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Sample records for differentiated thyroid carcinomas

  1. 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

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

    PubMed

    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 (99m)TcO4 (-) 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. External Beam Radiation in Differentiated Thyroid Carcinoma.

    PubMed

    Billan, Salem; Charas, Tomer

    2016-01-01

    The treatment of differentiated thyroid carcinoma (DTC) is surgery followed in some cases by adjuvant treatment, mostly with radioactive iodine (RAI). External beam radiotherapy (EBRT) is less common and not a well-established treatment modality in DTC. The risk of recurrence depends on three major prognostic factors: extra-thyroid extension, patient's age, and tumor with reduced iodine uptake. Increased risk for recurrence is a major factor in the decision whether to treat the patient with EBRT. Data about the use of EBRT in DTC are limited to small retrospective studies. Most series have demonstrated an increase in loco-regional control. The risk/benefit from giving EBRT requires careful patient selection. Different scoring systems have been proposed by different investigators and centers. The authors encourage clinicians treating DTC to become familiarized with those scoring systems and to use them in the management of different cases. The irradiated volume should include areas of risk for microscopic disease. Determining those areas in each case can be difficult and requires detailed knowledge of the surgery and pathological results, and also understanding of the disease-spreading pattern. Treatment with EBRT in DTC can be beneficial, and data support the use of EBRT in high-risk patients. Randomized controlled trials are needed for better confirmation of the role of EBRT. PMID:26886956

  5. 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

  6. 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

  7. 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

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

    PubMed

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

    2016-01-01

    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. PMID:26886954

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

    PubMed Central

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

    2016-01-01

    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. PMID:26886954

  10. Value of distinguishing differentiated thyroid carcinoma by miRNA

    PubMed Central

    XU, JIANLIN; ZHANG, DING; NIU, QIAN; NAN, YONGGANG; SHI, CHANGBEI; ZHAO, HUA; LIANG, XIAOYAN

    2016-01-01

    Current methods for diagnosing thyroid carcinoma are time consuming or expensive. Thus, alternative approaches are required. In the present study, microRNAs (miRNAs) with higher sensitivity and specificity were screened while distinguishing between differentiated thyroid carcinoma (DTC) and subtype papillary thyroid carcinoma (PTC). A total of 120 cases suspected of having thyroid carcinoma were selected and examined using clinical color Doppler ultrasound, and computed tomography scan at the same time. The tissue specimens were obtained with fine needle aspiration, multiphase biopsy and surgical resection. The expression of miR146b, miR221 and miR222 was detected uisng the RT-quantitative polymerase chain reaction method. The receiver operating characteristic curve was used to obtain the cut-off value. Pathological examination identified 8 cases of normal thyroid tissue; 9 cases of hyperplastic nodules; 12 cases of thyroid adenoma; and 91 cases of thyroid carcinoma, of which 59 cases were DTC, 15 cases were follicular carcinoma and 17 cases were undifferentiated carcinoma. In the thyroid carcinoma, the expression levels of miR146b, miR221 and miR222 were significantly higher than those of other tissues (P<0.05). The expression levels of these miRNAs in the differentiated type were also significantly higher than those in the undifferentiated type (P<0.05). A comparison of the differentiated subunit identified no statistically significant difference (P>0.05). Following diagnosis of DTC, the area under curve (AUC) of miR146b, miR221 and miR222 was 0.832, 0.806 and 0.745, respectively; the cut-off values were 1.346, 1.213 and 1.425, respectively; susceptibility was 72.8, 71.5 and 68.7%, respectively; and specificity was 62.3, 60.9 and 59.3%, respectively. The AUC of the combined miR-146b and −221 following diagnosis of PTC was 0.695; the cut-off values were 1.506 and 1.462, respectively; susceptibility was 78.9%; and specificity was 68.5%. The AUC of the combined mi

