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Sample records for differentiated thyroid carcinomas

  1. Etiopathogenesis of Differentiated Thyroid Carcinomas

    PubMed Central

    Makazlieva, Tanja; Vaskova, Olivija; Majstorov, Venjamin

    2016-01-01

    INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database. DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies. PMID:27703585

  2. Radiofrequency ablation for postsurgical thyroid removal of differentiated thyroid carcinoma

    PubMed Central

    Xu, Dong; Wang, Lipin; Long, Bin; Ye, Xuemei; Ge, Minghua; Wang, Kejing; Guo, Liang; Li, Linfa

    2016-01-01

    Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy. Surgical removal with radioactive iodine therapy is recommended for recurrent thyroid carcinoma, and the postsurgical thyroid removal is critical. This study evaluated the clinical values of radiofrequency ablation (RFA) in the postsurgical thyroid removal for DTC. 35 DTC patients who had been treated by subtotal thyroidectomy received RFA for postsurgical thyroid removal. Before and two weeks after RFA, the thyroid was examined by ultrasonography and 99mTcO4 - thyroid imaging, and the serum levels of free triiodothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH) and thyroglobulin (Tg) were detected. The efficacy and complications of RFA were evaluated. Results showed that, the postsurgical thyroid removal by RFA was successfully performed in 35 patients, with no significant complication. After RFA, the average largest diameter and volume were significantly decreased in 35 patients (P > 0.05), and no obvious contrast media was observed in ablation area in the majority of patients. After RFA, the serum FT3, FT4 and Tg levels were markedly decreased (P < 0.05), and TSH level was significantly increased (P < 0.05). After RFA, radioiodine concentration in the ablation area was significantly reduced in the majority of patients. The reduction rate of thyroid update was 0.69±0.20%. DTC staging and interval between surgery and RFA had negative correlation (Pearson coefficient = -0.543; P = 0.001), with no obvious correlation among others influential factors. RFA is an effective and safe method for postsurgical thyroid removal of DTC. PMID:27186311

  3. Differentiated thyroid carcinomas in children and adolescents

    SciTech Connect

    Samuel, A.M.; Sharma, S.M. )

    1991-04-15

    An analysis of differentiated thyroid carcinomas in children and adolescents revealed that the incidence was 3.05% of total number of patients with differentiated thyroid cancers in all age groups. There was a female preponderance. The incidence of papillary, follicular and papillary with follicular elements was equal. There were no papillary carcinomas observed in children younger than 10 years. The predominant mode of presentation was a solitary nodule of thyroid and some of them had associated cervical adenopathy. A considerable number presented with only cervical adenopathy. The incidence of nodal metastases was 50% at time of presentation and lung involvement was present in 15% of children at the time of diagnosis. Radioiodine treatment was given in 70% of children. Ablation was achieved in 86% of patients given two doses of radioiodine (200 millicuries). The more resistant cases were those with lung and nodal metastases. There was complete ablation in 100% with only residual thyroid tissue, 83% in those with associated nodal metastases, and 57% in those with lung involvement. Average duration of follow-up was 10.3 years (range, 2 to 19 years). Recurrence rate or relapse was observed in 8.5% and was in the regional nodes. There was no recorded mortality due to the disease.

  4. Follow-up of differentiated thyroid carcinoma.

    PubMed

    Bournaud, C; Raverot, V

    2015-02-01

    The aim of follow-up of differentiated thyroid carcinoma (CTD) is the assessment of remission, and, in further steps, the early recognition of patients who develop a recurrence. Tools for the follow-up of CTD include the assessment of thyroglobulin and imaging procedures. Thyroglobulin (Tg) is a strong marker of persistent or recurrent disease, but it must be known that Tg antibodies may give falsely low Tg concentration. TSH stimulation, mainly by the mean of recombinant human TSH, improves the sensitivity of Tg determination. New highly sensitive assays may preclude the need for TSH stimulation, at least in some situations. In the last decades, (131)iodine whole body scan gave place to neck ultrasonography (US) as the most performing imaging procedure in the follow-up of CTD. Criteria to identify cervical lymph node suspect of metastasis have been described, and standardized procedures proposed. Finally, the proof of tumoral invasion is brought by cytological analysis of fine needle biopsies of suspicious lymph nodes. (18)FDG PET is a valuable tool for diagnosis and prognosis in metastatic patients, especially with negative (131)I WBS. Initial response to therapy, assessed by Tg determination and neck US, allows re-stratification of the risk of relapse. According to this "reassessed risk", adapted rhythms and modalities of follow-up have been recently proposed. PMID:26826480

  5. Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas

    PubMed Central

    Soares, Paula; Lima, Jorge; Preto, Ana; Castro, Patricia; Vinagre, João; Celestino, Ricardo; Couto, Joana P; Prazeres, Hugo; Eloy, Catarina; Máximo, Valdemar; Sobrinho-Simões, M

    2011-01-01

    Thyroid gland presents a wide spectrum of tumours derived from follicular cells that range from well differentiated, papillary and follicular carcinoma (PTC and FTC, respectively), usually carrying a good prognosis, to the clinically aggressive, poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC). It is usually accepted that PDTC and UTC occur either de novo or progress from a pre-existing well differentiated carcinoma through a multistep process of genetic and epigenetic changes that lead to clonal expansion and neoplastic development. Mutations and epigenetic alterations in PDTC and UTC are far from being totally clarified. Assuming that PDTC and UTC may derive from well differentiated thyroid carcinomas (WDTC), it is expected that some PDTC and UTC would harbour genetic alterations that are typical of PTC and FTC. This is the case for some molecular markers (BRAF and NRAS) that are present in WDTC, PDTC and UTC. Other genes, namely P53, are almost exclusively detected in less differentiated and undifferentiated thyroid tumours, supporting a diagnosis of PDTC or, much more often, UTC. Thyroid-specific rearrangements RET/PTC and PAX8/PPARγ, on the other hand, are rarely found in PDTC and UTC, suggesting that these genetic alterations do not predispose cells to dedifferentiation. In the present review we have summarized the molecular changes associated with the two most aggressive types of thyroid cancer. PMID:22654560

  6. Genetic alterations in poorly differentiated and undifferentiated thyroid carcinomas.

    PubMed

    Soares, Paula; Lima, Jorge; Preto, Ana; Castro, Patricia; Vinagre, João; Celestino, Ricardo; Couto, Joana P; Prazeres, Hugo; Eloy, Catarina; Máximo, Valdemar; Sobrinho-Simões, M

    2011-12-01

    Thyroid gland presents a wide spectrum of tumours derived from follicular cells that range from well differentiated, papillary and follicular carcinoma (PTC and FTC, respectively), usually carrying a good prognosis, to the clinically aggressive, poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC).It is usually accepted that PDTC and UTC occur either de novo or progress from a pre-existing well differentiated carcinoma through a multistep process of genetic and epigenetic changes that lead to clonal expansion and neoplastic development. Mutations and epigenetic alterations in PDTC and UTC are far from being totally clarified. Assuming that PDTC and UTC may derive from well differentiated thyroid carcinomas (WDTC), it is expected that some PDTC and UTC would harbour genetic alterations that are typical of PTC and FTC. This is the case for some molecular markers (BRAF and NRAS) that are present in WDTC, PDTC and UTC. Other genes, namely P53, are almost exclusively detected in less differentiated and undifferentiated thyroid tumours, supporting a diagnosis of PDTC or, much more often, UTC. Thyroid-specific rearrangements RET/PTC and PAX8/PPARγ, on the other hand, are rarely found in PDTC and UTC, suggesting that these genetic alterations do not predispose cells to dedifferentiation. In the present review we have summarized the molecular changes associated with the two most aggressive types of thyroid cancer. PMID:22654560

  7. Genomic Landscape of poorly Differentiated and Anaplastic Thyroid Carcinoma.

    PubMed

    Xu, Bin; Ghossein, Ronald

    2016-09-01

    Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid tumors associated with a high mortality rate of 38-57 % and almost 100 % respectively. Several recent studies utilizing next generation sequencing techniques have shed lights on the molecular pathogenesis of these tumors, providing evidence to support a stepwise tumoral progression from well-differentiated to poorly differentiated, and finally to anaplastic thyroid carcinomas. While BRAF (V600E) and RAS mutations remain the main drivers in aggressive thyroid carcinoma, PDTC and ATC gains additional mutations, e.g., TERT promoter mutation, TP53 mutation, as well as frequent alterations in PIK3CA-PTEN-AKT-mTOR pathway, SWI-SNF complex, histomethyltransferases, and mismatch repair genes. RAS-mutated PDTCs are commonly associated with a histologic phenotype defined by Turin proposal, high frequency of distant metastasis, high thyroid differentiation score, and a RAS-like gene expression profile, whereas BRAF-mutated PDTCs are usually defined solely by the Memorial Sloan Kettering Cancer Center (MSKCC) criteria with a propensity for nodal metastasis and are less differentiated with a BRAF-like expression signature. Such demarcation is largely lost in ATC which is characterized by genomic complexity, heavy mutation burden, and profound undifferentiation. Additionally, several molecular events, e.g., EIF1AX mutation, mutation burden, and chromosome 1q gain in PDTCs, as well as EIF1AX mutation, chromosome 13q loss, and 20q gains in ATCs, may serve as adverse prognostic markers predicting poor clinical outcome. PMID:27372303

  8. Comparison of Clinical and Ultrasonographic Features of Poorly Differentiated Thyroid Carcinoma and Papillary Thyroid Carcinoma

    PubMed Central

    Zhang, Bo; Niu, Hui-Min; Wu, Qiong; Zhou, Jiong; Jiang, Yu-Xin; Yang, Xiao; Li, Jian-Chu; Zhao, Rui-Na; Wang, Ming; Li, Kang-Ning; Zhu, Shen-Ling; Xia, Yu; Zhong, Ding-Rong

    2016-01-01

    Background: The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. Methods: The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. Results: The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05). Conclusions: PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs. PMID:26830987

  9. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma.

    PubMed

    Na'ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-28

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC.

  10. Thyroid carcinoma

    SciTech Connect

    Friedman, M.; Skolnik, E.M.; Baim, H.M.; Becker, S.P.; Katz, A.H.; Mantravadi, R.V.

    1980-12-01

    Differentiated thyroid carcinoma was studied with regard to mode of presentation, initial findings, treatment and survival. The classic signs, symptoms, physical and scan findings were found to be present in approximately 70% of the patients. Prognosis was found to be dependent on age of presentation more than any other factor. Patients with prior exposure to radiation were found to have more extensive disease and require more extensive surgery but ultimately had the same prognosis for 15-year cure. Treatment for distant metastatic disease by surgery, radioactive iodine and external radiation all resulted in long-term survival in certain cases.

  11. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. MTC is very rare. It can occur in children and adults. Unlike other types ...

  12. Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

    PubMed Central

    Sen, Abhijit; Tsilidis, Konstantinos K; Allen, Naomi E; Rinaldi, Sabina; Appleby, Paul N; Almquist, Martin; Schmidt, Julie A; Dahm, Christina C; Overvad, Kim; Tjønneland, Anne; Rostgaard-Hansen, Agnetha L; Clavel-Chapelon, Françoise; Baglietto, Laura; Boutron-Ruault, Marie-Christine; Kühn, Tilman; Katze, Verena A; Boeing, Heiner; Trichopoulou, Antonia; Tsironis, Christos; Lagiou, Pagona; Palli, Domenico; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, HB(as); Peeters, Petra H; Hjartåker, Anette; Lund, Eiliv; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María- José; Arriola, Larraitz; Gavrila, Diana; Gurrea, Aurelio Barricarte; Tosovic, Ada; Hennings, Joakim; Sandström, Maria; Romieu, Isabelle; Ferrari, Pietro; Zamora-Ros, Raul; Khaw, Kay-Tee; Wareham, Nicholas J; Riboli, Elio; Gunter, Marc; Franceschi, Silvia

    2015-01-01

    Background: Results from several cohort and case–control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Compared with participants consuming 0.1–4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1–1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60–0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas. PMID:26313664

  13. Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

    PubMed Central

    Cunha, Lucas Leite; Morari, Elaine Cristina; Nonogaki, Suely; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

    2012-01-01

    OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis. CONCLUSIONS: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness. PMID:22666793

  14. The Effect of Thyroid-Stimulating Hormone on Tumor Size in Differentiated Thyroid Carcinoma.

    PubMed

    Ozemir, I A; Gurbuz, B; Bayraktar, B; Aslan, S; Başkent, A; Yalman, H; Yigitbasi, R; Alimoglu, O

    2015-12-01

    We evaluated the correlation between serum thyroid-stimulating hormone (TSH) levels and tumor size and other invasiveness parameters of tumor in patients with differentiated thyroid carcinoma (DTC). Several clinical studies have reported that TSH may also have a role as a regulator of the development and function of the thyroid gland. It is currently not clear whether TSH is involved in the existence of thyroid cancer or progression of thyroid cancer or both. Patients with DTC who underwent thyroid surgery between 2003 and 2008 were included this study. Preoperative serum T3, T4, and TSH levels were compared with the size and invasiveness of cancer, retrospectively. DTC was observed in 110 patients over the 5-year period. Seventy-seven (70 %) of them were euthyroid and classified as the "normal-TSH group" (NTG), and 33 (30 %) have an overt or subclinical hyperthyroidism, classified as the "low-TSH group" (LTG). The mean tumor diameter in the LTG was found to be 8.91 ± 8.03 mm; however, it was found to be 18.19 ± 16.24 mm in the NTG. There were significantly differences among the groups related to the diameter of tumor (p = 0.001). Microcarcinoma was determined in 36 patients (46.8 %) in the NTG and 23 patients (69.7 %) in the LTG (p = 0.027). Although there were no significant differences, tumor capsule invasion (33.8 vs. 18.2 %, p = 0.099) and lymphovascular invasion (16.9 vs. 6.1 %, p = 0.130) rates were higher in the NTG. These findings suggest that TSH has effects on growing and proliferation of not only normal thyroid cells but also cancer cells in DTC. This study revealed that serum TSH level can be explored as an important factor that affects the size and invasiveness of tumor in DTC.

  15. The Effect of Thyroid-Stimulating Hormone on Tumor Size in Differentiated Thyroid Carcinoma.

    PubMed

    Ozemir, I A; Gurbuz, B; Bayraktar, B; Aslan, S; Başkent, A; Yalman, H; Yigitbasi, R; Alimoglu, O

    2015-12-01

    We evaluated the correlation between serum thyroid-stimulating hormone (TSH) levels and tumor size and other invasiveness parameters of tumor in patients with differentiated thyroid carcinoma (DTC). Several clinical studies have reported that TSH may also have a role as a regulator of the development and function of the thyroid gland. It is currently not clear whether TSH is involved in the existence of thyroid cancer or progression of thyroid cancer or both. Patients with DTC who underwent thyroid surgery between 2003 and 2008 were included this study. Preoperative serum T3, T4, and TSH levels were compared with the size and invasiveness of cancer, retrospectively. DTC was observed in 110 patients over the 5-year period. Seventy-seven (70 %) of them were euthyroid and classified as the "normal-TSH group" (NTG), and 33 (30 %) have an overt or subclinical hyperthyroidism, classified as the "low-TSH group" (LTG). The mean tumor diameter in the LTG was found to be 8.91 ± 8.03 mm; however, it was found to be 18.19 ± 16.24 mm in the NTG. There were significantly differences among the groups related to the diameter of tumor (p = 0.001). Microcarcinoma was determined in 36 patients (46.8 %) in the NTG and 23 patients (69.7 %) in the LTG (p = 0.027). Although there were no significant differences, tumor capsule invasion (33.8 vs. 18.2 %, p = 0.099) and lymphovascular invasion (16.9 vs. 6.1 %, p = 0.130) rates were higher in the NTG. These findings suggest that TSH has effects on growing and proliferation of not only normal thyroid cells but also cancer cells in DTC. This study revealed that serum TSH level can be explored as an important factor that affects the size and invasiveness of tumor in DTC. PMID:27011492

  16. Dosimetry in differentiated thyroid carcinoma (12-1402R)

    SciTech Connect

    Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier; Fombellida, Jose Cruz

    2013-01-15

    Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. With those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose

  17. [Comparative rate of regional metastasis of high differentiated carcinoma of the thyroid gland].

    PubMed

    Konstantinova, N N; Evmenova, T D; Drozdova, D É

    2014-01-01

    The rate of metastasis of high differentiated carcinoma of the thyroid glands to the neck lymph nodes was studied in people of Kemerovo Region. The metastatic lesions of pretracheal lymph nodes (VI group) were detected in 49.5% patients with papillary carcinoma and 21.0% of patients with follicular cancer. Metastases in jungular lymph nodes were revealed in 37.3% patients with papillary carcinoma. It was noted that an extension of metastatic lesions of regional lymph nodes was observed in the case of primary tumour foci spread beyond borders of the capsula glandularis in patients with papillary carcinoma. There wasn't such a relation in a case of follicular cancer. Metastases in regional lymph nodes were detected more often (67.6%) in the case of papillary carcinoma in uncontaminated zone of the thyroid gland compared with other thyroid pathology (31.7%).

  18. Lu-177 labelled peptide treatment for radioiodine refractory differentiated thyroid carcinoma.

    PubMed

    Elboğa, Umut; Özkaya, Mesut; Sayiner, Zeynel A; Çelen, Yusuf Zeki

    2016-01-01

    Differentiated thyroid carcinoma (DTC) has good prognosis but 5% of the patients already have distant metastasis at the diagnosis. Tumour cells can lose their iodine uptake ability and enter a state of dedifferentiation. Treatment for differentiated thyroid carcinoma that is not suitable for the local surgery and unresponsive to radioactive iodine uptake is not always easy for physicians. We present a case of a 64-year-old man who had total thyroidectomy surgery and central lymph node dissection with diagnosis of multinodular goitre disease. Histopathological evaluation was papillary thyroid cancer with tall cell variant. Treatment using 150 mCi radioiodine was administered to the patient three times but could not effect a cure. We performed Ga-68 labelled DOTATE (synthetic somatostatin analogue peptide). This provided a good outcome. As evident from our case, Lu-177 radionuclide labelled synthetic somatostatin analogue peptides have therapeutic effect on radioiodine refractory DTC, as an alternative treatment modality. PMID:26957032

  19. Oncocytic variant of poorly differentiated thyroid carcinoma: “Is diagnosis possible by fine-needle aspiration?”

    PubMed Central

    Onenerk, Mine; Canberk, Sule; Gunes, Pembegul; Erkan, Murat; Kilicoglu, Gamze Z.

    2016-01-01

    Poorly differentiated thyroid carcinoma (PDTC) is a very rare entity, and the diagnosis can be made on histopathology specimens. However, recognition of characteristic features of PDTC is significant on fine-needle aspirations (FNAs) to differentiate this entity from well-differentiated and anaplastic thyroid carcinomas. Here, we present an FNA case concordant with “oncocytic variant of PDTC” and discuss whether definitive diagnosis can be given on FNAs to assess the prognosis in clinically inoperable patients. PMID:27761148

  20. Differential protein expression profiles of cyst fluid from papillary thyroid carcinoma and benign thyroid lesions.

    PubMed

    Dinets, Andrii; Pernemalm, Maria; Kjellin, Hanna; Sviatoha, Vitalijs; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Larsson, Catharina; Lehtiö, Janne; Höög, Anders

    2015-01-01

    Cystic papillary thyroid carcinoma (cPTC) is a subgroup of PTC presenting a diagnostic challenge at fine needle aspiration biopsy (FNAB). To further investigate this entity we aimed to characterize protein profiles of cyst fluids from cPTC and benign thyroid cystic lesions. In total, 20 cPTCs and 56 benign thyroid cystic lesions were studied. Profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on cyst fluids from a subset of cases after depletion, and selected proteins were further analyzed by Western blot (WB), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). A total of 1,581 proteins were detected in cyst fluids, of which 841 were quantified in all samples using LC-MS/MS. Proteins with different expression levels between cPTCs and benign lesions were identified by univariate analysis (41 proteins) and multivariate analysis (59 proteins in an orthogonal partial least squares model). WB analyses of cyst fluid and IHC on corresponding tissue samples confirmed a significant up-regulation of cytokeratin 19 (CK-19/CYFRA 21-1) and S100A13 in cPTC vs. benign lesions. These findings were further confirmed by ELISA in an extended material of non-depleted cyst fluids from cPTCs (n = 17) and benign lesions (n = 55) (p<0.05). Applying a cut-off at >55 ng/ml for CK-19 resulted in 82% specificity and sensitivity. For S100A13 a cut-off at >230 pg/ml revealed a 94% sensitivity, but only 35% specificity. This is the first comprehensive catalogue of the protein content in fluid from thyroid cysts. The up-regulations of CK-19 and S100A13 suggest their possible use in FNAB based preoperative diagnostics of cystic thyroid lesions. PMID:25978681

  1. Cribriform-morular variant of papillary thyroid carcinoma displaying poorly differentiated features.

    PubMed

    Nakazawa, Tadao; Celestino, Ricardo; Machado, José Carlos; Cameselle-Teijeiro, José Manuel; Vinagre, João; Eloy, Catarina; Benserai, Fátima; Lameche, Samia; Soares, Paula; Sobrinho-Simões, Manuel

    2013-08-01

    Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) usually occurs in the setting of familial adenomatous polyposis (FAP) although it can rarely arise sporadically. Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell-derived neoplasm with more aggressive behavior than well-differentiated carcinomas such as CMVPTC. We report the case of a 35-year-old woman without FAP history who presented a left neck mass and complained of back pain. Imagiological examinations revealed a nodule in the left lobe of thyroid and multiple nodular lesions in the bone and lungs suggestive of metastases. The patient was submitted to total thyroidectomy and radioactive iodine. The tumor was composed of CMVPTC and PDTC components that shared the same somatic APC gene mutation (p.Cys520Tyr_fsX534). Besides this mutation, no CTNNB1, BRAF, N-RAS, and H-RAS gene mutations were detected in any of the 2 components. To the best of our knowledge, this is the first report of a sporadic CMVPTC with transformation into PDTC. Although the majority of CMVPTCs carry an indolent clinical outcome, the coexistence of poorly differentiated areas may justify the aggressiveness of the CMVPTC reported here. PMID:23349472

  2. Thyroid carcinoma, version 2.2014.

    PubMed

    Tuttle, R Michael; Haddad, Robert I; Ball, Douglas W; Byrd, David; Dickson, Paxton; Duh, Quan-Yang; Ehya, Hormoz; Haymart, Megan; Hoh, Carl; Hunt, Jason P; Iagaru, Andrei; Kandeel, Fouad; Kopp, Peter; Lamonica, Dominick M; Lydiatt, William M; McCaffrey, Judith; Moley, Jeffrey F; Parks, Lee; Raeburn, Christopher D; Ridge, John A; Ringel, Matthew D; Scheri, Randall P; Shah, Jatin P; Sherman, Steven I; Sturgeon, Cord; Waguespack, Steven G; Wang, Thomas N; Wirth, Lori J; Hoffmann, Karin G; Hughes, Miranda

    2014-12-01

    These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

  3. Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells

    SciTech Connect

    Nakagawa, T.; Mabry, M.; De Bustros, A.; Ihle, J.N.; Nelkin, B.D.; Baylin, S.B.

    1987-08-01

    Medullary thyroid carcinoma (MTC) is an endocrine tumor of the thyroid C cells that expresses high levels of the neuroendocrine peptide hormone calcitonin. During tumor progression in the host, there is an apparent loss of differentiation in MTC cells that involves a consistent decrease in calcitonin content of the tumor cells associated with decreased expression of the calcitonin gene and/or changes in a mRNA alternative-processing pattern away from that characteristic of the parent thyroid C cell. The authors now report that introduction of the viral Harvey ras (v-Ha-ras) oncogene into cultured human MTC cells can reverse such changes in gene expression and can induce endocrine differentiation of the tumor cells. The expression of v-Ha-ras is associated with decreased cellular proliferation and DNA synthesis. There is a marked increase in the number of cytoplasmic secretory granules that are a classic feature of differentiated thyroid C cells. v-Ha-ras expression induces increased expression of the calcitonin gene and the processing of the primary gene transcript is shifted to favor calcitonin mRNA rather than calcitonin-gene-related peptide (CGRP) mRNA production. These studies with cultured human MTC cells provide a model system to study the role of Ha-ras and related genes in neuroendocrine differentiation. The findings suggest an important approach for identifying genes in solid tumors whose altered expression may play a role in the impaired maturational capacity characteristic of cancer cells during tumor progression.

  4. TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas

    PubMed Central

    Melo, Miguel; da Rocha, Adriana Gaspar; Vinagre, João; Batista, Rui; Peixoto, Joana; Tavares, Catarina; Celestino, Ricardo; Almeida, Ana; Salgado, Catarina; Eloy, Catarina; Castro, Patrícia; Prazeres, Hugo; Lima, Jorge; Amaro, Teresina; Lobo, Cláudia; Martins, Maria João; Moura, Margarida; Cavaco, Branca; Leite, Valeriano; Cameselle-Teijeiro, José Manuel; Carrilho, Francisco; Carvalheiro, Manuela; Máximo, Valdemar; Sobrinho-Simões, Manuel

    2014-01-01

    Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter

  5. Papillary thyroid carcinoma in children and adolescents.

    PubMed

    Chung, Bo Mi; Park, Sung Hee; Kim, Soo Jin; Seo, Jae Seung; Kim, Yang Soo; Shim, Hyung Jin; Lee, Jong Beum

    2014-09-01

    Differentiated thyroid carcinoma is uncommon in children and constitutes 0.5% to 3% of all pediatric malignancies. Few studies have reported imaging findings of childhood papillary thyroid carcinomas. We report 3 cases of papillary thyroid carcinomas in children. Among the 3 patients, the youngest was a 7-year-old girl. In the current report, we describe 2 cases of classic papillary thyroid carcinoma and 1 case of pediatric diffuse sclerosing variant of papillary thyroid carcinoma. The ultrasonographic features and diagnostic procedures in these pediatric patients are similar to those in adults.

  6. Radiofrequency Ablation to Treat Loco-Regional Recurrence of Well-Differentiated Thyroid Carcinoma

    PubMed Central

    Lee, Sun Jin; Kim, Bum Soo; Ahn, Kook Jin; Choi, Hyun Seok; Lim, Dong Jun; Kim, Min Hee; Bae, Ja Seong; Kim, Min Sik; Jung, Chan Kwon; Chong, Se Min

    2014-01-01

    Objective To evaluate the efficacy of radiofrequency ablation (RFA) in the treatment of loco-regional, recurrent, and well-differentiated thyroid carcinoma. Materials and Methods Thirty-five recurrent well-differentiated thyroid carcinomas (RTC) in 32 patients were treated with RFA, between March 2008 and October 2011. RTCs were detected by regular follow-up ultrasound and confirmed by biopsy. All patients had fewer than 3 RTCs in the neck and were at high surgical risk or refused to undergo repeated surgery. Average number of RFA sessions were 1.3 (range 1-3). Post-RFA biopsy and ultrasound were performed. The mean follow-up period was 30 months. Pre- and post-RFA serum thyroglobulin values were evaluated. Results Thirty-one patients with 33 RTCs were treated with RFA only, whereas 1 patient with 2 RTCs was treated with RFA followed by surgery. At the last follow-up ultrasound, 31 (94%) of the 33 RTCs treated with RFA alone completely disappeared and the remaining 2 (6%) RTCs showed decreased volume. The largest diameter and volume of the 33 RTCs were markedly decreased by 93.2% (from 8.1 ± 3.4 mm to 0.6 ± 1.8 mm, p < 0.001) and 96.4% (from 173.9 ± 198.7 mm3 to 6.2 ± 27.9 mm3, p < 0.001), respectively. Twenty of the 21 RTCs evaluated with post-RFA biopsies (95%) were negative for malignancy. One (5%) showed remaining tumor that was removed surgically. The serum thyroglobulin was decreased in 19 of 26 patients (73%). Voice change developed immediately after RFA in 6 patients (19%) and was spontaneously recovered in 5 patients (83%). Conclusion Radiofrequency ablation can be effective in treating loco-regional, recurrent, and well-differentiated thyroid carcinoma in patients at high surgical risk. PMID:25469095

  7. Assessment of female fertility and carconogenesis after iodine-131 therapy for differentiated thyroid carcinoma

    SciTech Connect

    Dottorini, M.E.; Lomuscio, G.; Mazzucchelli, L.

    1995-01-01

    The aim of this study was to evaluate female fertility, carcinogenic, and genetic effects after treatment with {sup 131}I of differentiated thyroid carcinoma. A total of 814 females of child-bearing age were studied. The fertility of 627 females who received {sup 131}I therapy was compared to 187 untreated females. Birth histories of the children born from these women were registered. The carcinogenic effect was evaluated by comparing the incidence of tumors in 730 patients treated with {sup 131}I with an internal control group, as well as with local population incidence. There was no significant difference in the fertility rate, birth weight and prematurity between the two groups. Only one case of a ventricular septal defect was observed in a child born to a woman treated with {sup 131}I. The overall standardized incidence ratio (SIR) of second tumors was 1.19 (95% CI: 0.76-1.77) in patients treated with {sup 131}I. An elevated SIR was registered for salivary gland tumors and melanoma. No case of leukemia was registered. The risk of long-term effects of {sup 131}I treatment of differentiated thyroid carcinoma is quite low. Iodine-131 may be safely used in treating cases with a high risk of recurrence. 35 refs., 7 tabs.

  8. Poorly differentiated forms of papillary thyroid carcinoma: distinctive entities or morphological patterns?

    PubMed

    Pilotti, S; Collini, P; Manzari, A; Marubini, E; Rilke, F

    1995-08-01

    The concept that poorly differentiated carcinomas (PDC) represent a group in an intermediate position in the spectrum of follicular cell-derived carcinomas of the thyroid gland is currently well established. Because at the well-differentiated end of the spectrum there are two groups of entities with distinct biological characteristics, ie, the papillary carcinoma (PC) and the follicular carcinoma (FC), we examined the group represented by PCs to ascertain whether papillary carcinoma-related PDCs (pPDC) represent merely a histologic variant or a distinct pathologic entity. For this purpose 227 consecutive PCs were reclassified according to current criteria. The association between the presence of a tumoral pattern consistent with pPDC (response variable), and prognostic factors such as gender age, pTNM (predictive variables) was evaluated in terms of odds ratio statistics. One hundred eighty-three of 227 cases, defined as PCs met the World Health Organization criteria of the not otherwise specified (NOS) (79 cases), microcarcinoma (65 cases), encapsulated (4 cases) and follicular (35 cases) variants. Forty-four cases, defined as pPDCs, met those of the tall cell (39 cases), columnar cell PC (2 cases) and mixed tall cell-columnar cell PC (3 cases) variants. Statistical analyses of the two groups of patients showed a significant correlation between differentiation and age above 40 years, extrathyroid tumor extension and low ratio of regional nodal involvement at the onset of disease. More strikingly they also showed that morphology, ie, a tumoral pattern consistent with pPDC (differentiation), is the strongest predictor of biological behavior including recurrences and recurrence-related deaths that appear to occur five and twenty times more frequently in pPDCs than in PCs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Prevalence of a hobnail pattern in papillary, poorly differentiated, and anaplastic thyroid carcinoma: a possible manifestation of high-grade transformation.

    PubMed

    Amacher, Anne Marie; Goyal, Bella; Lewis, James S; El-Mofty, Samir K; Chernock, Rebecca D

    2015-02-01

    Papillary thyroid carcinoma is the most common thyroid carcinoma and has a generally favorable prognosis. There are several well-characterized variants, some of which are associated with more aggressive clinical behavior. Hobnail is a recently described rare variant that appears to behave more aggressively. Initial reports characterizing this variant focused on primary tumors and excluded other recognized variants, as well as poorly differentiated and anaplastic thyroid carcinomas, from analysis. Here, we evaluate the frequency of hobnail features in both primary and metastatic papillary thyroid carcinomas, including in association with other known variants, and also in poorly differentiated and anaplastic thyroid carcinomas. Primary and metastatic papillary thyroid carcinomas from a 5-year period (2007 to 2011) and all available anaplastic and poorly differentiated thyroid carcinomas from a 22-year period (1989 to 2011) were retrieved from the files. Tumors from 478 papillary, 26 anaplastic, and 18 poorly differentiated thyroid carcinomas were reviewed for hobnail features present in >10% of each tumor. Hobnail features were most commonly observed in association with poorly differentiated thyroid carcinoma (4 of 18 cases, 22%) and were seen in only 1.3% of papillary thyroid carcinoma patients (6 of 478). One of 26 anaplastic carcinomas had hobnail features (3.8%). Among the papillary thyroid carcinomas, hobnail features were often associated with other histologic variants that are known to be more clinically aggressive, had increased mitotic activity, and/or necrosis and lymph node metastases at presentation. These findings suggest that hobnail features may be a manifestation of higher-grade transformation.

  10. [Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma].

    PubMed

    Díez, Juan J; Grande, Enrique; Iglesias, Pedro

    2015-01-01

    Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient.

  11. Is it still worthwhile to treat bone metastases from differentiated thyroid carcinoma with radioactive iodine?

    PubMed

    Proye, C A; Dromer, D H; Carnaille, B M; Gontier, A J; Goropoulos, A; Carpentier, P; Lefebvre, J; Decoulx, M; Wemeau, J L; Fossati, P

    1992-01-01

    From 1964 to 1989, bone metastases were found in 28 of 600 patients operated on for differentiated thyroid carcinoma. Bone metastasis was the presenting symptom in 15 (54%) patients, was detected from the initial symptom in 4 (14.5%) patients, and occurred subsequently in 9 (32%) patients, with an average lag time of 4.5 years after surgical treatment. Pathological pattern of the thyroid cancer was follicular in 26 (93%) patients and papillary in 2 (7%) patients. Bone metastatic involvement was multiple in 21 (75%) patients and associated with other synchronous or metachronous distant metastases in 13 (46%) patients, especially in the lung (10 patients) or the brain (3 patients). The primary treatment of thyroid carcinoma was total thyroidectomy in all 28 patients, with additional modified neck dissection in 8 patients. All 15 patients presenting with symptoms had bone metastases demonstrated by x-ray studies. Six of the bone metastases only took up radioactive iodine 6 weeks after total thyroidectomy, as did 2 of 4 bone metastases detected at initial observation and 4 of 9 metachronous bone metastases. All 12 patients with functioning bone metastases were given radioactive iodine therapy; 4 of the metastases were surgically resected. Only 2 patients with bone metastases showed a complete response after an ablative dose of I-131; none of the metastases had been demonstrated by x-ray studies. Radioactive iodine therapy cures no more than 17% of patients with bone metastases taking up radioactive iodine and 7% of all patients with bone metastases. All patients cured of bone metastases were given radioactive iodine, either alone, or combined with other treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Usefulness of thallium-201 imaging in the diagnosis of metastases from differentiated thyroid carcinoma

    SciTech Connect

    Kusakabe, K.; Kawasaki, S.; Maki, M.; Nara, S.; Kondo, C.; Nishioka, T.; Hiroe, M.; Kurihara, J.; Obara, T.; Yamasaki, T.

    1984-01-01

    To evaluate the usefulness and accuracy of Thallium-201 imaging for detecting metastases from thyroid carcinoma, the authors have compared it with radioiodine scans and serum thyroglobulin levels, which are currently the most sensitive technique for detecting and localizing metastases. Of the sixty-nine patients, fifty-three had lymph node, lung and/or bone metastases. All patients were treated for differentiated thyroid carcinoma with various combinations of total thyroidectomy, radioiodine ablation and thyroid hormone. Scintigraphy with Tl-210 chloride was abnormal in 39 of 53 patients (sensitivity 74%), whereas 34 of 47 patients with I-131 (sensitivity 72%). Positive ratio of I-131 was correlated with histological type (93% of follicular type and 48% of papillary), whereas in the results with Tl-201 no correlation with histopathology was seen. In 13 patients with I-131 scan was negative, but in 11 patients Tl-201 scan revealed the presence of non-functioning metastases. The positive ratio of Tl-201 scans was correlated well with the size of metastases tumors (P<0.005). Of 43 patients with metastases whose thyroglobulin levels (Tg) were measured by radioimmunoassay, Tg were elevated more than 20ng/ml in 37 (86%); the remaining 14% were below 20 ng/ml in spite of having functioning metastases. These patients were subsequently to have elevation of Tg (>80ng/ml) during hypothyroidism. These results indicate Tl-201 scans correlate with serum thyroglobulin levels and have the added advantage of detecting and localizing non-functioning metastases which would not be detected by I-131 scans.

  13. Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

    ClinicalTrials.gov

    2016-08-31

    Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IVA Differentiated Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVB Differentiated Thyroid Gland Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVC Differentiated Thyroid Gland Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

  14. A novel panel of antibodies that segregates immunocytochemically poorly differentiated carcinoma from undifferentiated carcinoma of the thyroid gland.

    PubMed

    Pilotti, S; Collini, P; Del Bo, R; Cattoretti, G; Pierotti, M A; Rilke, F

    1994-10-01

    The expression of bcl-2 and p53 was investigated by immunocytochemistry in combination with that of conventional structural and differentiation antigens on the archival material of 22 cases of undifferentiated carcinoma (UC) and 19 of poorly differentiated carcinoma (PDC) of the thyroid gland. The restriction of bcl-2 expression to PDC in comparison to UC was 84.2% versus 13.6% of cases, respectively, in contrast to an almost equal percentage of p53 expression in the two histologic types, that is, 52.6% and 54.5% of cases of PDC and UC, respectively. However, the pattern of distribution of p53-immunoreactive cells was definitely different, being restricted to areas showing active infiltrating growth in PDC and involving almost all tumor cells in UC. Furthermore, in the subset of cases of UC showing the residual presence of a differentiated component, a distinctive mutual exclusion of bcl-2 and p53 immunoreactivity was observed in the two components. The results suggest that the evaluation of bcl-2 expression may be usefully applied to the differentiation of PDC from UC, whereas all morphologic findings related to p53 expression are in keeping with a significant role of the deregulation of this gene in the mechanism of dedifferentiation and progression of the disease.

  15. Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma

    PubMed Central

    Zhang, Huairong

    2016-01-01

    Aim. We aim to identify protein kinases involved in the pathophysiology of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible molecular mechanisms. Materials and Methods. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway analysis. Results. The functional enrichment analysis indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.” MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel molecular therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. Conclusion. SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases. PMID:27703281

  16. Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature*

    PubMed Central

    Zhang, Wei-dong; Liu, Da-ren; Feng, Cheng-cheng; Zhou, Chuan-biao; Zhan, Chen-ni; Que, Ri-sheng; Chen, Li

    2014-01-01

    Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42–72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I131 adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment. PMID:25471838

  17. Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature.

    PubMed

    Zhang, Wei-dong; Liu, Da-ren; Feng, Cheng-cheng; Zhou, Chuan-biao; Zhan, Chen-ni; Que, Ri-sheng; Chen, Li

    2014-12-01

    Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42-72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I(131) adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.

  18. Differential expression of two activating transcription factor 5 isoforms in papillary thyroid carcinoma

    PubMed Central

    Vicari, Luisa; La Rosa, Cristina; Forte, Stefano; Calabrese, Giovanna; Colarossi, Cristina; Aiello, Eleonora; Salluzzo, Salvatore; Memeo, Lorenzo

    2016-01-01

    Background Activating transcription factor 5 (ATF5) is a member of the activating transcription/cAMP response element-binding protein family of basic leucine zipper proteins that plays an important role in cell survival, differentiation, proliferation, and apoptosis. The ATF5 gene generates two transcripts: ATF5 isoform 1 and ATF5 isoform 2. A number of studies indicate that ATF5 could be an attractive target for therapeutic intervention in several tumor types; however, so far, the role of ATF5 has not been investigated in papillary thyroid carcinoma (PTC). Methods Quantitative real-time reverse transcription polymerase chain reaction and immuno-histochemical staining were used to study ATF5 mRNA and protein expression in PTC. Results We report here that ATF5 is expressed more in PTC tissue than in normal thyroid tissue. Furthermore, this is the first study that describes the presence of both ATF5 isoforms in PTC. Conclusion These findings could provide potential applications in PTC cancer treatment. PMID:27785070

  19. Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis.

    PubMed

    Pozo, Karine; Hillmann, Antje; Augustyn, Alexander; Plattner, Florian; Hai, Tao; Singh, Tanvir; Ramezani, Saleh; Sun, Xiankai; Pfragner, Roswitha; Minna, John D; Cote, Gilbert J; Chen, Herbert; Bibb, James A; Nwariaku, Fiemu E

    2015-05-20

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis. PMID:25900242

  20. Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis

    PubMed Central

    Pozo, Karine; Hillmann, Antje; Augustyn, Alexander; Plattner, Florian; Hai, Tao; Singh, Tanvir; Ramezani, Saleh; Sun, Xiankai; Pfragner, Roswitha; Minna, John D.; Cote, Gilbert J.; Chen, Herbert

    2015-01-01

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis. PMID:25900242

  1. Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis.

    PubMed

    Pozo, Karine; Hillmann, Antje; Augustyn, Alexander; Plattner, Florian; Hai, Tao; Singh, Tanvir; Ramezani, Saleh; Sun, Xiankai; Pfragner, Roswitha; Minna, John D; Cote, Gilbert J; Chen, Herbert; Bibb, James A; Nwariaku, Fiemu E

    2015-05-20

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis.

  2. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

    SciTech Connect

    Pacini, F.; Gasperi, M.; Fugazzola, L.

    1994-09-01

    The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.

  3. [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.

  4. Metastatic Papillary Thyroid Carcinoma with Multifocal Synchronous Transformation to Anaplastic Thyroid Carcinoma

    PubMed Central

    Costa, Jose

    2016-01-01

    Papillary thyroid carcinoma is a common malignancy to affect the thyroid and is typified by a nonaggressive nature and low rates of mortality. In contrast, anaplastic thyroid carcinoma is the most aggressive thyroid malignancy with a mortality rate of nearly 90% and survival typically of only six months after the diagnosis is made. The transformation of papillary thyroid carcinoma to anaplastic thyroid carcinoma is well documented in the literature but is uncommon and in most instances is reported as a case report or small series only. Transformation of papillary thyroid carcinoma to anaplastic thyroid carcinoma usually takes place in the thyroid itself or in the adjacent lymph nodes. Only on rare occasions does a transformation occur in a papillary thyroid carcinoma metastasis outside of these locations. In the present case report and subsequent discussion we highlight an unusual case of PTC with transformation to anaplastic thyroid carcinoma, which is shown to involve numerous locations to include near total lung parenchyma obliteration. We also discuss the differential diagnostic challenges when faced with a thyroid malignancy that is negative for thyroglobulin. PMID:27774331

  5. Parameters Influencing Curative Effect of 131I Therapy on Pediatric Differentiated Thyroid Carcinoma: A Retrospective Study.

    PubMed

    Xu, Lu; Liu, Qiong; Liu, Ying; Pang, Hua

    2016-01-01

    BACKGROUND This study aimed to investigate the parameters influencing the effectiveness of first 131I thyroid remnant ablation and then 131I treatment of metastatic lesions in children and adolescents with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS A total of 88 children and adolescents with DTC were divided into 2 groups: 56 in the complete-ablation group and 32 in the incomplete-ablation group for the first 131I ablation; 32 in the incomplete-ablation group were further divided: 19 in the complete-remission group and 13 in the incomplete-remission group for subsequent 131I treatment of metastatic lesions. Influential parameters were analyzed using t test, t' test, rank-sum test, χ2-test, and Fisher exact test, and logistic regression analysis was performed. Radioactive iodine uptake (RAIU), lymph node metastases, and pulmonary metastases were selected as influential parameters. RESULTS After logistic regression analysis, RAIU, only lymph node metastases, and pulmonary metastasis were significantly associated with the complete-ablation rate. High levels of RAIU and serum thyroglobulin (Tg) were not conducive to disease remission after subsequent 131I treatment of metastatic lesions. The remission rate of patients with pulmonary metastasis was lower than the rate of patients with lymph node metastases or no metastases. CONCLUSIONS Results demonstrated that a high remission rate is associated with low postoperative RAIU and Tg. Lymph node metastasis and pulmonary metastasis reduce the complete-remission rate of first 131I ablation therapy. Pulmonary metastasis reduces the remission rate of subsequent 131I treatment. Also, 131I treatment for pediatric DTC with pulmonary metastasis achieved progression-free survival. PMID:27576533

  6. [15 years' results in the treatment of differentiated thyroid carcinoma in a region of endemic goiter].

    PubMed

    Perinetti, H A; Staneloni, L N; Vitale, R

    1990-01-01

    We have evaluated the results of differentiated thyroid carcinoma treatment after 15 years of follow up. The group consisted of 120 cases of papillary type and 144 cases of follicular type; the mean age of the patients was 38.2 years for papillary and 46.5 for the follicular. The ratio men/women was 1/4 for the papillary and 1/3.2 for the follicular. The prognostic factors evaluated included: a) histologic types according to WHO classification, b) clinical stage, c) age and d) sex. The staging of the disease followed the classification suggested by Smendal, stage I: intraglandular disease; stage II: regional lymph node metastases; stage III: invasion of other tissues in the neck or mediastinum and stage IV: distant metastases. The basic treatment was surgery with the use of 131I and thyroid hormone. The results were statistically analyzed with the conventional life table method or chi square. At 15 years the overall survival was 84 +/- 4% for the papillary type and 66 +/- 9% for the follicular type (p = 0.01) (Fig. 1). The patients treated in stage I had a survival of 90 +/- 5%, significantly higher than those in stage II (53 +/- 8%), p less than 0.03. In stage III and IV the small number of patients made it difficult to interpret the results statistically (Fig. 2). The age of the patients appears to be another prognostic factor. The group under 40 years had 85 +/- 5% of survival compared to 59 +/- 4% over 40 years, p less than 0.01 (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    SciTech Connect

    Van Nostrand, D.; Neutze, J.; Atkins, F.

    1986-10-01

    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach.

  8. Cervical neck dissection without drains in well-differentiated thyroid carcinoma.

    PubMed

    Abboud, Bassam; Sleilaty, Ghassan; Tannoury, Jenny; Daher, Ronald; Abadjian, Gerard; Ghorra, Claude

    2011-12-01

    This study aims to review the safety of thyroidectomy combined with cervical neck dissection without drainage in well-differentiated thyroid carcinoma (WDTC). The medical records of consecutive patients who underwent thyroidectomy without drainage for WDTC were retrospectively reviewed. Group 1 included 123 patients who underwent thyroidectomy with central neck dissection and Group 2 included 46 patients who underwent thyroidectomy with central and lateral neck dissection. One hundred twenty-seven patients underwent thyroidectomy without neck dissection and were included in Group 3. Overall, 16 patients (5%) developed postoperative hematoma and/or seroma, seven patients (6%) in the Group 1, three patients (7%) in the Group 2, and six patients (5%) in Group 3. All patients had minor bleeding or seroma not requiring surgical intervention. Overall, 68 patients (23%) had transient postoperative hypocalcaemia, and four patients(1%) had permanent hypoparathyroidism. Seventeen patients (6%) had transient postoperative hoarseness and three had permanent vocal cord paralysis (0.6%). The postoperative stay for all groups was 1 day in 91 per cent of the cases. Patients from Groups 1 and 2 had no increased perioperative local complications or length of stay as compared with Group 3. Cervical neck dissection and thyroidectomy without drains is safe and effective in the treatment of WDTC.

  9. Recombinant Human Thyrotropin-Aided Radioiodine Therapy in Patients with Metastatic Differentiated Thyroid Carcinoma

    PubMed Central

    Zagar, Ivana; Schwarzbartl-Pevec, Andreja A.; Vidergar-Kralj, Barbara; Horvat, Rika; Besic, Nikola

    2012-01-01

    Our aim was to test the efficacy of 131-I therapy (RIT) using recombinant human TSH (rhTSH) in patients with differentiated thyroid carcinoma (DTC) in whom endogenous TSH stimulation was not an option due to the poor patient's physical condition or due to the disease progression during L-thyroxin withdrawal. The study comprised 18 patients, who already have undergone total or near-total thyroidectomy and radioiodine ablation and 0–12 (median 5) RITs after L-thyroxin withdrawal. Our patients received altogether 44 RITs using rhTSH while on L-thyroxin. Six to 12 months after the first rhTSH-aided RIT, PR and SD was achieved in 3/18 (17%) and 4/18 patients (22%), respectively. In most patients (n = 12; 61%) disease progressed despite rhTSH-aided RITs. As a conclusion, rhTSH-aided RIT proved to add some therapeutic benefit in 39% our patients with metastatic DTC, who otherwise could not be efficiently treated with RIT. PMID:21876838

  10. Colon carcinoma metastatic to the thyroid gland

    SciTech Connect

    Lester, J.W. Jr.; Carter, M.P.; Berens, S.V.; Long, R.F.; Caplan, G.E.

    1986-09-01

    Metastatic carcinoma to the thyroid gland rarely is encountered in clinical practice; however, autopsy series have shown that it is not a rare occurrence. A case of adenocarcinoma of the colon with metastases to the thyroid is reported. A review of the literature reveals that melanoma, breast, renal, and lung carcinomas are the most frequent tumors to metastasize to the thyroid. Metastatic disease must be considered in the differential diagnosis of cold nodules on radionuclide thyroid scans, particularly in patients with a known primary.

  11. Treatment of thyroid follicular carcinoma.

    PubMed

    Ríos, Antonio; Rodríguez, José M; Parrilla, Pascual

    2015-12-01

    Differentiated thyroid carcinoma includes 2 different tumor types, papillary (PC) and follicular carcinoma (FC), and although similar, their prognosis is different. FC is uncommon, and this has led to it often being analyzed together with PC, and therefore the true reality of this tumor is difficult to know. As a result, the diagnostic and therapeutic management and the prognostic factors in differentiated carcinoma are more predictive of PC than FC. In this review we analyze the current state of many of the therapeutic aspects of this pathology. The best surgical technique and the usefulness of associated lymphadenectomy is also analyzed. Regarding post-surgical ablation with 131I, the indications, doses and usefulness are discussed. For the remaining therapies we analyze the few indications for radiotherapy and chemotherapy, and of new drugs such as tyrosine kinase inhibitors.

  12. Socioeconomic factors and the presentation, management, and outcome of patients with differentiated thyroid carcinoma.

    PubMed

    Ghori, Farah Y; Gutterman-Litofsky, Danielle R; Jamal, Amin; Yeung, Sai-Ching J; Arem, Ridha; Sherman, Steven I

    2002-11-01

    To determine whether patients from disadvantaged socioeconomic groups present with more advanced thyroid carcinoma or experience differing management and clinical outcomes, we retrospectively reviewed the charts of 292 patients seen at MD Anderson Cancer Center and Ben Taub General Hospital between 1987 and 1994. At diagnosis, the mean age was 42 +/- 16 years, 78% of patients were female, 76% of patients were low risk (TNM stage I or II), and 22% high risk (stage III or IV). Neighborhood income (+/- standard error of the mean [SEM]) (1990 census data) was lower in the high-risk group compared with the low-risk group (US dollars 26200 +/- 1670 vs. US dollars 30900 +/- 870, p = 0.012). Men were more likely than women to present at an older age (47.5 +/- 16.7 vs. 40.2 +/- 16.0, p = 0.0014) and in the high-risk group (46% vs. 15%, p < 0.0001). No socioeconomic factor (ethnicity, marital status, occupation prestige, neighborhood income, insurance type) influenced initial diagnostic assessment. Similarly, no socioeconomic factor influenced initial disease management or the type of follow-up received over the 12-year period. Married patients had a lower 5-year recurrence rate than those unmarried (18% vs. 32%, p = 0.03); however, this did not affect overall or disease-specific survival. Similarly, ethnicity, marital status, occupation prestige, and insurance type did not influence overall or disease-specific survival. Although 10-year overall survival rates were lower in patients in the lowest income quartile (57% vs. 70% for upper, p = 0.0024) and in men compared with women (39% vs. 76%, p < 0.0001), gender alone influenced 10-year disease-specific survival (80% for men, 89% for women, p = 0.047). In summary, no socioeconomic factor appears to affect initial treatment or follow-up pattern in patients with differentiated thyroid cancer. Income and gender may affect stage at initial disease presentation and may be risk factors affecting eventual clinical outcomes.

  13. TROP-2 immunohistochemistry: a highly accurate method in the differential diagnosis of papillary thyroid carcinoma.

    PubMed

    Bychkov, Andrey; Sampatanukul, Pichet; Shuangshoti, Shanop; Keelawat, Somboon

    2016-08-01

    We aimed to evaluate the diagnostic utility of the novel immunohistochemical marker TROP-2 on thyroid specimens (226 tumours and 207 controls). Whole slide immunohistochemistry was performed and scored by automated digital image analysis. Non-neoplastic thyroid, follicular adenomas, follicular carcinomas, and medullary carcinomas were negative for TROP-2 immunostaining. The majority of papillary thyroid carcinoma (PTC) specimens (94/114, 82.5%) were positive for TROP-2; however, the pattern of staining differed significantly between the histopathological variants. All papillary microcarcinomas (mPTC), PTC classic variant (PTC cv), and tall cell variant (PTC tcv) were TROP-2 positive, with mainly diffuse staining. In contrast, less than half of the PTC follicular variant specimens were positive for TROP-2, with only focal immunoreactivity. TROP-2 could identify PTC cv with 98.1% sensitivity and 97.5% specificity. ROC curve analysis found that the presence of >10% of TROP-2 positive cells in a tumour supported a diagnosis of PTC. The study of intratumoural heterogeneity showed that low-volume cytological samples of PTC cv could be adequately assessed by TROP-2 immunostaining. The TROP-2 H-score (intensity multiplied by proportion) was significantly associated with PTC variant and capsular invasion in encapsulated PTC follicular variant (p<0.001). None of the baseline (age, gender) and clinical (tumour size, nodal disease, stage) parameters were correlated with TROP-2 expression. In conclusion, TROP-2 membranous staining is a very sensitive and specific marker for PTC cv, PTC tcv, and mPTC, with high overall specificity for PTC. PMID:27311870

  14. Targeting vascular endothelial growth factor (VEGF) pathway in iodine-refractory differentiated thyroid carcinoma (DTC): from bench to bedside.

    PubMed

    Abdel-Rahman, Omar

    2015-04-01

    Thyroid cancer is the most common endocrine malignancy, representing 1% of all human malignancies; its incidence has been escalating worldwide during the last decades. In recent years important molecular pathways contributing to tumor progression and worse survival rates have been identified in iodine-refractory differentiated thyroid carcinoma (DTC) with the consequent development of molecular therapeutics to target these specific oncogenic pathways. For example, a positive correlation has been found between expression of vascular endothelial growth factor (VEGF) and a more aggressive phenotype of DTC. This has led to the widespread adoption of VEGF-targeted therapeutics in the preclinical and clinical settings. In this review we will provide an overview of the different aspects of the use of VEGF-pathway-oriented treatments in iodine-refractory DTC with particular focus on future prospects.

  15. Insulin-like growth factor-I and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition

    PubMed Central

    Schmidt, Julie A.; Allen, Naomi E.; Almquist, Martin; Franceschi, Silvia; Rinaldi, Sabina; Tipper, Sarah J.; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Dossus, Laure; Mesrine, Sylvie; Kaaks, Rudolf; Lukanova, Annekatrin; Boeing, Heiner; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Zanetti, Roberto; Bueno-de-Mesquita, H Bas; Peeters, Petra H; Lund, Eiliv; Menéndez, Virginia; Agudo, Antonio; Sánchez, María-José; Chirlaque, Maria-Dolores; Ardanaz, Eva; Larrañaga, Nerea; Hennings, Joakim; Sandström, Maria; Khaw, Kay-Tee; Wareham, Nick; Romieu, Isabelle; Gunter, Marc J.; Riboli, Elio; Key, Timothy J.; Travis, Ruth C.

    2014-01-01

    Background Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and anti-apoptotic properties. Methods This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study centre, sex, and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. Results There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the odds ratio for a doubling in IGF-I concentration was 1.48 (95% confidence interval: 1.06 – 2.08; ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. Conclusion These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. Impact This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association. PMID:24646451

  16. [Medullary thyroid carcinoma].

