Polymerase chain reaction in the detection of tumor cells: new approaches in diagnosis and follow-up of patients with thyroid cancer.

PubMed

Bojunga, Jörg; Kusterer, Klaus; Schumm-Draeger, Petra-Maria; Usadel, Klaus-Henning

2002-12-01

Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increasing frequency. In addition to other measures, diagnosis is based on fine-needle aspiration cytology examination. Recently, new assays using reverse transcription-polymerase chain reaction (PCR) are being tested to improve sensitivity and specificity of primary diagnosis and detection of recurrent thyroid cancer. In the preoperative diagnosis of thyroid cancer, several tissue- and/or tumor-specific mRNA have been described and in several cases, a higher sensitivity and specificity could be achieved using molecular techniques compared to conventional methods. In the postoperative follow-up of patients with thyroid cancer, conflicting data have been published and the use of PCR techniques revealed several problems of the molecular approach, which are based on some technical as well as biologic limitations. Despite these problems, which are discussed in detail in this review, molecular techniques may nevertheless improve the sensitivity and accuracy of fine-needle aspiration of thyroid nodules, fine-needle aspiration of metastases, and detection of recurrent disease in peripheral blood samples.

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening.

PubMed

Anania, Maria; Gasparri, Fabio; Cetti, Elena; Fraietta, Ivan; Todoerti, Katia; Miranda, Claudia; Mazzoni, Mara; Re, Claudia; Colombo, Riccardo; Ukmar, Giorgio; Camisasca, Stefano; Pagliardini, Sonia; Pierotti, Marco; Neri, Antonino; Galvani, Arturo; Greco, Angela

2015-10-27

The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies.

TRIADIMEFON INDUCES RAT THYROID TUMORS THROUGH A NON-TSH MEDIATED MODE OF ACTION

EPA Science Inventory

Conazoles are a class of fungicides used as agricultural and pharmaceutical products which inhibit ergosterol biosynthesis. Members of this class are hepatotoxic and cause mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. Triadimefon-induced rat thyroid tumor...

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.

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

PubMed

Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

2017-01-01

Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

Neurotrophin Receptors TrkA, p75NTR, and Sortilin Are Increased and Targetable in Thyroid Cancer.

PubMed

Faulkner, Sam; Jobling, Philip; Rowe, Christopher W; Rodrigues Oliveira, S M; Roselli, Severine; Thorne, Rick F; Oldmeadow, Christopher; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M; Hondermarck, Hubert

2018-01-01

Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75 NTR , and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75 NTR was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75 NTR , and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75 NTR , and sortilin as potential therapeutic targets in thyroid cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

Nucleophosmin is overexpressed in thyroid tumors

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

Pianta, Annalisa; Puppin, Cinzia; Franzoni, Alessandra

2010-07-02

Nucleophosmin (NPM) is a protein that contributes to several cell functions. Depending on the context, it can act as an oncogene or tumor suppressor. No data are available on NPM expression in thyroid cells. In this work, we analyzed both NPM mRNA and protein levels in a series of human thyroid tumor tissues and cell lines. By using immunohistochemistry, NPM overexpression was detected in papillary, follicular, undifferentiated thyroid cancer, and also in follicular benign adenomas, indicating it as an early event during thyroid tumorigenesis. In contrast, various levels of NPM mRNA levels as detected by quantitative RT-PCR were observed inmore » tumor tissues, suggesting a dissociation between protein and transcript expression. The same behavior was observed in the normal thyroid FRTL5 cell lines. In these cells, a positive correlation between NPM protein levels, but not mRNA, and proliferation state was detected. By using thyroid tumor cell lines, we demonstrated that such a post-mRNA regulation may depend on NPM binding to p-Akt, whose levels were found to be increased in the tumor cells, in parallel with reduction of PTEN. In conclusion, our present data demonstrate for the first time that nucleophosmin is overexpressed in thyroid tumors, as an early event of thyroid tumorigenesis. It seems as a result of a dysregulation occurring at protein and not transcriptional level related to an increase of p-Akt levels of transformed thyrocytes.« less

Primary mucinous carcinoma of thyroid gland with prominent signet-ring-cell differentiation: a case report and review of the literature.

PubMed

Wang, Jian; Guli, Qie-Re; Ming, Xiao-Cui; Zhou, Hai-Tao; Cui, Yong-Jie; Jiang, Yue-Feng; Zhang, Di; Liu, Yang

2018-01-01

This study reports a case of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation, and reviews the literature to evaluate its real incidence and the prognosis of these patients. A 74-year-old Chinese woman, presenting with a mass in the right lobe of thyroid gland, came to the hospital. Computed tomography revealed a mass in the right lobe of the thyroid gland, accompanied with right neck lymphadenectasis and airway deviation caused by tumor compression. Thyroid imaging suggested a thyroid malignant tumor and suspicious lymph node metastasis. Histologically, the tumor was characterized by the tumor cells arranged in small nests or trabeculae with an abundant extracellular mucoid matrix. The tumor cells formed diffuse invasion among thyroid follicles. In the peripheral regions, prominent signet-ring-cells formed a sheet-like structure and extended into the extrathyroidal fat tissue. The tumor cells were diffusely positive for thyroid transcription factor-1 (TTF-1) and PAX8, while they were focally positive for pan-cytokeratin (AE1/AE3) and weakly expressed thyroglobulin. Based on the histological features and immunohistochemical profile, a diagnosis of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation was rendered. Using a panel of immunohistochemical markers may be helpful for differential diagnosis and for determining whether the tumor is primary or not.

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

Metabolic Reprogramming in Thyroid Carcinoma

PubMed Central

Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

2018-01-01

Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

PubMed

Hurley, P M

1998-08-01

Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

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.

Comparison of transcriptomic signature of post-Chernobyl and postradiotherapy thyroid tumors.

PubMed

Ory, Catherine; Ugolin, Nicolas; Hofman, Paul; Schlumberger, Martin; Likhtarev, Illya A; Chevillard, Sylvie

2013-11-01

We previously identified two highly discriminating and predictive radiation-induced transcriptomic signatures by comparing series of sporadic and postradiotherapy thyroid tumors (322-gene signature), and by reanalyzing a previously published data set of sporadic and post-Chernobyl thyroid tumors (106-gene signature). The aim of the present work was (i) to compare the two signatures in terms of gene expression deregulations and molecular features/pathways, and (ii) to test the capacity of the postradiotherapy signature in classifying the post-Chernobyl series of tumors and reciprocally of the post-Chernobyl signature in classifying the postradiotherapy-induced tumors. We now explored if postradiotherapy and post-Chernobyl papillary thyroid carcinomas (PTC) display common molecular features by comparing molecular pathways deregulated in the two tumor series, and tested the potential of gene subsets of the postradiotherapy signature to classify the post-Chernobyl series (14 sporadic and 12 post-Chernobyl PTC), and reciprocally of gene subsets of the post-Chernobyl signature to classify the postradiotherapy series (15 sporadic and 12 postradiotherapy PTC), by using conventional principal component analysis. We found that the five genes common to the two signatures classified the learning/training tumors (used to search these signatures) of both the postradiotherapy (seven PTC) and the post-Chernobyl (six PTC) thyroid tumor series as compared with the sporadic tumors (seven sporadic PTC in each series). Importantly, these five genes were also effective for classifying independent series of postradiotherapy (five PTC) and post-Chernobyl (six PTC) tumors compared to independent series of sporadic tumors (eight PTC and six PTC respectively; testing tumors). Moreover, part of each postradiotherapy (32 genes) and post-Chernobyl signature (16 genes) cross-classified the respective series of thyroid tumors. Finally, several molecular pathways deregulated in post-Chernobyl tumors matched those found to be deregulated in postradiotherapy tumors. Overall, our data suggest that thyroid tumors that developed following either external exposure or internal (131)I contamination shared common molecular features, related to DNA repair, oxidative and endoplasmic reticulum stresses, allowing their classification as radiation-induced tumors in comparison with sporadic counterparts, independently of doses and dose rates, which suggests there may be a "general" radiation-induced signature of thyroid tumors.

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

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.

EFFECT OF HYPOTHYROIDISM AND THYROID GRAFTS ON LYMPHOID TUMOR DEVELOPMENT IN IRRADIATED C57BL MICE

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

Nagareda, C.S.; Kaplan, H.S.

1959-04-01

Studies on the effect of radiothyroidectomy and thyroid grafts on the incidence of thymic implant lymphomas in thymectomized-irradiated CS7BL mice are reported. Hypothyroidism significantly inhibited thymic implant tumor development in females. A similar reduction of lymphoma incidence in hypothyroid males was not statistically significant. When thyroid activity was restored by grafting normal thyroids to radiothyroidectomized animals, lymphoma incidence returned to the level seen in euthyroid animals. I/sup 131/ uptake measurements were made on a representative number of thyroids and thyroid grafts. There was no significant uptake by the I/sup 131/-treated thyroids. Thyroid grafts were just as active as thyroids frommore » control animals. Body weight decreased significantiy in hypothyroid animals and was restored to control euthyroid levels in radiothyroidectomized animals by thyroid grafts. The possible influence of secondary nutritional and endocrine disturbances on leukemogenesis are discussed; it seems likely that the observed inhibition is attributable to hypothyroidism per se, rather than to secondary influences on nutrition or other endocrine imbalances. Incidental observations on pituitary tumor development in lymphoma- free radiothyroldectomized animals are also reported. Pituitary tumor development was completely prevented by thyroid grafts after radiothyroidectomy. (auth)« less

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma.

PubMed

Song, Hai; Lin, Chuwen; Yao, Erica; Zhang, Kuan; Li, Xiaoling; Wu, Qingzhe; Chuang, Pao-Tien

2017-03-03

Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRP CreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53 , Rb , and Pten , in mature parafollicular C cells via an inducible Cre recombinase from CGRP CreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53 / Rb -induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRP CreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid.

PubMed

Nath, Meryl C; Erickson, Lori A

2018-05-01

Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.

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.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

The cytology of a thyroid granular cell tumor.

PubMed

Chang, Shu-Mei; Wei, Chang-Kuo; Tseng, Chih-En

2009-01-01

Granular cell tumor (GCT) of the thyroid is rare. Before this report, only four cases of thyroid GCT have been reported, none of which presented a cytopathological examination. In this paper, we report the fine needle aspiration cytology and pathological analysis of a thyroid GCT from a 12-year-old girl who presented with a painless neck mass. The tumor cells were single, in syncytial clusters, or pseudofollicles, contained small round, oval, or spindle nuclei, indistinct nucleoli, and a large amount of grayish, granular fragile cytoplasm. The background contained granular debris and naked nuclei. A differential diagnosis of thyroid GCT with more frequent thyroid lesions containing cytoplasmic granules, including Hurthle cells, macrophages, follicular cells, and cells of black thyroid syndrome, was also performed.

Vanishing thyroid gland tumors: Infarction as consequence of FNA?

PubMed

Kholová, Ivana

2016-07-01

Fine-needle aspiration (FNA)-induced secondary changes were described in various organs. Complete replacement of tumor by necrosis causes diagnostic and management problems. Seven cases of totally or partially vanished thyroid lesions were identified from the archive of Department of Pathology, Fimlab Laboratories within 5 year period. Histopathological slides were revised in all cases. Total thyroidectomy or lobectomy samples were from 4 females and 3 males patients aged 37-83 years (mean 67.1 years). Imaging data were available in 6 cases. Cytology slides and data were available only in 3 cases: two revealed follicular neoplasm and one was insufficient according to Bethesda system. In 5 cases, final histopathology revealed total necrosis of the lesion with only one case with available cytological diagnosis of oncocytic follicular neoplasm. In remaining 2 cases, replacement by necrosis was partial. Of note, in three cases, oncocytic metaplasia was present. Total histopathological blocking with thorough check of capsular areas is recommended in necrotic tumors. Vanishing thyroid lesion phenomenon is rare, but in cases of disappearance of tumor, preoperative cytology diagnosis is the only clue for the patient management. Diagn. Cytopathol. 2016;44:568-573. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

TGF-beta-induced apoptosis in human thyrocytes is mediated by p27kip1 reduction and is overridden in neoplastic thyrocytes by NF-kappaB activation.

PubMed

Bravo, Susana B; Pampín, Sandra; Cameselle-Teijeiro, José; Carneiro, Carmen; Domínguez, Fernando; Barreiro, Francisco; Alvarez, Clara V

2003-10-30

Millions of people worldwide suffer goiter, a proliferative disease of the follicular cells of the thyroid that may become neoplastic. Thyroid neoplasms have low proliferative index, low apoptotic index and a high incidence of metastasis. TGF-beta is overexpressed in thyroid follicular tumor cells. To investigate the role of TGF-beta in thyroid tumor progression, we established cultures of human thyrocytes from different proliferative pathologies (Grave's disease, multinodular goiter, follicular adenoma, papillary carcinoma), lymph node metastasis, and a normal thyroid sample. All cultures maintained the thyrocyte phenotype. TGF-beta induced cell-cycle arrest in all cultures, in contrast with results reported for other epithelial tumors. In deprived medium, TGF-beta induced apoptosis in normal thyrocyte cultures and all neoplastic cultures except the metastatic cultures. This apoptosis was mediated by a reduction in p27kip1 levels, inducing cell-cycle initiation. Antisense p27 expression induced apoptosis in the absence of TGF-beta. By contrast, in cells in which p27 was overexpressed, TGF-beta had a survival effect. In growth medium, a net survival effect occurs in neoplastic thyrocytes only, not normal thyrocytes, due to activation of the NF-kappaB survival program. Together, these findings suggest that (a) thyroid neoplasms are due to reduced apoptosis, not increased division, in line with the low proliferative index of these pathologies, and (b) TGF-beta induces apoptosis in normal thyrocytes via p27 reduction, but that in neoplastic thyrocytes this effect is overridden by activation of the NF-kappaB program.

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.

Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

PubMed Central

Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

2013-01-01

Background: Immunotherapeutic modalities to bolster tumor immunity by targeting specific sites of the immune network often result in immune dysregulation with adverse autoimmune sequelae. To understand the relative risk for opportunistic autoimmune disorders, we studied established breast cancer models in mice resistant to experimental autoimmune thyroiditis (EAT). EAT is a murine model of Hashimoto's thyroiditis, an autoimmune syndrome with established MHC class II control of susceptibility. The highly prevalent Hashimoto's thyroiditis is a prominent autoimmune sequela in immunotherapy, and its relative ease of diagnosis and treatment could serve as an early indicator of immune dysfunction. Here, we examined EAT-susceptible mice as a combined model for induction of tumor immunity and EAT under the umbrella of disrupted regulatory T cell (Treg) function. Methods: Tumor immunity was evaluated in female CBA/J mice after depleting Tregs by intravenous administration of CD25 monoclonal antibody and/or immunizing with irradiated mammary adenocarcinoma cell line A22E-j before challenge; the role of T cell subsets was determined by injecting CD4 and/or CD8 antibodies after tumor immunity induction. Tumor growth was monitored 3×/week by palpation. Subsequent EAT was induced by mouse thyroglobulin (mTg) injections (4 daily doses/week over 4 weeks). For some experiments, EAT was induced before establishing tumor immunity by injecting mTg+interleukin-1, 7 days apart. EAT was evaluated by mTg antibodies and thyroid infiltration. Results: Strong resistance to tumor challenge after Treg depletion and immunization with irradiated tumor cells required participation of both CD4+ and CD8+ T cells. This immunity was not altered by induction of mild thyroiditis with our protocol of Treg depletion and adjuvant-free, soluble mTg injections. However, the increased incidence of mild thyroiditis can be directly related to Treg depletion needed to achieve strong tumor immunity. Moreover, when a subclinical, mild thyroiditis was induced with soluble mTg and low doses of interleukin-1, to simulate pre-existing autoimmunity in patients subjected to cancer immunotherapy, mononuclear infiltration into the thyroid was enhanced. Conclusions: Our current findings indicate that genetic predisposition to autoimmune disease could enhance autoimmunity during induction of tumor immunity in thyroiditis-susceptible mice. Thus, HLA genotyping of cancer patients should be part of any risk assessment. PMID:23777580

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.

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.

Measurement of TFF3 mRNA in aspirates from thyroid nodules using mesh filtration: the first clinical trial in 130 cases.

PubMed

Yamada, Hiroya; Takano, Toru; Kihara, Minoru; Hirokawa, Mitsuyoshi; Yoshida, Hiroshi; Watanabe, Mikio; Iwatani, Yoshinori; Hidaka, Yoh; Miyauchi, Akira

2012-01-01

Measurement of gene expression levels in thyroid tumor cells in aspirates was difficult because it is interfered with peripheral blood cells or infiltrating lymphocytes. In this study, we established a novel method to separate thyroid tumor cells from blood cells efficiently with mesh filtration. The expression level of trefoil factor 3 (TFF3) mRNA was estimated using LGALS3 mRNA as an internal control (T/G ratio) in 148 preoperative thyroid aspirates. Intra-assay coefficients of variation (CV) of T/G ratio for high, moderate, and low samples were 6.5%, 2.5%, and 9.7%, respectively, and inter-assay CV for high, moderate, and low samples were 27.7%, 21.9%, and 38.2%, respectively. Nondiagnostic samples in terms of T/G ratio and cytology were 12.2% and 16.9%, respectively. We observed no interference with the data by contaminating blood cells. Among these patients, 12 patients received more than two repeated aspirations. We did not observe a marked day-to-day variation except in two cases. All 13 preoperative aspirates diagnosed as malignant by cytology showed an extremely low T/G ratio, whereas 93 aspirates diagnosed as benign by cytology showed extremely varied T/G ratios and 21.5% of them showed a T/G ratio below the cut-off value. Eleven cases underwent surgery. All nodules showing a low T/G ratio were diagnosed as papillary carcinoma by pathological diagnosis. However, one nodule diagnosed as follicular adenoma after surgery showed a high T/G ratio. Our present method may be a promising preoperative test for measuring mRNAs in thyroid aspirates.

Embryonic epithelial Pten deletion through Nkx2.1-cre leads to thyroid tumorigenesis in a strain-dependent manner

PubMed Central

Tiozzo, Caterina; Danopoulos, Soula; Lavarreda-Pearce, Maria; Baptista, Sheryl; Varimezova, Radka; Al Alam, Denise; Warburton, David; Virender, Rehan; De Langhe, Stijn; Di Cristofano, Antonio

2014-01-01

Even though the role of the tyrosine phosphatase Pten as a tumor suppressor gene has been well established in thyroid cancer, its role during thyroid development is still elusive. We therefore targeted Pten deletion in the thyroid epithelium by crossing Ptenflox/flox with a newly developed Nkx2.1-cre driver line in the BALB/c and C57BL/6 genetic backgrounds. C57BL/6 homozygous Pten mutant mice died around 2 weeks of age due to tracheal and esophageal compression by a hyperplasic thyroid. By contrast, BALB/c homozygous Pten mutant mice survived up to 2 years, but with a slightly increased thyroid volume. Characterization of the thyroid glands from C57BL/6 homozygous Pten mutant mice at postnatal day 14 (PN14) showed abnormally enlarged tissue with areas of cellular hyperplasia, disruption of the normal architecture, and follicular degeneration. In addition, differing degrees of hypothyroidism, thyroxine (T4) decrease, and thyroid-stimulating hormone elevation between the strains in the mutants and the heterozygous mutant were detected at PN14. Finally, C57BL/6 heterozygous Pten mutant mice developed thyroid tumors after 2 years of age. Our results indicate that Pten has a pivotal role in thyroid development and its deletion results in thyroid tumor formation, with the timing and severity of the tumor depending on the particular genetic background. PMID:22167068

A human thyroid cancer cell line, DH-14-3, newly established from poorly differentiated thyroid carcinoma.

PubMed

Teshima, Jin; Doi, Hideyuki; Fujimori, Keisei; Watanabe, Michio; Nakajima, Noriaki; Nakano, Tomoyuki; Takahashi, Yoshio; Ohuchi, Noriaki; Satomi, Susumu

2013-06-01

Poorly differentiated thyroid carcinoma (PDTC) is a newly recognized histological type of malignant thyroid tumor, accounting for about 2 - 13% of all thyroid carcinomas. PDTC is considered as a morphologically and biologically intermediate stage between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. PDTC preferentially manifests bone metastases. We here established a cell line from a resected tumor specimen from a 70-year-old male patient with PDTC who presented with multiple bone metastases. This new thyroid tumor cell line was designated as DH-14-3 and was subsequently grown in culture for several years. DH-14-3 cells express thyroglobulin in the cytoplasm and thyroid transcription factor-1 in the nuclei, both proteins of which are specific markers for the thyroid gland. Importantly, triiodothyronine (T3) was detected in the cultured medium of DH-14-3 cells, in which, however, thyroxine (T4) was undetectable. Moreover, DH-14-3 cells secreted interleukin-8, transforming growth factor-β1, vascular endothelial growth factor, matrix metalloproteinase-1 and parathyroid hormone-related protein, all of which may be responsible for the aggressiveness or bone metastasis of PDTC. Thus, the production of these proteins may reflect the metastatic potential of this cell line. DH-14-3 cells also express CXC chemokine receptor-4 and epidermal growth factor receptor, and carry a missense mutation in the p53 tumor suppressor gene. In fact, transplantation of DH-14-3 cells into the back of nude mice resulted in the formation of tumors, thereby confirming the capability of tumorigenesis. DH-14-3 cells may be useful for investigating the biological features of PDTC and will contribute to the therapeutic study of thyroid cancer.

Thyroid cancer outcomes in Filipino patients.

PubMed

Kus, Lukas H; Shah, Manish; Eski, Spiro; Walfish, Paul G; Freeman, Jeremy L

2010-02-01

To compare the outcomes of patients having thyroid cancer among Filipinos vs non-Filipinos. Retrospective medical record review. High-volume tertiary referral center in Toronto, Ontario, Canada. A total of 499 patients with thyroid cancer (36 Filipino and 463 non-Filipino) treated at Mount Sinai Hospital from January 1, 1984, to August 31, 2003, with a minimum 5-year follow-up period and a minimum 1.0-cm tumor size. Patients were identified from a thyroid cancer database. Data on patient, tumor, and treatment factors were collected along with outcomes. The presence of thyroid cancer recurrence, the rate of death from disease, and the time to recurrence. The 2 groups were similar for sex, age, history of head and neck radiation exposure, family history of thyroid cancer, follow-up time, tumor size, tumor pathologic findings, presence of tumor multifocality, stage of primary disease, type of thyroid surgery, use of postoperative radioactive iodine therapy, and use of external beam radiation therapy. Filipino patients experienced a thyroid cancer recurrence rate of 25% compared with 9.5% for non-Filipino patients (odds ratio, 3.20; 95% confidence interval, 1.23-7.49; P = .004). On multivariate analysis, the increased risk of thyroid cancer recurrence persisted for Filipino patients (odds ratio, 6.99; 95% confidence interval, 2.31-21.07; P < .001). No significant differences were noted between Filipino patients and non-Filipino patients regarding the rate of death from disease (5.6% vs 1.9%) and the time to recurrence (52.6 vs 53.1 months). Filipino patients have a significantly higher risk of thyroid cancer recurrence compared with non-Filipino patients. However, no significant difference was noted in the time to recurrence or the rate of death from disease. These findings justify a more aggressive initial management and follow-up regimen for Filipino patients with thyroid cancer.

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

[Autoimmune thyroiditis and thyroid cancer].

PubMed

Krátký, Jan; Jiskra, Jan

2015-10-01

Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence.

TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

PubMed

Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

2014-10-01

The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

Identification and treatment of aggressive thyroid cancers. Part 2: risk assessment and treatment.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-04-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radio-iodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article, which appeared in March, described in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, treatment, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2 covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

Identification and treatment of aggressive thyroid cancers. Part 1: subtypes.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-03-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radioiodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article describes in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2, which will appear in next month's issue, covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and the value of treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

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.

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

Notch3 as a novel therapeutic target in metastatic medullary thyroid cancer.

PubMed

Lou, Irene; Odorico, Scott; Yu, Xiao-Min; Harrison, April; Jaskula-Sztul, Renata; Chen, Herbert

2018-01-01

Medullary thyroid cancer portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in medullary thyroid cancer liver metastasis will decrease proliferation and growth of the tumor. TT cells were modified genetically to overexpress Notch3 in the presence of doxycycline, creating the TT-Notch3 cell line. Mice were injected intrasplenically with either TT-Notch3 or control vector TT-TRE cells. Each cell line had 3 treatment groups: control with 12 weeks of standard chow, early DOX with doxycycline chow at day 0 and for 70 days thereafter, and late DOX with doxycycline chow at 8 weeks. Each animal underwent micro-computed tomography to evaluate for tumor formation and tumor quantification was performed. Animals were killed at 12 weeks, and the harvested liver was stained with Ki-67, hematoxylin and eosin, and Notch3. Induction of Notch3 did not prevent formation of medullary thyroid cancer liver metastases as all mice in the early DOX group developed tumors. However, induction of Notch after medullary thyroid cancer liver tumor formation decreased tumor size, as seen on micro-computed tomography scans (late DOX group). This translated to a 37-fold decrease in tumor volume (P = .001). Notch3 overexpression also resulted in decreased Ki-67 index (P = .038). Moreover, Notch3 induction led to increased areas of neutrophil infiltration and necrosis on hematoxylin and eosin staining of the tumors CONCLUSION: Notch3 overexpression demonstrates an antiproliferative effect on established metastatic medullary thyroid cancer liver tumors and is a potential therapeutic target in treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

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

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

Trefoil factor 3 is required for differentiation of thyroid follicular cells and acts as a context-dependent tumor suppressor.

PubMed

Abols, A; Ducena, K; Andrejeva, D; Sadovska, L; Zandberga, E; Vilmanis, J; Narbuts, Z; Tars, J; Eglitis, J; Pirags, V; Line, A

2015-01-01

Trefoil factor 3 (TFF3) is overexpressed in a variety of solid epithelial cancers, where it has been shown to promote migration, invasion, proliferation, survival and angiogenesis. On the contrary, in the majority of thyroid tumors, it is downregulated, yet its role in the development of thyroid cancer remains unknown. Here we show that TFF3 exhibits strong cytoplasmic staining of normal thyroid follicular cells and colloid and the staining is increased in hyperfunctioning thyroid nodules, while it is decreased in all thyroid cancers of follicular cell origin. By meta-analysis of gene expression datasets, we found that in the thyroid cancer, conversely to the breast cancer, the expression of TFF3 mRNA was downregulated by estrogen signaling and confirmed this by treating thyroid cancer cells with estradiol. Forced expression of TFF3 in anaplastic thyroid cancer cells resulted in decreased cell proliferation, clonal spheroid formation and entry into the S phase. Furthermore, it induced acquisition of epithelial-like cell morphology and expression of the differentiation markers of thyroid follicular cells and transcription factors implicated in the thyroid morphogenesis and function. Taken together, this study provides the first evidence that TFF3 may act as a tumor suppressor or an oncogene depending on the cellular context.

Thyroid neoplasia following low-dose radiation in childhood

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

Ron, E.; Modan, B.; Preston, D.

1989-12-01

The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benignmore » tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.« less

Carcinoma showing thymus-like elements of the thyroid gland: report of three cases including one case with breast cancer history.

PubMed

Zhang, Guanjun; Liu, Xi; Huang, Wei; Li, Xiaofeng; Johnstone, Marianne; Deng, Yuan; Ke, Yongqiang; Nunes, Quentin M; Wang, Hongyan; Wang, Yili; Zhang, Xuebin

2015-01-01

Carcinoma showing thymus-like elements (CASTLE) is a rare malignant tumor of the thyroid or adjacent neck soft tissues, whose histogenesis is still debated. It may resemble other primary or metastatic poorly differentiated tumors histologically and the differential diagnosis is crucial for CASTLE has a better prognosis. However, CASTLE as a second primary tumor has not been reported in the literature. We report three cases of thyroid CASTLE, including a unique tumor following breast-conserving surgery for early-stage breast invasive carcinoma. There were two female and one male. All three tumors were located in the right lobe of the thyroid, and one tumor showed extension into the surrounding soft tissue. Histologically, all tumors showed expansive growth and consisted of cords, nests or sheets of epithelial cells divided into irregularly shaped lobules by fibrous connective tissue with lymphoplasmacytic infiltration. Focal squamous differentiation resembling Hassall's corpuscles were observed. All cases stained positively for CD5, CD117, high molecular weight cytokeratin, cytokeratin, P63, carcinoembryonic antigen and epithelial membrane antigen. Positive staining for Bcl-2 in two cases and chromogranin A in one case was noted. Ki-67 expression ranged from 15 to 25%. Thyroid transcription factor and CD3 were negative. There was no evidence of recurrent or metastatic disease at following surgery. These features demonstrated CASTLE may arise from branchial pouch remnants, the thyroid solid cell nests. CASTLE is a rare entity, awareness of its occurrence as a second primary tumor is important to avoid overtreatment because it is associated with a favorable prognosis.

Metastases to the thyroid gland: A report of 32 cases in PUMCH.

PubMed

Zhang, Liyang; Liu, Yuewu; Li, Xiaoyi; Gao, Weisheng; Zheng, Chaoji

2017-09-01

Metastases of nonthyroid malignancies to the thyroid gland are rare, and only sporadic cases have been reported in literature. We present our experience in treating patients with metastases to the thyroid gland at Peking Union Medical College Hospital. The clinical data of 32 patients who presented with secondary thyroid tumors were retrospectively analyzed. Eleven patients (34.5%) had thyroidectomy.Two patients (6.25%) had tracheostomies to alleviate compression caused by enlarged thyroid tumors. The most common primary lesion was in the lungs (14/32), followed by the kidney (5/32) and gastrointestinal system (5/32). The interval from the diagnosis of the primary tumor to thyroid metastasis varied from 0 month to 16 years. Ten patients (31.3%) are still alive, and the longest follow-up survival time was 7 years. Thyroid metastases are rare, and the lung was the most common primary site of origin. It seems that thyroidectomy has not been considered in cases with a high clinical stage of the neoplastic process such as lung cancer.

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A; Lazzi, S

1998-05-01

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.

Relative intranuclear magnesium and phosphorus contents in normal and tumor cells of the human thyroid gland as revealed by energy-dispersive X-ray microanalysis.

PubMed

Lukács, G L; Zs-Nagy, I; Steiber, J; Györi, F; Balázs, G

1996-01-01

Energy dispersive X-ray microanalysis was performed on altogether 42 surgically removed tissue specimens of 32 patients, which were taken either from intact thyroid parts or various histopathologically verified tumors of the thyroid gland. The tissue specimens were processed with the freeze-fracture-freeze-drying technique and then analyzed in the so-called bulk specimen form. The studies were carried out during the years 1980-81, when intranuclear monovalent ionic composition was studied in detail. From the retained total elemental peak list, it was possible to calculate retrospectively the relative intranuclear Mg and P contents. The data processed by nested (hierarchical) analysis of variance show that the intranuclear Mg content of the 5 diagnostic groups (normal thyroid tissue, thyroiditis, benign adenomas, differentiated carcinomas and undifferentiated thyroid tumors) increases significantly, in parallel with the increasing malignancy, but the P content remains unchanged. One can conclude that the elevated intranuclear Mg content in the tumors of high malignancy may be of diagnostic importance, and a warning signal for the therapeutic approaches based on Mg-supplementations.

Medullary thyroid cancer: the functions of raf-1 and human achaete-scute homologue-1.

PubMed

Chen, Herbert; Kunnimalaiyaan, Muthusamy; Van Gompel, Jamie J

2005-06-01

Medullary thyroid cancer (MTC) is a prototypic neuroendocrine tumor of the thyroid C cells. Other than surgery, there are no curative therapies for MTC. In this review, we detail recent studies that suggest that targeting specific signaling pathways may be a viable strategy to control MTC tumor progression. Specifically, we discuss the role of the raf-1 and achaete-scute homologue-1 pathways in the MTC tumor growth and differentiation.

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway.

PubMed

Wang, Yuanyuan; Lin, Xiangde; Fu, Xinghao; Yan, Wei; Lin, Fusheng; Kuang, Penghao; Luo, Yezhe; Lin, Ende; Hong, Xiaoquan; Wu, Guoyang

2018-06-18

Thyroid cancer is one of the most common malignant tumors of the endocrine system. Among all thyroid cancers, papillary thyroid carcinoma (PTC) is the most common type. The BRAF-activated non-coding RNA (BANCR) is a 693-bp nucleotide transcript which was first identified in melanoma. However, the role of BANCR in the development of thyroid cancer remains unclear. Therefore, the present study investigated the potential involvement of BANCR in the development of thyroid cancer in vitro using patient tissue samples and a panel of thyroid cancer cell lines, and in vivo using a xenograft mouse model. We observed that BANCR was expressed at a higher level in human thyroid tumor tissues than that noted in the adjacent normal tissues. The expression level of BANCR differed between cultured thyroid cancer cell lines; BANCR expression was lower in the BCPAP cell line than that observed in the CAL-62, WRO and FTC-133 cell lines. Western blot analysis and flow cytometry revealed that overexpression of BANCR in the BCPAP cell line resulted in increased expression of the cancer stem cell markers, LGR5 and EpCAM. Single-clone formation experiments showed that upregulated expression of BANCR in the BCPAP cell line promoted an increase in the number of clones formed. Similarly, in microsphere formation experiments, overexpression of BANCR resulted in increased number and size of microspheres compared with the control cell line. Western blotting experiments showed that BANCR overexpression in BCPAP upregulated the expression of phosphorylated c-Raf, MEK1/2 and ERK1/2. Inhibition of c-Raf via U0126 decreased the expression of LGR5 and EpCAM, as well as phosphorylated levels of c-Raf, MEK1/2 and ERK1/2 in the BCPAP cells, compared to levels in the DMSO controls. In the xenograft mouse model, BANCR overexpression in the thyroid cancer cells significantly increased tumor growth. Taken together, these results suggest that BANCR plays a role in PTC development by regulating the expression of cancer stem cell markers LGR5 and EpCAM via the c-Raf/MEK/ERK signaling pathway. Therefore, BANCR may be used as a novel prognostic marker for PTC.

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.

Comparison of the symptoms of menopause and symptoms of thyroid disease in Japanese women aged 35-59 years.

PubMed

Oi, N; Ohi, K

2013-10-01

In this study, we surveyed thyroid function abnormalities and menopausal symptoms in young as well as in menopausal women. We conducted a random survey among outpatients at our facility from September 2008 to June 2011. The study included 853 women aged 35-59 years. We assessed the subjects according to the Simplified Menopause Index, menstrual status, thyroid hormone measurements (thyroid stimulating hormone, free thyroxine, free triiodothyronine), the presence of Hashimoto's disease antibodies (anti-thyroid peroxidase antibody or anti-thyroglobulin antibody), the presence of Grave's disease (anti-TSH receptor antibody), markers of thyroid tumor (high thyroglobulin), and thyroid ultrasonography studies. The data were analyzed by means of the statistical program JMP version 8.0. 'Facial flushing', 'sweating', and 'thyroid tumor' were all positively related with age and menstrual status. 'Breathlessness and palpitations' were positively related to Grave's disease. Moreover, 'sweating', 'irritability', and 'stiff shoulders, low back pain, and joint pain' were related to thyroid tumors. 'Insomnia' decreased with age. Patients with Hashimoto's disease were very rare because they were usually treated at other hospitals that specialize in thyroid disease. The symptoms of thyroid function abnormalities were shown to be very similar to menopausal symptoms and were found to occur in younger women before the onset of menopause. This study shows the need to differentiate menopausal symptoms from those of thyroid diseases.

[Anaplastic carcinoma of the thyroid at the Instituto Nacional de la Nutrición Salvador Zubirán].

PubMed

Sierra, M; Gamboa-Domínguez, A; Herrera, M F; Barredo-Prieto, B; Alvarado de la Barrera, C; Llorente, L; Pérez-Enriquez, B; Rivera, R; González, O; Rull, J A

1997-01-01

Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor with a median survival rate of 6 months. To analyze presentation, treatment, morphology, immunohistochemistry, and nuclear DNA analysis of a cohort of patients with ATC. Twelve patients with ATC (11 female) with a mean age of 65 years were seen at our hospital from 1970-1995. The data were obtained from the clinical records and the morphology, immunohistochemic studies and DNA pattern were performed in slides obtained from archival specimens. Previous or coexisting thyroide disease was documented in 10 patients (9 multinodular goiters and one Grave's). The most frequent presentation was a rapidly growing tumor associated with dysphagia, cervical pain, hoarseness and dyspnea. A cold thyroid nodule was detected by thyroid scan in 10 patients. The most frequent subtype was the spindle cell variety. Papillary thyroid carcinoma coexisted in eight cases, two of them corresponded to the tall cell variant. Reactivity for S-100 protein and vimentin was studied in six patients: all were positive for S-100 protein and vimentin, 5/6 for epithelial membrane antigen, half for carcinoembriogenic antigen, 2/6 for thyroglobulin and calcitonin, and one for neuronal specific enolase. These six tumors showed a diploid DNA pattern. Tumor resection was achieved in 2/11 and none survived six years after diagnosis. ATC is a highly aggressive tumor coexisting with thyroid pathologies. Spindle cell variant is the most frequent with positive reactivity for S-100 protein, vimentin and epithelial membrane antigen. Most tumors have a diploid DNA content.

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways

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

Zhang, Li; Liu, Lianyong; Department of Endocrinology, Shanghai Punan Hospital, Shanghai 200125

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Ourmore » findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. - Highlights: • CHIP is significantly upregulated in thyroid cancer cells. • Overexpression of CHIP facilitates proliferation and tumorigenesis of thyroid cancer cells. • Silencing of CHIP inhibits the proliferation and tumorigenesis of thyroid cancer cells. • CHIP promotes thyroid cancer cell proliferation via activating the MAPK and AKT pathways.« less

Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene.

PubMed

Montero-Conde, Cristina; Leandro-Garcia, Luis J; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A; Bajorin, Dean F; Knauf, Jeffrey A; Riordan, Jesse D; Dupuy, Adam J; Fagin, James A

2017-06-20

Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with Hras G12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-Hras G12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7 , a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene.

Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene

PubMed Central

Montero-Conde, Cristina; Leandro-Garcia, Luis J.; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A.; Bajorin, Dean F.; Knauf, Jeffrey A.; Riordan, Jesse D.; Dupuy, Adam J.; Fagin, James A.

2017-01-01

Oncogenic RAS mutations are present in 15–30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-HrasG12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7, a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene. PMID:28584132

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.

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.

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

[A Case of Hereditary Medullary Thyroid Cancer (MEN2A/FMTC) Diagnosed at the Time of Recurrence].

PubMed

Enomoto, Keisuke; Shimizu, Kotaro; Hirose, Masayuki; Miyabe, Haruka; Morizane, Natsue; Takenaka, Yukinori; Shimazu, Kohki; Fushimi, Hiroaki; Uno, Atsuhiko

2015-03-01

We report a 42-year-old man with hereditary medullary thyroid cancer (multiple endocrine neoplasia, MEN2A/familial medullary thyroid carcinoma, FMTC), which was diagnosed at the time of tumor recurrence. He had a past history of a left thyroidectomy with neck dissection 7 years previously. A RET gene analysis revealed a point mutation (codon 618), and we diagnosed him as having hereditary medullary thyroid cancer. We resected the recurrent tumor in the right thyroid lobe together with performing a right lateral and central neck dissection. A RET gene analysis should be performed for patients with medullary thyroid cancer. When a RET gene mutation is present, a total thyroidectomy must be performed for the medullary thyroid cancer.

Consumptive hypothyroidism due to a gastrointestinal stromal tumor expressing type 3 iodothyronine deiodinase

PubMed Central

Yan, Lin-Hai; Mo, Xian-Wei; Qin, Yu-Zhou; Wang, Cheng; Chen, Zhi-Ning; Lin, Yuan; Chen, Jian-Si

2015-01-01

Context: Gastrointestinal stromal tumors (GISTs) are responsive to sunitinib (the tyrosine kinase inhibitor), this agent is widely used in prevention relapse of GISTs and neo-adjuvant chemotherapy in GIST patients without operation opportunity. The use of these agents has both advantages and disadvantages. On the one hand, it can improve the outcome for patient. On the other hand, it may lead to consumptive hypothyroidism, a rare syndrome caused by increased catabolism of T4 and T3 by increased type 3 iodothyronine deiodinase (D3) activity. D3 is the major physiologic inactivator of thyroid hormone, this selenoenzyme catalyzes the inner-ring deiodination of T(4) to reverse T(3) and T(3) to 3, 3;-diiodothyronine, both of which are biologically inactive [1]. Increased monitoring and supernormal thyroid hormone supplementation are required for affected patient. Objective: The aim of the study was to report the first case of consumptive hypothyroidism in an athyreotic patient after surgical resection of gastrointestinal stromal tumor. Design, setting, and patient: A 60-year-old athyreotic male was presented and he was euthyroid when receiving a stable therapeutic dose of thyroid hormone which was used to treat consumptive hypothyroidism resulting from the side effects of sunitinib, which is used for treatment of neo-adjuvant chemotherapy in gastrointestinal stromal tumor. With a discovery of large D3-expressing gastrointestinal stromal tumor, this patient suffered from marked Hyperthyrotropinemia, which instantly worsened after surgical resection of the gastrointestinal stromal tumor and then continued for 12 weeks after the surgical resection, in spite of further increases in levothyroxine therapy. The patient also had low serum T3 and elevated serum reverse T3 (rT3). Intervention: The patient’s consumptive hypothyroidism caused by marked overexpression of the thyroid hormone-inactivating D3 within the gastrointestinal stromal tumor and adjacent normal gastrointestinal tissue. Main outcome measures and results: D3 immunostaining of the patient’s gastrointestinal stromal tumor was positive, with no significant immunoreactivity in adjacent normal gastrointestinal tissue. The expression levels of CD34, CD117, and DOG1 in peri-tumor tissue samples was lower than that in tumor tissue. The mRNA expression level of KIT exon17 in peri-tumor tissue was higher than that in tumor tissue. Conclusions: This is the first case report of consumptive hypothyroidism in an adult after surgical partial resection of the gastrointestinal stromal tumor. This case demonstrates that hyperthyrotropinemia may worsen after surgical resection of the gastrointestinal stromal tumor. PMID:26770446

Ultrasonographic assessment of the thyroid gland structure in inflammatory bowel disease patients.