  11. Carcinoma showing thymus-like differentiation of the thyroid (CASTLE).

    PubMed

    Huang, Chuying; Wang, Li; Wang, Yan; Yang, Xibiao; Li, Qiu

    2013-10-01

    Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, probably arising from ectopic thymus or branchial pouch remnants. The tumor was first reported by Miyauchi et al. [1].The clinical and pathological features of this tumor were classified by Chan et al. [2] into 4 groups: ectopic hamartomatous thymoma, ectopic cervical thymoma, spindle ephithelial tumor with thymic-like differentiation (SETTLE), and carcinoma showing thymus-like differentiation (CASTLE). Recently, CASTLE has been designated as an independent clinicopathologic entity of thyroid tumors in the most recent edition of the World Health Organization classification of tumors of endocrine organs[3].To our knowledge, less than 100 cases of CASTLE have been reported in the literature, 45 cases of which (including one of the authors' patient) have been identified in China. We report a new case of this entity and suggest recommendations for diagnosis. PMID:23920320

  12. 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.

  13. 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. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  14. Medullary carcinoma of thyroid

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. Unlike other types of thyroid cancer, MTC is less likely to be caused by radiation therapy to the neck given ...

  15. A Unique Case of Intranasal Metastasis from Occult Poorly Differentiated Thyroid Carcinoma

    PubMed Central

    Kum, Rauf Oğuzhan; Aygenç, Erdinç; Somuk, Battal Tahsin; Börcek, Pelin; Özdem, Cafer

    2015-01-01

    Background: Poorly differentiated thyroid carcinomas (PDTCs) lie, both morphologically and behaviorally, between well-differentiated and undifferentiated carcinomas. Metastasis of poorly differentiated thyroid carcinoma to the intranasal cavity has not been reported previously in the literature. Case Report: A 48-year-old male patient presented with massive epistaxis and nasal obstruction. On nasal examination, a bleeding, vascular mass was seen filling the left nasal cavity. The histopathological report of the nasal mass was well-differentiated thyroid carcinoma metastasis. Whole body scintigraphy, ultrasonography and positron emission tomography were done to rule out other possible metastases in the body and determine the origin of the tumor, which was identified as the left lobe of the thyroid gland, and there were multiple metastases involving the lung, sacroiliac area, and left humerus. Histopathological examination of a thyroidectomy specimen revealed PDTC consisting of insular, follicular, and papillary components. Postoperatively, the patient received radioactive iodine ablation therapy (iodine-131) and a course of external beam radiation therapy to the sacroiliac area and other metastatic regions. No recurrences were observed in a follow-up period of 5 years after surgery. Conclusion: The metastasis of differentiated thyroid carcinoma as a component of PDTC to the intranasal cavity has not been reported before. It is interesting that the well-differentiated component of the tumor was metastasized in our patient. Due to the aggressiveness of PDTC and the poor survival rates in patients who undergo surgery alone, a multidisciplinary treatment approach is required. PMID:26185723

  16. 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

  17. 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

  18. A two miRNA classifier differentiates follicular thyroid carcinomas from follicular thyroid adenomas.

    PubMed

    Stokowy, Tomasz; Wojtaś, Bartosz; Krajewska, Jolanta; Stobiecka, Ewa; Dralle, Henning; Musholt, Thomas; Hauptmann, Steffen; Lange, Dariusz; Hegedüs, László; Jarząb, Barbara; Krohn, Knut; Paschke, Ralf; Eszlinger, Markus

    2015-01-01

    The inherent diagnostic limitations of thyroid fine needle aspiration (FNA), especially in the "indeterminate" category, can be partially overcome by molecular analyses. We aimed at the identification of miRNAs that could be used to improve the discrimination of indeterminate FNAs. miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). The microarray results underwent cross-comparison using three additional microarray data sets. Candidate miRNAs were validated by qPCR in an independent set of 32 FTCs and 46 FAs. Sixty-eight differentially expressed miRNAs were identified. Thirteen miRNAs could be confirmed by cross comparison. A two-miRNA-classifier was established improving the diagnostic applicability and resulted in a sensitivity of 82% and a specificity of 49%. We present a classifier that has the potential to be successfully evaluated in cytology material for its capability to discriminate (mutation negative) indeterminate cytologies and thereby improving the pre-surgical diagnostics of thyroid nodules. PMID:25258301