    PubMed

    Niccoli-Sire, P; Conte-Devolx, B

    2007-10-01

    Medullary thyroid carcinoma (MTC) is developed from thyroid C cells that secrete calcitonin (CT). MTC represents 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. Diagnosis is usually made by a solitary nodule often associated to nodal metastasis and confirmed by a high basal CT level which represents its biological marker. MTC may present as a sporadic form and in about 30% of case as a familial form as a part of multiple endocrine neoplasia syndrome, an hereditary dominant inherited disease related to germline mutation of the proto-oncogene RET. Both biological (CT) and genetic (RET) markers allows the optimal diagnosis and treatment of MTC; the former allows screening and early diagnosis of MTC by routinely CT measurements in nodular thyroid diseases that make the adequate and complete surgery required to be performed. The former leads to diagnose familial MTC and to identify at risk subjects in whom early or prophylactic surgery may be performed. Treatment of MTC is based on the complete surgical resection: total thyroidectomy associated to central and laterocervical nodal dissection. For locally advanced or metastatic MTC, complete cervical surgery is required and needs to be associated to other systemic treatments: as chemotherapy is not very efficient, radioimmunotherapy and RET target gene therapy (mainly tyrosine kinase inhibitors) appears as possible valuable therapeutic options for the future. Prognosis of MTC is mainly related to both the stage of the disease and the extend of the initial surgery. Ten-year survival is about 80% when the patients are not surgically cured and reaches 95% when the biological marker CT is normalized after surgery. PMID:17572372

  17. Thyroid carcinoma in patients with Graves' disease: an institutional experience.

    PubMed

    Wei, Shuanzeng; Baloch, Zubair W; LiVolsi, Virginia A

    2015-03-01

    Graves' disease (GD) is an autoimmune disorder characterized by diffuse hyperplasia and excessive production of thyroid hormone. The association between thyroid carcinoma and GD is controversial. The prevalence of thyroid carcinoma was investigated in patients with GD who underwent thyroidectomy for thyroid nodular lesions or GD from 1994 to 2013 at our institution. Three hundred and forty-seven patients were placed into two groups: Graves' disease with nodular lesions group (group GN) included 85 patients who had thyroidectomy for nodular lesion, and Graves' disease group (group G) included 262 patients who had thyroidectomy for hyperthyroidism. There were 59 patients with thyroid carcinomas in the 85 patients (69 %) of group GN, including 3 follicular carcinomas (5 %), 1 poorly differentiated carcinoma (2 %), and 55 papillary thyroid carcinomas (93 %). Among the 55 papillary thyroid carcinomas, 19 cases were papillary thyroid microcarcinomas (34 %); and 5 cases of tall cell variant (9 %) were identified. There were 8 cases with lymph node metastasis (14 %), 6 cases with lymphovascular invasion (10 %), and 12 cases with extrathyroidal invasion (20 %). In addition, 24 carcinomas showed multiple foci of tumor (41 %). In contrast, 51 patients (19 %) of 262 patients in group G had carcinoma, including 2 follicular carcinomas (4 %) and 49 papillary thyroid carcinomas (96 %). In the 49 cases of papillary thyroid carcinomas, 47 cases were microcarcinomas (96 %); and 2 cases of tall cell variant (4 %) were found. There were no lymph node metastasis or lymphovascular and extrathyroidal invasion, but 11 cases (22 %) demonstrated multiple carcinoma foci. In conclusion, thyroid nodular lesions in patients with GD should raise a high suspicion of carcinoma, and these lesions are frequently clinically significant tumors. Incidental thyroid carcinomas in patients with GD are not uncommon, but most of them are low-risk papillary thyroid microcarcinoma without lymph node

  18. [DNA methylation in thyroid carcinoma].

    PubMed

    Song, Xianyun; Shang, Xiaoling; Zhang, Yutuo

    2015-03-01

    Cancer has become clear that not merely gene variations but also epigenetic modifications may contribute to it. Epigenetic changes refer to stable alterations in gene expression with unrelated to changes in the underlying genetic sequence,resulting in heritable. DNA methylation is one of the common epigenetic changes. It control the gene expression through changing DNA conformation and stability, chromatin structer, DNA-protein interaction. The reversal of dysregulated DNA methylation has emerged as a potential strategy for the treatment of thyroid carcinoma. The artical will provide an overview of how DNA methylation contribute to thyroid carcinoma dissemination,invasion and metastasis and we will summarize the latest epigenetic therapies for thyroid carcinoma.

  19. [Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm].

    PubMed

    Naranjo-Gómez, José Manuel; Folqué-Gómez, Emilio; Moreno-Mata, Nicolás; Moldes-Rodríguez, Milagros; Martínez-Martínez, Patricia; González-Aragoneses, Federico; Orusco-Palomino, Eduardo

    2005-04-01

    Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by Carcangiu when he described its characteristic histology. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. However, most authors believe it to be an independent entity. The prognosis of this tumor is worse than that of classic carcinoma of the thyroid, and most authors advise aggressive therapy, which in some cases can achieved prolonged survival. We describe 2 patients who experienced recurrence after treatment for the primary tumor. The recurrences were treated but the clinical courses differed.

  20. Five-year longitudinal evaluation of quality of life in a cohort of patients with differentiated thyroid carcinoma

    PubMed Central

    Giusti, Massimo; Melle, Giulia; Fenocchio, Monica; Mortara, Lorenzo; Cecoli, Francesca; Caorsi, Valeria; Ferone, Diego; Minuto, Francesco; Rasore, Elda

    2011-01-01

    Differentiated thyroid carcinoma (DTC) generally has a favorable outcome. Thyroid disease, treatments, stress, and comorbidity can compromise health-related quality of life (QoL) and indirectly weigh upon the outcome. From 2004 to 2008, we evaluated QoL longitudinally in 128 DTC subjects. During scheduled examinations, subjects were asked to undergo a semi-structured psychiatric interview and five rated inventories. The same examination was conducted in 219 subjects after surgery for benign thyroid pathology. Low scores represent a better QoL. DTC and control subjects were similar in terms of age, male/female ratio, concomitant psychopharmacological treatments, and frequency of psychiatric diseases. In DTC subjects, Billewicz scale (BS) scores showed an increasing trend over time, especially among females. The ad hoc thyroid questionnaire (TQ) scores were similar in both groups and did not change over time, but at the end of the study ad hoc TQ and BS were significantly related. Ad hoc TQ scores were also related to age on entry to the study. In both male and female DTC subjects, Hamilton’s tests for anxiety (HAM-A), but not for depression (HAM-D), showed an improving trend. At the end of the study, HAM-A and HAM-D scores were comparable to those of the control group. HAM-A and HAM-D were both positively correlated with the stage of cancer and the time between diagnosis and treatment. Only HAM-D correlated with age on entry to the study. Kellner symptom questionnaire (KSQ) item scores were higher in DTC subjects than in controls. The change over time in the items including anxiety, somatization, depression, and hostility was significant. Somatization and hostility were more significantly reduced in DTC females than in DTC males. Hostility scores were significantly lower in DTC subjects than in controls at the end of the study. Somatization and depression were significantly related to staging on diagnosis and age on entry to the study. Our study confirms a wide

  1. Metastatic thyroid carcinoma of the mandibule.

    PubMed

    Erdag, T; Bilgen, C; Ceryan, K

    1999-01-01

    A case of metastatic papillary carcinoma to the mandible is presented. Though relatively rare, metastatic tumours of the mandible should be included in the differential diagnosis of the tumours in the parotid region. For the primary site; being in the cervicofacial region, the thyroid gland must be considered by the head and neck surgeon.

  2. Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma

    SciTech Connect

    Marcocci, C.; Pacini, F.; Elisei, R.; Schipani, E.; Ceccarelli, C.; Miccoli, P.; Arganini, M.; Pinchera, A. )

    1989-12-01

    Thirty (3.8%) of 780 patients with differentiated thyroid cancer seen between 1970 and 1987 had bone metastases. The primary tumor was follicular in 26 patients and papillary in four. Mean age at diagnosis was 61 years. The manifestation of bone metastases was the presenting symptom in 18 patients (60%). Treatment included total thyroidectomy, levothyroxine sodium therapy, and radioactive iodine treatments. Twenty-seven patients had bone metastases from the initial observation, with 44 sites involved. Of the sites, 27 (61%) were shown both on iodine 131 whole-body scan (WBS) and on x-ray film, 11 (25%) only on WBS, and six (14%) only on x-ray film. Multiple involvement was observed in 11 patients. The radiologic appearance was invariably osteolytic. Serum thyroglobulin was elevated in all patients. After radioactive iodine, no WBS+/X-ray+ metastases showed a complete response, although a sclerotic border was noted in several cases, whereas six WBS+/X-ray- lesions were no longer detectable by WBS. Treatment with radioactive iodine and bone surgery resulted in a complete cure in three patients and in a reduction of tumor mass in three. Twenty-one (70%) of the patients died of thyroid cancer after a mean survival of 86 months. Of the nine patients still alive, two are free of disease, three have a good quality of life, and four have severe disability.

  3. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    SciTech Connect

    Li, Luchuan; Lv, Bin; Chen, Bo; Guan, Ming; Sun, Yongfeng; Li, Haipeng; Zhang, Binbin; Ding, Changyuan; He, Shan; Zeng, Qingdong

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  4. Raf-1 kinase inhibitory protein expression in thyroid carcinomas.

    PubMed

    Kim, Hyun-Soo; Kim, Gou Young; Lim, Sung-Jig; Kim, Youn Wha

    2010-12-01

    Raf-1 kinase inhibitory protein (RKIP) has been implicated in several fundamental signal transduction pathways that control cellular growth, differentiation, apoptosis and migration. RKIP is reduced in a variety of human carcinomas, but RKIP expression in thyroid carcinomas has not been analyzed at the protein level. In this study, we examined the immunohistochemical expression of RKIP in various subtypes of thyroid carcinoma. Immunostaining for RKIP was performed on 104 cases of primary thyroid carcinoma (40 papillary, 29 follicular, 11 medullary, 11 poorly differentiated, and 13 anaplastic carcinomas) and 26 cases of nodal metastatic tumor (17 papillary, 4 medullary, and 5 anaplastic carcinomas). Normal thyroid tissue and all cases of follicular, papillary, and medullary carcinomas showed uniform, strong cytoplasmic immunoreactivity for RKIP. With the exception of one case, poorly differentiated carcinomas also revealed strong RKIP expression. In contrast, RKIP expression was completely absent in all anaplastic carcinomas. The transition zone from the differentiated carcinoma component (strong RKIP expression) to the anaplastic carcinoma component (no RKIP expression) demonstrated a completely opposite pattern of RKIP immunoreactivity. This reduction of RKIP expression in anaplastic carcinoma was statistically significant (P < 0.0001). Additionally, RKIP expression of nodal metastatic tumors corresponded with that of primary tumors: metastatic papillary and medullary carcinomas showed uniform, strong cytoplasmic RKIP immunoreactivity, in contrast, in metastatic anaplastic carcinomas, RKIP expression was completely absent. RKIP expression is significantly reduced in anaplastic thyroid carcinoma as compared to other subtypes of thyroid carcinoma. Further studies are necessary to elucidate the precise mechanism of RKIP action in anaplastic thyroid carcinoma.

  5. Thyroglossal Duct Papillary Thyroid Carcinoma and Synchronous Lingual Thyroid Atypia

    PubMed Central

    Yoo, Timothy; Kim, Yohanan; Simental, Alfred; Inman, Jared C.

    2016-01-01

    Thyroglossal duct and lingual thyroid ectopic lesions are exceedingly rare synchronous findings. Papillary thyroid carcinoma of these ectopic thyroid sites is well understood but still a rare finding. This case points to some management nuances in regard to ectopic thyroid screening with imaging and also shows the effectiveness of minimally invasive transoral robotic surgery for lingual thyroid. PMID:27119036

  6. Targeted therapy: a new hope for thyroid carcinomas.

    PubMed

    Perri, Francesco; Pezzullo, Luciano; Chiofalo, Maria Grazia; Lastoria, Secondo; Di Gennaro, Francesca; Scarpati, Giuseppina Della Vittoria; Caponigro, Francesco

    2015-04-01

    Thyroid carcinomas are rare and heterogeneous diseases representing less than 1% of all malignancies. The majority of thyroid carcinomas are differentiated entities (papillary and folliculary carcinomas) and are characterized by good prognosis and good response to surgery and radioiodine therapy. Nevertheless, about 10% of differentiated carcinomas recur and become resistant to all therapies. Anaplastic and medullary cancers are rare subtypes of thyroid cancer not suitable for radioiodine therapy. A small percentage of differentiated and all the anaplastic and medullary thyroid carcinomas often recur after primary treatments and are no longer suitable for other therapies. In the last years, several advances have been made in the field of molecular biology and tumorigenesis mechanisms of thyroid carcinomas. Starting from these issues, the targeted therapy may be employed as a new option. The MAP-Kinase pathway has been found often dysregulated in thyroid carcinomas and several upstream signals have been recognized as responsible for this feature. RET/PTC mutations are often discovered both in papillary and in medullary carcinomas, while B-RAF mutation is typical of papillary and anaplastic histologies. Also mTOR disruptions and VEGFR pathway disruption are common features in all advanced thyroid cancers. Some angiogenesis inhibitors and a number of RET/PTC pathway blocking agents are yet present in the clinical armamentarium. Vandetanib, cabozatinib and sorafenib have reached clinical use. A number of other biological compounds have been tested in phase II and III trials. Understanding the biology of thyroid cancers may help us to design a well shaped targeted therapy.

  7. Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

    ClinicalTrials.gov

    2016-07-04

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

  8. Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment - initial experience.

    PubMed

    Werner, R A; Lückerath, K; Schmid, J S; Higuchi, T; Kreissl, M C; Grelle, I; Reiners, C; Buck, A K; Lapa, C

    2016-01-01

    Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2-3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression. PMID:27306607

  9. Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

    PubMed Central

    Toledo, Sergio PA; Lourenço, Delmar M; Santos, Marcelo Augusto; Tavares, Marcos R; Toledo, Rodrigo A; de Menezes Correia-Deur, Joya Emilie

    2009-01-01

    Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2–4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%–100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and

  10. [Thyroid nodules and differentiated thyroid cancer: Brazilian consensus].

    PubMed

    Maia, Ana Luiza; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa M Zanini; Rosário, Pedro W; Vaisman, Mario

    2007-07-01

    Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

  11. The effect of thyroid stimulating hormone suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma.

    PubMed

    Moon, Jae Hoon; Jung, Kyong Yeun; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul

    2016-02-01

    Subclinical hyperthyroidism has been reported to increase the fracture risk. However, the effect of thyroid stimulating hormone (TSH) suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma (DTC) is still unclear. The aim of this study was to investigate the effect of TSH suppression on bone geometry in the hip area of pre- and postmenopausal women with DTC. We conducted a retrospective cohort study including 99 women with DTC (25 pre- and 74 postmenopausal) who had received TSH suppressive therapy for at least 3years and 297 control subjects (75 and 222, respectively) matched for sex and age. Bone mineral density (BMD) in the spine and hip area and bone geometry at the femoral neck measured by dual energy X-ray absorptiometry (DXA) were compared between patients and controls. The association between thyroid hormone and bone parameters was investigated. All analyses of bone parameters were adjusted for age, body mass index, and serum calcium levels. In premenopausal subjects, TSH suppressive therapy was not associated with poor bone parameters. In postmenopausal subjects, patients with DTC undergoing TSH suppression showed lower cross-sectional moment of inertia (CSMI), cross-sectional area, and section modulus and thinner cortical thickness at the femoral neck than those of control subjects, whereas their femoral neck BMD was comparable with controls. Total hip BMD was lower in postmenopausal patients than in controls. CSMI and section modulus at the femoral neck were independently associated with serum free T4 levels in postmenopausal patients. The difference in femoral neck bone geometry between patients and controls was only apparent in postmenopausal DTC patients with free T4 >1.79ng/dL (23.04pmol/l), and not in those with free T4 levels ≤1.79ng/dL (23.04pmol/l). TSH suppression in postmenopausal DTC patients was associated with decreased bone strength by altering bone geometry rather than BMD in the hip area

  12. The effect of thyroid stimulating hormone suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma.

    PubMed

    Moon, Jae Hoon; Jung, Kyong Yeun; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul

    2016-02-01

    Subclinical hyperthyroidism has been reported to increase the fracture risk. However, the effect of thyroid stimulating hormone (TSH) suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma (DTC) is still unclear. The aim of this study was to investigate the effect of TSH suppression on bone geometry in the hip area of pre- and postmenopausal women with DTC. We conducted a retrospective cohort study including 99 women with DTC (25 pre- and 74 postmenopausal) who had received TSH suppressive therapy for at least 3years and 297 control subjects (75 and 222, respectively) matched for sex and age. Bone mineral density (BMD) in the spine and hip area and bone geometry at the femoral neck measured by dual energy X-ray absorptiometry (DXA) were compared between patients and controls. The association between thyroid hormone and bone parameters was investigated. All analyses of bone parameters were adjusted for age, body mass index, and serum calcium levels. In premenopausal subjects, TSH suppressive therapy was not associated with poor bone parameters. In postmenopausal subjects, patients with DTC undergoing TSH suppression showed lower cross-sectional moment of inertia (CSMI), cross-sectional area, and section modulus and thinner cortical thickness at the femoral neck than those of control subjects, whereas their femoral neck BMD was comparable with controls. Total hip BMD was lower in postmenopausal patients than in controls. CSMI and section modulus at the femoral neck were independently associated with serum free T4 levels in postmenopausal patients. The difference in femoral neck bone geometry between patients and controls was only apparent in postmenopausal DTC patients with free T4 >1.79ng/dL (23.04pmol/l), and not in those with free T4 levels ≤1.79ng/dL (23.04pmol/l). TSH suppression in postmenopausal DTC patients was associated with decreased bone strength by altering bone geometry rather than BMD in the hip area

  13. Adrenal metastasis from differentiated thyroid carcinoma documented on post-therapy 131I scan: A case based discussion

    PubMed Central

    Ranade, Rohit; Thapa, Pradeep; Basu, Sandip

    2014-01-01

    Adrenal metastasis is an unusual site of disease involvement in the natural course of differentiated thyroid carcinoma (DTC). This paper discusses the clinical and imaging features of DTC with adrenal metastasis. An unusual case of unilateral solitary asymptomatic adrenal metastasis in the setting of DTC is described in this report with the imaging features including 131I scintigraphy and Fluorodeoxyglucose- Positron emission tomography/computed tomography. The adrenal metastasis was associated with other sites of metastatic disease involvement and was unidentified on initial pre-treatment evaluation studies. All such suspicious lesions should be further evaluated with clinicoradiological correlation by other imaging modalities. A post-radioiodine therapy scan revealed radioiodine uptake in the thyroid bed, sternum and a focus of intense radioiodine concentration in the left suprarenal region. Spot oblique images and single photon emission computed tomography of the upper abdomen was undertaken to ascertain the position and better characterization of the lesion. A subsequent whole body PET-CT (non-contrast) was done which revealed a well defined 6.5 cm × 5.0 cm left adrenal lesion with a SUVmax (standardized uptake value-maximum) of 9.5 in addition to a fluorodeoxyglucose avid osteolytic sternal lesion. The serum thyroglobulin level was significantly raised (more than 250 ng/mL) with thyroid stimulating hormone being 4.9 μΙU/mL (even following an adequate period of levothyroxine withdrawal), indicating the functioning nature of the metastases. In addition to demonstrating an atypical site of metastatic disease in DTC patients, this case emphasizes the importance of carefully interpreting and correlating a post radio-iodine therapy scan, particularly those with focal abdominal radio-iodine uptake which could aid in detecting metastatic lesions that are not characterized or identified on initial evaluation. The other important feature that can be deciphered from

  14. Unusual Adrenal and Brain Metastases From Follicular Thyroid Carcinoma Revealed by 131I SPECT/CT.

    PubMed

    Zhao, Zhen; Shen, Guo-hua; Liu, Bin; Kuang, An-ren

    2016-01-01

    The adrenal metastasis from differentiated thyroid carcinoma is uncommon. Metastatic involvement of both adrenal and brain in the same patient from differentiated thyroid carcinoma is rare. Here, we described an unusual case with iodine-avid lung, bone, adrenal, liver, and brain metastases from follicular thyroid carcinoma confirmed by 131I SPECT/CT. The utilization of SPECT/CT in thyroid cancer patients can detect the presence of metastases and also exclude potential false-positive lesions. Our case demonstrates that SPECT/CT is helpful in localizing and confirming metastatic lesions from differentiated thyroid carcinoma in rare and unusual sites.

  15. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review.

    PubMed

    Christou, Andri; Papastavrou, Evridiki; Merkouris, Anastasios; Frangos, Savvas; Tamana, Panayiota; Charalambous, Andreas

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000-10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  16. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review

    PubMed Central

    Papastavrou, Evridiki; Frangos, Savvas; Tamana, Panayiota

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000–10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  17. The Study of External Dose Rate and Retained Body Activity of Patients Receiving 131I Therapy for Differentiated Thyroid Carcinoma

    PubMed Central

    Zhang, Haiying; Jiao, Ling; Cui, Songye; Wang, Liang; Tan, Jian; Zhang, Guizhi; He, Yajing; Ruan, Shuzhou; Fan, Saijun; Zhang, Wenyi

    2014-01-01

    Radiation safety is an integral part of targeted radionuclide therapy. The aim of this work was to study the external dose rate and retained body activity as functions of time in differentiated thyroid carcinoma patients receiving 131I therapy. Seventy patients were stratified into two groups: the ablation group (A) and the follow-up group (FU). The patients’ external dose rate was measured, and simultaneously, their retained body radiation activity was monitored at various time points. The equations of the external dose rate and the retained body activity, described as a function of hours post administration, were fitted. Additionally, the release time for patients was calculated. The reduction in activity in the group receiving a second or subsequent treatment was more rapid than the group receiving only the initial treatment. Most important, an expeditious method was established to indirectly evaluate the retained body activity of patients by measuring the external dose rate with a portable radiation survey meter. By this method, the calculated external dose rate limits are 19.2, 8.85, 5.08 and 2.32 μSv·h−1 at 1, 1.5, 2 and 3 m, respectively, according to a patient’s released threshold level of retained body activity <400 MBq. This study is beneficial for radiation safety decision-making. PMID:25337944

  18. Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study.

    PubMed

    Zamora-Ros, Raul; Rinaldi, Sabina; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Boutron-Ruault, Marie-Christine; Rostgaard-Hansen, Agnetha Linn; Tjønneland, Anne; Clavel-Chapelon, Françoise; Mesrine, Sylvie; Katzke, Verena A; Kühn, Tilman; Förster, Jana; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Klinaki, Eleni; Masala, Giovanna; Sieri, Sabina; Ricceri, Fulvio; Tumino, Rosario; Mattiello, Amalia; Peeters, Petra H M; Bueno-de-Mesquita, H B As; Engeset, Dagrun; Skeie, Guri; Argüelles, Marcial; Agudo, Antonio; Sánchez, María-José; Chirlaque, María-Dolores; Barricarte, Aurelio; Chamosa, Saioa; Almquist, Martin; Tosovic, Ada; Hennings, Joakim; Sandström, Maria; Schmidt, Julie A; Khaw, Kay-Thee; Wareham, Nicholas J; Cross, Amanda J; Slimani, Nadia; Byrnes, Graham; Romieu, Isabelle; Riboli, Elio; Franceschi, Silvia

    2016-01-01

    Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4 vs .Q1 , 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4 vs .Q1 , 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI < 25. Moreover, inverse associations with starch and GI were observed in subjects with BMI < 25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI ≥ 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people.

  19. Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study.

    PubMed

    Zamora-Ros, Raul; Rinaldi, Sabina; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Boutron-Ruault, Marie-Christine; Rostgaard-Hansen, Agnetha Linn; Tjønneland, Anne; Clavel-Chapelon, Françoise; Mesrine, Sylvie; Katzke, Verena A; Kühn, Tilman; Förster, Jana; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Klinaki, Eleni; Masala, Giovanna; Sieri, Sabina; Ricceri, Fulvio; Tumino, Rosario; Mattiello, Amalia; Peeters, Petra H M; Bueno-de-Mesquita, H B As; Engeset, Dagrun; Skeie, Guri; Argüelles, Marcial; Agudo, Antonio; Sánchez, María-José; Chirlaque, María-Dolores; Barricarte, Aurelio; Chamosa, Saioa; Almquist, Martin; Tosovic, Ada; Hennings, Joakim; Sandström, Maria; Schmidt, Julie A; Khaw, Kay-Thee; Wareham, Nicholas J; Cross, Amanda J; Slimani, Nadia; Byrnes, Graham; Romieu, Isabelle; Riboli, Elio; Franceschi, Silvia

    2016-01-01

    Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4 vs .Q1 , 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4 vs .Q1 , 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI < 25. Moreover, inverse associations with starch and GI were observed in subjects with BMI < 25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI ≥ 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people. PMID:26190646

  20. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... some noncancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  1. Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-10-13

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

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

    ClinicalTrials.gov

    2016-10-05

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  3. Measuring the extent of total thyroidectomy for differentiated thyroid carcinoma using radioactive iodine imaging: relationship with serum thyroglobulin and clinical outcomes.

    PubMed

    Holsinger, F Christopher; Ramaswamy, Uma; Cabanillas, Maria E; Lang, Juntian; Lin, Heather Y; Busaidy, Naifa L; Grubbs, Elizabeth; Rahim, Sania; Sturgis, Erich M; Lee, Jeffrey E; Weber, Randal S; Clayman, Gary L; Rohren, Eric M

    2014-05-01

    IMPORTANCE Despite performing total thyroidectomy (TT), postoperative radioactive iodine (RAI) imaging often demonstrates the presence of residual thyroid tissue within the operative bed. OBJECTIVE To measure the extent of TT using postoperative RAI imaging and assessing serum thyroglobulin (Tg) level for patients with differentiated thyroid carcinoma (DTC). DESIGN, SETTING, AND PARTICIPANTS We evaluated 245 patients undergoing TT for clinically staged cT1-3N0M0 DTC, who underwent diagnostic postoperative RAI imaging. INTERVENTIONS Total thyroidectomy. MAIN OUTCOMES AND MEASURES On the basis of quantitative measurements, RAI uptake (RAIU) in the thyroid bed of 0.2% of administered activity was selected as the cutpoint to determine the presence or absence of thyroid remnant. RESULTS By postoperative RAI imaging, TT in 106 patients (43%) resulted in RAIU of less than 0.2%. In the remaining 139 patients (57%), there was measurable iodine-avid thyroid tissue and/or tumor in the thyroid bed (n = 117 [84%]), the neck (n = 4 [3%]), or both (n = 18 [13%]). For the entire study population, mean 24-hour RAIU was 0.62%. Stimulated serum Tg levels were obtained in 232 of 245 patients (95%). Measurable stimulated Tg level (≥1 ng/mL) (to convert to micrograms per liter, multiply by 1) was found in 26 of 102 patients (25%) without thyroid remnant and in 87of 133 patients (65%) with thyroid remnant (P < .001). CONCLUSIONS AND RELEVANCE A goal of postthyroidectomy RAIU of less than 0.2% helps maximize the likelihood of an unmeasurable postoperative Tg level, potentially simplifying follow-up evaluation and reducing the use of postoperative RAI in order to facilitate surveillance.

  4. [Differentiated thyroid cancer -- 2009].

    PubMed

    Konrády, András

    2011-01-30

    Three years ago continental guidelines were published referring management and follow-up of low risk thyroid cancer patients. The aim of this paper is to summarize the changes and new directions in this field. High risk patients require another protocol. Neck ultrasound plays important role in differential diagnosis and in detecting recurrences. Some new ultrasound techniques are discussed, too. FDG-PET can help to solve the problem of patients having negative scan and increased thyroglobulin level. In recent years there was an expansion of our knowledge about the pathomechanism of thyroid cancer. It appears that genetic alterations frequently play a key role in carcinogenesis. There are molecular methods that allow the detection of these genetic events in thyroid fine needle aspirations samples providing important information for diagnosis, management and prognosis. Instead of diagnostic whole body scanning the posttherapeutic scan became preferable but in high risk cases the diagnostic whole body scintigrams serve useful data. Primary therapy of thyroid cancer is an adequate surgery: total thyreoidectomy and, if necessary, lymph node dissection or limited surgery in selected cases. Nowadays radioguided surgery can help to improve the results. Radioiodine therapy (e.g. rest ablation) proved to be a safe and effective method to complete surgery. It can prevent relapses and results in longer survival. Thyroid hormone withdrawal or recombinant human thyrotropin stimulation can increase thyrotropin level before radioiodine treatment. These two methods have similar success rate of rest ablation but irradiation burden of blood is lower in the case of exogenous stimulation which avoids hypothyroid state and preserves quality of life. Since tumor cells fail to maintain the ability to perform physiological functions they undergo dedifferentiation. Therefore, an important aim is to reactivate some function of differentiated cells, e.g. iodine uptake, production of

  5. Gross Hematuria and Bladder Tumor in a Patient with Advanced Thyroid Papillary Carcinoma

    PubMed Central

    Matsuo, Yuki; Ikeoka, Toshiyuki; Oba, Kojiro; Miyata, Yasuyoshi; Sakai, Hideki; Abe, Kuniko; Kawakami, Atsushi

    2013-01-01

    We present a 73-year-old female with advanced thyroid papillary carcinoma who complained of gross hematuria. We found a bladder tumor and considered it the cause of her symptom. Cystoscopic findings of the tumor were unusual, with peri-tumor vessel formation. Pathological examination of the bladder tumor was consistent with metastasis of thyroid papillary carcinoma. Therefore, we identified thyroid carcinoma metastasis to the urinary bladder as the cause of hematuria in our patient. Thyroid carcinoma metastasis to the bladder is extremely rare, but it should be included among differential diagnoses for gross hematuria in patients with a clinical history of thyroid carcinoma. PMID:23762664

  6. High-throughput differential screening of mRNAs by serial analysis of gene expression: decreased expression of trefoil factor 3 mRNA in thyroid follicular carcinomas.

    PubMed

    Takano, T; Miyauchi, A; Yoshida, H; Kuma, K; Amino, N

    2004-04-19

    To find mRNAs whose expression differs between thyroid follicular adenomas and carcinomas, a high-throughput analysis of mRNAs in these two tumours was performed. This method, named high-throughput differential screening by serial analysis of gene expression (HDSS), combines a modified method of serial analysis of gene expression (SAGE) and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). A total of 40 candidate tag sequences that showed extremely different expression levels between a follicular carcinoma and a follicular adenoma in the SAGE analysis were analysed by real-time quantitative RT-PCR, using RNAs from an additional four typical follicular carcinomas and adenomas. One sequence tag that represents trefoil factor 3 (TFF3) mRNA showed a clear difference in its expression level between adenomas and carcinomas. The expression levels of TFF3 mRNA in 48 follicular adenomas and 29 follicular carcinomas were measured by real-time quantitative RT-PCR using a specific probe for TFF3. They were significantly decreased in follicular carcinomas, especially in widely invasive types and those with evident metastases. These results indicate that the decreased expression of TFF3 mRNA is a marker of follicular carcinomas, especially those with a high risk of invasion or metastasis.

  7. Integrated Genomic Characterization of Papillary Thyroid Carcinoma

    PubMed Central

    Agrawal, Nishant; Akbani, Rehan; Aksoy, B. Arman; Ally, Adrian; Arachchi, Harindra; Asa, Sylvia L.; Auman, J. Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B.; Behera, Madhusmita; Bernard, Brady; Beroukhim, Rameen; Bishop, Justin A.; Black, Aaron D.; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S.; Bowen, Jay; Bowlby, Reanne; Bristow, Christopher A.; Brookens, Robin; Brooks, Denise; Bryant, Robert; Buda, Elizabeth; Butterfield, Yaron S.N.; Carling, Tobias; Carlsen, Rebecca; Carter, Scott L.; Carty, Sally E.; Chan, Timothy A.; Chen, Amy Y.; Cherniack, Andrew D.; Cheung, Dorothy; Chin, Lynda; Cho, Juok; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Ciriello, Giovanni; Clarke, Amanda; Clayman, Gary L.; Cope, Leslie; Copland, John; Covington, Kyle; Danilova, Ludmila; Davidsen, Tanja; Demchok, John A.; DiCara, Daniel; Dhalla, Noreen; Dhir, Rajiv; Dookran, Sheliann S.; Dresdner, Gideon; Eldridge, Jonathan; Eley, Greg; El-Naggar, Adel K.; Eng, Stephanie; Fagin, James A.; Fennell, Timothy; Ferris, Robert L.; Fisher, Sheila; Frazer, Scott; Frick, Jessica; Gabriel, Stacey B.; Ganly, Ian; Gao, Jianjiong; Garraway, Levi A.; Gastier-Foster, Julie M.; Getz, Gad; Gehlenborg, Nils; Ghossein, Ronald; Gibbs, Richard A.; Giordano, Thomas J.; Gomez-Hernandez, Karen; Grimsby, Jonna; Gross, Benjamin; Guin, Ranabir; Hadjipanayis, Angela; Harper, Hollie A.; Hayes, D. Neil; Heiman, David I.; Herman, James G.; Hoadley, Katherine A.; Hofree, Matan; Holt, Robert A.; Hoyle, Alan P.; Huang, Franklin W.; Huang, Mei; Hutter, Carolyn M.; Ideker, Trey; Iype, Lisa; Jacobsen, Anders; Jefferys, Stuart R.; Jones, Corbin D.; Jones, Steven J.M.; Kasaian, Katayoon; Kebebew, Electron; Khuri, Fadlo R.; Kim, Jaegil; Kramer, Roger; Kreisberg, Richard; Kucherlapati, Raju; Kwiatkowski, David J.; Ladanyi, Marc; Lai, Phillip H.; Laird, Peter W.; Lander, Eric; Lawrence, Michael S.; Lee, Darlene; Lee, Eunjung; Lee, Semin; Lee, William; Leraas, Kristen M.; Lichtenberg, Tara M.; Lichtenstein, Lee; Lin, Pei; Ling, Shiyun; Liu, Jinze; Liu, Wenbin; Liu, Yingchun; LiVolsi, Virginia A.; Lu, Yiling; Ma, Yussanne; Mahadeshwar, Harshad S.; Marra, Marco A.; Mayo, Michael; McFadden, David G.; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Miller, Michael; Mills, Gordon; Moore, Richard A.; Mose, Lisle E.; Mungall, Andrew J.; Murray, Bradley A.; Nikiforov, Yuri E.; Noble, Michael S.; Ojesina, Akinyemi I.; Owonikoko, Taofeek K.; Ozenberger, Bradley A.; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J.; Parker, Joel S.; Paull, Evan O.; Pedamallu, Chandra Sekhar; Perou, Charles M.; Prins, Jan F.; Protopopov, Alexei; Ramalingam, Suresh S.; Ramirez, Nilsa C.; Ramirez, Ricardo; Raphael, Benjamin J.; Rathmell, W. Kimryn; Ren, Xiaojia; Reynolds, Sheila M.; Rheinbay, Esther; Ringel, Matthew D.; Rivera, Michael; Roach, Jeffrey; Robertson, A. Gordon; Rosenberg, Mara W.; Rosenthall, Matthew; Sadeghi, Sara; Saksena, Gordon; Sander, Chris; Santoso, Netty; Schein, Jacqueline E.; Schultz, Nikolaus; Schumacher, Steven E.; Seethala, Raja R.; Seidman, Jonathan; Senbabaoglu, Yasin; Seth, Sahil; Sharpe, Samantha; Mills Shaw, Kenna R.; Shen, John P.; Shen, Ronglai; Sherman, Steven; Sheth, Margi; Shi, Yan; Shmulevich, Ilya; Sica, Gabriel L.; Simons, Janae V.; Sipahimalani, Payal; Smallridge, Robert C.; Sofia, Heidi J.; Soloway, Matthew G.; Song, Xingzhi; Sougnez, Carrie; Stewart, Chip; Stojanov, Petar; Stuart, Joshua M.; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Tarnuzzer, Roy; Taylor, Barry S.; Thiessen, Nina; Thorne, Leigh; Thorsson, Vésteinn; Tuttle, R. Michael; Umbricht, Christopher B.; Van Den Berg, David J.; Vandin, Fabio; Veluvolu, Umadevi; Verhaak, Roel G.W.; Vinco, Michelle; Voet, Doug; Walter, Vonn; Wang, Zhining; Waring, Scot; Weinberger, Paul M.; Weinstein, John N.; Weisenberger, Daniel J.; Wheeler, David; Wilkerson, Matthew D.; Wilson, Jocelyn; Williams, Michelle; Winer, Daniel A.; Wise, Lisa; Wu, Junyuan; Xi, Liu; Xu, Andrew W.; Yang, Liming; Yang, Lixing; Zack, Travis I.; Zeiger, Martha A.; Zeng, Dong; Zenklusen, Jean Claude; Zhao, Ni; Zhang, Hailei; Zhang, Jianhua; Zhang, Jiashan (Julia); Zhang, Wei; Zmuda, Erik; Zou., Lihua

    2014-01-01

    Summary Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease. PMID:25417114

  8. The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma.

    PubMed

    Kim, Mee Kyoung; Yun, Kyung-Jin; Kim, Min-Hee; Lim, Dong-Jun; Kwon, Hyuk-Sang; Song, Ki-Ho; Kang, Moo-Il; Baek, Ki Hyun

    2015-02-01

    Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were -0.88, -1.3 and -0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine -2.1%, femoral neck -2.2%, and hip -2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period.

  9. Sorafenib: a review of its use in patients with radioactive iodine-refractory, metastatic differentiated thyroid carcinoma.

    PubMed

    Blair, Hannah A; Plosker, Greg L

    2015-03-01

    Sorafenib (Nexavar®) is the first tyrosine kinase inhibitor to be approved for the treatment of radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). In the pivotal phase III DECISION trial in patients with RAI-refractory, locally advanced or metastatic DTC, oral sorafenib 400 mg twice daily significantly prolonged median progression-free survival (PFS) relative to placebo. The PFS benefit of sorafenib over placebo was evident in all pre-specified clinical and genetic biomarker subgroups, and neither BRAF nor RAS mutation status was predictive of sorafenib benefit for PFS. The objective response rate was significantly higher in patients receiving sorafenib than in those receiving placebo; all objective responses were partial responses. The overall survival benefit of sorafenib is as yet unclear, with no significant benefit observed at the time of primary analysis or at 9 months following the primary analysis. Overall survival was possibly confounded by the crossover of patients in the placebo group to sorafenib upon disease progression. The adverse events associated with sorafenib in the DECISION trial were consistent with the known tolerability profile of the drug, with hand-foot skin reaction, diarrhea, and alopecia reported most commonly. Most treatment-emergent adverse events were grade 1 or 2 in severity and occurred early in treatment. However, a high proportion of patients discontinued sorafenib therapy or required dose reductions or interruptions because of toxicity. Although final overall survival data are awaited, current evidence suggests that sorafenib is a promising new treatment option for patients with RAI-refractory, metastatic DTC. PMID:25742918

  10. Gastrointestinal Side Effects of the Radioiodine Therapy for the Patients with Differentiated Thyroid Carcinoma Two Days after Prescription

    PubMed Central

    Pashnehsaz, Mehran; Takavar, Abbas; Izadyar, Sina; Zakariaee, Seyed Salman; Mahmoudi, Mahmoud; Paydar, Reza; Geramifar, Parham

    2016-01-01

    Iodine-131 (I-131) therapy is one of the conventional approaches in the treatment of patients with differentiated thyroid carcinoma (DTC). The radioiodine agents also accumulate in the other organs that cause pain and damage to the patients. Radioiodine therapy is associated with various gastrointestinal (GI) toxicities. In this study, GI side effects of the radioiodine therapy were investigated. GI toxicities of the radioiodine therapy were studied in 137 patients with histologically proven DTC in Jun-Nov 2014. All the patients were treated by radioiodine agents in the research institute of Shariati Hospital, Tehran, Iran. The patients were examined 48 h after prescription (before discharge) and their GI side effects were registered. Correlation of the age, gender, administered dose, administered dose per body weight as the independent factors, and GI side effects were analyzed using the Pearson correlation test with Statistical Package for the Social Sciences (SPSS) version 20. Regression coefficients and linearity of the variable were investigated by MATLAB software. Line fitting was performed using MATLAB curve-fitting toolbox. From the subjects, 38 patients had GI complaints (30.4%). Significant factors influencing GI side effects were dose per body weight and administered doses. There was no significant correlation between age and gender as the independent parameters and GI complaints. The most prevalent GI side effect was nausea that occurs in 26.4% of the patients. From the results, it could be concluded that the GI side effects could be prevented by administering a safe radioiodine dose value less than 5,550 MBq. PMID:27651737

  11. Gastrointestinal Side Effects of the Radioiodine Therapy for the Patients with Differentiated Thyroid Carcinoma Two Days after Prescription.

    PubMed

    Pashnehsaz, Mehran; Takavar, Abbas; Izadyar, Sina; Zakariaee, Seyed Salman; Mahmoudi, Mahmoud; Paydar, Reza; Geramifar, Parham

    2016-09-01

    Iodine-131 (I-131) therapy is one of the conventional approaches in the treatment of patients with differentiated thyroid carcinoma (DTC). The radioiodine agents also accumulate in the other organs that cause pain and damage to the patients. Radioiodine therapy is associated with various gastrointestinal (GI) toxicities. In this study, GI side effects of the radioiodine therapy were investigated. GI toxicities of the radioiodine therapy were studied in 137 patients with histologically proven DTC in Jun-Nov 2014. All the patients were treated by radioiodine agents in the research institute of Shariati Hospital, Tehran, Iran. The patients were examined 48 h after prescription (before discharge) and their GI side effects were registered. Correlation of the age, gender, administered dose, administered dose per body weight as the independent factors, and GI side effects were analyzed using the Pearson correlation test with Statistical Package for the Social Sciences (SPSS) version 20. Regression coefficients and linearity of the variable were investigated by MATLAB software. Line fitting was performed using MATLAB curve-fitting toolbox. From the subjects, 38 patients had GI complaints (30.4%). Significant factors influencing GI side effects were dose per body weight and administered doses. There was no significant correlation between age and gender as the independent parameters and GI complaints. The most prevalent GI side effect was nausea that occurs in 26.4% of the patients. From the results, it could be concluded that the GI side effects could be prevented by administering a safe radioiodine dose value less than 5,550 MBq. PMID:27651737

  12. Gastrointestinal Side Effects of the Radioiodine Therapy for the Patients with Differentiated Thyroid Carcinoma Two Days after Prescription

    PubMed Central

    Pashnehsaz, Mehran; Takavar, Abbas; Izadyar, Sina; Zakariaee, Seyed Salman; Mahmoudi, Mahmoud; Paydar, Reza; Geramifar, Parham

    2016-01-01

    Iodine-131 (I-131) therapy is one of the conventional approaches in the treatment of patients with differentiated thyroid carcinoma (DTC). The radioiodine agents also accumulate in the other organs that cause pain and damage to the patients. Radioiodine therapy is associated with various gastrointestinal (GI) toxicities. In this study, GI side effects of the radioiodine therapy were investigated. GI toxicities of the radioiodine therapy were studied in 137 patients with histologically proven DTC in Jun-Nov 2014. All the patients were treated by radioiodine agents in the research institute of Shariati Hospital, Tehran, Iran. The patients were examined 48 h after prescription (before discharge) and their GI side effects were registered. Correlation of the age, gender, administered dose, administered dose per body weight as the independent factors, and GI side effects were analyzed using the Pearson correlation test with Statistical Package for the Social Sciences (SPSS) version 20. Regression coefficients and linearity of the variable were investigated by MATLAB software. Line fitting was performed using MATLAB curve-fitting toolbox. From the subjects, 38 patients had GI complaints (30.4%). Significant factors influencing GI side effects were dose per body weight and administered doses. There was no significant correlation between age and gender as the independent parameters and GI complaints. The most prevalent GI side effect was nausea that occurs in 26.4% of the patients. From the results, it could be concluded that the GI side effects could be prevented by administering a safe radioiodine dose value less than 5,550 MBq.

  13. Anaplastic giant cell thyroid carcinoma.

    PubMed

    Wallin, G; Lundell, G; Tennvall, J

    2004-01-01

    Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of

  14. [Association of hyperthyroidism with differentiated thyroid cancer].

    PubMed

    Haraj, Nassim Essabah; Ahandar, Hayat; El Aziz, Siham; Chadli, Asma

    2016-01-01

    The presence of hyperthyroidism is no longer an insurance against the occurrence of thyroid cancer. The combination of the two is common. This is a retrospective study of 355 files of patients followed for differentiated thyroid cancer in the endocrinology department at CHU IBN ROCHD from 1986 to 2014. 12 of those patients were followed for hyperthyroidism, and a fortuitous association with differentiated thyroid cancer was found during the anatomopathological exam, giving us a 3.38% prevalence. The average age of discovery is 44.8 years, with a marked female predominance (8/12). Eight patients had a toxic nodule, 3 had Basedow's goiters, and one had Graves' disease. All underwent total thyroidectomy. In all patients, the cancer was a papillary carcinoma. Microcarcinoma was the most predominant (6 patients). An insular carcinoma was found in a patient with spinal and retro-orbital metastases. Treatment with radioactive iodine was prescribed to five patients. The diagnosis of hyperthyroidism does not eliminate the possibility of an associated thyroid cancer. Malignancy should always be kept in mind and therefore lead to a diagnostic approach comparable to that for any thyroid nodule. PMID:27583082

  15. Hyponatremia after Thyroid Hormone Withdrawal in a Patient with Papillary Thyroid Carcinoma

    PubMed Central

    Jo, Hyo Jin; Shin, Dong Hyun; Kim, Mi Jeoung; Lee, Sang Jin; Jeon, Dong Ok; Im, Sung Gyu; Jang, Sun Kyung; Choi, Jin Young

    2014-01-01

    Hyponatremia is an electrolyte abnormality commonly found in clinical practice. It is important to diagnose the underlying etiology of the hyponatremia and correct it appropriately because severe hyponatremia can cause serious complications and substantially increase the risk of mortality. Although hypothyroidism is known to be a cause of hyponatremia, it is rare that hyponatremia occurs in relation to hypothyroidism induced by thyroid hormone withdrawal in patients with differentiated thyroid cancer. We report a case of a 76-year-old woman with papillary thyroid carcinoma presenting with severe hyponatremia related to hypothyroidism induced by thyroid hormone withdrawal for radio-active iodine whole-body scanning, who was treated by thyroid hormone replacement and hydration. Considering that the incidence of differentiated thyroid cancer is rapidly increasing, physicians should be aware that, although uncommon, hyponatremia can occur in patients undergoing radioiodine therapy or diagnostic testing. PMID:24741458

  16. Anaplastic Thyroid Carcinoma, Version 2.2015

    PubMed Central

    Haddad, Robert I.; Lydiatt, William M.; Ball, Douglas W.; Busaidy, Naifa Lamki; Byrd, David; Callender, Glenda; Dickson, Paxton; Duh, Quan-Yang; Ehya, Hormoz; Haymart, Megan; Hoh, Carl; Hunt, Jason P.; Iagaru, Andrei; Kandeel, Fouad; Kopp, Peter; Lamonica, Dominick M.; McCaffrey, Judith C.; Moley, Jeffrey F.; Parks, Lee; Raeburn, Christopher D.; Ridge, John A.; Ringel, Matthew D.; Scheri, Randall P.; Shah, Jatin P.; Smallridge, Robert C.; Sturgeon, Cord; Wang, Thomas N.; Wirth, Lori J.; Hoffmann, Karin G.; Hughes, Miranda

    2016-01-01

    This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer. PMID:26358798

  17. Radioactive iodine treatment of metastatic thyroid carcinoma with clinical thyrotoxicosis

    SciTech Connect

    Smith, R.; Blum, C.; Benua, R.S.; Fawwaz, R.A.

    1985-12-01

    We present a case of well-differentiated follicular carcinoma of the thyroid with hyperfunctioning metastases and clinical thyrotoxicosis. The recommended I-131 treatment dose for patients with widespread bone metastases from thyroid carcinoma is 200 mCi. However, in a patient with hyperfunctioning metastatic tumor and increased radioiodine uptake, the treatment dose should be modified. Radiation dosimetry measurements performed on the patient in this study demonstrated that 132 mCi would be a safe therapeutic I-131 dose which would avoid injury to normal radiosensitive tissues. Consequently, she was given a 130-mCi therapeutic dose.

  18. Expression of epithelial-mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas.

    PubMed

    Buehler, Darya; Hardin, Heather; Shan, Weihua; Montemayor-Garcia, Celina; Rush, Patrick S; Asioli, Sofia; Chen, Herbert; Lloyd, Ricardo V

    2013-01-01

    Epithelial-mesenchymal transition is an important mechanism of epithelial tumor progression, local invasion and metastasis. The E-cadherin (CDH1) repressor SLUG (SNAI2) and the basic helix-loop-helix transcription factor TWIST1 inhibit CDH1 expression in poorly differentiated malignancies as inducers of epithelial-mesenchymal transition. Epithelial-mesenchymal transition has been implicated in progression from well to poorly differentiated/anaplastic thyroid carcinoma but the expression of SNAI2 and TWIST1 proteins and their phenotypic association in human thyroid cancers has not been extensively studied. We examined the expression of SNAI2, TWIST1 and CDH1 by immunohistochemistry in a panel of well-differentiated and anaplastic thyroid cancers and by qRT-PCR in thyroid cell lines. Ten normal thyroids, 33 follicular adenomas, 56 papillary thyroid carcinomas including 28 follicular variants, 27 follicular carcinomas and 10 anaplastic thyroid carcinomas were assembled on a tissue microarray and immunostained for SNAI2, TWIST1 and CDH1. Most (8/10) anaplastic thyroid carcinomas demonstrated strong nuclear immunoreactivity for SNAI2 with associated absence of CDH1 in 6/8 cases (75%). TWIST1 was expressed in 5/10 anaplastic thyroid carcinomas with absence of CDH1 in 3/5 (60%) cases. These findings were confirmed in whole sections of all anaplastic thyroid carcinomas and in a separate validation set of 10 additional anaplastic thyroid carcinomas. All normal thyroids, follicular adenomas, papillary and follicular thyroid carcinomas were negative for SNAI2 and TWIST1 (P<0.0001) and all showed strong diffuse immunoreactivity for CDH1 (P=0.026). Expression of SNAI2, TWIST1 and CDH1 mRNA varied in a normal thyroid, papillary carcinoma and two anaplastic thyroid carcinoma cell lines tested, but the highest levels of CDH1 mRNA were detected in the normal thyroid cell line while the anaplastic thyroid carcinoma cell line demonstrated the highest levels of SNAI2 and TWIST1 m

  19. Comparison of mathematical models for red marrow and blood absorbed dose estimation in the radioiodine treatment of advanced differentiated thyroid carcinoma

    NASA Astrophysics Data System (ADS)

    Miranti, A.; Giostra, A.; Richetta, E.; Gino, E.; Pellerito, R. E.; Stasi, M.

    2015-02-01

    Metastatic and recurrent differentiated thyroid carcinoma is preferably treated with 131I, whose administered activity is limited by red marrow (RM) toxicity, originally correlated by Benua to a blood absorbed dose higher than 2 Gy. Afterward a variety of dosimetric approaches has been proposed. The aim of this work is to compare the results of the Benua formula with the ones of other three blood and RM absorbed dose formulae. Materials and methods have been borrowed by the dosimetric protocol of the Italian Internal Dosimetry group and adapted to the routine of our centre. Wilcoxon t-tests and percentage differences have been applied for comparison purposes. Results are significantly different (p < 0.05) from each other, with an average percentage difference between Benua versus other results of -22%. The dosimetric formula applied to determine blood or RM absorbed dose may contribute significantly to increase heterogeneity in absorbed dose and dose-response results. Standardization should be a major objective.

  20. Gene expression profiling of normal thyroid tissue from patients with thyroid carcinoma

    PubMed Central

    Melaccio, Assunta; Di Meo, Giovanna; Trino, Stefania; Mazzoccoli, Carmela; Saltarella, Ilaria; Lamanuzzi, Aurelia; Morano, Annalisa; Gurrado, Angela; Pasculli, Alessandro; Lastilla, Gaetano; Musto, Pellegrino; Reale, Antonia; Dammacco, Franco; Vacca, Angelo; Testini, Mario

    2016-01-01

    Gene expression profiling (GEP) of normal thyroid tissue from 43 patients with thyroid carcinoma, 6 with thyroid adenoma, 42 with multinodular goiter, and 6 with Graves-Basedow disease was carried out with the aim of achieving a better understanding of the genetic mechanisms underlying the role of normal cells surrounding the tumor in the thyroid cancer progression. Unsupervised and supervised analyses were performed to compare samples from neoplastic and non-neoplastic diseases. GEP and subsequent RT-PCR analysis identified 28 differentially expressed genes. Functional assessment revealed that they are involved in tumorigenesis and cancer progression. The distinct GEP is likely to reflect the onset and/or progression of thyroid cancer, its molecular classification, and the identification of new potential prognostic factors, thus allowing to pinpoint selective gene targets with the aim of realizing more precise preoperative diagnostic procedures and novel therapeutic approaches. STATEMENT OF SIGNIFICANCE This study is focused on the gene expression profiling analysis followed by RT-PCR of normal thyroid tissues from patients with neoplastic and non-neoplastic thyroid diseases. Twenty-eight genes were found to be differentially expressed in normal cells surrounding the tumor in the thyroid cancer. The genes dysregulated in normal tissue samples from patients with thyroid tumors may represent new molecular markers, useful for their diagnostic, prognostic and possibly therapeutic implications. PMID:27105534

  1. Gene expression profiling of normal thyroid tissue from patients with thyroid carcinoma.

    PubMed

    Ria, Roberto; Simeon, Vittorio; Melaccio, Assunta; Di Meo, Giovanna; Trino, Stefania; Mazzoccoli, Carmela; Saltarella, Ilaria; Lamanuzzi, Aurelia; Morano, Annalisa; Gurrado, Angela; Pasculli, Alessandro; Lastilla, Gaetano; Musto, Pellegrino; Reale, Antonia; Dammacco, Franco; Vacca, Angelo; Testini, Mario

    2016-05-17

    Gene expression profiling (GEP) of normal thyroid tissue from 43 patients with thyroid carcinoma, 6 with thyroid adenoma, 42 with multinodular goiter, and 6 with Graves-Basedow disease was carried out with the aim of achieving a better understanding of the genetic mechanisms underlying the role of normal cells surrounding the tumor in the thyroid cancer progression. Unsupervised and supervised analyses were performed to compare samples from neoplastic and non-neoplastic diseases. GEP and subsequent RT-PCR analysis identified 28 differentially expressed genes. Functional assessment revealed that they are involved in tumorigenesis and cancer progression. The distinct GEP is likely to reflect the onset and/or progression of thyroid cancer, its molecular classification, and the identification of new potential prognostic factors, thus allowing to pinpoint selective gene targets with the aim of realizing more precise preoperative diagnostic procedures and novel therapeutic approaches.This study is focused on the gene expression profiling analysis followed by RT-PCR of normal thyroid tissues from patients with neoplastic and non-neoplastic thyroid diseases. Twenty-eight genes were found to be differentially expressed in normal cells surrounding the tumor in the thyroid cancer. The genes dysregulated in normal tissue samples from patients with thyroid tumors may represent new molecular markers, useful for their diagnostic, prognostic and possibly therapeutic implications.

  2. Gene expression profiling of normal thyroid tissue from patients with thyroid carcinoma.

    PubMed

    Ria, Roberto; Simeon, Vittorio; Melaccio, Assunta; Di Meo, Giovanna; Trino, Stefania; Mazzoccoli, Carmela; Saltarella, Ilaria; Lamanuzzi, Aurelia; Morano, Annalisa; Gurrado, Angela; Pasculli, Alessandro; Lastilla, Gaetano; Musto, Pellegrino; Reale, Antonia; Dammacco, Franco; Vacca, Angelo; Testini, Mario

    2016-05-17

    Gene expression profiling (GEP) of normal thyroid tissue from 43 patients with thyroid carcinoma, 6 with thyroid adenoma, 42 with multinodular goiter, and 6 with Graves-Basedow disease was carried out with the aim of achieving a better understanding of the genetic mechanisms underlying the role of normal cells surrounding the tumor in the thyroid cancer progression. Unsupervised and supervised analyses were performed to compare samples from neoplastic and non-neoplastic diseases. GEP and subsequent RT-PCR analysis identified 28 differentially expressed genes. Functional assessment revealed that they are involved in tumorigenesis and cancer progression. The distinct GEP is likely to reflect the onset and/or progression of thyroid cancer, its molecular classification, and the identification of new potential prognostic factors, thus allowing to pinpoint selective gene targets with the aim of realizing more precise preoperative diagnostic procedures and novel therapeutic approaches.This study is focused on the gene expression profiling analysis followed by RT-PCR of normal thyroid tissues from patients with neoplastic and non-neoplastic thyroid diseases. Twenty-eight genes were found to be differentially expressed in normal cells surrounding the tumor in the thyroid cancer. The genes dysregulated in normal tissue samples from patients with thyroid tumors may represent new molecular markers, useful for their diagnostic, prognostic and possibly therapeutic implications. PMID:27105534

  3. Second malignancies in patients with differentiated thyroid carcinoma treated with low and medium activities of radioactive I-131

    PubMed Central

    PICIU, DOINA; PESTEAN, CLAUDIU; BARBUS, ELENA; LARG, MARIA IULIA; PICIU, ANDRA

    2016-01-01

    Background and aim This study aimed at determining whether there is a risk regarding the development of second primary malignancies after patient exposure to the low and medium radioiodine activity used during the treatment of differentiated thyroid cancers (DTC). Methods Second primary malignancies that occurred after DTC were detected in 1,990 patients treated between 1970 and 2003. The mean long-term follow-up period was 182 months. Results Radioiodine I-131was administrated at a mean dose of 63.2 mCi. There were 93 patients with at least one second primary malignancy. The relative risk of development of second malignancy in DTC patients was increased (p<0.0001) for breast, uterine and ovarian cancers compared with the general population. Conclusions The overall risk concerning the development of second primary malignancies was related to the presence of DTC, but not to exposure to the low and medium activities of radioiodine administered as adjuvant therapy. PMID:27547058

  4. Survival discriminants for differentiated thyroid cancer

    SciTech Connect

    Cunningham, M.P.; Duda, R.B.; Recant, W.; Chmiel, J.S.; Sylvester, J.A.; Fremgen, A. )

    1990-10-01

    Since 1975, the American Cancer Society, Illinois Division, has published end results of major cancer sites drawn from patient data contributed voluntarily by hospital cancer registries throughout the state. The current study was undertaken, in part, to apprehend information regarding contested areas in the management of patients having differentiated (papillary/follicular) thyroid cancer. A total of 2,282 patients with either papillary or follicular carcinoma of the thyroid from 76 different Illinois hospitals and providing 10 years of follow-up information (life-table analysis) were retrospectively analyzed for demographic, disease, and treatment-related predictors of survival. Multivariate analysis using the Cox proportional hazards method was made for stage, age, race, sex, morphology, history of radiation exposure, presence of positive lymph nodes, initial surgical treatment, postoperative iodine 131 therapy, and replacement/suppressive thyroid hormone treatment. Statistically significant (p less than or equal to 0.05) predictors of favorable survival after thyroid cancer were low stage (I and II), young age (less than 50 years), white race, female sex, and the administration, postoperatively, of either thyroid hormone or radioactive iodine. Factors that had no influence on survival were lymph node status, choice of initial surgical treatment, and a history of prior irradiation. We suggest that where a prospective clinical trial is impracticable, a retrospective analysis of a large and detailed database, such as that available from cooperating hospital-based tumor registries, may yet provide useful insights to solutions of cancer management problems.