PubMed

Neubauer, Katarzyna; Woźniak-Stolarska, Barbara

2012-01-01

The etiopathogenesis of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is still not fully elucidated and seems to be multifactorial. It has been suggested that genetic, immunological and environmental factors participate in IBD development. IBD extraintestinal manifestations include rheumatic, metabolic, dermatologic, ophthalmologic, hepatobiliary, pancreatic, urologic, pulmonary, neurological, hematological and thromboembolic complications. Thyroid gland diseases have not been confirmed as extraintestinal manifestations of IBD. However, it is known that some thyroid diseases share an immunological background with IBD, and that dysfunction of the thyroid gland may induce gastrointestinal symptoms. Ultrasound examination is the gold standard for evaluation of thyroid gland morphology. This study was designed to assess the prevalence of abnormalities in the structure of the thyroid gland in IBD patients and to compare it to the control group. The study group consisted of 199 consecutive IBD patients (80 CD patients and 119 UC patients) hospitalized at the Department of Gastroenterology and Hepatology of Wroclaw Medical University (Poland). The control group consisted of 42 healthy volunteers and patients with functional gastrointestinal disorders. The most common finding in the ultrasound examination in IBD patients were tumors. Tumors, which were smaller than or equal to 10 mm were present in 11.5% of IBD patients; and tumors larger than 10 mm were present in 13.1%. These results show that small tumors (less than 10 mm in diameter) of the thyroid gland are more frequent among patients with CD and UC compared to the control group (p = 0.0001 and p = 0.001, respectively). Additionally, enlargement of the thyroid gland occurs more often in UC patients compared to the control group (p = 0.003). There was no difference in the frequency of thyroid abnormalities between UC and CD patients. In patients with inflammatory bowel diseases focal lesions relating to tumors of the thyroid gland are more common than in the control group. In patients with ulcerative colitis enlargement of the thyroid gland is more frequent than in the control group. Initial assessments of IBD patients should include ultrasound examinations of the thyroid gland.

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

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

PubMed

Fujio, Shingo; Ashari; Habu, Mika; Yamahata, Hitoshi; Moinuddin, F M; Bohara, Manoj; Arimura, Hiroshi; Nishijima, Yui; Arita, Kazunori

2014-01-01

Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 μ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer.

PubMed

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-04-12

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm². Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted.

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer

PubMed Central

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-01-01

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm2. Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. Conclusions: histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted. PMID:28417929

Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

NASA Astrophysics Data System (ADS)

Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

2017-06-01

Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. [Figure not available: see fulltext.

Spectroscopic analysis of normal and neoplastic (WI-FTC) thyroid tissue.

PubMed

Depciuch, Joanna; Stanek-Widera, Agata; Lange, Dariusz; Biskup-Frużyńska, Magdalena; Stanek-Tarkowska, Jadwiga; Czarny, Wojciech; Cebulski, Jozef

2018-06-07

Thyroid cancer holds the first place of the malignant tumors of the endocrine system. One of the less common thyroid cancers is follicular thyroid carcinoma (FTC), which is very difficult to diagnose because it gives the same image as adenoma, which is benign. Certainty of the diagnosis is gained only when FTC gives metastases. Therefore, it was decided to compare normal and neoplastic (FTC) thyroid tissues with Fourier Transform Infrared (FTIR) spectroscopy. The obtained FTIR spectra and Principal Component Analysis (PCA) allowed us to conclude that there are differences in the FTIR spectrum between normal tissues and those affected by cancer. In addition, the results indicate that there is a decrease in the number of functional groups that build cellular and tissue structures in tumoral tissues. The shifts of wave numbers corresponding to the protein and lipid function group vibrations, as well as the calculated second derivative of the FTIR spectra showed the structural changes in neoplastic tissues. Moreover, the deconvolution of the amide I massif indicates that in cancerous tissues the prevailing secondary structure is β-sheet structure, while in normal tissues it is α-helix. The obtained results allow us to conclude that infrared spectroscopy, in addition to providing information on the composition of tested samples, can be an excellent diagnostic tool contributing to understanding the FTC substrate. Copyright © 2018. Published by Elsevier B.V.

Thyroid-stimulating hormone pituitary adenomas.

PubMed

Clarke, Michelle J; Erickson, Dana; Castro, M Regina; Atkinson, John L D

2008-07-01

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare, representing < 2% of all pituitary adenomas. The authors conducted a retrospective analysis of patients with TSH-secreting or clinically silent TSH-immunostaining pituitary tumors among all pituitary adenomas followed at their institution between 1987 and 2003. Patient records, including clinical, imaging, and pathological and surgical characteristics were reviewed. Twenty-one patients (6 women and 15 men; mean age 46 years, range 26-73 years) were identified. Of these, 10 patients had a history of clinical hyperthyroidism, of whom 7 had undergone ablative thyroid procedures (thyroid surgery/(131)I ablation) prior to the diagnosis of pituitary adenoma. Ten patients had elevated TSH preoperatively. Seven patients presented with headache, and 8 presented with visual field defects. All patients underwent imaging, of which 19 were available for imaging review. Sixteen patients had macroadenomas. Of the 21 patients, 18 underwent transsphenoidal surgery at the authors' institution, 2 patients underwent transsphenoidal surgery at another facility, and 1 was treated medically. Patients with TSH-secreting tumors were defined as in remission after surgery if they had no residual adenoma on imaging and had biochemical evidence of hypo-or euthyroidism. Patients with TSH-immunostaining tumors were considered in remission if they had no residual tumor. Of these 18 patients, 9 (50%) were in remission following surgery. Seven patients had residual tumor; 2 of these patients underwent further transsphenoidal resection, 1 underwent a craniotomy, and 4 underwent postoperative radiation therapy (2 conventional radiation therapy, 1 Gamma Knife surgery, and 1 had both types of radiation treatment). Two patients had persistently elevated TSH levels despite the lack of evidence of residual tumor. On pathological analysis and immunostaining of the surgical specimen, 17 patients had samples that stained positively for TSH, 8 for alpha-subunit, 10 for growth hormone, 7 for prolactin, 2 for adrenocorticotrophic hormone, and 1 for follicle-stimulating hormone/luteinizing hormone. Eleven patients (61%) ultimately required thyroid hormone replacement therapy, and 5 (24%) required additional pituitary hormone replacement. Of these, 2 patients required treatment for new anterior pituitary dysfunction as a complication of surgery, and 2 patients with preoperative partial anterior pituitary dysfunction developed complete panhypopituitarism. One patient had transient diabetes insipidus. The remainder had no change in pituitary function from their preoperative state. Thyroid-stimulating hormone-secreting pituitary lesions are often delayed in diagnosis, are frequently macroadenomas and plurihormonal in terms of their pathological characteristics, have a heterogeneous clinical picture, and are difficult to treat. An experienced team approach will optimize results in the management of these uncommon lesions.

[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.

Combining doxorubicin-nanobubbles and shockwaves for anaplastic thyroid cancer treatment: preclinical study in a xenograft mouse model.

PubMed

Marano, Francesca; Frairia, Roberto; Rinella, Letizia; Argenziano, Monica; Bussolati, Benedetta; Grange, Cristina; Mastrocola, Raffaella; Castellano, Isabella; Berta, Laura; Cavalli, Roberta; Catalano, Maria Graziella

2017-06-01

Anaplastic thyroid cancer is one of the most lethal diseases, and a curative therapy does not exist. Doxorubicin, the only drug approved for anaplastic thyroid cancer treatment, has a very low response rate and causes numerous side effects among which cardiotoxicity is the most prominent. Thus, doxorubicin delivery to the tumor site could be an import goal aimed to improve the drug efficacy and to reduce its systemic side effects. We recently reported that, in human anaplastic thyroid cancer cell lines, combining doxorubicin-loaded nanobubbles with extracorporeal shock waves, acoustic waves used in lithotripsy and orthopedics without side effects, increased the intracellular drug content and in vitro cytotoxicity. In the present study, we tested the efficacy of this treatment on a human anaplastic thyroid cancer xenograft mouse model. After 21 days, the combined treatment determined the greatest drug accumulation in tumors with consequent reduction of tumor volume and weight, and an extension of the tumor doubling time. Mechanistically, the treatment induced tumor apoptosis and decreased cell proliferation. Finally, although doxorubicin caused the increase of fibrosis markers and oxidative stress in animal hearts, loading doxorubicin into nanobubbles avoided these effects preventing heart damage. The improvement of doxorubicin anti-tumor effects together with the prevention of heart damage suggests that the combination of doxorubicin-loaded nanobubbles with extracorporeal shock waves might be a promising drug delivery system for anaplastic thyroid cancer treatment. © 2017 Society for Endocrinology.

Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-Stimulated Radioiodide Accumulation in Thyroid Cells

PubMed Central

Lakshmanan, Aparna; Doseff, Andrea I.; Ringel, Matthew D.; Saji, Motoyasu; Rousset, Bernard; Zhang, Xiaoli

2014-01-01

Background: Selectively increased radioiodine accumulation in thyroid cells by thyrotropin (TSH) allows targeted treatment of thyroid cancer. However, the extent of TSH-stimulated radioiodine accumulation in some thyroid tumors is not sufficient to confer therapeutic efficacy. Hence, it is of clinical importance to identify novel strategies to selectively further enhance TSH-stimulated thyroidal radioiodine accumulation. Methods: PCCl3 rat thyroid cells, PCCl3 cells overexpressing BRAFV600E, or primary cultured tumor cells from a thyroid cancer mouse model, under TSH stimulation were treated with various reagents for 24 hours. Cells were then subjected to radioactive iodide uptake, kinetics, efflux assays, and protein extraction followed by Western blotting against selected antibodies. Results: We previously reported that Akt inhibition increased radioiodine accumulation in thyroid cells under chronic TSH stimulation. Here, we identified Apigenin, a plant-derived flavonoid, as a reagent to further enhance the iodide influx rate increased by Akt inhibition in thyroid cells under acute TSH stimulation. Akt inhibition is permissive for Apigenin's action, as Apigenin alone had little effect. This action of Apigenin requires p38 MAPK activity but not PKC-δ. The increase in radioiodide accumulation by Apigenin with Akt inhibition was also observed in thyroid cells expressing BRAFV600E and in primary cultured thyroid tumor cells from TRβPV/PV mice. Conclusion: Taken together, Apigenin may serve as a dietary supplement in combination with Akt inhibitors to enhance therapeutic efficacy of radioiodine for thyroid cancer. PMID:24400871

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.

Size of thyroid carcinoma by histotype and variants: A population-based study in a mildly iodine-deficient area.

PubMed

Marina, Michela; Ceda, Gian Paolo; Corcione, Luigi; Sgargi, Paolo; Michiara, Maria; Silini, Enrico Maria; Ceresini, Graziano

2017-10-01

Data relating the size of thyroid cancer with histological types and variants are scarce. All incident thyroid cancer diagnosed between 2003 and 2012 in a mildly iodine-deficient area were derived from a population-based tumor registry. Undifferentiated/anaplastic thyroid cancer and incidental cases were excluded. Major diameter of thyroid cancer, as assessed by pathological examination, was stratified in classes: ≤10 mm; 11-20 mm; 21-40 mm; and >40 mm. For each class, absolute and relative frequencies of histological types were calculated. Tumors >20 mm were more frequent among follicular thyroid carcinoma (FTC) and Hürthle cell carcinoma than in other histotypes, with median size of 22.50 mm (95% confidence interval [CI] 16.71-28.29) and 25.00 mm (95% CI 17.04-32.96) in FTC and Hürthle cell carcinoma, respectively. Odds ratio for tumors >20 mm was significant for FTC and Hürthle cell carcinoma only (P < .0001). Among the histotypes and variants of differentiated thyroid cancer, FTC and Hürthle cell carcinoma are characterized by the largest size. © 2017 Wiley Periodicals, Inc.

Thyroid metastasis as initial presentation of clear cell renal carcinoma

PubMed Central

Ramírez-Plaza, César Pablo; Domínguez-López, Marta Elena; Blanco-Reina, Francisco

2015-01-01

Introduction Metastatic tumors account for 1.4–2.5% of thyroid malignancies. About 25–30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. Presentation of the case A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles “suggestive” of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. Discussion Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. Conclusion The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of “de novo” thyroid nodules in oncologic patients must be always considered and studied. PMID:25827295

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.

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.

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.

Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis.

PubMed Central

Hard, G C

1998-01-01

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation. PMID:9681969

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid

PubMed Central

Heitkötter, Birthe; Steinestel, Konrad; Trautmann, Marcel; Grünewald, Inga; Barth, Peter; Gevensleben, Heidrun; Bögemann, Martin; Wardelmann, Eva; Hartmann, Wolfgang; Rahbar, Kambiz; Huss, Sebastian

2018-01-01

Aim PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining. Results PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified. Conclusions We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer. PMID:29515776

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.

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

Overt Skeletal Metastases in a Patient of Occult (Microscopic) Follicular Thyroid Carcinoma: a Rare Case.

PubMed

Jha, Chandan Kumar; Agrawal, Vinita; Mishra, Anjali; Pradhan, P K

2018-03-01

Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways.

PubMed

Zhang, Li; Liu, Lianyong; He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang; Tian, Jianqing

2016-08-26

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar: Benign Warthin Tumor of the Thyroid.

PubMed

Peckova, Kvetoslava; Daum, Ondrej; Michal, Michael; Curcikova, Radmila; Michal, Michal

2016-09-01

We report on an exceedingly rare lesion of the thyroid probably of a branchial cleft origin, which was not published in the world literature before. A 58-year-old woman underwent a total thyroidectomy for bilateral goiter. Grossly, there was one yellowish nodule sized 15 mm in the largest dimension found in the right lobe. Microscopically, the thyroid parenchyma showed signs of Hashimoto thyroiditis. The nodule in the right lobe was composed of a part of solid cell nests appearance, another part resembling a branchial cleft cyst, and a part resembling Warthin tumor. This lesion may belong to the histogenetically similar group of entities in the head and neck region which are derived from branchial cleft derivatives and which, under the inflammatory influence, have the ability to a cystic dilatation and proliferation of the epithelial component. The epithelium can afterwards become papillary and may undergo oncocytic transformation, thus gaining features that impart the resemblance of a Warthin tumor. Club members generally agreed with a submitted diagnosis of benign Warthin tumor of the thyroid.

“Nodule in Nodule” on Thyroid Ultrasonography: Possibility of Follicular Carcinoma Transformed from Benign Thyroid Tumor

PubMed Central

Kobayashi, Kaoru; Ota, Hisashi; Hirokawa, Mitsuyoshi; Yabuta, Tomonori; Fukushima, Mitsuhiro; Masuoka, Hiroo; Higashiyama, Takuya; Kihara, Minoru; Ito, Yasuhiro; Miya, Akihiro; Miyauchi, Akira

2017-01-01

Background It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. Case Description Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a “nodule in nodule” appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a “nodule in nodule” appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. Conclusion A small number of patients with follicular carcinomas or follicular neoplasms may present with a “nodule in nodule” appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis. PMID:28589092

Thyroid Cancer and Tumor Collaborative Registry (TCCR).

PubMed

Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

2016-01-01

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.

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.

The yield of adequate and conclusive fine-needle aspiration results in thyroid nodules is uniform across functional and goiter types.

PubMed

Liel, Y

1999-01-01

Relatively little is known about the cytological characteristics of hyperfunctioning (hot) thyroid nodules. Concern has been expressed that fine-needle aspiration (FNA) identifies hot nodules as follicular tumors or indeterminate, and as a consequence patients could be unnecessarily referred for surgery. Between 1979 and 1996, thyroid FNA was performed on 829 patients. Result of thyroid scan was available in 326; 69 (21%) patients had hot, and 257 (79%) had warm or cold thyroid nodules. Nodules in each of these major groups were divided into 2 subgroups: clinically solitary nodules and dominant nodules in multinodular goiters (MNG). The frequencies of adequate versus inadequate FNA samples, and of conclusive versus indeterminate FNA results were determined separately for each of the groups and subgroups. In addition, patients with hot nodules and overt hyperthyroidism were identified and evaluated separately. Bivariate analyses were performed for the frequency of adequate versus inadequate smears and conclusive versus indeterminate results between hot, toxic, and cold-warm nodules, and between solitary nodules and MNG. The frequency of adequate aspirations and conclusive results in the various groups and subgroups was found to be statistically indistinguishable. In conclusion, the yield of adequate samples and the rate of conclusive results of FNA in thyroid nodules is similar, irrespective of the functional state or of goiter presentation. Hot thyroid nodules do not seem to produce an increase in the rate of inadequate or indeterminate FNA results, and therefore, do not affect the overall performance of thyroid FNA.

Ultrasound-guided fine-needle aspiration biopsy of the thyroid.

PubMed

Tambouret, R; Szyfelbein, W M; Pitman, M B

1999-10-25

We reviewed the Massachusetts General Hospital experience with ultrasound-guided fine-needle aspiration biopsies (FNABs) of the thyroid to determine the indications, rate of unsatisfactory smears, correlation with excisional biopsy results, and verification of efficient use of personnel time. All radiologically guided FNABs of the thyroid from January 1993 through June 1997 were reviewed. As a measure of efficient use of technologist time, a sample of times spent by the technologist during the procedure for 20 cases in 1993 and 1997 was compared with that of an equal number of random nonthyroid image guided FNABs. Two hundred-ninety FNABs were identified in 251 patients, representing 12% of all thyroid FNABs and 11% of all radiologically guided FNABs. Indications in the 251 patients included multiple nodules (78), solitary nodules (61), complex nodules (39), prior failed FNAB (39), thyroid bed abnormalities post-thyroidectomy (21), difficult access (7), and investigation of recurrent tumor in residual thyroid lobe (6). Available records indicated 118 lesions were palpable and 45 were nonpalpable; the physical examination characteristics of the remainder (88) were not stated. Diagnoses included 44 unsatisfactory cases (15%), 103 macrofollicular lesions, 20 microfollicular lesions, 26 mixed macro/microfollicular lesions, 5 oxyphilic lesions, 1 trabecular pattern, 15 nonspecific follicular cell pattern, 9 follicular cell atypia, 30 cysts, 11 thyroiditis, 23 malignant tumors, and 3 other (1 parathyroid, 2 lymph node). Eighty-nine FNABs from 76 patients had subsequent surgical biopsy. Excisional biopsies in 14 unsatisfactory FNABs were benign. In the remaining 75 FNABs from 67 patients, 18 malignancies on FNAB were correctly diagnosed, but 3 other papillary carcinomas were only qualified as atypical follicular cells on cytology. No false-positive cases occurred. Of 15 macrofollicular lesions on cytology, 10 were adenomas on excision, only 2 of which were microfollicular adenomas, and 4 were adenomatous nodules. An aspirate of a parathyroid adenoma was misinterpreted as a macrofollicular lesion of the thyroid. Three microfollicular lesions on FNAB proved to be nodular hyperplasia on excision, and the other 11 were adenomas, 5 of them microfollicular. Average technologist time was significantly longer for thyroid FNABs than nonthyroid FNABs in 1993, but in the 1997 sample no significant difference was identified. Radiologically guided FNAB of the thyroid is a clinically useful procedure with a high correlation between benign lesions not needing excision (macrofollicular), and lesions that need excision (microfollicular/oxyphilic cell or malignant). Technologist time needed for immediate evaluation tends to decrease with increasing operator experience. Cancer (Cancer Cytopathol) Copyright 1999 American Cancer Society.

American Thyroid Association statement on preoperative imaging for thyroid cancer surgery.

PubMed

Yeh, Michael W; Bauer, Andrew J; Bernet, Victor A; Ferris, Robert L; Loevner, Laurie A; Mandel, Susan J; Orloff, Lisa A; Randolph, Gregory W; Steward, David L

2015-01-01

The success of surgery for thyroid cancer hinges on thorough and accurate preoperative imaging, which enables complete clearance of the primary tumor and affected lymph node compartments. This working group was charged by the Surgical Affairs Committee of the American Thyroid Association to examine the available literature and to review the most appropriate imaging studies for the planning of initial and revision surgery for thyroid cancer. Ultrasound remains the most important imaging modality in the evaluation of thyroid cancer, and should be used routinely to assess both the primary tumor and all associated cervical lymph node basins preoperatively. Positive lymph nodes may be distinguished from normal nodes based upon size, shape, echogenicity, hypervascularity, loss of hilar architecture, and the presence of calcifications. Ultrasound-guided fine-needle aspiration of suspicious lymph nodes may be useful in guiding the extent of surgery. Cross-sectional imaging (computed tomography with contrast or magnetic resonance imaging) may be considered in select circumstances to better characterize tumor invasion and bulky, inferiorly located, or posteriorly located lymph nodes, or when ultrasound expertise is not available. The above recommendations are applicable to both initial and revision surgery. Functional imaging with positron emission tomography (PET) or PET-CT may be helpful in cases of recurrent cancer with positive tumor markers and negative anatomic imaging.

American Thyroid Association Statement on Preoperative Imaging for Thyroid Cancer Surgery

PubMed Central

Bauer, Andrew J.; Bernet, Victor A.; Ferris, Robert L.; Loevner, Laurie A.; Mandel, Susan J.; Orloff, Lisa A.; Randolph, Gregory W.; Steward, David L.

2015-01-01

Background: The success of surgery for thyroid cancer hinges on thorough and accurate preoperative imaging, which enables complete clearance of the primary tumor and affected lymph node compartments. This working group was charged by the Surgical Affairs Committee of the American Thyroid Association to examine the available literature and to review the most appropriate imaging studies for the planning of initial and revision surgery for thyroid cancer. Summary: Ultrasound remains the most important imaging modality in the evaluation of thyroid cancer, and should be used routinely to assess both the primary tumor and all associated cervical lymph node basins preoperatively. Positive lymph nodes may be distinguished from normal nodes based upon size, shape, echogenicity, hypervascularity, loss of hilar architecture, and the presence of calcifications. Ultrasound-guided fine-needle aspiration of suspicious lymph nodes may be useful in guiding the extent of surgery. Cross-sectional imaging (computed tomography with contrast or magnetic resonance imaging) may be considered in select circumstances to better characterize tumor invasion and bulky, inferiorly located, or posteriorly located lymph nodes, or when ultrasound expertise is not available. The above recommendations are applicable to both initial and revision surgery. Functional imaging with positron emission tomography (PET) or PET-CT may be helpful in cases of recurrent cancer with positive tumor markers and negative anatomic imaging. PMID:25188202

Thyroid cancer profile in Mures County (Romania): a 20 years study.

PubMed

Cătană, Ramona; Boilă, Adela; Borda, Angela

2012-01-01

The aim of the present study was to present data on frequency of thyroid cancer in Mures County (Romania) and border counties, a goiter endemic area, and to analyze its histopathological characteristics, over a 20 years period (1990-2009). Demographic, clinical and pathological data were obtained from database registries. Histological subtypes of thyroid cancer were classified according to the WHO criteria (sixth edition, 2004) in the following categories: papillary thyroid carcinoma with its histological subtypes, follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, undifferentiated thyroid carcinoma, medullary carcinoma, lymphoma, metastatic tumors. Our analyze included 524 cases of thyroid cancer of the 3460 surgical thyroid specimens resected between 1990-2009: 410 (78.2%) cases of papillary carcinoma, 19 (3.6%) cases of follicular carcinoma, 24 (4.6%) cases of poorly differentiated carcinoma, 33 (6.3%) cases of undifferentiated carcinoma, 22 (4.1%) medullary carcinomas, eight (1.6%) lymphomas, and eight (1.6%) metastatic tumors. Papillary thyroid carcinoma is the most common histological form (78%) and an increasing incidence of this form was observed. A statistical significant increase in the incidence of the follicular variant of papillary carcinoma was noticed between 2000-2009, compared to 1990-2000. An increased incidence of small tumors was also found (6.66%, 1990-1999 vs. 23.5%, 2000-2009). The undifferentiated thyroid cancer had a marked decreasing trend (20%, 1990-1999 vs. 3.45%, 2000-2009). Our study demonstrates an increasing trend in the incidence of thyroid cancer in the last 20 years. This increase is mainly due to the small papillary cancers, by contrast to the undifferentiated thyroid cancers that have a decreasing trend. A better understanding and description of the morphological criteria could explained the increasing incidence of the follicular variant of papillary carcinoma.

The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors.

PubMed

Woodmansee, W W; Gordon, D F; Dowding, J M; Stolz, B; Lloyd, R V; James, R A; Wood, W M; Ridgway, E C

2000-07-01

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.

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

Gao, Xuemei; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells bymore » JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.« less

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

Extrathyroidal Extension Is Associated with Compromised Survival in Patients with Thyroid Cancer.

PubMed

Youngwirth, Linda M; Adam, Mohamed A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-05-01

Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer. The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors <4 cm), and extensive ETE (T4 tumors <4 cm). Patient demographic, clinical, and pathologic factors were evaluated for all patients. A Cox proportional hazards model was developed for each histology to identify factors associated with survival. In total, 241,118 patients with differentiated thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p < 0.01). After adjustment, minimal ETE (hazard ratio [HR] = 1.13; p < 0.01) and extensive ETE (HR = 1.74; p < 0.01) were associated with compromised survival for patients with differentiated thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p < 0.01). After adjustment, extensive ETE (HR = 1.63; p = 0.01) was associated with compromised survival for patients with medullary thyroid cancer. In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma.

PubMed

Urie, Bridget K; Russell, Duncan S; Kisseberth, William C; London, Cheryl A

2012-05-25

Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib's activity.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma

PubMed Central

2012-01-01

Background Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. Results mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. Conclusions Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib’s activity. PMID:22630170

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-04-18

BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; RAS Family Gene Mutation; Recurrent Thyroid Gland Carcinoma; 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

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.

Conservative multimodal management of a primitive neuroectodermal tumor of the thyroid.

PubMed

Natale, Romain; Thariat, Juliette; Vedrine, Pierre Olivier; Bozec, Alex; Peyrottes, Isabelle; Marcy, Pierre Yves; Haudebourg, Juliette; Pedeutour, Florence; Saâda, Esma; Thyss, Antoine

2013-04-15

Primitive neuroectodermal tumors (PNET) represent 1% of sarcomas. Head and neck peripheral PNETs have an intermediate prognosis between abdominopelvic disease and extremities. We here report the case of a 40-year old male who presented with primitive neuroectodermal tumor of the thyroid and was treated by multimodal treatment, including surgery, chemotherapy and intermediate dose radiotherapy. The patient is alive and fit with a functional larynx at 27 months. Multimodal treatments yield five-year survival rates of about 60%. Major drug regimens use vincristine, doxorubicin, ifosfamide or cyclophosphamide, dactinomycin and/or etoposide. Complete surgical excision is undertaken whenever possible to improve long-term survival. However, the relative radiosensitivity of tumors of the Ewing family, suggest multimodal treatment including adjuvant conformal radiotherapy in case of positive margins or poor response to chemotherapy rather than resection with 2-3 cm margins, which would imply laryngeal sacrifice for thyroid tumors. The role of expert rare tumor networks is crucial for optimal decision-making and management of such rare tumors on a case by case basis.

[Follicular thyroid tumor as a diagnostic and therapeutic problem].

PubMed

Król, Robert; Heitzman, Marek; Pawlicki, Jacek; Ziaja, Jacek; Cierpka, Lech

2004-01-01

Although the appearance of follicular thyroid tumors in the population is high, only a small part of them are malignant. Follicular tumors are built of follicular epithelial cells and are encapsulated. Cell atypia differentiates follicular adenoma from cancer. Follicular cancer is characterized by vascular invasion and causes metastases through blood vessels, mainly to lungs and bones. In the diagnosis of follicular thyroid neoplasm, pathological examination of postoperative material plays a leading role. In diagnosis before surgical treatment, physical examination, ultrasound (USG), and fine needle aspiration biopsy (FNAB) are of great importance. The choice of treatment in patients in which follicular neoplasm has been diagnosed by FNAB awakes controversies. In practice it is impossible to determine reliably before surgery whether the lesion is malignant or not. Because of the rare incidence of thyroid cancer in the general population, more and more authors tend to decide on partial resection of the thyroid gland and possible radicalization if cancer is diagnosed on paraffin specimen examination.

Primary Squamous Cell Carcinoma of the Thyroid: A Population-Based Analysis.

PubMed

Au, Joshua K; Alonso, Jose; Kuan, Edward C; Arshi, Armin; St John, Maie A

2017-07-01

Objectives To analyze the epidemiology and describe the prognostic indicators of patients with primary squamous cell carcinoma of the thyroid. Study Design and Setting Retrospective cohort study based on a national database. Methods The US National Cancer Institute's SEER registry (Surveillance, Epidemiology, and End Results) was reviewed for patients with primary squamous cell carcinoma of the thyroid from 1973 to 2012. Study variables included age, sex, race, tumor size, tumor grade, regional and distant metastases, and treatment modality. Survival measures included overall survival (OS) and disease-specific survival (DSS). Results A total of 199 cases of primary squamous cell carcinoma of the thyroid were identified. Mean age at diagnosis was 68.1 years; 58.3% were female; and 79.4% were white. Following diagnosis, 46.3% of patients underwent surgery; 55.7%, radiation therapy; and 45.8%, surgery with radiation therapy. Kaplan-Meier analysis demonstrated OS and DSS of 16% and 21% at 5 years, respectively. Median survival after diagnosis was 9.1 months. Multivariate Cox regression analysis showed that predictors of OS and DSS included age ( P < .001, P < .001, respectively), tumor grade ( P < .001, P = .001), and tumor size ( P < .001, P = .001). Surgical management was a predictor of OS but not DSS. Conclusion Squamous cell carcinoma of the thyroid is a rare malignancy with a very poor prognosis. Surgical resection confers an overall survival benefit. Age, tumor grade, and tumor size are predictors of OS and DSS.

Cathepsin D in normal and neoplastic thyroid tissues.

PubMed

Kraimps, J L; Métayé, T; Millet, C; Margerit, D; Ingrand, P; Goujon, J M; Levillain, P; Babin, P; Begon, F; Barbier, J

1995-12-01

Cathepsin D is a widely distributed lysosomal acidic endopeptidase. It is an estrogen-regulated protein that is a prognostic factor in breast cancer. The aim of this study was to measure cathepsin D concentrations in thyroid tissues and to correlate these concentrations with clinical and pathologic parameters. Cathepsin D and thyroglobulin concentrations were measured in the cytosol of normal thyroid tissues (n = 14), benign nodules (n = 6), and thyroid carcinomas (n = 32) with an immunoradiometric assay. Statistical analysis was based on the Kruskal-Wallis and Wilcoxon tests and on the Spearman rank correlation coefficient. The mean level of cathepsin D, expressed as picomoles per milligram protein minus thyroglobulin, was higher in the 32 carcinomas, 29.1 +/- 15.5, than in the 14 normal thyroid tissues, 8.4 +/- 2.5 (p < 0.001) or in the 6 benign nodules, 11.2 +/- 7.3 (p = 0.003). Cathepsin D concentrations correlated with tumor size; Spearman rank correlation coefficient was rs = 0.44 (p = 0.012). No significant difference was found regarding histologic type. Cathepsin D concentrations were inversely correlated with the thyroglobulin level in the tumor; Spearman rank correlation coefficient was rs = -0.60 (p < 0.001). Cathepsin D concentration is higher in thyroid carcinoma than in normal thyroid tissue. Increased cathepsin D concentrations correlate with thyroid tumor size but not with histologic type. Further studies should be done to confirm the potential prognostic value of cathepsin D in patients with thyroid carcinomas.

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

Increasing incidence of thyroid cancer in the Commonwealth of Pennsylvania.

PubMed

Bann, Darrin V; Goyal, Neerav; Camacho, Fabian; Goldenberg, David

2014-12-01

The incidence of thyroid cancer in the United States has increased rapidly and Pennsylvania is the state with the highest rate of thyroid cancer in the country, although the factors driving this increase are unknown. Moreover, it remains unclear whether the increase in thyroid cancer represents a true increase in disease or is the result of overdiagnosis. To compare the increase in thyroid cancer incidence and tumor characteristics in Pennsylvania with the rest of the United States and gain insight into the factors influencing the increased incidence of thyroid cancer. In a population-based study, data on thyroid cancer from the Surveillance Epidemiology and End Results 9 (SEER-9) registry and the Pennsylvania Cancer Registry (PCR) from 1985 through 2009 were collected and reviewed for information regarding sex, race, histologic type of thyroid cancer, staging, and tumor size at diagnosis. International Classification of Diseases for Oncology, Third Edition code C739 (thyroid carcinoma) was used to identify 110,615 records in the SEER-9 registry and 29,030 records in the PCR. Average annual percent change (AAPC) in thyroid cancer incidence across various demographic groups in Pennsylvania. The AAPC for thyroid cancer in Pennsylvania was 7.1% per year (95% CI, 6.3%-7.9%) vs 4.2% (95% CI, 3.7%-4.7%) per year in the remainder of the United States, and trends in incidence were significantly different (P < .001). Females experienced a higher AAPC (7.6% per year; 95% CI, 6.9%-8.3%) compared with males (6.1% per year; 95% CI, 4.9%-7.2%) (P < .01), and trend analysis revealed that thyroid cancer may be increasing more rapidly among black females (8.6% per year; 95% CI, 5.4%-11.9%) than among white females (7.6% per year; 95% CI, 6.8%-8.4) (P = .60; but despite the similarity in AAPC between the 2 groups, the joinpoint models fit to the data were not parallel [P < .005]). The rate of tumors with regional (7.0% per year; 95% CI, 5.8%-8.1%) or distant (1.1% per year; 95% CI, 0.3%-1.8%) spread (P < .05) and tumors that were 2 to 4 cm (7.1% per year; 95% CI, 5.2%-9.0%) (P < .05) or larger than 4 cm (6.4% per year; 95% CI, 4.5%-8.2%) (P < .05) at diagnosis also increased. The incidence of thyroid cancer is rising at a faster rate in Pennsylvania than in the rest of the nation, as is the rate of tumors that are larger and higher stage at diagnosis. These findings suggest that rising disease burden has contributed to the increased incidence of thyroid cancer. Etiologic factors promoting the rise in thyroid cancer in Pennsylvania must be investigated and may provide insight into the drivers of the national increase in thyroid cancer.

A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat

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

Finch, John M.; Osimitz, Thomas G.; Gabriel, Karl L.

2006-08-01

Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and for 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbitalmore » (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased thyroid gland weights, which were associated with follicular cell hypertrophy. Thyroid follicular cell replicative DNA synthesis was increased by treatment with Pyrethrins and NaPB for 7 and/or 14 days. Treatment with Pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T{sub 4}) and/or triiodothyronine (T{sub 3}). The effects of Pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of Pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.« less

Primary thyroid leiomyosarcoma: a case report and review of the literature

PubMed Central

CANU, G.L.; BULLA, J.S.; LAI, M.L.; MEDAS, F.; BAGHINO, G.; ERDAS, E.; MARIOTTI, S.

2018-01-01

Primary thyroid leiomyosarcoma (LMS) is an extremely rare tumor. We report a case of a 47-year-old male with a rapidly growing neck mass and disfagia. Preoperative investigations were diagnostic of anaplastic carcinoma. Total thyroidectomy with partial esophagectomy and dissection of right infrahyoid muscles was performed. Through histolological and immunohistochemical evaluations a primary thyroid high-grade LMS was diagnosed. At 2 months of follow-up a local recurrence was detected and consequently the patient was submitted to chemotherapy with partial response. He is still alive 9 months after surgery. Diagnosis of primary thyroid LMS is difficult due to its similarity to other more common thyroid tumors. To date, there is no standard therapy and prognosis is poor. PMID:29549682

Primary thyroid leiomyosarcoma: a case report and review of the literature.

PubMed

Canu, G L; Bulla, J S; Lai, M L; Medas, F; Baghino, G; Erdas, E; Mariotti, S; Calò, P G

2018-01-01

Primary thyroid leiomyosarcoma (LMS) is an extremely rare tumor. We report a case of a 47-year-old male with a rapidly growing neck mass and disfagia. Preoperative investigations were diagnostic of anaplastic carcinoma. Total thyroidectomy with partial esophagectomy and dissection of right infrahyoid muscles was performed. Through histolological and immunohistochemical evaluations a primary thyroid high-grade LMS was diagnosed. At 2 months of follow-up a local recurrence was detected and consequently the patient was submitted to chemotherapy with partial response. He is still alive 9 months after surgery. Diagnosis of primary thyroid LMS is difficult due to its similarity to other more common thyroid tumors. To date, there is no standard therapy and prognosis is poor.

The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

PubMed Central

Matos, Leandro Luongo; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Trufelli, Damila Cristina; Melo, Carina Mucciolo; Garcia, Larissa Ferraz; Oliveira, Olivia Capela Grimaldi; Matos, Maria Graciela Luongo; Kanda, Jossi Ledo; Nader, Helena Bonciani; Martins, João Roberto Maciel; Pinhal, Maria Aparecida Silva

2015-01-01

Introduction The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions. Methods HPSE and HPSE2 expression by qRT-PCR, immunohistochemistry evaluation, western blot analysis and HPSE enzymatic activity were evaluated. Results The expression of heparanases by qRT-PCR showed an increase of HPSE2 in thyroid carcinoma (P = 0.001). HPSE activity was found to be higher in the malignant neoplasms than in the benign tumors (P<0.0001). On Western blot analysis, HPSE2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P<0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100%, showing itself to be an accurate test for distinguishing between malignant and benign lesions. Conclusions This study shows, for the first time, a distinct profile of HPSE expression in thyroid carcinoma suggesting its role in carcinogenesis. PMID:26488476

Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors.

PubMed

Mei, Wenhan; Wang, Kemin; Huang, Jian; Zheng, Xinmin

2016-01-01

Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail. Although PTP1BΔE6 revealed no phosphatase activity compared with wild-type PTP1B and the PTP1BΔE5 mutant, its expression induced oncogenic transformation of rat fibroblasts without Src activation, indicating that it involved signaling pathways independent of Src. The transformed cells were tumourigenic in nude mice, suggesting that the PTP1BΔE6 affected other molecule(s) in the human tumors. These observations may provide a novel therapeutic target for colon and thyroid cancer.

Thyroid Cancer and Tumor Collaborative Registry (TCCR)

PubMed Central

Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B.; Sherman, Simon

2016-01-01

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer

PubMed Central

Severson, Jill J.; Serracino, Hilary S.; Mateescu, Valerica; Raeburn, Christopher D.; C.McIntyre, Robert; Sams, Sharon B.; Haugen, Bryan R.; French, Jena D.

2015-01-01

Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node (LN) metastases persist for years, generally without progression to distant metastases. While the immune system likely impedes disease progression, it is unsuccessful in eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)+ T cells were enriched in tumor-involved lymph nodes (TILN). Tumor-associated leukocytes and tumor cells were collected from grossly involved LNs from 12 patients to further characterize the phenotype and functional potential of mDTC-associated PD-1+ T cells. PD-1+CD4+ and PD-1+CD8+ T cells were enriched in 8/12 TILN samples. PD-1+ T cells co-expressed Tim-3 and CD69 and failed to down-regulate CD27. CD8+ T cells, but not CD4+ T cells, from these samples were variably deficient in their ability to produce effector cytokines when compared to control TILNs that lacked resident PD-1+ T cells. PD-1+CD8+ T cells were capable of exocytosis but lacked intracellular perforin. Surprisingly, T-cell proliferative capacity was largely maintained in all samples. Thus, while PD-1 expression by mDTC-associated CD8+ T cells was associated with dysfunction, exhaustion was not complete. Notably, molecular markers of exhaustion did not translate to dysfunction in all samples or in CD4+ T cells. Regulatory T (Treg) cells, PD-L1, and galectin-9 were commonly found in mDTC and likely contributed to the initiation of T-cell exhaustion and disease progression. Therapies that release the effects of PD-1 and Tim-3 and reduce the suppressive effects of Tregs may encourage tumor elimination in patients with mDTC. PMID:25701326

Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results.