  19. Genetic alterations of differentiated thyroid carcinoma in iodine-rich and iodine-deficient countries.

    PubMed

    Vuong, Huy Gia; Kondo, Tetsuo; Oishi, Naoki; Nakazawa, Tadao; Mochizuki, Kunio; Inoue, Tomohiro; Tahara, Ippei; Kasai, Kazunari; Hirokawa, Mitsuyoshi; Tran, Thong Minh; Katoh, Ryohei

    2016-08-01

    BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine-rich country (Japan) and an iodine-deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele-specific polymerase chain reaction (AS-PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT-PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E, RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine-rich and iodine-deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer. PMID:27264674

  20. Minimally invasive video-assisted thyroidectomy for the early-stage differential thyroid carcinoma

    PubMed Central

    2012-01-01

    Background Minimally invasive video-assisted thyroidectomy (MIVAT), the modified Miccoli’s thyroid surgery, is the most widespread minimally invasive technique and has been widely used for treatment of thyroid disease. This study aimed to verify the potential benefits of the modified Miccoli’s thyroid surgery, determine the feasibility of the MIVAT for early-stage differential thyroid carcinoma and evaluate the likelihood of the surgical method as a standard operation for early malignant thyroid carcinoma. Methods A total of 135 patients were retrospectively compared which included two groups of patients: the first group underwent the conventional thyroidectomy; the other group underwent MIVAT. Patients with thyroid nodule smaller than 20 mm and without previous neck surgery were included while those with wide-ranging and distant metastases of cervical tissues, or any suspected thyroid nodal metastases were excluded for analysis. MIVAT and the central compartment (level VI) lymph nodes dissection (LND) were considered as a new treatment method for this retrospective study. In addition to the comparison of surgical outcomes between the new treatment and the conventional thyroid surgery, other surgical parameters including operative time, operative volume of hemorrhage, incisional length, postoperative volume of drainage, length of hospitalization, accidence of hoarse voice, accidence of bucking, accidence of hypocalcemia and peak angle of cervical axial rotation were also compared. Results Out of 135 patients, 111 patients underwent conventional thyroid surgery and 24 patients underwent MIVAT plus level VI LND for treatment of early-stage differential malignant carcinoma. Patients who received the new surgical treatment had significantly shorter incisional length (3.1 cm vs. 6.9 cm, p < 0.0001), shorter operative time (109 min vs. 139 min, p = 0.014) and fewer operative hemorrhage (29.5 ml vs. 69.7 ml, p < 0.0001) when compared to the conventional treatment

  1. Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas.

    PubMed

    Paricharttanakul, N Monique; Saharat, Kittirat; Chokchaichamnankit, Daranee; Punyarit, Phaibul; Srisomsap, Chantragan; Svasti, Jisnuson

    2016-04-01

    Thyroid cancer is the most common human endocrine malignancy with increasing global incidence. Papillary thyroid carcinomas (PTC) and follicular thyroid carcinomas (FTC) are well-differentiated thyroid cancers (WDTC) accounting for 95% of all thyroid cancer cases, with survival rates of almost 100% when diagnosed early. Since PTC and FTC have different modes of metastasis, they require different treatment strategies. Standard diagnosis by fine needle aspiration with cytopathological examination can be inaccurate in approximately 10-30% of all cases and difficult to definitively classify as WDTC. Currently, there is no single or panel of biomarkers available for thyroid cancer diagnosis and classification. This study identified novel biomarkers for thyroid cancer diagnosis and classification using proteomics, which may be translated into a biomarker panel for clinical application. Two-dimensional SDS-PAGE and mass spectrometry were used to identify potential biomarkers in papillary and follicular thyroid carcinoma cell lines, and the biomarkers were validated in five PTC and five FTC tissues, with their adjacent normal tissues from Thai patients. Eight biomarkers could distinguish PTC from normal tissues, namely enolase 1, triose phosphate isomerase, cathepsin D, annexin A2, cofilin 1, proliferating cell nuclear antigen (PCNA), copine 1 and heat shock protein 27 kDa (HSP27). These biomarkers can also discriminate FTC from normal tissues, except for annexin A2. On the contrary, annexin A2, cofilin 1, PCNA and HSP27 can be used to classify the types of WDTC. These findings have potential for use as a novel multi-marker panel for more accurate diagnosis and classification to better guide physicians on thyroid cancer treatment. Moreover, our results suggest the involvement of proteins in cell growth and proliferation, and the p53 pathway in the carcinogenesis of WDTC, which may lead to targeted therapy for thyroid cancer. PMID:26782318