  5. Cytogenetic and dosimetric effects of (131)I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments.

    PubMed

    da Silva, Márcia Augusta; Valgôde, Flávia Gomes Silva; Gonzalez, Júlia Armiliato; Yoriyaz, Hélio; Guimarães, Maria Inês Calil Cury; Ribela, Maria Teresa Carvalho Pinto; Buchpiguel, Carlos Alberto; Bartolini, Paolo; Okazaki, Kayo

    2016-08-01

    A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of (131)I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24 h, 1 week, 1 month and 1 year after radioiodine administration (4995-7030 MBq) in both groups. An activity-response curve of (131)I (0.074-0.740 MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24 h after treatment were equivalent to those induced in vitro (0.2903 ± 0.1005 MBq/mL in group A and 0.2391 ± 0.1019 MBq/mL in group B), corresponding to absorbed doses of 0.65 ± 0.23 Gy and 0.53 ± 0.23 Gy, respectively. The effect on lymphocytes of internal radiation induced by (131)I therapy is minimal when based on the frequencies of CA 1 year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSH-aided therapy.

  6. Cytogenetic and dosimetric effects of (131)I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments.

    PubMed

    da Silva, Márcia Augusta; Valgôde, Flávia Gomes Silva; Gonzalez, Júlia Armiliato; Yoriyaz, Hélio; Guimarães, Maria Inês Calil Cury; Ribela, Maria Teresa Carvalho Pinto; Buchpiguel, Carlos Alberto; Bartolini, Paolo; Okazaki, Kayo

    2016-08-01

    A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of (131)I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24 h, 1 week, 1 month and 1 year after radioiodine administration (4995-7030 MBq) in both groups. An activity-response curve of (131)I (0.074-0.740 MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24 h after treatment were equivalent to those induced in vitro (0.2903 ± 0.1005 MBq/mL in group A and 0.2391 ± 0.1019 MBq/mL in group B), corresponding to absorbed doses of 0.65 ± 0.23 Gy and 0.53 ± 0.23 Gy, respectively. The effect on lymphocytes of internal radiation induced by (131)I therapy is minimal when based on the frequencies of CA 1 year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSH-aided therapy. PMID:27013085

  7. Medullary thyroid carcinoma: a rare presentation as a hypervascular tumour.

    PubMed

    Li, W Y; Tomlinson, M A; Bryson, J M; Hopkins, N F G

    2002-08-01

    Sporadic medullary thyroid carcinoma (MTC) usually presents with a thyroid mass, cervical lymphadenopathy or other local cervical symptoms. Often the diagnosis is unsuspected pre-operatively. We report a unique case of a mixed follicular medullary thyroid carcinoma presenting as a tumour with extreme vascularity. The management of hypervascular thyroid tumours is discussed together with current controversies regarding persistent hypercalcitoninaemia. PMID:12389699

  8. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines.

    PubMed

    Xu, Xiulong; Quiros, Roderick M; Gattuso, Paolo; Ain, Kenneth B; Prinz, Richard A

    2003-08-01

    The RAS-RAF-MEK-ERK-MAP kinase pathway mediates the cellular response to extracellular signals that regulate cell proliferation, differentiation, and apoptosis. Mutation of the RAS proto-oncogene occurs in various thyroid neoplasms such as papillary thyroid carcinomas (PTCs), follicular thyroid adenomas and carcinomas. A second genetic alteration frequently involved in PTC is RET/PTC rearrangements. Recent studies have shown that BRAF, which is a downstream signaling molecule of RET and RAS, is frequently mutated in melanomas. This study tests whether BRAF is also mutated in thyroid tumors and cell lines. We analyzed BRAF gene mutation at codon 599 in thyroid tumors using mutant-allele-specific PCR and in 10 thyroid tumor cell lines by DNA sequencing of the PCR-amplified exon 15. We found that BRAF was mutated in 8 of 10 thyroid tumor cell lines, including 2 of 2 papillary carcinoma cell lines, 4 of 5 anaplastic carcinoma cell lines, 1 of 2 follicular carcinoma cell lines, and 1 follicular adenoma cell line. BRAF mutation at codon 599 was detected in 21 of 56 PTC (38%) but not in 18 follicular adenomas and 6 goiters. BRAF mutation occurred in PTC at a significantly higher frequency in male patients than in female patients. To test whether BRAF mutation may cooperate with RET/PTC rearrangements in the oncogenesis of PTC, we tested whether BRAF-mutated PTCs were also positive for RET/PTC rearrangements. Immunohistochemical staining was conducted to evaluate RET/PTC rearrangements by using two different anti-RET antibodies. Surprisingly, we found that a large number of BRAF-mutated PTCs (8 of 21) also expressed RET, indicating that the RET proto-oncogene is rearranged in these BRAF-mutated PTCs. These observations suggest that mutated BRAF gene may cooperate with RET/PTC to induce the oncogenesis of PTC.

  9. Anaplastic Transformation in Mandibular Metastases of Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.

    PubMed

    Ambelil, Manju; Sultana, Sadia; Roy, Suvra; Gonzalez, Maria M

    2016-09-01

    Anaplastic transformation of well-differentiated thyroid carcinomas at distant metastatic sites is a rare condition. Most cases described in the literature have occurred in the thyroid or regional lymph nodes. We report a case of anaplastic transformation of the follicular variant of papillary thyroid carcinoma in mandibular metastases. A 76-year-old female presented with a painful and enlarging mandibular mass. She had been treated in the past for the follicular variant of papillary thyroid carcinoma. A palliative hemi-mandibulectomy was performed. Histology revealed a metastatic papillary thyroid carcinoma, follicular variant, with an unusual finding of solid pleomorphic epithelioid and spindle cell areas, consistent with anaplastic transformation. PMID:27650625

  10. Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma

    PubMed Central

    Igata, Motoyuki; Tsuruzoe, Kaku; Kawashima, Junji; Kukidome, Daisuke; Kondo, Tatsuya; Motoshima, Hiroyuki; Shimoda, Seiya; Furukawa, Noboru; Nishikawa, Takeshi; Miyamura, Nobuhiro

    2016-01-01

    Summary Resistance to thyroid hormone (RTH) is a syndrome of reduced tissue responsiveness to thyroid hormones. RTH is majorly caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. Here, we report a rare case of RTH with a papillary thyroid carcinoma (PTC). A 26-year-old woman was referred to our hospital due to a thyroid tumor and hormonal abnormality. She had elevated serum thyroid hormones and non-suppressed TSH levels. Genetic analysis of THRB identified a missense mutation, P452L, leading to a diagnosis of RTH. Ultrasound-guided fine-needle aspiration biopsy of the tumor and lymph nodes enabled the cytological diagnosis of PTC with lymph node metastases. Total thyroidectomy and neck lymph nodes dissection were performed. Following surgery, thyroxine replacement (≥500 μg) was necessary to avoid the symptoms of hypothyroidism and to maintain her TSH levels within the same range as before the operation. During the follow-up, basal thyroglobulin (Tg) levels were around 6 ng/ml and TSH-stimulated Tg levels were between 12 and 20 ng/ml. Up to present, the patient has had no recurrence of PTC. This indicates that these Tg values are consistent with a biochemical incomplete response or an indeterminate response. There is no consensus regarding the management of thyroid carcinoma in patients with RTH, but aggressive treatments such as total thyroidectomy followed by radioiodine (RAI) and TSH suppression therapy are recommended. Learning points There are only a few cases reporting the coexistence of RTH and thyroid carcinoma. Moreover, our case would be the first case presenting one with lymph node metastases. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. When total thyroidectomy is performed in

  11. Interleukin-1beta can mediate growth arrest and differentiation via the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells.

    PubMed

    Park, Jong-In; Strock, Christopher J; Ball, Douglas W; Nelkin, Barry D

    2005-02-01

    Interleukin-1beta (IL-1beta) is a pleiotropic cytokine that can induce several cellular signal transduction pathways. Here, we show that IL-1beta can induce cell cycle arrest and differentiation in the human medullary thyroid carcinoma (MTC) cell line, TT. IL-1beta induces cell cycle arrest accompanied by morphological changes and expression of the neuroendocrine marker calcitonin. These changes are blocked by the MEK1/2 specific inhibitor U0126, indicating that MEK1/2 is essential for IL-1beta signaling in TT cells. IL-1beta induces expression of leukemia inhibitory factor (LIF) and activation of STAT3 via the MEK/ERK pathway. This activation of STAT3 could be abrogated by treatment with anti-LIF neutralizing antibody or anti-gp130 blocking antibody, indicating that induction of LIF expression is sufficient and essential for STAT3 activation by IL-1beta. In addition to activation of the LIF/JAK/STAT pathway, IL-1beta also induced an MEK/ERK-mediated intracellular cell-autonomous signaling pathway that is independently sufficient for growth arrest and differentiation. Thus, IL-1beta activates the MEK/ERK pathway to induce growth arrest and differentiation in MTC cells via dual independent signaling mechanisms, the cell-extrinsic LIF/JAK/STAT pathway, and the cell-intrinsic autonomous signaling pathway.

  12. Incidental Thyroid Carcinoma Diagnosed after Total Thyroidectomy for Benign Thyroid Diseases: Incidence and Association with Thyroid Disease Type and Laboratory Markers

    PubMed Central

    Askitis, D.; Efremidou, E. I.; Karanikas, M.; Mitrakas, A.; Tripsianis, G.; Polychronidis, A.; Liratzopoulos, N.

    2013-01-01

    Objective. Currently, total thyroidectomy (TT) is widely used to treat benign thyroid diseases and thyroid carcinoma. The differential diagnosis between benign and malignant thyroid disorders and the potential identification of thyroid microcarcinomas with biochemical markers remain controversial. This retrospective study aimed to estimate the prognostic validity of thyroid autoantibodies, thyroglobulin (Tg), and the thyroid disease type in diagnostic approaches regarding the co-existence of incidental thyroid carcinoma (ITC) with benign thyroid diseases. Methods. A cohort of 228 patients was treated with TT for benign thyroid disorders between 2005 and 2010. Thyroid autoantibodies and Tg were preoperatively estimated. Patients were classified according to the preoperative and histologically established diagnoses, and the median values of the biochemical markers were compared between the groups. Results. ITC was detected in 33/228 patients and almost exclusively in the presence of nontoxic thyroid disorders (P = 0.014). There were no statistically significant differences in the median values of the biochemical markers between the benign and malignant groups. There was also no significant association between ITC and chronic lymphocytic thyroiditis. Conclusions. The co-existence of ITC with benign and especially nontoxic thyroid diseases is significant, and treatment of these disorders with TT when indicated can lead to the identification and definitive cure of microcarcinomas. Further studies are required to establish precise markers with prognostic validity for TC diagnosis. PMID:24348554

  13. Riedel's Thyroiditis Mimicking as Anaplastic Thyroid Carcinoma: Unusual Presentation.

    PubMed

    Hakeem, Arsheed Hussain; Chandramathyamma, Sreerenjini Kaithaparambil; Hakeem, Imtiyaz Hussain; Wani, Fozia Jeelani; Gomez, Ramesh

    2016-09-01

    Riedel's thyroiditis is a rare inflammatory process which not only involves thyroid gland but also the surrounding vital structures. It may also be associated with various forms of systemic fibrotic disorders. The exact etiology is not known, but currently most favored view is that of a localized form of systemic fibrotic process. We report a case of Riedel's thyroiditis in a patient, highlighting a rare presentation mimicking anaplastic carcinoma. Clinical awareness of such presentation of Riedel's thyroiditis would enhance our ability to make this diagnosis promptly. Apart from avoiding or minimizing aggressive surgical intervention, awareness of such clinical entity may avoid complications and hence morbidity. Our case also highlights the difficulty in histological diagnosis which is very important to rule out malignancy and avoiding any major surgical intervention fraught with complications. Good response to high dose steroids as seen in our case is the current accepted treatment of choice. PMID:27651702

  14. Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment – initial experience

    PubMed Central

    Werner, R. A.; Lückerath, K.; Schmid, J. S.; Higuchi, T.; Kreissl, M. C.; Grelle, I.; Reiners, C.; Buck, A. K.; Lapa, C.

    2016-01-01

    Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2–3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression. PMID:27306607

  15. [Thyroid metastasis due to right colonic carcinoma].

    PubMed

    Rauber, E; Pancrazio, F; Spivach, A; Stanta, G

    1998-12-01

    Clinical evident metastases to the thyroid gland are rarely found antemortem. A case of a 62 year-old man with a history of right colonic carcinoma, who presented a mass in the right lobe of his thyroid gland one year after the removal of a metachronous metastasis in his right lung, is presented. The tumour of the thyroid was found to be metastatic adenocarcinoma from his previous colonic cancer. The clinical finding of metastases to the thyroid gland is rare, particularly from a colorectal primary neoplasm. However, the possibility of a tumour of the thyroid gland representing a secondary malignancy is to be considered in any patient with a prior history of cancer.

  16. Prior irradiation and the development of coexistent differentiated thyroid cancer and hyperparathyroidism

    SciTech Connect

    Prinz, R.A.; Barbato, A.L.; Braithwaite, S.S.; Brooks, M.H.; Lawrence, A.M.; Paloyan, E.

    1982-03-01

    Twelve patients with coexistent well-differentiated thyroid carcinoma and primary hyperparathyoidism were studied to determine the frequency of previous radiation exposure. Eight were found to have received prior irradiation. External radiation was administered to the head and neck region for benign conditions such as tonsillar enlargement, acne, scrofula, and thyroid enlargement. One patient received 131I therapy for carcinoma of the thyroid. The observation that 67% of the patients in this series had previous radiation to the head and neck strongly implicates radiation exposure in the development of coexistent well-differentiated thyroid carcinoma and hyperparathyroidism.

  17. Follicular Thyroid Carcinoma Presenting as Bilateral Cheek Masses

    PubMed Central

    Kim, Dong-Wook; Hah, J. Hun; An, Soo-Youn; Chang, Hak

    2013-01-01

    Mandibular metastasis of thyroid carcinoma is extremely rare. We present the case of a 46-year-old woman who had bilateral huge cheek masses that had grown rapidly over several years. Intra-oral mucosal tissue biopsy and imaging work-up including computed tomography scan and magnetic resonance imaging were performed and the initial diagnosis was presumed to be central giant cell granuloma. Incidentally detected thyroid lesions were studied with ultra-sonography guided fine needle aspiration and diagnosed as simple benign nodules. Due to continuous oral bleeding and the locally destructive feature of the lesions, we decided to excise the mass surgically. To avoid functional deficit, a stepwise approach was performed: Firstly, the larger left mass was excised and the mandible was reconstructed with a fibular free flap. The final pathologic diagnosis was follicular thyroid cancer. Postoperative I-131 thyroid scan and whole body positron-emissions-tomography were performed. Right side mass was revealed as a thyroid malignancy. Multiple bony metastases were detected. Since further radioactive iodine therapy was required, additional total thyroidectomy and right side mandibulectomy with fibular free flap reconstruction was performed. The patient also underwent high dose radioactive iodine therapy and palliative extra-beam radiotherapy for the metastatic lumbar lesion. Follicular thyroid carcinoma should be considered as a differential diagnosis for mandibular mass lesions. PMID:23526730

  18. 3,5,3'-Triiodothyroacetic acid minimizes the pituitary thyrotrophin secretion in patients on levo-thyroxine therapy after ablative therapy for differentiated thyroid carcinoma.

    PubMed

    Mueller-Gaertner, H W; Schneider, C

    1988-04-01

    The aim of this study was to examine the influence of 3,5,3'-triiodothyroacetic acid (TRIAC) on serum thyrotrophin (TSH) concentration in 25 patients on levo-thyroxine (L-T4) therapy after ablative therapy for differentiated thyroid carcinoma. The daily L-T4 intake amounted to 2.6 +/- 0.7 micrograms/kg body weight (+/- SD). Serum TSH concentration was determined by means of a sensitive radioimmunometric method (lower detection limit 0.03 mU/l). The median (means) basal TSH concentration under L-T4 amounted to 0.11 mU/l (range less than 0.03 mU/l-7.39 mU/l). During supplementary intake of 500 micrograms TRIAC daily the median basal TSH decreased to 0.04 mU/l range less than 0.03 mU/l-0.24 mU/l; P less than 0.0003). The TRIAC-induced decrease in 17 out of 20 basal TSH-concentrations exceeding 0.03 mU/l ranged from 38% to as much as 98%. TRIAC reduced the median TRH-stimulated TSH concentration from 0.25 mU/l (range less than 0.03 mU/l-47.3 mU/l) to 0.04 mU/l (range less than 0.03 mU/l-1.43 mU/l; P less than 0.0001). A blunted TSH-response to TRH occurred in 8.7% prior to and in 52% of the patients during TRIAC medication. Side effects such as nervousness, cardiac arrhythmia or tachycardia under supplementary TRIAC (500 micrograms daily) were observed in four patients. The conclusion is that the supplementary medication of 500 micrograms TRIAC daily in euthyroid patients on L-T4 medication after thyroid gland ablation for differentiated thyroid cancer is an effective means to minimize serum-TSH concentration.

  19. Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule.

    PubMed

    Mousa, Umut; Gursoy, Alptekin; Ozdemir, Handan; Moray, Gokhan

    2013-07-01

    Serum calcitonin is a tumor marker used in the diagnosis and follow-up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61-year-old female patient with known Hashimoto's thyroditis and an 8-mm hypoechoic nodule was presented with one previously benign fine-needle aspiration cytology (FNAC). On referral to our department, she had a moderately high-serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high-serum calcitonin levels.

  20. Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.

    PubMed

    Pilotti, S; Collini, P; Mariani, L; Placucci, M; Bongarzone, I; Vigneri, P; Cipriani, S; Falcetta, F; Miceli, R; Pierotti, M A; Rilke, F

    1997-12-01

    We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

  1. Thyroid adenoma and nasopharyngeal carcinoma with metastasis to cervical lymph nodes is misdiagnosed and treated for thyroid carcinoma: A case report

    PubMed Central

    ZHANG, MIAO; WANG, HENG; PAN, XUEFENG; WU, WENBIN; ZHANG, HUI

    2016-01-01

    Lymph node metastasis of nasopharyngeal carcinoma follows an orderly pattern, and diagnosis of nasopharyngeal carcinoma is often made by lymph node biopsy. In the present study, following neck palpation, ultrasonography and cervical computer tomography, a 52-year-old female patient with thyroid adenoma and enlarged cervical lymph nodes was misdiagnosed as thyroid carcinoma without undergoing preoperative biopsy, followed by unnecessary total thyroidectomy. Systematic CT scan and nasal endoscopic biopsy confirmed the correct diagnosis of primary NPC concurrent with thyroid adenoma. The patient received palliative radiotherapy and L-thyroxine substitution therapy, and was followed up closely via internet-based approaches with life-style intervention, medication consultation and psychological support for improvement of life quality after radiotherapy. In conclusion, primary malignancies with thyroid metastasis must be considered in the differential diagnosis of thyroid tumors with enlarged cervical lymph nodes. PMID:27347179

  2. A Sensitive Tg Assay or rhTSH Stimulated Tg: What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

    PubMed Central

    Persoon, Adrienne C.M.; Jager, Pieter L.; Sluiter, Wim J.; Plukker, John T.M.; Wolffenbuttel, Bruce H.R.; P. Links, Thera

    2007-01-01

    Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1–34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg ≥1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on ≥1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg ≥1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures. PMID:17726546

  3. Value of post-therapeutic ¹³¹I scintigraphy in stimulated serum thyroglobulin-negative patients with metastatic differentiated thyroid carcinoma.

    PubMed

    Shen, Chen-Tian; Wei, Wei-Jun; Qiu, Zhong-Ling; Song, Hong-Jun; Luo, Quan-Yong

    2016-02-01

    Metastatic differentiated thyroid carcinoma (DTC) with positive (131)I scintigraphy, but negative stimulated Tg (sTg) is relatively rare in clinical practice. The clinical characteristics of these patients were analyzed in the current study. A total of 3367 consecutive histologically proven DTC patients were analyzed retrospectively from January 2007 to June 2013. Tg negativity was defined as a sTg level of <2 ng/mL without positive anti-Tg antibody (TgAb level of <100 IU/mL) under thyroid-stimulating hormone stimulation (TSH level of ≥30 mIU/L). Analyses were performed using the Statistical Package for the Social Sciences, version 20.0 (SPSS, Chicago, IL, USA). Seventy-one patients (median age 45 years, range 17-68 years) were post-therapeutic (131)I-SPECT/CT positive and sTg negative (PTP-TN) constituting 2.1 % of all patients. Of these 71 patients, 2 (2.8 %) had bone metastasis, 11 (15.5 %) had lung metastasis, and 59 (83.1 %) had lymph node metastasis. Fifty-six patients had cervical lymph node metastasis (cLNM), and US was positive in 15 patients (26.8 %), while negative in 41 patients (73.2 %). When compared to patients with concordant positive results for sTg and (131)I scintigraphy, US showed a relatively lower positive rate in the detection of cLNM in PTP-TN patients (28.8 vs. 53.8 %; χ (2) = 6.70; P = 0.01). In conclusion, even with sTg <2 ng/mL, there is a low risk of metastatic DTC. US had limitations in PTP-TN patients, while post-therapy (131)I-SPECT/CT demonstrated an advantage in the detection of functioning metastasis despite low sTg levels in patients with metastatic DTC.

  4. Hypoxia-Inducible Factor in Thyroid Carcinoma

    PubMed Central

    Burrows, Natalie; Babur, Muhammad; Resch, Julia; Williams, Kaye J.; Brabant, Georg

    2011-01-01

    Intratumoural hypoxia (low oxygen tension) is associated with aggressive disease and poor prognosis. Hypoxia-inducible factor-1 is a transcription factor activated by hypoxia that regulates the expression of genes that promote tumour cell survival, progression, metastasis, and resistance to chemo/radiotherapy. In addition to hypoxia, HIF-1 can be activated by growth factor-signalling pathways such as the mitogen-activated protein kinases- (MAPK-) and phosphatidylinositol-3-OH kinases- (PI3K-) signalling cascades. Mutations in these pathways are common in thyroid carcinoma and lead to enhanced HIF-1 expression and activity. Here, we summarise current data that highlights the potential role of both hypoxia and MAPK/PI3K-induced HIF-1 signalling in thyroid carcinoma progression, metastatic characteristics, and the potential role of HIF-1 in thyroid carcinoma response to radiotherapy. Direct or indirect targeting of HIF-1 using an MAPK or PI3K inhibitor in combination with radiotherapy may be a new potential therapeutic target to improve the therapeutic response of thyroid carcinoma to radiotherapy and reduce metastatic burden. PMID:21765994

  5. A Clinical Trial of Optimal Time Interval Between Ablation and Diagnostic Activity When a Pretherapy RAI Scanning Is Performed on Patients With Differentiated Thyroid Carcinoma

    PubMed Central

    Yin, Yafu; Mao, Qiufen; Chen, Song; Li, Na; Li, Xuena; Li, Yaming

    2015-01-01

    Abstract This article investigates the association of the time interval between the diagnostic dose and ablation with the stunning effect, when a 74 MBq 131I pretherapy scanning was performed on patients with differentiated thyroid carcinoma (DTC); the patients who were diagnosed as DTC and would be performed radioiodine (RAI) ablation of thyroid remnants or metastases were recruited during January 2011 and May 2012 in our hospital. Thirty-seven patients with DTC who had the RAI ablation of thyroid remnants or metastases for the first time were recruited. All the patients received a dose of 1850 to 7400 MBq of 131I for ablation and a diagnostic scan was performed 24 hours after the administration of 74 MBq 131I before ablation. A posttherapy scan was performed 2 to 7 days after the ablation. The patients were broken down into 3 groups (G1, G2, and G3) according to the interval time between the diagnostic dose and therapy (1–3, 4–7, and >7 days). The fractional concentrations of 131I in remnants or functional metastases were quantified and expressed as therapeutic/diagnostic (Rx/Dx). The level of significance was set at 0.05. Sixty-seven foci were found both on pretherapy and posttherapy scans, the mean ratio of Rx/Dx was 0.43 ± 0.29, and the ratio of 49 foci (73.13%) was <0.6. The ratios in G1, G2, and G3 were 0.46 ± 0.29, 0.29 ± 0.18, and 0.55 ± 0.33, respectively. The differences between G1 and G2, and G2 and G3 were statistically significant (t = 2.40, P = 0.021 and t = 3.28, P = 0.002), whereas the difference between G1 and G3 was not significant (t = 1.01, P = 0.319). By a diagnostic scan of 74 MBq 131I, stunning prominently occurs with a time of 4 to 7 days between the diagnostic dose and ablation. We recommend that for less stunning effect, RAI ablation should be performed within 3 days or postponed until 1 week after the diagnostic dose administrated. PMID:26252311

  6. Thyroglobulin in differentiated thyroid cancer.

    PubMed

    Evans, Carol; Tennant, Sarah; Perros, Petros

    2015-04-15

    Identification of differentiated thyroid cancer (DTC) is becoming increasingly common. Patients usually have an excellent prognosis. Most undergo total thyroidectomy, radioiodine ablation and treatment with suppressive doses of levothyroxine. Patients require long term follow-up which includes measurement of serum thyroglobulin (Tg). Interpretation of serum Tg requires knowledge of the concurrent thyroid stimulating hormone (TSH) concentration, as secretion is TSH dependant, and an awareness of the limitations of the methods used to measure it. These limitations include the heterogeneity of Tg in serum, the ability of assays to recognise forms of Tg secreted by a tumour, assay biases and not least the potential for interference in immunoassays for Tg from endogenous thyroglobulin antibodies (TgAbs) in patient serum. This review considers what the clinician wants to know and how Tg results can be interpreted in light of an awareness of assay limitations. PMID:25444737

  7. Macrofollicular encapsulated papillary thyroid carcinoma--a case report.

    PubMed

    Ravindra, Savithri; Niveditha, S R; Geethamani, V; Rangaswamy, R

    2006-01-01

    Macrofollicular encapsulated papillary thyroid carcinoma (MEPC) is a rare variant of papillary carcinoma of thyroid with a favourable clinical course. It could be mistaken for a follicular neoplasm or a hyperplastic nodule. We report cytological and histopathological features of this rare variant of papillary carcinoma in a 22 year old female with brief review of literature.

  8. BRAF mutation in papillary thyroid carcinoma.

    PubMed

    Cohen, Yoram; Xing, Mingzhao; Mambo, Elizabeth; Guo, Zhongmin; Wu, Guogun; Trink, Barry; Beller, Uziel; Westra, William H; Ladenson, Paul W; Sidransky, David

    2003-04-16

    The BRAF gene has been found to be activated by mutation in human cancers, predominantly in malignant melanoma. We tested 476 primary tumors, including 214 lung, 126 head and neck, 54 thyroid, 27 bladder, 38 cervical, and 17 prostate cancers, for the BRAF T1796A mutation by polymerase chain reaction (PCR)-restriction enzyme analysis of BRAF exon 15. In 24 (69%) of the 35 papillary thyroid carcinomas examined, we found a missense thymine (T)-->adenine (A) transversion at nucleotide 1796 in the BRAF gene (T1796A). The T1796A mutation was detected in four lung cancers and in six head and neck cancers but not in bladder, cervical, or prostate cancers. Our data suggest that activating BRAF mutations may be an important event in the development of papillary thyroid cancer.

  9. RET rearrangements in familial papillary thyroid carcinomas.

    PubMed

    Corvi, R; Lesueur, F; Martinez-Alfaro, M; Zini, M; Decaussin, M; Murat, A; Romeo, G

    2001-09-20

    Familial papillary thyroid carcinoma (FPTC) is an inherited tumor characterized by a more aggressive phenotype than that of its sporadic counterpart. Its mode of inheritance as well as its genetic and molecular bases are still poorly understood. On the contrary, genetic alterations in sporadic papillary thyroid carcinoma (PTC) are better characterized, the most common one involving the activation of the proto-oncogene RET through somatic rearrangements. In the present study, we investigated by interphase fluorescence in situ hybridization the presence of RET rearrangements in a series of 20 FPTC. We show that one FPTC and the adenoma from the same patient carry a RET rearrangement (type PTC1) and that this rearrangement is absent in the germline. Furthermore, we excluded a RET haplotype sharing in two brothers of the same family. These results show that RET rearrangements can indeed be found in FPTC and confirm that RET is not involved in the inherited predisposition to FPTC.

  10. Laryngeal acinic cell carcinoma following thyroid irradiation

    SciTech Connect

    Reibel, J.F.; McLean, W.C.; Cantrell, R.W.

    1981-01-01

    Only three examples of acinic cell carcinoma of the larynx or trachea are found in the recent literature. A case of acinic cell carcinoma of the subglottic larynx and trachea was diagnosed and treated at the University of Virginia Medical Center. To our knowledge this is the first such case with a prior history of radiation to the neck. The patient is a 56-year-old woman who was irradiated for hyperthyroidism 46 years ago. When seen she also had parathyroid hyperplasia and multiple thyroid adenomas, conditions that frequently follow irradiation of the thyroid in children. These findings in this case support the concept that radiation may be responsible for inducing this tumor, which otherwise rarely occurs in this location. The use of electron microscopy was extremely useful in the diagnosis of this tumor. She was treated with total laryngectomy and right neck dissection and is now free of disease one year after surgery.

  11. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6-NTRK3 fusion.

    PubMed

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Michael Tuttle, R; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-09-01

    ETV6-NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47-72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6-NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated with long

  12. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

    PubMed Central

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Tuttle, R Michael; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-01-01

    ETV6–NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47–72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6–NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated

  13. Use of vemurafenib in anaplastic thyroid carcinoma: a case report

    PubMed Central

    Marten, Kristen A; Gudena, Vinay K

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is a rare, poorly differentiated type of thyroid cancer occurring in less than 5% of all thyroid cancers. Patients typically have a poor prognosis with very few options for treatment.2 With current therapy of surgery, chemotherapy, and radiation, median survival is only 6 months from the time of diagnosis. Several mutations in cell cycle regulation have been discovered in ATC that contribute to its undifferentiated state, one of which is the BRAF kinase mutation. This mutation results in activation of the MAPK pathway and uncontrolled cell proliferation. In this case report, a 51 y old male presented with a 2-week history of hoarseness and was diagnosed with ATC. Genetic analysis revealed a mutation in BRAF kinase; the patient subsequently began therapy with vemurafenib, a BRAF kinase inhibitor indicated for melanoma. After an initial response, the patient quickly declined and consequently died from his disease. Anaplastic thyroid carcinoma is a deadly cancer without an effective treatment. Inhibiting mutated enzymes that drive the development of this cancer is a potential drug target that may improve outcomes in patients with ATC. PMID:26176686

  14. Use of vemurafenib in anaplastic thyroid carcinoma: a case report.

    PubMed

    Marten, Kristen A; Gudena, Vinay K

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is a rare, poorly differentiated type of thyroid cancer occurring in less than 5% of all thyroid cancers. Patients typically have a poor prognosis with very few options for treatment. (2) With current therapy of surgery, chemotherapy, and radiation, median survival is only 6 months from the time of diagnosis. Several mutations in cell cycle regulation have been discovered in ATC that contribute to its undifferentiated state, one of which is the BRAF kinase mutation. This mutation results in activation of the MAPK pathway and uncontrolled cell proliferation. In this case report, a 51 y old male presented with a 2-week history of hoarseness and was diagnosed with ATC. Genetic analysis revealed a mutation in BRAF kinase; the patient subsequently began therapy with vemurafenib, a BRAF kinase inhibitor indicated for melanoma. After an initial response, the patient quickly declined and consequently died from his disease. Anaplastic thyroid carcinoma is a deadly cancer without an effective treatment. Inhibiting mutated enzymes that drive the development of this cancer is a potential drug target that may improve outcomes in patients with ATC.

  15. RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma

    PubMed Central

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

    2016-01-01

    Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies. PMID:27725756

  16. RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  17. Primary adenoid cystic carcinoma of the trachea with thyroid invasion: a case report and literature review

    PubMed Central

    Qi, Dianjun; Feng, Liang; Li, Jian; Liu, Bing; Zhang, Qingfu

    2016-01-01

    Primary adenoid cystic carcinoma (ACC) of the trachea with thyroid invasion is very rare. In this report, we present a 46-year-old man with primary ACC of the trachea with thyroid invasion. ACC invasion of the thyroid is very rare and is easily misdiagnosed. The patient sought consultation due to a 6-month history of dysphagia and associated dyspnea. A contrast-enhanced computed tomography scan obtained at the time of admission revealed bilateral thyroid masses and tracheal wall thickening. The thyroid masses were fused to the trachea and the esophagus without discernible borders, intraoperatively. Frozen pathology suggested poorly differentiated cancer, and a bilateral partial thyroidectomy was performed. Postoperative pathology revealed primary tracheal ACC with thyroid invasion. The patient died 1 month after surgery. We have also summarized the literature on the clinical presentation, diagnosis, and treatment of thyroid-invasive ACC. PMID:27785076

  18. Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

    PubMed Central

    Hombach-Klonisch, Sabine; Bialek, Joanna; Trojanowicz, Bogusz; Weber, Ekkehard; Holzhausen, Hans-Jürgen; Silvertown, Josh D.; Summerlee, Alastair J.; Dralle, Henning; Hoang-Vu, Cuong; Klonisch, Thomas

    2006-01-01

    The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells. PMID:16877360

  19. Relaxin enhances the oncogenic potential of human thyroid carcinoma cells.

    PubMed

    Hombach-Klonisch, Sabine; Bialek, Joanna; Trojanowicz, Bogusz; Weber, Ekkehard; Holzhausen, Hans-Jürgen; Silvertown, Josh D; Summerlee, Alastair J; Dralle, Henning; Hoang-Vu, Cuong; Klonisch, Thomas

    2006-08-01

    The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells.

  20. Radiation and thyroid carcinoma: radiotherapy, head and neck regions, thyroid carcinoma.

    PubMed

    Auguste, L J; Sako, K

    1985-01-01

    Radiotherapy for benign conditions of the head and neck area was first linked to thyroid carcinoma in 1950. All the salivary glands, the parathyroids, and the facial skin can also develop neoplastic lesions in this setting. Thyroid carcinoma is most commonly papillary or mixed papillary and follicular. It is very often multifocal and can be detected by hand palpation, nuclear scanning, high resolution sonography, and needle aspiration. Each test has its limitations and appropriate protocols for screening and detection should be adapted to different medical centers. The surgical management is controversial and ranges from simple lobectomy to total thyroidectomy with adjuvant 131I treatment and thyroid suppression. We prefer total thyroidectomy if it can be performed safely. With adequate treatment the survival should be good. Prevention by administration of iodine at the time of exposure to radiation seems feasible and deserves further clinical trial.

  1. Hyperthyroidism with metastatic follicular thyroid carcinoma

    SciTech Connect

    Chapman, C.N.; Sziklas, J.J.; Spencer, R.P.; Bower, B.F.; Rosenberg, R.J.

    1984-04-01

    A 70-yr-old woman presented with hyperthyroidism and metastatic follicular carcinoma of the thyroid. The blood level of thyroid stimulating immunoglobulin (TSIg) was elevated. A total thyroidectomy was performed. One month later she remained hyperthyroid. Three weeks after therapy with 218 mCi of I-131 sodium iodide, the patient was euthyroid. Six months after the initial radioiodide therapy, she was again hyperthyroid and was given a second oral treatment dose of I-131 (220 mCi). Five months later, the patient had again become euthyroid. It is likely that initially the woman's metastases were producing sufficient hormone to render her hyperthyroid. After thyroidectomy and two large doses of radioiodide, she has remained euthyroid without having to take exogenous hormone.

  2. A functioning pleomorphic carcinoma of the thyroid.

    PubMed Central

    Karnauchow, P. N.

    1976-01-01

    A metastasizing functioning pleomorphic carcinoma of the thyroid displayed a morphologic piture ranging from follicular to sarcomatous and carcinoid-like patterns. Spindle-cell elements were believed to be the result of metaplasia of the follicular epithelium. Development of carcinoid-like lesions in the secondary deposits of tumour supported the contention that so-called parafollicular or c-cells may be a phenomenon of metaplasia and not a histologic entity. The tumour was associated with a chromophobe adenoma of the pituitary and a benign schwannoma of the stomach. Clinically the patient did not show any other endocrinologic abnormalities and lived for 4 years from the time of diagnosis of the thyroid tumour. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:1277059

  3. Frontal sinus mucocele mimicking a metastasis of papillary thyroid carcinoma.

    PubMed

    Matheja, P; Lerch, H; Schmid, K W; Kuwert, T; Schober, O

    1997-07-01

    Radioiodine scans are highly specific for detecting metastases of well-differentiated thyroid carcinomas. However, false-positive 131I whole-body scans may occur as illustrated in the following case report. In a 53-yr-old patient, abnormal 131I uptake was found in the right frontal skull 4 wk after total thyroidectomy and radioiodine therapy for papillary thyroid cancer. Bone scans and planar x-rays of the skull were unremarkable and the serum thyroglobulin level was within normal limits. X-ray CT revealed a small nodule in the right frontal sinus corresponding to the pathological focus of 131I uptake. Surgical removal and histopathological examination of this lesion yielded a mucocele, a slow-growing lesion of the paranasal sinuses accumulating mucous material. The postoperative 131I scan was unremarkable. The possibility of a false-positive finding on radioiodine scans should be considered, particularly when the serum thyroglobulin level is not elevated.

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

    PubMed

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

    2012-11-01

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

  5. Well differentiated follicular thyroid neoplasia: impact of molecular and technological advances on detection, monitoring and treatment.

    PubMed

    Gianoukakis, Andrew G; Giannelli, Silvana M; Salameh, Wael A; McPhaul, Laron W

    2011-01-30

    Our understanding of the molecular mechanisms responsible for follicular thyroid cell oncogenesis has been advanced significantly in recent years. Specific genetic alterations and the molecular pathways they affect have been associated with particular histologic subtypes of well-differentiated thyroid cancer and are now being evaluated for their utility as clinical tools with diagnostic, prognostic and even therapeutic relevance. This paper focuses on the most common and clinically relevant genetic alterations shown to be consistently associated with well-differentiated thyroid carcinoma. We review the impact of recent molecular and technological advances on thyroid cancer standard of care and the practice of clinical medicine.

  6. Differential Expression of Aquaporins and Its Diagnostic Utility in Thyroid Cancer

    PubMed Central

    Niu, Dongfeng; Kondo, Tetsuo; Nakazawa, Tadao; Kawasaki, Tomonori; Yamane, Tetsu; Mochizuki, Kunio; Kato, Yohichiro; Matsuzaki, Toshiyuki; Takata, Kuniaki; Katoh, Ryohei

    2012-01-01

    Background Aquaporin3 (AQP3) and Aquaporin4 (AQP4) play a major role in transcellular and transepithelial water movement as water channel membrane proteins. Little is known of their expression and significance in human thyroid tissues. Thus, we examined the expression of AQP3 and AQP4 in normal, hyperplastic and neoplastic thyroid tissues in conjunction with human thyroid cancer cell lines. Methods and Results Immunohistochemical analyses demonstrated AQP3 in the cytoplasmic membrane of normal C cells, but not in follicular cells. In contrast, AQP4 was not found in C cells but was identified in normal follicular cells. AQP4 was positive in 92% of Graves’ disease thyroids and 97% of multinodular goiters, and we failed to demonstrate AQP3 in these hyperplastic tissues. In neoplastic thyroid lesions, we observed AQP3 in 91% of medullary thyroid carcinomas but in no other follicular cell tumors. AQP4 was demonstrated in 100% of follicular adenomas, 90% of follicular carcinomas, and 85% of papillary carcinomas, while it was negative in all medullary carcinomas and undifferentiated carcinomas. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed AQP3 mRNA expression only in medullary carcinomas and AQP4 mRNA expression in follicular cell-derived tumors except for undifferentiated carcinomas. In thyroid cancer cell lines, using RT-PCR and western blotting, AQP3 mRNA and protein were only identified in the TT cell line (human medullary carcinoma cell line) and AQP4 in the other cell lines. In addition, AQP3 mRNA expression was up-regulated by FBS and calcium administration in both a dose and time dependent manner in TT cells. Conclusion The differential expressions of AQP3 and AQP4 may reflect the biological nature and/or function of normal, hyperplastic, and neoplastic thyroid cells and additionally may have value in determining differential diagnoses of thyroid tumors. PMID:22808259

  7. Safety of Completion Thyroidectomy for Initially Misdiagnosed Thyroid Carcinoma

    PubMed Central

    Kranthikumar, Gangiti; Syed, Nusrath; Nemade, Hemantkumar; Pawar, Satish; Chandra Sekhara Rao, L. M.; Subramanyeshwar Rao, T.

    2016-01-01

    Introduction Completion thyroidectomy is defined as the surgical removal of the remnant thyroid tissue following procedures of less than total or near-total thyroidectomy. Whether thyroid reoperations are associated with an increased complication risk is controversial. Objective A retrospective analysis was done of patients undergoing completion thyroidectomy for cancer of the thyroid who had undergone surgery elsewhere for solitary thyroid nodule. The incidence of surgical complications in these patients after reoperation was investigated in this study. Material and methods The study included a total of 53 patients who had undergone thyroid lobectomy for a solitary nodule as initial surgery elsewhere and were referred to our institute for completion thyroidectomy when the histopathology revealed malignancy. Results There were 53 patients, 43 females and 10 males. Their mean age was 34.7±12.12 years (range 19–65 years). After initial surgery, the histopathology revealed papillary carcinoma in 46 patients (86.8%), follicular carcinoma in 7 (13.2%). Fourteen out of 53 patients had recurrent laryngeal nerve palsy after initial surgery (26.4%). None of the patients had clinical hypocalcemia after the first surgery. One or more parathyroid glands were identified and preserved in 52 patients (98.1%) in the process of completion thyroidectomy. No patient had additional recurrent nerve injury at the second surgery. The mean serum calcium value preoperatively was 8.96±0.39 mg/dL, and six months after surgery serum calcium was 8.74±0.56 mg/dL. Mean follow-up was 18 months. Transient hypoparathyroidism occurred in 24.5% patients. Five patients were lost to follow-up. Permanent and symptomatic hyperparathyroidism occurred in eight patients (16.67%). Conclusions Completion thyroidectomy is a safe and appropriate option in the management of well-differentiated thyroid cancer. It removes disease on the ipsilateral and contralateral side of the thyroid and carries a low risk

  8. Overview of the 2015 American Thyroid Association guidelines for managing thyroid nodules and differentiated thyroid cancer.

    PubMed

    Matti, Bashar; Cohen-Hallaleh, Ruben

    2016-01-01

    The last few years have witnessed numerous publications addressing the management of thyroid nodules and differentiated thyroid cancers. The purpose of this review is to provide a simplified summary of the newly released guidelines by the American Thyroid Association. A systematic approach has been recommended to evaluate a thyroid nodule through clinical assessment, measurement of serum Thyroid Stimulating Hormone, neck ultrasonography and Fine Needle Aspiration where appropriate. This is followed by cytology analysis using the Bethesda scoring system to detect malignancy. Once diagnosed, thyroid cancers need to be staged and risk stratification needs to be applied to develop further treatment plans. Lastly, several recommendations have been presented to assure proper follow-up and support for thyroid cancer patients regardless of the treatment received. PMID:27607088

  9. Microarray technology to investigate genes associated with papillary thyroid carcinoma.

    PubMed

    Zhu, Xinyong; Yao, Jing; Tian, Wen

    2015-05-01

    DNA microarray data on thyroid tissue from patients with papillary thyroid carcinoma (PTC) and from healthy controls were compared in order to investigate the regulatory genes and uncover the underlying regulatory network in PTC. The DNA microarray data set, GSE3678, was downloaded from Gene Expression Omnibus database. This included seven thyroid tissue samples from patients with PTC and seven samples from healthy controls. Raw data were processed and differentially expressed genes (DEGs) were identified using corresponding R packages. Gene regulation analysis was conducted using TRANSFAC® and TRED. A total of 171 DEGs were obtained. A regulatory network was then established, using 104 of the DEGs. Subsequently, pathway enrichment analyses of the genes were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Three differentially expressed transcription factors were identified: Trefoil factor 3, cut‑like homeobox 2 and forkhead box protein A2. The most significant pathways involving the 104 DEGs were pathways involved in cancer. Biological process analysis using DAVID, suggested that these genes were associated with the positive regulation of gene expression, gene transcription and metabolic processes. The present study identified a range of genes associated with the development of PTC. The results of the present study were beneficial for understanding the regulatory mechanisms involved in PTC, and for developing clinical diagnostic and therapeutic approaches for this disease.

  10. Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

    PubMed Central

    Correia-Deur, Joya Emilie M.; Toledo, Rodrigo A.; Imazawa, Alice T.; Lourenço, Delmar M.; Ezabella, Marilza C. L.; Tavares, Marcos R.; Toledo, Sergio P. A.

    2009-01-01

    INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6–15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were

  11. Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin.

    PubMed

    Zielke, A; Tezelman, S; Jossart, G H; Wong, M; Siperstein, A E; Duh, Q Y; Clark, O H

    1998-06-01

    Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.

  12. Medullary thyroid carcinoma presenting as a supraglottic mass.

    PubMed

    White, Jeremy; Mohyeldin, Ahmed; Schwartz, Arnold; Bielamowicz, Steven

    2014-01-01

    We report a rare case of medullary thyroid carcinoma that presented as a metastasis to the supraglottic larynx. A 92-year-old man with a 3-month history of voice change and airway obstruction was diagnosed with medullary thyroid carcinoma metastatic to the supraglottis. Excision of the mass, total thyroidectomy, and elective neck dissection were recommended, but the patient declined because of his advanced age. Medullary carcinoma of the thyroid gland is a rare neuroendocrine tumor with a poor prognosis when associated with a distant metastasis. To the best of our knowledge, this is the first case of a medullary carcinoma of the thyroid presenting as a supraglottic mass. Total thyroidectomy, neck dissection, and surgical excision of the entire tumor comprise the treatment of choice. PMID:25397389

  13. Thyrotoxicosis associated with distant metastatic follicular carcinoma of the thyroid

    SciTech Connect

    Bowden, W.D.; Jones, R.E.

    1986-04-01

    In a man with metastatic follicular carcinoma of the thyroid, thyrotoxicosis developed after total thyroidectomy and was successfully treated with antithyroid medications. Treatment with radioactive iodine decreased the size of the distant metastasis and eventually diminished thyroid hormone production. Follicular carcinoma complicated by hyperthyroidism requires vigorous control of the hypermetabolic state. Treatment with radioactive iodine can effectively reduce metabolic complications and tumor bulk, and yields a remission rate as high as 33%.

  14. Cancer stem cells as a potential therapeutic target in thyroid carcinoma

    PubMed Central

    Vicari, Luisa; Colarossi, Cristina; Giuffrida, Dario; De Maria, Ruggero; Memeo, Lorenzo

    2016-01-01

    A number of studies have indicated that tumor growth and proliferation is dependent on a small subset of cells, defined as cancer stem cells (CSCs). CSCs have the capability to self-renew, and are involved with cancer propagation, relapse and metastatic dissemination. CSCs have been isolated from numerous tissues, including normal and cancerous thyroid tissue. A regulatory network of signaling pathways and microRNAs (miRNAs) control the properties of CSCs. Differentiated thyroid carcinoma is the most common type of endocrine cancer, with an increasing incidence. Anaplastic thyroid carcinoma is the most rare type of endocrine cancer; however, it also exhibits the highest mortality rate among thyroid malignancies, with an extremely short survival time. Thyroid CSCs are invasive and highly resistant to conventional therapies, including radiotherapy and chemotherapy, which results in disease relapse even when the primary lesion has been eradicated. Therefore, targeting thyroid CSCs may represent an effective treatment strategy against aggressive neoplasms, including recurrent and radioresistant tumors. The present review summarizes the current literature regarding thyroid CSCs and discusses therapeutic strategies that target these cells, with a focus on the function of self-renewal pathways and miRNAs. Elucidation of the mechanisms that regulate CSC growth and survival may improve novel therapeutic approaches for treatment-resistant thyroid cancers.

  15. Cancer stem cells as a potential therapeutic target in thyroid carcinoma

    PubMed Central

    Vicari, Luisa; Colarossi, Cristina; Giuffrida, Dario; De Maria, Ruggero; Memeo, Lorenzo

    2016-01-01

    A number of studies have indicated that tumor growth and proliferation is dependent on a small subset of cells, defined as cancer stem cells (CSCs). CSCs have the capability to self-renew, and are involved with cancer propagation, relapse and metastatic dissemination. CSCs have been isolated from numerous tissues, including normal and cancerous thyroid tissue. A regulatory network of signaling pathways and microRNAs (miRNAs) control the properties of CSCs. Differentiated thyroid carcinoma is the most common type of endocrine cancer, with an increasing incidence. Anaplastic thyroid carcinoma is the most rare type of endocrine cancer; however, it also exhibits the highest mortality rate among thyroid malignancies, with an extremely short survival time. Thyroid CSCs are invasive and highly resistant to conventional therapies, including radiotherapy and chemotherapy, which results in disease relapse even when the primary lesion has been eradicated. Therefore, targeting thyroid CSCs may represent an effective treatment strategy against aggressive neoplasms, including recurrent and radioresistant tumors. The present review summarizes the current literature regarding thyroid CSCs and discusses therapeutic strategies that target these cells, with a focus on the function of self-renewal pathways and miRNAs. Elucidation of the mechanisms that regulate CSC growth and survival may improve novel therapeutic approaches for treatment-resistant thyroid cancers. PMID:27698787

  16. Cerebral edema following iodine-131 therapy for thyroid carcinoma metastatic to the brain

    SciTech Connect

    Datz, F.L.

    1986-05-01

    Brain metastases are rare in well-differentiated thyroid carcinoma but when present they can lead to the patient's death. Iodine-131 therapy for intracerebral thyroid carcinoma metastases causes radiation-induced acute cerebral edema that can lead to CNS complications and even death. We present a case in which a patient with intracerebral /sup 131/I uptake developed seizures, slurred speech, and muscle weakness 12 hr following /sup 131/I therapy. The patient's CT scan, post-therapy, confirmed an intracranial metastasis with a significant amount of surrounding edema. Radiotherapists, when using external beam radiation to treat intracerebral metastases, commonly place these patients on steroids, glycerol, or mannitol prior to instituting therapy, to prevent complications from radiation-induced cerebral edema. This technique could be applied to /sup 131/I therapy of intracranial thyroid carcinoma metastases as well.

  17. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid.

  18. Association of thyroid carcinoma with pregnancy: A meta-analysis

    PubMed Central

    ZHOU, Y.Q.; ZHOU, Z.; QIAN, M.F.; GONG, T.; WANG, J.D.

    2015-01-01

    A number of scholars reported that reproductive factors play a significant role in thyroid cancer and the correlation between the two may affect the diagnosis and treatment of thyroid carcinoma during pregnancy. To determine whether pregnancy reproductive factors affect thyroid carcinoma, we conducted a meta-analysis of studies that investigated the association between pregnancy factors and thyroid carcinoma. PubMed, OVID and the Cochrane Library were searched from their inception to April 1st, 2013. The searched publications mainly investigated reproductive factors and the morbidity or prognosis of female thyroid carcinoma. The studies were filtered by predetermined standards and the quality of the included studies was evaluated by the Newcastle-Ottawa scale inventory. Two researchers independently extracted information on first author, year of publication, study design (case-control or prospective cohort), compared populations, inclusion and exclusion criteria and total sample size. Other researchers assessed the studies for publication bias and performed statistical analyses. Discrepancies were resolved by consensus. A total of 21 studies were selected for the meta-analysis, including 406,329 cases in total. Compared to the control group, the risk of thyroid carcinoma in women with a history of pregnancy was not significantly discrepant, [odds ratio (OR)=1.00, 95% confidence interval (CI): 0.91-1.11]. However, the risk of thyroid carcinoma in women with a history of ≥ 3 pregnancies was significantly increased (OR=1.39, 95% CI: 1.21-1.59). Furthermore, an interval of ≤ 5 years since the last pregnancy was closely associated with thyroid carcinoma (OR=1.53, 95% CI: 1.29-1.81). The patients developed thyroid carcinoma during pregnancy did not exhibit an increased risk of lymphatic metastasis (OR=0.94, 95% CI: 0.53-1.67); the risk of distant metastasis also did not increase significantly (OR=1.03, 95% CI: 0.86-1.24). Therefore, multiple pregnancies and a ≤ 5

  19. 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.

  20. High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring

    SciTech Connect

    Bal, Chandrasekhar . E-mail: csbal@hotmail.com; Kumar, Ajay; Tripathi, Madhavi; Chandrashekar, Narayana; Phom, Hentok; Murali, Nadig R.; Chandra, Prem; Pant, Gauri S.

    2005-10-01

    Background: We tried to evaluate the female fertility and genetic risk to the offspring from the exposure to high-dose {sup 131}I by assessing the pregnancy outcomes and health status of the children of female patients with differentiated thyroid cancer who had received therapeutic doses of {sup 131}I. Materials and Methods: From 1967 to 2002, a total of 1,282 women had been treated with {sup 131}I. Of these patients, 692 (54%) were in the reproductive age group (18-45 years). Forty women had a total of 50 pregnancies after high-dose {sup 131}I. Age at presentation ranged from 16 to 36 years (mean, 23 {+-} 4 years). Histopathology was papillary thyroid cancer in 32 cases and follicular thyroid cancer in 8 cases. Results: Single high-dose therapy was given in 30 cases, 2 doses were given in 7 cases, 3 doses were given in 2 cases, and four doses were given in 1 case in which lung metastases had occurred. In 37 patients (92%), disease was successfully ablated before pregnancy. Ovarian absorbed-radiation dose calculated by the MIRD method ranged from 3.5 to 60 cGy (mean, 12 {+-} 11 cGy). The interval between {sup 131}I therapy and pregnancy varied from 7 to 120 months (37.4 {+-} 28.2 months). Three spontaneous abortions occurred in 2 women. Forty-seven babies (20 females and 27 males) were born. Forty-four babies were healthy with normal birth weight and normal developmental milestones. Twenty women delivered their first baby after {sup 131}I therapy. The youngest child in our series is 11 months of age, and the oldest is 8.5 years of age. Conclusions: Female fertility is not affected by high-dose radioiodine treatment, and the therapy does not appear to be associated with any genetic risks to the offspring.

  1. Semiquantitative immunohistochemical marker staining and localization in canine thyroid carcinoma and normal thyroid gland.

    PubMed

    Pessina, P; Castillo, V; Sartore, I; Borrego, J; Meikle, A

    2016-09-01

    Immunoreactive proteins in follicular cells, fibroblasts and endothelial cells were assessed in canine thyroid carcinomas and healthy thyroid glands. No differences were detected in thyrotropin receptor and thyroglobulin staining between cancer and normal tissues, but expression was higher in follicular cells than in fibroblasts. Fibroblast growth factor-2 staining was more intense in healthy follicular cells than in those of carcinomas. Follicular cells in carcinomas presented two- to three-fold greater staining intensity of thyroid transcription factor-1 and proliferating cell nuclear antigen, respectively, than healthy cells, and a similar trend was found for the latter antigen in fibroblasts. Vascular endothelial growth factor staining was more intense in the endothelial cells of tumours than in those of normal tissues. In conclusion, greater expression of factors related to proliferation and angiogenesis was demonstrated in several cell types within thyroid carcinomas compared to healthy tissues, which may represent mechanisms of tumour progression in this disease.

  2. Is it practical and cost effective to detect differentiated thyroid carcinoma metastases by (18)F-FDG PET/CT, by (18)F-FDG SPET/CT or by (131)I SPET/CT?

    PubMed

    He, Xinjia; Wang, Xucai; Yu, Jinming; Ma, Chao

    2015-01-01

    Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography/computerized tomography ((18)F-FDG PET/CT) plays an important role in detecting differentiated thyroid carcinoma (DTC) metastases with elevated thyroglobulin (Tg) and negative radioiodine ((131)I) uptake. In conclusion, (18)F-FDG PET/CT may fail to detect all DTC metastases, while (131)I WBS combined with (131)I SPET/CT may be a better cheaper and diagnostic tool as suggested by the case we presented here. Positive metastases in both (131)I and (18)F-FDG SPET/CT may indicate worse prognosis. Future research may add more evidence as to which is the best diagnostic imaging modality and relate it to the molecular mechanism of the uptake of the radionuclide used.

  3. [Adenoid cystic carcinoma of the larynx, trachea and thyroid].

    PubMed

    Gryczyński, M; Piotrowski, S

    1995-01-01

    The aim of this article was to describe rarely occurred carcinoma adenoides cysticum located in the larynx, trachea and thyroid. Epidemiology, clinical course and medical therapy was demonstrated. In reported case concerning 65-year old woman early bilateral paresis of vocal folds was observed as results of the perineural infiltration. That caused sudden laryngeal dyspnea. It is important to pay attention on local extensiveness of neoplasm. Besides changes in larynx, neoplastic infiltration was found in trachea, preesophageal tissues and right lobe of thyroid. For above reasons there is no possible to exclude thyroid as a primary tumor of carcinoma adenoides cysticum.