PubMed

Castelblanco, Esmeralda; Gallel, Pilar; Ros, Susana; Gatius, Sonia; Valls, Joan; De-Cubas, Aguirre A; Maliszewska, Agnieszka; Yebra-Pimentel, M Teresa; Menarguez, Javier; Gamallo, Carlos; Opocher, Giuseppe; Robledo, Mercedes; Matias-Guiu, Xavier

2012-07-01

Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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.

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.

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

PubMed Central

Park, Jeong Won; Han, Cho Rong; Zhao, Li; Willingham, Mark C.; Cheng, Sheue-yann

2015-01-01

Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (ThrbPV/PVPten+/− mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. Wild type and ThrbPV/PVPten+/− mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition. S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase (CDK) 4, CDK 6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated ThrbPV/PVPten+/− mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated ThrbPV/PVPten+/− mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of epithelial-mesenchymal transition. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer. PMID:26552408

Preclinical Imaging for the Study of Mouse Models of Thyroid Cancer

PubMed Central

Greco, Adelaide; Orlandella, Francesca Maria; Iervolino, Paola Lucia Chiara; Klain, Michele; Salvatore, Giuliana

2017-01-01

Thyroid cancer, which represents the most common tumors among endocrine malignancies, comprises a wide range of neoplasms with different clinical aggressiveness. One of the most important challenges in research is to identify mouse models that most closely resemble human pathology; other goals include finding a way to detect markers of disease that common to humans and mice and to identify the most appropriate and least invasive therapeutic strategies for specific tumor types. Preclinical thyroid imaging includes a wide range of techniques that allow for morphological and functional characterization of thyroid disease as well as targeting and in most cases, this imaging allows quantitative analysis of the molecular pattern of the thyroid cancer. The aim of this review paper is to provide an overview of all of the imaging techniques used to date both for diagnosis and theranostic purposes in mouse models of thyroid cancer. PMID:29258188

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

Intake of Boron, Cadmium, and Molybdenum enhances rat thyroid cell transformation.

PubMed

Luca, Emilia; Fici, Laura; Ronchi, Anna; Marandino, Ferdinando; Rossi, Esther Diana; Caristo, Maria Emiliana; Malandrino, Pasqualino; Russo, Marco; Pontecorvi, Alfredo; Vigneri, Riccardo; Moretti, Fabiola

2017-06-02

Epidemiologic data in volcanic areas suggest that environmental factors might be involved in the increase of thyroid cancer (TC) incidence. Recent reports indicate that several heavy metals and metalloids are increased in volcanic areas. This study aims to evaluate the combined effect of three of these elements Boron (B), Cadmium (Cd), and Molybdenum (Mo) - all increased in the volcanic area of Mt. Etna, in Italy - on thyroid tumorigenesis in the rat. Female Wistar rats prone to develop thyroid tumors by low-iodine diet and methimazole treatment received ad libitum drinking water supplemented with B, Cd, and Mo at concentrations in the range found in the urine samples of residents of the volcanic area. At 5 and 10 months animals were euthanized, and their thyroid analysed. Statistical analysis was performed with a 2-way unpaired t-test. No toxic effect of the three elements on the growth of the animals was observed. A significant increase of histological features of transformation was observed in thyroid follicular cells of rats treated with B, Cd, and Mo compared with those of control group. These abnormalities were associated with decreased iodine content in the thyroid. This study provides the evidence that slightly increased environmental concentrations of B, Cd, and Mo can accelerate the appearance of transformation marks in the thyroid gland of hypothyroid rats.

[Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

PubMed

Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

2014-01-01

The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

Unusual Metastasis of Medullary Thyroid Carcinoma to the Breast: A Cytological and Histopathological Correlation

PubMed Central

Tanwar, Parul; Gandhi, Jatin S; Sharma, Anila; Gupta, Manoj; Choudhary, Partha S

2018-01-01

Breast metastases are a relatively rare condition and account for approximately 0.5–2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC) are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging. We present the case of a 45-year-old female presenting with a lump breast, which was later found out to be metastasis from medullary carcinoma thyroid. PMID:29643661

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma and Graves' disease.

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

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.

Increasing Incidence of Thyroid Cancer in the Commonwealth of Pennsylvania

PubMed Central

Bann, Darrin V.; Goyal, Neerav; Camacho, Fabian; Goldenberg, David

2015-01-01

IMPORTANCE The incidence of thyroid cancer in the United States has increased rapidly and Pennsylvania is the state with the highest rate of thyroid cancer in the country, although the factors driving this increase are unknown. Moreover, it remains unclear whether the increase in thyroid cancer represents a true increase in disease or is the result of overdiagnosis. OBJECTIVE To compare the increase in thyroid cancer incidence and tumor characteristics in Pennsylvania with the rest of the United States and gain insight into the factors influencing the increased incidence of thyroid cancer. DESIGN, SETTING, AND PARTICIPANTS In a population-based study, data on thyroid cancer from the Surveillance Epidemiology and End Results 9 (SEER-9) registry and the Pennsylvania Cancer Registry (PCR) from 1985 through 2009 were collected and reviewed for information regarding sex, race, histologic type of thyroid cancer, staging, and tumor size at diagnosis. International Classification of Diseases for Oncology, Third Edition code C739 (thyroid carcinoma) was used to identify 110 615 records in the SEER-9 registry and 29 030 records in the PCR. MAIN OUTCOMES AND MEASURES Average annual percent change (AAPC) in thyroid cancer incidence across various demographic groups in Pennsylvania. RESULTS The AAPC for thyroid cancer in Pennsylvania was 7.1% per year (95% CI, 6.3%–7.9%) vs 4.2% (95% CI, 3.7%–4.7%) per year in the remainder of the United States, and trends in incidence were significantly different (P < .001). Females experienced a higher AAPC (7.6% per year; 95% CI, 6.9%–8.3%) compared with males (6.1% per year; 95% CI, 4.9%–7.2%) (P < .01), and trend analysis revealed that thyroid cancer may be increasing more rapidly among black females (8.6% per year; 95% CI, 5.4%–11.9%) than among white females (7.6% per year; 95% CI, 6.8%–8.4) (P = .60; but despite the similarity in AAPC between the 2 groups, the joinpoint models fit to the data were not parallel [P < .005]). The rate of tumors with regional (7.0% per year; 95% CI, 5.8%–8.1%) or distant (1.1% per year; 95% CI, 0.3%–1.8%) spread (P < .05) and tumors that were 2 to 4 cm (7.1% per year; 95% CI, 5.2%–9.0%) (P < .05) or larger than 4 cm (6.4% per year; 95% CI, 4.5%–8.2%) (P < .05) at diagnosis also increased. CONCLUSIONS AND RELEVANCE The incidence of thyroid cancer is rising at a faster rate in Pennsylvania than in the rest of the nation, as is the rate of tumors that are larger and higher stage at diagnosis. These findings suggest that rising disease burden has contributed to the increased incidence of thyroid cancer. Etiologic factors promoting the rise in thyroid cancer in Pennsylvania must be investigated and may provide insight into the drivers of the national increase in thyroid cancer. PMID:25170647

Effects of Phenobarbital and Carbazole on Carcinogenesis of the Lung, Thyroid, Kidney, and Bladder of Rats Pretreated with N‐Bis(2‐hydroxypropyl)nitrosamine

PubMed Central

Masuda, Atsuko; Imaida, Katsumi; Ogiso, Tadashi; Ito, Nobuyuki

1988-01-01

Studies were made on potential modifying effects of phenobarbital (PB) and carbazole on tumor development induced by N‐bis(2‐hydroxypropyl)nitrosamine (DHPN), a wide‐spectrum carcinogen in rats. Effects on the lung, thyroid, kidney, bladder and liver were investigated. Male F344 rats were given 0.2% DHPN in their drinking water for 1 week and then 0.05% PB or 0.6% carbazole in their diet for 50 weeks. Control animals were treated with either DHPN or PB or carbazole only. Neither PB nor carbazole affected the incidence or histology of lung tumors. However, PB promoted the development of thyroid tumors and preneoplastic lesions of the liver, while carbazole promoted the induction of renal pelvic tumors. PMID:3133336

Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

PubMed Central

Antonello, ZA; Nucera, C

2015-01-01

Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for combinatorial approaches, which are expected to take place in the upcoming human thyroid cancer basic and clinical research. PMID:24362526

Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients.

PubMed

Schlumberger, Martin; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Bidart, Jean-Michel

2007-03-01

The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

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.

Tumors masquerading in patients with thyroid eye disease.

PubMed

Griepentrog, Gregory J; Burkat, Cat N; Kikkawa, Don O; Lucarelli, Mark J

2013-08-01

Thyroid eye disease (TED) is the most common cause of proptosis in adults. The external manifestations of TED are characteristic and the diagnosis is typically made without imaging. Although there are multiple descriptions of primary and secondary orbital tumors initially mistaken for TED in the literature, there are limited reports detailing the findings of patients with long-standing TED whom developed an orbital tumor at a later date. Herein, we present a 6-year retrospective multi-center report of three patients with long-standing TED who developed an initially unsuspected orbital or cavernous sinus tumor.

Modulation of Sodium Iodide Symporter in Thyroid Cancer

PubMed Central

Lakshmanan, Aparna; Scarberry, Daniel

2015-01-01

Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future. PMID:25234361

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.

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.

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.

A phase II study tests a new drug for patients with advanced thyroid cancer | Center for Cancer Research

Cancer.gov

A phase II trial of CUDC-907, a new drug that may be able to shrink thyroid tumors that have spread or gotten worse, is being tested in metastatic or advanced thyroid cancer.  Currently, there is no standard or effective treatment for the most aggressive types of thyroid cancer such as anaplastic and poorly differentiated thyroid cancer.  Learn more...

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

Hashimoto thyroiditis onset after laparoscopic removal of struma ovarii: an overview to unravel a rare and intriguing finding.

PubMed

Laganà, A S; Santoro, G; Triolo, O; Giacobbe, V; Certo, R; Palmara, V

2015-01-01

Struma ovarii is an uncommon type of ovarian tumor derived by germinal cells, characterized by the predominance of thyroid tissue (> 50%); 90-95% of these formations are benign and mainly affect the left ovary, while in 6% of the cases struma ovarii is bilateral. The malignant transformation is a rare condition that often occurs after 50 years. In most instances, diagnosis of malignant struma ovarii is made postoperatively during histological analysis. This tumor appears to derive by one germinal cell through loss of heterozygosity of the androgen receptor gene and of the X chromosome. Clinical symptoms comprise abdominopelvic mass, lower abdominal pain, abnormal vaginal bleeding, and ascites (the occurrence of this condition has been observed in one-third of the cases). The patients with struma ovarii generally do not manifest symptoms related to thyroid hyperfunction, reported only in 8% of the cases, and due to hyperstimulation of the thyroid by auto-antibodies. Thyroid tissue of the struma ovarii, often embedded in a teratoma, may be papillary, follicular or with mixed pattern and it can include elements of mucinous cystoadenomas, Brenner's tumor or carcinoid or melanomas cells. Here the authors report their experience with an unusual case of Hashimoto thyroiditis onset after laparoscopic removal of struma ovarii.

The role of prospero homeobox 1 (PROX1) expression in follicular thyroid carcinoma cells

PubMed Central

Rudzinska, Magdalena; Ledwon, Joanna K.; Gawel, Damian; Sikorska, Justyna; Czarnocka, Barbara

2017-01-01

The prospero homeobox 1 (Prox1) transcription factor is a key player during embryogenesis and lymphangiogenesis. Altered Prox1 expression has been found in a variety of human cancers, including papillary thyroid carcinoma (PTC). Interestingly, Prox1 may exert tumor suppressive or tumor promoting effect, depending on the tissue context. In this study, we have analyzed Prox1 expression in normal and malignant human thyroid carcinoma cell lines. Moreover, we determined the effect of Prox1 silencing and overexpression on the cellular processes associated with the metastatic potential of tumor cells: proliferation, migration, invasion, apoptosis and anchorage-independent growth, in the follicular thyroid carcinoma (FTC) FTC-133 cell line. We found that Prox1 expression was significantly higher in FTC-derived cells than in PTC-derived cells and normal thyroid, and it was associated with the PI3K/Akt signaling pathway. In the FTC-133 cells, it was associated with cell invasive potential, motility and wound closure capacities, but not with proliferation or apoptosis. Modifying Prox1 expression also induced substantial changes in the cytoskeleton structure and cell morphology. In conclusion, we have shown that Prox1 plays an important role in the development of FTC and that its suppression prevents, whereas its overexpression promotes, the malignant behavior of thyroid follicular cancer cells. PMID:29371975

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.

Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

PubMed Central

Miccichè, Francesca; Da Riva, Luca; Fabbi, Marina; Pilotti, Silvana; Mondellini, Piera; Ferrini, Silvano; Canevari, Silvana; Pierotti, Marco A.; Bongarzone, Italia

2011-01-01

Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology. PMID:21364949

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.

Tumor classification in well-differentiated thyroid carcinoma and sentinel lymph node biopsy outcomes: a direct correlation.

PubMed

Maniakas, Anastasios; Forest, Veronique-Isabelle; Jozaghi, Yelda; Saliba, Joe; Hier, Michael P; Mlynarek, Alex; Tamilia, Michael; Payne, Richard J

2014-04-01

Predicting locoregional metastasis in well-differentiated thyroid carcinoma (WDTC) is a challenge for thyroid cancer surgeons. Sentinel lymph node biopsy (SLNB) has been shown to be an effective predictive tool. To our knowledge, primary tumor (T) classification has yet to be studied with regard to SLNB. We hypothesized that larger primary tumors would correlate with the rate of malignancy in SLNBs. A retrospective chart review was conducted on patients operated for WDTC at the McGill Thyroid Cancer Center over a 36-month period. Patients who underwent a total thyroidectomy and SLNB for WDTC were included in this study. A total of 311 patients were included and separated into two groups (236 negative and 75 positive SLNBs). Among patients with negative SLNBs, 65% had T1 primary tumors, 17% T2, 16% T3, and 2% T4, whereas 18% of patients with positive SLNBs had T1 primary tumors, 5% T2, 45% T3, and 32% T4 (p<0.001). Patients under the age of 45 years had a higher rate of positive SLNs (36% in those <45 years vs. 17% in those ≥ 45 years; p<0.001). Age (<45 years) and higher T category were found to be associated with a higher rate of positive SLNBs.

CD8+ TIL recruitment may revert the association of MAGE A3 with aggressive features in thyroid tumors.

PubMed

Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Cunha, Lucas Leite; Morari, Elaine Cristina; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

2014-01-01

We aimed to investigate a possible role of MAGE A3 and its associations with infiltrated immune cells in thyroid malignancy, analyzing their utility as a diagnostic and prognostic marker. We studied 195 malignant tissues: 154 PTCs and 41 FTCs; 102 benign tissues: 51 follicular adenomas and 51 goiter and 17 normal thyroid tissues. MAGE A3 and immune cell markers (CD4 and CD8) were evaluated using immunohistochemistry and compared with clinical pathological features. The semiquantitative analysis and ACIS III analysis showed similar results. MAGE A3 was expressed in more malignant than in benign lesions (P < 0.0001), also helping to discriminate follicular-patterned lesions. It was also higher in tumors in which there was extrathyroidal invasion (P = 0.0206) and in patients with stage II disease (P = 0.0107). MAGE A3+ tumors were more likely to present CD8+ TIL (P = 0.0346), and these tumors were associated with less aggressive features, that is, extrathyroidal invasion and small size. There was a trend of MAGE A3+ CD8+ tumors to evolve free of disease. We demonstrated that MAGE A3 and CD8+ TIL infiltration may play an important role in malignant thyroid nodules, presenting an interesting perspective for new researches on DTC immunotherapy.

Spindle epithelial tumor with thymus-like differentiation of the thyroid in a 70-year-old man.

PubMed

Lee, Sunhye; Kim, Yon Seon; Lee, Jeong Hyeon; Hwang, Sung Ho; Oh, Yu-Hwan; Ko, Byung Kyun; Ham, Soo-Youn

2018-06-01

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland mostly occurring in young patients. The imaging findings of SETTLE tumors are yet to be defined. However, they are usually described as well-defined heterogeneously enhanced masses on CT scan. The current case has the potential growth as compared with a 2009 chest radiography. We took into account the possibility of SETTLE in the case of a bulky mass in patients over 70 years old, particularly in the lower neck. Herein, we report a case of the oldest patient so far. The patient underwent a right lobectomy of the thyroid and mass excision. Follow-up CT scans after 6 months revealed no local recurrence. Surgery is the gold standard treatment for SETTLE. Chemotherapy and radiotherapy could be another possible option for patients with advanced stage SETTLE.

Coexistence of brenner tumor and struma ovarii: case report.

PubMed

Takeuchi, K; Ohbayashi, C; Kitazawa, S; Ohara, N; Maruo, T

2005-01-01

There has been controversy regarding the histogenesis of Brenner tumors. It is generally accepted that Brenner tumors are derived directly from ovarian surface epithelium, which undergoes metaplasia to form the typical urothelial-like components, whereas some investigators assume that Brenner tumors arise from immature germ cells. We describe a well-documented case of the coexistence of struma ovarii regarded as a form of teratoma and Brenner tumor in the same ovary. Immunohistologically, not only columnar cells of thyroid follicles, but also transitional cells of Brenner nests were positive for thyroglobulin. In the present case, Brenner tumors and thyroid elements coexisted and were positive for thyroglobulin. While there is strong evidence that pure Brenner tumors originate mostly from the ovarian surface, at least Brenner tumors associated with teratomatous elements may have a germ cell origin.

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

Expression of the Na+/l- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

PubMed Central

Altorjay, Áron; Dohán, Orsolya; Szilágyi, Anna; Paroder, Monika; Wapnir, Irene L; Carrasco, Nancy

2007-01-01

Background The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. Methods Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. Results Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. Conclusion That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease. PMID:17214887

Role of Ultrasound in Predicting Tumor Invasiveness in Follicular Variant of Papillary Thyroid Carcinoma.

PubMed

Hahn, Soo Yeon; Shin, Jung Hee; Oh, Young Lyun; Kim, Tae Hyuk; Lim, Yaeji; Choi, Ji Soo

2017-09-01

Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC. From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient. Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups (p = 0.507). Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines.

Mps1 is associated with the BRAFV600E mutation but does not rely on the classic RAS/RAF/MEK/ERK signaling pathway in thyroid carcinoma.

PubMed

Li, Yike; Zhang, Yanyan; Xiao, Shuaishuai; Kong, Pengzhou; Cheng, Caixia; Shi, Ruyi; Wang, Fang; Zhang, Ling; Wang, Juan; Jia, Zhiwu; Wu, Shuai; Liu, Yun; Guo, Jiansheng; Cheng, Xiaolong; Cui, Yongping; Liu, Jing

2018-06-01

In previous studies, the B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation has been identified in multiple malignant tumors. BRAF V600E has been revealed to contribute to tumorigenesis by the activation of phospho-mitogen-activated protein kinases (MAPKs) and their downstream Monopolar spindle 1 (Mps1), leading to chromosome euploidy and tumor development. In the present study, the presence of phospho-MAPK and Mps1 in 161 thyroid carcinoma cases with complete clinical parameters was analyzed by immunohistochemistry, and the BRAF mutation was detected by polymerase chain reaction-direct sequencing. It was revealed that BRAF V600E was present in ~34% of thyroid cancer cases and was associated with age, clinical tumor stage and lymph node stage. However, the association of BRAF V600E with overall survival was not statistically significant. The expression of Mps1 was significantly increased in tumor tissues with BRAF V600E , however, this did not affect the expression of phospho-MAPK in thyroid carcinomas. Collectively, the results of the present study suggested that BRAF V600E may regulate the expression of Mps1 in MAP kinase independent ways in thyroid carcinoma. Therefore, Mps1 expression is associated with BRAF V600E while the upstream signaling of phospho-MAPK has no relevance. The specific mechanisms of BRAF V600E and the unknown pathway associated with Mps1 exhibit potential for further study, and provide a theoretical basis for the molecular treatment of thyroid carcinoma.

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.

Image analysis for TSH mRNA in situ hybridization in pituitary glands from rats with thyroid follicular cell hypertrophy after treatment with three different test compounds.

PubMed

Funk, Juergen; Ebeling, Martin; Singer, Thomas; Landes, Christian

2017-10-01

The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats. Compared to immunohistochemistry (IHC), in situ hybridization (ISH) for TSH was found to be more sensitive. With this technique we are able to exclude a direct effect of the test compound on the thyroid gland by showing the activation of thyrotrope cells from the pituitary gland and therefore this technique retrospectively enables us to exclude a possible risk for humans at an early stage of drug development. Also in case blood serum samples for evaluation of TSH are not available anymore or hepatocellular hypertrophy is not present (close metabolic relationship between thyroid gland and liver in rodents), the described method allows retrospective investigations on thyroid follicular cell hypertrophy or hyperplasia. This can be of high relevance in human safety assessment for certain drugs in order to exclude a primary effect on the thyroid gland especially when it comes to thyroid neoplasia in rodents as previously described. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Molecular pathobiology of thyroid neoplasms.

PubMed

Tallini, Giovanni

2002-01-01

Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.

[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.

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

PubMed

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

2015-04-01

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Expression of Stanniocalcin 1 in Thyroid Side Population Cells and Thyroid Cancer Cells

PubMed Central

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S.; Hewitt, Stephen M.; Ward, Jerrold M.

2015-01-01

Background: Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Method: Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Results: Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma–derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. Conclusion: These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer. PMID:25647164

Feasibility of Intravoxel Incoherent Motion for Differentiating Benign and Malignant Thyroid Nodules.

PubMed

Tan, Hui; Chen, Jun; Zhao, Yi Ling; Liu, Jin Huan; Zhang, Liang; Liu, Chang Sheng; Huang, Dongjie

2018-06-13

This study aimed to preliminarily investigate the feasibility of intravoxel incoherent motion (IVIM) theory in the differential diagnosis of benign and malignant thyroid nodules. Forty-five patients with 56 confirmed thyroid nodules underwent preoperative routine magnetic resonance imaging and IVIM diffusion-weighted imaging. The histopathologic diagnosis was confirmed by surgery. Apparent diffusion coefficient (ADC), perfusion fraction f, diffusivity D, and pseudo-diffusivity D* were quantified. Independent samples t test of IVIM-derived metrics were conducted between benign and malignant nodules. Receiver-operating characteristic analyses were performed to determine the optimal thresholds as well as the sensitivity and specificity for differentiating. Significant intergroup difference was observed in ADC, D, D*, and f (p < 0.001). Malignant tumors featured significantly lower ADC, D and D* values and a higher f value than that of benign nodules. The ADC, D, and D* could distinguish the benign from malignant thyroid nodules, and parameter f differentiate the malignant tumors from benign nodules. The values of the area under the curve for parameter ADC, D, and D* were 0.784 (p = 0.001), 0.795 (p = 0.001), and 0.850 (p < 0.001), separately, of which the area under the curve of f value was the maximum for identifying the malignant from benign nodules, which was 0.841 (p < 0.001). This study suggested that ADC and IVIM-derived metrics, including D, D*, and f, could potentially serve as noninvasive predictors for the preoperative differentiating of thyroid nodules, and f value performed best in identifying the malignant from benign nodules among these parameters. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

Depression, suicide ideation, and thyroid tumors among ukrainian adolescents exposed as children to chernobyl radiation.

PubMed

Contis, George; Foley, Thomas P

2015-05-01

The Chernobyl Childhood Illness Program (CCIP) was a humanitarian assistance effort funded by the United States Congress. Its purpose was to assist the Ukrainian Government to identify and treat adolescents who developed mental and physical problems following their exposure as young children to Chernobyl radiation. Thirteen years after the Chernobyl nuclear plant accident in 1986, the CCIP examined 116,655 Ukrainian adolescents for thyroid diseases. Of these, 115,191 were also screened for depression, suicide ideation, and psychological problems. The adolescents lived in five of Ukraine's seven most Chernobyl radiation contaminated provinces. They were up to 6 years of age or in utero when exposed to nuclear fallout, or were born up to 45 months after Chernobyl. Ukrainian endocrinologist and ultrasonographers used physical examination and ultrasonography of the neck to evaluate the adolescents for thyroid tumors. The adolescents were then screened for depression by the Children's Depression Inventory (CDI). After this, Ukrainian psychologists conducted individual psychological interviews to corroborate the adolescents' CDI responses. Papillary thyroid carcinoma was diagnosed in eight adolescents, a high prevalence rate similar to that reported by other studies from the Soviet Union. Screening identified thyroid nodules in 1,967 adolescents (1.7%). Depression was diagnosed in 15,399 adolescents (13.2%), suicide ideation in 813 (5.3%), and attempted suicide in 354 (2.3%). Underlying components of the participants' depression were negative mood, interpersonal difficulties, negative self-esteem, ineffectiveness, and anhedonia. Depression was greater in females (77%). Those with thyroid and psychological problems were referred for treatment. The adolescents screened by CCIP represent the largest Ukrainian cohort exposed to Chernobyl radiation as children who were evaluated for both thyroid tumors and depression. The group had an increased prevalence of thyroid cancer, thyroid tumors, depression, and suicide ideation. CCIP demonstrated that psychological problems among Chernobyl exposed adolescents began earlier in life than previously reported. They also experienced socioeconomic problems from their relocation from radiation-affected areas and from the Soviet's inadequate responses to their health needs. CCIP's findings underscore the requirement that governments prepare plans to deal promptly with the diagnosis and treatment of nuclear accident victims' medical and psychological problems.

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report.

PubMed

Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

2006-10-19

Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

PubMed Central

Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

2006-01-01

Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease. PMID:17052355

Use of radiofrequency ablation in benign thyroid nodules: a literature review and updates.

PubMed

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation.

Use of Radiofrequency Ablation in Benign Thyroid Nodules: A Literature Review and Updates

PubMed Central

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation. PMID:24298282

Stages of Pituitary Tumors

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

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.

Dabrafenib Plus Trametinib Approved for Melanoma, Thyroid Cancer

Cancer.gov

FDA recently approved the combination of dabrafenib (Taflinar) and trametinib (Mekinist) to treat some patients with melanoma and anaplastic thyroid cancer whose tumors have a mutation in the BRAF gene. As this Cancer Currents blog post explains, this is the first treatment approved specifically for anaplastic thyroid

STUDIES INTO THE MECHANISMS OF POTASSIUM BROMATE INDUCED THYROID CARCINOGENESIS

EPA Science Inventory

Studies into the Mechanisms of Potassium Bromate Induced Thyroid Carcinogenesis.

Potassium bromate (KBrO3) occurs in finished drinking water as a by-product of the ozonation disinfection process and has been found to induce thyroid follicular cell tumors in the rat after ...

Treatment Options for Pituitary Tumors

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

Treatment Option Overview (Pituitary Tumors)

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

Thermal Ablation for Benign Thyroid Nodules: Radiofrequency and Laser

PubMed Central

Lee, Jeong Hyun; Valcavi, Roberto; Pacella, Claudio M.; Rhim, Hyunchul; Na, Dong Gyu

2011-01-01

Although ethanol ablation has been successfully used to treat cystic thyroid nodules, this procedure is less effective when the thyroid nodules are solid. Radiofrequency (RF) ablation, a newer procedure used to treat malignant liver tumors, has been valuable in the treatment of benign thyroid nodules regardless of the extent of the solid component. This article reviews the basic physics, techniques, applications, results, and complications of thyroid RF ablation, in comparison to laser ablation. PMID:21927553

131I therapy of thyroid cancer patients.

PubMed

Reiners, C; Farahati, J

1999-12-01

Thyroid cancer is a rare malignancy with wide interethnic and geographic variations. In Germany thyroid carcinoma is the 13th most frequent malignancy (2.7 new cases yearly per 100,000 inhabitants). The overall temporal incidence is increasing slightly in recent years. The most common types of cancer are papillary (60-80%) and follicular cancers (10-20%). The relevant prognostic indicators are tumor stage and distant metastases. The mean survival rates in papillary thyroid cancer usually exceed 90%, whereas in follicular thyroid cancer they amount to approximately 80%. The standard treatment procedure in differentiated papillary and follicular thyroid cancer consists of total thyroidectomy followed by adjuvant ablative therapy with radioiodine. Only in papillary thyroid cancer stage pT1N0M0 lobectomy alone is considered to be appropriate. In patients with locally invasive differentiated thyroid cancers stage pT4 adjuvant percutaneous radiation therapy is a treatment option. Radioiodine therapy has to be performed under the stimulative influence of TSH. Usually TSH suppressive medication with Levothyroxine has to be withdrawn approximately 4 weeks prior to radioiodine therapy. In the future, exogenous stimulation by recombinant TSH may be used instead of thyroid hormone withdrawal. It has been proven by different studies that ablative radioiodine therapy reduces the frequency of recurrences and tumor spread in patients with thyroid cancer significantly. In patients with distant metastases, up to 50% of complete responses may be achieved with radioiodine treatment.

Thyrotoxicosis: a rare presenting symptom of Hurthle cell carcinoma of the thyroid.

PubMed

Wong, C P; AuYong, T K; Tong, C M

2003-10-01

Hurthle cell carcinoma of the thyroid is a rare type of thyroid neoplasm. The most common clinical presentation is a single palpable thyroid nodule. The neoplasm typically presents as a nonfunctioning or cold nodule on a Tc-99m sodium pertechnetate or radioiodine thyroid scan. We report a case of Hurthle cell carcinoma of the thyroid in a woman presenting with thyrotoxicosis. The Tc-99m thyroid scan was also interesting in that the nodule was a hot or hyperfunctioning area, resulting in a rare scintigraphic finding in a rare tumor. Clinicopathologic aspects and related issues are further discussed.

Synchronous thyroid metastasis from lung adenocarcinoma.

PubMed

Rossini, Matteo; Ruffini, Livia; Ampollini, Luca; Cozzani, Federico; Del Rio, Paolo

2015-01-01

Metastases from other primary malignancies to the thyroid gland are clinically uncommon, far less frequent than any malignant primary neoplasm, mostly affecting elderly patients. Recent autopsy studies have shown that metastases to the tyroid is relatively common, with a prevalence of of 1,9-24%. We present a case of a man (72 years old) with lung cancer and synchronous metastasis to thyroid gland. Typically the interval between the diagnosis of the primary tumor and the detection of thyroid metastasis is from one month to 26 years. Clinical manifestation of thyroid metastases are rare Thyroid cancer, Thyroid metastases, Thyroidectomy.

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.

PubMed

Skansing, Daniel Bräuner; Londero, Stefano Christian; Asschenfeldt, Pia; Larsen, Stine Rosenkilde; Godballe, Christian

2017-06-01

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

Incidence of breast carcinoma in women with thyroid carcinoma.

PubMed

Vassilopoulou-Sellin, R; Palmer, L; Taylor, S; Cooksley, C S

1999-02-01

Breast carcinoma and differentiated thyroid carcinoma(the most common endocrine malignancy) occur predominantly in women. An association between the two tumors has been suggested by some investigators, but the potential impact of treatment of one of these diseases on the development of the other remains unclear. The authors examined the relation between the occurrence of these two tumors. There were 41,686 patients with breast carcinoma and 3662 with thyroid carcinoma who registered at The University of Texas M. D. Anderson Cancer Center between March 1944 and April 1997. Women who received both diagnoses since 1976 were identified and incidence rates and relative risks of secondary tumor development were calculated. Surveillance, Epidemiology and End Results (SEER) program data on the age-adjusted incidences of these diseases during the same time period were used for the expected incidences in the same population. Among 18,931 women with a diagnosis of breast carcinoma since 1976, 11 developed differentiated thyroid carcinoma > or = 2 years after the diagnosis of breast carcinoma. These breast carcinoma patients contributed 129,336 person-years of follow-up; the observed incidence of thyroid carcinoma in this group was not different from that in a similar age group of women in the SEER database. Among 1013 women with a diagnosis of thyroid carcinoma since 1976, 24 developed breast carcinoma > or = 2 years after the diagnosis of thyroid carcinoma. These thyroid carcinoma patients contributed 8380 person-years of follow-up; the observed incidence of breast carcinoma in women ages 40-49 years was significantly higher than the expected incidence for women in the same age group in the SEER database. Breast carcinoma developing after thyroid carcinoma was diagnosed more frequently than expected in young adult women seen at the study institution since 1976. This potential association and plausible mechanisms of breast carcinoma development after thyroid carcinoma should be evaluated in larger cohorts of patients.

Recent Advances in the Classification of Low-grade Papillary-like Thyroid Neoplasms and Aggressive Papillary Thyroid Carcinomas: Evolution of Diagnostic Criteria.

PubMed

Guo, Zhenying; Ge, Minghua; Chu, Ying-Hsia; Asioli, Sofia; Lloyd, Ricardo V

2018-07-01

Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms.

Hyperthyroidism

PubMed Central

Sharma, Mala; Aronow, Wilbert S.; Patel, Laxesh; Gandhi, Kaushang; Desai, Harit

2011-01-01

Summary Hyperthyroidism is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormone. The most common cause of this syndrome is Graves’ disease, followed by toxic multinodular goitre, and solitary hyperfunctioning nodules. Autoimmune postpartum and subacute thyroiditis, tumors that secrete thyrotropin, and drug-induced thyroid dysfunction, are also important causes. PMID:21455118

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.

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.

Protection and Dissection of Recurrent Laryngeal Nerve in Salvage Thyroid Cancer Surgery to Patients with Insufficient Primary Operation Extent and Suspicious Residual Tumor.

PubMed

Yu, Wen-Bin; Zhang, Nai-Song

2015-01-01

Some thyroid cancer patients undergone insufficient tumor removal in the primary surgery in China . our aim is to evaluate the impact of dissection of the recurrent laryngeal nerve during a salvage thyroid cancer operation in these patients to prevent nerve injury. Clinical data of 49 enrolled patients who received a salvage thyroid operation were retrospectively reviewed. Primary pathology was thyroid papillary cancer. The initial procedure performed included nodulectomy (20 patients), partial thyroidectomy (19 patients) and subtotal thyroidectomy (10 patients). The effect of dissection and protection of the recurrent laryngeal nerve and the mechanism of nerve injury were studied. The cervical courses of the recurrent laryngeal nerves were successfully dissected in all cases. Nerves were adherent to or involved by scars in 22 cases. Three were ligated near the place where the nerve entered the larynx, while another three were cut near the intersection of inferior thyroid artery with the recurrent laryngeal nerve. Light hoarseness occurred to four patients without a preoperative voice change. In conclusion, accurate primary diagnosis allows for a sufficient primary operation to be performed, avoiding insufficient tumor removal that requires a secondary surgery. The most important cause of nerve damage resulted from not identifying the recurrent laryngeal nerve during first surgery , and meticulous dissection during salvage surgery was the most efficient method to avoid nerve damage.

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.

Thyroid Hormone Receptor β (THRB) Is a Major Target Gene for MicroRNAs Deregulated in Papillary Thyroid Carcinoma (PTC)

PubMed Central

Boguslawska, Joanna; Jendrzejewski, Jaroslaw; Liyanarachchi, Sandya; Pachucki, Janusz; Wardyn, Kazimierz A.; Nauman, Alicja

2011-01-01

Context: Loss of the thyroid hormone receptor is common in tumors. In mouse models, a truncated THRB gene leads to thyroid cancer. Previously, we observed up-regulation of the expression of eight microRNAs (miRs) in papillary thyroid carcinoma (PTC) tumors. Objective: Our objective was to determine whether THRB might be inhibited by miRs up-regulated in PTC. Design: The potential binding of miR to the 3′-untranslated region of THRB was analyzed in silico. Direct inhibition by miRs binding to the cloned 3′-untranslated region of THRB was evaluated using luciferase assays. Inhibition of endogenous THRB and its target genes (DIO1 and APP) was examined in cell lines transfected by pre-miRs. The impact on thyroid hormone response element (TRE) was evaluated in promoter assays. Correlations between the expression of THRB and miRs was evaluated in 13 PTC tumor/normal tissue pairs. Results: THRB contains binding sites for the top seven miRs up-regulated in PTC (P = 0.0000002). Direct interaction with THRB was shown for miR-21 and miR-146a. We observed lower levels of THRB transcripts in cell lines transfected with miR-21, -146a, and -221 (down-regulation of 37–48%; P < 0.0001), but not with miR-181a. THRB protein was suppressed down to 10–28% by each of four miRs. Concomitant expression of DIO1 and APP was affected (down-regulation of 32–66%, P < 0.0034 and up-regulation of 48–57%, P < 0.0002, respectively). All four miRs affected TRE activity in promoter assays. Down-regulation of luciferase occurred after transfection with pTRE-TK-Luc construct and each of four miRs. The analysis of tumor/normal tissue pairs revealed down-regulation of THRB in 11 of 13 pairs (1.3- to 9.1-fold), and up-regulation of miR-21, -146a, -181a, and -221 in almost all pairs. Conclusions: MiRs up-regulated in PTC tumors directly inhibit the expression of THRB, an important tumor suppressor gene. PMID:21159845

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.

NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States.

PubMed

Prasad, Manju L; Vyas, Monika; Horne, Matthew J; Virk, Renu K; Morotti, Raffaella; Liu, Zongzhi; Tallini, Giovanni; Nikiforova, Marina N; Christison-Lagay, Emily R; Udelsman, Robert; Dinauer, Catherine A; Nikiforov, Yuri E

2016-04-01

An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing. Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B-Raf proto-oncogene, serine/threonine kinase (BRAF) valine-to-glutamic acid mutation at position 600 (BRAF(V) (600E)) (13 of 27 tumors; 48%), 11 measured <2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with BRAF(V) (600E) PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; P = .05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; P < .001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; P = .02); BRAF(V) (600E) PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (NTRK1/TPR, n = 1; RET/PTC1, n = 1). Fusion oncogene PTC presents with more extensive disease and aggressive pathology than BRAF(V) (600E) PTC in the pediatric population. The high prevalence of the NTRK1/NTRK3 fusion oncogene PTCs in the United States is unusual and needs further investigation. © 2016 American Cancer Society.

Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer.

PubMed

Gurgul, Edyta; Kasprzak, Aldona; Blaszczyk, Agata; Biczysko, Maciej; Surdyk-Zasada, Joanna; Seraszek-Jaros, Agnieszka; Ruchala, Marek

2015-01-01

Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

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.

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.

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.

Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes.

PubMed

Pilli, T; Toti, P; Occhini, R; Castagna, M G; Cantara, S; Caselli, M; Cardinale, S; Barbagli, L; Pacini, F

2018-06-01

An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial. The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI). We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response. Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation. Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

Thyroid-like follicular carcinoma of the kidney: A report of two cases and literature review

PubMed Central

LIN, YUN-ZHI; WEI, YONG; XU, NING; LI, XIAO-DONG; XUE, XUE-YI; ZHENG, QING-SHUI; JIANG, TAO; HUANG, JIN-BEI

2014-01-01

There have only been a few reports of thyroid-like follicular carcinoma of the kidney (TLFCK) to date. In the present study, two patients with TLFCK are reported. Patient 1 was a 65-year-old male exhibiting repeated hematuria and right back pain. No tumors were located in the patient’s thyroid or lungs. The physical examination revealed percussion tenderness over the right kidney region was noticed. Enhanced computed tomography (CT) indicated a right renal pelvic carcinoma, for which the patient underwent a radical right nephrectomy. Patient 2 was a 59-year-old male with a mass in the right kidney, located during a health examination and who exhibited no obvious clinical symptoms. The patient was clinically diagnosed with right renal carcinoma, confirmed by an enhanced CT. The patient underwent a radical right nephrectomy. The clinical features, imaging results, pathology, immune phenotypes, treatment and prognosis were analyzed. The associated literature was also reviewed. The cut surface of each tumor showed gray-white material with a central solid area, including scattered gray-brown necrotic and gray hemorrhagic areas and small cystic cavities. Microscopically, the arrangement of the tumor cells mimicked thyroid follicles with red-stained colloid-like material in the lumen. No renal hilar lymph node involvement was noted. The tumor tissue of patient 1 was immunohistochemically positive for vimentin, epithelial membrane antigen (EMA), cytokeratin (CK), CK7, and neuron specific enolase; and negative for CK34BE12, synapsin (Syn), CK20, cluster of differentiation 56 (CD56), CD10, Wilm’s tumor-1 (WT-1), CD34, CD57, P53, CD99, thyroid transcription factor-1 (TTF-1), CD15 and thyroglobulin (TG); with a Ki-67 labeling index (LI) of 30%. The tumor tissue of patient 2 was immunohistochemically positive for vimentin, EMA, CK7 and CK20; and negative for CD56, CD10, WT-1, CD34, CD57, P53, CD117, TTF-1, CD15, CD99, TG, chromogranin A and Syn; with a Ki-67 LI of 20%. TLFCK is a rare renal tumor with low malignancy but medium invasiveness. It morphologically resembles thyroid follicular carcinoma but does not express TTF-1 or TG. Radical nephrectomy can achieve good patient outcomes. PMID:24932236

Thyroid-like follicular carcinoma of the kidney: A report of two cases and literature review.