  2. 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

  3. Thyroid carcinoma showing thymus-like differentiation: Case presentation of a young man

    PubMed Central

    Abeni, Chiara; Ogliosi, Chiara; Rota, Luigina; Bertocchi, Paola; Huscher, Alessandra; Savelli, Giordano; Lombardi, Mariano; Zaniboni, Alberto

    2014-01-01

    Ectopic thymic tissue can be present in the thyroid gland and a carcinoma showing thymus-like differentiation (CASTLE) may arise from such tissue. We are reported the case of a 26-year-old man with CASTLE, with cervical subcutaneous nodules relapse, who showed a good response to treatment with surgery, chemotherapy and radiotherapy. The problematic aspect of this case was the diagnosis; only on review were we able to make a final diagnosis. CASTLE is a very rare neoplasm. It is important to differentiate this cancer from others tumors such as primary or metastatic squamous cell carcinoma of the head and neck or squamous cell thyroid carcinoma, because the therapy and prognosis are different. Diagnosis is complicated and requires careful histological analysis (CD5- and P63-positive with presence of Hassall’s corpuscles); unfortunately there is no gold standard treatment so, in this case, we administered a sandwich of chemotherapy and radiotherapy. PMID:25493249

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

    PubMed Central

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

    2015-01-01

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

  5. Genetic Testing in Differentiated Thyroid Carcinoma: Indications and Clinical Implications

    PubMed Central

    Zolotov, Sagit

    2016-01-01

    Differentiated thyroid cancer (DTC) is a common and diverse endocrine malignancy. In most patients DTC results in an indolent and curable disease. Nevertheless, disease recurrence rates are relatively high (10%–30%), while 5% of the patients are resistant to conventional treatment and some of these patients are incurable. Over the past 20 years much progress has been made in identifying genetic changes that occur in DTC. In addition, studies aimed to understand the role of these genetic changes in tumorigenesis and their effects on the clinical characteristics of the disease have been conducted. The accrued knowledge has set the stage for development of genetic tests aimed to identify these changes in samples obtained from DTC patients and use this information in the clinical decision process. This paper reviews genetic changes that were identified in DTC, and how the emerging data obtained by genetic testing are currently used to gain key information on the diagnosis, risk stratification, and personalized care of DTC patients. PMID:26886957

  6. Thyroid Carcinoma Showing Thymic-Like Differentiation Causing Fracture of the Trachea

    PubMed Central

    Marini, Aikaterini; Kanakis, Meletios; Valakis, Konstantinos; Laschos, Nikolaos; Chorti, Maria; Lioulias, Achilleas

    2016-01-01

    Thyroid carcinoma showing thymic-like differentiation (CASTLE) comprises a rare neoplasm of the thyroid gland which arises from ectopic thymic tissue or remnants of brachial pouches. CASTLE is regarded as an indolent neoplasm with a favorable prognosis, irrespective of its metastatic potential. Diagnosis is difficult as clinicopathological features have not been yet well-defined. Radiological findings are not specific and only immunohistochemical positivity for CD5 and CD117 staining is highly suggestive of CASTLE. Despite lack of universally accepted treatment recommendations, the mainstay treatment includes thyroidectomy and systematic lymph node dissection. We report a case of CASTLE tumour with very uncommon characteristics developed in a 76-year-old man, who presented with rapidly deteriorating dyspnea and severe cough, resulting in respiratory failure. At surgery, a suspicious looking tumour arising from the upper pole of the right lobe of the thyroid gland, surrounding the trachea and displacing the right common carotid artery, was identified. The patient underwent en bloc resection of the tumour with the thyroid gland and regional lymph node dissection. This is the first reported case of CASTLE causing tracheal ring fracture. PMID:27110248

  7. Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma.