  4. Diffuse sclerosing variant of thyroid papillary carcinoma: diagnostic challenges occur with Hashimoto's thyroiditis.

    PubMed

    Chen, Chien-Chin; Chen, Wen-Chung; Peng, Shu-Ling; Huang, Shih-Ming

    2013-06-01

    Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is a relatively rare variant of papillary thyroid carcinoma with distinct histological features, radiological characteristics, and biological aggressiveness. Compared with conventional papillary thyroid carcinoma, DSPTC is characterized by scattered microscopic tumor islands, diffuse fibrosis, calcification, and abundant lymphocytic aggregation. A preoperative diagnosis is challenging in the absence of nodules and scanty fine needle aspiration cytology samples. We describe a unique DSPTC patient, an 18-year-old woman who presented with a neck mass that grew slowly for 2 years. The palpable neck mass was nontender, well defined, firm, and unmovable. Laboratory studies showed normal thyroid function and positive autoimmune markers: antithyroglobulin antibody = 1:1600 and antimicrosomal antibody = 1:1600. A neck ultrasound showed diffusely prominent microcalcifications with one small vague nodule. Hashimoto's thyroiditis with an accompanying malignancy was suspected. Based on the result of intraoperative pathology reports, the patient was given a total thyroidectomy. Lymph node dissection and histological analysis revealed bilateral DSPTC in addition to lymphocytic thyroiditis in nonmalignant areas of the thyroid. Clinical and histological diagnostic challenges usually occur when DSPTC presents with a diffuse thyroid enlargement, dispersed microscopic tumor islands (frequently without mass formation), extensive fibrosis, and abundant lymphocytic infiltration mimicking thyroiditis.

  5. Nonconventional papillary thyroid carcinomas with pleomorphic tumor giant cells: a diagnostic pitfall with anaplastic carcinoma.

    PubMed

    Hommell-Fontaine, Juliette; Borda, Angela; Ragage, Florence; Berger, Nicole; Decaussin-Petrucci, Myriam

    2010-06-01

    The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

  6. 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

  7. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas.

    PubMed

    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

  8. Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.

    PubMed

    Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-ichi

    2014-12-01

    The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm.

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

    PubMed

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

    2015-01-01

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

  10. Mandibular Metastases of Papillary Thyroid Carcinoma Treated by Hemimandibulectomy and Costochondral Rib Graft

    PubMed Central

    Cinar, Can; Cetinkale, Oguz

    2015-01-01

    Summary: Papillary thyroid carcinoma (PTC) is the most common and well-differentiated cancer of the thyroid. Unlike most cancers, spread to local lymph node does not worsen the survival rate of PTC, and complete resection of the metastases seems to be important and may have favorable effects on the prognosis. A 33-year-old woman was referred to our clinic with a mass involving the right angulus mandible. Incisional biopsy of the mass diagnosed follicular variant of papillary thyroid carcinoma. Right hemimandibulectomy was performed and reconstructed with costochondral rib graft. The patient survived for 5 years after the hemimandibulectomy. Metastases to the oral cavity indicate a grave prognosis, but PTC has relatively indolent biological behavior; long-term survival is usually possible even in patients with metastatic disease. PMID:25750844

  11. Coexistence of Papillary Thyroid Carcinoma With Thyroid MALT Lymphoma in a Patient With Hashimoto's Thyroiditis: A Clinical Case Report.

    PubMed

    Shen, Guohua; Ji, Ting; Hu, Shuang; Liu, Bin; Kuang, Anren

    2015-12-01

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid neoplasias; however, primary thyroid gland lymphoma (PTL) is uncommon and their simultaneous occurrence is very rare.Herein, we reported a 25-year-old female patient with Hashimoto's thyroiditis (HT), who developed a small goiter with a palpable 1.2-cm nodule in the right lobe. A fine-needle aspiration (FNA) biopsy revealed atypical follicular epithelial cells and lymphoid cells in a background of lymphocytic thyroiditis. A total thyroidectomy was performed. The pathology showed multicentric papillary thyroid carcinoma, concomitant thyroid mucosa-associated lymphoid tissue (MALT) lymphoma, and Hashimoto's thyroiditis. Postoperatively, he received chemotherapy and radioactive iodine ablation treatment. Nowadays the thyroglobulin of the patient is undetectable, without recurrences at 2 years of follow-up.It is concluded that the PTC and MALT lymphoma can exist concomitantly, especially in patients with HT. For the diagnostic workup and optional management of this rare coexistence, a multidisciplinary approach and close surveillance are needed.

  12. An additional case of breast tumor resembling the tall cell variant of papillary thyroid carcinoma.

    PubMed

    Colella, Renato; Guerriero, Angela; Giansanti, Michele; Sidoni, Angelo; Bellezza, Guido

    2015-05-01

    A type of breast tumor histopathologically similar to the papillary thyroid carcinoma has been described and named "Breast tumor resembling the tall cell variant of papillary thyroid carcinoma." Because breast is not an uncommon site for metastasis and about 5% of all such cases are of the thyroid origin, it is important to be aware of the existence of mammary tumors that can closely mimic a thyroid tumor representing a dangerous diagnostic pitfall that can also lead to unnecessary clinical investigations. Here, we describe a singular case of "Breast tumor resembling the tall cell variant of papillary thyroid carcinoma" showing an amazing macroscopic and microscopic resemblance with thyroid tissue harboring a papillary carcinoma.

  13. A Rare Constellation of Hürthle Cell Thyroid Carcinoma and Parathyroid Carcinoma.

    PubMed

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad; Bahadoram, Mohammad

    2015-12-01

    Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hürthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology.

  14. Significance of Interleukin-6 in Papillary Thyroid Carcinoma

    PubMed Central

    Kobawala, Toral P.; Trivedi, Trupti I.; Gajjar, Kinjal K.; Patel, Darshita H.; Patel, Girish H.

    2016-01-01

    This study sought to reveal the significance of IL-6 in papillary thyroid carcinoma by determining its circulating levels, tumoral protein, and mRNA expressions. As compared to the healthy individuals, serum IL-6 was significantly higher in patients with benign thyroid diseases and PTC. Further, its level was significantly higher in PTC patients as compared to patients with benign thyroid diseases. ROC curves also confirmed a good discriminatory efficacy of serum IL-6 between healthy individuals and patients with benign thyroid diseases and PTC. The circulating IL-6 was significantly associated with poor overall survival in PTC patients. IL-6 immunoreactivity was significantly high in PTC patients as compared to the benign thyroid disease patients. Significantly higher IL-6 mRNA expression was also observed in the primary tumour tissues of PTC patients than the adjacent normal tissues. The protein expression of IL-6 at both the circulating and tissue level correlated with disease aggressiveness in PTC patients. Moreover, a significant positive correlation was observed between the IL-6 protein and mRNA expression in the primary tumours of PTC patients. Finally in conclusion, IL-6 has an important role in thyroid cancer progression. Thus targeting IL-6 signalling can help in clinical management of thyroid carcinoma patients. PMID:27034885

  15. Hyperfunctioning metastatic follicular thyroid carcinoma in Pendred's syndrome

    SciTech Connect

    Abs, R.; Verhelst, J.; Schoofs, E.; De Somer, E. )

    1991-04-15

    A 66-year-old woman with Pendred's syndrome underwent a partial thyroidectomy when she was 17 years old. At the age of 52 years, she had a second thyroid operation because of hyperthyroidism due to a toxic multinodular goiter with a mediastinal extension consisting of several separate nodules. Five years later a hyperfunctioning metastatic follicular carcinoma was diagnosed histologically. After treatment with radioactive iodine, the patient was well. To the authors' knowledge, this is the first description of a metastatic follicular thyroid carcinoma in Pendred's syndrome and the first report of hyperthyroidism occurring after malignant degeneration of a dyshormonogenetic goiter.

  16. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

    PubMed Central

    Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

    2015-01-01

    Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

  17. Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

    PubMed

    Magers, Martin J; Dueber, Julie C; Lew, Madelyn; Pang, Judy C; Davenport, Robertson D

    2016-06-01

    Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

  18. Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma.

    PubMed

    Rossing, Maria; Borup, Rehannah; Henao, Ricardo; Winther, Ole; Vikesaa, Jonas; Niazi, Omid; Godballe, Christian; Krogdahl, Annelise; Glud, Martin; Hjort-Sørensen, Christian; Kiss, Katalin; Bennedbæk, Finn Noe; Nielsen, Finn Cilius

    2012-02-01

    The molecular determinants of thyroid follicular nodules are incompletely understood and assessment of malignancy is a diagnostic challenge. Since microRNA (miRNA) analyses could provide new leads to malignant progression, we characterised the global miRNA expression in follicular adenoma (FA) and follicular carcinoma (FC). Comparison of carcinoma and adenoma with normal thyroid revealed 150 and 107 differentially expressed miRNAs respectively. Most miRNAs were down-regulated and especially miR-199b-5p and miR-144 which were essentially lost in the carcinomas. Integration of the changed miRNAs with differentially expressed mRNAs demonstrated an enrichment of seed sites among up-regulated transcripts encoding proteins implicated in thyroid tumourigenesis. This was substantiated by the demonstration that pre-miR-199b reduced proliferation when added to cultured follicular thyroid carcinoma cells. The down-regulated miRNAs in FC exhibited a substantial similarity with down-regulated miRNAs in anaplastic carcinoma (AC) and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in AC. To examine the diagnostic potential of miRNA expression pattern in distinguishing malignant from benign nodules we employed a supervised learning algorithm and leave-one-out-cross-validation. By this procedure, FA and FC were identified with a negative predicted value of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated with major changes in miRNA expression that may promote malignant transformation by increasing the expression of transcripts encoding tumourigenic factors. Moreover, miRNA profiling may facilitate the diagnosis of carcinoma vs adenoma. PMID:22049245

  19. Long-term eradication of locally recurrent invasive follicular thyroid carcinoma after taxane-based concomitant chemoradiotherapy.

    PubMed

    Tulloch-Reid, Marshall; Skarulis, Monica C; Sherman, Steven I; Sarlis, Nicholas J; Santarpia, Libero

    2009-11-01

    A 46-year-old woman with history of radioiodine-refractory follicular thyroid carcinoma (FTC) presented with locally recurrent, high-risk, invasive disease. She was treated with paclitaxel/carboplatin concomitant chemoradiotherapy (CRT), which was well tolerated, resulting in complete remission and freedom from residual or recurrent FTC for longer than 5 years until her last follow-up at age 52. This case highlights the possibility of combining taxane-based chemotherapy with definitive radiotherapy (as CRT) for the management of locally aggressive recurrences in poorly differentiated thyroid carcinoma, thereby resulting in rapid and persistent disease eradication. Even in the light of recent data on the potential benefit of novel targeted therapy agents in poorly differentiated thyroid carcinoma, this approach in similar clinical settings deserves future investigation. PMID:20032418

  20. Occurrence of thyroid papillary carcinoma in young patients. A Chernobyl connection?

    PubMed

    Blackburn, D J; Michel, L A; Rosière, A; Trigaux, J P; Donckier, J E

    2001-05-01

    The risk of thyroid papillary carcinoma is increased by external radiation particularly in children under 15 years of age as shown by a marked increase in those exposed to radiation after Chernobyl. We were recently confronted in Belgium over a short period with four patients (3 F, 1 M) with papillary thyroid carcinoma who were aged 10 years, 2 months, 2 years and 6 years when the Chernobyl accident occurred. We thus raise the question of a possible relationship. The patients were aged 17, 11, 10, 19 years at presentation. They all presented fortuitously over 3 years which was a very unusual increase in our extensive experience in thyroid surgery (62 cases of thyroid cancer among 1014 thyroidectomies in adults vs 4 cases in 18 children since the Chernobyl accident in 1986). Two out of the four patients had psammoma bodies (identifiable on CT scanning and ultrasound) and thyroglobulin autoantibodies (TgAb). The first patient had positive lymph nodes at the time of surgery. The incidence of thyroid cancers in Belarus and Ukraine rose just 4 years after the Chernobyl disaster; because radioactive clouds passed over Belgium, we wonder whether the occurrence of thyroid cancer in our patients could be related to this irradiation. The mechanism of increased incidence of radiation-induced thyroid cancer is thought to be due to rearrangement of the tyrosine kinase domains of the RET and TTK genes. The other important similarities in our patients are the presence of psammoma bodies that can be visualized on radiological examination and the presence of TgAb that are more frequent in differentiated thyroid cancers. Whether or not these cases reflect an increased incidence in the population as a whole, clinicians must remain vigilant for this rare but curable cancer in young patients, especially if suggestive radiological features or TgAb are present.

  1. Hashimoto's thyroiditis and papillary carcinoma in an adolescent girl: A case report

    PubMed Central

    DONG, LI-QUN; SUN, XIAO-MEI; XIANG, CHENG-FA; WU, JIN; YU, PING

    2016-01-01

    Hashimoto's thyroiditis with thyroid cancer in childhood is not as common in the adult population. Hashimoto's thyroiditis is an autoimmune disease associated with autoantibodies, and the association between Hashimoto's thyroiditis and papillary carcinoma of the thyroid remains controversial. The present study reported a 15-year-old adolescent girl with the diagnosis of Hashimoto's thyroiditis with thyroid cancer. With the complexity of the clinical manifestations of Hashimoto's thyroiditis, it can be expressed as not only hyperthyroidism or hypothyroidism, but also normal thyroid function. The long-term treatment, and for children with thyroid cancer, early diagnosis is particularly difficult. In the present case, the diagnosis of Hashimoto's thyroiditis is primarily based on clinical manifestations, anti-thyroglobulin antibody and anti-thyroid microsomal antibody. The only diagnostic imaging ultrasound was negative. The present study discussed the possible reason and the identification of this unique case of Hashimoto's thyroiditis with thyroid cancer. PMID:27330783

  2. Volcanoes and carcinoma of the thyroid: a possible association.

    PubMed

    Kung, T M; Ng, W L; Gibson, J B

    1981-01-01

    Environmental factors contributing to incidences of thyroid carcinoma are re-evaluated and emphasized in this study. Thyroid cancers appear to occur independent of endemic goiter, based on epidemiologic and histologic evidence. While environmental factors appear to be important, the specific etiologic agent has not yet been identified or suggested. The number of thyroid cancer incidences available from cancer registries are analyzed in an attempt to identify a specific environmental carcinogenic agent. The presence of active volcanoes that produce abundant lava is found to be the common denominator of Iceland and Hawaii, where the incidence of thyroid cancer is outstandingly high. Comparison with other areas with active volcanoes is made. The presence of a carcinogenic agent in the lava is postulated and its possible mode of action on humans through fish products is hypothesized.

  3. The “next-generation” knowledge of papillary thyroid carcinoma

    PubMed Central

    Costa, Valerio; Esposito, Roberta; Pallante, Pierlorenzo; Ciccodicola, Alfredo; Fusco, Alfredo

    2015-01-01

    The application of Next-Generation Sequencing for studying the genetics of papillary thyroid carcinomas (PTC) has recently revealed new somatic mutations and gene fusions as potential new tumor-initiating events in patients without any known driver lesion. Gene and miRNA expression analyses defined clinically relevant subclasses correlated to tumor progression. In addition, it has been shown that tumor driver mutations in BRAF, and RET rearrangements - altogether termed “BRAF-like” carcinomas - have a very similar expression pattern and constitute a distinct category. Conversely, “RAS-like” carcinomas have a different genomic, epigenomic, and proteomic profile. These findings justify the need to reconsider PTC classification schemes. PMID:26030480

  4. Thyroid carcinoma and hyperthyroidism in a dog

    PubMed Central

    Bezzola, Pauli

    2002-01-01

    A 10-year old spayed, female Labrador retriever, with an 8-month history of weight loss, increased heart rate, and hyperactivity, was diagnosed with hyperthyroidism and a thyroid neoplasm. Thyrotoxic heart disease is documented in this case. PMID:11842596

  5. 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

  6. RNA Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Reduced Expression of Immune Function Genes in BRAF (V600E) Mutant vs BRAF Wild-Type Papillary Thyroid Carcinoma

    PubMed Central

    Chindris, Ana-Maria; Asmann, Yan W.; Casler, John D.; Serie, Daniel J.; Reddi, Honey V.; Cradic, Kendall W.; Rivera, Michael; Grebe, Stefan K.; Necela, Brian M.; Eberhardt, Norman L.; Carr, Jennifer M.; McIver, Bryan; Copland, John A.; Aubrey Thompson, E.

    2014-01-01

    Context: The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression. Objective: RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status. Design: BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2–3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes. Patients: BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes. Results: RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR. Conclusion: BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent

  7. AZD6244 in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

    ClinicalTrials.gov

    2016-09-02

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

  8. ["Incidental" thyroid carcinoma among patients in surgical treatment for nontumors thyroid desease].

    PubMed

    Nechaĭ, O P; Larin, O S; Cheren'ko, S M; Sheptukha, S A; Smoliar, V A; Zolotar'ov, P O

    2012-07-01

    Incidence of unexpected diagnosis of thyroid carcinoma among operations on benign thyroid surgical diseases (nodular goiter and Graves' disease) was studied in 608 patients within 2008-2009 years in specialized clinic of endocrine surgery. In 56 (9.2%) patients the "incidental" thyroid carcinoma including 43 (77%) - papillary microcarcinoma were diagnosed in histological investigations. In 10 (18%) patients which were performed within the first postoperative week. Repeated surgery demonstrates increased risk of complication (damage of parathyroid glands, recurrent laryngeal nerves and other anatomic structures of neck) considering less favoring conditions for secondary operations, it is worth to implement wider indications to frozen section, radical primary operation (total thyroidectomy at multi-nodular bilateral goiter and Graves' disease), and also maximal complete examination prior to surgery. PMID:23033769

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

    PubMed

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

    2015-11-01

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

  10. AXIN2 is Associated With Papillary Thyroid Carcinoma

    PubMed Central

    Liu, Xin; Li, Shuang; Lin, Xuejun; Yan, Kangkang; Zhao, Longyu; Yu, Qiong; Liu, Xiaodong

    2016-01-01

    Background: Findings of recent studies have demonstrated a rapid increase of the incidence of papillary thyroid carcinoma (PTC), which accounts for nearly 80% of thyroid cancers. Objectives: The aim of this study was to explore the association between AXIN2 gene polymorphism and papillary thyroid carcinoma (PTC). Patients and Methods: 106 blood samples (56 PTC patients and 50 healthy controls) were drawn from China-Japan Union Hospital in Jilin province, China, during October 2010 to March 2011. A case-control study was designed to examine the association between AXIN2 and PTC. Seven tag single nucleotide polymorphisms (tag SNPs) in AXIN2 were selected and genotyped. Frequencies of different genotypes and alleles were analyzed between the patients and the controls, using the R × C column contingency table χ2 test. The possible association of haplotypes constructed by the combined effects of two or more loci with PTC was analyzed through the UNPHASED 3.1.4 program. Results: Rs11655966, rs3923086 and rs7591 of AXIN2 showed significant associations with PTC (P < 0.05). The result of haplotypes analysis showed that rs11655966-rs3923086-rs4791169 had statistically significant differences between the two groups (P < 0.05). Conclusions: Together with the functions of the target genes, we further elucidated that AXIN2 is associated with papillary thyroid carcinoma in the Chinese Han population. PMID:27168945

  11. Thyroid-Like Follicular Carcinoma of the Kidney in a Patient with Skull and Meningeal Metastasis

    PubMed Central

    Dong, Liang; Huang, Jiayu; Huang, Luke; Shi, Oumin; Liu, Qiang; Chen, Haige; Xue, Wei; Huang, Yiran

    2016-01-01

    Abstract Thyroid-like follicular carcinoma of the kidney (TLFCK) is an extremely rare subtype of renal cell carcinoma with close resemblance to the well-differentiated thyroid follicular neoplasms. TLFCK has not been included in the 2004 World Health Organization (WHO) classification due to the limited data available. Only 27 cases have been reported in the literature to date. Herein, we report a unique case of TLFCK that presented as a striking skull and meningeal metastasis 5 years after the initial diagnosis; this is the first case of TLFCK with such a novel metastasis pattern. A 68-year-old woman was found to have a right renal lesion using computed tomography (CT) during her regular clinical follow-up visit for bladder cancer, but she exhibited no obvious clinical symptoms. The CT scan showed a 4.4-cm diameter, slightly lobulated soft tissue mass in the right lower kidney, the pathological findings of which showed a TLFCK. Five years later, the patient had progressed to skull and meningeal metastasis. Both the renal tumor and the metastasis lesion were composed almost entirely of follicles with a dense, colloid-like material that resembled thyroid follicular carcinoma. However, no lesion was found in the thyroid gland. The neoplastic epithelial cells were strongly immunoreactive for cytokeratin 7 (and vimentin but negative for thyroid transcription factor-1 and thyroglobulin. This is the first reported case of TLFCK to consist of widespread metastases to the skull and meninges and provides evidence that this rare variant of renal cell carcinoma has uncertain malignant potential and can be more clinically aggressive than previously believed. PMID:27082575

  12. 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.

  13. Recent Updates on the Management of Medullary Thyroid Carcinoma

    PubMed Central

    2016-01-01

    Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor derived from the thyroid C cells producing calcitonin. MTC accounts for 0.6% of all thyroid cancers and incidence of MTC increased steadily between 1997 and 2011 in Korea. It occurs either sporadically or in a hereditary form based on germline rearranged during transfection (RET) mutations. MTC can be cured only by complete resection of the thyroid tumor and any loco-regional metastases. The most appropriate treatment is still less clear in patients with residual or recurrent disease after initial surgery or those with distant metastases because most patients even with metastatic disease have indolent courses with slow progression for several years and MTC is not responsive to either radioactive iodine therapy or thyroid-stimulating hormone suppression. Recently, two tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib, are approved for use in patients with advanced, metastatic or progressive MTC. In this review, we summarize the current approach according to revised American Thyroid Association guidelines and recent advances in systemic treatment such as TKIs for patients with persistent or recurrent MTC after surgery. PMID:27586449

  14. [Renal cell carcinoma metastasis to the thyroid gland 15 years after nephrectomy].

    PubMed

    Mathiesen, Jes Sloth; Fleischer, Jens Geelmuyden; Godballe, Christian

    2015-01-26

    Renal cell carcinoma (RCC) metastasis to the thyroid gland is rare and can mimic primary thyroid carcinoma leading to diagnostic difficulties. We present a case of a 55-year-old female with RCC metastasis to the thyroid gland 15 years after nephrectomy. Diagnosis was made after total thyroidectomy. This case emphasizes the importance of considering metastasis in patients with increasing growth of the thyroid gland over a short period of time known with earlier RCC, even decades after nephrectomy. PMID:25612964

  15. Differentiated pediatric thyroid cancer: correlates with adult disease, controversies in treatment.

    PubMed

    Parisi, Marguerite T; Mankoff, David

    2007-09-01

    The biologic behavior of differentiated thyroid cancer can differ between adults and children, especially in those children younger than 10 years of age. Unlike adults, young children typically present with advanced disease at diagnosis. Despite this, children respond rapidly to therapy and have an excellent prognosis that is significantly better than that of their adult counterparts with advanced disease. In contradistinction to adults, children with thyroid cancer also have higher local and distant disease recurrences with progression-free survival of only 70% at 5 years, mandating life-long surveillance. Although thyroid cancer is the most common carcinoma in children, overall incidence is low, a factor that has prevented performance of a controlled, randomized, prospective study to determine the most efficacious treatment regimen in this age group. So, although extensively investigated, treatment of pediatric patients with differentiated thyroid cancer remains controversial. This article reviews the current controversies in the treatment of pediatric differentiated thyroid cancer, focusing on issues of optimal initial and subsequent therapy as well as that of long-term follow-up. Our approach to treatment is presented. In so doing, similarities and differences between adults and children with differentiated thyroid cancer as regards unique considerations in epidemiology, diagnosis, staging, treatment, therapy-related late effects, and disease surveillance are presented. The expanding use of and appropriate roles for thyrogen and fluorine-18-fluorodeoxyglucose positron emission tomography in disease evaluation and surveillance will be addressed.

  16. Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is cytopathological diagnosis possible?

    PubMed

    Kloboves-Prevodnik, Veronika; Jazbec, Janez; Us-Krasovec, Marija; Lamovec, Janez

    2002-05-01

    Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor of the thyroid gland which occurs predominantly in children, adolescents, and young adults. It usually presents as a painless neck or thyroid mass and only exceptionally as a diffusely enlarged thyroid gland, without metastatic disease at diagnosis. We report on the case of 12-yr-old girl who had diffusely enlarged thyroid gland for about 1 yr and was initially treated for thyroiditis. Fine-needle aspiration biopsy (FNAB) was performed 8 mo after the first admission. Cytological examination of smears showed unusual morphological features. FNAB smears were cellular, with dissociated cells, naked oval nuclei, aggregates, and groups. Three main cell types were observed: spindle, epithelioid, and epithelial. These cells were uniform, cytologically bland, with few mitotic figures. The distinction between these cells was not always unequivocal. In the background of the smears abundant red extracellular material in the form of fine, dust-like granules and irregular patches were present. It was also observed in some aggregates and groups of tumor cells. Spindle and epithelioid cells were immunocytochemically diffusely pan-cytokeratin-positive. In the differential diagnosis, medullary thyroid carcinoma and SETTLE were suggested. The final histological diagnosis was SETTLE. In cases of SETTLE presented as a diffuse thyromegaly the correct diagnosis may be delayed because clinically and ultrasonographically thyroiditis is suspected. To avoid such a delay, FNAB should be used preoperatively. It can provide specific cytological diagnosis based on morphological features and certain immunocytochemical characteristics of the tumor.

  17. "Mucin secreting" and "mucinous" primary thyroid carcinomas: pitfalls in mucin histochemistry applied to thyroid tumours.

    PubMed Central

    Rigaud, C; Bogomoletz, W V

    1987-01-01

    Forty primary carcinomas of the thyroid of different histological types were reviewed and studied histochemically, with the aim of identifying and assessing "mucin secretion". The patterns of extracellular "pure alcianophilia" and "mixed alcianophilia" were noted in 7.5% and about 50% of these tumours, respectively. A critical review of the pitfalls in methods and interpretation of mucin histochemistry--as performed in previously reported cases of "mucin secreting" or "mucinous" primary thyroid tumours--is presented. The apparent "mucin secretion" described in these unusual neoplasms could be due to histochemical staining of carbohydrate components or breakdown products of thyroglobulin and colloid. Images Fig 1 Fig 2 Fig 3 PMID:3654988

  18. Expression of YY1 in Differentiated Thyroid Cancer.

    PubMed

    Arribas, Jéssica; Castellví, Josep; Marcos, Ricard; Zafón, Carles; Velázquez, Antonia

    2015-05-01

    The transcription factor Yin Yang 1 (YY1) has an important regulatory role in tumorigenesis, but its implication in thyroid cancer has not been yet investigated. In the present study, we have analyzed the expression of YY1 in differentiated thyroid cancer and assessed the association of YY1 expression with clinical features. Expression of YY1 was evaluated in human thyroid cancer cell lines, a series of matched normal/tumor thyroid tissues and in a thyroid cancer tissue microarray, using real-time PCR, Western blot, and/or immunohistochemistry. YY1 was overexpressed in thyroid cancer cells, at transcription and protein levels. A significant increase of YY1 mRNA was also observed in tumor thyroid tissues. Moreover, immunohistochemical analysis of the thyroid cancer tissue microarray revealed that both papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) present increased YY1 protein levels (48 and 19%, respectively). After stratification by the level of YY1 protein, positive YY1 expression identifies 88% of patients with PTC. The association of YY1 expression with clinicopathological features in PTC and FTC showed that YY1 expression was related with age at diagnosis. Our data indicates for the first time overexpression of YY1 in differentiated thyroid cancer, with YY1 being more frequently overexpressed in the PTC subtype.

  19. "Hidden" bone metastasis from thyroid carcinoma: a clinical note.

    PubMed

    Sioka, C; Skarulis, M C; Tulloch-Reid, M K; Heiss, J D; Reynolds, J C

    2014-01-01

    The (131)I-iodide ((131)I) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body (131)I scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received (131)I therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECT or lateral imaging.

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

    ClinicalTrials.gov

    2015-06-01

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

  1. [Clinical characteristics of the thyroid follicular carcinoma].

    PubMed

    Gutiérrez-Hermosillo, Hugo; Tamez-Peréz, Héctor Eloy; Díaz de León-Gonzaléz, Enrique; Gutiérrez-Hermosillo, Violeta; Avila-Sanchéz, Jair

    2013-01-01

    Introducción: se ha identificado carcinoma folicular en 39 % de los pacientes con nódulos tiroideos cuya citología prequirúrgica ha indicado resultados indeterminados. El propósito de esta investigación fue conocer la prevalencia de esta entidad en un hospital de concentración. Métodos: se buscaron los reportes quirúrgicos con diagnóstico de carcinoma folicular. Se registró tamaño del tumor, sexo y edad del paciente, diagnósticos pre y posquirúrgico y patologías asociadas. Resultados: se diagnosticó carcinoma folicular en 35 pacientes: 30 mujeres (85 %) y cinco hombres (15 %). La edad en los hombres fue de 57 ± 6.6 y de 44 ± 16.9 en las mujeres. Los diagnósticos preoperatorios fueron carcinoma folicular en 14 (40 %), cáncer tiroideo en seis (17.1 %), adenoma folicular en cuatro (11.4 %), bocio en tres (8.5 %), nódulo tiroideo en tres (8.5 %); carcinoma papilar, tumor de tiroides, carcinoma poco diferenciado de tiroides, adenocarcinoma folicular bien diferenciado, cáncer medular en un paciente (2.8 %) cada uno. Las patologías asociadas fueron tiroiditis de Hashimoto y carcinoma papilar contralateral, con dos pacientes cada uno (5.6 %). Conclusiones: la edad de los pacientes y la presentación clínica del carcinoma folicular difirieron de las informadas en otras investigaciones.

  2. Approach to the Patient with Anaplastic Thyroid Carcinoma

    PubMed Central

    2012-01-01

    Anaplastic thyroid carcinoma is the least common but most lethal of thyroid cancers. All patients are classified as stage IV, with the primary lesion restricted to the thyroid gland in stage IVA; locoregional lymph nodes may exist in IVA/IVB; and IVC disease is defined by distant metastases. Prognosis is highly dependent on disease extent at presentation, and staging and establishing a plan of care must be accomplished quickly. Although almost all studies are biased due to their retrospective nature, the most important factors associated with longer survival are completeness of surgical resection (achievable in only a minority of patients) and high-dose (>40 Gy) external beam radiotherapy (preferably intensity modulated radiation therapy). Recent reports suggest that a multimodal approach (surgery, radiation, and chemotherapy) is beneficial. Given the high lethality even with apparent local disease, combination systemic therapy (cytotoxics and/or targeted agents) may improve outcomes in stage IVA/IVB patients. Newer, more effective drug combinations are urgently needed for IVC patients who want aggressive therapy. A candid discussion of the prognosis and management options, including palliative care/hospice, should be held with the patient and caregiver as soon as possible after diagnosis to clarify the patient's preference and expectations. Prospective multicenter clinical trials, incorporating molecular analyses of tumors, are required if we are to improve survival in anaplastic thyroid carcinoma. PMID:22869844

  3. Langerhans Cell Histiocytosis of the Thyroid with Multiple Cervical Lymph Node Involvement Accompanying Metastatic Thyroid Papillary Carcinoma

    PubMed Central

    Ceyran, A. Bahar; Şenol, Serkan; Bayraktar, Barış; Özkanlı, Şeyma; Cinel, Z. Leyla; Aydın, Abdullah

    2014-01-01

    A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma. PMID:25349760

  4. [Thyroid carcinoma: from diagnosis to therapy].

    PubMed

    Marrazzo, Antonio; Taormina, Pietra; David, Massimo; Riili, Ignazio; Casà, Luigi; Noto, Antonio; Romano, Giorgio; Marrazzo, Emilia; Buscemi, Giuseppe

    2008-01-01

    From 1999 to 2007 we performed 104 surgical operations for thyroid malignancies. Over the same period, 312 patients underwent surgery for benign lesions of the thyroid gland. The patients were subdivided on the basis of age bracket and gender and the distribution of cancer and benign nodules was evaluated. Feasibility and diagnostic accuracy of ultrasonography, scintigraphy and fine needle aspiration cytology were also evaluated. The incidence of thyroid cancer was 25% in all patients. Patients aged < 30 years and > 71 had the highest rate of malignancies: 52% of patients under 30 years of age and 46% over 70 years. Males showed a higher incidence than females. The scintigraphic findings were an area of low uptake in 19 cases (47.5%), an irregular pattern in 12 patients (30%) and a high uptake in 9 cases (22.5%); in 3 of them (7.5%), cancer was in the contralateral lobe and in 2 cases (5%) the dimensions were 8 and 4 mm. Forty-three patients had a single hypoechoic nodule at ultrasonography (41.3%), 3 (3%) were found with hypoechoic nodules containing calcifications and 1 (0.9%) a single anechoic nodule. Fifty-six patients (53.9%) had multiple nodules and 1 (0.9%) was admitted for a latero-cervical lymph node. FNAC revealed 11 cases of fibronectin expression (14.4%): in particular, 3 patients (4%) had cancer in the contralateral lobe and 3 patients (4%) had tumours measuring less than 5 mm. Thyroid surgery is safe and the morbidity rate is about 2%. We observed only one lesion of recurrent nerve (0.5% of patients), temporary recurrent palsy in 2.8% of patients and transient hypocalcaemia in 6.7% of cases. PMID:19062491

  5. HAND1 gene expression is negatively regulated by the High Mobility Group A1 proteins and is drastically reduced in human thyroid carcinomas.

    PubMed

    Martinez Hoyos, J; Ferraro, A; Sacchetti, S; Keller, S; De Martino, I; Borbone, E; Pallante, P; Fedele, M; Montanaro, D; Esposito, F; Cserjesi, P; Chiariotti, L; Troncone, G; Fusco, A

    2009-02-12

    HMGA1 proteins exert their major physiological function during embryonic development and play a critical role in neoplastic transformation. Here, we show that Hand1 gene, which codes for a transcription factor crucial for differentiation of trophoblast giant cells and heart development, is upregulated in hmga1 minus embryonic stem cells. We demonstrate that HMGA1 proteins bind directly to Hand1 promoter both in vitro and in vivo and inhibit Hand1 promoter activity. We have also investigated HAND1 expression in human thyroid carcinoma cell lines and tissues, in which HMGA proteins are overexpressed, with respect to normal thyroid; an inverse correlation between HMGA1 and HAND1 expression was found in all thyroid tumor histotypes. A correlation between HAND1 gene repression and promoter hypermethylation was found in anaplastic carcinomas but not in other thyroid tumor histotypes. Therefore, we can hypothesize that HMGA1 overexpression plays a key role on HAND1 silencing in differentiated thyroid carcinomas and that promoter hypermethylation occurs in later stages of thyroid tumor progression. Finally, the restoration of the HAND1 gene expression reduces the clonogenic ability of two human thyroid carcinoma-derived cell lines, suggesting that HAND1 downregulation may have a role in the process of thyroid carcinogenesis.

  6. Detection of human parvovirus B19 in papillary thyroid carcinoma

    PubMed Central

    Wang, J H; Zhang, W P; Liu, H X; Wang, D; Li, Y F; Wang, W Q; Wang, L; He, F R; Wang, Z; Yan, Q G; Chen, L W; Huang, G S

    2008-01-01

    To evaluate whether parvovirus B19, a common human pathogen, was also involved in papillary thyroid carcinoma (PTC), 112 paraffin-embedded thyroid specimens of benign nodules, papillary, medullary and follicular carcinomas, and normal controls were examined for B19 DNA and capsid protein by nested PCR, in situ hybridisation (ISH) and immunohistochemistry (IHC). The expression of the nuclear factor-κB (NF-κB) was investigated by IHC. The results showed B19 DNA commonly exists in human thyroid tissues; however, there were significant differences between PTC group and normal controls, and between PTC and nonneoplastic adjacent tissues (P<0.001). The presence of viral DNA in PTC neoplastic epithelium was confirmed by laser-capture microdissection and sequencing of nested PCR products. B19 capsid protein in PTC group was significantly higher than that of all the control groups and nonneoplastic adjacent tissues (P⩽0.001). Compared with control groups, the activation of NF-κB in PTC group was significantly increased (P⩽0.02), except for medullary carcinomas, and the activation of NF-κB was correlated with the viral protein presence (P=0.002). Moreover, NF-κB was colocalised with B19 DNA in the neoplastic epithelium of PTC by double staining of IHC and ISH. These results indicate for the first time a possible role of B19 in pathogenesis of PTC. PMID:18212749

  7. Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and Simultaneous Cushing's Syndrome

    PubMed Central

    Mazeh, Haggi; Orlev, Amir; Mizrahi, Ido; Gross, David J.; Freund, Herbert R.

    2015-01-01

    Background Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. Case Report A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. Conclusion We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently. PMID:25960965

  8. Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis

    PubMed Central

    Liu, Feng‐Hsuan; Kuo, Sheng‐Fong; Hsueh, Chuen; Chao, Tzu‐Chieh

    2015-01-01

    Background and Objectives : The purpose of this study was to retrospectively analyze the features of patients with papillary thyroid carcinoma (PTC) presenting with neck lymph node (LN) metastasis. Methods : The study enrolled 909 patients with PTC who had undergone total thyroidectomy. After a median follow‐up of 14.6 years, 73 (8.0%) patients died of thyroid cancer. A total of 536 patients had the tumor confined to the thyroid (intra‐thyroid), 111 had lymph node (LN) metastasis, 225 showed soft tissue invasion, and 37 had distant metastasis. Results : Compared with the intra‐thyroid group, the group with LN metastases showed larger tumor size, higher postoperative thyroglobulin levels, advanced TNM stage, higher recurrence rates (5.2% vs. 31.5%), and higher disease‐specific mortality (1.3% vs. 12.6%). Of the 111 patients with PTC and LN metastases, 35 (31.5%) were diagnosed with recurrence during a mean follow‐up period of 16.9 ± 0.6 years. Among the 35 patients with recurrent PTC, 14 (40.0%) died of thyroid cancer. The mortality group was characterized by older, mostly male patients who presented with larger initial tumor size compared with survivors. Conclusions : In patients with PTC, the rates of recurrence and cancer mortality were higher in the group with LN metastasis than that in the intra‐thyroid tumor group. J. Surg. Oncol. 2015 111:149–154. © 2015 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc. PMID:26175314

  9. Macrofollicular variant of papillary thyroid carcinoma with extensive lymph node metastases.

    PubMed

    Yeo, Min-kyung; Bae, Ja Seong; Oh, Woo Jin; Park, Gyeong Sin; Jung, Chan Kwon

    2014-09-01

    The macrofollicular variant of papillary thyroid carcinoma is a rare subtype of the follicular variant of papillary thyroid carcinoma and is usually characterized by an indolent clinical course. The tumors are prone to be misdiagnosed as benign due to their macrofollicular architecture and bland cytologic features. We report a rare case of the macrofollicular variant of papillary thyroid carcinoma with extensive lymph node metastases. The patient was a 48-year-old female with a right thyroid nodule and multiple enlarged lymph nodes in the right neck. It was not possible to make a definitive diagnosis of malignancy on fine-needle aspiration cytology and intraoperative frozen section. She underwent total thyroidectomy with right modified radical neck dissection. The surgical specimen showed a 2.5 × 1.5 × 10 cm, well-circumscribed macrofollicular variant of papillary thyroid carcinoma in the right lobe and multiple central and right lateral neck lymph node metastases. Molecular testing for BRAF, NRAS, HRAS, and KRAS was all negative. We then reviewed the demographic and clinicopathologic characteristics of 71 patients with the macrofollicular variant of papillary thyroid carcinoma. The cytologic or histopathologic diagnosis of macrofollicular variant of papillary thyroid carcinoma can be difficult. Extensive lymph node metastases caused by the macrofollicular variant of papillary thyroid carcinoma may occur even in the absence of capsular or lymphovascular invasion. This review will help to better understand the nature of the macrofollicular variant of papillary thyroid carcinoma.

  10. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    PubMed Central

    Le, Valerie H.; Camille, Nadia; Miles, Brett A.; Teng, Marita S.; Genden, Eric M.; Misiukiewicz, Krzysztof J.

    2016-01-01

    Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC. PMID:27747102

  11. Rare case of axillary lymph node metastasis in papillary thyroid carcinoma detected using Iodine-131 whole-body scintigraphy and single-photon emission computed tomography/computed tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Rajan, Firoz; Mohanan, Vyshak; Shinto, Ajit Sugunan

    2015-01-01

    Differentiated thyroid cancer is, usually, associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual. Only few cases of papillary carcinoma with axillary nodal metastasis were previously reported in the literature. We present a 38-year-old female who underwent Iodine-131 whole-body scintigraphy, after total thyroidectomy and bilateral neck lymph node dissection for papillary carcinoma of thyroid, showed intense uptake in the remnant thyroid, lung metastasis, left cervical and left axillary lymph nodes. Excision of left axillary lymph nodes confirmed metastatic papillary carcinoma. PMID:25829741

  12. Rare case of axillary lymph node metastasis in papillary thyroid carcinoma detected using Iodine-131 whole-body scintigraphy and single-photon emission computed tomography/computed tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Rajan, Firoz; Mohanan, Vyshak; Shinto, Ajit Sugunan

    2015-01-01

    Differentiated thyroid cancer is, usually, associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual. Only few cases of papillary carcinoma with axillary nodal metastasis were previously reported in the literature. We present a 38-year-old female who underwent Iodine-131 whole-body scintigraphy, after total thyroidectomy and bilateral neck lymph node dissection for papillary carcinoma of thyroid, showed intense uptake in the remnant thyroid, lung metastasis, left cervical and left axillary lymph nodes. Excision of left axillary lymph nodes confirmed metastatic papillary carcinoma.

  13. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    PubMed

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable.

  14. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    PubMed

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  15. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland

    PubMed Central

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  16. Gene expression in papillary thyroid carcinoma reveals highly consistent profiles

    PubMed Central

    Huang, Ying; Prasad, Manju; Lemon, William J.; Hampel, Heather; Wright, Fred A.; Kornacker, Karl; LiVolsi, Virginia; Frankel, Wendy; Kloos, Richard T.; Eng, Charis; Pellegata, Natalia S.; de la Chapelle, Albert

    2001-01-01

    Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligo-based DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase–PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8/8 tumors for 24 genes and in 7/8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase–PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6/6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7/8 tumors for eight genes and decreased in 6/8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use. PMID:11752453

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

    PubMed Central

    Atun, Jenny Maureen

    2016-01-01

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

  18. Unusual case of hepatic metastasis in follicular thyroid carcinoma detected using I-131 whole body scintigraphy and single-photon emission computerized tomography/computerized tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Natarajan, Sudhakar; Mohanan, Vyshak; Shinto, Ajit Sugunan

    2015-01-01

    Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Among these presentations, metastasis to the liver is even more unusual. Only 11 cases of DTC with liver metastasis were previously reported in the literature. We present a 55-year-old male on Iodine-131 whole body scintigraphy showed intense uptake in thyroid bed, metastasis in both lungs and right lobe of the liver. Radioiodine concentration in liver metastases made him amenable to high-dose radioiodine therapy patient. PMID:26430327

  19. Unusual case of hepatic metastasis in follicular thyroid carcinoma detected using I-131 whole body scintigraphy and single-photon emission computerized tomography/computerized tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Natarajan, Sudhakar; Mohanan, Vyshak; Shinto, Ajit Sugunan

    2015-01-01

    Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Among these presentations, metastasis to the liver is even more unusual. Only 11 cases of DTC with liver metastasis were previously reported in the literature. We present a 55-year-old male on Iodine-131 whole body scintigraphy showed intense uptake in thyroid bed, metastasis in both lungs and right lobe of the liver. Radioiodine concentration in liver metastases made him amenable to high-dose radioiodine therapy patient.

  20. Report of a case of papillary thyroid carcinoma in association with Hashimoto's thyroiditis.

    PubMed

    Okani, Chukwudi Onyeaghana; Otene, Benjamin; Nyaga, Terhemba; Ngbea, Joseph; Eke, Agaba; Edegbe, Felix; Anyiam, Daniel

    2015-01-01

    Hashimoto thyroiditis (HT) is an autoimmune disease, known to be the most common cause of hypothyroidism in nonendemic goitrous areas. It is usually characterized by symmetric, painless, and diffused but sometimes localized swelling of the thyroid gland with features of hypothyroidism. Papillary thyroid carcinoma (PTC), on the other hand, is the most common yet less aggressive form of thyroid cancer, especially in iodine-deficient areas. The coexistence of the two diseases is possible but not common. This case study reports a 50-year-old female with a 10-year history of a huge goiter, which was essentially symptom-free until about 3 months prior to presentation when the patient started complaining of neck pain, dysphagia, productive cough, and cold intolerance. Physical examination revealed focal cystic and tender area in the multinodular swelling and associated cervical lymphadenopathy on the left side of the neck. The serum thyroid stimulating hormone was high, sub-normal T3, and the T4 was low. The fine needle aspiration cytology yielded 10 ml of aspirate of pus admixed with altered blood which on microscopy showed a few suspicious follicular epithelial cells with open nuclei admixed with mainly neutrophil polymorphs, siderophages, and foam cells in a hemorrhagic background. The patient had an incision biopsy that showed areas displaying PTC and HT. PMID:26903704

  1. Thyrotropin in the development and management of differentiated thyroid cancer.

    PubMed

    McLeod, Donald S A

    2014-06-01

    Thyrotropin (TSH) is the major regulator and growth factor of the thyroid. TSH may be important in the development of human thyroid cancer, with both suggestive animal models and clinical evidence, although definitive proof is still required. Applications for TSH in thyroid cancer management include TSH stimulation of radioiodine uptake, enhancement of biochemical monitoring through thyroglobulin measurement, and long-term suppression of TSH with supraphysiologic levothyroxine. This review synthesizes current knowledge of TSH in both the development and management of differentiated thyroid cancer.

  2. The co-occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome.

    PubMed

    Durieux, Emeline; Descotes, Françoise; Mauduit, Claire; Decaussin, Myriam; Guyetant, Serge; Devouassoux-Shisheboran, Mojgan

    2016-05-01

    The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Pleuropulmonary blastoma is the most frequent lesion seen in this syndrome. Thyroid abnormalities are also a common finding, essentially concerning multinodular goiter. However, differentiated thyroid carcinoma is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 RNase IIIb catalytic domain in several tumor types, including ovarian Sertoli-Leydig cell tumors. We report two cases of differentiated thyroid carcinoma associated with ovarian Sertoli-Leydig cell tumor and with a heterozygous DICER1 gene mutation, occurring in two unrelated young girls without pleuropulmonary blastoma. Both thyroid carcinomas showed an E1813 mutation in exon 25 while the ovarian tumors harboured a somatic mutation in E1705 in exon 24 and a D1709 mutation in exon 25. Our observations confirm that the occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome. We contend that the possibility of a relationship between sporadic thyroid carcinoma in young patients and somatic DICER1 gene mutation needs further investigation. PMID:26983701

  3. The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma

    PubMed Central

    Dillon, Laura W.; Lehman, Christine E.; Wang, Yuh-Hwa

    2012-01-01

    The incidence of thyroid cancer is increasing, especially papillary thyroid carcinoma (PTC), making it currently the fastest-growing cancer among women. Reasons for this increase remain unclear, but several risk factors including radiation exposure and improved detection techniques have been suggested. Recently, the induction of chromosomal fragile site breakage was found to result in the formation of RET/PTC1 rearrangements, a common cause of PTC. Chromosomal fragile sites are regions of the genome with a high susceptibility to forming DNA breaks and are often associated with cancer. Exposure to a variety of external agents can induce fragile site breakage, which may account for some of the observed increase in PTC. This paper discusses the role of fragile site breakage in PTC development, external fragile site-inducing agents that may be potential risk factors for PTC, and how these factors are especially targeting women. PMID:22762011

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

    ClinicalTrials.gov

    2016-07-20

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

  5. Papillary Thyroid Carcinoma Arising in Children and Adolescent Hashimoto's Thyroiditis: Ultrasonographic and Pathologic Findings.

    PubMed

    Jeong, Sun Hye; Hong, Hyun Sook; Lee, Eun Hye; Kwak, Jeong Ja

    2016-01-01

    Objectives. We compared the ultrasonography and pathology features of papillary thyroid carcinoma (PTC) in pediatric and adolescents with Hashimoto's thyroiditis (HT) with those of non-HT patients. Materials and Methods. Eleven patients who were surgically confirmed to have pediatric or adolescent PTC from 2006 to 2014 were included in this study. We retrospectively analyzed the preoperative ultrasonography and pathology features of PTC arising in HT and non-HT patients. Results. On ultrasonography, thyroid gland was lobulated and enlarged, with many scattered microcalcifications in four of five HT patients. Four of six non-HT patients had suspicious masses with calcifications. The diffuse sclerosing variant of PTC (DSVPTC) was found in three of five HT patients, but none in non-HT patients. Macroscopic or microscopic extrathyroidal extension was evident in all of the HT patients and four of the non-HT patients. Neck lymph node metastases were in all HT patients and five of non-HT patients. Conclusions. Three of five PTCs in pediatric and adolescent HT patients were DSVPTC, whereas all PTCs of the non-HT patients were classic type. On ultrasonography, thyroid gland was diffusely enlarged with scattered microcalcifications in four of five HT patients. All five HT cases had aggressive disease, including extrathyroidal extension and cervical lymph node metastases. PMID:26977145

  6. Solitary thyroid metastasis from clear-cell renal carcinoma.

    PubMed Central

    Madore, P.; Lan, S.

    1975-01-01

    A 58-year-old woman underwent nephrectomy because of clear-cell renal carcinoma. Seven years later a solitary thyroid metastasis was detected. She is alive and well 17 months after thyroidectomy. The rarity of this manifestation is well known but its explanation is not clear. The long metastasis-free interval, a characteristic shared by other hormonally dependent neoplasms, has been explained in part by the concept of "dormant cells", which do not undergo division. The stimulus that provokes these cells into division is at present not known. Images FIG. 1 FIG. 2 PMID:1122443

  7. Significance of CK19, TPO, and HBME-1 expression for diagnosis of papillary thyroid carcinoma

    PubMed Central

    Liu, Zeming; Yu, Pan; Xiong, Yiquan; Zeng, Wen; Li, Xiaoyu; Maiaiti, Yusufu; Wang, Shuntao; Song, Haiping; Shi, Lan; Liu, Chunping; Cheng, Bo; Zhang, Bo; Ming, Jie; Dong, Fang; Ge, Hui; Nie, Xiu; Huang, Tao

    2015-01-01

    Objectives: To evaluate the expression and significance of CK19, TPO, and HBME-1 in the differential diagnosis of papillary thyroid carcinoma (PTC) and nonmalignant nodules. Methods: Tissue samples were obtained from 257 patients with PTC and 149 patients with nonmalignant thyroid specimens, and immunohistochemical staining for CK-19, TPO, and HBME-1 was performed. Results: The expression of CK-19, TPO, and HBME-1 was 96.3%, 12.0%, and 85.3%, respectively, for the PTC group. For nonmalignant thyroid lesions group, the expression of these markers was 40.4%, 86.2%, and 37.2%, respectively. Further, the expression of CK-19 and HBME-1 in PTCs was much higher than that in the benign thyroid lesions (P < 0.05). However, the positive expression of TPO in PTC specimens was much lower than that in the nonmalignant specimens (P < 0.05). CK-1 had the highest sensitivity (96.30%) for PTCs. The combination of the positive expression of CK-19 and negative expression of TPO had the highest sensitivity (98.50%), while that of the positive expression of HBME-1 and negative expression of TPO had the highest specificity (92.90%). Conclusions: The combination of positive expression of CK-19 or HBME-1 or negative expression of TPO can improve the specificity of the diagnosis of PTC. PMID:26064355

  8. TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells.

    PubMed

    Palladino, Giuseppe; Notarangelo, Tiziana; Pannone, Giuseppe; Piscazzi, Annamaria; Lamacchia, Olga; Sisinni, Lorenza; Spagnoletti, Girolamo; Toti, Paolo; Santoro, Angela; Storto, Giovanni; Bufo, Pantaleo; Cignarelli, Mauro; Esposito, Franca; Landriscina, Matteo

    2016-09-01

    Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role in thyroid carcinoma (TC), still unaddressed at present, was investigated by analyzing its expression in a cohort of 86 human TCs and evaluating its involvement in cancer cell survival and proliferation in vitro Indeed, TRAP1 levels progressively increased from normal peritumoral thyroid gland, to papillary TCs (PTCs), follicular variants of PTCs (FV-PTCs) and poorly differentiated TCs (PDTCs). By contrast, anaplastic thyroid tumors exhibited a dual pattern, the majority being characterized by high TRAP1 levels, while a small subgroup completely negative. Consistently with a potential involvement of TRAP1 in thyroid carcinogenesis, TRAP1 silencing resulted in increased sensitivity to paclitaxel-induced apoptosis, inhibition of cell cycle progression and attenuation of ERK signaling. Noteworthy, the inhibition of TRAP1 ATPase activity by pharmacological agents resulted in attenuation of cell proliferation, inhibition of ERK signaling and reversion of drug resistance. These data suggest that TRAP1 inhibition may be regarded as potential strategy to target specific features of human TCs, i.e., cell proliferation and resistance to apoptosis. PMID:27422900

  9. Aberrant Expression of Posterior HOX Genes in Well Differentiated Histotypes of Thyroid Cancers

    PubMed Central

    Cantile, Monica; Scognamiglio, Giosuè; La Sala, Lucia; La Mantia, Elvira; Scaramuzza, Veronica; Valentino, Elena; Tatangelo, Fabiana; Losito, Simona; Pezzullo, Luciano; Chiofalo, Maria Grazia; Fulciniti, Franco; Franco, Renato; Botti, Gerardo

    2013-01-01

    Molecular etiology of thyroid cancers has been widely studied, and several molecular alterations have been identified mainly associated with follicular and papillary histotypes. However, the molecular bases of the complex pathogenesis of thyroid carcinomas remain poorly understood. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have shown that HOX genes play a role in neoplastic transformation of several human tissues. In particular, the genes belonging to HOX paralogous group 13 seem to hold a relevant role in both tumor development and progression. We have identified a significant prognostic role of HOX D13 in pancreatic cancer and we have recently showed the strong and progressive over-expression of HOX C13 in melanoma metastases and deregulation of HOX B13 expression in bladder cancers. In this study we have investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX paralogous group 13 genes/proteins expression in thyroid cancer evolution and progression, also evaluating its ability to discriminate between main histotypes. Our results showed an aberrant expression, both at gene and protein level, of all members belonging to paralogous group 13 (HOX A13, HOX B13, HOX C13 and HOX D13) in adenoma, papillary and follicular thyroid cancers samples. The data suggest a potential role of HOX paralogous group 13 genes in pathogenesis and differential diagnosis of thyroid cancers. PMID:24189220

  10. Extensive laryngeal infiltration from a neglected papillary thyroid carcinoma: A case report

    PubMed Central

    Georgiades, Fanourios; Vasiliou, George; Kyrodimos, Efthimios; Thrasyvoulou, Giannis

    2016-01-01

    Papillary carcinoma of the thyroid is the commonest type of thyroid cancer. Laryngeal infiltration from papillary thyroid carcinoma is extremely rare, with only a few cases of partial invasion described in the literature. We present a very unusual case of complete infiltration of both thyroid and cricoid cartilages from a neglected papillary thyroid carcinoma in a 59-year-old male. This sequel resulted from refusal of the patient to undergo treatment when initially diagnosed. An invasion to such an extent has not been described in the literature before, and in this case warranted a total laryngectomy followed by radioactive iodine. Prompt management of papillary carcinomas is crucial for avoiding such complications. Future guidelines should include management options for the patients who deny treatment initially. PMID:27458595

  11. Mucinous Variant of Follicular Carcinoma of the Thyroid Gland: Case Report and Review of the Literature.

    PubMed

    Squillaci, Salvatore; Pitino, Antonio; Spairani, Cinzia; Ferrari, Mauro; Carlon, Eugenio; Cosimi, Maria Fabia

    2016-04-01

    The rare reports of mucinous variant of follicular carcinoma of the thyroid gland have not provided enough evidence to support the recognition of these tumors as a distinct clinicopathologic entity or to understand their etiopathogenesis. We report the fourth case of mucinous variant of follicular carcinoma displaying a minimally invasive tumor with diffuse expression of thyroglobulin, TTF-1, CD56, PAX-8, cytokeratins 7 and 19, in the absence of monoclonal carcinoembryonic antigen (CEA), cytokeratin 20, chromogranin, HBME-1, P63 expression, and BRAF gene mutation, in a 51-year-old woman who is alive without signs of disease 13 months after total thyroidectomy, bilateral neck dissection, and radioactive iodine. Herein, fine-needle aspiration cytology disclosed "worrisome" cytologic features consisting of large epithelial cells arranged in clusters or singularly, with high nucleocytoplasmic ratio, nuclear grooves and evident nucleoli which were shared by those of mucin-producing papillary thyroid carcinoma. Therefore, knowledge of the cytological and histopathological spectrum of this lesion is important to avoid misdiagnosis. The morphologic clues leading to the correct diagnosis of mucinous variant of follicular neoplasm have been correlated with the data of the literature, and the differential diagnosis is briefly discussed.

