deregulated microRNAs (miRNAs) in papillary thyroid cancer (PTC) tissue in comparison with benign thyroid nodules and normal thyroid tissues. However, the correlation between miRNA expressions and PTC recurrence still remains unclear. The PTC patients who scheduled to undergo total thyroidectomy by the same surgical team in Ningbo NO.2 Hospital from March 1998 to March 2008 were enrolled in this study. The clinical and pathological characteristics of each patient were recorded in detail. The selected miRNA expressions were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Potential predictive factors for cancer recurrence were evaluated by univariate and multivariate Cox proportional hazard analysis. A total of 78 patients were enrolled with 49 females at a mean age of 45.8 years. Enrolled patients were divided into two groups: nonrecurrent group (n = 54) and recurrent group (n = 24). The results from the univariate Cox proportional hazard analysis revealed that primary tumor size, TNM stage, extrathyroid extension, miR-221, and miR-222 expressions were significantly associated with PTC recurrence (P < 0.05). The tissue expression of miR-221 was the only independent risk factor for PTC recurrence (HR 1.41; 95%CI 1.14-1.95, P = 0.007) by multiple Cox proportional hazard analysis. This study identified the potential role of miR-221 as a prognostic biomarker for the recurrence in PTC.

The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma.

PubMed

Jara, Sebastian M; Carson, Kathryn A; Pai, Sara I; Agrawal, Nishant; Richmon, Jeremy D; Prescott, Jason D; Dackiw, Alan; Zeiger, Martha A; Bishop, Justin A; Tufano, Ralph P

2013-12-01

Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P < .001) and had a younger median age (43 vs. 47 years; P = .03), a lesser incidence of CNM (35% vs. 52.4%; P < .001), and a greater incidence of pT1a (40% vs. 25%; P < .001) and pT1b (38% vs. 29%; P < .001) tumors. Multivariate analysis showed that the presence of CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. Female patients of all ages with CLT and small PTCs have the least incidence of CNM. Copyright © 2013 Mosby, Inc. All rights reserved.

Variants in the ATM-CHEK2-BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma.

PubMed

Wójcicka, Anna; Czetwertyńska, Małgorzata; Świerniak, Michał; Długosińska, Joanna; Maciąg, Monika; Czajka, Agnieszka; Dymecka, Kinga; Kubiak, Anna; Kot, Adam; Płoski, Rafał; de la Chapelle, Albert; Jażdżewski, Krystian

2014-06-01

The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6-fold in first-degree relatives of PTC patients. The familial risk could be explained by high-penetrance mutations in yet unidentified genes, or polygenic action of low-penetrance alleles. Since the DNA-damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low-penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e-10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM- CHEK2- BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations. Copyright © 2014 Wiley Periodicals, Inc.

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

PubMed

dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

Thyroid tumors of uncertain malignant potential: morphologic and imunohistochemical analysis of 29 cases.

PubMed

Nechifor-Boila, Adela; Borda, Angela; Sassolas, Geneviève; Hafdi-Nejjari, Zakia; Cătană, Ramona; Borson-Chazot, Françoise; Berger, Nicole; Decaussin-Petrucci, Myriam

2015-04-01

Thyroid tumors of uncertain malignant potential (TT-UMP) include follicular and well-differentiated tumors of UMP (FT-UMP/WDT-UMP), as it refers to the presence of questionable capsular/vascular invasion or incompletely developed papillary thyroid carcinoma (PTC)-type nuclear changes. However, these tumors are difficult to diagnose in most cases. We aimed to investigate whether immunohistochemistry (HBME-1, cytokeratin-19, galectin-3, CD56 and p63) provides additional information concerning such lesions. We performed an immunohistochemical analysis on 29 TT-UMP cases (22 WDTs-UMP and 7 FTs-UMP) selected from the Rhone Alpes thyroid cancer registry and Departement of Pathology, Tîrgu-Mureş Emergency County Hospital database. The clinicopathological and follow-up data were obtained. In the WDT-UMP group, HBME-1 was positive in 9/22 (40.9%) cases. CD56, a marker whose expression is reduced or absent in thyroid carcinoma, showed a "malignant" profile (no expression) in 13/22 (59.1%) cases. 7/22 (31.9%) cases were both HBME-1+ and CD56-. One case showed the co-expression of HBME-1, CD56, galectin-3 and cytokeratin-19. In the FT-UMP group, two cases were positive for HBME-1, other two for both galectin-3 and CK19 and only one case revealed a "malignant" CD56 profile. The follow-up data showed no distant metastases or persistent disease. Our study demonstrated very heterogeneous immunohistochemical profiles for TTs-UMP, further supporting the borderline nature of these lesions. WDTs-UMP revealed a certain tendency toward a PTC profile, suggesting a possible pathogeneticlink between these two entities. However, immunohistochemistry is still to be regarded more as a supporting diagnostic tool, while morphological criteria should always prime in the diagnostic decision. Copyright © 2014 Elsevier GmbH. All rights reserved.