PubMed

Lin, Yun-Zhi; Wei, Yong; Xu, Ning; Li, Xiao-Dong; Xue, Xue-Yi; Zheng, Qing-Shui; Jiang, Tao; Huang, Jin-Bei

2014-06-01

There have only been a few reports of thyroid-like follicular carcinoma of the kidney (TLFCK) to date. In the present study, two patients with TLFCK are reported. Patient 1 was a 65-year-old male exhibiting repeated hematuria and right back pain. No tumors were located in the patient's thyroid or lungs. The physical examination revealed percussion tenderness over the right kidney region was noticed. Enhanced computed tomography (CT) indicated a right renal pelvic carcinoma, for which the patient underwent a radical right nephrectomy. Patient 2 was a 59-year-old male with a mass in the right kidney, located during a health examination and who exhibited no obvious clinical symptoms. The patient was clinically diagnosed with right renal carcinoma, confirmed by an enhanced CT. The patient underwent a radical right nephrectomy. The clinical features, imaging results, pathology, immune phenotypes, treatment and prognosis were analyzed. The associated literature was also reviewed. The cut surface of each tumor showed gray-white material with a central solid area, including scattered gray-brown necrotic and gray hemorrhagic areas and small cystic cavities. Microscopically, the arrangement of the tumor cells mimicked thyroid follicles with red-stained colloid-like material in the lumen. No renal hilar lymph node involvement was noted. The tumor tissue of patient 1 was immunohistochemically positive for vimentin, epithelial membrane antigen (EMA), cytokeratin (CK), CK7, and neuron specific enolase; and negative for CK34BE12, synapsin (Syn), CK20, cluster of differentiation 56 (CD56), CD10, Wilm's tumor-1 (WT-1), CD34, CD57, P53, CD99, thyroid transcription factor-1 (TTF-1), CD15 and thyroglobulin (TG); with a Ki-67 labeling index (LI) of 30%. The tumor tissue of patient 2 was immunohistochemically positive for vimentin, EMA, CK7 and CK20; and negative for CD56, CD10, WT-1, CD34, CD57, P53, CD117, TTF-1, CD15, CD99, TG, chromogranin A and Syn; with a Ki-67 LI of 20%. TLFCK is a rare renal tumor with low malignancy but medium invasiveness. It morphologically resembles thyroid follicular carcinoma but does not express TTF-1 or TG. Radical nephrectomy can achieve good patient outcomes.

Palliative Care

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

A new appraisal of iodine refractory thyroid cancer.

PubMed

Vaisman, Fernanda; Carvalho, Denise P; Vaisman, Mario

2015-12-01

Thyroid cancer incidence is increasing all over the world - mostly due to an increase in the detection of small tumors that were previously undetected. A small percentage of these tumors lose the ability to uptake and/or to respond to radioiodine (RAI) therapy, especially in metastatic patients. There are several new therapeutic options that have emerged in the last 5 years to treat RAI refractory thyroid cancer patients, however, it is very important to properly identify RAI refractory patients and to clarify those appropriate for these treatments. In this review, we discuss the RAI refractory definitions and the criteria that have been suggested based on RAI uptake in the post therapy scan, as well as the response after RAI therapy and the possible molecular mechanisms involved in this process. We offer a review of the therapeutic options available at the moment and the therapeutic considerations based on a patient's individualized personal characteristics, primary tumor histology, tumor burden and location and velocity of lesion growth. © 2015 Society for Endocrinology.

Therapeutic potential of Dickkopf-1 in wild-type BRAF papillary thyroid cancer via regulation of β-catenin/E-cadherin signaling.

PubMed

Cho, Sun Wook; Kim, Young A; Sun, Hyun Jin; Ahn, Hwa Young; Lee, Eun Kyung; Yi, Ka Hee; Oh, Byung-Chul; Park, Do Joon; Cho, Bo Youn; Park, Young Joo

2014-09-01

Aberrant activation of the Wnt/β-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC). Immunohistochemical β-catenin staining was performed in tissue microarray containing 148 PTCs and five normal thyroid tissues. In vivo effects of Dkk-1 were explored using ectopic tumors with BHP10-3SC cells. In 27 PTC patients, 60% of patients showed β-catenin up-regulation and Dkk-1 down-regulation in tumor vs normal tissues. Tissue microarray analysis showed that 14 of 148 PTC samples exhibited cytoplasmic-dominant β-catenin expression compared to membranous-dominant expression in normal tissues. Aberrant β-catenin expression was significantly correlated with higher rates of the loss of membranous E-cadherin expression and poor disease-free survival than that in the normal membranous expression group over a median follow-up period of 14 years. Implantation of Dkk-1-overexpressing BHP10-3SC cells revealed delayed tumor growth, resulting from the rescue of membranous β-catenin and E-cadherin expressions. Furthermore, tissue microarray analysis demonstrated that BRAF(WT) patients had higher rates of aberrant expressions of β-catenin and E-cadherin than BRAF(V600E) patients. Indeed, the inhibitory effects of Dkk-1 on cell survival were more sensitive in BRAF(WT) (BHP10-3SC and TPC-1) than in BRAF(V600E) (SNU-790 and BCPAP) cells. Overexpression of BRAF(V600E) in normal thyroid epithelial (H tori) cells also reduced the effects of Dkk-1 on cell survival. A subset of PTC patients showed aberrant expression of β-catenin/E-cadherin signaling and poor disease-free survival. Dkk-1 might have a therapeutic role, particularly in BRAF(WT) patients.

[Apathetic hyperthyroidism with heart failure in an elderly patient with Plummer's disease].

PubMed

Narisawa, Manabu; Okada, Yosuke; Arao, Tadashi; Kuno, Fumi; Tanaka, Yoshiya

2014-12-01

We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

Relapse or Recurrence

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

Tests and Procedures

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

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.

Secondary tumors involving the thyroid gland: A multi-institutional analysis of 28 cases diagnosed on fine-needle aspiration.

PubMed

HooKim, Kim; Gaitor, Jennifer; Lin, Oscar; Reid, Michelle D

2015-11-01

Fine-needle aspiration (FNA) is routinely used to evaluate primary thyroid lesions (PTLs), however, its role in diagnosing secondary thyroid neoplasms (STNs) has not been extensively studied. The goal was to examine the clinical and cytopathologic features of STNs diagnosed on FNA. The clinico-pathologic features of 28 STNs were analyzed. All PTLs, lymphomas, and locally invasive tumors were excluded. There were 28 STNs (0.18% incidence) out of 15,800 thyroid FNAs (12 males, 16 females, 32 - 85 years), all occurring metachronously (3 weeks-20 years, average 78.3 months) comprising 24 (85.7%) metastatic carcinomas (14 [50%] renal; 4 [14.3%] head and neck squamous cell carcinomas, 3 [10.7%] breast, and 1 [3.6%] colorectal, uterine serous carcinoma, and lung adenosquamous carcinoma, respectively), 3 sarcomas (10.7%) and 1 melanoma (3.6%). STNs are rare and diverse tumors which may occur decades after primary malignancy. Renal carcinomas are the most common. Prior history of malignancy, high index of suspicion, and attention to key distinguishing cytologic clues are critical for accurate diagnosis. © 2015 Wiley Periodicals, Inc.

Variations in clinicopathologic characteristics of thyroid cancer among racial ethnic groups: analysis of a large public city hospital and the SEER database.

PubMed

Moo-Young, Tricia A; Panergo, Jessel; Wang, Chih E; Patel, Subhash; Duh, Hong Yan; Winchester, David J; Prinz, Richard A; Fogelfeld, Leon

2013-11-01

Clinicopathologic variables influence the treatment and prognosis of patients with thyroid cancer. A retrospective analysis of public hospital thyroid cancer database and the Surveillance, Epidemiology and End Results 17 database was conducted. Demographic, clinical, and pathologic data were compared across ethnic groups. Within the public hospital database, Hispanics versus non-Hispanic whites were younger and had more lymph node involvement (34% vs 17%, P < .001). Median tumor size was not statistically different across ethnic groups. Similar findings were demonstrated within the Surveillance, Epidemiology and End Results database. African Americans aged <45 years had the largest tumors but were least likely to have lymph node involvement. Asians had the most stage IV disease despite having no differences in tumor size, lymph node involvement, and capsular invasion. There is considerable variability in the clinical presentation of thyroid cancer across ethnic groups. Such disparities persist within an equal-access health care system. These findings suggest that factors beyond socioeconomics may contribute to such differences. Copyright © 2013 Elsevier Inc. All rights reserved.

Spectrum of lesions derived from branchial arches occurring in the thyroid: from solid cell nests to tumors.

PubMed

Srbecka, Kristyna; Michalova, Kvetoslava; Curcikova, Radmila; Michal, Michael; Dubova, Magdalena; Svajdler, Marian; Michal, Michal; Daum, Ondrej

2017-09-01

There is a group of lesions in the head and neck region derived from branchial arches and related structures which, when inflamed, are characterized by the formation of cysts lined by squamous or glandular epithelium and surrounded by a heavy inflammatory infiltrate rich in germinal centers. In the thyroid, the main source of various structures which may cause diagnostic dilemma is the ultimobranchial body. To investigate the spectrum of such thyroid lesions, the consultation files were reviewed for thyroid samples containing pathological structures regarded to arise from the ultimobranchial body. Positive reaction with antibodies against CK5/6, p63, galectin 3, and CEA, and negative reaction with antibodies against thyroglobulin, TTF-1, and calcitonin were used to confirm the diagnosis. The specific subtype of the ultimobranchial body-derived lesion was then determined based on histological examination of H&E-stained slides. Twenty-one cases of ultimobranchial body-derived lesions were retrieved from the consultation files, 20 of them along with clinical information (M/F = 6/14, mean age 55 years, range 36-68 years). Lesions derived from the ultimobranchial body were classified as follows: (hyperplastic) solid cell nests (nine cases), solid cell nests with focal cystic change (five cases), cystic solid cell nests (two cases), branchial cleft-like cyst (four cases), and finally a peculiar Warthin tumor-like lesion (one case). We suggest that the common denominator of these structures is that they all arise due to activation of inflammatory cells around the vestigial structures, which leads to cystic dilatation and proliferation of the epithelial component.

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.

Anxiety Around Medical Procedures

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

Primary mucinous carcinoma with rhabdoid cells of the thyroid gland: a case report.

PubMed

Matsuo, Mioko; Tuneyoshi, Masazumi; Mine, Mari

2016-06-10

Primary mucinous carcinoma of the thyroid gland is a rare disease; only 6 cases of primary mucinous carcinoma of the thyroid have been previously reported. Primary mucinous carcinoma of the thyroid gland with incomplete tumor resection tends to be associated with a poor prognosis, resulting in death within a few months. An early and appropriate diagnosis may contribute to improvement in patient prognosis; however, it is extremely difficult to diagnose primary mucinous carcinoma of the thyroid. We present the seventh reported case of primary mucinous carcinoma in the thyroid gland; moreover, rhabdoid cells were detected, which, to our knowledge, is a novel finding. An 81-year-old Japanese woman was initially diagnosed with a poorly differentiated thyroid carcinoma, and she underwent a hemithyroidectomy. Pathological examination revealed the presence of abundant mucus and agglomeration of large atypical cells. Rhabdoid cells were also seen scattered among the tumor cells. Immunostaining was performed for various markers, and on the basis of these results, we diagnosed the lesion as primary mucinous carcinoma with rhabdoid cells in the thyroid gland. Ten months after surgery, recurrence was noted in the paratracheal lymph nodes; therefore, total resection of the residual thyroid gland and paratracheal lymphadenectomy with thyroid-stimulating hormone suppression were performed. The patient is currently alive and disease-free. The current case is of interest not only because of the rare histological findings, but also because the patient achieved long-term survival following diagnosis of a mucinous carcinoma. We believe this report will be helpful for diagnosing future cases of mucinous carcinoma of the thyroid.

Depression, Suicide Ideation, and Thyroid Tumors Among Ukrainian Adolescents Exposed as Children to Chernobyl Radiation

PubMed Central

Contis, George; Foley, Thomas P.

2015-01-01

Background The Chernobyl Childhood Illness Program (CCIP) was a humanitarian assistance effort funded by the United States Congress. Its purpose was to assist the Ukrainian Government to identify and treat adolescents who developed mental and physical problems following their exposure as young children to Chernobyl radiation. Thirteen years after the Chernobyl nuclear plant accident in 1986, the CCIP examined 116,655 Ukrainian adolescents for thyroid diseases. Of these, 115,191 were also screened for depression, suicide ideation, and psychological problems. The adolescents lived in five of Ukraine’s seven most Chernobyl radiation contaminated provinces. They were up to 6 years of age or in utero when exposed to nuclear fallout, or were born up to 45 months after Chernobyl. Methods Ukrainian endocrinologist and ultrasonographers used physical examination and ultrasonography of the neck to evaluate the adolescents for thyroid tumors. The adolescents were then screened for depression by the Children’s Depression Inventory (CDI). After this, Ukrainian psychologists conducted individual psychological interviews to corroborate the adolescents’ CDI responses. Results Papillary thyroid carcinoma was diagnosed in eight adolescents, a high prevalence rate similar to that reported by other studies from the Soviet Union. Screening identified thyroid nodules in 1,967 adolescents (1.7%). Depression was diagnosed in 15,399 adolescents (13.2%), suicide ideation in 813 (5.3%), and attempted suicide in 354 (2.3%). Underlying components of the participants’ depression were negative mood, interpersonal difficulties, negative self-esteem, ineffectiveness, and anhedonia. Depression was greater in females (77%). Those with thyroid and psychological problems were referred for treatment. Conclusions The adolescents screened by CCIP represent the largest Ukrainian cohort exposed to Chernobyl radiation as children who were evaluated for both thyroid tumors and depression. The group had an increased prevalence of thyroid cancer, thyroid tumors, depression, and suicide ideation. CCIP demonstrated that psychological problems among Chernobyl exposed adolescents began earlier in life than previously reported. They also experienced socioeconomic problems from their relocation from radiation-affected areas and from the Soviet’s inadequate responses to their health needs. CCIP’s findings underscore the requirement that governments prepare plans to deal promptly with the diagnosis and treatment of nuclear accident victims’ medical and psychological problems. PMID:25780482

Sympathetic Nerve Injury in Thyroid Cancer.

PubMed

Diamantis, Evangelos; Farmaki, Paraskevi; Savvanis, Spyridon; Athanasiadis, Georgios; Troupis, Theodoros; Damaskos, Christos

The double innervation of the thyroid comes from the sympathetic and parasympathetic nervous system. Injury rates during surgery are at 30% but can be minimized by upwardly preparing the thyroid vessels at the level of thyroid capsule. Several factors have been accused of increasing the risk of injury including age and tumor size. Our aim was to investigate of there is indeed any possible correlations between these factors and a possible increase in injury rates following thyroidectomy. Seven studies were included in the meta-analysis. Statistical correlation was observed for a positive relationship between injury of the sympathetic nerve and thyroid malignancy surgery (p 2 = 74%) No statistical correlations were observed for a negative or positive relationship between injury of the sympathetic nerve and tumor size. There was also no statistically significant value observed for the correlation of the patients' age with the risk of sympathetic nerve injury (p = 0.388). Lack of significant correlation reported could be due to the small number of studies and great heterogeneity between them.

Cari Kitahara Explores Medical Radiation Exposures and Thyroid Cancer Etiology

Cancer.gov

Dr. Cari Kitahara has built a multidisciplinary research program to explore cancer risks from occupational and medical radiation exposures, and to investigate the etiology of radiosensitive tumors, including thyroid cancer.

Pituitary Tumors

MedlinePlus

... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

Thyroid lymphoma: diagnostic pitfalls on pre-operative ago-biopsy.

PubMed

Antonino, Antonio; Rosato, Andrea; Barbato, Filomena; De Dominicis, Gianfranco; De Palma, Maurizio

2013-01-01

Thyroid cancer has the highest prevalence of all endocrine malignancies. Malignancy can be of thyroid or non-thyroid origin. Sarcomas and primary thyroid lymphomas (PTL) are rare and surgery is treatment of choice in the former but not in latter. To describe thyroid lymphomas histological types of thyroid cancer found in a reference center. Medical chart review from admitted patients diagnosed with thyroid cancer in the period from january 2007 to june 2012. Demographic, diagnostic, therapeutic and histopathological information were collected. 1604 records of patients admitted with thyroid disease were reviewed. Among 307 thyroid cancer, the cases diagnosed with rare tumors were: 10 cases of anaplastic carcinoma (3.5%), followed by 4 cases of medullary carcinoma (1.3%), 1 cases of teratoma (0.03%), 2 cases of lymphoma (0.06%). The most frequent clinical presentation was a palpable thyroid nodule. All patients with lymphoma died. Thyroid lymphomas are uncommon and tend to worse outcomes.

Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water.

PubMed

Collí-Dulá, Reyna Cristina; Friedman, Marvin A; Hansen, Benjamin; Denslow, Nancy D

2016-01-01

Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis such as DNA repair, DNA replication, chromosome segregation, among others; animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were increased in acrylamide-treated rats sampled at night, but not in quiescent animals when compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.

IR Spectroscopic signs of malignant neoplasms in the thyroid gland

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Skornyakov, I. V.; Butra, V. A.

2012-03-01

We use Fourier transform IR spectroscopy to study thyroid tumor tissues which were removed during surgery. The IR spectra of the tissues with pathological foci are compared with data from histologic examination. In the region of N-H, C-H, and C = O stretching vibrations, the IR spectra of the tissues for thyroid cancer are different from the IR spectra of tissues without malignant formations. We identify the spectral signs of thyroid cancer. We show that IR analysis is promising for identification of thyroid pathology at the molecular level.

Primary chondrosarcoma of the thyroid cartilage: Surgery-based management of a rare case

PubMed Central

Sun, Guo-Hua; Wang, Yuan-Jin; Gao, Li-Li; Qu, Ning; Mu, Xiang-Ming; Shi, Rong-Liang; Ji, Qing-Hai

2016-01-01

In this study, we present a case of a 52-year-old male with a chondrosarcoma of the left lamina of the thyroid cartilage. Pre-operative evaluations detected typical calcifications and delineated the extent of the tumor. The patient underwent a total laryngectomy to ensure the complete resection of the tumor. The tumor was histopathologically found to consist of chondrocytes in a hyaline cartilage matrix. The patient's post-operative course has been successful apart from the permanent tracheostomy. Herien, we discuss the methods and rationales for the diagnosis and management of and recovery from this rare tumor, and also provide a review of the literature. PMID:28101206

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.

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.

Nonthyroid Metastasis to the Thyroid Gland: Case Series and Review with Observations by Primary Pathology.

PubMed

Russell, Jonathon O; Yan, Kenneth; Burkey, Brian; Scharpf, Joseph

2016-12-01

Nonthyroid metastases to the thyroid gland can cause morbidity, including dysphagia, dysphonia, and airway compromise. Because metastatic malignancies portend a poor prognosis, obtaining equipoise between treatment morbidity and local disease progression is paramount. We reviewed cases of nonthyroid metastases to determine treatment and prognostic recommendations. Case series with chart review. Tertiary care hospital. We searched PubMed for reported cases between 1994 and September 2013 using search terms as follows: any combination of primary tumor locations and thyroid, as well as the terms thyroid and metastasis. Only unique cases of nonthyroid metastases were included. Combined with 17 additional tumors at our own institution, we found 818 unique nonthyroid metastases, of which 384 had management and survival data available. Renal cell carcinoma was most common, presenting in 293 (35.8%) patients, followed by lung and gastrointestinal malignancies. Patients were treated with total thyroidectomy (34.0%), subtotal thyroidectomy including lobectomy (32.6%), and no surgery (33.5%). Surgical management was associated with improved survival duration (P < .01). Locoregional recurrence was less likely in patients treated with total versus partial thyroidectomy (4.8% vs 13%). Extent of surgical management did not have a significant effect on patient survival. Delayed presentation was associated with improved survival duration (P = .01). Nonthyroid metastases to the thyroid gland are unusual tumors. Surgical intervention is associated with improved survival, but expected morbidity of untreated tumors is difficult to assess. Site of origin, time to diagnosis, and surgical approach are related to survival and recurrence rates. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Primary synovial sarcoma of the thyroid with locally repeated relapses in short periods: A case report

PubMed Central

SHI, RONG-LIANG; QU, NING; GAO, LI-LI; LU, ZHONG-WU; SUN, GUO-HUA; JI, QING-HAI

2016-01-01

The primary occurrence of synovial sarcoma (SS) in the thyroid is quite rare. As other SS arise from the head and neck structure, it tends to present poor biological behaviors and is generally treated as a high-grade sarcoma. The present study reports the case of a 31-year-old male who presented a neck mass, involving the thyroid, as shown by ultrasonography. The tumor was resected by total thyroidectomy and diagnosed as SS by histopathology. However, the initial surgery was considered as incomplete (R2) and no adjuvant protocol was followed. At the follow-up, neck recurrences within local lymph nodes were found repeatedly. The tumor grade increased for the metastatic lesions, indicating poorer differentiations with repeated relapses. The accurate evaluations of the primary tumor facilitated it to tailor the initial treatments, otherwise, the prognosis may be deteriorated by inappropriate management. PMID:27330751

Cytologic diagnosis of medullary carcinoma of the thyroid gland.

PubMed

Papaparaskeva, K; Nagel, H; Droese, M

2000-06-01

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 91 histologiacally verified medullary carcinomas of the thyroid (MCT) were investigated. FNA was able to diagnose neoplasms with indications of surgical removal in 98.9% of cases and moreover, was accurate in specific tumor typing in 89% of cases. The most important cytologic criteria of MCT with FNA are: dispersed cell-pattern of polygonal or triangular cells, azurophilic cytoplasmic granules, and extremely eccentrically placed nuclei with coarse granular chromatin and amyloid. These and other cytologic features of MCT are discussed in detail. Fourteen cases of thyroid tumors originally diagnosed as MCT by cytology are illustrated to discuss the differential diagnosis of MCT and its potential pitfalls. If MCT is cytologically presumed but amyloid and azurophilic cytoplasmic granules are not demonstrated, the use of immunostaining is necessary for a correct tumor typing. The application of immunocytochemistry in MCT is discussed. Copyright 2000 Wiley-Liss, Inc.

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.

PPARδ INDUCES CELL PROLIFERATION BY A CYCLIN E1-DEPENDENT MECHANISM AND IS UPREGULATED IN THYROID TUMORS

PubMed Central

Zeng, Lingchun; Geng, Yan; Tretiakova, Maria; Yu, Xuemei; Sicinski, Peter; Kroll, Todd G.

2008-01-01

Peroxisome proliferator-activated receptors (PPARs) are lipid sensing nuclear receptors that have been implicated in multiple physiologic processes including cancer. Here, we determine that PPARδ induces cell proliferation through a novel cyclin E1-dependent mechanism and is upregulated in many human thyroid tumors. The expression of PPARδ was induced coordinately with proliferation in primary human thyroid cells by activation of serum, TSH/cAMP/pKa or EGF/MEK/ERK mitogenic signaling pathways. Engineered overexpression of PPARδ increased thyroid cell number, the incorporation of BrdU and the phosphorylation of Rb 40–45% in just 2 days, one usual cell population doubling. The synthetic PPARδ agonist GW501516 augmented these PPARδ proliferation effects in a dose-dependent manner. Overexpression of PPARδ increased cyclin E1 protein 9-fold, whereas knock down of PPARδ by siRNA reduced both cyclin E1 protein and cell proliferation 2-fold. Induction of proliferation by PPARδ wasabrogated by knockdown of cyclin E1 by siRNA in primary thyroid cells and by knockout of cyclin E1 in mouse embryo fibroblasts, confirming a cyclin E1 dependence for this PPARδ pathway. In addition, the mean expression of native PPARδ was increased 2- to 5-fold (p<0.0001) and correlated with that of the in situ proliferation marker Ki67 (R=0.8571; p=0.02381) in six different classes of benign and malignant human thyroid tumors. Our experiments identify a PPARδ mechanism that induces cell proliferation through cyclin E1 and is regulated by growth factor and lipid signals. The data argue for systematic investigation of PPARδ antagonists as anti-neoplastic agents and implicate altered PPARδ-cyclin E1 signaling in thyroid and other carcinomas. PMID:18701481

[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.

Infrared signature analysis of the thyroid tumors

NASA Astrophysics Data System (ADS)

Gavriloaia, Gheorghe; Ghemigian, Adina-Mariana; Gavriloaia, Mariuca-Roxana

2009-07-01

Cancer is a leading cause of death worldwide, and about 30% of cancer deaths can be prevented. In the next future, the number of global cancer deaths is projected to increase 45% in the future. A general treatment has not yet been found. The best defense against cancer is early detection, when tumor dimensions are very small. The methods as mammography, ultrasounds, MRI, CT, etc., can detect anatomic or structural changes like tumors and cysts. They are anatomical imaging procedures, consequently, they have the ability to locate the area of the tumor, but they cannot detect a fast-growing cancer in the pre-invasive stage. Thermograms are looking for the physiologic changes in tissue; which may indicate a risk of developing cancer in the future. The results using a new device, operating in infrared band, are described. The paper focuses on thyroid cancer because it allows investigations on larger areas before surgery and on residual, smaller areas following surgery. The experiment results for 24 patients with thyroid nodules are described. Malign tumors have a distinct infrared signature. Only the area affected is thermal registered and that has an irregular shape and a strong nonuniform structure with rapid variations on skin temperature.

Mature cystic teratoma with high proportion of solid thyroid tissue: a controversial case with unusual imaging findings.

PubMed

Gil, Rui; Cunha, Teresa Margarida; Rolim, Ines

2017-07-01

We describe a case of a mature cystic teratoma of the ovary with high proportion of solid thyroid tissue (< 50% of the entire tumor) in a childbearing woman. The patient presented with non-specific abdominal bloating. Pelvic ultrasound and magnetic resonance imaging revealed a complex cystic-solid tumor confined to the left ovary with an anterior fat-containing locus compatible with mature cystic teratoma and a posterior predominantly solid component with low signal intensity on T2-weighted images that was histopatologically diagnosed as benign thyroid tissue. Thyroglobulin levels were in normal range. Although thyroid tissue is present in up to 20% of mature cystic teratomas, with exception of struma ovarii, it is not usually macroscopically nor radiologically identified. The differential diagnosis should include T2-hypointense adnexal lesions associated with mature cystic teratoma, malignant transformation of mature teratoma, and immature teratoma.

Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

PubMed

Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

2013-06-01

Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

The Rate and Clinical Significance of Incidental Thyroid Uptake as Detected by Gallium-68 DOTATATE Positron Emission Tomography/Computed Tomography

PubMed Central

Nockel, Pavel; Millo, Corina; Keutgen, Xavier; Klubo-Gwiezdzinska, Joanna; Shell, Jasmine; Patel, Dhaval; Nilubol, Naris; Herscovitch, Peter; Sadowski, Samira M.

2016-01-01

Background: Gallium-68 (Ga-68) DOTATATE is a radiolabeled peptide–imaging modality that targets the somatostatin receptor (SSTR), especially subtype 2 (SSTR2). Benign and malignant thyroid tumors have been observed to express SSTR. The aim of this study was to evaluate the frequency and clinical significance of incidental atypical thyroid uptake as detected by Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT). Methods: A retrospective analysis was conducted of a prospective study in which 237 patients underwent Ga-68 DOTATATE PET/CT as part of a work-up for metastatic and unknown primary neuroendocrine tumors. The types of uptake in the thyroid gland (focal/diffuse) and maximum standardized uptake value (SUVmax) levels were evaluated and compared with the background uptake in the liver and salivary glands. Results: Of 237 patients, 26 (11%) had atypical thyroid uptake as detected by Ga-68 DOTATATE PET/CT. There were no significant clinical or biochemical variables associated with atypical thyroid uptake. Fourteen (54%) patients had positive focal uptake, and 12 (46%) patients had diffuse uptake. Of the 14 patients with atypical focal uptake, 10 (71%) had thyroid nodules on the corresponding side, as detected by anatomic imaging. Three of 10 patients (21%) were found to have papillary thyroid cancer, and seven (70%) had adenomatoid nodules. Of the 12 patients with diffuse increased uptake, six (50%) had a history of hypothyroidism, five (42%) had chronic lymphocytic thyroiditis, and one (8%) had nontoxic multinodular goiter. Conclusions: Patients with an incidental focal abnormal thyroid uptake on Ga-68 DOTATATE PET/CT scan should have further clinical evaluation to exclude a diagnosis of thyroid cancer. PMID:27094616

Thyroid cancer in a patient with Lynch syndrome - case report and literature review.

PubMed

Fazekas-Lavu, Monika; Parker, Andrew; Spigelman, Allan D; Scott, Rodney J; Epstein, Richard J; Jensen, Michael; Samaras, Katherine

2017-01-01

Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1 , MSH2 , MSH6 , and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient's metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient's known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2 , suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers.

NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features

PubMed Central

Tavares, Catarina; Coelho, Maria João; Eloy, Catarina; Melo, Miguel; da Rocha, Adriana Gaspar; Pestana, Ana; Batista, Rui; Ferreira, Luciana Bueno; Rios, Elisabete; Selmi-Ruby, Samia; Cavadas, Bruno; Pereira, Luísa; Sobrinho Simões, Manuel

2018-01-01

Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the SLC5A5 gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied SLC5A5 expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, SLC5A5 expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring BRAFV600E mutation. Analysis of SLC5A5 expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/or distant metastases or harboring RAS, BRAF and/or TERT promoter (TERTp) mutations presented significantly less SLC5A5 expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for BRAF, NRAS and TERTp mutations. SLC5A5 mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving BRAF, RAS and TERTp. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. SLC5A5 mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features. PMID:29298843

Inhibition of Tumorigenesis by the Thyroid Hormone Receptor β in Xenograft Models

PubMed Central

Kim, Won Gu; Zhao, Li; Kim, Dong Wook; Willingham, Mark C.

2014-01-01

Background: Previous studies showed a close association between several types of human cancers and somatic mutations of thyroid hormone receptor β (TRβ) and reduced expression of TRβ due to epigenetic inactivation and/or deletion of the THRB gene. These observations suggest that TRβ could act as a tumor suppressor in carcinogenesis. However, the mechanisms by which TRβ could function to inhibit tumorigenesis are less well understood. Methods: We used the human follicular thyroid cancer cell lines (FTC-133 and FTC-236 cells) to elucidate how functional expression of the THRB gene could affect tumorigenesis. We stably expressed the THRB gene in FTC cells and evaluated the effects of the expressed TRβ on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. Results: Expression of TRβ in FTC-133 cells, as compared with control FTC cells without TRβ, reduced cancer cell proliferation and impeded migration of tumor cells through inhibition of the AKT-mTOR-p70 S6K pathway. TRβ expression in FTC-133 and FTC-236 led to less tumor growth in xenograft models. Importantly, new vessel formation was significantly suppressed in tumors induced by FTC cells expressing TRβ compared with control FTC cells without TRβ. The decrease in vessel formation was mediated by the downregulation of vascular endothelial growth factor in FTC cells expressing TRβ. Conclusions: These findings indicate that TRβ acts as a tumor suppressor through downregulation of the AKT-mTOR-p70 S6K pathway and decreased vascular endothelial growth factor expression in FTC cells. The present results raise the possibility that TRβ could be considered as a potential therapeutic target for thyroid cancer. PMID:23731250

Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma.

PubMed

Yin, De Tao; Xu, Jianhui; Lei, Mengyuan; Li, Hongqiang; Wang, Yongfei; Liu, Zhen; Zhou, Yubing; Xing, Mingzhao

2016-02-02

Some studies showed an association of coiled-coil domain-containing (CCDC) genes with cancers. Our previous limited data specifically suggested a possible pathogenic role of CCDC67 in papillary thyroid cancer (PTC), but this has not been firmly established. The present study was to further investigate and establish this role of CCDC67 in PTC. The expression of CCDC67, both at mRNA and protein levels, was sharply down-regulated in PTC compared with normal thyroid tissues. Lower CCDC67 expression was significantly associated with aggressive tumor behaviors, such as advanced tumor stages and lymph node metastasis, as well as BRAF mutation. Introduced expression of CCDC67 in TPC-1 cells robustly inhibited cell proliferation, colony formation and migration, induced G1 phase cell cycle arrest, and increased cell apoptosis. Primary PTC tumors and matched normal thyroid tissues were obtained from 200 unselected patients at the initial surgery for detection of CCDC67 mRNA and protein by RT-PCR and Western blotting analyses, respectively. Genomic DNA sequencing was performed to detect BRAF mutation in PTC tumors. Clinicopathological data were retrospectively reviewed for correlation analyses. PTC cell line TPC-1 with stable transfection of CCDC67 was used to investigate the functions of CCDC67. This large study demonstrates down-regulation of CCDC67 in PTC, an inverse relationship between CCDC67 expression and PTC aggressiveness and BRAF mutation, and a robust inhibitory effect of CCDC67 on PTC cellular activities. These results are consistent with CCDC67 being a novel and impaired tumor suppressor gene in PTC, providing important prognostic and therapeutic implications for this cancer.

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.

Thyroid-Stimulating Hormone Suppression for Protection Against Hypothyroidism Due to Craniospinal Irradiation for Childhood Medulloblastoma/Primitive Neuroectodermal Tumor

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

Massimino, Maura; Gandola, Lorenza; Collini, Paola

Purpose: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. Patients and Methods: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginningmore » and end of CSI. From 14 days before and up to the end of CSI, patients were administered L-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 {mu}M/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. Results: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the 'adequately TSH-suppressed' group and 20% for the 'inadequately TSH-suppressed' group (p = 0.02). Conclusions: Thyroid-stimulating hormone suppression with L-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.« less

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.

Clear cell variant of follicular thyroid carcinoma with normal thyroid-stimulating hormone value: a case report

PubMed Central

2014-01-01

Introduction Clear cell carcinomas of the thyroid gland with normal thyroid-stimulating hormone value are very rare, but clear cell changes are described in most reported cases of thyroidal lesions. Case presentation In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor was 1cm in diameter and consisted of pure clear cells. Conclusion Clear cell variants of follicular thyroid carcinoma are rarely seen, especially it is misdiagnosed with metastatic renal cell carcinoma. In this report, we describe the case of a patient with a clear cell variant of follicular thyroid carcinoma with an interesting pathology. PMID:24884725

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

PubMed

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

Assessment of the usefulness of the standardized uptake values and the radioactivity levels for the preoperative diagnosis of thyroid cancer measured by using 18F-FDG PET/CT dual-time-point imaging

NASA Astrophysics Data System (ADS)

Lee, Hyeon-Guck; Hong, Seong-Jong; Cho, Jae-Hwan; Han, Man-Seok; Kim, Tae-Hyung; Lee, Ik-Han

2013-02-01

The purpose of this study was to assess and compare the changes in the SUV (standardized uptake value), the 18F-FDG (18F-fluorodeoxyglucose) uptake pattern, and the radioactivity level for the diagnosis of thyroid cancer via dual-time-point 18F-FDG PET/CT (positron emission tomographycomputed tomography) imaging. Moreover, the study aimed to verify the usefulness and significance of SUV values and radioactivity levels to discriminate tumor malignancy. A retrospective analysis was performed on 40 patients who received 18F-FDG PET/CT for thyroid cancer as a primary tumor. To set the background, we compared changes in values by calculating the dispersion of scattered rays in the neck area and the lung apex, and by comparing the mean and SD (standard deviation) values of the maxSUV and the radioactivity levels. According to the statistical analysis of the changes in 18F-FDG uptake for the diagnosis of thyroid cancer, a high similarity was observed with the coefficient of determination being R2 = 0.939, in the SUVs and the radioactivity levels. Moreover, similar results were observed in the assessment of tumor malignancy using dual-time-point. The quantitative analysis method for assessing tumor malignancy using radioactivity levels was neither specific nor discriminative compared to the semi-quantitative analysis method.

Use of a thin-layer technique in thyroid fine needle aspiration.

PubMed

Malle, Despoina; Valeri, Rosalia-Maria; Pazaitou-Panajiotou, Kalliopi; Kiziridou, Anastasia; Vainas, Iraklis; Destouni, Charicleia

2006-01-01

To investigate the efficacy of the ThinPrep Processor (Cytyc Corporation, Boxborough, Massachusetts, U.S.A) in fine needle aspiration (FNA) of thyroid gland lesions. This study included 459 thyroid FNA specimens obtained from patients who came to our endocrinology department with various thyroid disorders over 3 years. The cytologic material was prepared using both the conventional and ThinPrep method in the first 2 years (285 cases), while in the last one only the ThinPrep method was used (1 74 cases). The smears were stained using a modified Papanicolaou procedure and May-Grünwald-Giemsa stain. Immunocytochemistry was performed on thin-layer slides using specific monoclonal antibodies when needed. Thin-layer and direct smear diagnoses were compared with the final cytologic or histologic diagnoses, when available. Our cases included 279 adenomatoid nodules, 15 cases of Hashimoto thyroiditis, 45 follicular neoplasms, 14 Hürthle cell tumors, 58 papillary carcinomas and 1 5 anaplastic carcinomas. Thin-layer preparations showed a trend toward a lower proportion of inadequate specimens and a lower false negative rate. Cytomorphologic features showed some differences between the 2 methods. Colloid was less frequently observed on ThinPrep slides, while nuclear detail and micronucleoli were more easily detected with this technique. Moreover, ThinPrep appeared to be the appropriate method for the use of ancillary techniques in suspicious cases. Thin-layer cytology improves the diagnostic accuracy of thyroid FNA and offers the possibility of performing new techniques, such as immunocytochemistry, on the same sample in order to detect malignancy as well as the type and origin of thyroid gland neoplasms.

Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways.

PubMed

Gunda, V; Bucur, O; Varnau, J; Vanden Borre, P; Bernasconi, M J; Khosravi-Far, R; Parangi, S

2014-03-06

Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAF(V600E) have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAF(V600E) inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis.

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia distinct from the salivary type.

PubMed

Hirokawa, Mitsuyoshi; Takada, Nami; Abe, Hideyuki; Suzuki, Ayana; Higuchi, Miyoko; Miya, Akihiro; Hayashi, Toshitetsu; Fukushima, Mitsuhiro; Kawahara, Akihiko; Miyauchi, Akira

2018-04-26

We report three cases of thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE), which is an extremely rare variant of mucoepidermoid carcinoma (MEC). The aims of this report were to describe the clinicopathological findings, including results from immunohistochemical and fluorescence in situ hybridization analysis of thyroid SMECE, as well as to discuss the distinction between thyroid SMECE and its salivary counterpart. The cases included a 63-year-old female, a 44-year-old male, and a 66-year-old female, with all patients presenting with Hashimoto's thyroiditis. Nodal metastasis was not found in any of the three cases. Neither regional recurrences nor distant metastases were found in any patient during the follow-up, which was 20 years, 3 years, and 18 months, respectively. Histologically, tumors were composed of epidermoid carcinoma cells, intermediate type carcinoma cells, and goblet cell-type mucus-secreting carcinoma cells, with all tumors displaying a sclerotic stroma with eosinophilic and lymphocytic infiltration. The formation of eosinophilic abscess in the tumor nests that might be a novel characteristic finding of SMECE was observed. Immunohistochemically, the carcinoma cells were positive for cytokeratin 34βE12, TTF-1, and PAX8, but negative for thyroglobulin. In two cases, increased IgG4-positive plasma cells were observed. Mastermind-like transcriptional coactivator 2 (MAML2), according to fluorescence in situ hybridization, was intact in all cases. In conclusion, thyroid SMECE has favorable outcomes and seems to be genetically different from salivary MEC. This is the first report to describe the presence of increased IgG4-positive plasma cells in the stroma of SMECE.

Gelsolin: a novel thyroid hormone receptor-beta interacting protein that modulates tumor progression in a mouse model of follicular thyroid cancer.

PubMed

Kim, Caroline S; Furuya, Fumihiko; Ying, Hao; Kato, Yasuhito; Hanover, John A; Cheng, Sheue-yann

2007-03-01

Follicular thyroid cancer (FTC) is known to metastasize to distant sites via hematogenous spread; however, the underlying pathways that contribute to metastasis remain unknown. Recent creation of a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta (TRbeta(PV/PV) mouse) that spontaneously develops thyroid cancer with metastasis similar to humans has provided new opportunities to study contributors to FTC metastasis. This study evaluates the role of gelsolin, an actin-regulatory protein, in modulating the metastatic potential of FTC. Gelsolin was previously found by cDNA microarray analysis to be down-regulated in TRbeta(PV/PV) mice as compared with wild-type mice. This study found an age-dependent reduction of gelsolin protein abundance in TRbeta(PV/PV) mice as tumorigenesis progressed. Knockdown of gelsolin by small interfering RNA resulted in increased tumor cell motility and increased gelsolin expression by histone deacetylase inhibitor (trichostatin A) led to decreased cell motility. Additional biochemical analyses demonstrated that gelsolin physically interacted with TRbeta1 or PV in vivo and in vitro. The interaction regions were mapped to the C terminus of gelsolin and the DNA binding domain of TR. The physical interaction of gelsolin with PV reduced its binding to actin, leading to disarrayed cytoskeletal architectures. These results suggest that PV-induced alteration of the actin/gelsolin cytoskeleton contributes to increased cell motility. Thus, the present study uncovered a novel PV-mediated oncogenic pathway that could contribute to the local tumor progression and metastatic potential of thyroid carcinogenesis.

MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.

PubMed

Lassalle, Sandra; Zangari, Joséphine; Popa, Alexandra; Ilie, Marius; Hofman, Véronique; Long, Elodie; Patey, Martine; Tissier, Frédérique; Belléannée, Geneviève; Trouette, Hélène; Catargi, Bogdan; Peyrottes, Isabelle; Sadoul, Jean-Louis; Bordone, Olivier; Bonnetaud, Christelle; Butori, Catherine; Bozec, Alexandre; Guevara, Nicolas; Santini, José; Hénaoui, Imène Sarah; Lemaire, Géraldine; Blanck, Olivier; Vielh, Philippe; Barbry, Pascal; Mari, Bernard; Brest, Patrick; Hofman, Paul

2016-05-24

In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib.Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.

Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer

PubMed Central

Bastman, Jill J.; Serracino, Hilary S.; Zhu, Yuwen; Koenig, Michelle R.; Mateescu, Valerica; Sams, Sharon B.; Davies, Kurtis D.; Raeburn, Christopher D.; McIntyre, Robert C.; Haugen, Bryan R.

2016-01-01

Context: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3–5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. Objective: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. Design: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. Setting: The study was conducted at the University of Colorado Hospital. Patients: Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. Intervention: There were no interventions. Main Outcome Measure: Immune markers were analyzed for association with disease severity. Results: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3+ (P < .0001), PD-1+CD8+ (P = .0058), and PD-1+CD4+ (P = .0104) T cells were enriched in DTC biopsies. CD8+ and FoxP3+ T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1+ lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAFV600E mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. Conclusions: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer. PMID:27045886

[RET/PTC Gene Rearrangements in the Sporadic and Radiogenic Thyroid Tumors: Molecular Genetics, Radiobiology and Molecular Epidemiology].

PubMed

Ushenkova, L N; Koterov, A N; Biryukov, A P

2015-01-01

A review of molecular genetic, radiobiological and molecular epidemiological studies of gene (chromosome) rearrangements RET/PTC in the cells of the thyroid gland as well as the laws in relation to radiation exposure in vitro, in vivo and human populations identified with them are submitted. The data on the c-RET gene and its chimeric constructs with the gene-donors (RET/PTC rearrangements) are considered. The information about the history of the RET/PTC discovery, their types, carcinogenic potential and specificity both to tumor and non-tumor thyroid disease especially for papillary thyroid carcinoma are provided. The data (seven studies) on the induction of RET/PTC after irradiation of tumor and normal thyroid cells in vitro and mice are reviewed. The mechanisms of RET/PTC induction may be associated with DNA double strand breaks and oxidative stress. Some information (three publications) about the possibility of RET/PTC induction by low doses of radiation with low LET (to 0.1 Gy) is given and it is concluded that their potential evidentiary is generally weak. The achievements in the molecular epidemiology of RET/PTC frequency for exposed and unexposed cohorts are stated. At the same time it is noted that, despite the vast array. of data accumulated from 30 countries of the world and more than 20 years of research, the formed provisions are weakly confirmed statistically and have no base corresponding to the canons of evidence-based medicine. The possibility of use of the RET/PTC presence or their frequencies as markers of the papillary thyroid carcinomas and, specifically, their radiogenic forms, is considered. In the first case the answer may be positive, while in the second, the situation is characterized by uncertainty. Based to the above mentioned we came to a conclusion about the need of a pooled or meta-analysis of the totality of the published data.

Perchlorate Contamination of Drinking Water: Regulatory Issues and Legislative Actions

DTIC Science & Technology

2005-02-23

health risks of perchlorate exposures include effects on the developing nervous systems and thyroid tumors, based on rat studies that observed benign...supplies nationwide. The regulation required monitoring by all water systems serving more than 10,000 persons and by a representative sample of smaller... systems . In 2004, EPA reported that perchlorate has been detected in public water systems in 24 states and Puerto Rico.4 The agency also reported

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

Immunoproteasome Overexpression Underlies the Pathogenesis of Thyroid Oncocytes and Primary Hypothyroidism: Studies in Humans and Mice

PubMed Central

Kimura, Hiroaki J.; Chen, Cindy Y.; Tzou, Shey-Cherng; Rocchi, Roberto; Landek-Salgado, Melissa A.; Suzuki, Koichi; Kimura, Miho; Rose, Noel R.; Caturegli, Patrizio

2009-01-01

Background Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown. Methodology/Principal Findings Using transgenic mice chronically expressing IFNγ in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors. Conclusions/Significance In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism. PMID:19924240

Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma

PubMed Central

Jung, Seung-Hyun; Kim, Min Sung; Jung, Chan Kwon; Park, Hyun-Chun; Kim, So Youn; Liu, Jieying; Bae, Ja-Seong; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-01-01

Follicular thyroid adenoma (FTA) precedes follicular thyroid carcinoma (FTC) by definition with a favorable prognosis compared to FTC. However, the genetic mechanism of FTA to FTC progression remains unknown. For this, it is required to disclose FTA and FTC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of 14 FTAs and 13 FTCs, which exhibited previously-known gene mutations (NRAS, HRAS, BRAF, TSHR and EIF1AX) and copy number alterations (CNAs) (22q loss and 1q gain) in follicular tumors. In addition, we found eleven potential cancer-related genes with mutations (EZH1, SPOP, NF1, TCF12, IGF2BP3, KMT2C, CNOT1, BRIP1, KDM5C, STAG2 and MAP4K3) that have not been reported in thyroid follicular tumors. Of note, FTA genomes showed comparable levels of mutations to FTC in terms of the number, sequence composition and functional consequences (potential driver mutations) of mutations. Analyses of evolutionary ages using somatic mutations as molecular clocks further identified that FTA genomes were as old as FTC genomes. Whole-transcriptome sequencing did not find any gene fusions with potential significance. Our data indicate that FTA genomes may be as old as FTC genomes, thus suggesting that follicular thyroid tumor genomes during the transition from FTA to FTC may stand stable at genomic levels in contrast to the discernable changes at pathologic and clinical levels. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful for the molecular diagnosis and therapeutics of follicular tumor patients. PMID:27626165

Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma.

PubMed

Jung, Seung-Hyun; Kim, Min Sung; Jung, Chan Kwon; Park, Hyun-Chun; Kim, So Youn; Liu, Jieying; Bae, Ja-Seong; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-10-25

Follicular thyroid adenoma (FTA) precedes follicular thyroid carcinoma (FTC) by definition with a favorable prognosis compared to FTC. However, the genetic mechanism of FTA to FTC progression remains unknown. For this, it is required to disclose FTA and FTC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of 14 FTAs and 13 FTCs, which exhibited previously-known gene mutations (NRAS, HRAS, BRAF, TSHR and EIF1AX) and copy number alterations (CNAs) (22q loss and 1q gain) in follicular tumors. In addition, we found eleven potential cancer-related genes with mutations (EZH1, SPOP, NF1, TCF12, IGF2BP3, KMT2C, CNOT1, BRIP1, KDM5C, STAG2 and MAP4K3) that have not been reported in thyroid follicular tumors. Of note, FTA genomes showed comparable levels of mutations to FTC in terms of the number, sequence composition and functional consequences (potential driver mutations) of mutations. Analyses of evolutionary ages using somatic mutations as molecular clocks further identified that FTA genomes were as old as FTC genomes. Whole-transcriptome sequencing did not find any gene fusions with potential significance. Our data indicate that FTA genomes may be as old as FTC genomes, thus suggesting that follicular thyroid tumor genomes during the transition from FTA to FTC may stand stable at genomic levels in contrast to the discernable changes at pathologic and clinical levels. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful for the molecular diagnosis and therapeutics of follicular tumor patients.

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.

Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

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

O'Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko

2010-08-19

Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene couldmore » be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC).« less

Spindle epithelial tumor with thymus-like differentiation: a case report and review of literature.

PubMed

Misra, R K; Mitra, Shaila; Yadav, Rajesh; Bundela, Alpana

2013-01-01

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare type of thyroid tumor with fewer than 35 reported cases available in the literature so far, most of them having been diagnosed histologically after resection. The tumor is believed to be derived from branchial-pouch or thymic remnants, occurring in young adults, predominantly in males, with a male:female ratio 1.8:1. A 14-year-old girl presented with a nodular mass in her right thyroid that had been present for 1 year. Ultrasonological study revealed a heterogeneous solid mass (2.5 × 1.5 × 1.5 cm) in the right lobe of the thyroid. Fine-needle aspiration (FNA) smears were highly cellular and comprised of predominantly dissociated uniform spindle cells with naked oval nuclei along with some aggregates and groups. Occasional islands of epithelial cells were also present. Cytologically, the spindle cells had bland nuclear chromatin, with very scanty mitotic figures. Upon examination of the FNA smears, a provisional diagnosis of SETTLE was suggested along with a request for an incisional biopsy to rule out another differential diagnosis of medullary carcinoma thyroid. On the resected tissue specimen, diagnosis was histologically confirmed to be SETTLE. Immunohistochemical study revealed a strong and diffuse positivity for high-molecular-weight keratin and vimentin, and negativity for thyroglobulin, calcitonin, S-100 protein, desmin, chromogranin and synaptophysin. Cytologically, SETTLE can safely be considered, especially if spindle elements are observed along with the occasional group of epithelial cells in FNA smears from the thyroid of young adults. It can help in the preoperative recognition of lesions based on distinctive cytomorphological features and immunohistochemical characteristics, allowing a more sound therapeutic approach because these patients can present with delayed metastasis. Copyright © 2013 S. Karger AG, Basel.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER

PubMed Central

Davies, Louise; Morris, Luc G.T.; Haymart, Megan; Chen, Amy Y.; Goldenberg, David; Morris, John; Ogilvie, Jennifer B.; Terris, David J.; Netterville, James; Wong, Richard J.; Randolph, Gregory

2016-01-01

Objective (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. Methods Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. Results The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. Conclusion Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers. PMID:26135963

The Putative PAX8/PPARγ Fusion Oncoprotein Exhibits Partial Tumor Suppressor Activity through Up-Regulation of Micro-RNA-122 and Dominant-Negative PPARγ Activity.

PubMed

Reddi, Honey V; Madde, Pranathi; Milosevic, Dragana; Hackbarth, Jennifer S; Algeciras-Schimnich, Alicia; McIver, Bryan; Grebe, Stefan K G; Eberhardt, Norman L

2011-01-01

In vitro studies have demonstrated that the PAX8/PPARγ fusion protein (PPFP), which occurs frequently in follicular thyroid carcinomas (FTC), exhibits oncogenic activity. However, paradoxically, a meta-analysis of extant tumor outcome studies indicates that 68% of FTC-expressing PPFP are minimally invasive compared to only 32% of those lacking PPFP (χ(2) = 6.86, P = 0.008), suggesting that PPFP favorably impacts FTC outcomes. In studies designed to distinguish benign thyroid neoplasms from thyroid carcinomas, the previously identified tumor suppressor miR-122, a major liver micro-RNA (miR) that is decreased in hepatocellular carcinoma, was increased 8.9-fold (P < 0.05) in all FTC versus normal, 9.2-fold in FTC versus FA (P < 0.05), and 16.8-fold (P < 0.001) in FTC + PPFP versus FTC - PPFP. Constitutive expression of PPFP in the FTC-derived cell line WRO (WRO-PPFP) caused a 5-fold increase of miR-122 expression (P < 0.05) and a striking 5.1-fold reduction (P < 0.0001) in tumor progression compared to WRO-vector cells in a mouse xenograft model. Constitutive expression of either miR-122 or a dominant-negative PPARγ mutant in WRO cells was less effective than PPFP at inhibiting xenograft tumor progression (1.8-fold [P < 0.001] and 1.7-fold [P < 0.03], respectively). PPFP-induced up-regulation of miR-122 expression was independent of its known dominant-negative PPARγ activity. Up-regulation of miR-122 negatively regulates ADAM-17, a known downstream target, in thyroid cells, suggesting an antiangiogenic mechanism in thyroid carcinoma. This latter inference is directly supported by reduced CD-31 expression in WRO xenografts expressing PPFP, miR-122, and DN-PPARγ. We conclude that, in addition to its apparent oncogenic potential in vitro, PPFP exhibits paradoxical tumor suppressor activity in vivo, mediated by multiple mechanisms including up-regulation of miR-122 and dominant-negative inhibition of PPARγ activity.

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.

Pathogenesis of Hyperthyroidism.

PubMed

Singh, Ishita; Hershman, Jerome M

2016-12-06

Hyperthyroidism is a form of thyrotoxicosis in which there is excess thyroid hormone synthesis and secretion. Multiple etiologies can lead to a common clinical state of "thyrotoxicosis," which is a consequence of the high thyroid hormone levels and their action on different tissues of the body. The most common cause of thyrotoxicosis is Graves' disease, an autoimmune disorder in which stimulating thyrotropin receptor antibodies bind to thyroid stimulating hormone (TSH) receptors on thyroid cells and cause overproduction of thyroid hormones. Other etiologies include: forms of thyroiditis in which inflammation causes release of preformed hormone, following thyroid gland insult that is autoimmune, infectious, mechanical or medication induced; secretion of human chorionic gonadotropin in the setting of transient gestational thyrotoxicosis and trophoblastic tumors; pituitary thyrotropin release, and exposure to extra-thyroidal sources of thyroid hormone that may be endogenous or exogenous. © 2017 American Physiological Society. Compr Physiol 7:67-79, 2017. Copyright © 2017 John Wiley & Sons, Inc.

A taxonomy of epithelial human cancer and their metastases

PubMed Central

2009-01-01

Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA) and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics. Moreover, a signature was developed based on our unsupervised clustering of breast tumors and this was predictive for disease-specific survival in three independent studies. Next, the metastases from ovarian, breast, lung and vulva cluster with their tissue of origin while metastases from colon showed a bimodal distribution. A significant part clusters with tissue of origin while the remaining tumors cluster with the tissue of destination. Conclusion Our molecular taxonomy of epithelial human cancer indicates surprising correlations over tissues. This may have a significant impact on the classification of many cancer sites and may guide pathologists, both in research and daily practice. Moreover, these results based on unsupervised analysis yielded a signature predictive of clinical outcome in breast cancer. Additionally, we hypothesize that metastases from gastrointestinal origin either remember their tissue of origin or adapt to the tissue of destination. More specifically, colon metastases in the liver show strong evidence for such a bimodal tissue specific profile. PMID:20017941

[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.

[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 %).

Expression of BMP-4 in papillary thyroid carcinoma and its correlation with tumor invasion and progression.

PubMed

Meng, Xiaomei; Zhu, Peng; Li, Ning; Hu, Jinchen; Wang, Shaoguang; Pang, Shuguang; Wang, Jiahui

2017-04-01

Bone morphogenetic protein 4 (BMP-4) is a member of the BMP protein family. BMP-4 was reported to induce epithelial-mesenchymal transition (EMT) and promote tumor cell immigration and invasion. This study aimed to investigate the expression of BMP-4 in papillary thyroid carcinoma (PTC) and its correlation with the patients' clinicophathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 82 patients admitted to the Department of Thyroid Surgery of Yantai Yuhuangding Hospital between Feb 1st and May 31st, 2016 were collected. The expression level of BMP-4 in PTC tissues was examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between BMP-4 expression and the clinical pathological features of PTC. Our result showed that BMP-4-positive cell rate and staining intensity were positively correlated with the patient's age (P=0.031, 0.037), tumor size (P=0.033, 0.019), capsular invasion (P=0.001, 0.002) and TNM stage (P=0.001, 0.004), while not correlated with gender, multicentricity of tumor or lymphatic metastasis. In conclusion, this study identified BMP-4 as a potential molecular marker for predicting the invasion and progression of PTC. Copyright © 2017 Elsevier GmbH. All rights reserved.

Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias

PubMed Central

Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo

2000-01-01

High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549

Applications of Raman spectroscopy in life science

NASA Astrophysics Data System (ADS)

Martin, Airton A.; T. Soto, Cláudio A.; Ali, Syed M.; Neto, Lázaro P. M.; Canevari, Renata A.; Pereira, Liliane; Fávero, Priscila P.

2015-06-01

Raman spectroscopy has been applied to the analysis of biological samples for the last 12 years providing detection of changes occurring at the molecular level during the pathological transformation of the tissue. The potential use of this technology in cancer diagnosis has shown encouraging results for the in vivo, real-time and minimally invasive diagnosis. Confocal Raman technics has also been successfully applied in the analysis of skin aging process providing new insights in this field. In this paper it is presented the latest biomedical applications of Raman spectroscopy in our laboratory. It is shown that Raman spectroscopy (RS) has been used for biochemical and molecular characterization of thyroid tissue by micro-Raman spectroscopy and gene expression analysis. This study aimed to improve the discrimination between different thyroid pathologies by Raman analysis. 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. 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. It will be also report the application of in vivo confocal Raman spectroscopy as an important sensor for detecting advanced glycation products (AGEs) on human skin.

Modeling anaplastic thyroid carcinoma in the mouse.

PubMed

Champa, Devora; Di Cristofano, Antonio

2015-02-01

Anaplastic thyroid carcinoma is the least common form of thyroid cancer; however, it accounts for the majority of deaths associated with this family of malignancies. A number of genetically engineered immunocompetent mouse models recapitulating the genetic and histological features of anaplastic thyroid cancer have been very recently generated and represent an invaluable tool to dissect the mechanisms involved in the progression from indolent, well-differentiated tumors to aggressive, undifferentiated carcinomas and to identify novel therapeutic targets. In this review, we focus on the relevant characteristics associated with these models and on what we have learned in terms of anaplastic thyroid cancer biology, genetics, and response to targeted therapy.

Modeling anaplastic thyroid carcinoma in the mouse

PubMed Central

Champa, Devora; Di Cristofano, Antonio

2014-01-01

Anaplastic thyroid carcinoma is the least common form of thyroid cancer; however, it accounts for the majority of deaths associated with this family of malignancies. A number of genetically engineered immunocompetent mouse models recapitulating the genetic and histological features of anaplastic thyroid cancer have been very recently generated and represent an invaluable tool to dissect the mechanisms involved in the progression from indolent, well differentiated tumors to aggressive, undifferentiated carcinomas, and to identify novel therapeutic targets. In this review, we focus on the relevant characteristics associated with these models and on what we have learned in terms of anaplastic thyroid cancer biology, genetics, and response to targeted therapy. PMID:25420535

[Consensus statement for accreditation of multidisciplinary thyroid cancer units].

PubMed

Díez, Juan José; Galofré, Juan Carlos; Oleaga, Amelia; Grande, Enrique; Mitjavila, Mercedes; Moreno, Pablo

2016-03-01

Thyroid cancer is the leading endocrine system tumor. Great advances have recently been made in understanding of the origin of these tumors and the molecular biology that makes them grow and proliferate, which have been associated to improvements in diagnostic procedures and increased availability of effective local and systemic treatments. All of the above makes thyroid cancer a paradigm of how different specialties should work together to achieve the greatest benefit for the patients. Coordination of all the procedures and patient flows should continue throughout diagnosis, treatment, and follow-up, and is essential for further optimization of resources and time. This manuscript was prepared at the request of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition, and is aimed to provide a consensus document on the definition, composition, requirements, structure, and operation of a multidisciplinary team for the comprehensive care of patients with thyroid cancer. For this purpose, we have included contributions by several professionals from different specialties with experience in thyroid cancer treatment at centers where multidisciplinary teams have been working for years, with the aim of developing a practical consensus applicable in clinical practice. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

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.

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.

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.

Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.

PubMed

Strosberg, Jonathan R

2013-02-01

Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the "diffuse neuroendocrine system," they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and treatment of these rare neoplasms. Copyright © 2013 Elsevier Inc. All rights reserved.

[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.

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.

Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in vivo.

PubMed

Stenner, Frank; Liewen, Heike; Zweifel, Martin; Weber, Achim; Tchinda, Joelle; Bode, Beata; Samaras, Panagiotis; Bauer, Stefan; Knuth, Alexander; Renner, Christoph

2008-09-01

Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies, being responsible for the majority of thyroid cancer-related deaths. Despite multimodal therapy including surgery, chemotherapy, and radiotherapy, the outcome of ATC is poor. The human ATC cell line MB1, derived from tumor tissue of a 57-year-old man with thyroid cancer and pronounced neutrophilia, was established from surgically excised tumor tissue. The karyotype of the cell line shows many chromosomal abnormalities. Preclinical investigations have shown antitumor activity and effectiveness of the BRAF kinase inhibitor Sorafenib and the proteasome inhibitor Bortezomib. After establishment of the MB1 cell line these agents were applied in vitro and, showing activity in a cell culture model, were also used for in vivo treatment. Sorafenib had some clinical effect, namely normalization of leucocytosis, but had no sustained impact on subsequent tumor growth and development of distant metastasis. Molecular diagnostics of the tumor demonstrated no BRAF mutations in exons 11 and 15 concordant with a rather modest effect of Sorafenib on MB1 cell growth. Clinical benefit was seen with subsequent bortezomib therapy inducing a temporary halt to lymph node growth and a progression-free interval of 7 weeks. Our observations together with previous data from preclinical models could serve as a rationale for selecting those patients suffering from ATC most likely to benefit from targeted therapy. A prospective controlled randomized trial integrating kinase and proteasome inhibitors into a therapeutic regime for ATC is warranted.

Activating BRAF and PIK3CA mutations cooperate to promote anaplastic thyroid carcinogenesis.

PubMed

Charles, Roch-Philippe; Silva, Jillian; Iezza, Gioia; Phillips, Wayne A; McMahon, Martin

2014-07-01

Thyroid malignancies are the most common type of endocrine tumors. Of the various histologic subtypes, anaplastic thyroid carcinoma (ATC) represents a subset of all cases but is responsible for a significant proportion of thyroid cancer-related mortality. Indeed, ATC is regarded as one of the more aggressive and hard to treat forms of cancer. To date, there is a paucity of relevant model systems to critically evaluate how the signature genetic abnormalities detected in human ATC contribute to disease pathogenesis. Mutational activation of the BRAF protooncogene is detected in approximately 40% of papillary thyroid carcinoma (PTC) and in 25% of ATC. Moreover, in ATC, mutated BRAF is frequently found in combination with gain-of-function mutations in the p110 catalytic subunit of PI3'-Kinase (PIK3CA) or loss-of-function alterations in either the p53 (TP53) or PTEN tumor suppressors. Using mice with conditional, thyrocyte-specific expression of BRAF(V600E), we previously developed a model of PTC. However, as in humans, BRAF(V600E)-induced mouse PTC is indolent and does not lead to rapid development of end-stage disease. Here, we use mice carrying a conditional allele of PIK3CA to demonstrate that, although mutationally activated PIK3CA(H1047R) is unable to drive transformation on its own, when combined with BRAF(V600E) in thyrocytes, this leads to development of lethal ATC in mice. Combined, these data demonstrate that the BRAF(V600E) cooperates with either PIK3CA(H1074R) or with silencing of the tumor-suppressor PTEN, to promote development of anaplastic thyroid carcinoma. This genetically relevant mouse model of ATC will be an invaluable platform for preclinical testing of pathway-targeted therapies for the prevention and treatment of thyroid carcinoma. ©2014 American Association for Cancer Research.

Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics.

PubMed

Hilly, Ohad; Raz, Raanan; Vaisbuch, Yona; Strenov, Yulia; Segal, Karl; Koren, Rumelia; Shvero, Jacob

2012-11-01

Indications for thyroidectomy during laryngectomy are controversial. We examined whether clinicopathologic features can predict thyroid gland involvement, and the prognostic effect of thyroid gland involvement in patients undergoing total laryngectomy. The study set out to review preoperative assessment, operation findings, pathologic findings, and follow-up data. Thyroid gland involvement was found in 11 of 53 patients (21%) undergoing total laryngectomy and thyroidectomy. Preoperative work-up failed to predict thyroid gland involvement. Thyroid gland involvement was associated with salvage procedures (p = .025), paratracheal metastases (p = .003), and poor overall survival (hazard ratio = 2.74, p = .008). Thyroid gland involvement in patients undergoing total laryngectomy is frequent and is associated with poor prognosis. Preoperative assessment failed to predict thyroid gland involvement. We believe that thyroidectomy should be considered in cases with paratracheal lymphatic spread irrespective of tumor location within the larynx. Copyright © 2011 Wiley Periodicals, Inc.

The BRAFT1799A mutation is not associated with occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma.

PubMed

Wan, Han-Feng; Zhang, Bin; Yan, Dan-Gui; Xu, Zhen-Gang

2015-01-01

The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the BRAFT1799A mutation is associated with aggressive PTMC, the relationship between BRAFT1799A mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including BRAFT1799A mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. From January 2011 to December 2013,we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. BRAFT1799A mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was 0.33±0.21 cm. The BRAFT1799A mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model.

PubMed

Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

2016-06-07

Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/-mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/-mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/-mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/-mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/-mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model

PubMed Central

Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

2016-01-01

Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/−mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/−mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/−mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/−mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/−mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer. PMID:27145454

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

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.

Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

ClinicalTrials.gov

2016-07-14

Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models.

PubMed

Morrison, Jennifer A; Pike, Laura A; Lund, Greg; Zhou, Qiong; Kessler, Brittelle E; Bauerle, Kevin T; Sams, Sharon B; Haugen, Bryan R; Schweppe, Rebecca E

2015-06-01

Thyroid cancer incidence has been increasing over time, and it is estimated that ∼1950 advanced thyroid cancer patients will die of their disease in 2015. To combat this disease, an enhanced understanding of thyroid cancer development and progression as well as the development of efficacious, targeted therapies are needed. In vitro and in vivo studies utilizing thyroid cancer cell lines and animal models are critically important to these research efforts. In this report, we detail our studies with a panel of authenticated human anaplastic and papillary thyroid cancer (ATC and PTC) cell lines engineered to express firefly luciferase in two in vivo murine cancer models-an orthotopic thyroid cancer model as well as an intracardiac injection metastasis model. In these models, primary tumor growth in the orthotopic model and the establishment and growth of metastases in the intracardiac injection model are followed in vivo using an IVIS imaging system. In the orthotopic model, the ATC cell lines 8505C and T238 and the PTC cell lines K1/GLAG-66 and BCPAP had take rates >90 % with final tumor volumes ranging 84-214 mm(3) over 4-5 weeks. In the intracardiac model, metastasis establishment was successful in the ATC cell lines HTh74, HTh7, 8505C, THJ-16T, and Cal62 with take rates ≥70 %. Only one of the PTC cell lines tested (BCPAP) was successful in the intracardiac model with a take rate of 30 %. These data will be beneficial to inform the choice of cell line and model system for the design of future thyroid cancer studies.

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.

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.

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.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

PubMed

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-09-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Distribution of Thyroid Cancer in the Eastern Part of Turkey 27 Years After the Chernobyl Accident.

PubMed

Sahin, Serap Baydur; Yucel, Ahmet Fikret; Gucer, Hasan; Pergel, Ahmet; Bedir, Recep; Aydin, Ibrahim; Sehitoglu, Ibrahim; Sahin, Dursun Ali; Sahin, Osman Zikrullah

2013-12-01

The Chernobyl accident caused widespread effects across Europe and huge areas where radiocontaminated. The effects of the Chernobyl accident on thyroid cancer have been investigated in most European countries. According to the data of the Turkish Atomic Energy Authority, the eastern part of the Black Sea region was the most radiocontaminated area in Turkey at the time of Chernobyl accident. We therefore aimed to examine the data of thyroid cancers at our center, Rize city which is located in the eastern Black Sea region. This retrospective study included the patients with histologically proven thyroid cancer at our center between January 2008 and May 2012. Pathologic examinations of thyroidectomy materials were reviewed. We evaluated patients' age, gender, size of the primary tumor (all sizes, < 1 cm, 1 - 2.9 cm, 3 - 3.9 cm and ≥ 4 cm), multicentricity, histologic subtypes of thyroid cancer, the presence of lymphatic, vascular, capsule and the extrathyroidal invasion. Five hundred and forty-seven of the 3,556 patients were diagnosed with thyroid cancer. The mean age of the patients was 49.31 ± 0.49 years. The histopathologic diagnosis of patients was papillary carcinoma in 533 (97.4%) and the tumor size was < 1 cm in 53.6% of the patients. The presence of multicentricity was detected in 47% of the patients. The portion of thyroid carcinomas in all thyroidectomies was 15.4% in our institution 27 years after the Chernobyl accident.

Distribution of Thyroid Cancer in the Eastern Part of Turkey 27 Years After the Chernobyl Accident

PubMed Central

Sahin, Serap Baydur; Yucel, Ahmet Fikret; Gucer, Hasan; Pergel, Ahmet; Bedir, Recep; Aydin, Ibrahim; Sehitoglu, Ibrahim; Sahin, Dursun Ali; Sahin, Osman Zikrullah

2013-01-01

Background The Chernobyl accident caused widespread effects across Europe and huge areas where radiocontaminated. The effects of the Chernobyl accident on thyroid cancer have been investigated in most European countries. According to the data of the Turkish Atomic Energy Authority, the eastern part of the Black Sea region was the most radiocontaminated area in Turkey at the time of Chernobyl accident. We therefore aimed to examine the data of thyroid cancers at our center, Rize city which is located in the eastern Black Sea region. Methods This retrospective study included the patients with histologically proven thyroid cancer at our center between January 2008 and May 2012. Pathologic examinations of thyroidectomy materials were reviewed. We evaluated patients’ age, gender, size of the primary tumor (all sizes, < 1 cm, 1 - 2.9 cm, 3 - 3.9 cm and ≥ 4 cm), multicentricity, histologic subtypes of thyroid cancer, the presence of lymphatic, vascular, capsule and the extrathyroidal invasion. Results Five hundred and forty-seven of the 3,556 patients were diagnosed with thyroid cancer. The mean age of the patients was 49.31 ± 0.49 years. The histopathologic diagnosis of patients was papillary carcinoma in 533 (97.4%) and the tumor size was < 1 cm in 53.6% of the patients. The presence of multicentricity was detected in 47% of the patients. Conclusion The portion of thyroid carcinomas in all thyroidectomies was 15.4% in our institution 27 years after the Chernobyl accident. PMID:29147362

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib

PubMed Central

Wang, Weibin; Kang, Helen; Zhao, Yinu; Min, Irene; Wyrwas, Brian; Moore, Maureen; Teng, Lisong; Zarnegar, Rasa; Jiang, Xuejun

2017-01-01

Context: The RAF inhibitor vemurafenib has provided a major advance for the treatment of patients with BRAF-mutant metastatic melanoma. However, BRAF-mutant thyroid cancer is relatively resistant to vemurafenib, and the reason for this disparity remains unclear. Anticancer therapy–induced autophagy can trigger adaptive drug resistance in a variety of cancer types and treatments. To date, role of autophagy during BRAF inhibition in thyroid cancer remains unknown. Objective: In this study, we investigate if autophagy is activated in vemurafenib-treated BRAF-mutant thyroid cancer cells, and whether autophagy inhibition improves or impairs the treatment efficacy of vemurafenib. Design: Autophagy level was determined by western blot assay and transmission electron microscopy. The combined effects of autophagy inhibitor and vemurafenib were assessed in terms of cell viability in vitro and tumor growth rate in vivo. Whether the endoplasmic reticulum (ER) stress was in response to vemurafenib-induced autophagy was also analyzed. Results: Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells. Inhibition of autophagy by either a pharmacological inhibitor or interfering RNA knockdown of essential autophagy genes augmented vemurafenib-induced cell death. Vemurafenib-induced autophagy was independent of MAPK signaling pathway and was mediated through the ER stress response. Finally, administration of vemurafenib with the autophagy inhibitor hydroxychloroquine promoted more pronounced tumor suppression in vivo. Conclusions: Our data demonstrate that vemurafenib induces ER stress response–mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. PMID:27754804

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.

PubMed

Wang, Weibin; Kang, Helen; Zhao, Yinu; Min, Irene; Wyrwas, Brian; Moore, Maureen; Teng, Lisong; Zarnegar, Rasa; Jiang, Xuejun; Fahey, Thomas J

2017-02-01

The RAF inhibitor vemurafenib has provided a major advance for the treatment of patients with BRAF-mutant metastatic melanoma. However, BRAF-mutant thyroid cancer is relatively resistant to vemurafenib, and the reason for this disparity remains unclear. Anticancer therapy-induced autophagy can trigger adaptive drug resistance in a variety of cancer types and treatments. To date, role of autophagy during BRAF inhibition in thyroid cancer remains unknown. In this study, we investigate if autophagy is activated in vemurafenib-treated BRAF-mutant thyroid cancer cells, and whether autophagy inhibition improves or impairs the treatment efficacy of vemurafenib. Autophagy level was determined by western blot assay and transmission electron microscopy. The combined effects of autophagy inhibitor and vemurafenib were assessed in terms of cell viability in vitro and tumor growth rate in vivo. Whether the endoplasmic reticulum (ER) stress was in response to vemurafenib-induced autophagy was also analyzed. Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells. Inhibition of autophagy by either a pharmacological inhibitor or interfering RNA knockdown of essential autophagy genes augmented vemurafenib-induced cell death. Vemurafenib-induced autophagy was independent of MAPK signaling pathway and was mediated through the ER stress response. Finally, administration of vemurafenib with the autophagy inhibitor hydroxychloroquine promoted more pronounced tumor suppression in vivo. Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. Copyright © 2017 by the Endocrine Society

International PPB Registry for PPB, DICER1 and Associated Conditions

ClinicalTrials.gov

2017-12-18

Pleuropulmonary Blastoma; Sertoli-Leydig Cell Tumor; DICER1 Syndrome; Cystic Nephroma; Wilms Tumor; Pineoblastoma; Renal Sarcoma; Nodular Hyperplasia of Thyroid; Nasal Chondromesenchymal Hamartoma; Ciliary Body Medulloepithelioma; Neuroblastoma; Pituitary Cancer; Embryonal Rhabdomyosarcoma

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.

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review.

PubMed

Lai, Chi-Yun; Chao, Tzu-Chieh; Lin, Jen-Der; Hsueh, Chuen

2015-01-01

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) was first described by Chan et al in 1991. It is characterized by nest or strands of epidermoid tumor cells with squamous differentiation, rare mucous cells, prominent sclerotic stroma, eosinophilic and lymphoplasmacytic infiltration, and a background of chronic lymphocytic thyroiditis in the non-neoplastic thyroid gland. It is important to recognize SMECE of thyroid and differentiate it from squamous cell carcinoma or other neoplasms with squamous differentiation/metaplasia. In published cases, the SMECE of thyroid gland predominantly occurs in women. We report a case of SMECE of thyroid in a 45-year-old male patient. All cases in male patients were Caucasian described in English literature, and our case is the first one in Asian.

Management of locally invasive well-differentiated thyroid cancer.

PubMed

Ark, Nebil; Zemo, Sessunu; Nolen, David; Holsinger, F Christopher; Weber, Randal S

2008-01-01

Thyroid carcinoma invasion of the aerodigestive tract and recurrent laryngeal nerve (RLN) are important factors with increase in morbidity and mortality. Primary treatment is surgery; the decision about the extent of surgery is difficult, because preserving function is as essential as removal of the tumor. This article discusses the literature relating to the assessment of disease, surgical management, and adjuvant therapy for invasive thyroid cancer of the aerodigestive tract and RLN and makes suggestions based on the authors' experience.

Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

PubMed

Hubalewska-Hola, Alicja; Fröss, Katarzyna; Kostecka-Matyja, Marta; Sowa-Staszczak, Anna; Szybiński, Zbigniew; Huszno, Bohdan; Ptak, Marzena

2003-01-01

Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma (histopathologically a chromophobic adenoma). The example of presented patients suggests that clinical course of the pituitary tumor producing TSH and the rate of the tumor growth may differ significantly. Surgical resection of TSH producing adenoma is the most effective therapy. It should be proceeded by octreotide administration in patients with macroadenoma.

Management of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma.

PubMed

Arslanoğlu, Seçil; Eren, Erdem; Özkul, Yılmaz; Ciğer, Ejder; Kopar, Aylin; Önal, Kazım; Etit, Demet; Tütüncü, G Yazgı

2016-02-01

The objective of this study was to determine the incidence of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma; and the association between clinicopathological parameters and thyroid gland invasion. Medical records of 75 patients with laryngeal and hypopharyngeal squamous cell carcinoma who underwent total laryngectomy with thyroidectomy were reviewed, retrospectively. Preoperative computed tomography scans, clinical and operative findings, and histopathological data of the specimens were evaluated. There were 73 male and two female patients with an age range of 41-88 years (mean 60.4 years). Hemithyroidectomy was performed in 62 (82.7 %) and total thyroidectomy was performed in 13 patients (17.3 %). Four patients had histopathologically proven thyroid gland invasion (5.3 %). In three patients, thyroid gland involvement was by means of direct invasion. Thyroid gland invasion was significantly correlated with thyroid cartilage invasion. Therefore, prophylactic thyroidectomy should not be a part of the treatment policy for these tumors.

Sternal resection for metastasis from thyroid carcinoma and reconstruction with the sandwiched Marlex and stainless steel mesh.

PubMed

Haraguchi, Shuji; Yamashita, Yasuo; Yamashita, Koji; Hioki, Masafumi; Matsumoto, Koshi; Shimizu, Kazuo

2004-04-01

A case of 69-year-old woman with a solitary sternal bone metastasis from thyroid carcinoma undergoing surgical therapy was reported here. On admission, most part of the body of the sternum was destroyed by tumor. Subtotal sternectomy was performed and a part of the major pectoral muscles adherent to the sternal tumor was also resected. The chest wall defect was reconstructed with a sandwiched Marlex and stainless steel mesh. Pathological examination of the resected specimen revealed metastatic papillary carcinoma of the thyroid. Her postoperative course was uneventful. The reconstruction with Marlex and stainless steel mesh seemed to be an appropriate procedure to prevent paradoxical movement of the thorax and protect the intrathoracic organs. Stainless steel mesh compensated for limited resiliency of Marlex mesh and remained rigid in all directions.

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.

MicroRNAs in thyroid development, function and tumorigenesis.

PubMed

Fuziwara, Cesar Seigi; Kimura, Edna Teruko

2017-11-15

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that modulate the vast majority of cellular processes. During development, the correct timing and expression of miRNAs in the tissue differentiation is essential for organogenesis and functionality. In thyroid gland, DICER and miRNAs are necessary for accurately establishing thyroid follicles and hormone synthesis. Moreover, DICER1 mutations and miRNA deregulation observed in human goiter influence thyroid tumorigenesis. The thyroid malignant transformation by MAPK oncogenes is accompanied by global miRNA changes, with a marked reduction of "tumor-suppressor" miRNAs and activation of oncogenic miRNAs. Loss of thyroid cell differentiation/function, and consequently iodine trapping impairment, is an important clinical characteristic of radioiodine-refractory thyroid cancer. However, few studies have addressed the direct role of miRNAs in thyroid gland physiology. Here, we focus on what we have learned in the thyroid follicular cell differentiation and function as revealed by cell and animal models and miRNA modulation in thyroid tumorigenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

PubMed

Kleinstreuer, Nicole C; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Paul, Katie B; Reif, David M; Crofton, Kevin M; Hamilton, Kerry; Hunter, Ronald; Shah, Imran; Judson, Richard S

2013-01-01

Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways.

Impact of Enhanced Detection on the Increase in Thyroid Cancer Incidence in the United States: Review of Incidence Trends by Socioeconomic Status Within the Surveillance, Epidemiology, and End Results Registry, 1980–2008

PubMed Central

Li, Nan; Du, Xianglin L.; Reitzel, Lorraine R.; Xu, Li

2013-01-01

Background In the past 3 decades, the incidence of thyroid cancer in the United States has been increasing. There has been debate on whether the increase is real or an artifact of improved diagnostic scrutiny. Our hypothesis is that both improved detection and a real increase have contributed to the increase. Methods Because socioeconomic status (SES) may be a surrogate for access to diagnostic technology, we compared thyroid cancer incidence trends between high- and low-SES counties within the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries. The incidence trends were assessed using joinpoint regression analysis. Results In high-SES counties, thyroid cancer incidence increased moderately (annual percentage change 1 [APC1]=2.5, p<0.05) before the late 1990s and more pronounced (APC2=6.3, p<0.05) after the late 1990s. In low-SES counties, incidence increased steadily with an APC of 3.5 (p<0.05) during the entire study period (1980–2008). For tumors ≤4.0 cm, incidence was higher in high-SES counties, and APC was higher for high- than low-SES counties after the late 1990s. For tumors >4.0 cm, high- and low-SES counties had similar increasing incidence trends. Similarly, for tumors ≤2.0 cm, the incidence trends differed between counties that are in or adjacent to metropolitan areas and counties that are in rural areas, whereas for tumors >2.0 cm, all counties regardless of area of residence had similar increasing trends. Conclusions Enhanced detection likely contributed to the increased thyroid cancer incidence in the past decades, but cannot fully explain the increase, suggesting that a true increase exists. Efforts should be made to identify the cause of this true increase. PMID:23043274

Impact of enhanced detection on the increase in thyroid cancer incidence in the United States: review of incidence trends by socioeconomic status within the surveillance, epidemiology, and end results registry, 1980-2008.