  12. UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas

    PubMed Central

    Pallante, P; Berlingieri, M T; Troncone, G; Kruhoffer, M; Orntoft, T F; Viglietto, G; Caleo, A; Migliaccio, I; Decaussin-Petrucci, M; Santoro, M; Palombini, L; Fusco, A

    2005-01-01

    The hybridisation of an Affymetrix HG_U95Av2 oligonucleotide array with RNAs extracted from six human thyroid carcinoma cell lines and a normal human thyroid primary cell culture led us to the identification of the UbcH10 gene that was upregulated by 150-fold in all of the carcinoma cell lines in comparison to the primary culture cells of human normal thyroid origin. Immunohistochemical studies performed on paraffin-embedded tissue sections showed abundant UbcH10 levels in thyroid anaplastic carcinoma samples, whereas no detectable UbcH10 expression was observed in normal thyroid tissues, in adenomas and goiters. Papillary and follicular carcinomas were only weakly positive. These results were further confirmed by RT–PCR and Western blot analyses. The block of UbcH10 protein synthesis induced by RNA interference significantly reduced the growth rate of thyroid carcinoma cell lines. Taken together, these results would indicate that UbcH10 overexpression is involved in thyroid cell proliferation, and may represent a marker of thyroid anaplastic carcinomas. PMID:16106252

  13. 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

  14. Sonographic and cytopathologic correlation of papillary thyroid carcinoma variants.

    PubMed

    Lee, Ji Hyun; Shin, Jung Hee; Lee, Hyun-Woo; Oh, Young Lyun; Hahn, Soo Yeon; Ko, Eun Young

    2015-01-01

    Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and constitutes more than 70% of thyroid malignancies. Although TNM staging is the most widely used parameter for determination of therapeutic plans, recent studies have suggested that different histopathologic variants of PTC can also have different clinical courses and patient prognoses. Sonographic criteria for PTC are well established and include a taller-than-wide shape, an irregular margin, microcalcifications, and marked hypoechogenicity. The role of sonography has expanded to enable the characterization of PTC variants based on their sonographic features. Tall cell and diffuse sclerosing variants appear to have more aggressive clinical courses with unfavorable prognoses, whereas the more recently described cribriform-morular and Warthin-like variants have relatively indolent clinical courses. The prognoses of patients with follicular, solid, columnar cell, and oncocytic variants are still controversial and may be similar to the prognosis of conventional PTC. Understanding the sonographic characteristics of PTC variants with clinicopathologic correlation may be helpful for suggesting an appropriate treatment plan.

  15. Follicular variant of papillary thyroid carcinoma: an unusual cause of thyrotoxicosis.

    PubMed

    Rees, David Owen; Anthony, Victoria Angharad; Jones, Keston; Stephens, Jeffrey W

    2015-05-06

    Thyroid carcinoma presenting as a hyperfunctioning thyroid nodule is rare. A further complexity is added when interpretation of the histopathology itself is not straightforward. We describe a case of a 16-year-old girl presenting with clinical and biochemical evidence of thyrotoxicosis, and a 4 cm thyroid mass. An ultrasound and thyroid uptake scan demonstrated a toxic adenoma. Owing to the nodule size, fine needle aspiration of the thyroid adenoma was performed, which showed findings consistent with toxic adenoma. However, in view of the size of the nodule, a hemithyroidectomy was performed. Histological examination of the thyroid revealed a follicular variant of papillary carcinoma of the thyroid, and the patient underwent completion thyroidectomy. We report on the case and briefly review the available literature relating to the diagnostic challenge of this presentation.

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-10-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored. PMID:27566169

  18. Radioiodine in the treatment of medullary carcinoma of the thyroid.

    PubMed

    Hellman, D E; Kartchner, M; Van Antwerp, J D; Salmon, S E; Patton, D D; O'Mara, R

    1979-03-01

    Medullary carcinoma (MC) of the thyroid, in contrast to papillary-follicular carcinoma, fails to concentrate iodine and thus has not been treated with radioactive iodine. We have successfully treated a 16-yr-old Mexican-American girl with residual MC after maximal thyroidectomy (Tx), utilizing radioiodine (131I) to deliver radiation to residual follicular cells in the tumor bed. Immediately after Tx, plasma thyrocalcitonin levels before and during calcium infusion were all elevated (640--1200 pg/ml). 131I (150 mCi) was administered 12 days after Tx after four daily im injections of bovine TSH. Three months after 131I therapy, thyrocalcitonin levels before and during calcium infusion were all normal (less than 50 pg/ml). Ten months after 131I therapy, thyrocalcitonin levels before and after iv pentagastrin were all normal (less than 60 pg/ml). These results suggest that parafollicular cells are radiosensitive, and that therapeutic levels of radiation can be delivered to these cells after Tx if iodine trapping by the remaining follicular cells is enhanced by high levels of circulating TSH. 131I may be the therapy of choice for MC after Tx, if disease has not spread beyond the area proximate to the thyroid gland.

  19. Hypopharyngeal and Parapharyngeal Space Metastasis of Papillary Thyroid Carcinoma: A Case Report

    PubMed Central

    Batıoğlu-Karaaltın, Ayşegül; Azizli, Elad; Ersözlü, İlker; Yiğit, Özgür; Cansız, Harun

    2014-01-01

    Background: Carcinoma of the thyroid gland is one of the most commonly encountered endocrine malignancies. Papillary carcinoma is the most common histological type, and its spread is usually lymphatic. About 30–80% patients with papillary carcinoma develop lymphatic metastases. Case Report: We present here the case of a 70-year-old female patient who had undergone total thyroidectomy 10 years previously, with a histological diagnosis of papillary thyroid carcinoma. A neck dissection was performed ten years after the primary operation due to a mass in the parapharyngeal space and hypopharynx. The mass was diagnosed histologically as papillary thyroid cancer metastasis after the operation. Conclusion: Lymphatic and vascular metastases of papillary thyroid carcinoma separately to the parapharyngeal space and hypopharynx have rarely been reported. In our case, both hypopharyngeal and parapharyngeal space involvement were presented, which is a very rare condition. PMID:25207192

  20. Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

    PubMed Central

    Song, Young Shin; Lim, Jung Ah

    2015-01-01

    Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians. PMID:26435130

  1. The Oncogenic Activity of RET Point Mutants for Follicular Thyroid Cells May Account for the Occurrence of Papillary Thyroid Carcinoma in Patients Affected by Familial Medullary Thyroid Carcinoma

    PubMed Central

    Melillo, Rosa Marina; Cirafici, Anna Maria; De Falco, Valentina; Bellantoni, Marie; Chiappetta, Gennaro; Fusco, Alfredo; Carlomagno, Francesca; Picascia, Antonella; Tramontano, Donatella; Tallini, Giovanni; Santoro, Massimo

    2004-01-01

    Activating germ-line point mutations in the RET receptor are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma (MTC), whereas somatic RET rearrangements are prevalent in papillary thyroid carcinomas (PTCs). Some rare kindreds, carrying point mutations in RET, are affected by both cancer types, suggesting that, under specific circumstances, point mutations in RET can drive the generation of PTC. Here we describe a family whose siblings, affected by both PTC and MTC, carried a germ-line point mutation in the RET extracellular domain, converting cysteine 634 into serine. We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. We show that the various RET point mutants, but not wild-type RET, scored constitutive kinase activity and exerted mitogenic effects for thyroid PC Cl 3 cells, albeit at significantly lower levels compared to RET/PTC1. The low mitogenic activity of RET point mutants paralleled their reduced kinase activity compared to RET/PTC. Furthermore, RET point mutants maintained a protein domain, the intracellular juxtamembrane domain, that exerted negative effects on the mitogenic activity. In conclusion, RET point mutants can behave as dominant oncogenes for thyroid follicular cells. Their transforming activity, however, is rather modest, providing a possible explanation for the rare association of MTC with PTC. PMID:15277225

  2. [Sonoelastography in differential diagnosis of thyroid nodes].

    PubMed

    Zubarev, A V; Bashilov, V P; Gazhonova, V E; Kartavykh, A A; Churkina, S O; Selivanov, E S

    2011-01-01

    The study was aimed to assess the diagnostic possibilities of the new method of sonoelastography. 68 patients with different thyroid nodes were studied. Sonoelastography increased the sensitivity of the routine ultrasound investigation from 89 to 94.8%, the specificity from the 83 to 93%, and the accuracy of the method from 76 to 89%. The method assignes the information of the structural changes of the thyroid, unavailable by the routine ultrasound investigation. PMID:21606917

  3. Natural history, treatment, and course of papillary thyroid carcinoma

    SciTech Connect

    DeGroot, L.J.; Kaplan, E.L.; McCormick, M.; Straus, F.H. )

    1990-08-01

    We have analyzed the course of papillary thyroid carcinoma in 269 patients managed at the University of Chicago, with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20-40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recurrences, but not increased deaths. Extrathyroidal invasion carried an increased risk of 5.8-fold for death, and distant metastases increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections.

  4. Effect of BRAF mutational status on expression profiles in conventional papillary thyroid carcinomas

    PubMed Central

    2015-01-01

    Background Whereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a BRAF mutation (BRAFmut), unified biomarkers for the genetically heterogeneous group of BRAF wild type (BRAFwt) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional BRAFwt and BRAFmut PTCs. Methods Microarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11 BRAFwt PTCs including five micro PTCs, 14 BRAFmut PTCs, and 7 normal thyroid specimens. A p-value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data. BRAF mutational status was established by direct sequencing the hotspot region of exon 15. Results We identified 237 annotated genes that were significantly differentially expressed between BRAFwt and BRAFmut PTCs. Of these, 110 genes were down- and 127 were upregulated in BRAFwt compared to BRAFmut PTCs. A number of molecules involved in thyroid hormone metabolism including thyroid peroxidase (TPO) were differentially expressed between both groups. Among cancer-associated molecules were ERBB3 that was downregulated and ERBB4 that was upregulated in BRAFwt PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set. Conclusions The expression study focusing on affected genes that are differentially expressed between BRAFwt and BRAFmut conventional PTCs identified a number of molecules which are connected in a network and affect

  5. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    PubMed

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome.

  6. The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas.

    PubMed

    El-Maqsoud, Nehad M R Abd; Tawfiek, Ehab Rifat; Abdelmeged, Ayman; Rahman, Mohamed Fathy Abdel; Moustafa, Alaa A E

    2016-03-01

    Napsin A and thyroid transcription factor-1 (TTF-1) are useful biomarkers for differentiating lung adenocarcinoma from squamous cell carcinoma and also for differentiating primary lung adenocarcinoma from metastatic lung carcinoma. Pair-boxed 8 (PAX8) can help in distinguishing primary lung carcinoma from metastatic carcinomas and help to determine the primary sites of metastatic carcinomas. Immunohistochemistry for Napsin A, TTF-1, and PAX8 were performed on 193 cases of carcinoma: 50 primary lung carcinoma and 143 carcinomas from other sites. Napsin A and TTF-1 were positive in 54, 52 % of lung carcinomas cases, respectively. While in adenocarcinoma cases, their expressions were 86.7 and 83.3 %, respectively. PAX8 was negative in all lung carcinomas. TTF-1 and PAX8 were positive in 93.3 and 96.7 % of thyroid carcinoma cases and in 87.5 and 93.8 % of papillary carcinoma respectively, and both were positive in 100 % of follicular carcinoma. Napsin A was negative in all thyroid carcinomas. Napsin A and PAX8 were positive in 50 and 93.3 % of renal carcinoma cases and in 81.8 and 100 % of papillary carcinoma, 38.5 and 92.3 % of clear cell carcinoma, and 16.7 and 83.3 % of chromophobe carcinoma respectively. TTF-1 was negative in all renal carcinomas. PAX8 was positive in 80 % of ovarian carcinoma cases; 100 and 60 % of serous mucinous carcinomas, respectively. It was also positive in 100 % of endometrial carcinoma. Napsin A and TTF-1 were negative in both ovarian and endometrial carcinomas. Our data demonstrated that combined use of Napsin A, TTF-1, and PAX8 may help in differentiating between primary lung adenocarcinoma and metastatic lung carcinomas.

  7. Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid

    PubMed Central

    2015-01-01

    Background Follicular variant of papillary thyroid carcinoma (FVPTC) and follicular adenoma (FA) are histologically closely related tumors and differential diagnosis remains challenging. RNA expression profiling is an established method to unravel molecular mechanisms underlying the histopathology of diseases. Methods BRAF mutational status was established by direct sequencing the hotspot region of exon 15 in six FVPTCs and seven FAs. Whole-transcript arrays were employed to generate expression profiles in six FVPTCs, seven FAs and seven normal thyroid tissue samples. The threshold of significance for differential expression on the gene and exon level was a p-value with a false discovery rate (FDR) < 0.05 and a fold change cutoff > 2. Two dimensional average linkage hierarchical clustering was generated using differentially expressed genes. Network, pathway, and alternative splicing utilities were employed to interpret significance of expression data on the gene and exon level. Results Expression profiling in FVPTCs and FAs, all of which were negative for a BRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCs vs. FAs. Amongst the most significantly upregulated genes in FVPTCs were GABA B receptor, 2 (GABBR2), neuronal cell adhesion molecule (NRCAM), extracellular matrix protein 1 (ECM1), heparan sulfate 6-O-sulfotransferase 2 (HS6ST2), and retinoid X receptor, gamma (RXRG). The most significantly downregulated genes in FVPTCs included interaction protein for cytohesin exchange factors 1 (IPCEF1), G protein-coupled receptor 155 (GPR155), Purkinje cell protein 4 (PCP4), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1), and glutamate receptor interacting protein 1 (GRIP1). Alternative splicing analysis detected 87 genes, 52 of which were also included in the list of 55 differentially expressed genes. Network analysis demonstrated multiple interactions

  8. 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

  9. 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.

  10. [BRAF-STATUS OF PAPILLARY THYROID CARCINOMAS AND STRATEGY OF SURGICAL TREATMENT].

    PubMed

    Tarashchenko, Yu N; Kovalenko, A E; Bolgov, M Yu; Guda, B B; Shelkovoy, E A; Nekrasov, K A; Mankovskaya, S; Kashuba, V I

    2015-06-01

    Analyzed the presence of BRAF V600E mutation in the focal thyroid gland in the preoperative diagnosis of papillary carcinoma (PC). Molecular genetic testing conducted on puncture aspirates from 26 patients before surgery. The diagnosis was verified according to the morphological investigations. Mutations in BRAF V600E detected only in patients with the thyroid PC. Thus, the definition of BRAF V600E mutation may be a marker in the preoperative diagnosis of thyroid PC. Analyzed the presence of BRAF V600E mutation in the focal thyroid gland in the preoperative diagnosis of papillary carcinoma (PC). Molecular genetic testing conducted on puncture aspirates from 26 patients before surgery. The diagnosis was verified according to the morphological investigations. Mutations in BRAF V600E detected only in patients with the thyroid PC. Thus, the definition of BRAF V600E mutation may be a marker in the preoperative diagnosis of thyroid PC.

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

    PubMed Central

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

    2015-01-01

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

  12. Thyroid Hormone Activates Brown Adipose Tissue and Increases Non-Shivering Thermogenesis - A Cohort Study in a Group of Thyroid Carcinoma Patients

    PubMed Central

    Broeders, Evie P. M.; Vijgen, Guy H. E. J.; Havekes, Bas; Bouvy, Nicole D.; Mottaghy, Felix M.; Kars, Marleen; Schaper, Nicolaas C.; Schrauwen, Patrick; Brans, Boudewijn; van Marken Lichtenbelt, Wouter D.

    2016-01-01

    Background/Objectives Thyroid hormone receptors are present on brown adipose tissue (BAT), indicating a role for thyroid hormone in the regulation of BAT activation. The objective of this study was to examine the effect of thyroid hormone withdrawal followed by thyroid hormone in TSH-suppressive dosages, on energy expenditure and brown adipose tissue activity. Subjects/Methods This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to treatment protocol). Paired two-tailed t-tests and linear regression analyses were used. Results Basal metabolic rate (BMR) was significantly higher after treatment with synthetic thyroid hormone (levothyroxine) than in the hypothyroid state (BMR 3.8 ± 0.5 kJ/min versus 4.4 ± 0.6 kJ/min, P = 0.012), and non-shivering thermogenesis (NST) significantly increased from 15 ± 10% to 25 ± 6% (P = 0.009). Mean BAT activity was significantly higher in the subclinical hyperthyroid state than in the hypothyroid state (BAT standard uptake value (SUVMean) 4.0 ± 2.9 versus 2.4 ± 1.8, P = 0.039). Conclusions Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT. Trial Registration ClinicalTrials.gov NCT02499471 PMID:26784028

  13. Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report

    PubMed Central

    Sun, Jianyi; Liu, Xiaosun; Zhang, Qing; Hong, Yanyun; Song, Bin; Teng, Xiaodong

    2016-01-01

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation. PMID:27390548

  14. Molecular perspectives in differentiated thyroid cancer.

    PubMed

    Buffet, C; Groussin, L

    2015-02-01

    Progress in understanding the molecular genetics of thyroid cancer in the last 20 years has accelerated recently with the advent of high-throughput sequencing technologies known as Next-Generation Sequencing. Besides classical molecular abnormalities involving the MAPK (Mitogen Activated Protein Kinase) and PI3K (PhosphoInositide 3-Kinase) pathways that play a key role in follicular-derived thyroid tumorigenesis, new molecular abnormalities have been discovered. The major advances in recent years have been the discovery of new somatic driver gene point mutations (such as RASAL1 [RAS protein activator Like 1] mutations in follicular cancer) and/or mutations that have prognostic value (such as TERT [Telomerase reverse transcriptase] promoter mutations); new chromosomal rearrangements, usually having close connection with exposure to ionizing radiation (such as ALK [Anaplastic Lymphoma Kinase] rearrangements); and deregulation of some gene or microRNA expression representing a molecular signature. Progress made in understanding the molecular mechanisms of thyroid cancer offers new perspectives for the diagnosis of the benign or malignant status of a thyroid nodule, to refine prognosis and offer new perspectives of targeted therapy for radioiodine-refractory cancers.

  15. [Mucoepidermoid carcinoma of the thyroid: a case report and literature review].

    PubMed

    França, Sabrina R; Caldas, Dayse; Alcebíades, V; de Oliveira, Carlos A B

    2006-10-01

    The mucoepidermoid carcinoma is a neoplasia that usually occurs at salivary glands, breast, pancreas and gastrointestinal tract. The primary occurrence on thyroid gland is rare and only 33 cases were previously published. Although the majority of cases of mucoepidermoid carcinoma of the thyroid (MECT) show a benign evolution, this paper describes a patient with an aggressive tumor. A literature review over clinical, histopathological, immunohistochemical features and histogenetic origin was discussed.

  16. What is the Minimal Surgery for Papillary Thyroid Carcinoma?

    PubMed Central

    Fridman, Eran; Gil, Ziv

    2016-01-01

    Although thyroid surgery for treatment of papillary thyroid carcinoma (PTC) has been practiced for more than 100 years, there is still controversy regarding the minimal surgery needed for cure. The main reason for this controversy is lack of prospective randomized trials. The data accumulated in the last four decades indicate that hemithyroidectomy can be sufficient and safely practiced in low-risk patients with PTC. Patients <45 years of age with a single tumor less than 2 cm, with no lymphatic spread, and in the absence of other risk factors, can be equally managed by hemithyroidectomy or total thyroidectomy. A slight increase in the risk of vocal cord paralysis and hypocalcemia after total thyroidectomy suggests that hemithyroidectomy is appropriate for the management of patients with stage T1 disease. Any choice regarding the extent of surgery should be made with the patient and his family and in a multidisciplinary setup, which has been shown to improve decision-making procedures before the operation and during follow-up. PMID:26886960

  17. Cervical Cord Compression as Initial Presentation of Papillary Thyroid Carcinoma: a Case Report.

    PubMed

    Selvakumar, Veda Padma Priya; Goel, Ashish; Kumar, Kapil

    2016-09-01

    Cervical cord compression secondary to extension of a long standing papillary thyroid carcinoma as well as multiple cases of distal cord compression from occult follicular thyroid carcinoma have been reported. But cervical cord compression from Papillary Thyroid Carcinoma has not been reported so far. Forty eight year old lady presented with progressive quadriparesis of 2 months duration. MRI of the cervical spine showed destructive lesion with soft tissue component in vertebral bodies and posterior elements of C4-C6 vertebrae with cord compression along with a large thyroid mass extending to retrosternal region likely malignant. USG guided FNAC & Biopsy of thyroid lesion was inconclusive. She underwent Preoperative Selective angioembolisation for vertebral metastasis followed by total thyroidectomy with cervical cord decompression, bone grafting and plating. HPE reported follicular variant of Papillary Thyroid carcinoma. Four weeks postoperatively she underwent radioiodine ablation by 263 mci of I 131. She then received palliative EBRT to cervical and dorsal spine 30 Gy/10 fractions. She is alive and neurologically stable at 6 months follow up. Papillary thyroid carcinoma has an excellent prognosis. Hence a prompt management of primary disease and aggressive approach to metastatic lesion may prolong survival and allow favorable prognosis. PMID:27651699

  18. Identification of Genes Associated with Papillary Thyroid Carcinoma (PTC) for Diagnosis by Integrated Analysis.

    PubMed

    Li, W-B; Zhou, J; Xu, L; Su, X-L; Liu, Q; Pang, H

    2016-04-01

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and our understanding of its pathogenesis is incomplete. To elucidate the mechanisms underlying such progression and identify novel diagnostic markers, we aimed to discover the underlying gene associated with PTC. Integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between PTCs and normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis were then performed to uncover the functions of DEGs. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed. Five GEO datasets were obtained. Totally, 154 DEGs across the studies were identified, including 26 upregulated and 128 downregulated DEGs. In the PPI network, MLLT1, DLG2, and EFEMP1 were the hub proteins, in which DLG2 and EFEMP1 were involved in tumor progression. Among the top 10 up- and downregulated genes, the dysregulation genes of TPO, CDH16, and MPPED2 may be closely related to the tumorigenesis of PTC. By integrated analysis of multiple gene expression profiles, we propose that the dysregulation genes of TPO and MPPED2 will be the promising diagnostic markers for PTCs.

  19. (99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

    PubMed

    Basu, Sandip; Joshi, Amit

    2014-07-01

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

  20. Value of TIRADS, BSRTC and FNA-BRAFV600E mutation analysis in differentiating high-risk thyroid nodules

    PubMed Central

    Zhang, Yu-zhi; Xu, Ting; Cui, Dai; Li, Xiao; Yao, Qing; Gong, Hai-yan; Liu, Xiao-yun; Chen, Huan-huan; Jiang, Lin; Ye, Xin-hua; Zhang, Zhi-hong; Shen, Mei-ping; Duan, Yu; Yang, Tao; Wu, Xiao-hong

    2015-01-01

    The thyroid imaging reporting and data system (TIRADS) and Bethesda system for reporting thyroid cytopathology (BSRTC) have been used for interpretation of ultrasound and fine-needle aspiration cytology (FNAC) results of thyroid nodules. BRAFV600E mutation analysis is a molecular tool in diagnosing thyroid carcinoma. Our objective was to compare the diagnostic value of these methods in differentiating high-risk thyroid nodules. Total 220 patients with high-risk thyroid nodules were recruited in this prospective study. They all underwent ultrasound, FNAC and BRAFV600E mutation analysis. The sensitivity and specificity of TIRADS were 73.1% and 88.4%. BSRTC had higher specificity (97.7%) and similar sensitivity (77.6%) compared with TIRADS. The sensitivity and specificity of BRAFV600E mutation (85.1%, 100%) were the highest. The combination of BSRTC and BRAFV600E mutation analysis significantly increased the efficiency, with 97.8% sensitivity, 97.7% specificity. In patients with BSRTC I-III, the mutation rate of BRAFV600E was 64.5% in nodules with TIRADS 4B compared with 8.4% in nodules with TIRADS 3 or 4A (P < 0.001). Our study indicated that combination of BSRTC and BRAFV600E mutation analysis bears a great value in differentiating high-risk thyroid nodules. The TIRADS is useful in selecting high-risk patients for FNAB and patients with BSRTC I-III for BRAFV600E mutation analysis. PMID:26597052

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

    ClinicalTrials.gov

    2016-06-17

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

  2. Morphological and immunohistological characteristics of follicular-compact thyroid carcinoma in dog.

    PubMed

    Ciaputa, Rafal; Nowak, Marcin; Kandefer-Gola, Malgorzata; Dziedzic, Katarzyna; Halupka, Pawel; Pula, Bartosz; Kielbowicz, Maciej

    2014-01-01

    The case of a 14-year-old mongrel dog with a thyroid tumor treated by thyreoidectomy is described. The resected tumor was subjected to a detailed morphological and immunohistochemical analysis utilizing antibodies directed against thyroglobulin, calcitonin, chromogranin A, cytokeratin 19, thyroid transcription factor-1, CD31, Ki-67 and minichromosome maintenance protein 3. Expression level of the above mentioned antigens allowed to characterize the resected tumor as thyroid follicular-compact carcinoma. Common application of immunohistochemistry may increase the diagnosis precision and efficacy of thyroid tumor treatment in dogs.

  3. [The principles of differentiated thyroid cancer surgery and anesthesia in pregnancy: three case reports].

    PubMed

    Bayır, Ömer; Polat, Reyhan; Saylam, Güleser; Öcal, Bülent; Çakal, Erman; Delibaşı, Tuncay; Korkmaz, Mehmet Hakan

    2015-01-01

    Development of thyroid nodule during pregnancy is rare, however the cancer rate of this nodule is high. Herein, we present medical outcomes of three pregnant women who were operated with the diagnosis of differentiated thyroid carcinoma in the light of literature. As sonographic findings of three cases showed malignant characteristics, fine needle aspiration biopsy (FNAB) was performed. Cytological examination result was reported as papillary thyroid carcinoma (PTC). Surgery was performed in the second trimester in all cases. One case underwent total thyroidectomy with neck dissection at level III and VI and two cases underwent total thyroidectomy with neck dissection at level VI. Pathological examination result was also reported as PTC. Lymph node metastases in the dissected materials were detected. During the intraoperative and early postoperative period, no complications occurred and no findings of recurrence or residues were observed during one-year follow-up following surgery. In conclusion, as the first trimester has an increased risk of congenital malformations, elective surgery should be performed at the second trimester, if applicable. In pregnants with malignant sonographic features and PTC confirmed by FNAB, surgery can be applied safely by taking precautions during pre-/peri- and postoperative period. These patients should not be given premedication for anesthesia, should be properly positioned and teratogenic agents should be avoided. After surgery, mother and fetus should be monitored closely. PMID:26572180

  4. Incidental finding of bilateral papillary thyroid carcinoma in a patient with primary hyperparathyroidism.

    PubMed

    Alavi, Mehr Sadat; Azarpira, Negar; Mojallal, Mehra

    2010-01-01

    Primary hyperparathyroidism (PHP) affects 0.5%-1% of the adult population and presents with classical signs of renal lithiasis, cholecystolithiasis, gastrointestinal ulcerations, depression, and osteoporosis. Parathyroid adenoma, hyperplasia and rarely carcinoma are the underlying pathology. Synchronous thyroid and parathyroid pathologies are described in multiple endocrine neoplasia. We report a case of a 47 years old woman with non-syndromic concomitant occurrence of bilateral non-medullary thyroid carcinoma diagnosed by histopathology, and with PHP confirmed by (99m)Tc-MIBI scintigraphy, hypercalcemia and elevated serum parathyroid hormone. A head and neck surgeon needs to be aware of the possible coexistence of thyroid and parathyroid lesions. To our knowledge, this is the first report of concomitant PHP and bilateral papillary thyroid cancer in the literature. In conclusion, it is optimal to remove both tumors in one operative procedure. Therefore careful thyroid evaluation should be considered for all patients with PHP.

  5. Clinical pathological impacts of microRNAs in papillary thyroid carcinoma: A crucial review.

    PubMed

    Chruścik, Anna; Lam, Alfred King-yin

    2015-12-01

    MicroRNAs (miRNA) deregulation is an important event in the pathogenesis of papillary thyroid carcinoma. The alternations of miRNAs could be measured at the cancer tissue or serum so that the clinical impacts of them in papillary thyroid carcinoma could be studied. Using the approach, miRNA deregulation was reported to be associated with pathological stages in papillary thyroid carcinoma as reflected by the differences in extent of extra-thyroidal invasion, size of the tumour as well as presence of lymph nodes metastases. The most common miRNAs involved in these processes are miRNA-146, miRNA-222 and miRNA-221. Also, miRNA-222 and miRNA-146b deregulation are commonly associated with cancer recurrence in patients with papillary thyroid carcinoma. Additionally, miRNA-146, miRNA-222, and miRNA-221 are the top-regulated miRNAs involved in the pathogenesis confirmed by deep-sequencing and have their function studied in vitro. Targeting these subsets of miRNAs may be useful in management of patients with papillary thyroid carcinoma.

  6. [Brain metastasis from papillary thyroid carcinoma with acute intracerebral hemorrhage: a surgical case report].

    PubMed

    Chonan, Masashi; Mino, Masaki; Yoshida, Masahiro; Sakamoto, Kazuhiro

    2012-05-01

    We report a rare case of brain metastasis from papillary thyroid carcinoma with intracerebral hemorrhage. A 79-year-old woman presented with sudden headache and monoplegia of the right upper limb 10 years after diagnosis of thyroid papillary adenocarcinoma. Despite the known metastatic lesions in the cervical lymph nodes and lungs, she had been well for 10 years since thyroidectomy, focal irradiation and internal radiation of 131I. CT demonstrated intracerebral hemorrhage in the left temporal lobe. Magnetic resonance imaging showed marked signal heterogeneity. She underwent radical surgery on the day of the onset and the histological diagnosis was metastatic brain tumor of thyroid papillary carcinoma. Postoperative course was uneventful, and the monoplegia was improved. Papillary thyroid carcinoma has a relatively benign course, and surgical removal of the brain metastasis is able to contribute to longer survival times for patients.

  7. Papillary thyroid carcinoma-like tumor of the kidney: a case report.

    PubMed

    Khoja, Hatim A; Almutawa, Abdulmonem; Binmahfooz, Ali; Aslam, Muhammad; Ghazi, Abdullah A; Almaiman, Sara

    2012-08-01

    Thyroid carcinoma-like tumor of the kidney is an extremely rare variant of renal cell carcinoma. Most previously reported cases were incidental finding; and none of them showed papillary thyroid carcinoma (PTC) nuclear features. This study reports the first case of PTC (follicular variant)-like tumor of the kidney in which a female patient presented with hematuria, weight loss, and flank pain. Imaging studies revealed a left renal mass with enlarged hilar lymph nodes. Histologically, the renal tumor had a striking resemblance to follicular variant of PTC. However, no radiological abnormalities were found in the thyroid, mediastinum, or pelvis. Tumor cells were negative for thyroid markers (thyroglobulin and TTF1). According to the authors, this is the first case of PTC (follicular variant)-like tumor of the kidney. PMID:22158951

  8. Lymph node metastases from an occult sclerosing carcinoma of the thyroid. A case report.

    PubMed

    Santini, L; Pezzullo, L; D'Arco, E; De Rosa, N; Guerriero, O; Salza, C

    1989-01-01

    Lymph node metastases from occult thyroid papillary carcinoma are not a rare event. An unusual case of cystic lymph node metastases from this type of carcinoma is reported, suggesting that fine needle aspiration biopsy or frozen section biopsies should always be performed in the presence of a cystic lesion of the neck.

  9. New Insights in Risk Stratification of Differentiated Thyroid Cancer

    PubMed Central

    Papaleontiou, Maria; Haymart, Megan R.

    2014-01-01

    Purpose of review Numerous staging and scoring systems exist for differentiated thyroid cancer (DTC), but all harbor limitations. This has prompted investigation for new factors with prognostic implications for DTC. Recent findings Several new factors that may be involved in DTC risk stratification have emerged, such as thyroid stimulating hormone and molecular markers. In addition, others are controversial and being challenged, such as age, gender and lymph node involvement. Summary The purpose of this review is to present recent updates in the literature on new potential risk stratification predictors for DTC. PMID:24285100

  10. Pituitary metastases from the oncocytic variant of follicular thyroid carcinoma: a case report and diagnostic dilemmas.

    PubMed

    Matyja, Ewa; Zieliński, Grzegorz; Witek, Przemysław; Kamiński, Grzegorz; Grajkowska, Wiesława; Maksymowicz, Maria

    2013-01-01

    Metastases to the pituitary gland and sella turcica are uncommon. The distinction between primary and secondary metastatic pituitary tumours is challenging as carcinomas from distant sites might closely resemble, both clinically and histopathologically, non-functional adenomas or primary pituitary carcinomas. Among metastases to pituitary gland ones from thyroid carcinoma are extremely rare. We present a unique case of a 53-year-old male patient with a past history of thyroid carcinoma who underwent repeated surgeries over a period of 7 years for a sellar-parasellar mass with paranasal sinus involvement. Morphologically, the tumour was composed of solid sheaths of monomorphic cells exhibiting oncocytic features. In electron microscope images, the cytoplasm of tumour cells was filled with numerous mitochondria. The tumour was negative for pituitary hormones but exhibited immunoreactivity for cytokeratin AE1/AE3, thyroglobulin and thyroid transcription factor 1 (TTF-1). Based on the clinical data and immunophenotypic profile, the tumour was finally diagnosed as an oncocytic variant of follicular thyroid carcinoma. To our knowledge, this is probably the first report of such peculiar histopathological variant of follicular thyroid carcinoma metastasizing to the pituitary gland. The diagnostic dilemmas considering oncocytic features of the presented case are discussed. PMID:24114644

  11. Accuracy of fine-needle aspiration biopsy for predicting neoplasm or carcinoma in thyroid nodules 4 cm or larger

    PubMed Central

    Pinchot, Scott N.; Al-Wagih, Hatem; Schaefer, Sarah; Sippel, Rebecca; Chen, Herbert

    2010-01-01

    Hypothesis All thyroid nodules ≥4 cm should be surgically removed regardless of fine-needle aspiration biopsy (FNAB) results due to an unacceptably high rate of false-negative pre-operative biopsies in these large nodules. Design Retrospective cohort study. Setting Single institution, tertiary academic referral center. Patients and Methods A retrospective analysis was done on all patients who underwent surgery for a thyroid nodule ≥4 cm from 5/94 through 1/07. Preoperative FNAB results were correlated with final surgical pathologic results. FNAB results were reported as non-diagnostic, benign, inconclusive (follicular neoplasm), or malignant while final surgical pathologic data was reported as benign or malignant. Results Of 155 patients who had a thyroidectomy for a ≥4cm nodule, 21 patients (14%) had clinically significant thyroid carcinoma within the ≥4cm nodule on final pathology. Preoperative cytology of the ≥4cm mass was obtained and read as benign in 52/97 patients, inconclusive in 23/97 patients, non-diagnostic in 11/97 patients, and malignant in 11/97 patients. In lesions ≥4cm, 26/52 (50%) FNAB results reported as benign turned out to be either neoplastic (22/52) or malignant (4/52) on final pathology. Among patients with non-diagnostic FNAB, the risk of malignancy was 27%. Conclusions In patients with thyroid nodules ≥4cm, FNAB results are highly inaccurate, misclassifying half of all patients with reportedly benign lesions on FNAB. Furthermore, those patients with a non-diagnostic FNAB display a very high risk of differentiated thyroid carcinoma. Therefore, we recommend that diagnostic lobectomy, at a minimum, be performed in patients with thyroid nodules ≥4 cm regardless of FNA cytology. PMID:19620545

  12. 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.

  13. Results of Surgical Therapy in Patients with Medullary Thyroid Carcinoma.

    PubMed

    Vlad, Mihaela; Zosin, Ioana; Timar, Bogdan; Lazar, Fulger; Vlad, Adrian; Timar, Romulus; Cornianu, Marioara

    2016-08-01

    Medullary thyroid carcinoma (MTC) is a rare form of malignancy, having an intermediate prognosis. Controversies exist regarding the best surgical approach. The aim of the study was to analyze the outcome in a group of patients with MTC, diagnosed and followed up in a single care center. We performed a retrospective analysis of all the patients diagnosed with MTC in the Department of Endocrinology from the County Emergency Hospital Timisoara between 1992 and 2012. The study group included 19 patients, 6 men (31.6 %), mean age 41.2 ± 12.5 years (20-72 years). The preoperative diagnosis was based on the protocol for nodular thyroid disease. Total or near-total thyroidectomy was performed in 10 out of 16 patients who could be operated. Postoperative follow-up included repeated measurements of serum calcitonin and imaging investigations. Nine out of the total of 19 (47.3 %) patients had hereditary forms of MTC. Most of the cases (84.2 %) were submitted to surgery. The median duration of follow-up was 84 months. The pTNM staging indicated that the majority of the patients with hereditary MTC were diagnosed in an earlier stage. Disease remission was achieved in 7 cases (43.8 %). Four patients, all with sporadic forms, died. Survival rates at 1, 5 and 10 years were significantly higher (p = 0.048) in patients with hereditary MTC. An early diagnosis of MTC allows a better surgical approach and an improved survival rate. We support the general recommendation that modified radical neck dissection is not necessary for all the patients with MTC. PMID:27574350

  14. Trefoil factor 3 (TFF3): a promising indicator for diagnosing thyroid follicular carcinoma.

    PubMed

    Takano, Toru; Yamada, Hiroya

    2009-01-01

    Since the introduction of fine needle aspiration biopsy (FNAB) in the 1970's, a preoperative diagnostic technique for thyroid follicular carcinoma has long been awaited. Many markers that distinguish follicular carcinomas from adenomas have been reported; however, most of them have not been confirmed to be beneficial for clinical use. Trefoil factor 3 (TFF3) is a relatively new family of peptides that bears the three-loop trefoil domain. Several groups have reported that the suppression of TFF3 mRNA expression is related to malignant characteristics of thyroid follicular cell-derived tumors and the expression level of TFF3 mRNA is the most promising indicator for diagnosing follicular carcinoma. Development of TFF3-based diagnostic methods is now ongoing and it may not be long before thyroid follicular carcinoma can be diagnosed preoperatively using an aspirated sample from the tumor.

  15. Thyroid function after radiotherapy and laryngectomy for carcinoma of the larynx

    SciTech Connect

    Palmer, B.V.; Gaggar, N.; Shaw, H.J.

    1981-01-01

    Total levels of thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured in 37 patients who had previously had carcinoma of the larynx treated by radiotherapy and total laryngectomy with thyroid lobectomy. Ten percent of the patients had clinical features of hypothyroidism and 30% had total T4 levels below the lower limit of normal. A further 40% had results in the low normal range. Forty-four percent of patients had raised TSH levels, 90% of these having low or low normal T4 levels. The histology of the thyroid gland was normal in all 37 patients. Attention should be given to preserving intact the vasculature of the contralateral thyroid lobe whenever it is necessary to remove the ipsilateral thyroid lobe during a laryngectomy. Proper postoperative assessment of thyroid gland function is desirable in all these patients to identify those at risk of hypothyroidism and to avoid unnecessary morbidity.

  16. Oncologic Safety of Robot Thyroid Surgery for Papillary Thyroid Carcinoma: A Comparative Study of Robot versus Open Thyroid Surgery Using Inverse Probability of Treatment Weighting.

    PubMed

    Sung, Tae-Yon; Yoon, Jong Ho; Han, Minkyu; Lee, Yi Ho; Lee, Yu-Mi; Song, Dong Eun; Chung, Ki-Wook; Kim, Won Bae; Shong, Young Kee; Hong, Suck Joon

    2016-01-01

    The aim of this study was to evaluate the oncologic safety of robot thyroid surgery compared to open thyroid surgery for papillary thyroid carcinoma (PTC). We enrolled 722 patients with PTC who underwent a total thyroidectomy with central compartment node dissection (CCND) from January 2009 to December 2010. These patients were classified into open thyroid surgery (n = 610) or robot thyroid surgery (n = 112) groups. We verified the impact of robot thyroid surgery on clinical recurrence and ablation/control-stimulated thyroglobulin (sTg) levels predictive of non-recurrence using weighted logistic regression models with inverse probability of treatment weighting (IPTW). Age, sex, thyroid weight, extent of CCND, and TNM were significantly different between the two groups (p < 0.05); however, there was no significant difference in recurrence between the open and robot groups (1.5% vs. 2.7%; p = 0.608). The proportion of patients with ablation sTg < 10.0 ng/mL and control sTg < 1.0 ng/mL was comparable between the two groups (p > 0.05). Logistic regression with IPTW using the propensity scores estimated by adjusting all of the parameters demonstrated that robot thyroid surgery did not influence the clinical recurrence (OR; 0.784, 95% CI; 0.150-3.403, p = 0.750), ablation sTg (OR; 0.950, 95% CI; 0.361-2.399, p = 0.914), and control sTg levels (OR; 0.498, 95% CI; 0.190-1.189, p = 0.130). Robot thyroid surgery is comparable to open thyroid surgery with regard to oncologic safety in PTC patients.

  17. Oncologic Safety of Robot Thyroid Surgery for Papillary Thyroid Carcinoma: A Comparative Study of Robot versus Open Thyroid Surgery Using Inverse Probability of Treatment Weighting

    PubMed Central

    Sung, Tae-Yon; Yoon, Jong Ho; Han, Minkyu; Lee, Yi Ho; Lee, Yu-mi; Song, Dong Eun; Chung, Ki-Wook; Kim, Won Bae; Shong, Young Kee; Hong, Suck Joon

    2016-01-01

    The aim of this study was to evaluate the oncologic safety of robot thyroid surgery compared to open thyroid surgery for papillary thyroid carcinoma (PTC). We enrolled 722 patients with PTC who underwent a total thyroidectomy with central compartment node dissection (CCND) from January 2009 to December 2010. These patients were classified into open thyroid surgery (n = 610) or robot thyroid surgery (n = 112) groups. We verified the impact of robot thyroid surgery on clinical recurrence and ablation/control-stimulated thyroglobulin (sTg) levels predictive of non-recurrence using weighted logistic regression models with inverse probability of treatment weighting (IPTW). Age, sex, thyroid weight, extent of CCND, and TNM were significantly different between the two groups (p < 0.05); however, there was no significant difference in recurrence between the open and robot groups (1.5% vs. 2.7%; p = 0.608). The proportion of patients with ablation sTg < 10.0 ng/mL and control sTg < 1.0 ng/mL was comparable between the two groups (p > 0.05). Logistic regression with IPTW using the propensity scores estimated by adjusting all of the parameters demonstrated that robot thyroid surgery did not influence the clinical recurrence (OR; 0.784, 95% CI; 0.150–3.403, p = 0.750), ablation sTg (OR; 0.950, 95% CI; 0.361–2.399, p = 0.914), and control sTg levels (OR; 0.498, 95% CI; 0.190–1.189, p = 0.130). Robot thyroid surgery is comparable to open thyroid surgery with regard to oncologic safety in PTC patients. PMID:27285846

  18. Pluripotency markers are differentially induced by MEK inhibition in thyroid and melanoma BRAFV600E cell lines.

    PubMed

    Dorris, Emma R; Blackshields, Gordon; Sommerville, Gary; Alhashemi, Mohsen; Dias, Andrew; McEneaney, Victoria; Smyth, Paul; O'Leary, John J; Sheils, Orla

    2016-05-01

    Oncogenic mutations in BRAF are common in melanoma and thyroid carcinoma and drive constitutive activation of the MAPK pathway. Molecularly targeted therapies of this pathway improves survival compared to chemotherapy; however, responses tend to be short-lived as resistance invariably occursCell line models of melanoma and thyroid carcinoma, +/- BRAF(V600E) activating mutation, were treated with the MEK inhibitor PD0325901. Treated and naive samples were assayed for expression of key members of the MAPK pathway. Global microRNA expression profiling of naive and resistant cells was performed via next generation sequencingand indicated pluripotency pathways in resistance. Parental cell lines were progressed to holoclones to confirm the miRNA stemness profileMembers of the MIR302/373/374/520 family of embryonic stem cell specific cell cycle regulating (ESCC) microRNAs were identified as differentially expressed between resistant BRAF(V600E) melanoma and thyroid cell lines. Upregulated expression of gene and protein stemness markers, upregulated expression of MAPK pathway genes and downregulation of the ESCC MIR302 cluster in BRAF(V600E) melanoma indicated an increased stem-like phenotype in resistant BRAF(V600E) melanoma. Conversely, downregulated expression of gene and protein stemness markers, downregulated expression of MAPK pathway genes, upregulation of the ESCC MIR520 cluster, reeexpression of cell surface receptors, and induced differentiation-associated morphology in resistant BRAF(V600E) indicate a differentiated phenotype associated with MEK inhibitor resistance in BRAF(V600E) thyroid cellsThe differential patterns of resistance observed between BRAF(V600E) melanoma and thyroid cell lines may reflect tissue type or de novo differentiation, but could have significant impact on the response of primary and metastatic cells to MEK inhibitor treatment. This study provides a basis for the investigation of the cellular differentiation/self-renewal access and its

  19. Pluripotency markers are differentially induced by MEK inhibition in thyroid and melanoma BRAFV600E cell lines.

    PubMed

    Dorris, Emma R; Blackshields, Gordon; Sommerville, Gary; Alhashemi, Mohsen; Dias, Andrew; McEneaney, Victoria; Smyth, Paul; O'Leary, John J; Sheils, Orla

    2016-05-01

    Oncogenic mutations in BRAF are common in melanoma and thyroid carcinoma and drive constitutive activation of the MAPK pathway. Molecularly targeted therapies of this pathway improves survival compared to chemotherapy; however, responses tend to be short-lived as resistance invariably occursCell line models of melanoma and thyroid carcinoma, +/- BRAF(V600E) activating mutation, were treated with the MEK inhibitor PD0325901. Treated and naive samples were assayed for expression of key members of the MAPK pathway. Global microRNA expression profiling of naive and resistant cells was performed via next generation sequencingand indicated pluripotency pathways in resistance. Parental cell lines were progressed to holoclones to confirm the miRNA stemness profileMembers of the MIR302/373/374/520 family of embryonic stem cell specific cell cycle regulating (ESCC) microRNAs were identified as differentially expressed between resistant BRAF(V600E) melanoma and thyroid cell lines. Upregulated expression of gene and protein stemness markers, upregulated expression of MAPK pathway genes and downregulation of the ESCC MIR302 cluster in BRAF(V600E) melanoma indicated an increased stem-like phenotype in resistant BRAF(V600E) melanoma. Conversely, downregulated expression of gene and protein stemness markers, downregulated expression of MAPK pathway genes, upregulation of the ESCC MIR520 cluster, reeexpression of cell surface receptors, and induced differentiation-associated morphology in resistant BRAF(V600E) indicate a differentiated phenotype associated with MEK inhibitor resistance in BRAF(V600E) thyroid cellsThe differential patterns of resistance observed between BRAF(V600E) melanoma and thyroid cell lines may reflect tissue type or de novo differentiation, but could have significant impact on the response of primary and metastatic cells to MEK inhibitor treatment. This study provides a basis for the investigation of the cellular differentiation/self-renewal access and its

  20. Pluripotency markers are differentially induced by MEK inhibition in thyroid and melanoma BRAFV600E cell lines

    PubMed Central

    Dorris, Emma R.; Blackshields, Gordon; Sommerville, Gary; Alhashemi, Mohsen; Dias, Andrew; McEneaney, Victoria; Smyth, Paul; O'Leary, John J.; Sheils, Orla

    2016-01-01

    ABSTRACT Oncogenic mutations in BRAF are common in melanoma and thyroid carcinoma and drive constitutive activation of the MAPK pathway. Molecularly targeted therapies of this pathway improves survival compared to chemotherapy; however, responses tend to be short-lived as resistance invariably occursCell line models of melanoma and thyroid carcinoma, +/− BRAFV600E activating mutation, were treated with the MEK inhibitor PD0325901. Treated and naive samples were assayed for expression of key members of the MAPK pathway. Global microRNA expression profiling of naive and resistant cells was performed via next generation sequencingand indicated pluripotency pathways in resistance. Parental cell lines were progressed to holoclones to confirm the miRNA stemness profileMembers of the MIR302/373/374/520 family of embryonic stem cell specific cell cycle regulating (ESCC) microRNAs were identified as differentially expressed between resistant BRAFV600E melanoma and thyroid cell lines. Upregulated expression of gene and protein stemness markers, upregulated expression of MAPK pathway genes and downregulation of the ESCC MIR302 cluster in BRAFV600E melanoma indicated an increased stem-like phenotype in resistant BRAFV600E melanoma. Conversely, downregulated expression of gene and protein stemness markers, downregulated expression of MAPK pathway genes, upregulation of the ESCC MIR520 cluster, reeexpression of cell surface receptors, and induced differentiation-associated morphology in resistant BRAFV600E indicate a differentiated phenotype associated with MEK inhibitor resistance in BRAFV600E thyroid cellsThe differential patterns of resistance observed between BRAFV600E melanoma and thyroid cell lines may reflect tissue type or de novo differentiation, but could have significant impact on the response of primary and metastatic cells to MEK inhibitor treatment. This study provides a basis for the investigation of the cellular differentiation/self-renewal access and its role

  1. Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors

    PubMed Central

    Menachem, A; Bodner, O; Pastor, J; Raz, A; Kloog, Y

    2015-01-01

    Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma. PMID:27551476

  2. Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors.

    PubMed

    Menachem, A; Bodner, O; Pastor, J; Raz, A; Kloog, Y

    2015-01-01

    Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma. PMID:27551476

  3. [Echotomography and color-Doppler in the diagnosis of thyroid carcinoma].

    PubMed

    Messina, G; Viceconti, N; Trinti, B

    1996-01-01

    Ultrasound examination of the thyroid gland is used extensively in the diagnosis of thyroid carcinoma: it is easy and rapid to perform and widely available. Ultrasound enables easy identification of the image of disease foci within the gland, especially when high frequency probes (7.5-10 MHz) are used. Thyroid nodules are subdivided on the basis of their echostructure into hypoechoic solid, isoechoic solid, and hyperechoic solid, mixed, and liquid. In neoplastic pathologies, a hypoechoic echostructure is not pathognomonic of malignancy but must be regarded with suspicion, especially if it is an isolated nodule in a male patient and continues to grow during suppressive therapy. In fact, thyroid neoplasms evidence a hypoechoic echostructure in 60-70% of the cases, while a hyperechoic echostructure is present in only 2-4%. Only 15-25% of neoplasms appear as isoechoic nodules; a mixed echostructure is rarely (5-10% of the cases) seen. Color-Doppler patterns are classified into four types: I) nodules without internal or perinodular vascularization; II) nodules with vascularization confined to extranodular tissue; III) nodules with significant intra- and perinodular vascularization; IV) increased vascularization (or "thyroid inferno"). The vast majority of thyroid carcinoma (90%) presents type III vascularization. We therefore suggest the routine use of ultrasonography and color-Doppler studies in conjunction with fine-needle aspiration cytology for the diagnostic evaluation of thyroid carcinoma.

  4. Malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously: A case report.

    PubMed

    Ozgun, Alpaslan; Tuncel, Tolga; Emirzeoglu, Levent; Celik, Serkan; Bilgi, Oguz; Haholu, Abdullah; Urhan, Muammer; Karagoz, Bulent

    2015-01-01

    Malignant melanoma can be successfully treated when it is identified in its early stages, but the disease is associated with a poor prognosis when it is detected in an advanced stage. Papillary thyroid carcinoma is a thyroid cancer that has a good prognosis. The present study reports a rare case of malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously. The present patient was a 37-year-old male, in whom examination of a skin biopsy that was obtained from a lesion in the right retroauricular region revealed the lesion to be consistent with malignant melanoma. The patient underwent radical neck dissection upon the detection of malignant melanoma metastasis to the sentinel lymph node. Metastases of papillary thyroid carcinoma were detected in four out of 38 lymph nodes. The patient was then diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The patient was administered with high-dose followed by moderate-dose interferon-α therapy for the treatment of malignant melanoma. The patient also received concurrent radioactive iodine therapy for the treatment of papillary thyroid carcinoma, at the same time as the interferon therapy. The two primary tumors of the patient were treated successfully. During therapy, no serious side-effects were observed, with the exception of fever caused by high-dose interferon therapy. Malignant melanoma and papillary thyroid carcinoma may occur concurrently, although this is rarely observed. The present study reports a rare case that demonstrates that the two tumors can be successfully treated simultaneously. PMID:25436010

  5. Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma.

    PubMed

    Izkhakov, Elena; Somjen, Dalia; Sharon, Orli; Knoll, Esther; Aizic, Asaf; Fliss, Dan M; Limor, Rona; Stern, Naftali

    2016-05-01

    Genes regulated cell-cell and cell-matrix adhesion and degradation of the extracellular matrix (ECM) have been screened as potential markers of malignant thyroid nodules. The mRNA expression levels of two of them, the ECM protein-1 (ECM1) and the type II transmembrane serine protease-4 (TMPRSS4), were shown to be an independent predictor of an existing thyroid carcinoma. The vitamin D receptor (VDR) is expressed in epithelial cells of the normal thyroid gland, as well as in malignant dividing cells, which respond to the active metabolite of vitamin D by decreased proliferative activity in vitro. We evaluated the relationship between mRNA gene expressions of TMPRSS4, ECM1 and VDR in 21 papillary thyroid carcinoma samples and compared it to 21 normal thyroid tissues from the same patients. Gene expression was considered as up- or down-regulated if it varied by more or less than 2-fold in the cancer tissue relative to the normal thyroid tissue (Ca/N) from the same patient. We found an overall significant adjusted correlation between the mRNA expression ratio (ExR) of VDR and that of ECM1 in Ca/N thyroid tissue (R=0.648, P<0.001). There was a high ExR of VDR between Ca/N thyroid tissue from the same patient (3.06±2.9), which also exhibited a high Ca/N ExR of ECM1 and/or of TMPRSS4 (>2, P=0.05).The finding that increased VDR expression in human thyroid cancer cells is often linked to increased ECM1 and/or TPMRSS4 expression warrants further investigation into the potential role of vitamin D analogs in thyroid carcinoma.

  6. Serum calprotectin: a new potential biomarker for thyroid papillary carcinoma.

    PubMed

    Tabur, S; Korkmaz, H; Özkaya, M; Elboğa, U; Tarakçıoglu, M; Aksoy, N; Akarsu, E

    2015-09-01

    The aim of this study was to evaluate serum calprotectin levels and oxidative stress status in patients with papillary thyroid carcinoma (PTC) and the changes in their levels after total thyroidectomy. The study involved 30 patients with PTC and 30 healthy controls. Blood samples were obtained from the PTC patients before and 1 month after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analysed for calprotectin, total antioxidant status (TAS), total oxidant status (TOS) and lipid hydroperokside (LOOH). The preoperative calprotectin, TOS, OSI and LOOH levels of the patients with PTC were significantly higher compared to those of the control group (p < 0.001, for each). The levels of calprotectin decreased significantly in patients with PTC after the operation (p < 0.001), while TAS, TOS and OSI levels remained unchanged (p = 0.313, p = 0.085 and p = 0.163, respectively). Preoperative serum calprotectin levels were positively correlated with TOS, OSI and LOOH levels and negatively correlated with TAS levels in patients with PTC. In conclusion, serum calprotectin levels is increased in patients with PTC, and calprotectin is positively correlated with TOS and LOOH. Serum calprotectin levels is significantly decreased after total thyroidectomy.

  7. Gene expression and the biological phenotype of papillary thyroid carcinomas.

    PubMed

    Delys, L; Detours, V; Franc, B; Thomas, G; Bogdanova, T; Tronko, M; Libert, F; Dumont, J E; Maenhaut, C

    2007-12-13

    The purpose of this paper is to correlate the molecular phenotype of papillary thyroid carcinoma (PTC) to their biological pathology. We hybridized 26 PTC on microarrays and showed that nearly 44% of the transcriptome was regulated in these tumors. We then combined our data set with two published PTC microarray studies to produce a platform- and study-independent list of PTC-associated genes. We further confirmed the mRNA regulation of 15 genes from this list by quantitative reverse transcription-PCR. Analysis of this list with statistical tools led to several conclusions: (1) there is a change in cell population with an increased expression of genes involved in the immune response, reflecting lymphocyte infiltration in the tumor compared to the normal tissue. (2) The c-jun N-terminal kinase pathway is activated by overexpression of its components. (3) The activation of ERKK1/2 by genetic alterations is supplemented by activation of the epidermal growth factor but not of the insulin-like growth factor signaling pathway. (4) There is a downregulation of immediate early genes. (5) We observed an overexpression of many proteases in accordance with tumor remodeling, and suggested a probable role of S100 proteins and annexin A2 in this process. (6) Numerous overexpressed genes favor the hypothesis of a collective migration mode of tumor cells.

  8. Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves’ Disease

    PubMed Central

    Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

    2014-01-01

    Abstract Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves’ disease. She was diagnosed with Graves’ disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves’ disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves’ disease, few reports about thyroid cancer accompanied by Graves’ disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves’ disease. PMID:24790388

  9. Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines.

    PubMed

    Parisi, Marguerite T; Eslamy, Hedieh; Mankoff, David

    2016-03-01

    First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association.

  10. [Mucocele of the frontal sinus simulating metastasis of follicular thyroid carcinoma in an 131I scan].