Solid cell nests of the thyroid gland: morphological, immunohistochemical and genetic features.

PubMed

Manzoni, Marco; Roversi, Gaia; Di Bella, Camillo; Pincelli, Angela I; Cimino, Vincenzo; Perotti, Mario; Garancini, Mattia; Pagni, Fabio

2016-05-01

The correct identification of solid cell nests (SCNs) is an important issue in thyroid pathology because of the spectrum of differential diagnoses of this type of lesion. Ten cases of 295 consecutive thyroidectomies showed the presence of SCNs at histological examination. The identification of the exact SCN type required the distinction of the cystic and solid pattern; SCNs were usually composed of a mixture of main cells (MCs) and C-cells (CCs). The immunohistochemical calcitonin stain identified CCs easily, both inside SCNs and dispersed in islets at the periphery. For the characterization of MCs, we added the utility of p40 to p63. The use of thyroid transcription factor-1 (TTF-1) helped in their identification, as MCs did not react with this marker; the combination of TTF-1 and p40 or p63 IHC stains was useful for the characterization of cystic SCNs of both types 3 and 4. The negativity of mouse monoclonal mesothelioma antibody (HMBE-1) and a very low proliferative index (MIB-1) supported the diagnosis. [Correction added on 23 November 2015, after online publication: MIB-1 was incorrectly defined, the expanded form was deleted.] We discourage the use of galectin-3 (Gal-3) and cytokeratin-19 (CK-19), as they have an important overlap with papillary thyroid carcinoma. The complete absence of any B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations is an additional fundamental finding. We reviewed the most relevant morphological and immunohistochemical features of SCNs and have provided a genetic analysis of the BRAF gene because of its expanding use in thyroid pathology. © 2015 John Wiley & Sons Ltd.

Efficacy of Superselective Neck Dissection in Detecting Metastasis in Patients with cN0 Papillary Thyroid Carcinoma at High Risk of Lateral Neck Metastasis

PubMed Central

An, Changming; Zhang, Xiwei; Wang, Shixu; Zhang, Zongmin; Yin, Yulin; Xu, Zhengang; Tang, Pingzhang; Li, Zhengjiang

2017-01-01

Background This study aimed to evaluate superselective neck dissection (SSND) in patients with cN0 papillary thyroid carcinoma (PTC) at high risk of lateral cervical lymph node (LN) metastasis. Material/Methods This study enrolled 138 patients with PTC who underwent SSND. These patients were at high risk for LN metastasis and the rate of cervical LN metastasis was recorded. Results In all, 146 lateral neck dissections were performed in 138 patients. Intraoperative pathological data revealed LN metastasis from 55 cases, for which Level II and V dissection were performed. Ninety SSNDs were performed in the other 83 patients without metastasis identified in frozen sections. Occult lymph node metastasis (OLNM) rates were 56.8% and 43.5% in the central compartment and lateral neck, respectively. OLNM rates of Level II–VI were 17.8%, 31.5%, 36.3%, 1.4%, and 56.8%, respectively. Level VI metastasis (p<0.001), extra thyroidal extension (p=0.003), and tumor size (p=0.011) were significant factors for lateral neck LN metastasis. Conclusions SSND might be effective for early diagnosis of lateral neck metastases of PTC. Patients with OLNM should receive level II, III, and IV dissection, but level V dissection could be omitted. PMID:28469126

MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma

NASA Astrophysics Data System (ADS)

Huang, Chen-Tsung; Oyang, Yen-Jen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

2014-09-01

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA-target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.