PubMed

Li, Nan; Du, Xianglin L; Reitzel, Lorraine R; Xu, Li; Sturgis, Erich M

2013-01-01

In the past 3 decades, the incidence of thyroid cancer in the United States has been increasing. There has been debate on whether the increase is real or an artifact of improved diagnostic scrutiny. Our hypothesis is that both improved detection and a real increase have contributed to the increase. Because socioeconomic status (SES) may be a surrogate for access to diagnostic technology, we compared thyroid cancer incidence trends between high- and low-SES counties within the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries. The incidence trends were assessed using joinpoint regression analysis. In high-SES counties, thyroid cancer incidence increased moderately (annual percentage change 1 [APC1]=2.5, p<0.05) before the late 1990s and more pronounced (APC2=6.3, p<0.05) after the late 1990s. In low-SES counties, incidence increased steadily with an APC of 3.5 (p<0.05) during the entire study period (1980-2008). For tumors ≤4.0 cm, incidence was higher in high-SES counties, and APC was higher for high- than low-SES counties after the late 1990s. For tumors >4.0 cm, high- and low-SES counties had similar increasing incidence trends. Similarly, for tumors ≤2.0 cm, the incidence trends differed between counties that are in or adjacent to metropolitan areas and counties that are in rural areas, whereas for tumors >2.0 cm, all counties regardless of area of residence had similar increasing trends. Enhanced detection likely contributed to the increased thyroid cancer incidence in the past decades, but cannot fully explain the increase, suggesting that a true increase exists. Efforts should be made to identify the cause of this true increase.

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.

Alveolar soft part sarcoma presenting as a breast metastasis in a patient with a history of thyroid cancer: a case report

PubMed Central

Bychkov, Andrey; Sampatanukul, Pichet

2015-01-01

Metastases to the breast are uncommon, accounting for 0.5% of breast tumors, and most of them are originated from lymphoma, melanoma and carcinomas of various organs. Alveolar soft part sarcoma (ASPS) is a very rare neoplasm that is usually found in the lower extremities. Lungs are the common site of dissemination and may represent initial manifestation of disease. We report a clinically unsuspected case of ASPS presenting as a breast metastasis in a 25-year-old woman. The patient’s medical history was notable for a thyroid cancer treated by surgery and radioiodine ablation 2 years ago. Core needle biopsy of slowly growing breast mass yielded polygonal cells with abundant eosinophilic cytoplasm arranged into solid pattern. Differential diagnosis between apocrine cell carcinoma, paraganglioma, granular cell tumor, neuroendocrine carcinoma, ASPS and metastatic hepatocellular and renal cell carcinoma was rendered by immunohistochemistry. Strong nuclear TFE3 immunoreactivity confirmed a diagnosis of ASPS. Retrospectively a primary tumor was found in the thigh. Most likely, ASPS and thyroid cancer in the patient were growing synchronously and independently. PMID:26464747

FOLLICULAR CELL CARCINOMA OF THE THYROID GLAND IN THREE CAPTIVE AGED RACCOON DOGS (NYCTEREUTES PROCYONOIDES).

PubMed

Kido, Nobuhide; Itagaki, Iori; Ono, Kaori; Omiya, Tomoko; Matsumoto, Rei

2015-12-01

The clinical and histologic features of thyroid carcinoma in raccoon dogs have not been previously reported. Three of four raccoon dogs (Nyctereutes procyonoides) over 8 yr of age at the Nogeyama Zoological Gardens developed thyroid follicular cell carcinomas that were detected at necropsy. The affected raccoon dogs were rescued from the wild and were housed at the Nogeyama Zoological Gardens for 8 yr 8 mo, 8 yr 10 mo, and 10 yr 3 mo, respectively. Although all of them appeared lethargic and developed partial alopecia or desquamation of their skin, they did not display any other specific clinical signs associated with a thyroid lesion. Serum thyroid hormone values were examined in two of the affected raccoon dogs and the average and standard deviation values (free-thyroxin [FT4]: 0.078 ± 0.077 pM/L and 0.062 ± 0.0039 pM/L; free-triiodothyronine [FT3]: 3.261 ± 0.765 pM/L and 3.407 ± 0.919 pM/L) were lower than the reference range (FT4: 0.141 ± 0.117 pM/L; FT3: 5.139 ± 2.412 pM/L) derived from a clinically normal raccoon dog. On necropsy, the thyroid lobes were markedly enlarged bilaterally. Histopathologically, the neoplastic cells in the thyroid gland appeared round or oval and columnar or cuboidal with minimal heteromorphism. Moreover, mostly small (but occasionally large) follicles were identified, and the neoplastic cells had infiltrated into the surrounding capsule and blood vessels. The histopathologic features of the thyroid tumors in the raccoon dogs revealed that the tumors were derived from follicular cells.

How reliably can computed tomography predict thyroid invasion prior to laryngectomy?

PubMed

Harris, Andrew S; Passant, Carl D; Ingrams, Duncan R

2018-05-01

There is little evidence to support the removal of thyroid tissue during total laryngectomy. Although oncological control of the tumor is the priority, thyroidectomy can lead to hypothyroidism and hypoparathyroidism. This study aimed to test the usefulness of preoperative computed tomography in predicting histological invasion of the thyroid. Ambispective cohort study. All patients undergoing total laryngectomy for squamous cell carcinoma at one center from 2006 to 2016 were included. Data were recorded prospectively as part of the patients' standard care, but were collated retrospectively, giving this study an ambispective design. The histology report for thyroid invasion was taken as the gold standard. The computed tomography report was categorized by invasion of tumor into intralaryngeal, laryngeal cartilage involvement, and extralaryngeal tissues. Seventy-nine patients were included. Nine patients had thyroid involvement on histology, translating to an incidence of 11.29% in this population. The positive predictive value for cartilage involvement on computed tomography for thyroid invasion was 52.9% (95% confidence interval [CI]: 28.5%-76.1%) and the negative predictive value was 100% (95% CI: 92.7%-100%).The positive predictive value for extralaryngeal spread on computed tomography for thyroid involvement was 100% (95% CI: 62.9%-100%), and the negative predictive value was also 100% (95% CI: 93.5%-100%). This study has shown that preoperative computed tomography is an effective method of ruling out thyroid gland invasion. The absence of extralaryngeal spread on computed tomography has been shown to be the most useful finding, with a high negative predictive value and a narrow 95% CI. 4. Laryngoscope, 128:1099-1102, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

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

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature.

PubMed

Cabibi, Daniela; Pipitone, Giulia; Porcasi, Rossana; Ingrao, Sabrina; Benza, Ignazio; Porrello, Calogero; Cajozzo, Massimo; Giannone, Antonino Giulio

2017-08-15

Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood cells and containing Alcian blue positive material. The tumor showed positive immunostaining for Vimentin, CD31, CK7, D2-40, c-MYC, Ki67, focal positivity for PanCK, and negative immunostaining for Factor VIII, CD34, WT1, CK5/6, Calretinin, EMA, HBME-1, CEA, p63, EpCAM, Bcl-2, TTF1 and Thyroglobulin. CD99 showed a granular/paranuclear pattern of positivity. The histological and immunohistochemical features were consistent with "pleural angiosarcoma with lymphatic differentiation, epithelioid variant". Epithelioid angiosarcoma with lymphatic differentiation is very rare and aggressive. Moreover, the positivity for c-MYC suggests the relationship with radiometabolic therapy. To our knowledge, this is the first case of pleural c-MYC-positive angiosarcoma with lymphatic differentiation reported in the literature and the first one arisen after radiometabolic therapy for thyroid carcinoma.

Treatment Option Overview (Pancreatic Neuroendocrine Tumors / Islet Cell Tumors)

MedlinePlus

... Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All Cancer ... also called nuclear magnetic resonance imaging (NMRI). Somatostatin receptor scintigraphy : A type of radionuclide scan that may ...

Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

ClinicalTrials.gov

2018-06-13

Breast Cancer; Cholangiocarcinoma; Colorectal Cancer; Head and Neck Neoplasms; Lymphoma, Large-Cell, Anaplastic; Melanoma; Neuroendocrine Tumors; Non-Small Cell Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Primary Brain Tumors; Renal Cell Carcinoma; Sarcomas; Salivary Gland Cancers; Adult Solid Tumor

Epigenetic modulators of thyroid cancer.

PubMed

Rodríguez-Rodero, Sandra; Delgado-Álvarez, Elías; Díaz-Naya, Lucía; Martín Nieto, Alicia; Menéndez Torre, Edelmiro

2017-01-01

There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

PubMed Central

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-01-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

An Atypical Metastasis of Follicular-Type Adenocarcinoma of the Thyroid Gland to Thumb

PubMed Central

Huri, Gazi

2011-01-01

Bone metastasis in the hand is rare. The etiology of metastatic hand cancers is different from other bones. Bronchogenic carcinoma is the most common primary tumor metastasis to hand. In this paper a rare case of thumb metastasis from “follicular-type carcinoma” of the thyroid is presented. PMID:23198224

Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.

PubMed

Sun, Dawei; Han, Shen; Liu, Chao; Zhou, Rui; Sun, Weihai; Zhang, Zhijun; Qu, Jianjun

2016-04-11

BACKGROUND The objective of this study was to explore the role of miR-199a-5p in the development of thyroid cancer, including its anti-proliferation effect and downstream signaling pathway. MATERIAL AND METHODS We conducted qRT-PCR analysis to detect the expressions of several microRNAs in 42 follicular thyroid carcinoma patients and 42 controls. We identified CTGF as target of miR-491, and viability and cell cycle status were determined in FTC-133 cells transfected with CTGF siRNA, miR-199a mimics, or inhibitors. RESULTS We identified an underexpression of miR-199a-5p in follicular thyroid carcinoma tissue samples compared with controls. Then we confirmed CTGF as a target of miR-199a-5p thyroid cells by using informatics analysis and luciferase reporter assay. Additionally, we found that mRNA and protein expression levels of CTGF were both clearly higher in malignant tissues than in benign tissues. miR-199a-5p mimics and CTGF siRNA similarly downregulated the expression of CTGF, and reduced the viability of FTC-133 cells by arresting the cell cycle in G0 phase. Transfection of miR-199a-5p inhibitors increased the expression of CTGF and promoted the viability of the cells by increasing the fraction of cells in G2/M and S phases. CONCLUSIONS Our study proves that the CTGF gene is a target of miR-199a-5p, demonstrating the negatively related association between CTGF and miR-199a. These findings suggest that miR-199a-5p might be a novel therapeutic target in the treatment of follicular thyroid carcinoma.

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.

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts.

PubMed

Sudha, Thangirala; Bharali, Dhruba J; Sell, Stewart; Darwish, Noureldien H E; Davis, Paul J; Mousa, Shaker A

2017-06-01

Thyroid hormone as L-thyroxine (T 4 ) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T 4 on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvβ3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T 4 action at αvβ3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of human GBM xenografts in immunodeficient mice, NDAT administered daily for 10 days subcutaneously as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p < 0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p < 0.001), without intratumoral hemorrhage. Up to 80% of tumor cells were necrotic in various microscopic fields (p < 0.001 vs. control tumors), an effect attributable to devascularization. There was substantial evidence of apoptosis in other fields (p < 0.001 vs. control tumors). Induction of apoptosis in cancer cells is a well-described quality of NDAT. In summary, systemic NDAT has been shown to be effective by multiple mechanisms in treatment of GBM xenografts.

Therapeutic options in locally advanced thyroid carcinoma. Our experience.

PubMed

Avenia, Nicola; Monacelli, Massimo; Sanguinetti, Alessandro; Santoprete, Stefano; Pecoriello, Roberta; Ragusa, Mark; Puma, Francesco

2012-01-01

Thyroid cancer is the most common endocrine malignancy with an incidence equal to 1% of all malignant tumors. Prognostic factors affecting survival are manifold, including in several classifications (AMES, AGES, CORN and TNM). In this sense, the invasion of adjacent structures is one of the most important variables. The authors describe the experience of a single center in surgical treatment of advanced thyroid cancer. Between 1986 and 2010 , 1565 patients were undergoing surgery with thyroid cancer. In particular, 1403 interventions were made for differentiated cancer, 97 for medullary carcinoma, 25 for insular carcinoma, 29 for anaplastic carcinoma, 2 for plasmacytoma, and 7 for lymphoma and 2 for angiosarcoma. Among these 896 showed invasion of adjacent structures and / or distant metastases. There were no perioperative deaths or major complications. Surgical procedures consisted of: 13 loboistmectomy, 519 total thyroidectomy (TT), 325 TT with lymphadenectomy of the central compartment, 7 TT with radical lymphectomy, 621 TT with functional lymphectomy, 6 TT with breast lumpectomy, 5 TT with with video-assisted lung metastasectomy, 16-TT with resection and tracheal anastomosis, 6 TT with laryngotracheal resection, 3 TT with laryngectomy, 4 TT with trachetomy, 28 TT with respiratory stent placement, 12 tracheotomy. At present, 1328 patients were free of disease, while 104 showed recurrence. Total of 133 deaths were recorded, all linked to disease relapse. The role of surgery in the treatment of advanced thyroid cancer is still undeniable. In the presence of extracapsular trespassing, in fact, the adoption of interventions demolition permits long-term survival, given the lack of aggressiveness of the tumor differentiated representing the majority of cases. The aim of surgical radicalization addition, even in the presence of distant metastases, it is justified by the possibilities offered by the therapeutic radioiodine treatment, which is not feasible in the presence of significant amounts of thyroid tissue which picks. In the presence of undifferentiated tumors, finally, endoscopic or surgical treatment may be indicated by simple purpose of palliation of respiratory symptoms.

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.

Suprasellar chordoid neoplasm with expression of thyroid transcription factor 1: evidence that chordoid glioma of the third ventricle and pituicytoma may form part of a spectrum of lineage-related tumors of the basal forebrain.

PubMed

Hewer, Ekkehard; Beck, Jürgen; Kellner-Weldon, Frauke; Vajtai, Istvan

2015-07-01

Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Variously interpreted as either astrocytic- or ependymal-like, and speculatively ascribed to the lamina terminalis/subcommissural organ, its histogenesis remains, nevertheless, unsettled. Here, we report on a suprasellar chordoid glioma occurring in a 52-year-old man. Although displaying otherwise typical morphological features, the tumor was notable for expression of thyroid transcription factor 1, a marker of tumors of pituicytic origin in the context of the sellar region. We furthermore found overlapping immunoprofiles of this example of chordoid glioma and pituicytic tumors (pituicytoma and spindle cell oncocytoma), respectively. Specifically, phosphorylated ribosomal protein S6, a marker of mTOR pathway activation, was expressed in both groups. Based on these findings, we suggest that chordoid glioma and pituicytic tumors may form part of a spectrum of lineage-related neoplasms of the basal forebrain. Copyright © 2015 Elsevier Inc. All rights reserved.

Thyroid nodule as a first manifestation of Hodgkin lymphoma–report of two cases and literature review

PubMed Central

2013-01-01

Abstract Lymphomas account for less than 5% of thyroid malignant lesions. Vast majority of them are B-cell non-Hodgkin lymphomas (NHL), while Hodgkin lymphoma (HL) is extremely rare. Here we present two cases of HL, at baseline manifesting as a thyroid lesion. First patient, 29-year-old pregnant female, initially suspected for metastatic medullary thyroid cancer, was eventually diagnosed with mixed cellularity type of thyroid HL. Second patient, 22-year-old woman with suspicion of advanced thyroid cancer, was in the end diagnosed with an extra-lymphatic classical HL of the thyroid. In both cases, despite repeated fine-needle aspiration biopsy, cytological examination gave inconclusive or misleading results. On histopathological examination, thyroid tumor cells were positive for CD15 and CD30 antigen, which is typical for Reed-Sternberg cells. In the report authors also discuss difficulties in management as well as potential importance of novel methods such as FISH, PCR and other molecular techniques in diagnostics of thyroid lymphomas. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2896947559559648 PMID:23856094

Causes of appearance of scintigraphic hot areas on thyroid scintigraphy analyzed with clinical features and comparative ultrasonographic findings.

PubMed

Iwata, Masahiro; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Fujita, Toru; Konishi, Junji

2002-06-01

This study was done retrospectively to analyze the ultrasonographic (US) findings in thyroid scintigraphic hot areas (HA). Three-thousand, eight-hundred and thirty-nine consecutive patients who underwent 99mTc-pertechnetate (n = 3435) or 123I (n = 457) scintigraphy were analyzed. HA were regarded as present when the tracer concentration was greater than the remaining thyroid tissue, or when hemilobar uptake was observed. High-resolution US examinations were performed with a real-time electronic linear scanner with a 7.5 or 10 MHz transducer. One hundred and four (2.7%) were found to be scintigraphic HA (n = 120). US revealed a nodular lesion or well-demarcated thyroid tissue corresponding to the HA in 94 areas (78.4%, Category 1), an ill-defined region with different echogenicity in 13 areas (10.8%, Category 2), and no correlating lesion in 13 areas (10.8%, Category 3). These 104 patients included 43 with adenomatous goiter (59 areas), 33 with adenoma, 11 with Hashimoto's thyroiditis, 5 with primary thyroid cancer, 4 with euthyroid ophthalmic Graves' disease (EOG), 3 with hemilobar atrophy or hypogenesis, 2 with hemilobar agenesis, 2 with hypothyroidism with blocking-type TSH-receptor antibodies (TSHRAb), I with acute suppurative thyroiditis. Among the 59 adenomatous nodules and 33 adenomas, 51 (86.4%) and 32 (97.0%), respectively, belonged to Category 1. A solitary toxic nodule was significantly larger and occurs more often in older patients than in younger patients. On the other hand, all 17 patients with known autoimmune thyroid diseases including Hashimoto's thyroiditis, EOG and hypothyroidism with blocking TSHRAb belonged to Category 2 or 3. Possible underlying mechanisms are 1) hyperfunctioning tumors or nodules, 2) localized functioning thyroid tissue freed from autoimmune destruction, inflammation or tumor invasion, 3) congenital abnormality, 4) clusters of hyperactive follicular cells caused by long-term TSH and/or TSHRAb stimulation, 5) asymmetry, etc. Scintigraphic HA are observed in patients with various thyroid diseases and high-resolution US appears to be helpful clinically for the differential diagnosis of the above mentioned disorders.

Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.

PubMed

Sáez, Carmen; Martínez-Brocca, M Asunción; Castilla, Carolina; Soto, Alfonso; Navarro, Elena; Tortolero, María; Pintor-Toro, José A; Japón, Miguel A

2006-04-01

Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. The study was conducted at a tertiary university hospital. Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied. The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05). Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.

RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis

PubMed Central

Huang, Peng; Chang, Shi; Jiang, Xiaolin; Su, Juan; Dong, Chao; Liu, Xu; Yuan, Zhengtai; Zhang, Zhipeng; Liao, Huijun

2015-01-01

A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma. PMID:25755717

Primary pulmonary adenoid cystic carcinoma: clinicopathological analyses of 12 cases.

PubMed

Qing, Song; Zhou, Keming; Liu, Xia; Li, Xiaohong; Deng, Feiyan; Ma, Yuqing

2015-01-01

Adenoid cystic primary pulmonary carcinomas (adenoid cystic carcinomas or ACCs) are rare tumors, so we described the clinical and pathological features of these tumors and related these findings with diagnosis and prognosis of ACC, comparing our data to the existing literature. Clinical and pathological features of 12 ACC cases were observed and described. Immunohistochemical EnVision staining, fluorescent PCR detection, and FISH were used to characterize tumor samples and the literature was reviewed. Of the 12 ACC cases (7 male; average 53.1 years-of-age; range 33-78 years), the chief presentation symptom was cough, followed by expectoration, gasping, and bloody sputum. Microscopically, histopathology revealed cribriform, tubular, or solid cords. CD117 was overexpressed in glandular epithelia in 9 cases and calcitonin and thyroid transcription factor-1 (TTF-1) were overexpressed in 4 cases. One case was positive for EML4 ALK gene rearrangement. ACC is a low-grade malignant tumor with poor prognosis and high recurrence and metastases. TTF-1 expression indicates a primary tumor and CD117 expression is not significant to prognosis.

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.

[DIAGNOSTIC AND TREATMENT STRATEGY IN FOLLICULAR TUMOR OF THYROID GLAND].

PubMed

Mikhaĭlova, M V; Zubarovskiĭ, I N; Osipenko, S K

2015-01-01

The article is based on the treatment results of 44 patients with follicular tunor of thyroid gland. A staged morphological assessment of thyroid nodes was performed for all patients: in case of preoperative fine-needle biopsy, urgent intraoperative study and according to results of final histological research. The urgent histological study of surgical material was conducted for 44 patients with diagnosis "follicular tumor" according to fine-needle biopsy. The data of final histological study were matched with findings of intraoperative research. A micro-follicular adenoma was detected in 22 patients (50%) and 6 (13,6%) patients had this diagnosis combined with autoimmune thyroiditis. The general part of patients didn't changed in final study, but the rate of diagnosis "micro-follicular adenoma against the background of autoimmune thyroiditis" increased. Papillary carcinoma was revealed in 5 (11,4%) patients and follicular cancer had 4 (9,1%) patients detected in intraoperative study and 3 (6,8%) more patients according to data of final research. The histopathologic feature of colloid goiter was observed in 7 (15,9%) cases and a part of such patients reduced to 6,8% during final study. One of the patients (2,3%) had final diagnosis "oncocytoma". In case of thyroid nodules detection the needle biopsy should be carried out regardless to the size of nodule. The authors recommended performing the surgery with the urgent histological study in case of undetermined histological report. The following surgical strategy was specified by the results of the urgent histological report.

Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

PubMed Central

Gershengorn, M C; Weintraub, B D

1975-01-01

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed. PMID:1159077

A Multicenter Phase 2 Trial of Pazopanib in Metastatic and Progressive Medullary Thyroid Carcinoma: MC057H

PubMed Central

Suman, Vera J.; Molina, Julian R.; Smallridge, Robert C.; Maples, William J.; Menefee, Michael E.; Rubin, Joseph; Karlin, Nina; Sideras, Kostandinos; Morris, John C.; McIver, Bryan; Hay, Ian; Fatourechi, Vahab; Burton, Jill K.; Webster, Kevin P.; Bieber, Carolyn; Traynor, Anne M.; Flynn, Patrick J.; Cher Goh, Boon; Isham, Crescent R.; Harris, Pamela; Erlichman, Charles

2014-01-01

Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%–27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities. PMID:24606083

Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system

PubMed Central

Zhang, Jialing; Rector, John; Lin, John Q.; Young, Jonathan H.; Sans, Marta; Katta, Nitesh; Giese, Noah; Yu, Wendong; Nagi, Chandandeep; Suliburk, James; Liu, Jinsong; Bensussan, Alena; DeHoog, Rachel J.; Garza, Kyana Y.; Ludolph, Benjamin; Sorace, Anna G.; Syed, Anum; Zahedivash, Aydin; Milner, Thomas E.; Eberlin, Livia S.

2018-01-01

Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules. We used the MasSpec Pen for ex vivo molecular analysis of 20 human cancer thin tissue sections and 253 human patient tissue samples including normal and cancerous tissues from breast, lung, thyroid, and ovary. The mass spectra obtained presented rich molecular profiles characterized by a variety of potential cancer biomarkers identified as metabolites, lipids, and proteins. Statistical classifiers built from the histologically validated molecular database allowed cancer prediction with high sensitivity (96.4%), specificity (96.2%), and overall accuracy (96.3%), as well as prediction of benign and malignant thyroid tumors and different histologic subtypes of lung cancer. Notably, our classifier allowed accurate diagnosis of cancer in marginal tumor regions presenting mixed histologic composition. Last, we demonstrate that the MasSpec Pen is suited for in vivo cancer diagnosis during surgery performed in tumor-bearing mouse models, without causing any observable tissue harm or stress to the animal. Our results provide evidence that the MasSpec Pen could potentially be used as a clinical and intraoperative technology for ex vivo and in vivo cancer diagnosis. PMID:28878011

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-01-12

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011).

PubMed

Imaizumi, Misa; Ohishi, Waka; Nakashima, Eiji; Sera, Nobuko; Neriishi, Kazuo; Yamada, Michiko; Tatsukawa, Yoshimi; Takahashi, Ikuno; Fujiwara, Saeko; Sugino, Keizo; Ando, Takao; Usa, Toshiro; Kawakami, Atsushi; Akahoshi, Masazumi; Hida, Ayumi

2015-02-01

Few studies have evaluated the association of radiation dose with thyroid nodules among adults exposed to radiation in childhood. To evaluate radiation dose responses on the prevalence of thyroid nodules in atomic bomb survivors exposed in childhood. This survey study investigated 3087 Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years at exposure and participated in the thyroid study of the Adult Health Study at the Radiation Effects Research Foundation. Thyroid examinations including thyroid ultrasonography were conducted between October 2007 and October 2011, and solid nodules underwent fine-needle aspiration biopsy. Data from 2668 participants (86.4% of the total participants; mean age, 68.2 years; 1213 men; and 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; median dose, 0.018 Gy; dose range, 0-4.040 Gy) were analyzed. The prevalence of all thyroid nodules having a diameter of 10 mm or more (consisting of solid nodules [malignant and benign] and cysts), prevalence of small thyroid nodules that were less than 10 mm in diameter detected by ultrasonography, and atomic bomb radiation dose-responses. Thyroid nodules with a diameter of 10 mm or more were identified in 470 participants (17.6%): solid nodules (427 cases [16.0%]), malignant tumors (47 cases [1.8%]), benign nodules (186 cases [7.0%]), and cysts (49 cases [1.8%]), and all were significantly associated with thyroid radiation dose. Excess odds ratios per gray unit were 1.65 (95% CI, 0.89-2.64) for all nodules, 1.72 (95% CI, 0.93-2.75) for solid nodules, 4.40 (95% CI, 1.75-9.97) for malignant tumors, 2.07 (95% CI, 1.16-3.39) for benign nodules, and 1.11 (95% CI, 0.15-3.12) for cysts. The interaction between age at exposure and the dose was significant for the prevalence of all nodules (P = .003) and solid nodules (P < .001), indicating that dose effects were significantly higher with earlier childhood exposure. No interactions were seen for sex, family history of thyroid disease, antithyroid antibodies, or seaweed intake. No dose-response relationships were observed for small (<10-mm diameter) thyroid nodules. Radiation effects on thyroid nodules exist in atomic bomb survivors 62 to 66 years after their exposure in childhood. However, radiation exposure is not associated with small thyroid nodules.

Management of thyroid carcinoma with radioactive 131I.

PubMed

Paryani, S B; Chobe, R J; Scott, W; Wells, J; Johnson, D; Kuruvilla, A; Schoeppel, S; Deshmukh, A; Miller, R; Dajani, L; Montgomery, C T; Puestow, E; Purcell, J; Roura, M; Sutton, D; Mallett, R; Peer, J

1996-08-01

To evaluate the role of radioactive 131I in the management of patients with well differentiated carcinoma of the thyroid. Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131I. With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131I therapy. Radioactive 131I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131I.

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.

Unusual presentation of Warthin variant of Papillary thyroid carcinoma with lymph nodal metastases in a patient of Graves' disease.

PubMed

Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Arun, B R

2015-01-01

Warthin-like Papillary thyroid carcinoma (WPTC) is a rare variant of papillary carcinoma of thyroid, PTC which derives its name by closely resembling Warthin's tumor of salivary gland. Hallmark histological feature of this variant is papillary folding lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. It is thought to be one of those differentiated thyroid cancers with favorable prognosis. We report a case of Graves' disease with a cold nodule harboring WPTC with initial presentation of lymph nodal metastases. It is important to identify this peculiar variant of PTC as 5 to 10% of them undergo dedifferentiation and 30% have the lymph nodal metastases and extra thyroidal extension.

Thyroid Hormone in the Clinic and Breast Cancer.

PubMed

Hercbergs, Aleck; Mousa, Shaker A; Leinung, Matthew; Lin, Hung-Yun; Davis, Paul J

2018-06-01

There is preclinical and recent epidemiological evidence that thyroid hormone supports breast cancer. These observations raise the issue of whether management of breast cancer in certain settings should include consideration of reducing the possible contribution of thyroid hormone to the advancement of the disease. In a preliminary experience, elimination of the clinical action of endogenous L-thyroxine (T 4 ) in patients with advanced solid tumors, including breast cancer, has favorably affected the course of the cancer, particularly when coupled with administration of exogenous 3,5,3'-triiodo-L-thyronine (T 3 ) (euthyroid hypothyroxinemia). We discuss in the current brief review the possible clinical settings in which to consider whether endogenous thyroid hormone-or exogenous thyroid hormone in the patient with hypothyroidism and coincident breast cancer-is significantly contributing to breast cancer outcome.

Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules.

PubMed

Nikiforova, Marina N; Mercurio, Stephanie; Wald, Abigail I; Barbi de Moura, Michelle; Callenberg, Keith; Santana-Santos, Lucas; Gooding, William E; Yip, Linwah; Ferris, Robert L; Nikiforov, Yuri E

2018-04-15

Molecular tests have clinical utility for thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology, although their performance requires further improvement. This study evaluated the analytical performance of the newly created ThyroSeq v3 test. ThyroSeq v3 is a DNA- and RNA-based next-generation sequencing assay that analyzes 112 genes for a variety of genetic alterations, including point mutations, insertions/deletions, gene fusions, copy number alterations, and abnormal gene expression, and it uses a genomic classifier (GC) to separate malignant lesions from benign lesions. It was validated in 238 tissue samples and 175 FNA samples with known surgical follow-up. Analytical performance studies were conducted. In the training tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations, including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions, 22q loss, and gene expression alterations. GC cutoffs were established to distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity, and 92.1% accuracy. This correctly classified most papillary, follicular, and Hurthle cell lesions, medullary thyroid carcinomas, and parathyroid lesions. In the FNA validation set, the GC sensitivity was 98.0%, the specificity was 81.8%, and the accuracy was 90.9%. Analytical accuracy studies demonstrated a minimal required nucleic acid input of 2.5 ng, a 12% minimal acceptable tumor content, and reproducible test results under variable stress conditions. The ThyroSeq v3 GC analyzes 5 different classes of molecular alterations and provides high accuracy for detecting all common types of thyroid cancer and parathyroid lesions. The analytical sensitivity, specificity, and robustness of the test have been successfully validated and indicate its suitability for clinical use. Cancer 2018;124:1682-90. © 2018 American Cancer Society. © 2018 American Cancer Society.

Thyroid and associated polyglandular neoplasms in patients who received head and neck irradiation during childhood

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

Katz, A.D.

One hundred fifty-one patients with a history of childhood irradiation to the head, neck, and thorax had neck explorations (142 for cold thyroid nodules and 9 for hypercalcemia). Fifty-nine of the patients had thyroid carcinoma, and associated glandular tumors were found in 20 others. In addition, 6 female patients developed breast carcinoma; 4 of these women also had thyroid carcinoma. In this series, 48.6% of the patients irradiated for acne and 36.4% with tonsil and adenoid irradiation developed thyroid carcinoma, but only 10.5% with thymic irradiation did so. It is suggested that the workup on these patients include not onlymore » complete thyroid and parathyroid testing, but also a careful examination of all salivary glands, both major and minor. Women should have thorough breast examinations and should perhaps be followed as if they were in the potentially high-risk breast group. When thyroid surgery is performed, a total thyroidectomy is recommended.« less

Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes.

PubMed

Paolino, Donatella; Cosco, Donato; Gaspari, Marco; Celano, Marilena; Wolfram, Joy; Voce, Pasquale; Puxeddu, Efisio; Filetti, Sebastiano; Celia, Christian; Ferrari, Mauro; Russo, Diego; Fresta, Massimo

2014-08-01

Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. 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.

Expression of Hypoxia-Associated Protein HIF-1α in Follicular Thyroid Cancer is Associated with Distant Metastasis.

PubMed

Klaus, Aumayr; Fathi, Osmen; Tatjana, Traub-Weidinger; Bruno, Niederle; Oskar, Koperek

2018-04-01

Follicular thyroid carcinomas (FTCs) are the second most common malignant neoplasia of the thyroid and in general its prognosis is quite favorable. However, the occurrence of metastases or non-responsiveness to radioiodine therapy worsens the prognosis considerably. We evaluated immunohistochemically the expression of hypoxia-associated proteins by hypoxia-induced factor 1α (HIF-1α), the stroma-remodeling marker Tenascin C, as well as markers for the epithelial-mesenchymal transition (EMT), namely E-cadherin and slug in a series of 59 sporadic FTCs. In addition, various clinicopathologic parameters were assessed like TNM-staging, age, tumor size as well as tumor characteristics like desmoplasia, necrosis, and calcification. Overexpression of HIF-1α was seen in 29 of 59 tumors (49.2%) including 21 (35.6%) FTC with strong expression of tumor cell groups. HIF-1α correlated significantly with metastasis (p < 0.001; Mann-Whitney U test), degree of desmoplasia (p = 0.042, Kruskal-Wallis test), tenascin C expression (p = 0.042, Kruskal-Wallis test), calcification (p < 0.025, Kruskal-Wallis test), necrosis (p = 0.002), age (p = 0.011, Kruskal-Wallis test) and tumor stage UICC (p = 0.022, Kruskal-Wallis test). Furthermore, metastasis was associated with the degree of desmoplasia (p = 0.014; Fisher's exact test), calcification (p = 0.008, Fisher's exact test), necrosis (p = 0.042, Fisher's exact test), tumor size (p = 0.015, Mann-Whitney U test), and age (p = 0.001, Mann-Whitney U test). In a Cox proportional hazards model, only metastasis remained as an independent risk factor for overall survival (hazard rate: 10.2 [95% CI, 02.19 to 47.26]; p = 0.003). Our data suggest that HIF-1α plays a critical role in the remodeling of the extracellular matrix as well as metastasizing process of follicular thyroid carcinoma and targeting hypoxia-associated and -regulated proteins may be considered as potential targets for personalized medicine.

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

PubMed Central

Fröhlich, Eleonore; Wahl, Richard

2017-01-01

Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

Expression of DNA repair proteins MSH2, MLH1 and MGMT in human benign and malignant thyroid lesions: An immunohistochemical study

PubMed Central

Giaginis, Constantinos; Michailidi, Christina; Stolakis, Vasileios; Alexandrou, Paraskevi; Tsourouflis, Gerasimos; Klijanienko, Jerzy; Delladetsima, Ioanna; Theocharis, Stamatios

2011-01-01

Summary Background DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, and minimizes cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations in the expression levels of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins MSH2, MLH1 and MGMT in benign and malignant thyroid lesions. Material/Methods MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 90 patients with benign and malignant lesions. Results The expression levels of MLH1 was significantly upregulated in cases with malignant compared to those with benign thyroid lesions (p=0.038). The expression levels of MGMT was significantly downregulated in malignant compared to benign thyroid lesions (p=0.001). Similar associations for both MLH1 and MGMT between cases with papillary carcinoma and hyperplastic nodules were also noted (p=0.014 and p=0.026, respectively). In the subgroup of malignant thyroid lesions, MSH2 downregulation was significantly associated with larger tumor size (p=0.031), while MLH1 upregulation was significantly associated with the presence of lymphatic and vascular invasion (p=0.006 and p=0.002, respectively). Conclusions Alterations in the mismatch repair proteins MSH2 and MLH1 and the direct repair protein MGMT may result from tumor development and/or progression. Further studies are recommended to draw definite conclusions on the clinical significance of DNA repair proteins in thyroid neoplasia. PMID:21358597

Bexarotene via CBP/p300 induces suppression of NF-κB-dependent cell growth and invasion in thyroid cancer.

PubMed

Cras, Audrey; Politis, Béatrice; Balitrand, Nicole; Darsin-Bettinger, Diane; Boelle, Pierre Yves; Cassinat, Bruno; Toubert, Marie-Elisabeth; Chomienne, Christine

2012-01-15

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells. A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging. In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation. This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway. ©2011 AACR.

New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy.

PubMed

Zhang, Lei; Liu, Wen; Wang, Qun; Li, Qinpei; Wang, Huijuan; Wang, Jun; Teng, Tieshan; Chen, Mingliang; Ji, Ailing; Li, Yanzhang

2018-03-02

Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach. Computationally-based molecular modeling studies suggested that IMCA has a high affinity for the ligand binding pocket of NR4A1. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] and apoptosis assays demonstrated that IMCA resulted in significant thyroid cancer cell death. Immunofluorescence assays showed that IMCA induced NR4A1 translocation from the nucleus to the cytoplasm in thyroid cancer cell lines, which may be involved in the cell apoptotic process. In this study, the quantitative polymerase chain reaction results showed that the IMCA-induced upregulation of sestrin1 and sestrin2 was dose-dependent in thyroid cancer cell lines. Western blot showed that IMCA increased phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and decreased phosphorylation of ribosomal protein S6 kinase (p70S6K), which is the key enzyme in the mammalian target of rapamycin (mTOR) pathway. The experimental results suggest that IMCA is a drug candidate for MTC therapy and may work by increasing the nuclear export of NR4A1 to the cytoplasm and the tumor protein 53 (p53)-sestrins-AMPK-mTOR signaling pathway.

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.

Glomus Tumor of the Neck Detected With 99mTc EDDA HYNIC-TOC.

PubMed

Girotto, Neva; Bogović-Crnčić, Tatjana; Grbac-Ivanković, Svjetlana; Valković-Zujić, Petra

2017-10-01

A 54-year-old woman was referred to thyroid evaluation because of a lump on the left side of the neck. Ultrasound exam did not show any thyroid abnormality, but highly perfused nodule at the left common carotid artery bifurcation was found. Because of the specific location, somatostatin receptor scintigraphy with Tc EDDA HYNIC-TOC was performed, starting with perfusion images and followed with SPECT/CT imaging at 2 and 4 hours. Well-perfused nodule with intensive accumulation and no other visible pathology in the body raised suspicion of a glomus tumor, consistent with MR exam performed later. Subsequent surgical removal confirmed carotid paraganglioma.

Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer.

PubMed

Xing, Mingzhao

2010-07-01

Aberrant activation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway plays a fundamental role in thyroid tumorigenesis, particularly in follicular thyroid cancer (FTC) and aggressive thyroid cancer, such as anaplastic thyroid cancer (ATC). As the drivers of this process, many genetic alterations activating the PI3K/Akt pathway have been identified in thyroid cancer in recent years. This review summarizes the current knowledge on major genetic alterations in the PI3K/Akt pathway. These include PIK3CA mutations and genomic amplification/copy gain, Ras mutations, PTEN mutations, RET/PTC and PPARgamma/Pax8 rearrangements, as well as amplification/copy gain of PIK3CB, PDK1, Akt, and various receptor tyrosine kinase genes. Most of these genetic alterations are particularly common in FTC and many of them are even more common in ATC; they are generally less common in papillary thyroid cancer (PTC), in which the MAP kinase (MAPK) pathway activated by the BRAF mutation instead plays a major role. Methylation and, thus, epigenetic silencing of PTEN, a major negative regulator of the PI3K/Akt pathway, occurs in close association with activating genetic alterations of the PI3K/Akt pathway, constituting a unique self-enhancement mechanism for this pathway. Many of these genetic alterations are mutually exclusive in differentiated thyroid tumors, but with increasing concurrence from benign tumors to FTC to ATC. RET/PTC, Ras, and receptor tyrosine kinase could dually activate the PI3K/Akt and MAPK pathways. Most cases of ATC harbor genetic alterations in these genes or other genetic combinations that can activate both pathways. It is proposed that genetic alterations in the PI3K/Akt pathway promote thyroid cell transformation to FTC and that genetic alterations in the MAPK pathway promote cell transformation to PTC; accumulation of multiple genetic alterations that can activate both pathways promotes thyroid cancer aggressiveness and progression to ATC. Genetic alterations are common in the PI3K/Akt pathway in thyroid cancer and play a fundamental role in the tumorigenesis and progression of this cancer. This provides a strong basis for the emerging development of novel genetic-based diagnostic, prognostic, and therapeutic strategies for thyroid cancer.

Immune Response in Thyroid Cancer: Widening the Boundaries

PubMed Central

Ward, Laura Sterian

2014-01-01

The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. PMID:25328756

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.

Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.

PubMed

Galdiero, Francesca; Bello, Anna Maria; Spina, Anna; Capiluongo, Anna; Liuu, Sophie; De Marco, Margot; Rosati, Alessandra; Capunzo, Mario; Napolitano, Maria; Vuttariello, Emilia; Monaco, Mario; Califano, Daniela; Turco, Maria Caterina; Chiappetta, Gennaro; Vinh, Joëlle; Chiappetta, Giovanni

2018-01-30

BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

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

Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning.