    PubMed

    Duque Gallo, J J; Miguel Martínez, M B; Castillo López, L; Ruiz Pérez, E; Rubio Sanz, M J; Zamora Pérez, B; Casado Pérez, C; Rodríguez Salazar, A; Claver Criado, M; Calvo Del Castillo, J I

    1999-12-01

    The 131I scan is the preferred test in the follow-up of differentiated thyroid cancer patients although the many unusual circumstances of radioiodine uptake that can provide false positive results must be identified. We present the case of a woman who had undergone a thyroidectomy and was being treated for follicular carcinoma with an ablative dose os radioiodine whose pre- and post-treatment scans only revealed post-surgical residual thyroid tissues. A total body scan with 131I performed at one year demonstrated the success of the ablation. However, a left supra-orbital pathological deposit was observed during a subsequent routine 131I scan. The thyroglobulin serum level was below the sensitivity level for the assay (< 1 ng/ml) and the serum antibodies against thyroglobulin were not detected. A simple x-ray and bone scintigraphy were inconclusive. The CT and MRI revealed the presence of a mucocele in the left frontal sinus which was confirmed through histological examination. The possibility of a false positive results in an 131I scan must always be kept in mind, especially in the presence of atypical uptakes and undetectable thyroglobulin serum levels. As far as we know, only one similar case has been published previously.

  11. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging of an isolated subcutaneous loin metastasis from primary papillary carcinoma of the thyroid

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Shibu, Deepu; Edathurthy, Radhakrishnan; Shinto, Ajit Sugunan

    2014-01-01

    Differentiated thyroid cancer frequently metastasizes but generally spreads to regional cervical lymph nodes and, in advanced cases, to the lungs and/or skeleton. Metastases to the skin/subcutaneous tissue are rare. We report 45-year-old male patient presented with a loin swelling which on biopsy showed a papillary carcinoma and referred for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) to find out the primary disease. PET/CT showed abnormal FDG uptake within a loin metastasis and right lobe thyroid nodule. Fine-needle aspiration from nodule showed papillary carcinoma. Because thyroid cancer can rarely metastasize to the skin, attention should be given to that region during interpretation of the images. He was advised total thyroidectomy and metastasis excision. PMID:24761062

  12. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging of an isolated subcutaneous loin metastasis from primary papillary carcinoma of the thyroid.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Shibu, Deepu; Edathurthy, Radhakrishnan; Shinto, Ajit Sugunan

    2014-04-01

    Differentiated thyroid cancer frequently metastasizes but generally spreads to regional cervical lymph nodes and, in advanced cases, to the lungs and/or skeleton. Metastases to the skin/subcutaneous tissue are rare. We report 45-year-old male patient presented with a loin swelling which on biopsy showed a papillary carcinoma and referred for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) to find out the primary disease. PET/CT showed abnormal FDG uptake within a loin metastasis and right lobe thyroid nodule. Fine-needle aspiration from nodule showed papillary carcinoma. Because thyroid cancer can rarely metastasize to the skin, attention should be given to that region during interpretation of the images. He was advised total thyroidectomy and metastasis excision.

  13. Thyroid-like Follicular Carcinoma of the Kidney and Papillary Renal Cell Carcinoma with Thyroid-like Feature: Comparison of Two Cases and Literature Review.

    PubMed

    Li, Congcong; Dong, Hongyan; Fu, Weiwei; Qi, Mei; Han, Bo

    2015-01-01

    Thyroid-like follicular carcinoma of the kidney (TLFCK) is a provisional new entity of renal cell carcinoma (RCC). We herein reported and compared one TLFCK case and one PRCC case with thyroid-like feature. The former entirely consisted of thyroid-like follicular architecture and the tumor cells were diffusely positive for PAX-8, but negative for CK7, AMACR, and CD10. By contrast, both papillary architecture (~60%) and thyroid-like follicular architecture (~40%) were identified in the latter. Tumor cells in both histological components exhibited diffusely positive staining for PAX-8, CK7, AMACR, but negative for CD10. FISH analysis showed no aberration in TLFCK case but trisomy of chromosome 17 in PRCC case. Along with a brief literature review, we presented that recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features. Additionally, a diagnosis of TLFCK should be cautiously made when papillary component is present in the tumor. PMID:26663803

  14. Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma

    PubMed Central

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

    2016-01-01

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

  15. Histopathological and immunohistochemical findings of primary and metastatic medullary thyroid carcinoma in a young dog

    PubMed Central

    Vieson, Miranda D.; Ramos-Vara, José A.; Moon-Larson, Martha; Saunders, Geoffrey

    2014-01-01

    This report describes the gross, histological, and immunohistochemical features of medullary thyroid carcinoma (MTC) with pulmonary metastases in a young dog. Sheets of pleomorphic cells supported by fibrous stroma characterized the primary mass, while metastatic nodules had a neuroendocrine pattern. Despite differing histologic features, all masses showed marked immunoreactivity against calcitonin and multiple neuroendocrine markers consistent with MTC. Although MTC is a well-recognized entity, it may be difficult to distinguish this mass from other thyroid neoplasms, necessitating immunohistochemical characterization. PMID:24690600

  16. RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture.

    PubMed

    Santoro, Massimo; Melillo, Rosa Marina; Fusco, Alfredo

    2006-11-01

    Papillary thyroid carcinoma (PTC) is frequently associated with RET gene rearrangements that generate the so-called RET/PTC oncogenes. In this review, we examine the data about the mechanisms of thyroid cell transformation, activation of downstream signal transduction pathways and modulation of gene expression induced by RET/PTC. These findings have advanced our understanding of the processes underlying PTC formation and provide the basis for novel therapeutic approaches to this disease.

  17. RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture.

    PubMed

    Santoro, Massimo; Melillo, Rosa Marina; Fusco, Alfredo

    2006-11-01

    Papillary thyroid carcinoma (PTC) is frequently associated with RET gene rearrangements that generate the so-called RET/PTC oncogenes. In this review, we examine the data about the mechanisms of thyroid cell transformation, activation of downstream signal transduction pathways and modulation of gene expression induced by RET/PTC. These findings have advanced our understanding of the processes underlying PTC formation and provide the basis for novel therapeutic approaches to this disease. PMID:17062879

  18. Recurrence of papillary thyroid carcinoma presenting as a focal neurologic deficit

    SciTech Connect

    Parker, L.N.; Wu, S.Y.; Kim, D.D.; Kollin, J.; Prasasvinichai, S.

    1986-10-01

    Papillary-follicular thyroid carcinoma usually remains localized to the thyroid bed and, in cases of metastasis, almost always involves the lung, bone, or liver. The two patients described here presented with papillary carcinoma and neurologic dysfunction. Total body iodine 131 scans disclosed cerebral uptake, and cerebral masses were confirmed by computed tomographic scan. Both patients presented diagnostic and therapeutic dilemmas, and ultimately underwent craniotomy. One patient's cerebral metastasis recurred and was treated by a second craniotomy. The other patient received postoperative external cerebral radiotherapy and a novel intraoperative treatment: implantation of 22 iodine 125 seeds in the tumor bed, estimated to yield 16,000 rad (160 Gy) in one year. To date, cerebral metastases have not recurred in the latter patient, although tumor has reappeared in other sites. There is little reported in the medical literature concerning cerebral metastases of thyroid carcinoma, and the present report reviews this experience and discusses treatment alternatives.

  19. MEN1 Mutations in Hürthle Cell (Oncocytic) Thyroid Carcinoma

    PubMed Central

    Kasaian, Katayoon; Chindris, Ana-Maria; Wiseman, Sam M.; Mungall, Karen L.; Zeng, Thomas; Tse, Kane; Schein, Jacqueline E.; Rivera, Michael; Necela, Brian M.; Kachergus, Jennifer M.; Casler, John D.; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Copland, John A.; Thompson, E. Aubrey; Smallridge, Robert C.

    2015-01-01

    Context and Objective: Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Design and Patients: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. Results: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. Conclusion: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis. PMID:25625803

  20. Heterogeneous echogenicity of the thyroid parenchyma does not influence the detection of multi-focality in papillary thyroid carcinoma on preoperative ultrasound staging.

    PubMed

    Herh, Sun Jin; Kim, Eun-Kyung; Sung, Ji Min; Yoon, Jung Hyun; Moon, Hee Jung; Kwak, Jin Young

    2014-05-01

    Heterogeneous echogenicity and micro-nodulations of diffuse thyroid disease on ultrasonography (US) might influence the diagnostic performance of pre-operative US staging, especially the detection of multi-focality. This study was designed to determine whether heterogeneous echogenicity of the thyroid parenchyma influences the diagnostic performance of US in the detection of multi-focality in papillary thyroid carcinoma. Between December 2010 and April 2011, 811 patients underwent pre-operative staging US for papillary thyroid carcinoma and surgery. Twelve radiologists performed the pre-operative US for T and N staging. Underlying parenchymal echogenicity and unilateral and bilateral multi-focality of the thyroid nodules were also evaluated. Patients were divided into two groups on the basis of the underlying echogenicity of the thyroid gland. To evaluate the diagnostic accuracy of US with respect to underlying echogenicity, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated and compared between the two groups. Among the 811 patients included, US revealed underlying heterogeneous echogenicity of the thyroid parenchyma in 204 (25.2%) and underlying homogeneous echogenicity of the thyroid parenchyma in 607 (74.8%). There were no significant differences between the two groups in the diagnostic performance of pre-operative staging US in predicting unilateral multi-focality and bilaterality. Underlying heterogeneous echogenicity in a thyroid gland with Hashimoto's thyroiditis does not significantly influence the detection of multi-focality in papillary thyroid cancer on pre-operative US staging.

  1. BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl.

    PubMed

    Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

    2015-11-20

    After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0-18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF(V600E) in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF(V600E) was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF(V600E) may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.

  2. BRAFV600E mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl

    PubMed Central

    Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

    2015-01-01

    After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0–18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAFV600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAFV600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAFV600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs. PMID:26584635

  3. BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl.

    PubMed

    Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

    2015-01-01

    After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0-18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF(V600E) in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF(V600E) was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF(V600E) may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs. PMID:26584635

  4. Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA

    SciTech Connect

    Edington, H.D.; Watson, C.G.; Levine, G.; Tauxe, W.N.; Yousem, S.A.; Unger, M.; Kowal, C.D.

    1988-12-01

    Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

  5. Impact of Squamous Differentiation in Breast Carcinoma.

    PubMed

    Pai, Trupti; Shet, Tanuja; Desai, Sangeeta; Patil, Asawari; Nair, Nita; Parmar, Vani; Gupta, Sudeep; Budrukkar, Ashwini; Sarin, Rajiv; Badwe, Rajendra

    2016-09-01

    This study attempted to review the impact of extent of squamous differentiation in 56 infiltrating duct carcinomas (IDC) with squamous differentiation (metaplastic squamous carcinomas [MSC]). Tumors showing 100% squamous elements were labeled as primary squamous carcinomas (PSC; n = 28) and compared with 28 MSC showing lesser squamous components. A clinicopathological comparison revealed that lymphovascular emboli were never seen in any PSC but were noted in 7/28 of other MSC, while perineural invasion was seen only in PSC and not in MSC. Nodal metastasis was significantly more in other MSC as opposed to PSC. Most MSC presented with 2- to 5-cm sized tumors while PSC were 5 to 10 cm in size. PSC showed cystic change while MSC did not. Disease free survival (DFS) for MSC versus PSC was 64% versus 39.8%, while overall survival (OAS) was 72.7% in MSC versus 66.7% in PSC. Tumor stage affected DFS in MSC while none of the factors affected DFS/OAS in PSC. The extent of squamous differentiation affected DFS with best behavior for metaplastic carcinomas showing <40% squamous elements and worse for those with >90% squamous component (P = .024). PSC of breast is an aggressive disease and show distinct clinicopathological features from other MSC, and though the current definition of MSC does not advocate quantifying the squamous element, clearly this affects prognosis. PMID:27076454

  6. Impact of Squamous Differentiation in Breast Carcinoma.

    PubMed

    Pai, Trupti; Shet, Tanuja; Desai, Sangeeta; Patil, Asawari; Nair, Nita; Parmar, Vani; Gupta, Sudeep; Budrukkar, Ashwini; Sarin, Rajiv; Badwe, Rajendra

    2016-09-01

    This study attempted to review the impact of extent of squamous differentiation in 56 infiltrating duct carcinomas (IDC) with squamous differentiation (metaplastic squamous carcinomas [MSC]). Tumors showing 100% squamous elements were labeled as primary squamous carcinomas (PSC; n = 28) and compared with 28 MSC showing lesser squamous components. A clinicopathological comparison revealed that lymphovascular emboli were never seen in any PSC but were noted in 7/28 of other MSC, while perineural invasion was seen only in PSC and not in MSC. Nodal metastasis was significantly more in other MSC as opposed to PSC. Most MSC presented with 2- to 5-cm sized tumors while PSC were 5 to 10 cm in size. PSC showed cystic change while MSC did not. Disease free survival (DFS) for MSC versus PSC was 64% versus 39.8%, while overall survival (OAS) was 72.7% in MSC versus 66.7% in PSC. Tumor stage affected DFS in MSC while none of the factors affected DFS/OAS in PSC. The extent of squamous differentiation affected DFS with best behavior for metaplastic carcinomas showing <40% squamous elements and worse for those with >90% squamous component (P = .024). PSC of breast is an aggressive disease and show distinct clinicopathological features from other MSC, and though the current definition of MSC does not advocate quantifying the squamous element, clearly this affects prognosis.

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

    SciTech Connect

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

    1994-02-01

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

  8. Expression of estrogen and progesterone receptors in papillary thyroid carcinoma

    PubMed Central

    Jalali-Nadoushan, Mohammad-Reza; Amirtouri, Reza; Davati, Ali; Askari, Samaneh; Siadati, Sepideh

    2016-01-01

    Background: Papillary thyroid carcinoma (PTC), occurs mostly in women and sex hormones may play a role in the pathogenesis and clinical course. The objective of this study was to determine the status and prevalence of estrogen and progesterone receptors in PTC with regard to age, gender, tumor size and lymph node involvement. Methods: Immunohistochemical stains were performed on 92 tissue blocks of PTC for estrogen receptor (ER) and progesterone receptor (PR) expression in tumor cells. Chi-square test and Mann-Whitney U test were used to determine statistical difference using statistical software SPSS. Results: The mean age of patients was 39.32±1.7 years (range 13-80) with 79(85.9%) women and 13 (14.1%) men. Lymph node involvement was seen in 76.1% of patients. The average tumor size was 3.6±2.21 cm. The rate of ER and PR expression were 46.75% and 5.6%, respectively. ER expression for females was higher than males (P=0.014), but no relation was found between males and females in PR expression (P=0.7). Also there was no statistical difference between ER and PR expression with respect to age, lymph node involvement and tumor size. Conclusion: Our study showed higher ER expression in females than males with PTC. No relation was found between the expression of these receptors and age of presentation, lymph node involvement and tumor size. Further investigation is required to determine the prognostic importance of ER and PR in PTC.

  9. Cervix carcinoma and incidental finding of medullary thyroid carcinoma by 18F-FDG PET/CT--clinical case.

    PubMed

    Chaushev, Borislav; Bochev, Pavel; Klisarova, Anelia; Yordanov, Kaloyan; Encheva, Elitsa; Dancheva, Jivka; Yordanova, Cvetelina; Hristozov, Kiril; Krasnaliev, Ivan; Radev, Radoslav; Nenkov, Rumen

    2014-01-01

    Thyroid nodules are encountered in clinical practice during the diagnostic procedures or patients' follow-up due to other diseases quite far from the thyroid gland with prevalence 4-50% in general population, depending on age, diagnostic method and race. The prevalence of thyroid nodules increases with age and their clarification should be done for their adequate treatment. An 18F-FDG PET/CT was done with a PET/CT scanner (Philips Gemini TF), consisting of dedicated lutetium orthosilicate full ring PET scanner and 16 slice CT. The PET/CT scan of the whole-body revealed on the CT portion a hypodense nodular lesion in the left lobe of the thyroid gland with increased uptake of 18F-FDG on the PET with SUVmax 10.3 and demonstrated a complete response to the induction therapy of the main oncological disease of the patient--squamous cell carcinoma. This clinical case demonstrates that whole-body 18F-FDG-PET/CT has an increasingly important role in the early evaluation of thyroid cancer as a second independent malignant localization. Focal thyroid lesion with high risk of thyroid malignancy was incidentally found on 18F-FDG PET/CT. PMID:25088110

  10. Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation.

    PubMed

    Damiola, Francesca; Byrnes, Graham; Moissonnier, Monika; Pertesi, Maroulio; Deltour, Isabelle; Fillon, Aurélie; Le Calvez-Kelm, Florence; Tenet, Vanessa; McKay-Chopin, Sandrine; McKay, James D; Malakhova, Irina; Masyakin, Vladimir; Cardis, Elisabeth; Lesueur, Fabienne; Kesminiene, Ausrele

    2014-04-01

    A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after childhood exposure to ionizing radiation from the Chernobyl nuclear accident has been described as the largest number of tumors of one type due to one cause that have ever occurred. inter-individual variations in response to radiation have been documented and the role of genetics in sporadic PTC is well established, suggesting that genetic factors may also affect the risk of radiation-related PTC. To investigate how environmental and host factors interplay to modify PTC risk, we genotyped 83 cases and 324 matched controls sampled from children living in the area contaminated by fallout from the Chernobyl power plant accident for 19 polymorphisms previously associated with PTC, thyroid biology or radiation-induced second primary tumors. Significant association with PTC was found for rs1801516 (D1853N) in ATM (odds ratio (OR) = 0.34, 95% confidence interval (CI) 0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR = 1.55, 95% CI 1.03, 2.34). Analysis of additional polymorphisms confirmed the association between these two genes and PTC. Our findings suggest that both DNA double-strand break repair pathway and thyroid morphogenesis pathway or dysregulation of thyroid differentiated state maintenance are involved in the etiology of PTC, and that the studied genetic polymorphisms and radiation dose appear to act as independent multiplicative risk factors for PTC.

  11. Significance of IMP3, nucleophosmin, and Ki-67 expression in papillary thyroid carcinoma.

    PubMed

    Yorukoglu, Aygun; Yalcin, Nagihan; Avci, Arzu; Cakalagaoglu, Fulya; Yaylali, Guzin; Akin, Fulya; Haciyanli, Mehmet; Ozden, Akin

    2015-02-01

    The purpose of our study was to investigate the diagnostic value of expression of IMP3, nucleophosmin, and correlation of these markers with Ki-67 proliferation index in papillary thyroid carcinoma and benign neoplasms of thyroid gland. The aim was also to investigate whether there is a difference between papillary and micropapillary carcinomas with regard to clinicopathologic parameters beside IMP3, nucleophosmin, and Ki-67 proliferation index. It was concluded that IMP3 and nucleophosmin cannot be a routine diagnostic marker for discrimination of papillary carcinomas and benign lesions. IMP3 positive staining was quite scarce in IMP3 positive papillary carcinomas although specifity of IMP3 is 100%. A statistically significant correlation was not detected between nucleophosmin, IMP-3, and Ki-67 proliferation index. A statistically significant correlation was found between tumor size, lymphovascular embolism, and Ki-67 proliferation index. There was also significant correlation between tumor size and lymphovascular embolism.

  12. Medullary thyroid carcinoma: a review on ethical considerations in treatment of children.

    PubMed

    Nozhat, Zahra; Hedayati, Mehdi

    2016-06-01

    Thyroid carcinoma is the most common malignancy of the endocrine system and it accounts approximately 1%-3% of all human cancers. Among the three subtypes of thyroid cancers, medullary thyroid carcinoma (MTC) is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN2A), MEN type 2B (MEN2B) and familial medullary thyroid carcinoma (FMTC). Generally, MTC accounts for up to 10% of all types of thyroid cancers. It is one of the aggressive forms of thyroid carcinoma which is manifested in childhood ages more than adults, and it comprises about 17% of all pediatric thyroid cancer. Like the other cancers, prevention of MTC is easier than its cure. In the recent decades (from 1993) the diagnosis of asymptomatic child carrying RET mutations in the affected families by MTC, has been provided by genetic screening, and prophylactic thyroidectomy is an efficacy therapeutic procedure. On the one hand, according to near the complete penetrance of the disease and its onset in the early years of life, it is required to accelerate the protection of at-risk children with relative affected by MTC and on the other hand, there are several obstructions to MTC treatment including: 1) the proband's refusal to disclose the RET mutation genetic testing results, 2) children's vulnerability because of their inability to participate in the informed consent, and 3) the existence of conflict between physicians and children's guardian. In this review article, the recommendations and ethical issues of MTC treatment in asymptomatic and at-risk children have been summarized. PMID:26974132

  13. CT-detected solitary thyroid calcification: an important imaging feature for papillary carcinoma

    PubMed Central

    Yang, Tian-tian; Huang, Yong; Jing, Xu-quan; Gai, Xiu-juan; Li, Wen-wu

    2016-01-01

    Purpose To evaluate computed tomography (CT) detection of solitary thyroid calcification for identifying thyroid papillary carcinoma and to determine whether the predictive ability changes when the size increases after enhancement. Materials and methods CT scans on all 96 patients with thyroid nodules who underwent both enhanced CT examination of neck and thyroidectomy from 2014 to 2016 in the Shandong Cancer Hospital affiliated to Shandong University were reviewed. The cases without calcification and the cases with peripheral calcification, multiple coarse calcifications, or punctate calcification were excluded. Imaging features, including location and size of the lesions, were reviewed on plain and contrast-enhanced CT. The patients were grouped by histological results. The comparisons were evaluated by using Fisher’s exact test and binary logistic regression. Results The study population consisted of 96 patients (74 females, 22 males; mean age 49.8±11.3 years). Papillary thyroid carcinoma was observed in both solitary calcified thyroid nodules (85.4%) and solely coarse calcifications surrounded by low-density focus (58.2%). The difference was significant (P=0.006). Of 64 patients with an amplification of lesions after contrast enhancement, 58 (90.6%) were diagnosed with a malignant lesion. At the same time, of the 32 patients with no increase in size, 10 (31.2%) were diagnosed with carcinoma and 22 (68.8%) with nodular goiter. This difference was significant (P<0.001), and after binary logistic regression, increasing size was an independent risk factor for cancer. Conclusion Solitary calcified thyroid nodules detected on CT represent a high risk for papillary thyroid carcinoma, especially when the size of the lesions increases after contrast- enhanced CT. PMID:27785075

  14. Helicase-like transcription factor: a new marker of well-differentiated thyroid cancers

    PubMed Central

    2014-01-01

    Background The preoperative characterization of thyroid nodules is a challenge for the clinicians. Fine-needle aspiration (FNA) is the commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. There is an urgent need to identify biomarkers that could be used with the FNA to distinguish benign thyroid nodules from malignant tumors. The purpose of the study is to examine the level of expression of the helicase-like transcription factor (HLTF) in relation to neoplastic progression of thyroid carcinomas. Methods The presence of HLTF was investigated using quantitative and semi-quantitative immunohistochemistry in a series of 149 thyroid lesion specimens. Our first clinical series was composed of 80 patients, including 20 patients presenting thyroid adenoma, 40 patients presenting thyroid papillary carcinoma, 12 patients presenting thyroid follicular carcinoma and 8 patients presenting anaplastic carcinoma. These specimens were assessed quantitatively using computer assisted microscopy. Our initial results were validated on a second clinical series composed of 40 benign thyroid lesions and 29 malignant thyroid lesions using a semi-quantitative approach. Finally, the HLTF protein expression was investigated by Western blotting in four thyroid cancer cell lines. Results The decrease of HLTF staining was statistically significant during thyroid tumor progression in terms of both the percentage of mean optical density (MOD), which corresponds to the mean staining intensity (Kruskall-Wallis: p < 0.0005), and the labelling index (LI), which corresponds to the percentage of immunopositive cells (Kruskall-Wallis: p < 10−6). Adenomas presented very pronounced nuclear HLTF immunostaining, whereas papillary carcinomas exhibited HLTF only in the cytoplasm. The number of HLTF positive nuclei was clearly higher in the adenomas group (30%) than in the

  15. 25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma

    PubMed Central

    Danilovic, Debora Lucia Seguro; Ferraz-de-Souza, Bruno; Fabri, Amanda Wictky; Santana, Nathalie Oliveira; Kulcsar, Marco Aurelio; Cernea, Claudio Roberto; Marui, Suemi; Hoff, Ana Oliveira

    2016-01-01

    Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules. PMID:27737011

  16. Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis

    PubMed Central

    Donkol, Ragab Hani; Nada, Aml Mohamed; Boughattas, Sami

    2013-01-01

    AIM: To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning. METHODS: Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups: 18 cases with Graves’ disease and 8 cases with Hashimoto’s thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves’ disease and Hashimoto’s thyroiditis was supported by the clinical picture and follow up of patients. RESULTS: Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves’ disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis. CONCLUSION: Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients. PMID:23671754

  17. Nodular thyroid disease in children and adolescents: a high incidence of carcinoma

    SciTech Connect

    McHenry, C.; Smith, M.; Lawrence, A.M.; Jarosz, H.; Paloyan, E.

    1988-07-01

    Over a period of 32 years from 1954 to 1986, 65 patients under the age of 21 years, 52 girls and 13 boys, were operated for nodular thyroids: the overall incidence of carcinoma was 37 per cent. It was 46 per cent in those patients presenting with a solitary nodule. Among the 24 patients with a malignancy, the carcinoma was of the papillary variety in 63 per cent, follicular in 25 per cent and medullary in 12 per cent. Two thirds of the patients had metastatic disease at the time of presentation. All patients with thyroid carcinoma were treated with total thyroidectomy. Other measures included neck dissection and radioactive iodine. When the eight patients with a history of head and neck irradiation and the three patients with medullary carcinoma were excluded, the incidence of carcinoma was 28 per cent. In summary, in spite of the decline in radiation associated cases, the incidence of carcinoma in nodular thyroid disease in the population under 21 years, remains at the relatively high figure of 28 per cent.

  18. Differentiated thyroid cancer in patients with resistance to thyroid hormone syndrome. A novel case and a review of the literature.

    PubMed

    Vinagre, João; Borges, Fátima; Costa, António; Alvelos, Maria Inês; Mazeto, Glaúcia; Sobrinho-Simões, Manuel; Soares, Paula

    2014-01-01

    Resistance to thyroid hormone (RTH) represents a syndrome in which patients present elevated circulating thyroid hormones in the presence of non-suppressed TSH. We report a novel case where a patient with RTH presented a differentiated thyroid cancer. A19 year-old female had been referred due to thyroid disease that disclosed features characteristic of a RTH. During the follow up it was detected a follicular tumor that led to the recommendation for thyroid surgical ablation, where an incidental papillary thyroid microcarcinoma (mPTC) was found. The increase of thyroglobulin (TG) levels following thyroid removal referred the patient for radioiodine treatment. Post-treatment, it was detected jugular adenopathies and the patient was subjected to cervical lymph node drainage where metastases of the mPTC were found. RTH syndrome was confirmed by the detection of a THRB germline mutation. A BRAF mutation was also found in the mPTC but not detected in the follicular adenoma or normal adjacent tissue. The young age of the patient, the rarity of BRAF mutations in childhood and the high dissemination of the malignancy, lead us to the speculation that increased TSH stimulation in a RTH background and oncogenic activation of BRAF could have served as (co) drivers and might have triggered an advanced stage of the neoplastic disease. These findings together with a review of published cases add novel information to the management of RTH patients with differentiated thyroid cancer. PMID:25988151

  19. Differentiated thyroid cancer in patients with resistance to thyroid hormone syndrome. A novel case and a review of the literature

    PubMed Central

    Vinagre, João; Borges, Fátima; Costa, António; Alvelos, Maria Inês; Mazeto, Glaúcia; Sobrinho-Simões, Manuel; Soares, Paula

    2014-01-01

    Resistance to thyroid hormone (RTH) represents a syndrome in which patients present elevated circulating thyroid hormones in the presence of non-suppressed TSH. We report a novel case where a patient with RTH presented a differentiated thyroid cancer. A19 year-old female had been referred due to thyroid disease that disclosed features characteristic of a RTH. During the follow up it was detected a follicular tumor that led to the recommendation for thyroid surgical ablation, where an incidental papillary thyroid microcarcinoma (mPTC) was found. The increase of thyroglobulin (TG) levels following thyroid removal referred the patient for radioiodine treatment. Post-treatment, it was detected jugular adenopathies and the patient was subjected to cervical lymph node drainage where metastases of the mPTC were found. RTH syndrome was confirmed by the detection of a THRB germline mutation. A BRAF mutation was also found in the mPTC but not detected in the follicular adenoma or normal adjacent tissue. The young age of the patient, the rarity of BRAF mutations in childhood and the high dissemination of the malignancy, lead us to the speculation that increased TSH stimulation in a RTH background and oncogenic activation of BRAF could have served as (co) drivers and might have triggered an advanced stage of the neoplastic disease. These findings together with a review of published cases add novel information to the management of RTH patients with differentiated thyroid cancer. PMID:25988151

  20. [Postradial sialozoadenitis in patients with papillary carcinoma of the thyroid gland].

    PubMed

    Kovalenko, V A; Kopchak, A V; Kovalenko, A E

    2015-01-01

    The authors present the results of investigation of 42 patients with salivary gland dysfunction after radioactive iodine-131 ablation therapy concerning papillary thyroid carcinoma. Clinical manifestations of postradial sialodenitis with secretory insufficiency of different degree were revealed. These side effects required an application of the special therapy.

  1. Combined Endonasal-Transcervical Approach to a Metastatic Parapharyngeal Space Papillary Thyroid Carcinoma

    PubMed Central

    Benet, Arnau; El-Sayed, Ivan

    2015-01-01

    Purpose: Although papillary thyroid carcinoma metastases to the parapharyngeal space are rare, the high amount of fat tissue allows tumors to grow clinically undetectable until they invade most of the parapharyngeal space. We describe for the first time a combined endonasal and transcervical approach for a parapharyngeal metastasis from a papillary thyroid carcinoma. Materials and Methods: A 51-year-old male with a previous history of papillary thyroid carcinoma presented with left ear fullness and left-sided facial numbness. Imaging revealed a 4x3 cm pre-styloid parapharyngeal space mass invading the foramen ovale and extending below the palate. Needle biopsy confirmed metastatic papillary thyroid carcinoma. Results: The lesion was resected with a combined endoscopic endonasal and transcervical approach. Postoperative MRI revealed gross total resection, and the patient recovered from his symptoms. Conclusion: This novel approach provides access to pre-styloid parapharyngeal tumors with superior extension to the skull base, avoiding more extensive traditional open approaches. PMID:26203403

  2. Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma.

    PubMed

    Van Nostrand, Douglas; Atkins, Frank; Yeganeh, Fred; Acio, Elmo; Bursaw, Randy; Wartofsky, Leonard

    2002-02-01

    In the absence of definitive studies relating radioiodine dose to outcomes, selection of a dose of radioiodine to treat metastatic thyroid carcinoma is problematic, and several approaches have been used. These include empiric fixed doses and doses used on dosimetric approaches specific for each patient. This paper is a review of the rationale and technique for dosimetrically-determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. This review (1) discusses the alternatives for selection of a dose, (2) discusses the two major approaches for determining radioiodine doses dosimetrically, (3) briefly reviews several modifications of these approaches, (4) reviews the literature regarding the results, (5) discusses the side effects of these different approaches, and (6) concludes with recommendations for patient management and future research. This review does not address use of dosimetrically-determined doses of radioiodine for the initial ablation of thyroid tissue postoperatively.

  3. AHR Over-Expression in Papillary Thyroid Carcinoma: Clinical and Molecular Assessments in a Series of Italian Acromegalic Patients with a Long-Term Follow-Up

    PubMed Central

    Mian, Caterina; Ceccato, Filippo; Barollo, Susi; Watutantrige-Fernando, Sara; Albiger, Nora; Regazzo, Daniela; de Lazzari, Paola; Pennelli, Gianmaria; Rotondi, Sandra; Nacamulli, Davide; Pelizzo, Maria Rosa; Jaffrain-Rea, Marie-Lise; Grimaldi, Franco; Occhi, Gianluca; Scaroni, Carla

    2014-01-01

    Aim Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3–7%. Germline mutations in the aryl-hydrocarbon receptor (AHR) interacting protein (AIP) have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC) in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer. Methods Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied. Results 12 DTCs (10 papillary and 2 follicular carcinomas) were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status. Conclusions The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma. PMID:25019383

  4. Serum levels of sex hormones and expression of their receptors in thyroid tissue in female patients with various types of thyroid neoplasms.

    PubMed

    Liu, Jia; Chen, Guang; Meng, Xian-Ying; Liu, Zhong-Hui; Dong, Su

    2014-12-01

    Previous studies have demonstrated the expression of estrogen receptor (ER) and progesterone receptor (PR) in thyroid cancer; however, little is known regarding the levels of estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum and the expression of ER, PR, FSH receptor (FSHR), and LH receptor (LHR) in thyroid tissues of patients with different types of thyroid neoplasms. Serum levels of estrogen, progesterone, FSH, and LH were measured by chemiluminescence, and expression of ER, PR, FSHR, and LHR in thyroid tissue was detected by immunohistochemistry in female patients with thyroid adenoma (n = 70), nodular goiter (n = 73), thyroid papillary cancer (n = 149), poorly differentiated thyroid carcinoma (n = 12), or undifferentiated thyroid carcinoma (n = 8) and in normal controls (n = 60). The positive rates of serum estrogen level and ERα expression were significantly greater in patients with various types of thyroid neoplasms than in normal controls. The positive rates of ERβ expression were significantly less in various types of thyroid neoplasms than in normal thyroid tissues, especially in poorly differentiated carcinoma and undifferentiated carcinoma. The negative rates of serum progesterone level and positive rates of PR expression in thyroid tissue were significantly greater in patients with thyroid adenoma, nodular goiter, or thyroid papillary cancer than in normal controls. The positive rates of serum FSH and LH levels and FSHR and LHR expression were significantly greater in the thyroid adenoma group than in other groups. Our findings suggest that thyroid neoplasms might be sex hormone-dependent. The positive expression of ERα and PR often indicates thyroid papillary carcinoma, and the ERβ expression status is important for the diagnosis of poorly differentiated carcinoma and undifferentiated carcinoma. In addition, thyroid adenoma is often accompanied by an increase in serum FSH and LH levels, as well as

  5. Aberrant Lipid Metabolism in Anaplastic Thyroid Carcinoma Reveals Stearoyl CoA Desaturase 1 as a Novel Therapeutic Target

    PubMed Central

    von Roemeling, Christina A.; Marlow, Laura A.; Pinkerton, Anthony B.; Crist, Angela; Miller, James; Tun, Han W.; Smallridge, Robert C.

    2015-01-01

    Context: Currently there are no efficacious therapies for patients with anaplastic thyroid carcinoma (ATC) that result in long-term disease stabilization or regression. Objective: We sought to identify pathways critical for ATC cell progression and viability in an effort to develop new therapeutic strategies. We investigated the effects of targeted inhibition of stearoyl-CoA desaturase 1 (SCD1), a constituent of fatty acid metabolism overexpressed in ATC. Design: A gene array of ATC and normal thyroid tissue was performed to identify gene transcripts demonstrating altered expression in tumor samples. Effects of pharmacological and the genetic inhibition of SCD1 on tumor cell viability as well as cell signaling responses to therapy were evaluated in in vitro and in vivo models of this rare, lethal malignancy. Results: The gene array analysis revealed consistent distortion of fatty acid metabolism and overexpression of SCD1 in ATC and well-differentiated thyroid carcinomas. SCD1 is critical for ATC cell survival and proliferation, the inhibition of which induced endoplasmic reticulum stress, activation of the unfolded protein response, and apoptosis. Combined suppression of endoplasmic reticulum-associated degradation, a prosurvival component of the unfolded protein response, using proteasome inhibitors resulted in a synergistic decrease in tumor cell proliferation and increased cell death. Conclusions: SCD1 is a novel oncogenic factor specifically required for tumor cell viability in ATC. Furthermore, the expression of SCD1 appears to be correlated with thyroid tumor aggressiveness and may serve as a prognostic biomarker. These findings substantiate SCD1 as a novel tumor-specific target for therapy in patients with ATC and should be further investigated in a clinical setting. PMID:25675381

  6. [Thyroiditis].

    PubMed

    Buffet, Camille; Groussin, Lionel

    2013-02-01

    The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

  7. Differentiated Thyroid Cancer: Indications and Extent of Central Neck Dissection—Our Experience

    PubMed Central

    Calò, Pietro Giorgio; Boi, Francesco; Baghino, Germana; Nicolosi, Angelo

    2013-01-01

    The aim of this retrospective study was to determine the rate of metastases in the central neck compartment and examine the morbidity and rate of recurrence in patients with differentiated thyroid cancer treated with or without a central neck dissection. Two hundred and fifteen patients undergoing total thyroidectomy with preoperative diagnosis of differentiated thyroid cancer, in the absence of suspicious nodes, were divided in two groups: those who underwent a thyroidectomy only (group A; n = 169) and those who also received a central neck dissection (group B; n = 46). Five cases (2.32%) of nodal recurrence were observed: 3 in group A and 2 in group B. Tumor histology was associated with a risk of recurrence: Hürthle cell-variant and tall cell-variant carcinomas were associated with a high risk of recurrence. Multifocality and extrathyroidal invasion also presented a higher risk, while smaller tumors were at lower risk. The results of this study suggest that prophylactic central neck dissection should be reserved for high-risk patients only. A wider use of immunocytochemical and genetic markers to improve preoperative diagnosis and the development of methods for the intraoperative identification of metastatic lymph nodes will be useful in the future for the improved selection of patients for central neck dissections. PMID:24282633

  8. Charcoal tattoo localization for differentiated thyroid cancer recurrence in the central compartment of the neck.

    PubMed

    Soprani, F; Bondi, F; Puccetti, M; Armaroli, V

    2012-04-01

    Recurrence of differentiated thyroid cancer can often require further surgical options. Reoperations may carry significant risk of surgical complications; additionally, as the anatomy is subverted, there is the possibility of leaving residual neoplasm. In order to avoid such problems during reoperation for differentiated thyroid cancer recurrence, we have introduced the technique of preoperative ultrasound-guided tattooing localization of the lymphatic structure to be removed with a 4% solution of active charcoal. Using ultrasound guidance, the lesion is identified and 0.5-2 ml of colloidal charcoal is injected near the lesion. The extraction of the needle is accompanied by injection at constant pressure of other charcoal as to leave a trace of colouring along the path of the needle up to the skin. The preoperative injection was well tolerated in all cases. In the last 5 years, we have used this technique in 13 patients with suspected recurrence in the central compartment (all from papillary carcinomas). Postoperative ultrasound and histological examination confirmed the removal of the lesion in all patients; in one case, the lesion was a parathyroid cyst. Complications were observed in two of 13 (15.4%) cases (one transitory hypoparathyroidism, and one transitory vocal cord paresis). Considering our experience, charcoal tattoo localization can be considered a safe, low-cost technique that is extremely useful for facilitating surgical procedures, and reduces the risk of iatrogenic damage.

  9. Expression of ARE-binding proteins AUF1 and HuR in follicular adenoma and carcinoma of thyroid gland.

    PubMed

    Trojanowicz, B; Sekulla, C; Dralle, H; Hoang-Vu, C

    2016-01-01

    Both adenylate-uridylate rich elements binding proteins AUF1 and HuR may participate in thyroid carcinoma progression. In this study we investigated the expression of both factors on a protein level with a special focus on follicular adenoma and follicular thyroid carcinoma. By employment of immunofluorescence and western blot on 68 thyroid tissues including 7 goiter, 16 follicular adenoma (4 adenomatous hyperplasia), 19 follicular thyroid carcinomas, 13 papillary thyroid carcinomas and 14 undifferentiated thyroid carcinomas we investigated protein expression of AUF1 and HuR. In addition to previous results we demonstrated that AUF1 and HuR are significantly up-regulated in carcinoma tissues as compared with follicular adenoma or goiter tissues. Furthermore, by evaluation of AUF1 or HuR expression, or combination of both proteins on total tissue lysates, we were able to demonstrate a significant difference between follicular adenoma and follicular thyroid carcinoma. Overexpression of AUF1 and HuR is a common finding observed in thyroid malignancy. Analysis of the tissues obtained by surgical resection as demonstrated in this study is comparable to a fine needle aspiration and in combination with AUF1/HuR immuno-analysis may support the conventional immunohistological investigations. The promising results of this study were performed on relatively small collective, but justify future development of a quick thyroid diagnostic test on larger cohort of the patients, especially for thyroid samples which are inadequate for histological examinations.

  10. Poly r(C) binding protein (PCBP) 1 is a negative regulator of thyroid carcinoma

    PubMed Central

    Zhang, Mingpeng; Wang, Xin; Tan, Jin; Zhao, Minghui; Lian, Linjuan; Zhang, Weisan

    2016-01-01

    Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein functional in multiple biological processes. PCBP1 has been shown to function as a tumor suppressor by negatively regulating translation of EMT inducer proteins in different cancers. Loss of PCBP1 expression or its Akt2-mediated phosphorylation at serine residue 43 has both been indicated to de-repress its regulation of EMT inducer proteins. However, its role in thyroid carcinoma has not been elucidated. Here we report that PCBP1 expression is significantly downregulated in thyroid carcinoma patients. In vitro kinase assay revealed that immunoprecipitated PCBP1 from transient or stably transfected thyroid carcinoma cells can be phosphorylated by recombinant Akt2 kinase. In situ analysis revealed that PCBP1 is a putative target of miR-490-3p, which was further confirmed by PCBP1 3’UTR-based reporter assays using the wild-type or a miR-490 seed mutant 3’UTR. The endogenous regulation of the PCBP1 3’UTR reporter by miR-490-3p could be rescued by transfection of miR-490 antagomir in WRO and BCPAP cells. Stably overexpressing PCBP1 BCPAP cells attenuated tumor formation completely as compared to empty vector overexpressing cells in xenograft assay. Cumulatively, our results indicate that PCBP1 functions as a tumor suppressor in thyroid carcinoma and that its expression is down regulated by high expression of the miR-490-3p observed in thyroid carcinoma patients. PMID:27648147

  11. Poly r(C) binding protein (PCBP) 1 is a negative regulator of thyroid carcinoma.

    PubMed

    Zhang, Mingpeng; Wang, Xin; Tan, Jin; Zhao, Minghui; Lian, Linjuan; Zhang, Weisan

    2016-01-01

    Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein functional in multiple biological processes. PCBP1 has been shown to function as a tumor suppressor by negatively regulating translation of EMT inducer proteins in different cancers. Loss of PCBP1 expression or its Akt2-mediated phosphorylation at serine residue 43 has both been indicated to de-repress its regulation of EMT inducer proteins. However, its role in thyroid carcinoma has not been elucidated. Here we report that PCBP1 expression is significantly downregulated in thyroid carcinoma patients. In vitro kinase assay revealed that immunoprecipitated PCBP1 from transient or stably transfected thyroid carcinoma cells can be phosphorylated by recombinant Akt2 kinase. In situ analysis revealed that PCBP1 is a putative target of miR-490-3p, which was further confirmed by PCBP1 3'UTR-based reporter assays using the wild-type or a miR-490 seed mutant 3'UTR. The endogenous regulation of the PCBP1 3'UTR reporter by miR-490-3p could be rescued by transfection of miR-490 antagomir in WRO and BCPAP cells. Stably overexpressing PCBP1 BCPAP cells attenuated tumor formation completely as compared to empty vector overexpressing cells in xenograft assay. Cumulatively, our results indicate that PCBP1 functions as a tumor suppressor in thyroid carcinoma and that its expression is down regulated by high expression of the miR-490-3p observed in thyroid carcinoma patients. PMID:27648147

  12. Poly r(C) binding protein (PCBP) 1 is a negative regulator of thyroid carcinoma

    PubMed Central

    Zhang, Mingpeng; Wang, Xin; Tan, Jin; Zhao, Minghui; Lian, Linjuan; Zhang, Weisan

    2016-01-01

    Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein functional in multiple biological processes. PCBP1 has been shown to function as a tumor suppressor by negatively regulating translation of EMT inducer proteins in different cancers. Loss of PCBP1 expression or its Akt2-mediated phosphorylation at serine residue 43 has both been indicated to de-repress its regulation of EMT inducer proteins. However, its role in thyroid carcinoma has not been elucidated. Here we report that PCBP1 expression is significantly downregulated in thyroid carcinoma patients. In vitro kinase assay revealed that immunoprecipitated PCBP1 from transient or stably transfected thyroid carcinoma cells can be phosphorylated by recombinant Akt2 kinase. In situ analysis revealed that PCBP1 is a putative target of miR-490-3p, which was further confirmed by PCBP1 3’UTR-based reporter assays using the wild-type or a miR-490 seed mutant 3’UTR. The endogenous regulation of the PCBP1 3’UTR reporter by miR-490-3p could be rescued by transfection of miR-490 antagomir in WRO and BCPAP cells. Stably overexpressing PCBP1 BCPAP cells attenuated tumor formation completely as compared to empty vector overexpressing cells in xenograft assay. Cumulatively, our results indicate that PCBP1 functions as a tumor suppressor in thyroid carcinoma and that its expression is down regulated by high expression of the miR-490-3p observed in thyroid carcinoma patients.

  13. Composite Mucoepidermoid Carcinoma and Columnar Cell Variant of Papillary Carcinoma of the Thyroid: A Case Report and Review of the Literature.

    PubMed

    Taconet, Sarah; Bosq, Jacques; Hartl, Dana; Schlumberger, Martin; Leboulleux, Sophie; Scoazec, Jean-Yves; Al-Ghuzlan, Abir

    2016-06-01

    Primary mucoepidermoid carcinoma (MEC) of the thyroid and columnar cell variant of papillary carcinoma of the thyroid (PCT) are uncommon neoplasms. We report the first case of composite MEC and columnar cell variant of PCT. An 86-year-old man consulted for a 47-mm thyroid nodule, cytologically compatible with PCT. Total thyroidectomy was performed. Histological diagnosis, with support of histochemistry and immunohistochemistry, was mixed primary carcinoma of the thyroid, associating an MEC component with predominantly columnar cell variant of PCT. Sixteen months after surgery and external beam radiation therapy, the patient was free of recurrence or distant metastasis. This case report offers an opportunity to highlight the potential pitfalls concerning the interpretation of mucin histochemistry in thyroid tumors. PMID:26755714

  14. Thyrotoxicosis caused by functioning metastatic thyroid carcinoma. A rare and elusive cause of hyperthyroidism with low radioactive iodine uptake

    SciTech Connect

    Ober, K.P.; Cowan, R.J.; Sevier, R.E.; Poole, G.J.

    1987-05-01

    A patient with progressively worsening thyrotoxicosis, refractory to medical therapy, is described. Repeated measurements of thyroidal RAI uptake over a 13 month period were low consistently and could not be explained by iodine ingestion, thyroiditis, or administration of exogenous thyroid hormone. An I-131 scan ultimately revealed striking activity at the base of the skull, reflecting ectopic excessive production of thyroid hormone by a solitary functioning metastatic thyroid carcinoma. The thyrotoxic state resolved after large doses of therapeutic I-131. Typical features of this rare cause of hyperthyroidism are discussed.

  15. Papillary thyroid carcinoma risk factors in the Yunnan plateau of southwestern China

    PubMed Central

    Zeng, Rong; Shou, Tao; Yang, Kun-xian; Shen, Tao; Zhang, Jin-ping; Zuo, Rong-xia; Zheng, Yong-qing; Yan, Xin-ming

    2016-01-01

    Objective This study investigated clinical and pathological characteristics and risk factors in papillary thyroid carcinoma (PTC) patients’ native to Yunnan plateau in southwestern China. Methods Clinical data from 1,198 patients diagnosed with PTC (n=578) and control subjects (n=620) with benign thyroid disease (ie, thyroid nodule disease, benign thyroid diseases [BTD]) in Yunnan province were analyzed retrospectively. Results The mean patient age was lower for PTC than for BTD. Positive ratios of thyroid peroxidase antibody, thyroglobulin antibody (TGAb), and thyrotrophin receptor antibody (TRAb) were higher in PTC than in BTD patients. The ratio of PTC coexisting with Hashimoto’s thyroiditis (HT) or with lymphocytic thyroiditis was higher than that of BTD. The number of patients whose age at menarche was ≤13 years, who had given birth to less than or equal to two children, or who were in premenopause were higher in the PTC than in the BTD group. Multivariate conditional logistic regression analyses revealed that age >45 years, nodal size >1 cm, and elevated TG levels were protective factors against PTC. Abnormally elevated TGAb and TRAb levels were independent risk factors for PTC in females. Conclusion HT was not an independent risk factor for but was associated with PTC. TRAb is a risk factor for PTC in individuals living in the Yunnan plateau, but not for those in the plains region. PMID:27418831

  16. Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense Capacity.

    PubMed

    Rovcanin, Branislav R; Gopcevic, Kristina R; Kekic, Dusan Lj; Zivaljevic, Vladan R; Diklic, Aleksandar Dj; Paunovic, Ivan R

    2016-01-01

    Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor's biological behavior. PMID:27615359

  17. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  18. [Case of papillary carcinoma of the thyroid gland with concurrent tuberculous lymphadenitis].

    PubMed

    Ishinaga, Hajime; Hamaguchi, Noriko; Suzuki, Hiroshi; Miyamura, Tomotaka; Nakamura, Satoshi; Otsu, Kazuya; Takeuchi, Kazuhiko

    2013-12-01

    We report a case of papillary carcinoma of the thyroid gland and cervical lymph node metastases with concurrent tuberculous lymphadenitis that was diagnosed preoperatively. A 35-year-old woman presented with multiple lymph node swellings and an anterior neck mass. No findings suggesting the coexistence of pulmonary tuberculosis were present. The patient underwent a total thyroidectomy with bilateral neck dissection together with medication. Measures to prevent tuberculosis were undertaken during the perioperative period. The histopathological diagnosis was papillary carcinoma with both metastatic and tuberculous lymphadenitis of the lymph nodes in the neck. The possible coexistence of tuberculous lymphadenitis must be ruled out when lymph node swellings are observed in patients with head and neck cancer, including thyroid carcinoma.

  19. The role of Ile3434Thr XRCC7 gene polymorphism in Differentiated Thyroid Cancer risk in an Iranian population

    PubMed Central

    Rahimi, Maryam; Fayaz, Shima; Fard-Esfahani, Armaghan; Hossein Modarressi, Mohammad; Akrami, Seyed Mohammad; Fard-Esfahani, Pezhman

    2012-01-01

    Background The aim of this study was to understand any association between differentiated thyroid carcinoma (DTC) and Ile3434Thr XRCC7 gene polymorphism (GenBank accession number: rs7830743). DTC is the most prevalent thyroid neoplasm, which includes papillary and follicular cell carcinoma. XRCC7 gene encodes a protein that functions in non-homologous end joining DNA repair pathway. Non-synonymous polymorphisms in this gene may alter DNA repair capacity of the cell and change the risk of developing cancers. Methods DTC patients (n = 173) and cancer free individuals (n = 204) were enrolled in a case-control study. The Ile3434Thr polymorphic alleles were discriminated by using amplification refractory mutation system-PCR method. The frequencies of this single nucleotide polymorphism in case and control groups were compared. Also, risk ratio for developing DTC in dichotomized genotypes was estimated by multivariate logistic regression analysis. Results Dichotomized genotypes into those with and without the 3434Thr allele showed that this allele was associated with DTC (OR [odd ratio]: 1.89, 95% confidence interval (CI) = 1.29-2.79, P<0.001). Also, TC genotype was significantly associated with increased risk of DTC (OR: 2.42, 95% CI = 1.55-3.81, P = 0.0001) in individuals carrying this genotype. Conclusion Allele 3434Thr in XRCC7 gene might be associated with differentiated thyroid cancer risk. Further studies with larger samples are needed to verify these initial findings. PMID:23183621

  20. Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells.

    PubMed

    Kurmann, Anita A; Serra, Maria; Hawkins, Finn; Rankin, Scott A; Mori, Munemasa; Astapova, Inna; Ullas, Soumya; Lin, Sui; Bilodeau, Melanie; Rossant, Janet; Jean, Jyh C; Ikonomou, Laertis; Deterding, Robin R; Shannon, John M; Zorn, Aaron M; Hollenberg, Anthony N; Kotton, Darrell N

    2015-11-01

    Differentiation of functional thyroid epithelia from pluripotent stem cells (PSCs) holds the potential for application in regenerative medicine. However, progress toward this goal is hampered by incomplete understanding of the signaling pathways needed for directed differentiation without forced overexpression of exogenous transgenes. Here we use mouse PSCs to identify key conserved roles for BMP and FGF signaling in regulating thyroid lineage specification from foregut endoderm in mouse and Xenopus. Thyroid progenitors derived from mouse PSCs can be matured into thyroid follicular organoids that provide functional secretion of thyroid hormones in vivo and rescue hypothyroid mice after transplantation. Moreover, by stimulating the same pathways, we were also able to derive human thyroid progenitors from normal and disease-specific iPSCs generated from patients with hypothyroidism resulting from NKX2-1 haploinsufficiency. Our studies have therefore uncovered the regulatory mechanisms that underlie early thyroid organogenesis and provide a significant step toward cell-based regenerative therapy for hypothyroidism. PMID:26593959

  1. Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas

    PubMed Central

    Selmansberger, Martin; Kaiser, Jan Christian; Hess, Julia; Güthlin, Denise; Likhtarev, I.; Shpak, Victor; Tronko, Mykola; Brenner, Alina; Abend, Michael; Blettner, Maria; Unger, Kristian; Jacob, Peter; Zitzelsberger, Horst

    2015-01-01

    A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to 131iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The ‘Genrisk-T’ cohort consisted of 45 PTCs and the ‘UkrAm’ cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation. PMID:25957251

  2. Metabolomics of papillary thyroid carcinoma tissues: potential biomarkers for diagnosis and promising targets for therapy.

    PubMed

    Shang, Xingchen; Zhong, Xia; Tian, Xingsong

    2016-08-01

    Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. Our study was to construct a tissue-targeted metabolomics analysis method based on untargeted and targeted metabolic multi-platforms to identify a comprehensive PTC metabolic network in clinical samples. We applied untargeted gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) for preliminary screening of potential biomarkers. With diagnostic models constructed using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), 45 differentially abundant metabolites with a variable importance in the projection (VIP) value greater than 1 and a P value less than 0.05 were identified, and we show that our approach was able to discriminate PTC tissues from healthy tissues. We then performed validation experiments based on targeted GC-TOF-MS combined with ultra-high-performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) through constructing linear standard curves of analytes. Ultimately, galactinol, melibiose, and melatonin were validated as significantly altered metabolites (p < 0.05). These three metabolites were defined as a combinatorial biomarker to assist needle biopsy for PTC diagnosis as demonstrated by receiver operating characteristic (ROC) curve analysis, which revealed an area under the ROC curve (AUC) value of 0.96. Based on the metabolite enrichment analysis results, the galactose metabolism pathway was regarded as an important factor influencing PTC development by affecting energy metabolism. Alpha-galactosidase (GLA) was considered to be a potential target for PTC therapy. PMID:26935059

  3. Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas.

    PubMed

    Selmansberger, Martin; Kaiser, Jan Christian; Hess, Julia; Güthlin, Denise; Likhtarev, I; Shpak, Victor; Tronko, Mykola; Brenner, Alina; Abend, Michael; Blettner, Maria; Unger, Kristian; Jacob, Peter; Zitzelsberger, Horst

    2015-07-01

    A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to (131)iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The 'Genrisk-T' cohort consisted of 45 PTCs and the 'UkrAm' cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation.

  4. Thrombospondin-1 in differentiated thyroid cancer: Dr. Jekyll and Mr. Hyde.

    PubMed

    Ghoneim, Christelle; Soula-Rothhut, Mahdhia; Rothhut, Bernard

    2008-01-01

    Thrombospondin-1 (TSP-1) is a member of a family of five structurally related extracellular glycoproteins that plays a major role in cell-matrix and cell-cell interactions. Due to its multifunctional nature and its ability to bind to a variety of cell surface receptors and matrix proteins, TSP-1 has been identified as a potential regulator of angiogenesis and tumor progression. In this review, we summarize recent results that we obtained in our laboratory dealing with the regulation of thombospondin-1 expression by epidermal growth factor and hepatocyte growth factor. Our results show that TSP-1 can have opposite effects on cell invasion depending upon the type of differentiated thyroid carcinoma studied. PMID:18661355

  5. Thyroid

    MedlinePlus

    Thyroid is used to treat the symptoms of hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, ...

  6. Thyroiditis

    MedlinePlus

    ... Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the United States. Postpartum thyroiditis, which causes ... hormone levels in the blood) followed by temporary hypothyroidism, is a common cause of thyroid problems after ...

  7. Thyroid carcinoma after radioiodide therapy for hyperthyroidism. Analysis based on age, latency, and administered dose of I-/sup 131/

    SciTech Connect

    Spencer, R.P.; Chapman, C.N.; Rao, H.

    1983-05-01

    Twenty-five reports in the medical literature of thyroid carcinomas which were detected after radioiodide therapy for hyperthyroidism were reviewed. These cases did not show a usual characteristic of radiation-associated tumors, namely a long latency period. That is, in 8/25 the latency period was under five years, and the mean latency was only 7.3 years. Further, there was no relationship between latency and age at treatment, or between latency and the dose of radioiodide employed. In 15/25 of the cases, there were known thyroid nodules. Three of the patients had thyroiditis (which itself has a correlation with thyroid carcinoma), and one individual had prior head and neck external radiation. There was no substantiating evidence that radioiodide treatment for hyperthyroidism was the cause of these thyroid carcinomas.