    PubMed

    Tomoda, Chisato; Ogimi, Yuna; Saito, Fumi; Masaki, Chie; Akaishi, Junko; Matsuzu, Kenichi; Suzuki, Akifumi; Uruno, Takashi; Ohkuwa, Keiko; Shibuya, Hiroshi; Kitagawa, Wataru; Nagahama, Mitsuji; Sugino, Kiminori; Ito, Koichi

    2016-01-01

    Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE. PMID:26655349

  8. 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.

  9. Diagnostic usefulness of PCR profiling of the differentially expressed marker genes in thyroid papillary carcinomas.

    PubMed

    Hamada, Aiko; Mankovskaya, Svetlana; Saenko, Vladimir; Rogounovitch, Tatiana; Mine, Mariko; Namba, Hiroyuki; Nakashima, Masahiro; Demidchik, Yuri; Demidchik, Eugeny; Yamashita, Shunichi

    2005-06-28

    The study was set out to determine whether characteristic changes in the gene expression profile in papillary thyroid carcinoma (PTC) discovered by microarray assays can be used for conventional molecular diagnosis. Expression levels of five reported to be overexpressed and three underexpressed genes were examined in PTC and normal human tissues by real-time PCR and semi-quantitative duplex PCR. Stepwise logistic regression analysis, duplex PCR data evaluation with recursive partition machine algorithm and hierarchical cluster analysis identified SFTPB (upregulated) and TFF3 (downregulated) gene combination as most favorable for differential molecular diagnosis of PTC. Sensitivity, specificity and accuracy obtained in a series of histologically characterized thyroid tumor and normal tissue samples were 88.9, 96.7 and 94.9%, respectively. Applicability of the method to fine needle aspiration biopsy (FNAB) samples was demonstrated using a collection of needle washouts. In spite individual thyroid tumor and normal tissues as well as FNAB samples displayed a substantial degree of variability in the expression levels of analyzed genes, simultaneous molecular analysis of a panel of optimal markers allows making a high probability predictive estimate and may be considered as an informative method of preoperative PTC diagnosis. PMID:15914279

  10. 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.

  11. 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

  12. Human thyreoglobulin (HTG) for the diagnosis of recurrent differentiated thyroid carcinoma: Evaluation by ROC - analysis

    SciTech Connect

    Laubenbacher, C.; Schrafstetter, C.; Senekowitsch, R.

    1995-05-01

    The value of hTg-measurements are still discussed controversially. Also, there are no tables with sensitivity/specificity pairs for different cutoffs, since valuable information is lost by presenting only one sensitivity/specificity pair. Therefore, we wanted to determine these values for hTg by a ROC-analysis. Inclusion criteria were: (a) differentiated thyroid carcinoma (papillary or follicular), (b) no thyroid-rest after primary therapy (e.g. no detectable hTg and nc iodine accumulating foci in iodine-whole body scan), (c) no detectable hTg- antibodies, (d) an observation period of at least 1 year, hTg was determined by TG-RIA and hTg-antibodies by IMMUtest anti-Tg. Recurrence was proven by iodine-whole-body scans under maximal endogenous TSH-stimulation or by histology. Sensitivity and specificity were calculated for different hTg-cutoffs. During 10/80 and 10/89 93 patients met these criteria. There were 71 female and 22 male with a mean age of 48.6 {plus_minus} 16.3 years. 51 patients had papillary carcinomas, 42 patients follicular carcinomas. The observation period was 78.4 {plus_minus} 40.9 months. In these 93 patients there were 16 recurrences during the observation period. Sensitivity/specificity pairs for different cutoffs are given. These sensitivity/specificity pairs avoid the reduction of the original continuous data to a Yes/No decision. The knowledge of these data and of the ROC-curve could improve the intuitive rating of a laboratory result by the physician.

  13. 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

  14. Thallium-201 imaging in the follow-up of differentiated thyroid carcinoma

    SciTech Connect

    Brendel, A.J.; Guyot, M.; Jeandot, R.; Lefort, G.; Manciet, G.