PubMed

Ogawa, Yoshikazu; Niizuma, Kuniyasu; Tominaga, Teiji

2017-11-01

Craniopharyngioma is a slow-growing tumor, but long-term tumor control with maintenance of quality of life is sometimes very difficult to achieve, and hypothalamic disturbance should be strictly avoided in the treatment. However, management of the pituitary gland and/or pituitary stalk varies among surgeons and institutions. This retrospective review identified 44 patients, 24 males and 20 females with craniopharyngiomas who were initially treated by surgery through the extended transsphenoidal approach with pituitary stalk sectioning at a single institute. If the tumor bed involved the posterior lobe of the pituitary gland, pituitary stalk, anterior and/or mid portion of the third ventricle floor, these structures were removed en-bloc together with the tumor. The closest attention was paid to preserve fine arteries running along the surface of optic chiasm and the lateral walls of the third ventricle. Surgical outcome and changes in postoperative endocrinological status were investigated. Gross total removal was achieved in 40 of 44 patients (91%), and all patients could discharge without autonomic and/or thermal disturbances. Tumor remnants were identified with tight adhesion to the perforating arteries in 2 cases, tight adhesion to mammillary bodies in 1, and optic chiasm in 1. Administration of anti-diuretic hormone could be discontinued in 23 of 44 patients (52.3%) with improved diabetes insipidus (DI), although no patient could discontinue glucocorticoid administration. Preservation of thyroid function was achieved in another 23 of 44 patients (52.3%), and recovery from DI was correlated with preservation of thyroid function (p=0.016). Pituitary dysfunction is partially reversible even with pituitary stalk sectioning. Regrowth of tumor in the anterior and/or mid portion of the third ventricle floor including pituitary stalk can possibly be prevented by aggressive tumor removal, and co-achievement of long-term tumor control with maintenance of quality of life could be possible to preserve the lateral wall of the third ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors of metastasis to lymph nodes posterior to the right recurrent laryngeal nerve in differentiated thyroid carcinoma: A prospective study.

PubMed

Liu, Ziwen; Sun, Mengqing; Xiao, Yiding; Yang, Jing; Zhang, Taiping; Zhao, Yupei

2017-07-01

To study the clinicopathological characteristics and the risk factors of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in differentiated thyroid carcinoma; and to identify the indication for LN-prRLN dissection. We treated 145 patients with differentiated thyroid carcinoma with appropriate surgical intervention. The specimens were examined by the pathologists. The right paratracheal lymph nodes were divided into two groups: anterior or posterior to right recurrent laryngeal nerve (VIa or VIp compartment, respectively). We recorded the clinical characteristics, histopathological features of the primary tumors, and lymph node metastasis of the patients. The results were statistically analyzed. There were 85 patients (58.6%) with central lymph node metastasis, of whom 61 (42.1%) had metastasis in VIa compartment; 16 patients (11.0%) had VIp subdistrict metastasis; and 25 patients had lateral lymph node metastasis. Multiplicity, larger tumor (≥1 cm), and coexistence of central lymph node metastasis, VIa compartment metastasis, and lateral lymph node metastasis were all significantly related with LN-prRLN metastasis, while sex, age, location of the tumor, and extrathyroid extension of the tumor showed no significant relation (p > 0.05). The incidence of LN-prRLN metastasis was lower than other central lymph nodes, as well as lymph nodes anterior to right recurrent laryngeal nerve. When there were multiple foci of tumors, or the tumor was larger than 1 cm, or central or lateral LN metastasis was indicated by preoperative ultrasound or confirmed by intraoperative frozen sections, it is strongly recommended that exploration and dissection of the LN-prRLN should only be performed by experienced surgeons. Copyright © 2016. Published by Elsevier Taiwan.

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

PubMed

Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

2011-01-01

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

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.

Thyroid Hormone Receptor β Suppression of RUNX2 is Mediated by Brahma Related Gene 1 Dependent Chromatin Remodeling.

PubMed

Gillis, Noelle E; Taber, Thomas H; Bolf, Eric L; Beaudet, Caitlin M; Tomczak, Jennifer A; White, Jeffrey H; Stein, Janet L; Stein, Gary S; Lian, Jane B; Frietze, Seth; Carr, Frances E

2018-05-09

Thyroid hormone receptor beta (TRβ) suppresses tumor growth through regulation of gene expression, yet the associated TRβ-mediated changes in chromatin assembly are not known. The chromatin ATPase Brahma Related Gene 1 (BRG1, SMARCA4), a key component of chromatin remodeling complexes, is altered in many cancers, but its role in thyroid tumorigenesis and TRβ-mediated gene expression is unknown. We previously identified the oncogene runt-related transcription factor 2 (RUNX2) as a repressive target of TRβ. Here we report differential expression of BRG1 in non-malignant and malignant thyroid cells concordant with TRβ. BRG1 and TRβ have similar nuclear distribution patterns and significant co-localization. BRG1 interacts with TRβ and together are part of the regulatory complex at the RUNX2 promoter. Loss of BRG1 increases RUNX2 levels whereas re-introduction of TRβ and BRG1 synergistically decrease RUNX2 expression. RUNX2 promoter accessibility corresponded to RUNX2 expression levels. Inhibition of BRG1 activity ncreased accessibility of the RUNX2 promoter and corresponding expression. Our results reveal a novel mechanism of TRβ repression of oncogenic gene expression: TRβ recruitment of BRG1 to induce chromatin compaction and diminished RUNX2 expression. Therefore, BRG1-mediated chromatin remodeling may be obligatory for TRβ transcriptional repression and tumor suppressor function in thyroid tumorigenesis.

[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.

Warthin-Like Papillary Carcinoma of the Thyroid Gland: Case Report and Review of the Literature

PubMed Central

Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario

2012-01-01

We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable. PMID:23243533

Warthin-like papillary carcinoma of the thyroid gland: case report and review of the literature.

PubMed

Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario

2012-01-01

We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable.

[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.

HISTOPATHOLOGIC CHARACTERISTICS OF THYROID GLAND NEOPLASMS IN THOMSON'S GAZELLES ( EUDORCUS THOMSONII).

PubMed

French, Stephanie J; Garner, Michael M; Kiupel, Matti

2018-03-01

Published reports of neoplasms in Thomson's gazelles ( Eudorcas thomsonii) are very rare, but thyroid tumors were the most common neoplasm of this species, accounting for 12% of reported pathologies in a 1998-2012 retrospective study of cases submitted for histologic review of grossly enlarged thyroid glands. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms in 10 Thomson's gazelles from five different zoological collections. Neoplasms were submitted as biopsies from six gazelles or collected during necropsy from four gazelles. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Radiographic mineral density was detected in one of the neoplastic masses. Histologically, the neoplasms were classified as microfollicular thyroid adenoma ( n = 2), solid thyroid adenoma ( n = 2), papillary thyroid adenoma ( n = 1), and solid thyroid carcinoma ( n = 5). Neoplastic cells in all 10 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin, but negative for calcitonin. While five cases had histologic features of malignancy, there was no evidence of metastatic disease either clinically (biopsies) or on necropsy. Numerous concurrent diseases, including cardiomyopathies and nephropathies, were present and led to choice for euthanasia in several cases.

Critical Pitfalls in the use of BRAF Mutation as a Diagnostic Tool in Thyroid Nodules: a Case Report.

PubMed

Kuhn, Elisabetta; Ragazzi, Moira; Zini, Michele; Giordano, Davide; Nicoli, Davide; Piana, Simonetta

2016-09-01

Thyroid fine-needle aspiration (FNA) cytology is the primary tool for the diagnostic evaluation of thyroid nodules. BRAF mutation analysis is employed as an ancillary tool in indeterminate cases, as recommended by the American Thyroid Association management guidelines. Hereby, we report the case of a 73-year-old woman who presented an 8-mm-size, ill-defined, left thyroid nodule. FNA resulted "suspicious for papillary thyroid carcinoma". BRAF mutation status was analyzed, and somatic BRAF (V600E) mutation identified. The patient underwent a total thyroidectomy. At histological examination, the nodule was composed of Langerhans cells, admixed with many eosinophils. A final diagnosis of Langerhans cell histiocytosis of the thyroid was made. Our case emphasizes the critical diagnostic pitfalls due to the use of BRAF (V600E) mutation analysis in thyroid FNA. Notably, BRAF (V600E) mutation is common in melanoma, colorectal carcinoma, lung carcinoma, ovarian carcinoma, brain tumors, hairy cell leukemia, multiple myeloma, and histiocytoses. Therefore, in cases of indeterminate FNA with unclassifiable atypical cells BRAF (V600E) mutated, the possibility of a localization of hystiocytosis or a secondary thyroid malignancy should be taken into account.

Thyrotoxicosis presenting as hypogonadism: a case of central hyperthyroidism.

PubMed

Childress, R Dale; Qureshi, M Nauman; Kasparova, Meri; Oktaei, Hooman; Williams-Cleaves, Beverly; Solomon, Solomon S

2004-11-01

Herein, we present a case of central thyrotoxicosis with well-documented serial therapeutic interventions. Thyroid-stimulating hormone (TSH)-secreting pituitary tumors represent a rare cause of hyperthyroidism. It is being diagnosed more frequently with the third-generation TSH assay. Many conditions can produce normal or elevated TSH levels in combination with elevated thyroid hormone levels. The differential diagnosis includes resistance to thyroid hormone (RTH, Refetoff's syndrome), assay interference from anti-T4/T3 and heterophile antibodies, elevated or altered binding proteins, drugs affecting peripheral metabolism, and noncompliance with thyroid replacement therapy. In contrast to RTH, our patient presented had high alpha-subunit-to-TSH molar ratio, failed TSH response to thyrotropin-releasing hormone stimulation, and a large pituitary mass. Normal or high TSH in the presence of elevated T4 or T3 is a fairly common clinical scenario with many etiologic possibilities. This TSH-producing adenoma represents an unusual initial clinical presentation, as hypogonadism appeared before features of thyrotoxicosis were appreciated. This case represents the most modern therapeutic approach to the management of this rare disease. Our patient has done well on octreotide with control of thyrotoxicosis and an additional 30% shrinkage of his tumor mass.

Inverse association between age at the time of radiation exposure and extent of disease in cases of radiation-induced childhood thyroid carcinoma in Belarus.

PubMed

Farahati, J; Demidchik, E P; Biko, J; Reiners, C

2000-03-15

Increased incidence of childhood thyroid carcinoma, particularly in the youngest children, has been reported from Belarus since the nuclear reactor accident at Chernobyl in 1986. The relation between disease severity and age at the time of the accident, not previously established in this cohort, was analyzed in this study. The authors studied the association between disease severity, expressed by TNM classification, and age at radiation exposure in a cohort of 483 patients younger than 8 years at the time of the Chernobyl accident who have been diagnosed with differentiated thyroid carcinoma since 1986 at the Center for Thyroid Cancer in Minsk. The associations between age at radiation exposure and TNM categories were compared among 4 groups of patients who were ages <2, 2.1-4, 4.1-6, and 6.1-8 years at the time of the accident. Multivariate discriminant analysis was performed to examine the effects of age at the time of the accident, gender, histology, tumor stage, and N classification on the frequency of distant metastasis. Younger age at the time of the Chernobyl accident was associated with greater extrathyroidal tumor extension (P<0.01) and more lymph node involvement (P<0.0001) and tended to be associated with more distant metastases (P = 0.09). Compared with patients who were ages 6.1-8 years at the time of the accident, patients who were younger than 2 years had significantly more extrathyroidal tumor invasion (P = 0.004), lymph node involvement (P = 0.004), and distant metastases (P = 0.05). The age at diagnosis increased with older age at the time of radiation exposure (linear regression analysis; correlation coefficient = 0. 67; P<0.001). Multivariate analysis revealed that younger age at the time of the accident (P = 0.001) and advanced locoregional tumor extension (P<0.001) were the only powerful factors influencing the risk for distant metastasis of this malignancy. The severity of disease was associated inversely with age at the time of radiation exposure in these cases of radiation-induced childhood thyroid carcinoma. Copyright 2000 American Cancer Society.

Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.

PubMed Central

Xu, X. C.; el-Naggar, A. K.; Lotan, R.

1995-01-01

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7677193

IgG4-related Mikulicz's disease associated with thyroiditis: a case report and review of the literature.

PubMed

Zhang, Yujiao; Du, Yi; Li, Kaijun; He, Jianfeng

2014-03-01

To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis. We describe a 25-year-old Chinese man who presented with bilateral, painless swellings of the lachrymal glands, parotid glands, and thyroid nodules. The patient underwent left-sided dacryoadenectomy and the diagnosis of IgG4-related Mikulicz's disease was pathologically confirmed. The size of the right-sided lachrymal gland and parotid glands recovered fundamentally after one month of glucocorticoid therapy. IgG4-related Mikulicz's disease associated with thyroiditis should be considered in the differential diagnosis of bilateral swellings of lachrymal glands, salivary glands, and thyroid nodules. Surgical excision is recommended in order to treat the tumor and to ensure the pathological diagnosis. Glucocorticoid therapy should be considered in association with surgery after removal.

Silk-elastin-like protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus.

PubMed

Price, Daniel L; Li, Pingdong; Chen, Chun-Hao; Wong, Danni; Yu, Zhenkun; Chen, Nanhai G; Yu, Yong A; Szalay, Aladar A; Cappello, Joseph; Fong, Yuman; Wong, Richard J

2016-02-01

Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. © 2014 Wiley Periodicals, Inc.

BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

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

Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei

2009-03-09

Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relativelymore » rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.« less

Silk-elastin-like protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus

PubMed Central

Price, Daniel L.; Li, Pingdong; Chen, Chun-Hao; Wong, Danni; Yu, Zhenkun; Chen, Nanhai G.; Yu, Yong A.; Szalay, Aladar A.; Cappello, Joseph; Fong, Yuman; Wong, Richard J.

2016-01-01

Background Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. Methods Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. Results GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. Conclusion The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. PMID:25244076

Single photon emission computed tomography imaging for temporal dynamics of thyroidal and salivary radionuclide accumulation in 17-allyamino-17-demothoxygeldanamycin-treated thyroid cancer mouse model

PubMed Central

Liu, Yu-Yu; Brandt, Michael P; Shen, Daniel H; Kloos, Richard T; Zhang, Xiaoli; Jhiang, Sissy M

2014-01-01

Selective iodide uptake and prolonged iodine retention in the thyroid is the basis for targeted radioiodine therapy for thyroid cancer patients; however, salivary gland dysfunction is the most frequent nonthyroidal complications. In this study, we have used noninvasive single photon emission computed tomography functional imaging to quantify the temporal dynamics of thyroidal and salivary radioiodine accumulation in mice. At 60 min post radionuclide injection, radionuclide accumulation in the salivary gland was generally higher than that in thyroid due to much larger volume of the salivary gland. However, radionuclide accumulation per anatomic unit in the salivary gland was lower than that in thyroid and was comparable among mice of different age and gender. Differently, radionuclide accumulation per anatomic unit in thyroid varied greatly among mice. The extent of thyroidal radioiodine accumulation stimulated by a single dose of exogenous bovine TSH (bTSH) in triiodothyronine (T3)-supplemented mice was much less than that in mice received neither bTSH nor T3 (nontreated mice), suggesting that the duration of elevated serum TSH level is important to maximize thyroidal radioiodine accumulation. Furthermore, the extent and duration of radioiodine accumulation stimulated by bTSH was less in the thyroids of the thyroid-targeted RET/PTC1 (thyroglobulin (Tg)-PTC1) mice bearing thyroid tumors compared with the thyroids in wild-type (WT) mice. Finally, the effect of 17-allyamino-17-demothoxygeldanamycin on increasing thyroidal, but not salivary, radioiodine accumulation was validated in both WT mice and Tg-PTC1 preclinical thyroid cancer mouse model. PMID:20943721

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.

[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.

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

Age, tumor size, and in-office ultrasonography are predictive parameters of malignancy in follicular neoplasms of the thyroid.

PubMed

Paramo, Juan C; Mesko, Thomas

2008-01-01

To identify clinical predictors of malignancy in patients with intraoperative frozen-section diagnosis of follicular neoplasm of the thyroid. We performed a retrospective cross-sectional study of 71 patients with intraoperative frozen-section diagnosis of follicular neoplasm who underwent thyroidectomy between January 1992 and December 2000. Age, sex, tumor size, and in-office ultrasonography characteristics of the lesions were assessed. These clinical factors were compared between cases that had benign definitive pathologic findings and those that were found to be carcinomas on permanent sections. Nine (13%) of the 71 follicular neoplasms were found to be carcinomas after definitive pathologic evaluation. The incidence of malignancy was 13% (2/16) in men and 13% (7/55) in women (P>.5). Patients younger than 45 years had a 27% (8/30) incidence of malignancy compared with 2% (1/41) in patients 45 years or older (P<.01). Of tumors smaller than 4 cm, 7% (4/55) were ultimately diagnosed as carcinomas compared with 31% (5/16) of those 4 cm or larger (P = .05). When the in-office ultrasonography findings were interpreted as benign, only 7% (3/46) of cases were malignant compared with 40% (4/10) when the ultrasonography findings were suspicious (P = .02). Age and tumor size are predictive parameters of malignancy in follicular neoplasm of the thyroid. Suspicious ultrasonography findings also have an important predictive role. Total thyroidectomy is reasonable in patients with follicular neoplasm on frozen section if they are young (<45 years old), with large (>4 cm) tumors or if there are suspicious findings on in-office ultrasonography.

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

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.

Benign breast disease and risk of thyroid cancer.

PubMed

Luo, Juhua; Hendryx, Michael; Nassir, Rami; Cheng, Ting-Yuan David; Lane, Dorothy; Margolis, Karen L

2017-09-01

It has been suggested that breast and thyroid diseases may be linked. The aim of this study was to investigate the association between benign breast disease and subsequent risk of thyroid cancer. Postmenopausal women (n = 133,875) aged 50-79 years were followed up for a mean of 14 years. Benign breast disease was defined by history of biopsy. Incident thyroid cancer cases were confirmed by medical record review. Multivariable Cox proportional hazard modeling was used to estimate hazard ratios. There were 370 incident thyroid cancer cases during the follow-up period. Compared to women without BBD, women with BBD had a significant increased risk of thyroid cancer after adjusting for potential confounders (HR 1.38 95% CI 1.10-1.73), especially for women with more than two biopsies (HR 1.59 95% CI 1.10-2.26). There were no significant differences in thyroid tumor size, stage or histologic types between women with and without BBD. Our large prospective study observed that postmenopausal women with BBD had an increased risk for thyroid cancer compared with women without BBD. A more detailed investigation of thyroid cancer risk according to different subtypes of benign breast disease is needed to better understand the association observed between thyroid and benign breast diseases.

Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

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

Dagrosa, Maria Alejandra; Thomasz, Lisa M.Sc.; Longhino, Juan

Purpose: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Methods and Materials: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60more » mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10{sup 8} n/cm{sup 2}/sec for 83.4 min. Results: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm{sup 3} or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Conclusions: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.« less

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.

Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors.

PubMed

Fukuda, Takahiro; Akiyama, Nobutake; Ikegami, Masahiro; Takahashi, Hitoshi; Sasaki, Atsushi; Oka, Hidehiro; Komori, Takashi; Tanaka, Yuko; Nakazato, Youichi; Akimoto, Jiro; Tanaka, Masahiko; Okada, Yoshikazu; Saito, Saburo

2010-05-01

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.

Morphological and immunohistochemical characterization of spontaneous thyroid gland neoplasms in guinea pigs (Cavia porcellus).

PubMed

Gibbons, P M; Garner, M M; Kiupel, M

2013-03-01

Reports of thyroid gland neoplasms in guinea pigs (Cavia porcellus) are rare, but thyroid tumors are among the most common neoplasms seen in cases submitted to Northwest ZooPath. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms and lists the concurrent conditions found in guinea pig cases submitted to Northwest ZooPath during 1998 to 2008. Of 526 guinea pig case submissions, 19 had thyroid neoplasms. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Neoplasms were removed as an excisional biopsy from 7 guinea pigs, and 3 of these animals died within a few days after surgery. Radiographic mineral density was detected in 2 masses. Five of the neoplasms were reported as cystic; 5 were black or a dark color. Histologically, the neoplasms were classified as macrofollicular thyroid adenoma (8), thyroid cystadenoma (1), papillary thyroid adenoma (3), follicular thyroid carcinoma (5), follicular-compact thyroid carcinoma (1), and small-cell thyroid carcinoma (1). Osseous metaplasia was present in 8 neoplasms, and myeloid hyperplasia was present in 1 neoplasm. All 19 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin but negative for parathyroid hormone and calcitonin. Numerous concurrent diseases, including hepatopathies, cardiomyopathies, and nephropathies, were present and considered to be the cause of death in many cases. Research is needed to determine the appropriate modalities for antemortem diagnosis and treatment and whether thyroid disease plays a role in the pathogenesis of chronic degenerative diseases in guinea pigs.

Role of PTEN in the Tumor Microenvironment

DTIC Science & Technology

2009-06-01

OS, Boers M, Molthoff CF, van Diest PJ. (2008). Hexokinase III, cyclin A and galectin - 3 are overexpressed in malignant follicular thyroid nodules...2009 2. REPORT TYPE Annual 3 . DATES COVERED (From - To) 4. TITLE AND SUBTITLE Role of PTEN in the Tumor Microenvironment 5a. CONTRACT NUMBER...

78 FR 8410 - Thiacloprid; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

...) were noted in dog, rat, and mouse studies. Increased prostate weight and prostatic hypertrophy were... acetylcholine receptors. In the neurotoxicity studies in rats, there was a reduction in motor and locomotor... uterine tumors in rats, thyroid follicular adenomas in rat and ovarian tumors in mice. A cancer slope...

Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

PubMed

Wolf, Douglas C; Allen, James W; George, Michael H; Hester, Susan D; Sun, Guobin; Moore, Tanya; Thai, Sheau-Fung; Delker, Don; Winkfield, Ernest; Leavitt, Sharon; Nelson, Gail; Roop, Barbara C; Jones, Carlton; Thibodeaux, Julie; Nesnow, Stephen

2006-01-01

Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular mode of toxic and tumorigenic action for these compounds is not known, however it has been proposed that triadimefon-induced rat thyroid tumors arise through the specific mechanism of increased TSH. The present study was designed to identify commonalities of effects across the different conazoles and to determine unique features of the tissue responses that suggest a toxicity pathway and a mode of action for the observed thyroid response for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500, 1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000 ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs, body and liver weight, histopathology of thyroid and liver, hepatic metabolizing enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose-dependent increase in liver weight but not body weight for all treatments. The indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD) activity, had a dose-related increase at all time points for all conazoles. Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme measured as glucuronidation of 1-naphthol, was induced to the same extent after 30 and 90 days for all three conazoles. Livers from all high dose treated rats had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid follicular cell hypertrophy, increased follicular cell proliferation, and colloid depletion were present only after 30 days in rats treated with the high dose of triadimefon. A dose-dependent decrease in T4 was present after 4 days with all 3 compounds but only the high doses of propiconazole and triadimefon produced decreased T4 after 30 days. T3 was decreased after high-dose triadimefon after 4 days and in a dose-dependent manner for all compounds after 30 days. Thyroid hormone levels did not differ from control values after 90 days and TSH was not increased in any exposure group. A unique pattern of toxic responses was not identified for each conazole and the hypothesized mode of action for triadimefon-induced thyroid gland tumors was not supported by the data.

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

[Intraoperative frozen sections of the thyroid gland].

PubMed

Synoracki, S; Ting, S; Siebolts, U; Dralle, H; Koperek, O; Schmid, K W

2015-07-01

The goal of evaluation of intraoperative frozen sections of the thyroid gland is to achieve a definitive diagnosis which determines the subsequent surgical management as fast as possible; however, due to the specific methodological situation of thyroid frozen sections evaluation a conclusive diagnosis can be made in only some of the cases. If no conclusive histological diagnosis is possible during the operation, subsequent privileged processing of the specimen allows a final diagnosis at the latest within 48 h in almost all remaining cases. Applying this strategy, both pathologists and surgeons require a high level of communication and knowledge regarding the specific diagnostic and therapeutic peculiarities of thyroid malignancies because different surgical strategies must be employed depending on the histological tumor subtype.

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

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.

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.

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.

[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.

Small cell lung cancer with metastasis to the thyroid in a patient with toxic multinodular goiter.

PubMed

Ozgu, Eylem Sercan; Gen, Ramazan; Ilvan, Ahmet; Ozge, Cengiz; Polat, Ayşe; Vayisoglu, Yusuf

2012-11-01

Thyroid metastasis of lung cancer is rarely observed in clinical practice. The primary cancers which metastasize to the thyroid gland are mostly renal cell carcinoma, lung cancer, and breast cancer. Transient destructive thyrotoxicosis is caused by massive metastasis of extrathyroid tumors. We herein present a case report of a patient with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. A 66-year-old man complained of swelling around the right side of the neck, dyspnea, progressive weight loss, and palpitation starting since 3 months before his admission. The patient was diagnosed with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. The case report presented here illustrates the challenge of making a definitive and adequate diagnosis, particularly if the patient presents with 2 potential causes of thyrotoxicosis. Thyroid scintigraphy is an important tool for differential diagnosis of thyrotoxicosis.

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

Revising the embryonic origin of thyroid C cells in mice and humans

PubMed Central

Johansson, Ellen; Andersson, Louise; Örnros, Jessica; Carlsson, Therese; Ingeson-Carlsson, Camilla; Liang, Shawn; Dahlberg, Jakob; Jansson, Svante; Parrillo, Luca; Zoppoli, Pietro; Barila, Guillermo O.; Altschuler, Daniel L.; Padula, Daniela; Lickert, Heiko; Fagman, Henrik; Nilsson, Mikael

2015-01-01

Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail–chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca2+ homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development. PMID:26395490

Vemurafenib-resistance via de novo RBM genes mutations and chromosome 5 aberrations is overcome by combined therapy with palbociclib in thyroid carcinoma with BRAFV600E.

PubMed

Antonello, Zeus A; Hsu, Nancy; Bhasin, Manoj; Roti, Giovanni; Joshi, Mukta; Van Hummelen, Paul; Ye, Emily; Lo, Agnes S; Karumanchi, S Ananth; Bryke, Christine R; Nucera, Carmelo

2017-10-17

Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF V600E represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF WT/V600E -positive PTC patient-derived cells with P16 -/- (CDKN2A -/- ). Following treatment with vemurafenib, we expanded a sub-population of cells with primary resistance and characterized them genetically and cytogenetically. We have used exome sequencing, metaphase chromosome analysis, FISH and oligonucleotide SNP-microarray assays to assess clonal evolution of vemurafenib-resistant cells. Furthermore, we have validated our findings by networks and pathways analyses using PTC clinical samples. Vemurafenib-resistant cells grow similarly to naïve cells but are refractory to apoptosis upon treatment with vemurafenib, and accumulate in G2-M phase. We find that vemurafenib-resistant cells show amplification of chromosome 5 and de novo mutations in the RBM (RNA-binding motifs) genes family (i.e. RBMX, RBM10). RBMX knockdown in naïve-cells contributes to tetraploidization, including expansion of clones with chromosome 5 aberrations (e.g. isochromosome 5p). RBMX elicits gene regulatory networks with chromosome 5q cancer-associated genes and pathways for G2-M and DNA damage-response checkpoint regulation in BRAF WT/V600E -PTC. Importantly, combined therapy with vemurafenib plus palbociclib (inhibitor of CDK4/6, mimicking P16 functions) synergistically induces stronger apoptosis than single agents in resistant-cells and in anaplastic thyroid tumor cells harboring the heterozygous BRAF WT/V600E mutation. Critically, our findings suggest for the first time that targeting BRAF WT/V600E and CDK4/6 represents a novel therapeutic strategy to treat vemurafenib-resistant or vemurafenib-naïve radioiodine-refractory BRAF WT/V600E -PTC. This combined therapy could prevent selection and expansion of aggressive PTC cell sub-clones with intrinsic resistance, targeting tumor cells either with primary or secondary resistance to BRAF V600E inhibitor.

Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma.

PubMed

Yano, Seiichi; Ashida, Kenji; Nagata, Hiromi; Ohe, Kenji; Wada, Naoko; Takeichi, Yukina; Hanada, Yuki; Ibayashi, Yuta; Wang, Lixiang; Sakamoto, Shohei; Sakamoto, Ryuichi; Uchi, Hiroshi; Shiratsuchi, Motoaki; Furue, Masutaka; Nomura, Masatoshi; Ogawa, Yoshihiro

2018-06-08

Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85 years; 54% female) were retrospectively analyzed. Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

NITROBENZENE CARCINOGENICITY IN ANIMALS AND HUMAN HAZARD EVALUATION

EPA Science Inventory

Nitrobenzene (NB) human cancer studies have not been reported, but animals studies have. Three rodent strains inhaling NB produce cancer at eight sites. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, F344/N male rats respond with ...

Deletion of tumor progression locus 2 attenuates alcohol induced hepatic inflammation

USDA-ARS?s Scientific Manuscript database

BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammator...

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.

In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is associated with poor prognosis, in contrast to BRAF V600E mutation.

PubMed

Nasirden, Almira; Saito, Tsuyoshi; Fukumura, Yuki; Hara, Kieko; Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Asahina, Miki; Yamashita, Atsushi; Tomomasa, Ran; Hayashi, Takuo; Arakawa, Atsushi; Yao, Takashi

2016-12-01

The prognostic value of BRAF V600E and TERT promoter mutation in papillary thyroid carcinoma (PTC) is controversial. We examined alterations in BRAF V600E and TERT promoter by PCR-direct sequencing in PTC of 144 Japanese patients. Alternative lengthening of telomeres was examined as another mechanism of telomere maintenance by immunohistochemical staining for ATRX and DAXX. Of the clinicopathological characteristics, regional lymph node metastasis, extra-thyroid extension, multifocality/intrathyroidal spread, and advanced stage (III/V) were associated with shorter disease-free survival rate (DFSR). TERT promoter mutation was found in eight patients (6 %), and this was significantly associated with total thyroidectomy, multifocality/intrathyroidal spread, lymph node metastasis and advanced stage. The BRAF V600E mutation was found in 53 patients (38.2 %) but was not associated with any clinicopathological factors. TERT mutations were not correlated with BRAF V600E mutation status. TERT mutation-positive tumors (TERT+) showed lower DFSR than BRAF V600E -mutation-positive tumors (BRAF V600E +), and TERT+/BRAF V600E + tumors showed lower DFSR than BRAF V600E + tumors. No cases showed loss of ATRX/DAXX expression by immunohistochemistry. TERT promoter mutations showed a lower prevalence in our series and appeared to be associated with aggressive behavior. In PTCs, telomerase activation by TERT promoter mutation might be more important than alternative lengthening of telomeres.

Anaplastic thyroid carcinoma with rhabdoid features.

PubMed

Feng, Gong; Laskin, William B; Chou, Pauline M; Lin, Xiaoqi

2015-05-01

Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive neoplasm, characterized by complete or partial composition by undifferentiated cells. We report a case of ATC with rhabdoid features in a 68-year-old male, who presented with a rapidly enlarging neck mass. Fine-needle aspiration (FNA) of the thyroid mass showed discohesive, pleomorphic round to polygonal rhabdoid cells with one to multiple eccentric, large, rounded nuclei with a prominent nucleolus, moderate to abundant, globoid cytoplasm which oftentimes harbor a pale para-nuclear inclusion. The cytoplasm of some cells contained variously sized, eosinophilic granules. Rare cells contained neutrophils in their cytoplasm. Mitoses including atypical mitotic figures and necrosis were readily seen. Histologic examination of needle core biopsy (NCB) revealed individual dispersed and sheets of pleomorphic neoplastic cells with similar cytomorphologic features as described above. The tumor extensively infiltrated a myxocollagenous stroma containing lymphocytes and neutrophils, and demonstrated foci of necrosis. Tumor cells were immunoreactive for keratins AE1/AE3, CAM5.2, and CK19; PAX-8, and p63, but negative for S-100, HMB-45, calcitonin, TTF-1, thyroglobulin, CD56, HBME-1, glypican-3, PAX-5, myogenin, CD31, and INI-1. The differential diagnosis of this malignant rhabdoid tumor is discussed. © 2015 Wiley Periodicals, Inc.

The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma

PubMed Central

Cai, Ye-Feng; Wang, Qing-Xuan; Ni, Chun-Jue; Guo, Gui-Long; Li, Quan; Wang, Ou-Chen; Wu, Liang; Du, Hai-Yan; You, Jie; Zhang, Xiao-Hua

2015-01-01

Abstract This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients. We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection. Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 ± 0.6 vs 1.3 ± 0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 ± 0.9 vs 1.0 ± 0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT. Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients. PMID:26554782

The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma: A Large Case-control Study.

PubMed

Cai, Ye-Feng; Wang, Qing-Xuan; Ni, Chun-Jue; Guo, Gui-Long; Li, Quan; Wang, Ou-Chen; Wu, Liang; Du, Hai-Yan; You, Jie; Zhang, Xiao-Hua

2015-11-01

This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients.We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection.Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 ± 0.6 vs 1.3 ± 0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 ± 0.9 vs 1.0 ± 0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT.Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients.

The impact of thyroid hormones on patients with hepatocellular carcinoma.

PubMed

Pinter, Matthias; Haupt, Lukas; Hucke, Florian; Bota, Simona; Bucsics, Theresa; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

2017-01-01

Hypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients. Of 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated. Thyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9-15.7 months) vs. 7.3 months (5.4-9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5-13.6 months) vs. 3.3 months (2.2-4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3-3.3); p = 0.002) in multivariate analysis. TSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

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.

Thyroid C-Cell Biology and Oncogenic Transformation

PubMed Central

Cote, Gilbert J.; Grubbs, Elizabeth G.; Hofmann, Marie-Claude

2017-01-01

The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies. PMID:26494382

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.

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

Comparison of the Light Charged Particles on Scatter Radiation Dose in Thyroid Hadron Therapy

PubMed Central

Azizi, M; Mowlavi, AA

2014-01-01

Background: Hadron therapy is a novel technique of cancer radiation therapy which employs charged particles beams, 1H and light ions in particular. Due to their physical and radiobiological properties, they allow one to obtain a more conformal treatment, sparing better the healthy tissues located in proximity of the tumor and allowing a higher control of the disease. Objective: As it is well known, these light particles can interact with nuclei in the tissue, and produce the different secondary particles such as neutron and photon. These particles can damage specially the critical organs behind of thyroid gland. Methods: In this research, we simulated neck geometry by MCNPX code and calculated the light particles dose at distance of 2.14 cm in thyroid gland, for different particles beam: 1H, 2H, 3He, and 4He. Thyroid treatment is important because the spine and vertebrae is situated right behind to the thyroid gland on the posterior side. Results: The results show that 2H has the most total flux for photon and neutron, 1.944E-3 and 1.7666E-2, respectively. Whereas 1H and 3He have best conditions, 8.88609E-4 and 1.35431E-3 for photon, 4.90506E-4 and 4.34057E-3 for neutron, respectively. The same calculation has obtained for energy depositions for these particles. Conclusion: In this research, we investigated that which of these light particles can deliver the maximum dose to the normal tissues and the minimum dose to the tumor. By comparing these results for the mentioned light particles, we find out 1H and 3He is the best therapy choices for thyroid glands whereas 2H is the worst. PMID:25505774

Fibroblast-mediated in vivo and in vitro growth promotion of tumorigenic rat thyroid carcinoma cells but not normal Fisher rat thyroid follicular cells.

PubMed

Saitoh, Ohki; Mitsutake, Norisato; Nakayama, Toshiyuki; Nagayama, Yuji

2009-07-01

It is known that genetic abnormalities in oncogenes and/or tumor suppressor genes promote carcinogenesis. Numerous recent articles, however, have demonstrated that epithelial-stromal interaction also plays a critical role for initiation and progression of carcinoma cells. Furthermore, ionizing radiation induces alterations in the tissue microenvironments that promote carcinogenesis. There is little or no information on epithelial-stromal interaction in thyroid carcinoma cells. The objective of this study was to determine if epithelial-stromal interaction influenced the growth of thyroid carcinoma cells in vivo and in vitro and to determine if radiation had added or interacting effects. Normal Fisher rat thyroid follicular cells (FRTL5 cells) and tumorigenic rat thyroid carcinoma cells (FRTL-Tc cells) derived from FRTL5 cells were employed. The cells were injected into thyroids or subcutaneously into left flanks of rats alone or in combination with skin-derived fibroblasts. In groups of rats, fibroblasts were irradiated with 0.1 or 4 Gy x-ray 3 days before inoculation. In vitro growth of FRTL-Tc and FRTL-5 cells were evaluated using the fibroblast-conditioned medium and in a co-culture system with fibroblasts. The in vivo experiments demonstrated that FRTL-Tc cells injected intrathyroidally grew faster than those injected subcutaneously, and that admixed fibroblasts enhanced growth of subcutaneous FRTL-Tc tumors, indicating that the intrathyroidal milieu, particularly in the presence of fibroblasts, confer growth-promoting advantage to thyroid carcinoma cells. This in vivo growth-promoting effect of fibroblasts on FRTL-Tc cells was duplicated in the in vitro experiments using the fibroblast-conditioned medium. Thus, our data demonstrate that this effect is mediated by soluble factor(s), is reversible, and is comparable to that of 10% fetal bovine serum. However, normal FRTL5 cells did not respond to the fibroblast-conditioned medium. Furthermore, high- and low-dose irradiation enhanced and suppressed, respectively, the in vivo fibroblast-mediated growth promotion. This effect was, however, not observed in the in vitro experiment with conditioned medium or even that allowing cell-cell contact. The intrathyroidal stromal microenvironments, particularly fibroblasts, appear to enhance the growth of thyroid carcinomas through soluble factor(s), which is modulated differently by high- and low-dose irradiation. To our knowledge this is the first study to show epithelial-stromal interaction in thyroid carcinoma.

Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21.

PubMed

Lam, K Y; Lo, C Y; Chan, K W; Wan, K Y

2000-03-01

To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.

Comparison of in vitro and in vivo bioassays to measure thyroid hormone disrupting activity in water extracts.

PubMed

Leusch, Frederic D L; Aneck-Hahn, Natalie H; Cavanagh, Jo-Anne E; Du Pasquier, David; Hamers, Timo; Hebert, Armelle; Neale, Peta A; Scheurer, Marco; Simmons, Steven O; Schriks, Merijn

2018-01-01

Environmental chemicals can induce thyroid disruption through a number of mechanisms including altered thyroid hormone biosynthesis and transport, as well as activation and inhibition of the thyroid receptor. In the current study six in vitro bioassays indicative of different mechanisms of thyroid disruption and one whole animal in vivo assay were applied to 9 model compounds and 4 different water samples (treated wastewater, surface water, drinking water and ultra-pure lab water; both unspiked and spiked with model compounds) to determine their ability to detect thyroid active compounds. Most assays correctly identified and quantified the model compounds as agonists or antagonists, with the reporter gene assays being the most sensitive. However, the reporter gene assays did not detect significant thyroid activity in any of the water samples, suggesting that activation or inhibition of the thyroid hormone receptor is not a relevant mode of action for thyroid endocrine disruptors in water. The thyroperoxidase (TPO) inhibition assay and transthyretin (TTR) displacement assay (FITC) detected activity in the surface water and treated wastewater samples, but more work is required to assess if this activity is a true measure of thyroid activity or matrix interference. The whole animal Xenopus Embryonic Thyroid Assay (XETA) detected some activity in the unspiked surface water and treated wastewater extracts, but not in unspiked drinking water, and appears to be a suitable assay to detect thyroid activity in environmental waters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Laminin-5γ-2 (LAMC2) Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Progression, Migration, and Invasion by Modulating Signaling of EGFR

PubMed Central

Kanojia, Deepika; Okamoto, Ryoko; Jain, Saket; Madan, Vikas; Chien, Wenwen; Sampath, Abhishek; Ding, Ling-Wen; Xuan, Meng; Said, Jonathan W.; Doan, Ngan B.; Liu, Li-Zhen; Yang, Henry; Gery, Sigal; Braunstein, Glenn D.; Koeffler, H. Phillip

2014-01-01

Context: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit-γ-2 (LAMC2) is an epithelial basement membrane protein involved in cell migration and tumor invasion and might represent an ideal target for the development of novel therapeutic approaches for ATC. Objective: The objective of the investigation was to study the role of LAMC2 in ATC tumorigenesis. Design: LAMC2 expression was evaluated by RT-PCR, Western blotting, and immunohistochemistry in tumor specimens, adjacent noncancerous tissues, and cell lines. The short hairpin RNA (shRNA) approach was used to investigate the effect of LAMC2 knockdown on the tumorigenesis of ATC. Results: LAMC2 was highly expressed in ATC samples and cell lines compared with normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed the migration, invasion, and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered the expression of genes associated with migration, invasion, proliferation, and survival. Immunoprecipitation studies showed that LAMC2 bound to epidermal growth factor receptor (EGFR) in the ATC cells. Silencing LAMC2 partially blocked epidermal growth factor-mediated activation of EGFR and its downstream pathway. Interestingly, cetuximab (an EGFR blocking antibody) or EGFR small interfering RNA additively enhanced the antiproliferative activity of the LAMC2 knockdown ATC cells compared with the control cells. Conclusions: To our knowledge, this is the first report investigating the effect of LAMC2 on cell growth, cell cycle, migration, invasion, and EGFR signaling in ATC cells, suggesting that LAMC2 may be a potential therapeutic target for the treatment of ATC. PMID:24170107

A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses.