  8. Risk Stratification in Differentiated Thyroid Cancer: An Ongoing Process.

    PubMed

    Omry-Orbach, Gal

    2016-01-28

    Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts postoperatively with histopathologic staging, based on the AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and, if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low, intermediate, or high risk for recurrence. Over the course of time, a response-to-therapy variable is incorporated, and patients essentially undergo continuous risk stratification. Additional tools such as biochemical markers, genetic mutations, and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality

  9. Risk Stratification in Differentiated Thyroid Cancer: An Ongoing Process.

    PubMed

    Omry-Orbach, Gal

    2016-01-01

    Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts postoperatively with histopathologic staging, based on the AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and, if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low, intermediate, or high risk for recurrence. Over the course of time, a response-to-therapy variable is incorporated, and patients essentially undergo continuous risk stratification. Additional tools such as biochemical markers, genetic mutations, and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality

  10. Copper as ancillary diagnostic tool in preoperative evaluation of possible papillary thyroid carcinoma in patients with benign thyroid disease.

    PubMed

    Dragutinović, Vesna V; Tatić, Svetislav B; Nikolić-Mandić, Snežana D; Tripković, Tatjana M; Dunđerović, Duško M; Paunović, Ivan R

    2014-09-01

    Preoperative diagnosis of papillary thyroid carcinoma (PTC) comprises numerous diagnostic procedures which are mostly applicable in tertiary institutions. Normal thyroid function depends on the presence of many trace elements and copper (Cu) and zinc (Zn) are some of those. The study is based on retrospective review of 118 patients with preoperatively diagnosed benign thyroid disease (BTD) and 12 with PTC, who underwent thyroid surgery at the Center for Endocrine Surgery Clinical Center of Serbia, Belgrade, between 2010 and 2012. The objective was to evaluate concentrations of Cu and Zn in serum as possible prediction markers for PTC in patients who underwent surgery for preoperatively diagnosed BTD. Concentrations of Cu and Zn ions in serum were measured using atomic absorption spectrophotometer. Data were analyzed using methods of descriptive statistics, Anova and t-test (p < 0.05 was considered statistically significant). Definitive pathohistological findings revealed PTC in 23 (19.5%) and papillary microcarcinoma-mPTC in 13 (11.0%) of BTD patients. The concentrations of Cu ions in serum of PTC patients as well as in serum of patients with mPTC were significantly higher than in serum of BTD patients (p < 0.05). The concentrations of Zn ions and Cu/Zn ratio in serum of PTC and mPTC patients were not significantly higher than in serum of BTD patients. The concentration of Cu ions in serum of patients before thyroid surgery can be useful, easy available, and a low-cost tool in prediction of preoperatively undiagnosed PTC in patients with BTD.

  11. mRNA Expression in Papillary and Anaplastic Thyroid Carcinoma: Molecular Anatomy of a Killing Switch

    PubMed Central

    Hébrant, Aline; Dom, Geneviève; Dewaele, Michael; Andry, Guy; Trésallet, Christophe; Leteurtre, Emmanuelle; Dumont, Jacques E.; Maenhaut, Carine

    2012-01-01

    Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents the end stage of thyroid tumor progression. No effective treatment exists so far. ATC frequently derive from papillary thyroid carcinomas (PTC), which have a good prognosis. In this study, we analyzed the mRNA expression profiles of 59 thyroid tumors (11 ATC and 48 PTC) by microarrays. ATC and PTC showed largely overlapping mRNA expression profiles with most genes regulated in all ATC being also regulated in several PTC. 43% of the probes regulated in all the PTC are similarly regulated in all ATC. Many genes modulations observed in PTC are amplified in ATC. This illustrates the fact that ATC mostly derived from PTC. A molecular signature of aggressiveness composed of 9 genes clearly separates the two tumors. Moreover, this study demonstrates gene regulations corresponding to the ATC or PTC phenotypes like inflammatory reaction, epithelial to mesenchymal transition (EMT) and invasion, high proliferation rate, dedifferentiation, calcification and fibrosis processes, high glucose metabolism and glycolysis, lactate generation and chemoresistance. The main qualitative differences between the two tumor types bear on the much stronger EMT, dedifferentiation and glycolytic phenotypes showed by the ATC. PMID:23115614

  12. Differential expression of the Na+/I− symporter protein in thyroid cancer and adjacent normal and nodular goiter tissues

    PubMed Central

    WANG, SHASHA; LIANG, JUN; LIN, YANSONG; YAO, RUYONG

    2013-01-01

    The ability of differentiated thyroid cancer and adjacent thyroid cells to concentrate iodine is dependent on their expression of a functional NA+/I− symporter (NIS). Thyroid cancer is insensitive to 131I treatment if the thyroid cells lack the ability to concentrate iodide. Thus, in this study, we aimed to determine whether the NIS protein was differentially expressed in thyroid cancer and various surrounding tissues. We recruited 114 cases of papillary thyroid carcinoma (PTC) and divided them into two groups: 60 patients of 9 males and 51 females with a mean age of 49.55 years who had PTC with surrounding nodular goiter tissue (simplified as GNG), and 54 patients of 8 males and 46 females with a mean age of 45.78 years who had PTC with surrounding normal tissue (Gnormal) after total or near total thyroidectomy. Formalin-fixed and paraffin-embedded tissue sections were prepared for immunohistochemical staining of the NIS protein and semi-quantitative analysis. The NIS protein was expressed in the basolateral membrane of the normal epithelium, while PTC and nodular goiter cells expressed NIS in the cytoplasm and basolateral membrane. The expression levels of the NIS protein were higher in the adjacent normal tissues compared with those of the surrounding nodular goiter tissues (P=0.002) and expression levels of the NIS protein were higher in PTC tissues compared with the surrounding nodular goiter tissues (P=0.008). The data from this study indicate that cancer-surrounding tissues may play a significant role in mediating the sensitivity of PTC patients to radioactive iodine treatment. PMID:23255951

  13. Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma

    PubMed Central

    Rosignolo, Francesca; Sponziello, Marialuisa; Durante, Cosimo; Puppin, Cinzia; Mio, Catia; Baldan, Federica; Di Loreto, Carla; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2016-01-01

    PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis. PMID:27249794

  14. Post-surgical treatment of thyroid carcinoma in dogs with retinoic acid 9 cis improves patient outcome

    PubMed Central

    Castillo, V.; Pessina, P.; Hall, P.; Blatter, M.F. Cabrera; Miceli, D.; Arias, E. Soler; Vidal, P.

    2016-01-01

    The objective of the present study was to compare the effects of isotretinoin 9-cis (RA9-cis) as a post-surgery treatment of thyroid carcinoma to a traditional treatment (doxorubicin) and no treatment. Owners who did not want their dogs to receive treatment were placed into the control group A (GA; n=10). The remaining dogs were randomly placed into either group B (GB; n=12) and received doxorubicin at a dose of 30 mg/m2 every three weeks, for six complete cycles or group C (GC; n=15) and treated with RA9-cis at a dose of 2 mg/kg/day for 6 months. The time of the recurrence was significantly shorter in the GA and GB compared to GC (P=0.0007; P=0.0015 respectively), while we did not detect differences between GA and GB. The hazard ratio of recurrence between GA and GB compared to GC were 7.25 and 5.60 times shorter, respectively. We did not detect any differences between the other groups. The risk ratio of recurrence was 2.0 times higher in GA compared to GC and 2.1 times higher in GB compared to GC. The type of carcinoma had an effect on time of survival with follicular carcinomas having an increased mean survival time than follicular-compact carcinomas (P<0.0001) and follicular-compact carcinomas had a longer mean survival time than compact carcinomas. The interaction among treatment and type was significant, but survival time in follicular carcinomas did not differ between treatments. In follicular-compact carcinomas the survival time of GC was greater than GB (P<0.05), but we did not detect a difference between GA and GB. In conclusion, this study shows that the use of surgery in combination with RA9-cis treatment significantly increases survival rate and decreases the time to tumor recurrence when compared to doxorubicin treated or untreated dogs. The histological type of carcinoma interacted with treatment for time to recurrence and survival time, with more undifferentiated carcinomas having a worse prognosis than differentiated carcinomas. PMID:26862515

  15. Post-surgical treatment of thyroid carcinoma in dogs with retinoic acid 9 cis improves patient outcome.

    PubMed

    Castillo, V; Pessina, P; Hall, P; Blatter, M F Cabrera; Miceli, D; Arias, E Soler; Vidal, P

    2016-01-01

    The objective of the present study was to compare the effects of isotretinoin 9-cis (RA9-cis) as a post-surgery treatment of thyroid carcinoma to a traditional treatment (doxorubicin) and no treatment. Owners who did not want their dogs to receive treatment were placed into the control group A (GA; n=10). The remaining dogs were randomly placed into either group B (GB; n=12) and received doxorubicin at a dose of 30 mg/m(2) every three weeks, for six complete cycles or group C (GC; n=15) and treated with RA9-cis at a dose of 2 mg/kg/day for 6 months. The time of the recurrence was significantly shorter in the GA and GB compared to GC (P=0.0007; P=0.0015 respectively), while we did not detect differences between GA and GB. The hazard ratio of recurrence between GA and GB compared to GC were 7.25 and 5.60 times shorter, respectively. We did not detect any differences between the other groups. The risk ratio of recurrence was 2.0 times higher in GA compared to GC and 2.1 times higher in GB compared to GC. The type of carcinoma had an effect on time of survival with follicular carcinomas having an increased mean survival time than follicular-compact carcinomas (P<0.0001) and follicular-compact carcinomas had a longer mean survival time than compact carcinomas. The interaction among treatment and type was significant, but survival time in follicular carcinomas did not differ between treatments. In follicular-compact carcinomas the survival time of GC was greater than GB (P<0.05), but we did not detect a difference between GA and GB. In conclusion, this study shows that the use of surgery in combination with RA9-cis treatment significantly increases survival rate and decreases the time to tumor recurrence when compared to doxorubicin treated or untreated dogs. The histological type of carcinoma interacted with treatment for time to recurrence and survival time, with more undifferentiated carcinomas having a worse prognosis than differentiated carcinomas.

  16. 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. PMID:26667546

  17. 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.

  18. [Medullary thyroid carcinoma in a 10-month-old child with multiple endocrine neoplasia 2B].

    PubMed

    Mathiesen, Jes Sloth; Døssing, Helle; Bender, Lars; Godballe, Christian

    2014-01-27

    In infants at risk of multiple endocrine neoplasia type 2B (MEN2B) the American Thyroid Association recommends genetic testing as soon as possible after birth and that thyroidectomy should be performed in MEN2B RET-mutation positive individuals as soon as possible and if possible within the first year of life. We present a ten-month-old girl with MEN2B who had prophylactic thyroidectomy. The surgical specimen showed medullary thyroid carcinoma. This case emphasizes the need for early diagnosis and prophylactic thyroidectomy in MEN2B patients. PMID:27498810

  19. Quadruple Cancers of Non-producing Multiple Myeloma, Cholangiocellular Carcinoma, and Two Different Thyroid Cancers.

    PubMed

    Mizutani, Shinsuke; Kuroda, Junya; Sasaki, Nana; Kiyota, Miki; Tatekawa, Shotaro; Tsukamoto, Taku; Maegawa, Saori; Chinen, Yoshiaki; Shimura, Yuji; Nagoshi, Hisao; Kobayashi, Tsutomu; Horiike, Shigeo; Tando, So; Fushiki, Shinji; Taniwaki, Masafumi

    2016-01-01

    We report the case of a 72-year-old man who presented with non-producing multiple myeloma (MM) with three additional concomitant solid tumors that were identified by postmortem autopsy. The disease was refractory to anti-MM therapy including bortezomib and lenalidomide, and he finally died of bacterial pneumonia with diffuse alveolar damage 8 months after the diagnosis. An autopsy revealed that he was also affected by three other solid cancers, cholangiocellular carcinoma, medullary thyroid cancer and papillary thyroid cancer that were clinically asymptomatic and remained undiagnosed before death. A review of the literature suggests that primary quadruple cancers including MM are extremely rare. PMID:27150876

  20. Long noncoding RNA are aberrantly expressed in human papillary thyroid carcinoma

    PubMed Central

    YANG, MEILIU; TIAN, JINLI; GUO, XIN; YANG, YING; GUAN, RUHUA; QIU, MINGYUE; LI, YUKAI; SUN, XUELING; ZHEN, YANFENG; ZHANG, YAZHONG; CHEN, CHUNYOU; LI, YANBING; FANG, HUI

    2016-01-01

    Long noncoding RNAs (lncRNAs) have emerged as key regulatory molecules at almost every level of gene expression regulation. The altered expression of lncRNAs is a characteristic of numerous types of cancer, and lncRNAs have been demonstrated to promote the development, invasion and metastasis of tumors through various mechanisms. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) remain unclear. In the present study, differentially expressed lncRNAs and mRNAs were detected by human lncRNA microarray in three pairs of PTC and adjacent noncancerous samples. The microarray results revealed that 675 lncRNAs and 751 mRNAs were abnormally expressed in the three PTC samples compared with adjacent noncancerous samples (fold change ≥2.0; P<0.05). To validate the microarray results, 8 differentially expressed lncRNAs were randomly selected for quantitative polymerase chain reaction (qPCR). The results of qPCR were consistent with the microarray data; the 8 lncRNAs had an aberrant expression in the PTC samples compared with the adjacent noncancerous samples. Gene ontology and pathway analysis indicated that there were 7 downregulated pathways and 29 upregulated pathways in PTC. LncRNA classification and subgroup analysis revealed 7 pairs of enhancer-like lncRNA-mRNA, 9 pairs of antisense lncRNA-mRNA and 45 pairs of lncRNA-mRNA were differentially expressed between PTC and their paired noncancerous samples. In conclusion, the present study identified a series of novel PTC-associated lncRNAs. Further study with these lncRNAs is instrumental for the identification of novel target molecules that could lead to improved diagnosis and treatment for PTC. PMID:27347178

  1. Radioactive iodine treatment of a functional thyroid carcinoma producing hyperthyroidism in a dog

    SciTech Connect

    Peterson, M.E.; Kintzer, P.P.; Hurley, J.R.; Becker, D.V.

    1989-01-01

    Radioactive iodine (/sup 131/I) was used in the treatment of a 12-year-old female dog with hyperthyroidism resulting from a large, unresectable (and metastatic) thyroid carcinoma associated with signs of severe inspiratory stridor and dyspnea. Hyperthyroidism was diagnosed on the basis of clinical signs (polyuria, polydipsia, polyphagia, weight loss, nervousness) and high basal serum thyroxine (T4) concentrations, as well as thyroid radioiodine kinetic studies that showed a high radioiodine uptake into the thyroid (% thyroid uptake) and markedly increased serum concentrations of protein-bound iodine-131 (PB/sup 131/I) after /sup 131/I tracer injection. Thyroid imaging revealed diffuse radionuclide accumulation by the tumor, which involved both thyroid lobes. The dog was treated with three large doses of radioiodine (/sup 131/I), ranging from 60 to 75 mCi, given at intervals of 5 to 7 months. The dog became euthyroid, and the size of the tumor decreased by approximately 25% after each /sup 131/I treatment, improving the severe inspiratory stridor and dyspnea, but both the hyperthyroid state and breathing difficulty recurred within a few months of each treatment. The dog was euthanatized 5 months after the last treatment because of progressive tracheal compression and pulmonary metastasis.

  2. Shear wave elastography diagnosis of the diffuse sclerosing variant of papillary thyroid carcinoma: A case report

    PubMed Central

    Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei

    2016-01-01

    The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC. PMID:27446574

  3. Differentiated Thyroid Cancer in Navarra (Spain): Historic Cohort Results (1987–2003)

    PubMed Central

    Salvador Egea, María Pilar; Echegoyen Silanes, Ana Aranzazu; Layana Echezuri, Eduardo; Anda Apiñariz, Emma; Puras Gil, Ana; Menéndez Torre, Edelmiro; Forga Llenas, Lluis; Sainz de los Terreros, Amaya

    2011-01-01

    Introduction. Navarra has the highest incidence of differentiated thyroid cancer in Spain. The aim of this study was to review its management carried out by the Navarra's multidisciplinary Thyroid Disease Unit, from 1987 to 2003. Material and Methods. 325 patients were studied to find the incidence, prevalence, and prognostic factors. Statistical analysis comprised univariate and multivariate Cox proportional hazards regression models for survival and tumor recurrence. Results. The average annual incidence was 3.6 per 100,000 inhabitants, with a final prevalence of 82.4 per 100,000. Regarding survival and recurrence, statistical significance was observed for stage IV, follicular carcinoma, capsular and prethyroid muscles invasion, and T4 group. Only survival was related to tumour size larger than 40 mm. Only recurrence was related to lymph node metastases and radioiodine dose higher than 100 mCi. Conclusions. Attendance of patients in a functional unit setting has allowed us to classify them into three risk groups. PMID:22084734

  4. Jugular Vein Invasion Diagnosis and Prognosis in Thyroid Carcinomas

    PubMed Central

    Marcy, Pierre Yves; Thariat, Juliette; Chevenet, Carole; Lacout, Alexis

    2016-01-01

    Summary Diagnosis of venous jugular invasion by means of traditional imaging is very rarely reported in the literature. Doppler ultrasound definitively helps to diagnose the tumor thrombus, the extent, and helps in redefining the TNM stage of such an aggressive thyroid tumor. PMID:27354880

  5. CT-scan prediction of thyroid cartilage invasion for early laryngeal squamous cell carcinoma.

    PubMed

    Hartl, Dana M; Landry, Guillaume; Bidault, François; Hans, Stéphane; Julieron, Morbize; Mamelle, Gérard; Janot, François; Brasnu, Daniel F

    2013-01-01

    Treatment choice for laryngeal cancer may be influenced by the diagnosis of thyroid cartilage invasion on preoperative computed tomography (CT). Our objective was to determine the predictive value of CT for thyroid cartilage invasion in early- to mid-stage laryngeal cancer. Retrospective study (1992-2008) of laryngeal squamous cell carcinoma treated with open partial laryngectomy and resection of at least part of the thyroid cartilage. Previous laser surgery, radiation therapy, chemotherapy and second primaries were excluded. CT prediction of thyroid cartilage invasion was determined by specialized radiologists. Tumor characteristics and pathologic thyroid cartilage invasion were compared to the radiologic assessment. 236 patients were treated by vertical (20 %), supracricoid (67 %) or supraglottic partial laryngectomy (13 %) for tumors staged cT1 (26 %), cT2 (55 %), and cT3 (19 %). The thyroid cartilage was invaded on pathology in 19 cases (8 %). CT's sensitivity was 10.5 %, specificity 94 %, positive predictive value 13 %, and negative predictive value 92 %. CT correctly predicted thyroid cartilage invasion in only two cases for an overall accuracy of 87 %. Among the false-positive CT's, tumors involving the anterior commissure were significantly over-represented (61.5 % vs. 27 %, p = .004). Tumors with decreased vocal fold (VF) mobility were significantly over-represented in the group of false-negatives (41 vs. 13 %, p = .0035). Preoperative CT was not effective in predicting thyroid cartilage invasion in these early- to mid-stage lesions, overestimating cartilage invasion for AC lesions and underestimating invasion for lesions with decreased VF mobility.

  6. The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence

    PubMed Central

    Walczyk, Agnieszka; Pałyga, Iwona; Gąsior-Perczak, Danuta; Gadawska-Juszczyk, Klaudia; Szymonek, Monika; Trybek, Tomasz; Lizis-Kolus, Katarzyna; Szyska-Skrobot, Dorota; Mikina, Estera; Hurej, Stefan; Słuszniak, Janusz; Mężyk, Ryszard; Góźdź, Stanisław

    2016-01-01

    Context There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course. Materials and Methods This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system. Results The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases). Conclusions The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification. PMID:27078258

  7. Diffuse sclerosing variant of papillary thyroid carcinoma--an update of its clinicopathological features and molecular biology.

    PubMed

    Pillai, Suja; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y

    2015-04-01

    Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma. The aim of this review is to critically analyse the features of this entity. A search of the literature revealed 25 clinicopathological studies with in-depth analysis of features of DSVPTC. Overall, the prevalence of DSVPTC varies from 0.7-6.6% of all papillary thyroid carcinoma. Higher prevalence of DSVPTC was noted in paediatric patients and in patients affected by irradiation. DSVPTC tends to occur more frequently in women and in patients in the third decade of life. Macroscopically, DSVPTC can involve the thyroid gland extensively without forming a dominant mass. Microscopic examination of DSVPTC revealed extensive fibrosis, squamous metaplasia and numerous psammoma bodies. The latter pathological feature can aid in the pre-operative diagnosis of the entity by fine needle aspiration and ultrasound. Compared to conventional papillary thyroid carcinoma, DSVPTC had a higher incidence of lymph node metastases at presentation. Distant metastases were noted in approximately 5% of the cases. Patients with DSVPTC were recommended to be managed by aggressive treatment protocols. It is likely that as a result of this, the prognosis of the patients with DSVPTC was noted to be similar to conventional papillary thyroid carcinoma. Overall, cancer recurrence and cancer related mortality have been reported in 14% and 3%, respectively, of patients with DSVPTC. In immunohistochemical studies, DSVPTC showed different expression patterns of epithelial membrane antigen, galectin 3, cell adhesion molecules, p53 and p63 when compared to conventional papillary thyroid carcinoma. On genetic analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC and activation of RET/PTC rearrangements are common. To conclude, DSVPTC has different clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

  8. Comparison of 2 monoclonal antibodies for immunohistochemical detection of BRAF V600E mutation in malignant melanoma, pulmonary carcinoma, gastrointestinal carcinoma, thyroid carcinoma, and gliomas.

    PubMed

    Routhier, Caitlin Ann; Mochel, Mark C; Lynch, Kerry; Dias-Santagata, Dora; Louis, David N; Hoang, Mai P

    2013-11-01

    BRAF mutation is seen in a variety of human neoplasms including cutaneous malignant melanoma, papillary thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, pleomorphic xanthoastrocytoma, and others. Currently, there are 2 commercially available monoclonal antibodies for the detection of BRAF V600E mutation; however, a full and practical comparison of their performance in various tumor types on an automated staining platform has not been done. We investigated their sensitivity and specificity in detecting the BRAF V600E mutation in a series of 152 tumors including 31 malignant melanomas, 25 lung carcinomas, 32 gastrointestinal carcinomas, 23 thyroid carcinomas, 35 gliomas, and 6 other malignancies. In this series, the concordance rate between immunohistochemistry (IHC) and mutational analyses was 97% (148/152) for VE1 and 88% (131/149) for anti-B-Raf. The sensitivity and specificity were 98% (60/61) and 97% (88/91) for monoclonal VE1 and 95% (58/61) and 83% (73/88) for anti-B-Raf, respectively. There were 4 cases with discordant IHC and mutational results for monoclonal VE1 in contrast to 18 cases for anti-B-Raf. Our studies showed that IHC with monoclonal VE1 has a better performance compared with anti-B-Raf in an automated staining platform and confirmed that clone VE1 provides excellent sensitivity and specificity for detecting the BRAF V600E mutation in a variety of tumor types in a clinical setting.

  9. Feasibility Study of Ultrasonographic Criteria for Microscopic and Macroscopic Extra-Thyroidal Extension Based on Thyroid Capsular Continuity and Tumor Contour in Patients with Papillary Thyroid Carcinomas.

    PubMed

    Rim, Jee Hyun; Chong, Semin; Ryu, Han Suk; Chung, Bo Mi; Ahn, Hye Shin

    2016-10-01

    Our purpose was to evaluate the feasibility of using ultrasonographic criteria of thyroid capsular continuity and tumor contour to differentiate macroscopic extra-thyroidal extension (ETE) from microscopic ETE, as well as non-ETE from ETE. On ultrasonography, we evaluated thyroid capsular continuity (C0 = continuous, C1 = discontinuous, C2 = invisible), and thyroid tumor contour (P0 = in normal parenchyma, P1 = abutting, P2 = bulging), which were grouped into type 1-9 classifications. Either C1-2 or P1-2 was more prevalent in ETE than non-ETE. C1 and P2 tended to be associated with macroscopic ETE, whereas C0 and P1 were significantly associated with microscopic ETE. Types 6, 8 and 9 were more likely to have ETE than non-ETE; type 6 (C1 P2) and type 9 (C2 P2) were significantly associated with macroscopic ETE, whereas type 8 (C2 P1) was associated more with microscopic ETE. Macroscopic and microscopic ETE, as well as non-ETE and ETE, can be differentiated using these pre-operative ultrasonographic criteria.

  10. Feasibility Study of Ultrasonographic Criteria for Microscopic and Macroscopic Extra-Thyroidal Extension Based on Thyroid Capsular Continuity and Tumor Contour in Patients with Papillary Thyroid Carcinomas.

    PubMed

    Rim, Jee Hyun; Chong, Semin; Ryu, Han Suk; Chung, Bo Mi; Ahn, Hye Shin

    2016-10-01

    Our purpose was to evaluate the feasibility of using ultrasonographic criteria of thyroid capsular continuity and tumor contour to differentiate macroscopic extra-thyroidal extension (ETE) from microscopic ETE, as well as non-ETE from ETE. On ultrasonography, we evaluated thyroid capsular continuity (C0 = continuous, C1 = discontinuous, C2 = invisible), and thyroid tumor contour (P0 = in normal parenchyma, P1 = abutting, P2 = bulging), which were grouped into type 1-9 classifications. Either C1-2 or P1-2 was more prevalent in ETE than non-ETE. C1 and P2 tended to be associated with macroscopic ETE, whereas C0 and P1 were significantly associated with microscopic ETE. Types 6, 8 and 9 were more likely to have ETE than non-ETE; type 6 (C1 P2) and type 9 (C2 P2) were significantly associated with macroscopic ETE, whereas type 8 (C2 P1) was associated more with microscopic ETE. Macroscopic and microscopic ETE, as well as non-ETE and ETE, can be differentiated using these pre-operative ultrasonographic criteria. PMID:27471119

  11. Virtual touch tissue imaging on acoustic radiation force impulse elastography: a new technique for differential diagnosis between benign and malignant thyroid nodules.

    PubMed

    Zhang, Yi-Feng; He, Yong; Xu, Hui-Xiong; Xu, Xiao-Hong; Liu, Chang; Guo, Le-Hang; Liu, Lin-Na; Xu, Jun-Mei

    2014-04-01

    Objectives- Acoustic radiation force impulse elastography is a newly developed ultrasound elasticity imaging technique that included both Virtual Touch tissue quantification and Virtual Touch tissue imaging (VTI; Siemens Medical Solutions, Mountain View, CA). This study aimed to evaluate the usefulness of VTI in differentiating malignant from benign thyroid nodules. Methods- This study included 192 consecutive patients with thyroid nodules (n = 219) who underwent surgery for compressive symptoms or suspicion of malignancy. Tissue stiffness on VTI elastography was scored from 1 (soft) to 6 (hard). The VTI scores between malignant and benign thyroid nodules were compared. The intraobserver and interobserver agreement for VTI elastography was also assessed. Results- On VTI elastography: score 1 was found in 84 nodules (all benign); score 2 in 37 nodules (3 papillary carcinomas and 34 benign nodules); score 3 in 25 nodules (1 medullary carcinoma, 6 papillary carcinomas, and 18 benign nodules); score 4 in 53 nodules (50 papillary carcinomas and 3 benign nodules); score 5 in 17 nodules (14 papillary carcinomas and 3 benign nodules); and score 6 in 3 nodules (all papillary carcinomas). A VTI elasticity score of 4 or greater was highly predictive of malignancy (P< .01), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.0% (67 of 77), 95.8% (136 of 142), 91.8% (67 of 73), 93.1% (136 of 146), and 92.7% (203 of 219), respectively. The κ values were 0.69 for intraobserver agreement and 0.85 for interobserver agreement. Conclusions- Virtual Touch tissue elasticity imaging has great potential as an adjunctive tool combined with conventional sonography for differential diagnosis between benign and malignant thyroid nodules.

  12. Preoperatively diagnosed case with co-existence of papillary thyroid carcinoma and cervical tuberculous lymphadenitis

    PubMed Central

    Ito, Taku; Saito, Hiroaki; Kishine, Naomi; Takeda, Takamori; Mizushima, Kota

    2015-01-01

    Introduction Papillary thyroid cancer (PTC) is the most frequent histological subtype of thyroid cancer. The lymph node metastasis is found in a high proportion of patients with PTC at the time of surgery. In contrast, tuberculous lymphadenitis remains a common cause of cervical lymphadenopathy in Asian countries. Presentation of case We present a 60-year-old woman with coexistence of papillary thyroid carcinoma (PTC) and cervical tuberculous lymphadenitis and to show the usefulness of fine-needle aspiration biopsy (FNAB) and quantiferon testing to distinguish a lymph node metastasis of PTC from tuberculous lymphadenitis. Discussion FNAB and quantiferon testing are useful tools to check if enlargement of cervical lymph node is due to tuberculous infection, and a surgical plan should be carefully determined to avoid unnecessary surgical complications and the spread of tuberculous infection. Conclusion The coexistence of cervical tuberculosis should be considered in the etiology of an enlarged lymph node for patients with PTC. PMID:26318132

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

    NASA Astrophysics Data System (ADS)

    Kim, Edward; Baloch, Zubair; Kim, Caroline

    2015-03-01

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

  14. Evaluation of whole-body retention of iodine-131 ((131)I) after postoperative remnant ablation for differentiated thyroid carcinoma - thyroxine withdrawal versus rhTSH administration: A retrospective comparison.

    PubMed

    Carvalho, Maria Raquel; Ferreira, Teresa C; Leite, Valeriano

    2012-03-01

    Previous studies demonstrated that preparation with recombinant human thyroid-stimulating hormone (rhTSH) for thyroid remnant ablation results in lower extrathyroidal radiation compared to hypothyroidism. The results of 50 radioiodine therapies (RITs) under rhTSH, regarding iodine half-life, were evaluated and compared with 50 RITs performed on patients with hypothyroidism following thyroxine withdrawal. The patients were treated with 3700 MBq (100 mCi) of (131)I. Forty-eight hours after RIT, patients were measured with a radiation detector at a 1-meter (m) distance for evaluation of the effective dose (μSv/h). TSH and thyroglobulin (Tg) maximal values were also compared. rhTSH-stimulated patients had a significantly lower whole-body retention of (131)I (8.5±7.3 μSv/h), extrapolated from the measurements of the effective dose at a 1-m distance, compared to endogenously stimulated patients (13.6±8.1 μSv/h; p=0.001). Furthermore, TSH mean and Tg median levels were significantly higher in the rhTSH-stimulated patients (89.9±15.3 mU/l and 7.7 ng/ml, respectively) compared to the hypothyroid group (59.2±25.1 mU/l and 3.3 ng/ml; p<0.001 and p=0.003, respectively). Compared to thyroid hormone withdrawal, the use of rhTSH prior to RIT was associated with significantly lower whole-body retention of (131)I and with greater efficacy in reaching TSH levels greater than 30 mU/l, confirming data previously described.

  15. Evolving Approaches to Patients with Advanced Differentiated Thyroid Cancer

    PubMed Central

    Sherman, Steven I.

    2013-01-01

    Advanced differentiated thyroid cancer (DTC), defined by clinical characteristics including gross extrathyroidal invasion, distant metastases, radioiodine (RAI) resistance, and avidity for 18-fluorodeoxyglucose (positron emission tomography-positive), is found in approximately 10–20% of patients with DTC. Standard therapy (surgery, RAI, TSH suppression with levothyroxine) is ineffective for many of these patients, as is standard chemotherapy. Our understanding of the molecular mechanisms leading to DTC and the transformation to advanced DTC has rapidly evolved over the past 15–20 years. Newer targeted therapy, specifically inhibitors of intracellular kinase signaling pathways, and cooperative multicenter clinical trials have dramatically changed the therapeutic landscape for patients with advanced DTC. In this review focusing on morbidities, molecules, and medicinals, we present a patient with advanced DTC, explore the genetics and molecular biology of advanced DTC, and review evolving therapies for these patients including multikinase inhibitors, selective kinase inhibitors, and combination therapies. PMID:23575762

  16. Testosterone enhancement of thyroid carcinoma in rats: the role of TSH

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; McCall, A.; Paloyan, E.

    1986-12-01

    Radiation treatment of Long-Evans male rats (40 mu Ci Na131I at the age of 2 months) led to a high incidence of thyroid follicular carcinomas at the age of 24 months; castration of males before irradiation caused a significant reduction in incidence of this tumor. In this study, replacement testosterone (T) was administered to castrated male rats by means of implanted, slow-release hormone-containing pellets (T-physiologic dose). Three testosterone doses (0.1T, 1.0T, and 30T) were used to treat groups of castrated irradiated and castrated nonirradiated rats from 2 to 18 months of age. The incidence of thyroid follicular carcinoma at 18 months in irradiated rats depended on the dose of replacement testosterone used. Tumor incidence was 8%, 14%, 41%, and 50% after treatment with 0T, 0.1T, 1.0T, and 30T, respectively. The incidence of thyroid follicular carcinoma in nonirradiated rats ranged from 0 to 7%. Mean serum thyroid-stimulating hormone (TSH) values in irradiated animal groups were elevated significantly above those for age-matched nonirradiated animals. The degree of TSH elevation in irradiated animals was related directly to the testosterone-replacement level. All rat groups showed age-dependent decreases in serum T4 levels, and T4 levels were also lowered by replacement testosterone in nonirradiated castrated animals. In aging irradiated animals, serum T4 levels were similarly decreased by testosterone, despite elevated TSH levels in these groups. In this study, testosterone appeared to act indirectly to promote development of irradiation-induced thyroid tumors by early and prolonged elevation of TSH levels.

  17. Papillary thyroid carcinoma: correlations between prognosis, age, and clinicopathological and histomorphological findings.

    PubMed

    Godballe, C; Asschenfeldt, P; Sørensen, J A; Sørensen, M W; Jørgensen, K

    1994-06-01

    The age influence on the prognosis of papillary thyroid carcinoma was analyzed in a group of 67 patients. A marked decline in cause-specific survival was found for patients older than 60 years of age at the time of diagnosis. In order to find a tumor-biological explanation of the prognostic difference between patients below and above 60 years of age, several clinicopathological and histomorphological features were analyzed. Tumors from patients older than 60 years of age showed significantly more mitotic activity and nuclear polymorphism, fewer psammoma bodies, and more frequent extrathyroidal invasion and distant metastases. The results indicate that 60 years of age the time of diagnosis may be the "prognostic break-point" for papillary thyroid carcinoma. PMID:8196451

  18. Ectopic ACTH Production Leading to Diagnosis of Underlying Medullary Thyroid Carcinoma.

    PubMed

    Matheny, Leslee N; Wilson, Jessica R; Baum, Howard B A

    2016-01-01

    Medullary thyroid carcinoma (MTC) has been described as a source of ectopic ACTH secretion in patients with Cushing's syndrome. This is an infrequent association, occurring in less than 1% of MTC cases. Among these, it is even more unusual for an initial diagnosis of hypercortisolism to lead to the discovery of underlying MTC. Here we present a case of a patient with weakness, diarrhea, and hypokalemia who was found first to have Cushing's syndrome and later diagnosed with metastatic MTC. The patient was treated initially with oral agents to control his hypercortisolism, then with an etomidate infusion after experiencing intestinal perforation. He also received vandetanib therapy targeting his underlying malignancy, as this has been shown to reverse clinical signs of Cushing's syndrome in patients with MTC and subsequent ectopic ACTH secretion. Bilateral adrenalectomy was ultimately required. Medullary thyroid carcinoma should be considered in patients presenting with Cushing's syndrome due to ectopic ACTH secretion, and a multimodality treatment approach is often required. PMID:27141514

  19. Immunocytochemical localization and identification of prosomatostatin gene products in medullary carcinoma of human thyroid gland.

    PubMed

    Scopsi, L; Ferrari, C; Pilotti, S; Holst, J J; Rehfeld, J F; Fossati, G; Rilke, F

    1990-08-01

    Thirty-three cases of histologically proven calcitonin-positive medullary thyroid carcinoma were studied immunocytochemically for the occurrence of prosomatostatin-related peptides. Positive cells, identified with a panel of antisera raised against four different regions of the prosomatostatin molecule, were found in 100% of the tumors. Most but not all somatostatin-positive cells were also immunoreactive for calcitonin. Notably, seven patients harboring somatostatin-rich tumors revealed a more favorable clinical course. The results (1) indicate that somatostatin production is a universal concomitant of thyroid medullary carcinoma, (2) suggest that these cells are likely to produce a somatostatin precursor molecule similar to mammalian prosomatostatin, and (3) imply that somatostatin-reactive cells may have as yet unknown roles in these tumors, possibly in the realm of paracrine and autocrine regulation of cell growth.

  20. Follicular Thyroid Carcinoma Characterized by Abundant Stromal Components with Chondroid and Osseous Metaplasia in a Dog

    PubMed Central

    KOBAYASHI, Ryosuke; YAMADA, Naoaki; KITAMORI, Takashi; KITAMORI, Fumiyo; SATO, Kazunari; DOI, Takuya; WAKO, Yumi; SATO, Junko; TSUCHITANI, Minoru

    2014-01-01

    ABSTRACT A dog developed a cervical mass, and computed tomography verified a mass surrounding the trachea with some pulmonary masses. Histopathologically, the cervical mass was composed of malignant neoplastic cells showing follicular appearance which reacted positive for thyroglobulin on immunohistochemistry. A characteristic feature of the tumor was abundant and metaplastic stromal components. Anastomosed collagenous tissues connecting to capsule of the tumor were abundant in the stroma. In parts of the collagenous tissues, mature cartilages and bones were continuously formed. There was no cellular atypia or invasion in the components. We diagnosed this case as follicular thyroid carcinoma with metaplastic stroma. This is the first case report that characterizes stromal components with chondroid and osseous metaplasia in a canine thyroid carcinoma. PMID:24805905

  1. Thyroid Growth and Cancer

    PubMed Central

    Williams, Dillwyn

    2015-01-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term ‘cancer’ to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID

  2. 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.

  3. Hypoxia promotes thyroid differentiation of native murine induced pluripotent stem cells.

    PubMed

    Yang, Yipeng; Lu, Yunshu; Chen, Tong; Zhang, Shenglai; Chu, Bingfeng; Gong, Yurong; Zhao, Weixin; Zhu, Jian; Liu, Yingbin

    2016-01-01

    Hypothyroidism is a very common hormonal deficiency and the stem cell technology which developed in the recent years may offer a therapeutic strategy for treating this disorder. Hypoxia has been demonstrated to play an important role in embryonic formation and development and to modulate stem cell differentiation. However, the influence of oxygen tension on thyroid differentiation has not been studied. In this study, we used murine induced pluripotent stem (iPS) cells for thyroid cell differentiation under normoxic and hypoxic conditions and compared differentiation efficiency in morphology, function, gene and protein expression under both conditions. We found that hypoxia promoted adhesion and outgrowth of embryoid bodies (EBs) derived from murine iPS cells. Expression of endodermal markers (Foxa2 and Gata4) and thyroid transcription factors (Pax8 and Nkx2.1) was increased by hypoxia at both gene and protein levels during early-mid differentiation stages (p<0.05). And so were the thyroid specific markers NIS and TSHR at the end of the experiment (p<0.05). In addition, functional iodide uptake by differentiated cells was also increased after hypoxia. Thyroid differentiation from iPS cells is enhanced under hypoxia and this may involve hypoxia inducible factors (HIFs) and their downstream gene FGF2. Our data offer a foundation for understanding thyroid development and provide a potentially more efficient way to use cell therapy for treating thyroid deficiency. PMID:27389981

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

    PubMed Central

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

    2016-01-01

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

  5. Mixed medullary-papillary carcinoma of the thyroid: report of two cases and review of the literature.

    PubMed

    Gurkan, Eren; Gurbuz, Yesim; Tarkun, Ilhan; Canturk, Zeynep; Cetinarslan, Berrin

    2014-01-01

    Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are two distinct types of thyroid carcinoma with considerable difference in terms of cellular origin, histopathological appearance, clinical course and prevalence. The histogenetic origin and possible molecular mechanisms responsible for the development of mixed medullary-papillary carcinoma of the thyroid are still unclear. The most widely accepted hypotheses considering co-occurrence of MTC and PTC are stem cell theory, collision effect theory and hostage theory. Herein we describe two rare cases of mixed medullary-papillary thyroid carcinoma with co-occurrence of MTC and PTC which developed with concomitant MEN 2A and different sites of lymph node metastasis in the first patient, while with atypical clinical presentation in the second patient. In conclusion, co-expression of thyroglobulin, synaptophysin and chromogranin by the papillary component of mixed tumor seems to support stem cell theory in our first case, whereas positive staining for calcitonin but not for thyroglobulin in the medullary component of the tumor along with separation of these two tumors from each other by a normal thyroid tissue seem to indicates the likelihood of collision effect theory in our second case.

  6. Dramatic response of follicular thyroid carcinoma with superior vena cava syndrome and tracheal obstruction to external-beam radiotherapy

    SciTech Connect

    Wilford, M.R.; Chertow, B.S.; Lepanto, P.B.; Leidy, J.W. Jr. )

    1991-06-01

    We report a patient with follicular thyroid carcinoma progressing to superior vena cava (SVC) syndrome and tracheal obstruction despite multiple doses of radioactive iodine therapy but subsequently responding dramatically to external-beam radiotherapy (RT). Although RT is not considered to be the treatment of choice for follicular carcinoma, RT in our patient produced unequivocal improvement of SVC syndrome and tracheal obstruction.

  7. Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis.

    PubMed

    Chitikova, Zhanna; Pusztaszeri, Marc; Makhlouf, Anne-Marie; Berczy, Margaret; Delucinge-Vivier, Celine; Triponez, Frederic; Meyer, Patrick; Philippe, Jacques; Dibner, Charna

    2015-05-10

    We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-frozen and FFPE samples. NanoString analysis of 51 transcripts in 17 PTC and 17 benign nodule samples obtained from different donors and in 24 pairs of benign and PTC nodules, obtained from the same donor (multinodular goiters), confirmed significant alterations in the levels of BMAL1, c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was established for each sample, based on the combined expression levels of BMAL1, CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this predictive score closely correlated with the clinicopathological characteristics of the analyzed thyroid nodules. Our study identified new thyroid transcripts with altered levels in PTC using the NanoString approach. A predictive score correlation coefficient might contribute to improve the preoperative diagnosis of thyroid nodules.

  8. Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland.

    PubMed

    Postiglione, M P; Parlato, R; Rodriguez-Mallon, A; Rosica, A; Mithbaokar, P; Maresca, M; Marians, R C; Davies, T F; Zannini, M S; De Felice, M; Di Lauro, R

    2002-11-26

    The thyroid-stimulating hormone/thyrotropin (TSH) is the most relevant hormone in the control of thyroid gland physiology in adulthood. TSH effects on the thyroid gland are mediated by the interaction with a specific TSH receptor (TSHR). We studied the role of TSHTSHR signaling on gland morphogenesis and differentiation in the mouse embryo using mouse lines deprived either of TSH (pit(dw)pit(dw)) or of a functional TSHR (tshr(hyt)tshr(hyt) and TSHR-knockout lines). The results reported here show that in the absence of either TSH or a functional TSHR, the thyroid gland develops to a normal size, whereas the expression of thyroperoxidase and the sodium/iodide symporter are reduced greatly. Conversely, no relevant changes are detected in the amounts of thyroglobulin and the thyroid-enriched transcription factors TTF-1, TTF-2, and Pax8. These data suggest that the major role of the TSH/TSHR pathway is in controlling genes involved in iodide metabolism such as sodium/iodide symporter and thyroperoxidase. Furthermore, our data indicate that in embryonic life TSH does not play an equivalent role in controlling gland growth as in the adult thyroid.

  9. The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis.

    PubMed

    Riesco-Eizaguirre, Garcilaso; Wert-Lamas, León; Perales-Patón, Javier; Sastre-Perona, Ana; Fernández, Lara P; Santisteban, Pilar

    2015-10-01

    The presence of differentiated thyroid cells in thyroid cancer is critical for the antitumor response to radioactive iodide treatment, and loss of the differentiated phenotype is a key hallmark of iodide-refractory metastatic disease. The role of microRNAs (miRNA) in fine-tuning gene expression has become a major regulatory mechanism by which developmental and pathologic processes occur. In this study, we performed next-generation sequencing and expression analysis of eight papillary thyroid carcinomas (PTC) to comprehensively characterize miRNAs involved in loss of differentiation. We found that only a small set of abundant miRNAs is differentially expressed between PTC tissue and normal tissue from the same patient. In addition, we integrated computational prediction of potential targets and mRNA sequencing and identified a master miRNA regulatory network involved in essential biologic processes such as thyroid differentiation. Both mature products of mir-146b (miR-146b-5p and -3p) were among the most abundantly expressed miRNAs in tumors. Specifically, we found that miR-146b-3p binds to the 3'-untranslated region of PAX8 and sodium/iodide symporter (NIS), leading to impaired protein translation and a subsequent reduction in iodide uptake. Furthermore, our findings show that miR-146b and PAX8 regulate each other and share common target genes, thus highlighting a novel regulatory circuit that governs the differentiated phenotype of PTC. In conclusion, our study has uncovered the existence of a miR-146b-3p/PAX8/NIS regulatory circuit that may be exploited therapeutically to modulate thyroid cell differentiation and iodide uptake for improved treatment of advanced thyroid cancer.

  10. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

    SciTech Connect

    Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella

    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 and 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.

  11. Initial Treatment Patterns in Younger Adult Patients with Differentiated Thyroid Cancer in California

    PubMed Central

    Semrad, Alison M.; Farwell, D. Gregory; Chen, Yingjia; Cress, Rosemary

    2015-01-01

    Background: Differentiated thyroid cancer (DTC) is among the most common malignancies in the adolescent and young adult (age 15–39 years) population, and its incidence is rising. Younger age (<45 years) is an important prognostic indicator and is incorporated into the TNM classification system. This study hypothesized that this would result in distinct treatment patterns for younger and older patients. Methods: Using the California Cancer Registry, 24,362 patients with DTC from 2004 to 2011 were identified, and they were divided into younger (<45 years) and older (≥45 years) cohorts. Demographic and clinical variables were tabulated and then compared using chi-square tests. Treatment variables included total or near total thyroidectomy, other types of thyroid surgery, and the administration of radioiodine as part of the initial treatment. Multivariable logistic regression was used to identify independent predictors of treatment administered. Results: Younger patients were more likely to be Hispanic (32.5% vs. 21.2%) and female (82.7% vs. 74.7%), and to have papillary carcinoma (92.9% vs. 90.9%) and lymph node involvement (32.8% vs. 19.7%; p<0.0001). On multivariable analysis, younger patients (OR 1.20 [CI 1.11–1.30]), higher T-stage tumors, higher socioeconomic status (SES), and papillary carcinoma were predictors of undergoing total thyroidectomy versus less than total thyroid surgery. After adjustment, predictors of radioiodine administration included younger age (OR 1.12 [CI 1.05–1.18]), higher SES, total thyroidectomy, higher T stage, and lymph node positivity. Conclusions: Younger patients with DTC in California are more likely to be female and Hispanic with papillary histology. After adjustment for disease and demographic characteristics, younger patients are more likely to undergo total thyroidectomy as their initial surgery and are more likely to receive radioiodine. Given their excellent prognosis and the potential for adverse sequelae from initial

  12. FOXE1 Association with Differentiated Thyroid Cancer and Its Progression

    PubMed Central

    Penna-Martinez, Marissa; Epp, Friederike; Kahles, Heinrich; Ramos-Lopez, Elizabeth; Hinsch, Nora; Hansmann, Martin-Leo; Selkinski, Ivan; Grünwald, Frank; Holzer, Katharina; Bechstein, Wolf O.; Zeuzem, Stefan; Vorländer, Christian

    2014-01-01

    Background: Single nucleotide polymorphisms (SNPs) near thyroid transcription factor genes (FOXE1 rs965513/NKX2-1 rs944289) have been shown to be associated with differentiated thyroid cancer (DTC) in Caucasoid populations. We investigated the role of those SNPs in German patients with DTC and also extended our analysis to tumor stages and lymphocytic infiltration of the tumors (ITL). Methods: Patients with DTC (n=243; papillary, PTC; follicular, FTC) and healthy controls (HC; n=270) were analyzed for the rs965513 and rs944289 SNPs. Results: The case-control analysis for rs965513 SNP showed that the genotypes “AA,” “AG,” and minor allele “A” were more frequent in patients with DTC than in HC (pronounced in PTC pgenotype=0.000084, pallele=0.006 than FTC pgenotype=0.29 and pallele=0.06). Furthermore, subgroup analysis of the DTC patients stratified for primary tumor stage (T1–T2, T3–T4), the absence or presence of regional lymph node metastases (N0, N1), for distant metastases (M0, M1), as well as for ITL, showed an association of rs965513 with stages T1–T2, T1–T3, N1, and absence of ITL. The NKX2-1 SNP rs944289, however, was not associated with DTC. Conclusion: Our results confirm that the FOXE1 rs965513 SNP confers an increased risk for DTC in the German population, particularly allele “A” and the genotypes “AA” and “AG” for PTC. This increased risk was also observed in advanced tumor stages and absence of ITL, which may reflect the course of a more aggressive disease. The NKX2-1 rs944289 SNP, however, appears to play a secondary role in the development of DTC in the German population. PMID:24325646

  13. Solitary fibrous tumor of the thyroid: cytopathologic findings and differential diagnosis.

    PubMed

    Parwani, Anil V; Galindo, Rene; Steinberg, David M; Zeiger, Martha A; Westra, William H; Ali, Syed Z

    2003-04-01

    Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that arises primarily from the pleura. Extrapleural occurrences are rare. To our knowledge, there is no published account of this entity in the thyroid in the cytopathology literature. We report the case of a 61-yr-old man who was evaluated at The Johns Hopkins Hospital for a slow-growing thyroid mass that was present for 2 yr despite thyroid hormone suppression. Thyroid-stimulating hormone (TSH) was within normal limits. The patient underwent ultrasound-guided fine-needle aspiration (FNA), which showed predominantly discohesive slender spindle-shaped cells and fragments of collagenized stromal tissue. After the FNA diagnosis of "thyroid neoplasm" was made, the patient underwent a near-total thyroidectomy, which revealed a SFT. Differential diagnosis of spindle cell lesions in thyroid is also presented.

  14. Clonality analysis of multifocal papillary thyroid carcinoma by using genetic profiles.

    PubMed

    Lu, Zheming; Sheng, Jindong; Zhang, Yujie; Deng, Jianhua; Li, Yong; Lu, Aiping; Zhang, Juan; Yu, Huan; Zhang, Min; Xiong, Zikai; Yan, Hai; Diplas, Bill H; Lu, Youyong; Liu, Baoguo

    2016-05-01

    Papillary thyroid carcinoma (PTC) is the most common adult thyroid malignancy and often presents with multiple anatomically distinct foci within the thyroid, known as multifocal papillary thyroid carcinoma (MPTC). The widespread application of the next-generation sequencing technologies in cancer genomics research provides novel insights into determining the clonal relationship between multiple tumours within the same thyroid gland. For eight MPTC patients, we performed whole-exome sequencing and targeted region sequencing to identify the non-synonymous point mutations and gene rearrangements of distinct and spatially separated tumour foci. Among these eight MPTCs, completely discordant mutational spectra were observed in the distinct cancerous nodules of patients MPTC1 and 5, suggesting that these nodules originated from independent precursors. In another three cases (MPTC2, 6, and 8), the distinct MPTC foci of these patients had no other shared mutations except BRAF V600E, also indicating likely independent origins. Two patients (MPTC3 and 4) shared almost identical mutational spectra amongst their separate tumour nodules, suggesting a common clonal origin. MPTC patient 7 had seven cancer foci, of which two foci shared 66.7% of mutations, while the remaining cancer foci displayed no common non-synonymous mutations, indicating that MPTC7 has multiple independent origins accompanied by intraglandular disease dissemination. In this study, we found that 75% of MPTC cases arose as independent tumours, which supports the field cancerization hypothesis describing multiple malignant lesions. MPTC may also arise from intrathyroidal metastases from a single malignant clone, as well as multiple independent origins accompanied by intrathyroidal metastasis.

  15. Radioactive iodine (RAI) therapy for distantly metastatic differentiated thyroid cancer (DTC) in juvenile versus adult patients.

    PubMed

    Kammori, Makoto; Fukumori, Tatsuya; Sugishita, Yoshiyuki; Hoshi, Masae; Shimizu, Kazuo; Yamada, Tetsu

    2015-01-01

    In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent characteristics and favorable prognosis are observed in comparison with many other carcinomas. However, recurrence is frequent, necessitating additional treatment, including radioactive iodine (RAI) therapy. In this report, the probability of recurrence, prognostic factors, treatment, and outcomes in both juvenile- and adult-onset DTC were analyzed and compared. At our institution, a total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection. The patients included 23 in their teens, 118 in their twenties, and 1412 in their thirties or older. The risk factors for distant metastases for DTC were male gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node metastases from PTC, and the presence of more than two distant metastatic foci. Patients with the highest risk underwent RAI ablation in line with institutional guidelines. Although the overall outcome in our juvenile patients was excellent, during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3% achieved complete remission, 4.35% partial remission, and 4.35% stable disease, with no disease-related deaths. Among the 118 patients in their twenties to thirties, 1 (0.8%) experienced progressive disease and disease-related death. A younger age at diagnosis and less radical primary surgery without subsequent RAI ablation are factors strongly predictive of distant metastases in patients with juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with high- and intermediate-risk juvenile DTC.

  16. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    PubMed Central

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  17. Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2015-09-28

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  18. [Experience with a Thyroid Carcinoma in Which Symptoms Were Moderated by Local Excision].

    PubMed

    Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2015-11-01

    Thyroid carcinoma have almost improvement of thing ingredient doing sacculation in a portion is most. We report a case of a giant thyroid carcinoma with a cyst that was operated on. A 64-year-old man showed giant cyst characteristics on cervical ultrasonography, with a mass with calcification on the left lobe. The findings showed an exclusion of tracheal deviation and the esophagus and left total jugular veins were shown. We observed giant calcification in the left lobe center, and the cervical CT laboratory findings showed sacculation on the outside. The cyst showed partial exclusion of the total jugular veins. We preliminarily diagnosed class Ⅳ papillary cancer by cytology. The chosen treatment was hypervolemia control on the bottom, plus total thyroidectomy and a lymphodectomy. A perioperative portion of the cyst ingredients was washed away. The whole thyroid gland was firm, and the right lobe showed a tumor. We left one part of the cyst that stuck to a blood vessel in situ. The cervical intracranial pressure, which was the palliative purpose of operating, seemed significantly improved. PMID:26805141

  19. Iodine-131 in breast milk following therapy for thyroid carcinoma

    SciTech Connect

    Robinson, P.S.; Barker, P.; Campbell, A.

    1994-11-01

    This study evaluates breast milk secretion of {sup 131}I following therapeutic adminstration of 4000 MBq of {sup 131}I-iodide during lactation. Breast milk {sup 131}I activity concentration was measured over a 32-day period. Dosimetry calculations were undertaken to estimate the period for discontinuation of breast feeding and the equivalent dose to the breasts. To achieve an infant effective dose <1 mSv and an infant thyroid dose <10 mSv, breast feeding would need to be discontinued for at least 52 days. The estimated equivalent dose to the breasts was 1.6 Gy. It is suggested that {sup 131}I-iodide adminstration is not undertaken during lactation and that breast feeding is discontinued several days prior to administration. 26 refs., 2 figs., 2 tabs.

  20. Osteoclastome-like giant cell thyroid carcinoma controlled by intensive radiation and adriamycin, in a patient with meningioma and multiple myeloma treated by radiation and cytoxan

    SciTech Connect

    Vizel-Schwartz, M.

    1981-01-01

    The eighth cases of osteoclastome-like giant cell carcinoma of the thyroid, and the first one to be treated with adriamycin in addition to surgery and radiation, is reported. This rare variant of anaplastic thyroid carcinoma appeared in a patient operated on for meningioma and treated for multiple myeloma with cranial radiation and chronic administration of cytoxan.