PubMed

Nasreldin, Magda H A; Ibrahim, Eman A; Saad El-Din, Somaia A

2016-01-01

Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations.

A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses

PubMed Central

Nasreldin, Magda H. A.; Ibrahim, Eman A.; Saad El-Din, Somaia A.

2016-01-01

Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations. PMID:26819565

Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo.

PubMed

Sato, K; Yamazaki, K; Shizume, K; Kanaji, Y; Obara, T; Ohsumi, K; Demura, H; Yamaguchi, S; Shibuya, M

1995-09-01

To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo. Human thyroid follicles, cultured in the absence of endothelial cells, secreted de novo-synthesized thyroid hormone in response to thyroid-stimulating hormone (TSH) and Graves' IgG. The thyroid follicles produced VEGF mRNA but not flt-1 mRNA. The expression of VEGF mRNA was enhanced by insulin, tumor-promoting phorbol ester, calcium ionophore, dibutyryl cAMP, TSH, and Graves' IgG. When rats were fed thiouracil for 4 wk, their serum levels of TSH were increased at day 3. VEGF mRNA was also increased on day 3, accompanied by an increase in flt family (flt-1 and KDR/ flk-1) mRNA expression. These in vitro and in vivo findings suggest that VEGF is produced by thyroid follicles in response to stimulators of TSH receptors, via the protein kinase A and C pathways. VEGF, a secretable angiogenesis factor, subsequently stimulates Flt receptors on endothelial cells in a paracrine manner, leading to their proliferation and producing hypervascularity of the thyroid gland, as seen in patients with Graves' disease.

Physical and radiological findings specific for medullary carcinoma of the thyroid gland.

PubMed

Fujimoto, Y; Oka, A; Fukumitsu, M; Obara, T; Akisada, M

1975-06-01

Preoperative physical and radiological findings, if specific to a certain extent, are important for detecting patients with sporadic form of medullary thyroid carcinoma and especially for the first patient in the family having a hereditary form of medullary thyroid carcinoma and pheochromocytoma syndrome. To delineate clinical features of medullary thyroid carcinoma, a total of 9 patients with this tumor were reviewed retrospectively. In most patients, the thyroid lesions were located in the upper two thirds of the lobe, which was determined by careful palpation or 131I scintiscanning of the thyroid. The primary lesion in the thyroid could be felt more or less as a round, sharply demarcated nodule with fairly good mobility. These findings suggested rather a benign thyroid nodule when there was no lymph node involvement. However, it could be considered a sign suggesting medullary thyroid carcinoma when accompanied by marked lymph node metastasis. In our recent 2 cases, the diagnosis of medullary thyroid carcinoma was strongly suspected on these clinical bases, one of the cases being presented in detail. In 4 patients, lymph node metastasis in the central neck extended to either submandibular or upper mediastinal regions or both. In about one third of the patients, calcified deposits were shown in the cervical roentgenograms. With the use of soft tissue roentgenography, grossly punctate calcific deposits associated with psammoma-like shadows were recognized and the pattern was a criterion for definitive diagnosis of medullary thyroid carcinoma.

Thyroid nodules in the population living around Semipalatinsk nuclear test site: possible implications for dose-response relationships study.

PubMed

Zhumadilov, Zhaxybay

2006-02-01

The risk of radiation-induced nodules is higher than the risk for radiation-induced cancer. Risk factors and specific modifiers of the dose-response relationship may vary among different populations and not be well recognized. Many thyroid studies have considered thyroid nodularity itself, but not specific morphological types of thyroid nodules. There are many specific types of thyroid nodules which follow a morphological classification of thyroid lesions, including some congenital and tumor-like conditions. Modern equipment and technique can help us to identify particular specific types of thyroid nodules. In this study we report some results of a clinically applicable approach to materials derived from three studies. From 1999 through 2002, we have screened 571 current residents from 4 exposed and 1 control village near the Semipalatinsk Nuclear Test Site area, who were of similar ages (<20) at the time of major radiation fallout events at the SNTS. Prevalent nodules were identified by ultrasound and fine-needle aspiration biopsy, cytopathology results. Analysis of ultrasound images and cytopathology of thyroid lesions among exposed and non-exposed population allowed us to distinguish some interesting ultrasound features for specific types of thyroid nodules. We believe that it would be interesting and possibly more informative for thyroid dosimetry studies to consider specific morphological types of thyroid nodules. We need more detailed research to clarify the feasibility of applying these findings for study of the dose-response relationship.

Glycyrrhizin, a Direct HMGB1 Antagonist, Ameliorates Inflammatory Infiltration in a Model of Autoimmune Thyroiditis via Inhibition of TLR2-HMGB1 Signaling.

PubMed

Li, Chenyan; Peng, Shiqiao; Liu, Xin; Han, Cheng; Wang, Xinyi; Jin, Ting; Liu, Shanshan; Wang, Weiwei; Xie, Xiaochen; He, Xue; Zhang, Hanyi; Shan, Ling; Fan, Chenling; Shan, Zhongyan; Teng, Weiping

2017-05-01

High mobility group box-1 (HMGB1), a non-histone protein, plays an important role in autoimmune diseases. However, the significance of HMGB1 in the pathogenesis of autoimmune thyroiditis has not been reported. The purpose of this study was to explore whether HMGB1 participates in the pathogenesis of autoimmune thyroiditis, and whether glycyrrhizin (GL), a direct inhibitor of HMGB1, attenuates the severity of thyroid inflammatory infiltration in a murine model of autoimmune thyroiditis. A total of 80 male NOD.H-2 h4 mice were randomly divided into a control or iodine supplement (NaI) group at four weeks of age, and the control group was fed with regular water, whereas the NaI group was supplied with 0.005% sodium iodine water. Another 24 male NOD.H-2 h4 mice were also randomized into three groups (eight mice per group) as follows: control, NaI, and GL treatment after iodine supplementation (NaI + GL). The NOD.H-2 h4 mice were fed with 0.005% sodium iodide water for eight weeks to enhance autoimmune thyroiditis. After iodine treatment, the mice received intraperitoneal injections of GL for four weeks. The severity of lymphocytic infiltration in the thyroid gland was measured by histopathological studies. The serum levels of HMGB1, tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, and thyroglobulin antibody titers were measured using an enzyme-linked immunosorbent assay. HMGB1 expression was measured by immunohistochemical staining and real-time polymerase chain reaction. TLR2, HMGB1, MyD88, and nuclear transcription factor κB were measured by Western blot. The mRNA expression of HMGB1 was significantly higher at 8 and 16 weeks in the NaI group than it was in the control group. Serum levels of thyroglobulin antibodies, HMGB1, tumor necrosis factor alpha, IL-6, and IL-1β were significantly increased in the NaI group, but they were dramatically attenuated with GL injection. The prevalence of thyroiditis and the infiltration of lymphocytes were significantly decreased in the NaI + GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and nuclear transcription factor κB in the thyroid gland and attenuated the severity of thyroiditis. HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. GL effectively attenuated thyroiditis in the iodine-induced NOD.H-2 h4 mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.

A Continuation Study Using Sunitinib Malate For Patients Leaving Treatment On A Previous Sunitinib Study.

ClinicalTrials.gov

2015-10-07

Metastatic Breast Cancer [F]; Advanced Breast Cancer; Metastatic Castration Resistant Prostate Cancer; Metastatic Renal Cell Cancer; Non-Small Cell Lung Cancer; Thyroid Cancer; Advanced/Metastatic Non-Small Cell Lung Cancer; Advanced Gastric Cancer; Gastrointestinal Stromal Tumor; Hepatocellular Carcinoma; Pancreatic Islet Cell Carcinoma; Pancreatic Neuroendocrine Tumor

Preliminary evidence for biologic activity of toceranib phosphate (Palladia®) in solid tumors

PubMed Central

London, Cheryl; Mathie, Tamra; Stingle, Nicole; Clifford, Craig; Haney, Siobhan; Klein, Mary K.; Beaver, Linda; Vickery, Kate; Vail, David M.; Hershey, Betsey; Ettinger, Susan; Vaughan, Andrew; Alvarez, Francisco; Hillman, Lorin; Kiselow, Mike; Thamm, Doug; Higginbotham, Mary Lynn; Gauthier, Meredith; Krick, Erika; Phillips, Brenda; LaDue, Tracy; Jones, Pam; Bryan, Jeffery; Gill, Virginia; Novasad, Andrew; Fulton, Lisa; Carreras, Janet; McNeill, Conor; Henry, Carolyn; Gillings, Sarah

2013-01-01

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®) in select solid tumors in dogs. Cases in which toceranib was used to treat dogs with anal sac anal gland adenocarcinoma, metastatic osteosarcoma, thyroid carcinoma, head and neck carcinoma, and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 anal sac tumors (8PR, 20SD), 11/23 osteosarcomas (1PR, 10SD), 12/15 thyroid carcinomas (4PR, 8SD), 7/8 head and neck carcinomas (1CR, 5PR, 1SD) and 5/7 (1CR, 4SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg/kg, 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis, and 47/63 (74.6%) were treated 4 months or longer. While these data povide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumors, future prospective studies are necessary to define its true activity. PMID:22236194

Combination Effects of Forty Carcinogens Administered at Low Doses to Male Rats

PubMed Central

Takayama, Shozo; Hasegawa, Hirokazu; Ohgaki, Hiroko

1989-01-01

An investigation was conducted to determine whether a mixture of low doses of forty carcinogens that target different organs, including the liver, intestine, thyroid, urinary bladder, and skin, is effective for tumor induction in F344/DuCrj rats. The dose of each carcinogen in the diet was 1/50 of the TD50 value, treatment being continued for 102 weeks. Significant numbers of neoplastic nodules of the liver and follicular cell tumors of the thyroid developed in the animals exposed to the carcinogen mixture, although the question of whether the observed carcinogenic effects were synergistic or additive could not be answered. The results serve to evaluate carcinogenic risk in the search for causes of human cancer. PMID:2511179

Thyroid c-cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

PubMed

Miller, Debra L; Styer, Eloise L; Stobaeus, Janeen K; Norton, Terry M

2002-12-01

A 3-yr-old African pygmy hedgehog (Atelerix albiventris) was submitted with dysphagia, weight loss, and tetraparesis. A palpable mass was found on the ventral neck. Histologic examination revealed replacement of the thyroid gland by a highly cellular, expansile, and infiltrative mass composed of lobules of polygonal cells separated by fine fibrovascular septa. Examination of ultrathin sections revealed tumor cells with few to many dense-core neuroendocrine granules, approximately 100-200 nm in diameter, and stromal amyloid. Immunohistochemical stains were positive for neuron-specific enolase. Only rare cells had positive immunohistochemical staining for calcitonin. Findings are consistent with a neuroendocrine tumor of C-cell origin. This is the first report of a C-cell carcinoma in a hedgehog.

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.

Analysis of thyroid hormones in biological samples using stable isotope dilution liquid chromatography-tandem mass spectrometry

EPA Science Inventory

This poster presentation will describe analytical chemistry methods for measuring thyroid hormones and related precursors and metabolites in very small tissue or plasma samples. These methods are amenable to measure thyroid hormones in amphibian tadpoles or small mammals used as ...

Thyroid cancer in a long-term nonprogressor HIV-1 infection

PubMed Central

Phatak, Uday A.; Chitale, P. V.; Jagdale, Rakhi V.

2015-01-01

Long-term non-progressor HIV infection (LTNP-HIV) is seen in <1 percent of HIV-afflicted population. There are definite criteria for the diagnosis of LTNP-HIV. Malignancies either solid tumors or haematological cancers have not been reported in such population. We report here a rare case of follicular thyroid carcinoma in LTNP-HIV infection. She never had any opportunistic infections. She did not receive anti-retroviral therapy in the entire course of illness and continued to have good quality of life. Treatment of follicular thyroid cancer was similar to other patients without HIV infection. This could be the first case study from India. PMID:26692617

Update in TSH Receptor Agonists and Antagonists

PubMed Central

Neumann, Susanne

2012-01-01

The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. PMID:23019348

Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer.

PubMed

Komorowski, Jan; Pasieka, Z; Jankiewicz-Wika, J; Stepień, H

2002-08-01

Stimulation of growth of endothelial cells from preexisting blood vessels, i.e., angiogenesis, is one of the essential elements necessary to create a permissive environment in which a tumor can grow. During angiogenesis, the matrix metalloproteinase (MMP) family of tissue enzymes contributes to normal (embriogenesis or wound repair) and pathologic tissue remodeling (chronic inflammation and tumor genesis). The proposed pathogenic roles of MMPs in cancer are tissue breakdown and remodeling during invasive tumor growth and tumor angiogenesis. Tissue inhibitors of metalloproteinases (TIMPs) form a complex with MMPs, which in turn inhibits active MMPs. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are unique among mediators of angiogenesis with synergistic effect, and both can also be secreted by thyroid cancer cells. The goal of the study was to evaluate the plasma blood concentration of VEGF, bFGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and TIMP-2 in patients with cancer and in normal subjects. Twenty-two patients with thyroid cancers (papillary cancer, 11; partly papillary and partly follicular cancer, 3; anaplastic cancer, 5; medullary cancer, 3) and 16 healthy subjects (controls) were included in the study. VEGF, bFGF MMPs, and TIMPs were evaluated by enzyme-linked immunosorbent assay (ELISA). In patients with thyroid cancer, normal VEGF concentrations (74.29 +/- 13.38 vs. 84.85 +/- 21.71 pg/mL; p > 0.05) and increased bFGF (29.52 +/- 4.99 vs. 6.05 +/- 1.43 pg/mL; p < 0.001), MMP-2 (605.95 +/- 81.83 vs. 148.75 +/- 43.53 ng/mL; p < 0.001), TIMP-2 (114.19 +/- 6.62 vs. 60.75 +/- 9.18 ng/mL; p < 0.001), as well as lower MMP-1 (0.70 +/- 0.42 vs. 3.87 +/- 0.53; p < 0.001) levels have been noted. Increased plasma levels of MMP-3 and MMP-9 were also found in patients with medullary carcinoma. In conclusion, predominance of MMP-2 over TIMP-2 and TIMP-1 over MMP-1 as well as increased concentration of bFGF in peripheral blood are common features in patients with thyroid cancer.

Radioiodine: the classic theranostic agent.

PubMed

Silberstein, Edward B

2012-05-01

Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and kinetics must be overcome, and long-term outcome studies following (131)I given based on this new dosimetry must be completed before the nuclear medicine community will be able to predictably cure our thyroid cancer patients with this technology. Copyright © 2012 Elsevier Inc. All rights reserved.

Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer.

PubMed

Khatami, Fatemeh; Larijani, Bagher; Heshmat, Ramin; Keshtkar, Abbasali; Mohammadamoli, Mahsa; Teimoori-Toolabi, Ladan; Nasiri, Shirzad; Tavangar, Seyed Mohammad

2017-01-01

Promoter methylation in a number of tumor-suppressor genes (TSGs) can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1). The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73), SLC5 (OR = 6.15), RASSF1 (OR = 4.16), PTEN (OR = 3.61), DAPK (OR = 3.51), P16 (OR = 3.31), TSHR (OR = 2.93), and RARβ2 (OR = 1.50). Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.

Percutaneous laser ablation of benign and malignant thyroid nodules.

PubMed

Papini, Enrico; Bizzarri, Giancarlo; Pacella, Claudio M

2008-10-01

Percutaneous image-guided procedures, largely based on thermal ablation, are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. In several uncontrolled clinical trials and in two randomized clinical trials, laser ablation has demonstrated a good efficacy and safety for the shrinkage of benign cold thyroid nodules. In hyperfunctioning nodules, laser ablation induced a nearly 50% volume reduction with a variable frequency of normalization of thyroid-stimulating hormone levels. Laser ablation has been tested for the palliative treatment of poorly differentiated thyroid carcinomas, local recurrences or distant metastases. Laser ablation therapy is indicated for the shrinkage of benign cold nodules in patients with local pressure symptoms who are at high surgical risk. The treatment should be performed only by well trained operators and after a careful cytological evaluation. Laser ablation does not seem to be consistently effective in the long-term control of hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy. Laser ablation may be considered for the cytoreduction of tumor tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid malignancy that are not amenable to surgical or radioiodine treatment.

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

Emerging Therapeutics for Advanced Thyroid Malignancies: Rationale and Targeted Approaches

PubMed Central

Harris, Pamela; Bible, Keith C.

2011-01-01

Introduction Thyroid cancer is an emerging public health concern. In the U.S., its incidence has doubled in the past decade, making it the 8th most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Areas covered Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Expert opinion Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity modulated radiation therapy appears to extend survival for patients with locoregionally-confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes. PMID:21910667

[Surgical Diagnosis and Treatment of Primary Hyperthyroidism Complicated with Occult Thyroid Carcinoma].

PubMed

Wu, Xin; Yu, Jian-chun; Kang, Wei-ming; Ma, Zhi-qiang; Ye, Xin

2015-08-01

To evaluate the surgical diagnosis and treatment of primary hyperthyroidism complicated with occult thyroid carcinoma. Data of 51 cases of primary hyperthyroidism complicated with occult thyroid carcinoma admitted during January 2004 to November 2014 were analyzed retrospectively. The incidence of occult thyroid carcinoma was 5.03% in hyperthyroidism,and 47 cases (92.16%) were female. The preoperative diagnosis of all these 51 cases was primary hyperthyroidism and 11 cases were diagnosed thyroid carcinoma at the same time;25 cases were diagnosed thyroid carcinoma by frozen section and the remaining 26 cases were diagnosed by postoperative pathology. Finally,26 cases underwent subtotal thyroidectomy,4 cases underwent total thyroidectomy, and 21 cases underwent total thyroidectomy with lymphadenectomy. The tumor size ranged from 0.1 to 1.0 cm [mean:(0.63 ± 0.35) cm]. The lesions were less than or equal to 0.5 cm in 28 cases (54.9%). The follow-up lasted from 1 to 121 months [mean:(28.6 ± 22.7)months] in 43 patients,and all of them survived. Primary hyperthyroidism complicated with occult thyroid carcinoma is commonly found in female patients. Preoperative diagnosis is difficult. Ultrasound is the major examining method. Frozen section can increase the detection rate. The postoperative prognosis of hyperthyroidism complicated with occult thyroid carcinoma is satisfactory.

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.

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

Primary Synovial Sarcoma of the Thyroid Gland: Case Report and Review of the Literature

PubMed Central

Boudin, Laurys; Fakhry, Nicolas; Chetaille, Bruno; Perrot, Delphine; Nguyen, Anh Tuan; Daidj, Nassima; Guiramand, Jérôme; Sarran, Anthony; Moureau-Zabotto, Laurence; Bertucci, François

2014-01-01

Synovial sarcoma (SVS) of the thyroid gland is exceedingly rare. We report the case of a 55-year-old man with a rapidly growing 7-cm neck mass. Because of suspicion of anaplastic thyroid carcinoma, a total thyroidectomy was planned, without preoperative cytology. During surgery, the tumor ruptured, leading to fragmented and incomplete resection. The morphological and immunohistochemical aspects suggested thyroid SVS, which was confirmed by fluorescent in situ hybridization (SYT gene rearrangement). The patient experienced immediate local relapse in close contact with large vessels and the thyroid cartilage and was referred to our institution. Doxorubicin-ifosfamide chemotherapy led to a minor response that authorized secondary conservative surgery. Because of microscopically incomplete resection, adjuvant radiotherapy was chosen and is ongoing 10 months after initial surgery. The prognosis of thyroid SVS is associated with a high risk for local and metastatic relapses. Pretreatment diagnosis is fundamental and may benefit from molecular analysis. Margin-free monobloc surgical excision is the best chance for cure, but adjuvant chemotherapy and radiotherapy deserve to be discussed. PMID:24575008

Primary synovial sarcoma of the thyroid gland: case report and review of the literature.

PubMed

Boudin, Laurys; Fakhry, Nicolas; Chetaille, Bruno; Perrot, Delphine; Nguyen, Anh Tuan; Daidj, Nassima; Guiramand, Jérôme; Sarran, Anthony; Moureau-Zabotto, Laurence; Bertucci, François

2014-01-01

Synovial sarcoma (SVS) of the thyroid gland is exceedingly rare. We report the case of a 55-year-old man with a rapidly growing 7-cm neck mass. Because of suspicion of anaplastic thyroid carcinoma, a total thyroidectomy was planned, without preoperative cytology. During surgery, the tumor ruptured, leading to fragmented and incomplete resection. The morphological and immunohistochemical aspects suggested thyroid SVS, which was confirmed by fluorescent in situ hybridization (SYT gene rearrangement). The patient experienced immediate local relapse in close contact with large vessels and the thyroid cartilage and was referred to our institution. Doxorubicin-ifosfamide chemotherapy led to a minor response that authorized secondary conservative surgery. Because of microscopically incomplete resection, adjuvant radiotherapy was chosen and is ongoing 10 months after initial surgery. The prognosis of thyroid SVS is associated with a high risk for local and metastatic relapses. Pretreatment diagnosis is fundamental and may benefit from molecular analysis. Margin-free monobloc surgical excision is the best chance for cure, but adjuvant chemotherapy and radiotherapy deserve to be discussed.

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.

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.

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Thyroid hormones and thyroid disease in relation to perchlorate dose and residence near a superfund site.

PubMed

Gold, Ellen B; Blount, Benjamin C; O'Neill Rasor, Marianne; Lee, Jennifer S; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-07-01

Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Residential blocks were randomly selected from areas: (1) with potential perchlorate exposure via drinking water; (2) with potential exposure to environmental contaminants; and (3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20-50 years during 1988-1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Residential location and current perchlorate dose were not associated with thyroid function or disease. No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped.

Elevated interleukin-1β in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

PubMed

Sun, Li; Zhang, Xiaoxu; Dai, Fang; Shen, Jijia; Ren, Cuiping; Zuo, Chunlin; Zhang, Qiu

2016-08-01

To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT. Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer.

PubMed

Shaha, Ashok R

2004-03-01

The outcome in differentiated thyroid cancer generally depends on the stage of the disease at the time of presentation; prognostic factors such as age, grade, size, extension, or distant metastasis; and risk groups (eg, low or high risk). The author has reviewed a large number of patients with differentiated thyroid cancer to analyze their hypothesis and to confirm that various risk groups have a major implication in relation to extent of the treatment and outcome. Differentiated thyroid cancers make up 90% of all thyroid tumors. The prognostic factors are well defined, such as age, size of the tumor, extrathyroidal extension, presence of distant metastasis, histological appearance, and grade of the tumor. The author has previously divided the risk groups into low-, intermediate-, and high-risk categories based on prognostic factors. The study describes the author's treatment approach related to the extent of thyroidectomy and adjuvant therapy based on various risk groups and the long-term survival. Retrospective. In a retrospective review of 1038 patients with differentiated thyroid carcinoma, various prognostic factors were studied by univariate and multivariate analysis. The significant prognostic factors were studied in detail and, based on these prognostic factors, the patients were divided into low-, intermediate- and high-risk groups. The survival curves were plotted by Kaplan-Meier method. The long-term survivals in low-, intermediate- and high-risk groups were 99%, 87%, and 57% respectively. Based on these risk groups, a decision tree was made regarding extent of thyroidectomy and adjuvant treatment. In the high-risk group and selected patients in the intermediate-risk group, aggressive surgery including removal of all gross disease and extrathyroidal extension with postoperative radioactive iodine ablation is recommended. In the low-risk group and selected patients in the intermediate-risk group, lobectomy appears to be satisfactory with excellent long-term outcome. The surgical treatment offers the best long-term results in low-risk patients, and the role of adjuvant treatment in this group is questionable. The decisions in the management of well-differentiated thyroid cancer should be based on various prognostic factors and risk groups. The long-term survival in the low-risk group is excellent, and consideration should be given to conservative surgical resection depending on the extent of the disease. In the high-risk group and selected patients in the intermediate-risk group, total thyroidectomy with radioactive ablation is warranted. A consideration may be given to external-beam radiation therapy in selected high-risk patients. It is apparent, based on the author's clinical experience and critical retrospective analysis, that the author's hypothesis that risk groups are extremely important in the long-term outcome of patients with differentiated thyroid cancer is correct. Based on various risk groups, the author currently is able to guide the treatment policies for thyroid cancer.

Tumors and other diseases following childhood x-ray treatment for ringworm of the scalp (Tinea capitis).

PubMed

Shore, Roy E; Moseson, Miriam; Harley, Naomi; Pasternack, Bernard S

2003-10-01

The objective of the study is to characterize the risk of tumors from radiation exposure to the head and neck. A cohort of 2,224 children given x-ray treatment and 1,380 given only topical medications for ringworm of the scalp (tinea capitis) during 1940-1959 have been followed up for a median of 39 y to determine tumor incidence. Follow-ups were by mail/telephone questionnaire, with 84-88% of the original cohort followed and with medical verification of diseases of interest. Sixteen intracranial tumors [7 brain cancers, 4 meningiomas, and 5 acoustic neuromas (vestibular schwannomas)] occurred in the x-irradiated group following an average brain dose of about 1.4 Gy, compared to 1 acoustic neuroma in the control group. The standardized incidence ratio (SIR) for brain cancer was 3.0 [95% confidence interval (CI): 1.3, 5.9]. Even though the dose to the thyroid gland was only about 60 mGy, 2 thyroid cancers were found in the irradiated group vs. none among controls, and 11 vs. 1 thyroid adenomas were found in the respective groups. Following an average dose of about 4 Gy to cranial marrow, 8 cases of leukemia (SIR = 3.2, CI: 1.5, 6.1) were observed in the irradiated group and 1 in the control group. There was also a suggestive excess of blood dyscrasias. There was no difference between the groups in the frequency of other cancers of the head and neck (excluding nonmelanoma skin cancer) or in total mortality.

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

PubMed

Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

2016-01-01

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

PubMed Central

Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W.

2017-01-01

The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions. PMID:28775711

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.

Thyroid Cysts in Cats: A Retrospective Study of 40 Cases.

PubMed

Miller, M L; Peterson, M E; Randolph, J F; Broome, M R; Norsworthy, G D; Rishniw, M

2017-05-01

Thyroid cysts are rare in cats and poorly documented. To report distinguishing clinical features and treatment responses of cats with thyroid cysts. Forty client-owned cats. Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded. Cats ranged in age from 8 to 20 years with no apparent breed or sex predilection. 37 of 40 (93%) cats were hyperthyroid (duration, 1-96 months). Clinical findings included palpable neck mass (40/40, 100%), weight loss (15/40, 38%), dysphagia (8/40, 20%), decreased appetite (5/40, 13%), and dyspnea (4/40, 10%). Cysts were classified as small (≤8 cm 3 ) in 16 (40%) and large (>8 cm 3 ) in 24 (60%) cats. Of 25 cats treated with radioiodine, hyperthyroidism resolved in 23 (92%), whereas thyroid cysts resolved in 12 (50%). Radioiodine treatment resolved small cysts in 8 of 13 (62%) cats and large cysts in 4 of 11 (36%) cats. Eight cats, including 2 euthyroid cats, underwent thyroid-cystectomy; 3 with bilateral thyroid involvement were euthanized postoperatively for hypocalcemia. Excised cystic thyroid masses were identified as cystadenoma (4) and carcinoma (4). Thyroid cysts are encountered in hyperthyroid and euthyroid cats with benign and malignant thyroid tumors. Radioiodine treatment alone inconsistently resolved thyroid cysts. Thyroid-cystectomy could be considered in cats with unilateral thyroid disease or when symptomatic cysts persist despite successful radioiodine treatment of hyperthyroidism. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for metastatic bladder cancer and sarcoma.

PubMed

Yavuz, Sahzene; Apolo, Andrea B; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A; Shawker, Thomas; Reynolds, James; Celi, Francesco S

2014-08-01

Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event.

Cabozantinib-Induced Thyroid Dysfunction: A Review of Two Ongoing Trials for Metastatic Bladder Cancer and Sarcoma

PubMed Central

Yavuz, Sahzene; Apolo, Andrea B.; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A.; Shawker, Thomas; Reynolds, James

2014-01-01

Background: Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. Methods: We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Results: Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. Conclusion: TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event. PMID:24724719

Nicotine Nasal Spray

MedlinePlus

... disease or Raynaud's phenomena, hyperthyroidism (an overactive thyroid), pheochromocytoma (a tumor on a small gland near the ... effects. Call your doctor if you have any unusual problems while using this medication.

Nicotine Oral Inhalation

MedlinePlus

... disease or Raynaud's phenomena, hyperthyroidism (an overactive thyroid), pheochromocytoma (a tumor on a small gland near the ... effects. Call your doctor if you have any unusual problems while using this medication.

Immunoscore in Rectal Cancer

ClinicalTrials.gov

2017-06-13

Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

Municipal mortality due to thyroid cancer in Spain

PubMed Central

Lope, Virginia; Pollán, Marina; Pérez-Gómez, Beatriz; Aragonés, Nuria; Ramis, Rebeca; Gómez-Barroso, Diana; López-Abente, Gonzalo

2006-01-01

Background Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. Methods It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. Results From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. Conclusion The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor. PMID:17173668

Pioglitazone Induces a Proadipogenic Antitumor Response in Mice with PAX8-PPARγ Fusion Protein Thyroid Carcinoma

PubMed Central

Dobson, Melissa E.; Diallo-Krou, Ericka; Grachtchouk, Vladimir; Yu, Jingcheng; Colby, Lesley A.; Wilkinson, John E.; Giordano, Thomas J.

2011-01-01

Approximately 35% of follicular thyroid carcinomas harbor a chromosomal translocation that results in expression of a paired box gene 8-peroxisome proliferator-activated receptor γ gene (PPARγ) fusion protein (PPFP). To better understand the oncogenic role of PPFP and its relationship to endogenous PPARγ, we generated a transgenic mouse model that combines Cre-dependent PPFP expression (PPFP;Cre) with homozygous deletion of floxed Pten (PtenFF;Cre), both thyroid specific. Although neither PPFP;Cre nor PtenFF;Cre mice develop thyroid tumors, the combined PPFP;PtenFF;Cre mice develop metastatic thyroid cancer, consistent with patient data that PPFP is occasionally found in benign thyroid adenomas and that PPFP carcinomas have increased phosphorylated AKT/protein kinase B. We then tested the effects of the PPARγ agonist pioglitazone in our mouse model. Pioglitazone had no effect on PtenFF;Cre mouse thyroids. However, the thyroids in pioglitazone-fed PPFP;PtenFF;Cre mice decreased 7-fold in size, and metastatic disease was prevented. Remarkably, pioglitazone caused an adipogenic response in the PPFP;PtenFF;Cre thyroids characterized by lipid accumulation and the induction of a broad array of adipocyte PPARγ target genes. These data indicate that, in the presence of pioglitazone, PPFP has PPARγ-like activity that results in trans-differentiation of thyroid carcinoma cells into adipocyte-like cells. Furthermore, the data predict that pioglitazone will be therapeutic in patients with PPFP-positive carcinomas. PMID:21952241

Welcoming the new WHO classification of pituitary tumors 2017: revolution in TTF-1-positive posterior pituitary tumors.

PubMed

Shibuya, Makoto

2018-04-01

The fourth edition of the World Health Organization classification of endocrine tumors (EN-WHO2017) was released in 2017. In this new edition, changes in the classification of non-neuroendocrine tumors are proposed particularly in tumors arising in the posterior pituitary. These tumors are a distinct group of low-grade neoplasms of the sellar region that express thyroid transcription factor-1, and include pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and sellar ependymoma. This short review focuses on the classification of posterior pituitary tumors newly proposed in EN-WHO2017, and controversies in their pathological differential diagnosis are discussed based on recent cases.

Polymyositis associated with hypothyroidism or hyperthyroidism: two cases and review of the literature.

PubMed

Wang, Han; Li, Hong; Kai, Cui; Deng, Juelin

2011-04-01

Studies confirming a possible relationship of polymyositis within thyroid dysfunction, either hypothyroidism or hyperthyroidism, are hardly available. To define the association, identify clinical, laboratory, electromyographic, and pathologic features in polymyositis (PM) patients with hypothyroidism or hyperthyroidism, we conducted a MEDLINE and Chinese biomedicine database search to identify relevant literature published in the past 25 years. Seventeen cases were included. All patients were female (10 hypothyroidism patients, seven hyperthyroidism patients). The mean (SD) age of PM, hypothyroidism, and hyperthyroidism at diagnosis was 54.8 (16.7), 55.5 (16.5), and 32.7 years (10.2), respectively. PM diagnosis can precede or parallel hypothyroidism while PM may occur following the diagnosis of hyperthyroidism. The most common comorbidities were malignant tumors in these disorders, including thymoma, colon cancer, and thyroid cancer. Muscle weakness was described in 100% of patients. Other common manifestations included muscles' atrophy and pain, deep tendon reflexes, polyarthralgia, and dysphagia. Most patients had markedly elevated creatine kinase and the presence of anti-Sjogren's syndrome A (SSA) antibodies was also found in two cases. Malignancy associated with PM may more frequently occur in hypothyroidism than in hyperthyroidism. The abnormalities on electromyography and biopsy did not differ from those findings of PM. Therapy consisting of corticosteroids, thyroid hormone, or anti-thyroid drugs was administrated; however, poor prognosis seemed to be associated with malignant tumors as well as older age and the presence of anti-SSA antibodies. It is reasonable to suggest that those patients should be routinely evaluated for thyroid function, especially in older female and patients suffering from cancers.

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.

The Clinical Values of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Levels in Blood and Thyroid Nodules

PubMed Central

Altas, Ayfer; Can, Murat; Barut, Figen; Kokturk, Furuzan; Ilikhan, Sevil Uygun; Bayraktaroglu, Taner

2017-01-01

Aim Insulin-like growth factor-1 (IGF-1) is a potent mitogen for many cells. IGF-1 plays a role in the pathogenesis of various tumors with its mutagenic and antiapoptotic properties. The aim of this study was to determine both the serum and intranodular levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with nodular thyroid diseases. Materials and Methods In this study, 80 subjects who performed fine-needle aspiration biopsy (FNAB) were required in order to investigate the effects of serum and intranodular IGF-1 and IGFBP-3 in the pathogenesis of nodules. After performing FNAB, IGF-1 and IGFBP-3 levels were determined in blood and aspiration samples. Results The serum levels of IGF-1 (232.8 ± 12.9 ng/ml) and IGFBP-3 (4.8 μg/ml) were found significantly higher than that of the intranodular IGF-1 (39.1 ng/ml) and intranodular IGFBP-3 levels (0.173 μg/ml) (p < 0.01). Intranodular levels of IGF-1 and IGFBP-3 were higher in subjects with multinodular thyroid gland than those of subjects with solitary nodules (p = 0.043). A positive correlation between the nodule size and the serum IGFBP-3 levels was detected (p = 0.042, r = 0.23). Conclusion This study demonstrated the possible role of both IGF-1 and IGFBP-3 in the growth and the formation of multinodularity of thyroid nodules. PMID:29081797

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.

Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations.

PubMed

Celano, Marilena; Sponziello, Marialuisa; Tallini, Giovanni; Maggisano, Valentina; Bruno, Rocco; Dima, Mariavittoria; Di Oto, Enrico; Redler, Adriano; Durante, Cosimo; Sacco, Rosario; Filetti, Sebastiano; Russo, Diego

2013-02-01

Autonomously functioning thyroid nodules (AFTN) are known to receive an increased blood influx necessary to sustain their high rate of growth and hormone production. Here, we investigated the expression of hematic and lymphatic vases in a series of 20 AFTN compared with the contralateral non-tumor tissues of the same patients, and the transcript levels of proteins involved in the control of vascular proliferation, including the vascular endothelial growth factor (VEGF) and platelet-derived growth factors (PDGF) and their receptors and the endothelial nitric oxide synthase (eNOS). In parallel, the expression of the differentiation markers sodium/iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (Tg), and TSH receptor (TSHR) was also investigated. The data were further analyzed comparing subgroups of tumors with or without mutations in the TSHR gene. Analysis by means of CD31 and D2-40 immunostaining showed in AFTN an increased number of hematic, but not lymphatic, vessels in parallel with an enhanced proliferation rate shown by increased Ki67 staining. Quantitative RT-PCR analysis revealed an increase of VEGF, VEGFR1 and 2, PDGF-A, PDGF-B, and eNOS expression in tumor versus normal tissues. Also, higher transcript levels of NIS, TPO, and Tg were detected. Comparison of the two subgroups of samples revealed only few differences in the expression of the genes examined. In conclusion, these data demonstrate an increased expression of angiogenesis-related factors associated with an enhanced proliferation of hematic, but not lymphatic, vessels in AFTNs. In this context, the presence of TSHR mutations may only slightly influence the expression of pro-angiogenic growth factors.

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.

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

Primary Squamous Cell Carcinoma of the Thyroid Gland

PubMed Central

Ibrahim, Mohd-Irman-Shah; Jusoh, Yusri-Rahimi; Adam, Nurul-Nadhihah; Mohamad, Irfan

2018-01-01

Introduction: Primary squamous cell carcinoma (SCC) of the thyroid gland is one of the rarest types of all reported thyroid malignancies worldwide. It is very aggressive in nature and carries a poor prognosis. The surgical resection with adjuvant radiotherapy and chemotherapy is the most recommended treatment despite its poor reported outcome. Case Report: A 74-year-old woman presented with a rapidly progressive neck swelling, with hoarseness and compressive symptoms. Physical examination revealed a multilobulated firm thyroid mass with unilateral vocal cord palsy. Histopathological findings confirmed the diagnosis of SCC while radiological investigations and panendoscopy findings ruled out the possibility of other primary tumors. A surgical intervention was performed; however, the patient eventually succumbed to death prior to undergoing an oncological treatment. Conclusion: With no standard consensus to guide the management plan, SCC of the thyroid gland presents a great challenge for the managing team to come up with the best treatment option, due to its unfavorable rate of survival. PMID:29387667

Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus.

PubMed

Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário

2013-06-01

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

17-Ketosteroids urine test

MedlinePlus

... problems such as tumor, Cushing syndrome Imbalance of sex hormones in females ( polycystic ovary syndrome ) Ovarian cancer Testicular cancer Overactive thyroid Obesity Stress Decreased levels of 17-ketosteroids may be due ...

Selumetinib and Olaparib in Solid Tumors

ClinicalTrials.gov

2018-05-02

Malignant Neoplasm of Breast; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands

Postoperative radioactive iodine-131 ablation is not necessary among patients with intermediate-risk differentiated thyroid carcinoma: a population-based study.

PubMed

Zhang, Hong; Cai, Yuechang; Zheng, Li; Zhang, Zhanlei; Jiang, Ningyi

2017-01-01

To assess the effectiveness of radioactive iodine (RAI) ablation among patients with intermediate-risk differentiated thyroid cancer (DTC) following surgery. This population based study obtained information from the Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1973-2013). National Cancer Institute, DCCPS, Surveillance Research Programme, Surveillance Systems Branch, released April 2016, based on the November 2015 submission. A total of 93,530 patients with primary thyroid cancer were identified in the SEER database during the period of 2004-2013 and focused on patients with DTC post-operatively treated or not treated with radioactive iodine (RAI). From these 9,127 patients were selected who had intermediate-risk DTC. A total of 8,601 patients were included in this study. For the overall population, the mean age of the population was 47.3 years and the majority were female (70.5%). Kaplan-Meier analysis found the mean overall survival time (os) for subjects with no radiation therapy which was 112.9 months and 114.9 months for those who received RAI ablation treatment (P<0.001). However, thyroid cancer-specific survival was not significantly different between treatment groups (117.7 vs. 118.0 months, log-rank test P=0.164). Overall survival and thyroid cancer-specific 1 year, 5 years, and 10-years survival rates were ≥89.8% and were similar between both treated groups. Multivariate analysis found age, gender, histologic type, and degree of lymph node metastases to be associated with OS, and age, gender, degree of lymph node metastasis and extra-thyroid tumor spread were independent factors for cancer-specific survival. In DTC patients with intermediate cancer risk multivariate analysis found that RAI was associated with a reduced risk of mortality compared with no radiation therapy (HR=0.710, 95% CI: 0.562-0.897, P=0.004) but no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category. In DTC patients with intermediate cancer risk although postoperative RAI ablation following surgery showed a benefit in overall survival, no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category.

Cushing Syndrome: Diagnostic Workup and Imaging Features, With Clinical and Pathologic Correlation.

PubMed

Wagner-Bartak, Nicolaus A; Baiomy, Ali; Habra, Mouhammed Amir; Mukhi, Shalini V; Morani, Ajaykumar C; Korivi, Brinda R; Waguespack, Steven G; Elsayes, Khaled M

2017-07-01

Cushing syndrome (CS) is a constellation of clinical signs and symptoms resulting from chronic exposure to excess cortisol, either exogenous or endogenous. Exogenous CS is most commonly caused by administration of glucocorticoids. Endogenous CS is subdivided into two types: adrenocorticotropic hormone (ACTH) dependent and ACTH independent. Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood

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

Lollert, André, E-mail: andre.lollert@unimedizin-mainz.de; Gies, Christina; Laudemann, Katharina

Purpose: The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Methods and Materials: Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations throughmore » 2014 (median follow-up time: 48 months). Results: A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Conclusions: Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy.« less