  1. Analysis of Risk Factors Contributing to Recurrence of Papillary Thyroid Carcinoma in Chinese Patients Who Underwent Total Thyroidectomy

    PubMed Central

    Zhang, Wei; Jiao, De; Liu, Baoguo; Sun, Shanping

    2016-01-01

    Background Thyroid cancer is a very common endocrine malignancy, with a rate of total thyroidectomy reported to be up to 27.8%. However, studies analyzing the risk factors that contribute to recurrence of papillary thyroid carcinoma (PTC) after total thyroidectomy in China are still scarce. Material/Methods A total of 536 patients with PTC who underwent total thyroidectomy were retrospectively analyzed. Patients were divided into 2 groups: patients with no recurrent tumor were included in group 1 and patients with tumor recurrence were included in group 2. Results Of 536 patients, 65 patients (12.1%) developed a recurrence of PTC, and 471 patients (87.9%) did not have a recurrence. Univariate analysis indicated that male sex, age ≥50 years, tumor ≥1 cm, poor differentiation, lymph node metastasis, bilaterality, and multifocality may be related to PTC recurrence. Additionally, the results of the logistic regression analysis indicated that male sex, age ≥50 years, primary tumor ≥1 cm, poor dedifferentiation of the tumor, lymph node metastasis, and multifocality may be independent factors contributing to PTC recurrence. Conclusions Male sex, age more than 50 years, primary tumor larger than 1 cm, poor dedifferentiation of the primary tumor, lymph node metastasis, and multifocality were found to increase the risk of PTC recurrence in patients who underwent total thyroidectomy. Additionally, it is necessary to use strictly aggressive and extensive surgery, as well as close monitoring, after the operation. PMID:27084873

  2. Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma

    PubMed Central

    Oh, Woo Jin; Chung, Arthur Minwoo; Kim, Jee Soon; Han, Ji Heun; Hong, Sung Hoo; Lee, Ji Yeol; Choi, Yeong Jin

    2016-01-01

    Background The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities. Methods A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary’s Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor. Results The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively. Conclusions Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically. PMID:27498545

  3. Conserved Telomere Length in Human Ectopic Thyroids: An Argument Against Premature Differentiation Causing Arrested Migration

    PubMed Central

    Larrivée-Vanier, Stéphanie; Magne, Fabien; Patey, Natalie; Chanoine, Jean-Pierre; Vuissoz, Jean-Marc; Van Vliet, Guy; Deladoëy, Johnny

    2016-01-01

    Background In humans, the cause of arrested migration of the median thyroid anlage resulting in an ectopic sublingual gland is unknown. These ectopic glands have a normal follicular architecture but their thyrotropin-induced growth is insufficient, leading to congenital hypothyroidism in the vast majority of affected subjects. We hypothesized that arrested migration is due to premature differentiation [reflected by decreased telomere length (TL)], as observed in neural tube defects in mice. Methods Absolute TL and telomerase reverse transcriptase (hTERT) expression was measured in four ectopic and six orthotopic thyroids. TL was measured by quantitative polymerase chain reaction of genomic DNA, whereas hTERT expression was measured by quantitative polymerase chain reaction of total RNA. Results The mean ± standard deviation TL (in kilobases per diploid genome) was 140.45 ± 40.07 in ectopic and 97.50 ± 30.48 in orthotopic thyroids (p = 0.12). Expression of hTERT was quiescent in both ectopic and orthotopic thyroids. Conclusions Compared with orthotopic thyroids, TL shortening is not observed in ectopic thyroid tissues and, consequently, no compensatory hTERT expression was measured. This makes premature differentiation an unlikely cause of arrested migration and it suggests, indirectly, that ectopic thyroids are not at higher risk of cancer than orthotopic thyroids. PMID:26131731

  4. Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.

    PubMed

    Gordon, Michael S; Gordon, Murray B

    2016-01-01

    Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH. PMID:27656301

  5. Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus

    PubMed Central

    2016-01-01

    Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I131 therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH. PMID:27656301

  6. Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus

    PubMed Central

    2016-01-01

    Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I131 therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.

  7. "Intercellular bridges" in a case of well differentiated squamous carcinoma.

    PubMed

    Nguyen, Michaela; Mikita, Geoffrey; Hoda, Rana S

    2016-02-01

    Intercellular bridges may aide in definitive identification of malignant cell origin, especially in squamous cell carcinoma. They are difficult to identify in routine cytologic specimens and are especially rare in smear preparations. Herein, we present images of intercellular bridges from a case of well differentiated squamous cell carcinoma of the esophagus in a cytologic specimen obtained from FNA of a paraesophageal lymph node.

  8. Serum thyroglobulin in the monitoring of differentiated thyroid cancer.

    PubMed

    Evans, Carol; Tennant, Sarah; Perros, Petros

    2016-01-01

    Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement. The limitations of Tg immunoassay are well described and include potential interference from TgAb. For the majority of patients with DTC who are TgAb-negative, Tg measurement remains the most useful method of follow-up. For the TgAb-positive minority, interference and the possibility of producing erroneous results is a concern. Some assays are less badly affected than others and laboratories are advised to choose their assays carefully. Laboratories have sought to identify interferences using measurement of TgAb, lack of concordance between RIAs and immunometric assays and recovery of added Tg. More recently LC-MSMS assays to quantify Tg have been developed. They are not currently as sensitive as Tg immunoassays and it is likely these assays will, like immunoassays, be limited by Tg heterogeneity and standardization issues, although initial evaluations indicate that they may have value in the clinical setting as a second line test in antibody-positive DTC patients in whom Tg is unmeasurable by immunoassay. PMID:27542000

  9. miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma

    PubMed Central

    Minna, Emanuela; Romeo, Paola; Dugo, Matteo; De Cecco, Loris; Todoerti, Katia; Pilotti, Silvana; Perrone, Federica; Seregni, Ettore; Agnelli, Luca; Neri, Antonino; Greco, Angela; Borrello, Maria Grazia

    2016-01-01

    Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta-analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation. Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia. PMID:26871295

  10. miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma.

    PubMed

    Minna, Emanuela; Romeo, Paola; Dugo, Matteo; De Cecco, Loris; Todoerti, Katia; Pilotti, Silvana; Perrone, Federica; Seregni, Ettore; Agnelli, Luca; Neri, Antonino; Greco, Angela; Borrello, Maria Grazia

    2016-03-15

    Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta-analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation.Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia. PMID:26871295

  11. BGP serum levels in patients with thyroid carcinoma before and 4-14 weeks after radioiodine therapy.

    PubMed

    Stracke, H; Federlin, K

    1993-01-01

    In the present short paper we compared the BGP and AP levels of 26 patients with thyroid carcinoma during radio-iodine therapy. BGP values reflect the bone turnover before and after radio-iodine therapy. There were no significant AP changes during this period. These results suggest that thyroid hormone has a direct effect on osteoblast function and that this effect can be best monitored by determination of BGP levels.

  12. Serum calcitonin-lowering effect of magnesium in patients with medullary carcinoma of the thyroid.

    PubMed Central

    Anast, C; David, L; Winnacker, J; Glass, R; Baskin, W; Brubaker, L; Burns, T

    1975-01-01

    The effect of magnesium chloride or magnesium sulfate infusion on circulating levels of immunoreactive calcitonin (iCT) was evaluated on nine occasions in three patients with metastatic medullary carcinoma of the thyroid. One patient was normocalcemic and had normal circulating levels of immunoreactive parathyroid hormone (iPTH), one patient was hypocalcemic and had surgical hypoparathyroidism, and one patient had mild to moderate hypercalcemia associated with bone metastases. The basal serum iPTH levels were undetectable in the latter two patients. In every instance magnesium administration produced a rapid and striking fall in circulating iCT and usually a detectable fall in serum calcium. During the hypermagnesemic state, serum iPTH fell from normal to undetectable in the patient with normal parathyroid function, while serum iPTH levels remained undetectable in the hypoparathyroid patient and in the patient with hypercalcemia associated with bone metastases. The results of these studies indicate that: (a) contrary to what has been reported in normal experimental animals, magnesium administration lowers circulating iCT in human subjects with thyroid medullary carcinoma and (b) the calcium-lowering effect produced by magnesium in patients with medullary carcinoma may, in part at least, be due to a redistribution of body calcium that is not mediated by the actions of either parathyroid hormone or clacitonin. PMID:1202087

  13. Medullary Carcinoma of the Thyroid With Axillary Metastasis: A Case Report

    PubMed Central

    Ozdemir, Murat; Makay, Ozer; Simsir, Ilgin; Ertan, Yeşim; Icoz, Gokhan; Saygili, Füsun; Akyildiz, Mahir

    2015-01-01

    We report a case of axillary lymph node metastasis as a consequence of medullary thyroid carcinoma (MTC) in a 42-year-old man. On January 2009, the patient was referred to us for the management of right cervical lymph node enlargement. Total thyroidectomy was performed with right-sided functional neck dissection. Postoperative histopathology revealed MTC in the right lobe of the thyroid, with extrathyroidal extension and right-sided neck metastases. Multiple left cervical, mediastinal, and right axillary lymphadenopathies were detected at the third year follow-up exam. Left-sided functional neck dissection, axillary lymph node dissection, and mediastinal lymph node dissection were performed, and the pathologic outcomes revealed as the metastatic dissemination of MTC. After a disease-free term for 1 year, multiple metastatic lesions were detected in the patient. PMID:25785315

  14. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence.

    PubMed

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  15. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    PubMed Central

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  16. Evaluating Positron Emission Tomography Use in Differentiated Thyroid Cancer

    PubMed Central

    Esfandiari, Nazanene H.; Papaleontiou, Maria; Worden, Francis P.; Haymart, Megan R.

    2015-01-01

    Background: Using the Surveillance, Epidemiology, and End Results—Medicare database, a substantial increase was found in the use of positron emission tomography (PET) scans after 2004 in differentiated thyroid cancer (DTC) patients. The reason for the increased utilization of the PET scan was not clear based on available the data. Therefore, the indications for and outcomes of PET scans performed at an academic institution were evaluated. Methods: A retrospective cohort study was performed of DTC patients who underwent surgery at the University of Michigan Health System from 2006 to 2011. After identifying patients who underwent a PET scan, indications, rate of positive PET scans, and impact on management were evaluated. For positive scans, the location of disease was characterized, and presence of disease on other imaging was determined. Results: Of the 585 patients in the cohort, 111 (19%) patients had 200 PET scans performed for evaluation of DTC. Indications for PET scan included: elevated thyroglobulin and negative radioiodine scan in 52 scans (26.0%), thyroglobulin antibodies in 13 scans (6.5%), rising thyroglobulin in 18 scans (9.0%), evaluation of abnormality on other imaging in 22 scans (11.0%), evaluation of extent of disease in 33 scans (16.5%), follow-up of previous scan in 57 scans (28.5%), other indications in two scans (1.0%), and unclear indications in three scans (1.5%). The PET scan was positive in 124 studies (62.0%); positivity was identified in the thyroid bed on 25 scans, cervical or mediastinal lymph nodes on 105 scans, lung on 28 scans, bone on four scans, and other areas on 14 scans. Therapy following PET scan was surgery in 66 cases (33.0%), chemotherapy or radiation in 23 cases (11.5%), observation in 110 cases (55.0%), and palliative care in one case (0.5%). Disease was identifiable on other imaging in 66% of cases. PET scan results changed management in 59 cases (29.5%). Conclusions: In this academic medical center, the PET scan was

  17. C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

    PubMed

    Nakazawa, Tadao; Cameselle-Teijeiro, José; Vinagre, João; Soares, Paula; Rousseau, Emmanuel; Eloy, Catarina; Sobrinho-Simões, Manuel

    2014-09-01

    In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery. PMID:24599901

  18. Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma

    PubMed Central

    Lee, Hyekyung; Baek, Tae Hwa; Park, Meeja; Lee, Seung Yun; Son, Hyun Jin; Kang, Dong Wook; Kim, Joo Heon; Kim, Soo Young

    2016-01-01

    Background There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. Methods We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. Results From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. Conclusions Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma. PMID:27550048

  19. Cribriform-morular variant of papillary thyroid carcinoma at pediatric age - case report and review of the literature.

    PubMed

    Brehar, Andreea Cristiana; Terzea, Dana Cristina; Ioachim, Dumitru Lucian; Procopiuc, Camelia; Brehar, Felix Mircea; Bulgăr, Alexandra Cătălina; Ghemigian, Mircea Vasile; Dumitrache, Constantin

    2016-01-01

    Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor, which exceptionally occurs at pediatric age. CMV-PTC may develop in patients with familial adenomatous polyposis (FAP) or may be a sporadic tumor. The authors present a case of CMV-PTC in a 10-year-old girl patient without FAP history, who presented with a left neck mass. The patient underwent total thyroidectomy with central compartment neck dissection. Histopathological diagnosis was compatible with cribriform-morular variant of papillary thyroid carcinoma and Hashimoto's thyroiditis. Immunostaining was positive for thyroglobulin, β-catenin, CD10 and p53. Molecular test showed the absence of BRAF, K-RAS mutations, deletions or duplications of APC (adenomatosis polyposis coli) gene and showed the presence of RET÷PTC (rearranged during transfection÷papillary thyroid carcinoma) rearrangements. At 32 months follow-up, the patient was without signs of recurrence. This particular form of thyroid carcinoma should raise suspicion of a possible familial cancer syndrome, therefore early diagnosis and thoroughly evaluation, which includes colonoscopy and genetic screening are mandatory. PMID:27516030

  20. Renal cell carcinoma and synchronous thyroid metastasis with neoplastic thrombosis of the internal jugular vein: report of a case.

    PubMed

    Matei, Deliu-Victor; Brescia, Antonio; Nordio, Andrea; Spinelli, Matteo Giulio; Melegari, Sara; Cozzi, Gabriele; Andrioli, Massimiliano; Salvatori, Pietro

    2011-12-01

    A case of thyroid metastasis of a renal clear cell carcinoma is presented. The fine-needle aspiration cytology pointed out the primary tumor origin. The patient underwent robot-assisted radical nephrectomy and contextual thyroidectomy. During the operative procedure, a neoplastic thrombus extending from the thyroid metastasis and protruding into the internal jugular vein was found. As a result, thrombectomy and ligation of the internal jugular vein were required. In cases of single synchronous thyroid metastases form RCC, radical surgery should be advisable. Robotic approach allows to associate major surgery procedures, as nephrectomy, with radical metastasectomy.

  1. Use of Color Doppler Ultrasonography to Measure Thyroid Blood Flow and Differentiate Graves' Disease from Painless Thyroiditis

    PubMed Central

    Hiraiwa, Tetsuya; Tsujimoto, Naoyuki; Tanimoto, Keiji; Terasaki, Jungo; Amino, Nobuyuki; Hanafusa, Toshiaki

    2013-01-01

    Backgrounds Color Doppler ultrasonography (CDU) has not yet been established as a method to investigate the pathogenesis of thyrotoxicosis. Objectives Our first objective was to determine whether the measurement of peak systolic blood-flow velocity in the superior thyroid artery (STV) and thyroid tissue blood flow (TBF) using CDU could differentiate Graves' disease (GD) from painless thyroiditis (PT). The second objective was to examine the factors mediating increased blood flow to the thyroid gland in GD. Methods Recruited patients had untreated GD or PT and visited the Department of Internal Medicine (I), Osaka Medical College, between April 1, 2006 and May 31, 2010. Age, gender, blood pressure, pulse rate, thyroid-stimulating hormone, free thyroxine, tri-iodothyronine, TSH receptor antibody and thyroid volume were evaluated in patients. In addition, bilateral measurements of STV, TBF and peak systolic velocity in the common carotid artery (CCV) were also performed. TBF was quantified by calculating the ratio of blood-flow pixels to total pixels in the region of interest using sagittal section images of the thyroid gland. Receiver-operating characteristic curve analysis was performed to determine the ability of STV and TBF measurements to differentiate GD from PT. Results For the average of STV measured on both sides, the area under the receiver-operating characteristic curve (AUC) was 0.956. For the average of TBF measured on both sides, the AUC was 0.920. At an average STV cut-off value of 43 cm/s, the sensitivity to discriminate GD from PT was 0.87 and the specificity was 1.00. At an average TBF cut-off value of 3.8%, the sensitivity was 0.71 and the specificity was 1.00. In the GD group, neither blood pressure nor pulse rate correlated with the average STV or TBF. Moreover, there was no correlation between STV and CCV or between TBF and CCV on either side. However, STV was correlated with TBF (right side: R = 0.47; left side: R = 0.52). Conclusions The

  2. Differentiation of complicated cholecystitis from gallbladder carcinoma by computed tomography

    SciTech Connect

    Smathers, R.L.; Lee, J.K.T.; Heiken, J.P.

    1984-08-01

    Differentiation between complicated cholecystitis and advanced gallbladder carcinoma can be difficult when clinical findings are confusing. Computed tomographic (CT) scans were reviewed from 22 patients with a surgical diagnosis of complicated cholecystitis (11 cases) or advanced gallbladder carcinoma (11 cases). The presence of a curvilinear low-attenuation halo around the gallbladder wall was specific for complicated cholecystitis. Findings indicative of gallbladder carcinoma included a focal soft-invasion or metastases. Knowledge of these differential CT findings may result in a more accurate preoperative diagnosis.

  3. Iodine-131 MIBG uptake in metastatic medullary carcinoma of the thyroid. A patient treated with somatostatin

    SciTech Connect

    Keeling, C.A.; Basso, L.V.

    1988-04-01

    A 47-year-old man with multiple endocrine neoplasia (MEN) type 2a syndrome in whom metaiodobenzylguanidine (MIBG) concentrated in lesions from metastatic medullary carcinoma of the thyroid is reported. A somatostatin analogue (Sandostatin SMS 201-995) alleviated the symptoms of flushing and diarrhea associated with the elevated calcitonin levels but it did not alter either the course of the disease or the MIBG images. A review of the literature is presented of the noncatecholamine secreting tumors associated with MIBG uptake. Similarities between this case and metastatic carcinoid syndrome are discussed. 27 references.

  4. Follicular carcinoma of the thyroid with functioning metastases and clinical hyperthyroidism.

    PubMed Central

    McConnon, J. K.; von Westarp, C.; Mitchell, R. I.

    1975-01-01

    Hyperthyroidism associated with metastatic follicular carcinoma of the thyroid gland is rare. In one patient the mass of functioning follicular tissue in the primary and metastatic tumour was so great that excessive amounts of thyroxine and triiodothyronine were produced and, as a result, clinical hyperthyroidism developed. This was in spite of the fact that the activity per unit of tissue was not supranormal and may even have been slightly subnormal. The initial response of the metastases to 131I ablative therapy was excellent. Images FIG. 1 FIG. 2 FIG. 3A FIG. 3B FIG. 4 FIG. 5 PMID:1122444

  5. Utility of Thyroglobulin measurement in fine-needle aspiration biopsy specimens of lymph nodes in the diagnosis of recurrent thyroid carcinoma

    PubMed Central

    Baloch, Zubair W; Barroeta, Julieta E; Walsh, Janet; Gupta, Prabodh K; LiVolsi, Virginia A; Langer, Jill E; Mandel, Susan J

    2008-01-01

    Introduction The most common site for the metastasis of papillary carcinoma of the thyroid (PTC) is regional lymph nodes. Ultrasound (US) imaging may identify abnormal appearing lymph nodes, suspicious for PTC recurrence. Although fine needle aspiration biopsy (FNAB) of abnormal lymph nodes is often diagnostic of recurrence, small or cystic lymph nodes may be non-diagnostic due to lack of tumor cells. The measurement of thyroglobulin (TG) levels in FNAB specimens from lymph nodes suspicious for recurrent PTC can serve as an adjunct to the cytologic diagnosis. Materials and methods 115 abnormal appearing lymph nodes were aspirated under ultrasound guidance in 89 patients with history of thyroid carcinoma. In addition to obtaining material for cytologic interpretation, an additional aspirate was obtained by FNAB and rinsed in 1 ml of normal saline for TG level measurements. Results The cytologic diagnoses included: 35 (30%) reactive lymph node, no tumor seen (NTS), 39 (34%) PTC, 23 (20%) inadequate for evaluation due to lack of lymphoid or epithelial cells (NDX) 15 (13%) atypical/suspicious for PTC, and 3 (3%) other (e.g. paraganglioma, poorly differentiated carcinoma and carcinoma not otherwise specified). TG levels were markedly elevated (median 312 ng/ml; normal < 10 ng/ml) in 28 (72%) cases of PTC lymph node recurrence identified on cytology. TG measurements were also elevated in 5 lymph nodes classified as NTS and 4 NDX on cytology which resulted in 5 and 3 carcinoma diagnoses respectively on histological follow-up. Of the 9 atypical/suspicious cases with elevated TG levels all resulted in carcinoma diagnoses on follow-up. Conclusion The measurement of TG in FNAB specimens from lymph node in patients with history of PTC is useful in detecting recurrent disease, especially in cases when the specimen is known to be or likely to be inadequate for cytologic evaluation. PMID:18237420

  6. Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma.

    PubMed

    Czajka, Agnieszka Anna; Wójcicka, Anna; Kubiak, Anna; Kotlarek, Marta; Bakuła-Zalewska, Elwira; Koperski, Łukasz; Wiechno, Wiesław; Jażdżewski, Krystian

    2016-01-01

    Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARβ). However, expression of RARβ is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients. PMID:27011326

  7. Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma.

    PubMed

    Czajka, Agnieszka Anna; Wójcicka, Anna; Kubiak, Anna; Kotlarek, Marta; Bakuła-Zalewska, Elwira; Koperski, Łukasz; Wiechno, Wiesław; Jażdżewski, Krystian

    2016-01-01

    Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARβ). However, expression of RARβ is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients.

  8. Development and Characterization of Six New Human Papillary Thyroid Carcinoma Cell Lines

    PubMed Central

    Henderson, Ying C.; Ahn, Soon-Hyun; Ryu, Junsun; Chen, Yunyun; Williams, Michelle D.; El-Naggar, Adel K.; Gagea, Mihai; Schweppe, Rebecca E.; Haugen, Bryan R.; Lai, Stephen Y.

    2015-01-01

    Context: Cell lines are a widely used tool in cancer research. However, despite the relatively high incidence of papillary thyroid carcinoma (PTC), there are only four PTC cell lines available for international research audience. Objective: The objective of this study was to establish and characterize new PTC cell lines that represent primary tumor biology. Surgical specimens were obtained to generate PTC cell lines. Short tandem repeat profiling was used to confirm the uniqueness of the cell lines against databases of known cell lines and mutations were assessed using Sequenom. The expression of thyroid-specific genes was examined using real-time PCR. Tumorigenicity was determined using an orthotopic thyroid xenograft tumor mouse model. Results: Six PTC cell lines (five conventional PTCs and one follicular variant of PTC) were generated and found to be unique when compared by short tandem repeat profiling against databases of all existing cell lines. The five conventional PTC cell lines carry the BRAF V600E mutation and the follicular variant of PTC cell line had an NRAS mutation. Five of the six cell lines had a mutation in the promoter of the human telomerase reverse transcriptase gene. None of the cell lines have RET/PTC rearrangements. Three cell lines were tumorigenic in the orthotopic thyroid xenograft tumor mouse model. Conclusions: These five characterized conventional PTC cell lines and the unique follicular variant of PTC cell line should be valuable reagents for thyroid cancer research. The three tumorigenic cell lines can be used for in vivo testing of targeted therapeutic and novel agents. PMID:25427145

  9. Surgical procedures for papillary thyroid carcinoma located in the thyroid isthmus: an intention-to-treat analysis

    PubMed Central

    Lei, Jianyong; Zhu, Jinqiang; Li, Zhihui; Gong, Rixiang; Wei, Tao

    2016-01-01

    Objective We sought to evaluate and compare the outcomes of different surgical protocols for papillary thyroid cancer (PTC) located in the isthmus in a retrospective intention-to-treat analysis. Patients and methods The data of 3,068 patients who received thyroidectomy due to thyroid cancer in our center were reviewed. Of these, 103 patients had a dominant carcinoma located in the isthmus. Various baseline and tumor characteristics and surgical outcomes were evaluated and compared with respect to the different surgical protocols (85 cases with total thyroidectomy and 18 cases with less-than-total thyroidectomy). Univariate and multivariate analyses were performed to identify resected patients who developed recurrence with isthmic PTC. Results The postoperative complication rates were comparable between the two groups (17.6% versus 11.1%, P=0.500). Although the total thyroidectomy group showed a much higher rate (P=0.004) and number (P<0.001) of parathyroidectomies, long-term follow-up indicated that parathyroid autotransplantation did not significantly damage the function of the parathyroid (P>0.05). Tumor recurrence was observed in five patients, including two patients in the total thyroidectomy group and three patients in the less-than-total thyroidectomy group; the tumor recurrence rate in the total thyroidectomy group was significantly lower than that in the less-than-total thyroidectomy group (P=0.040). Univariate and multivariate analyses indicated less-than-total thyroidectomy as a risk factor for tumor recurrence in PTC cases with tumors located at the isthmus (hazard ratio: 1.870, 95% confidence interval: 1.320–2.218, P<0.001). Conclusion Our findings indicate that total thyroidectomy is an appropriate initial surgical protocol for isthmic PTC due to the lower recurrence rate, comparable postoperative complication rate, and parathyroid function recovery. PMID:27578987

  10. Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions.

    PubMed

    Davidson, Ben; Stavnes, Helene Tuft; Holth, Arild; Chen, Xu; Yang, Yanqin; Shih, Ie-Ming; Wang, Tian-Li

    2011-03-01

    Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities.With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies,as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina.Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3,PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery.

  11. Establishment and characterization of a human thyroid carcinoma cell line (HOTHC) producing colony stimulating factor.

    PubMed

    Ishiwata, Isamu; Ono, Isao; Kiguchi, Kazushige; Ishiwata, Chieko; Soma, Masayuki; Ishikawa, Hiroshi

    2005-09-01

    A cell line designated HOTHC was established from an anaplastic carcinoma (giant cell type) of the thyroid gland of 80-year-old woman. The HOTHC line grew rapidly in multilayer without contact inhibition, and more than 120 serial passages were made within 27 months. The cells were spindle or polygonal in shape and revealed neoplastic and pleomorphic features. These cells were characterized as containing coloid droplets and poorly developed rough-endoplasmic reticulum in the cytoplasm. Doubling time was about 24 hours and plating efficiency was about 70%. The karyotype exhibits hyperploidy and marker chromosomes, and the modal chromosome number ranged between 77-90. The HOTHC cells were transplanted into the subcutis of BALB/c nude mice and produced anaplatic carcinomas (giant cell type) resembling the original tumor. The HOTHC cells produced colony stimulating factor (CSF) and caused granulocytosis in the mice. PMID:17022149

  12. False positive diagnosis on (131)iodine whole-body scintigraphy of differentiated thyroid cancers.

    PubMed

    Triggiani, Vincenzo; Giagulli, Vito Angelo; Iovino, Michele; De Pergola, Giovanni; Licchelli, Brunella; Varraso, Antonio; Dicembrino, Franca; Valle, Guido; Guastamacchia, Edoardo

    2016-09-01

    (131)Iodine is used both to ablate any residual thyroid tissue or metastatic disease and to obtain whole-body diagnostic images after total thyroidectomy for differentiated thyroid cancer (DTC). Even though whole-body scan is highly accurate in showing thyroid residues as well as metastases of DTC, false positive results can be found, possibly leading to diagnostic errors and unnecessary treatments. This paper reviews the physiological and pathological processes involved as well as the strategy to recognize and rule out false positive radioiodine images.

  13. Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

    PubMed Central

    Caria, Paola; Cantara, Silvia; Frau, Daniela Virginia; Pacini, Furio; Vanni, Roberta; Dettori, Tinuccia

    2016-01-01

    Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of HER2 (Human Epidermal Growth Factor Receptor 2) amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL and BRAF mutational status. We analyzed HER2 gene amplification and the integrity of ALK, ETV6, RET, and BRAF genes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzed BRAFV600E mutation and RTL by qRT-PCR. Significant HER2 amplification (p = 0.0076), which was restricted to scattered groups of cells, was found in fPTC samples. HER2 amplification in fPTCs was invariably associated with BRAFV600E mutation. RTL was shorter in fPTCs than sPTCs (p < 0.001). No rearrangements of other tested genes were observed. These findings suggest that the association of HER2 amplification with BRAFV600E mutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy. PMID:27775641

  14. Single nucleotide polymorphisms of ataxia telangiectasia mutated and the risk of papillary thyroid carcinoma.

    PubMed

    Song, Chang Myeon; Kwon, Tack-Kyun; Park, Byung Lae; Ji, Yong Bae; Tae, Kyung

    2015-01-01

    Genetic factors associated with susceptibility to papillary thyroid carcinoma (PTC) are not well known. We evaluated the association between single nucleotide polymorphisms (SNPs) of ataxia telangiectasia mutated (ATM) and the risk of PTC. A total of 437 histologically confirmed PTC cases and 184 cancer-free controls without thyroid nodules were recruited. Genotypes with respect to five ATM SNPs (rs189037, rs664677, rs373759, rs664143, and rs4585) were determined by the TaqMan assay, and odds ratios and 95% confidence intervals were obtained by logistic regression analysis. Linkage disequilibria and haplotypes were examined from the genotype data. When evaluated separately the genotype distributions of the five ATM SNPs were similar in the PTC cases and controls. Three ATM SNPs (rs373759, rs664143, and rs4585) were found to be in strong linkage disequilibrium (D' = 1.00, P < 0.001). When the three haplotypes (C-A-G), (T-G-T), and (C-G-T) of these three ATM SNP sites were analyzed, ATM haplotype (C-G-T) +/- was associated with a lower risk of PTC than ATM haplotype (C-G-T) -/- (P = 0.03) after adjusting for age and gender. Our results suggest that genetic polymorphisms of ATM may play an important role in the development of thyroid cancer in the Korean population.

  15. Arachidonate 5 Lipoxygenase Expression in Papillary Thyroid Carcinoma Promotes Invasion via MMP-9 Induction

    PubMed Central

    Kummer, Nicolas T.; Nowicki, Theodore S; Azzi, Jean Paul; Reyes, Ismael; Iacob, Codrin; Xie, Suqing; Swati, Ismatun; Suslina, Nina; Schantz, Stimson; Tiwari, Raj K.; Geliebter, Jan

    2012-01-01

    Arachidonate 5-lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP-9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP-9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)-hydroxyeicosatetraenoic acid also increased MMP-9 protein expression by BCPAP in a dose-dependent manner. Inhibitors of MMP-9 and ALOX5 reversed ALOX5-enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP-9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC. PMID:22253131

  16. [Differential diagnosis of squamous epithelial carcinoma of the salivary glands].

    PubMed

    Seifert, G; Donath, K

    1998-05-01

    Primary squamous cell carcinomas (SCC) of the salivary glands are localized predominantly in the major salivary glands and must be distinguished from metastases of extraglandular SCC of the skin, especially the head and neck area. Squamous cell metaplasia in non-tumourous diseases of the salivary gland (e.g. necrotizing sialometaplasia) as well as in benign or malignant salivary gland tumours (e.g. metaplastic Warthin tumour) can simulate SCC. Other differential diagnostic problems are the structural variants of SCC which develop predominantly in the minor salivary glands, but not in the major salivary glands. Special types include the very rare adenoid SCC with pseudoglandular structures as the result of acantholysis, the biphasic adenosquamous carcinoma with differentiation as SCC and adenocarcinoma, the biphasic basaloid squamous carcinoma with a structure as SCC and solid basaloid carcinoma (analogous to the solid type of adenoid-cystic carcinoma) and the poorly differentiated mucoepidermoid carcinoma (grade III) with biphasic structure of undifferentiated epidermoid and intermediate cells as well as inclusion of small groups of mucous-producing goblet cells. The differential diagnostic criteria are analysed concerning prognosis and treatment.

  17. Coefficient of variation of nuclear diameters as a prognostic factor in papillary thyroid carcinoma.

    PubMed

    Chang, T C; Kuo, S H; How, S W

    1991-12-01

    To determine whether the coefficient of variation (CV) of nuclear diameters can be used as a prognostic factor in papillary thyroid carcinoma, we reviewed fine needle aspiration smears with Riu's stain from 55 operated-on and pathologically verified cases with a median follow-up of 6.5 years. For each case we measured the nuclear diameters of 100 cancer cells by ocular micrometry and calculated the CV of the nuclear diameters. Then we correlated the CV with the clinical stage, recurrence and death. There was a positive correlation between the CV of the nuclear diameters and the clinical stage (r = .59, P less than .0001). Recurrent cases (n = 10) had a higher CV than did those without recurrence (n = 45) (18.04 +/- 4.1% [mean +/- SD] versus 13.2 +/- 2.7%, P less than .0005). All recurrent cases had a CV greater than 13%. The cases in which death occurred (n = 5) had a higher CV than did those with survival (n = 50) (20.1 +/- 4.9% versus 13.5 +/- 2.7%, P less than .0005). All cases in which death occurred had a CV greater than 15%. The extent of variation of nuclear diameters was one of the factors influencing prognosis in papillary thyroid carcinoma. It offers a prognostic adjunct to standard clinical and histologic analysis.

  18. Blue-dye sentinel node mapping in thyroid carcinoma: debatable results of feasibility.

    PubMed

    Peparini, N; Maturo, A; Di Matteo, F M; Tartaglia, F; Marchesi, M; Campana, E P

    2006-01-01

    The present study aims to investigate the feasibility and influence of the lymphatic mapping and sentinel node biopsy on determination of the nodal status in thyroid carcinoma using blue-dye method. Nine consecutive patients with cytological diagnosis of papillary carcinoma were included in this study. To detect the sentinel lymphnode, intra- or perinodular injection of an average quantity of 0.5 ml (range : 0.1-1.2) of Ble Patenté V was performed intraoperatively in 8 cases only, as in one case a solitary cystic nodule occupied the entire lobe and thus any injection was impossible. After an average time of 16 minutes (range : 5-25) before dissection of the thyroid , no lymphnodes and no lymphatic afferent thereto visibly coloured were evidenced, except for spread of the vital dye into adjacent tissue and disrupted blood and lymphatic vessels at the injection site. Our results evidence that : intranodular injection, does not allow proper diffusion of the dye in the adjacent parenchyma, and in nodules smaller than 1 cm it may be difficult ; and that it is hazardous in cystic nodule because of the rupture risk; perinodular injection, at the four cardinal points, is impossible when the nodule occupies the entire lobe or the isthmus; multinodular goiter complicates the identification by palpation of the neoplastic nodule in which the dye should be injected or, if perinodular injection is given, to detect the parenchyma surrounding the nodule. PMID:17168262

  19. Blue-dye sentinel node mapping in thyroid carcinoma: debatable results of feasibility.

    PubMed

    Peparini, N; Maturo, A; Di Matteo, F M; Tartaglia, F; Marchesi, M; Campana, E P

    2006-01-01

    The present study aims to investigate the feasibility and influence of the lymphatic mapping and sentinel node biopsy on determination of the nodal status in thyroid carcinoma using blue-dye method. Nine consecutive patients with cytological diagnosis of papillary carcinoma were included in this study. To detect the sentinel lymphnode, intra- or perinodular injection of an average quantity of 0.5 ml (range : 0.1-1.2) of Ble Patenté V was performed intraoperatively in 8 cases only, as in one case a solitary cystic nodule occupied the entire lobe and thus any injection was impossible. After an average time of 16 minutes (range : 5-25) before dissection of the thyroid , no lymphnodes and no lymphatic afferent thereto visibly coloured were evidenced, except for spread of the vital dye into adjacent tissue and disrupted blood and lymphatic vessels at the injection site. Our results evidence that : intranodular injection, does not allow proper diffusion of the dye in the adjacent parenchyma, and in nodules smaller than 1 cm it may be difficult ; and that it is hazardous in cystic nodule because of the rupture risk; perinodular injection, at the four cardinal points, is impossible when the nodule occupies the entire lobe or the isthmus; multinodular goiter complicates the identification by palpation of the neoplastic nodule in which the dye should be injected or, if perinodular injection is given, to detect the parenchyma surrounding the nodule.

  20. Non-autocrine, constitutive activation of Met in human anaplastic thyroid carcinoma cells in culture

    PubMed Central

    Bergström, J D; Hermansson, A; Ståhl, T Diaz de; Heldin, N-E

    1999-01-01

    Activation of Met by its ligand HGF has been shown to elicit both mitogenic and motogenic responses in thyrocytes in vitro. In the present study we have investigated the expression of Met in human anaplastic thyroid carcinoma cells in culture. There was a variation in expression level and size of Met in the different cell lines; high Met expression was found in four cell lines, compared to non-neoplastic human thyrocytes. Treatment with glucoproteinase F showed that the size differences observed were due to variances in the degree of glycosylation. Interestingly, in cell lines with high expression of Met, the receptor proteins were found to be constitutively tyrosine phosphorylated. None of these cell lines expressed HGF mRNA, and addition of suramin did not affect the level of tyrosine phosphorylation of Met in unstimulated cells, suggesting the absence of autocrine stimulatory pathways. Furthermore, we did not observe MET gene amplification, activating mutations or phosphatase defects. The tyrosine phosphorylated receptors appeared functionally active since the receptors associated with the adaptor molecule Shc. In summary, we have found ligand-independent constitutively activated Met in four out of six anaplastic thyroid carcinoma cell lines. © 1999 Cancer Research Campaign PMID:10360640

  1. Ectopic ACTH Production Leading to Diagnosis of Underlying Medullary Thyroid Carcinoma

    PubMed Central

    Matheny, Leslee N.; Wilson, Jessica R.; Baum, Howard B. A.

    2016-01-01

    Medullary thyroid carcinoma (MTC) has been described as a source of ectopic ACTH secretion in patients with Cushing’s syndrome. This is an infrequent association, occurring in less than 1% of MTC cases. Among these, it is even more unusual for an initial diagnosis of hypercortisolism to lead to the discovery of underlying MTC. Here we present a case of a patient with weakness, diarrhea, and hypokalemia who was found first to have Cushing’s syndrome and later diagnosed with metastatic MTC. The patient was treated initially with oral agents to control his hypercortisolism, then with an etomidate infusion after experiencing intestinal perforation. He also received vandetanib therapy targeting his underlying malignancy, as this has been shown to reverse clinical signs of Cushing’s syndrome in patients with MTC and subsequent ectopic ACTH secretion. Bilateral adrenalectomy was ultimately required. Medullary thyroid carcinoma should be considered in patients presenting with Cushing’s syndrome due to ectopic ACTH secretion, and a multimodality treatment approach is often required. PMID:27141514

  2. Papillary thyroid carcinoma involving cervical neck lymph nodes: correlations with lymphangiogenesis and ultrasound features.

    PubMed

    Choi, Yoonjung; Park, Kyung Joo; Ryu, Seungho; Kim, Dong-Hoon; Yun, Jisup; Kang, Doo Kyoung; Chun, Mison

    2012-01-01

    Stratification of risk factors for cervical lymph node metastasis (LNM) in thyroid papillary carcinoma is important for providing standards for post-operative adjuvant radio-iodine therapy and for patient prognosis. We investigated pathological factors based on the lymphatic vessel system and radiological features associated with tumor with cervical neck LNM. Among patients who had undergone thyroidectomy confirmed to be papillary thyroid carcinoma, we selected 126 age-sex matched paired patients without cervical LNM (group 1) and with LNM (group 2) to evaluate risk factors. Pathological factors evaluated were size, multiplicity, and extra thyroid extension state, based on the pathological reports using stored data. The lymphatic vessel density (LVD) of each tumor was evaluated by staining for VEGFR-3 and D2-40 and correlated with cervical LNM state. Malignant ultrasound features were evaluated to compare the differences between these two groups. Larger tumor size, multiplicity, extrathyroid extension were more common in group 2 (p<0.05). The median percentage of VEGFR-3 for group 1 was 20 (range 0-30) and D2-40 was 13 (range 7-23) while for group 2, VEGFR-3 was 80 (70-90) and D2-40 was 78 (54-114). LVD measured by intratumoral D2-40 staining was 20.6% and 79.4% for group 1 and group 2, respectively. Intra-tumoral lymphatics measured by D2-40 stain had a strong correlation with cervical LNM (Odds 1.230, CI 1.01.-1.499 p value 0.040). Ultrasound (US) features had no significant differences between the two groups although calcifications tended to be higher in group 2 (84% vs. 76% p=0.264). Lymphatic vessel density and nodule echogenicity were not associated with LNM. Intratumoral lymphangiogenesis was most strongly associated with LNM and thus, could be a useful predictive marker for cervical LNM.

  3. Patterns of FOXE1 Expression in Papillary Thyroid Carcinoma by Immunohistochemistry

    PubMed Central

    Bychkov, Andrey; Nakashima, Masahiro; Mitsutake, Norisato; Rogounovitch, Tatiana; Nikitski, Alyaksandr; Orim, Florence; Yamashita, Shunichi

    2013-01-01

    Background FOXE1, a thyroid-specific transcription factor also known as TTF-2, was recently identified as a major genetic risk factor for papillary thyroid carcinoma (PTC). Its role in thyroid carcinogenesis, however, remains unknown. The purpose of the present study was to assess the relationship between the FOXE1 immunohistochemical features and the clinical and genetic characteristics of PTC. Methods Immunohistochemical staining of FOXE1 was performed in 48 PTC cases. Two single nucleotide polymorphisms immediately inside (rs1867277) or in the vicinity (rs965513) of the FOXE1 gene were genotyped by direct sequencing. Histopathological, clinical, and genetic data were included in statistical analyses. Results FOXE1 exhibited cytoplasmic overexpression in tumor tissue compared to the normal counterpart (p<0.001). Both cancer and normal thyroid cells demonstrated the highest FOXE1 scores in the areas closest to the tumor border (<300 μm) compared with more distant areas (p<0.001). No differences in FOXE1 staining distributions were found between microcarcinomas and PTC of larger size, between different histopathological variants of PTC, and encapsulated and nonencapsulated tumors. Multivariate regression analysis revealed that nuclear FOXE1 expression in neoplastic cells in the vicinity of the tumor border independently associated with the genotype at rs1867277 (the dominant model of inheritance, p=0.037) and tumor multifocality (p=0.032), and with marginal significance with capsular invasion (p=0.051). Conclusions FOXE1 overexpression and translocation to the cytoplasm are phenotypic hallmarks of tumor cells suggesting that FOXE1 is involved in the pathogenesis of PTC. Nuclear FOXE1 expression in tumor cells in the vicinity of the PTC border is associated with the presence of a risk allele of rs1867277 (c.-238G>A) in the 5′ untranslated region of the FOXE1 gene, as well as with pathological characteristics of PTC, suggesting possible FOXE1 involvement in the

  4. Identification of occult tumors by whole-specimen mapping in solitary papillary thyroid carcinoma.

    PubMed

    Park, Seog Yun; Jung, Yuh-S; Ryu, Chang Hwan; Lee, Chang Yoon; Lee, You Jin; Lee, Eun Kyung; Kim, Seok-Ki; Kim, Tae Sung; Kim, Tae Hyun; Jang, Jeyun; Park, Daeyoon; Dong, Seung Myung; Kang, Jae-Goo; Lee, Jin Soo; Ryu, Junsun

    2015-08-01

    We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study are 82 consecutive patients who underwent a total thyroidectomy under a preoperative diagnosis of solitary PTC. All thyroidectomy specimens were serially sectioned in 2 mm thickness and whole-thyroid mapping was carried out for additional foci of occult PTC. The frequencies of occult lesions detected in the whole and contralateral lobe were determined, and clinicopathologic factors associated with multifocality were assessed. Whole-thyroid mapping revealed 66 occult PTC lesions missed by preoperative ultrasound in 37 (45.1%) of the 82 patients. The great majority (92.5%) of the occult PTC was smaller than 3 mm in size and 25 patients (30.5%) had contralateral lesions. We found that the male sex was an independent predictor of multifocality (odds ratio (OR), 3.00; 95% CI, 1.11-8.14), adjusting for preoperative findings. Analysis with pathologic parameters showed that the male sex (OR, 5.03; 95% CI, 1.68-15.08) and extrathyroidal extensions (OR, 3.03; 95% CI, 1.03-8.95) were associated with multifocal PTC. However, none of the clinicopathologic factors evaluated predicted contralateral PTC. Our study demonstrates the diagnostic limitations of ultrasound for the detection of multifocal PTC and the need to consider the possibility of occult lesions in the management of solitary PTC, especially in male patients.

  5. Chemically induced bidirectional differentiation of embryonal carcinoma cells in vitro.

    PubMed Central

    Speers, W. C.; Birdwell, C. R.; Dixon, F. J.

    1979-01-01

    N,N-dimethylacetamide, hexamethylene bisacetamide, and Polybrene induced rapid and extensive differentiation in vitro in an otherwise slowly differentiating subline of embryonal carcinoma cells. The type of differentiated cell induced was dependent on the spatial organization of the stem cells during drug treatment. In monalayer culture "epithelial" cells were produced exclusively. However, treatment of aggregated suspension cultures yielded predominantly "fibroblast-like" cells. The undifferentiated embryonal carcinoma cells and the two differentiated cell types were morphologically distinct when examined by light microscopy, scanning electron microscopy, and transmission electron microscopy; and they had differences in cell surface antigens. Both differential cell types produced large amounts of fibronectin, whereas the embryonal carcinoma cells produced only minimal amounts. This system provides a convenient way to induce relatively synchronous differentiation of embryonal carcinoma cells into specific differentiated cell types. Images Figure 5 Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:507191

  6. Polysplenia Syndrome With Splenic and Skeletal Muscle Metastases From Thyroid Carcinoma Evaluated by FDG PET/CT: Case Report and Literature Review: A Care-Compliant Article.

    PubMed

    Li, Zu-Gui; Lin, Zhi-Chun; Mu, Hai-Yu

    2016-01-01

    Polysplenia syndrome (PSS) is a rare congenital abnormality. Metastases to spleen and skeletal muscle from differentiated thyroid cancer (DTC) are also extremely rare. Our case report aims to present an interesting case of PSS associated with splenic metastasis (SM) and skeletal muscle metastasis (SMM) from advanced papillary thyroid carcinoma which was evaluated on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). An 84-year-old Chinese man was admitted with the history of multiple enlarged masses in bilateral neck, right axillary, and inguinal areas for >2 months. The results of ultrasonography examination were highly suggestive of malignancy. The histological results of the following biopsy were consistent with papillary thyroid carcinoma with involvement of multiple regional lymph nodes. He was referred for an FDG PET/CT imaging to evaluate the situation. FDG PET/CT showed that an intense FDG-avid thyroid mass with widespread regional lymph node involvement and distant metastases in the body. Unexpected sites of metastases were detected in the spleens and skeletal muscles. Most interestingly, FDG PET/CT imaging also described the typical imaging findings of PSS including the 2 right-sided spleens, azygos and hemiazygos continuation of inferior vena cava (IVC), right-sided stomach, middle line liver, a short pancreas, preduodenal portal vein (PPV), and malrotation of gut. Whole body FDG PET/CT imaging can accurately evaluate the situation of DTC by detecting regional lymph node involvement, common and rare sites of distant metastases which are closely related to staging, management, and prognosis of this disease. Whole-body FDG PET/CT is also valuable in demonstrating the typical imaging features of PSS. PMID:26825891

  7. Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

    PubMed Central

    Prasad, Nijaguna B.; Somervell, Helina; Tufano, Ralph P.; Dackiw, Alan P.B.; Marohn, Michael R.; Califano, Joseph A.; Wang, Yongchun; Westra, William H.; Clark, Douglas P.; Umbricht, Christopher B.; Libutti, Steven K.; Zeiger, Martha A.

    2011-01-01

    Purpose Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as “suspicious” or “indeterminate.” Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions. Experimental Design In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician. Results Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription – PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription – PCR data. Conclusions Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions. PMID:18519760

  8. [The case of carcinoma adenoides cysticum of the tongue, the trachea and the thyroid gland].

    PubMed

    Wojdas, Andrzej; Jurkiewicz, Dariusz; Kenig, Dagmara; Rapiejko, Piotr

    2004-01-01

    We present a case of a 65-year-old female patient who was for the first time admitted to the clinic in 1997 due to a tuber of the tongue root. The removed tuber turned out to be histopatologically a polymorphic adenoma. The patient was re-admitted to the Clinic in 2001 due to a tuber of the tongue and of the oral cavity bottom. The tuber was removed entirely through a central incision, and an apart hypertrophic change has been found on the posterior pharynx wall and in the scar after the tracheostomy carried out during the previous surgery. In all cases carcinoma adenoides cysticum has been found, as well as metastasis into the thyroid gland and the lungs. The patient was qualified for chemotherapy in the Institute of Oncology, which she has been going through periodically every two weeks until now. In 2002 the patient was operated on a small tuber located hypodermically in the scar after the tracheotomy, which was removed. Carcinoma adenoides cysticum was found. In November 2002, during the surgery a tumorous infiltration of the thyroid gland was found comprehending trachea and reaching the mediastenum. In February 2003 the patient was re-admitted to the Clinic due to dyspnoea caused by a significant contraction of the trachea which occurred as a result of a focus of carcinoma adenoides cysticum and significantly enlarged lymph glands near the trachea. The patient was qualified for stent placement in the Institute of Pulmonary Disease and Tuberculosis (Instytut Chorób Płuc i Gruźlicy). The presented case describes an exceptionally aggressive and polyfocal regrowth and transformation of a polymorphic adenoma into cancer.

  9. Can New Ultrasound Signs Help in Identifying Follicular Variant of Papillary Carcinoma of Thyroid? – A Pilot Study

    PubMed Central

    Anuradha, C.; Manipadam, M. T.; Asha, H. S.; Dukhabandhu, N.; Abraham, D.; Paul, M. J.

    2016-01-01

    Aim: To describe two new ultrasound signs for thyroid nodules – “nodule in nodule” and “hypoechoic internal septae” and assess their usefulness in differentiating follicular variant of papillary thyroid carcinoma (FVPTC) from benign thyroid nodules (BTN). Methodology: Ultrasound findings of 210 patients with histopathologically proven FVPTC (68 nodules, M:F=13:47 with mean age of 39.5±11.9 years) and BTN (165 nodules, (M:F=41:109 with mean age of 44±11.3 years) were retrospectively reviewed from PACS by a single radiologist blinded to the final diagnosis. Logistic regression analysis was performed to identify the best predictors of FVPTC and their diagnostic performance was assessed. Results: The “nodule in nodule” sign was seen in 80.9% of FVPTC and only 12.1% of BTN. The “hypoechoic internal septae” sign was seen in 44.1% of FVPTC and 17% of BTN. Younger patients, heterogeneous echotexture, nodule in nodule sign, thick incomplete non-uniform halo and presence of significant nodes were the best predictors of FVPTC (p<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and relative risk for FVPTC given as odds ratio (95% CI) for heterogeneous echotexture and nodule in nodule sign which were the best 2 predictors of FVPTC were 91.2%, 81.8%, 67.3%, 95.7%, 84.5%, 46.5 (18.5–117.4) and 80.9%, 87.7%, 74.3%, 91.2%, 86.2%, 32.5 (15.04–70.2), respectively. There was improvement in the specificity (91.5%) and accuracy (86.6%) when a combined criterion of heterogeneous echotexture and nodule in nodule sign was applied to predict FVPTC. Conclusion: The “nodule in nodule” sign is common in FVPTC and when combined with heterogeneous echotexture can differentiate FVPTC and BTN with high specificity. PMID:27689170

  10. Can New Ultrasound Signs Help in Identifying Follicular Variant of Papillary Carcinoma of Thyroid? – A Pilot Study

    PubMed Central

    Anuradha, C.; Manipadam, M. T.; Asha, H. S.; Dukhabandhu, N.; Abraham, D.; Paul, M. J.

    2016-01-01

    Aim: To describe two new ultrasound signs for thyroid nodules – “nodule in nodule” and “hypoechoic internal septae” and assess their usefulness in differentiating follicular variant of papillary thyroid carcinoma (FVPTC) from benign thyroid nodules (BTN). Methodology: Ultrasound findings of 210 patients with histopathologically proven FVPTC (68 nodules, M:F=13:47 with mean age of 39.5±11.9 years) and BTN (165 nodules, (M:F=41:109 with mean age of 44±11.3 years) were retrospectively reviewed from PACS by a single radiologist blinded to the final diagnosis. Logistic regression analysis was performed to identify the best predictors of FVPTC and their diagnostic performance was assessed. Results: The “nodule in nodule” sign was seen in 80.9% of FVPTC and only 12.1% of BTN. The “hypoechoic internal septae” sign was seen in 44.1% of FVPTC and 17% of BTN. Younger patients, heterogeneous echotexture, nodule in nodule sign, thick incomplete non-uniform halo and presence of significant nodes were the best predictors of FVPTC (p<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and relative risk for FVPTC given as odds ratio (95% CI) for heterogeneous echotexture and nodule in nodule sign which were the best 2 predictors of FVPTC were 91.2%, 81.8%, 67.3%, 95.7%, 84.5%, 46.5 (18.5–117.4) and 80.9%, 87.7%, 74.3%, 91.2%, 86.2%, 32.5 (15.04–70.2), respectively. There was improvement in the specificity (91.5%) and accuracy (86.6%) when a combined criterion of heterogeneous echotexture and nodule in nodule sign was applied to predict FVPTC. Conclusion: The “nodule in nodule” sign is common in FVPTC and when combined with heterogeneous echotexture can differentiate FVPTC and BTN with high specificity.

  11. The truncated isoform of somatostatin receptor5 (sst5TMD4) is associated with poorly differentiated thyroid cancer.

    PubMed

    Puig-Domingo, Manel; Luque, Raúl M; Reverter, Jordi L; López-Sánchez, Laura M; Gahete, Manuel D; Culler, Michael D; Díaz-Soto, Gonzalo; Lomeña, Francisco; Squarcia, Mattia; Mate, José Luis; Mora, Mireia; Fernández-Cruz, Laureano; Vidal, Oscar; Alastrué, Antonio; Balibrea, Jose; Halperin, Irene; Mauricio, Dídac; Castaño, Justo P

    2014-01-01

    Somatostatin receptors (ssts) are expressed in thyroid cancer cells, but their biological significance is not well understood. The aim of this study was to assess ssts in well differentiated (WDTC) and poorly differentiated thyroid cancer (PDTC) by means of imaging and molecular tools and its relationship with the efficacy of somatostatin analog treatment. Thirty-nine cases of thyroid carcinoma were evaluated (20 PDTC and 19 WDTC). Depreotide scintigraphy and mRNA levels of sst-subtypes, including the truncated variant sst5TMD4, were carried out. Depreotide scans were positive in the recurrent tumor in the neck in 6 of 11 (54%) PDTC, and in those with lung metastases in 5/11 cases (45.4%); sst5TMD4 was present in 18/20 (90%) of PDTC, being the most densely expressed sst-subtype, with a 20-fold increase in relation to sst2. In WDTC, sst2 was the most represented, while sst5TMD4 was not found; sst2 was significantly increased in PDTC in comparison to WDTC. Five depreotide positive PDTC received octreotide for 3-6 months in a pilot study with no changes in the size of the lesions in 3 of them, and a significant increase in the pulmonary and cervical lesions in the other 2. All PDTC patients treated with octreotide showed high expression of sst5TMD4. ROC curve analysis demonstrated that only sst5TMD4 discriminates between PDTC and WDTC. We conclude that sst5TMD4 is overexpressed in PDTC and may be involved in the lack of response to somatostatin analogue treatment.

  12. Diagnostic and Prognostic Markers in Differentiated Thyroid Cancer

    PubMed Central

    Gómez Sáez, José M

    2011-01-01

    The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. Moreover, it is additionally pointed out that genetic, as well as epigenetic DNA changing via aberrant methylation of several tumor suppressor and thyroid-specific genes is associated with tumor aggressiveness, being a jointly responsible mechanism for thyroid tumorigenesis. In the present manuscript the currently developed diagnostic and prognostic genetic/epigenetic markers are presented; the understanding of this molecular mechanism provides access to novel molecular therapeutic strategies. PMID:22654559

  13. 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.

  14. Lipid Peroxidation and Antioxidant Status in Patients with Medullary Thyroid Carcinoma: A Case-Control Study

    PubMed Central

    Hosseini-Zijoud, Seyed-Mostafa; Ebadi, Seyed Alireza; Goodarzi, Mohammad Taghi; Hedayati, Mehdi; Abbasalipourkabir, Roghayeh; Mahjoob, Mohammad Parsa; Poorolajal, Jalal; Zicker, Fabio

    2016-01-01

    Introduction Oxidative stress or oxidant/antioxidant imbalance has a crucial role in the pathogenesis of some diseases like cancer. Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and includes 3-4% of the malignant neoplasms that have an effect on this gland. The aetiology of MTC has not been clarified. However, oxidative stress may be one of the factors involved. Aim The aim of the current study was to evaluate the antioxidant enzyme activity of catalase (CAT), Glutathione (GSH), total antioxidant capacity (TAC) and the levels of the lipid peroxidation product malondialdehyde (MDA) in blood samples of MTC patients as compared to healthy controls. Materials and Methods A case-control study was designed enrolling patients with confirmed MTC diagnosis and age-and sex group matched healthy volunteers referred to the clinic of the Research Institute for Endocrine Sciences, Tehran, Iran from April 2013 to July 2015. Fasting blood samples were taken for study. Catalase, GSH, MDA and TAC levels were measured by colorimetry using commercial kits (ZellBio GmbH, Germany). Data were analysed using SPSS 17 software, comparing mean±SD through t-test and difference between proportions through chi-square. Results No statistical difference was observed in the demographic characteristic between cases and controls. The final MTC group included 40 males and 45 females with a mean age of 30±12.9 year, and the control group 40 males and 47 females, with a mean age of 31.2±12.3 year. Anthropometric parameters, dietary and thyroid hormones levels (T3, T4 and TSH) were similar. Serum TAC (p=0.015), GSH (p=0.029) and CAT (p<0.001) levels were found to be significantly lower in the MTC patients, while serum MDA levels were significantly higher in MTC patients than controls (p<0.001). Conclusion These preliminary findings suggest that oxidant/antioxidant imbalance may be associated with or possibly indicate an increased risk to medullary thyroid carcinoma

  15. Alternative surgical strategies in patients with sporadic medullary thyroid carcinoma: Long-term follow-up.

    PubMed

    Ma, Shi Hong; Liu, Qin Jiang; Zhang, You Cheng; Yang, Rong

    2011-09-01

    The extent of surgical resection in patients with sporadic medullary thyroid carcinoma (SMTC) remains controversial. The aim of the present study was to discuss the prognosis of sporadic medullary thyroid carcinoma with different surgical treatments. Of 73 patients with SMTC (mean age of 43.78 years at diagnosis), 70 patients were followed up for 12.0-169.0 months (median 90.0). Having given their informed consent, 12 patients underwent total thyroidectomy with bilateral central neck dissection (group A), 40 underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with ipsilateral modified radical neck dissection (group B), and 18 patients underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with bilateral modified radical neck dissection (group C). The diagnosis was confirmed by a pathology examination. The incidences of hypoparathyroidism and recurrent laryngeal nerve injury, the cancer recurrence rates and survival time wer