    1988-09-01

    Since thallium-201 imaging has been reported as a potential means of follow-up of patients with differentiated thyroid carcinoma (DTC) during ongoing thyroid suppression therapy, the authors evaluated the diagnostic sensitivity of this procedure in 31 patients known to have metastases or local recurrence. Among 51 tumor sites /sup 201/TI imaging had a detection rate of 45% whereas 84% was noted for imaging with /sup 131/I administered in therapeutic doses. Thus, even though the effectiveness of the two radionuclides is not strictly comparable due to the difference in the administered doses, Thallium imaging cannot be recommended as the only modality for the follow-up of patients with DTC. Six of the eight tumor sites negative with /sup 131/I were positive with /sup 201/TI (especially metastatic cervico-mediastinal lymph nodes). So /sup 201/TI imaging may particularly be helpful in localizing metastases or recurrences in patients with a negative /sup 131/I scan and abnormal levels of serum thyroglobulin.

  15. 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

  16. The Role of Prophylactic Central Neck Dissection in Differentiated Thyroid Carcinoma: Issues and Controversies

    PubMed Central

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

    2011-01-01

    Prophylactic central neck dissection (pCND) in differentiated thyroid carcinoma (DTC) is one of the most controversial surgical subjects in recent times. To date, there is little evidence to support the practice of pCND in patients with DTC undergoing total thyroidectomy. Although the recently revised American Thyroid Association (ATA) guideline has clarified many inconsistencies regarding pCND and has recommended pCND in “high-risk” patients, many issues and controversies surrounding the subject of pCND in DTC remain. The recent literature has revealed an insignificant trend toward lower recurrence rate in patients with DTC who undergo total thyroidectomy and pCND than those who undergo total thyroidectomy alone. However, this was subjected to biases, and there are concerns whether pCND should be performed by all surgeons who manage DTC because of increased surgical morbodity. Performing a unilateral pCND may be better than a bilateral pCND given its lower surgical morbidity. Further studies in this controversial subject are much needed. PMID:21977029

  17. Changing trends in the management of well-differentiated thyroid carcinoma in Korea.

    PubMed

    Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

    2016-06-30

    A questionnaire administered in 2009 found that members of the Korean Association of Thyroid-Endocrine Surgeons (KATES) favored more aggressive treatment of well-differentiated thyroid carcinoma (WDTC) than physicians from other countries. This study assessed the changes in practical management of WDTC in Korea from the previous survey. Questionnaires were sent by e-mail to KATES members. A total of 101 members completed the questionnaire. Their responses were compared with response for the 2009 survey. Of the respondents, 53.5% and 80.2% indicated that they would perform fine-needle aspiration cytology on nodules that were <0.5 cm and 0.5-1.0 cm in diameter, respectively. If the cytology was positive, a large number of respondents favored surgical treatment, regardless of tumor size. Compared with the 2009 survey, a slightly higher percentage favored observation for patients with tumors that were <0.5 cm in diameter, and a larger percentage recommended less-than-total thyroidectomy for patients with T1 cancers. Respondents in 2014 favored aggressive lymph node dissection less, irrespective of tumor size, preferring short-term treatment with thyroid stimulating hormone suppressors. The percentage preferring postoperative high-dose radioactive iodine therapy slightly increased, whereas the percentage favoring external irradiation decreased, in 2014 compared with 2009. The management of Korean patients with WDTC changed from 2009 to 2014. In 2009, Korean respondents favored more aggressive treatment of WDTC compared with respondents from other countries. In 2014, however, Korean respondents favored a more conservative approach, especially in patients with microcarcinomas. PMID:26961223

  18. 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.

  19. Survival rates in patients with differentiated thyroid carcinoma. Influence of postoperative external radiotherapy

    SciTech Connect

    Benker, G.; Olbricht, T.; Reinwein, D.; Reiners, C.; Sauerwein, W.; Krause, U.; Mlynek, M.L.; Hirche, H. )

    1990-04-01

    Nine hundred thirty-two patients with papillary and follicular thyroid carcinomas were seen at the Departments of Medicine, Surgery, and Radiology of the University of Essen, Essen, Germany, between 1970 and 1986. In addition to standard treatment by surgery, radioactive iodine and medical thyroid stimulating hormone (TSH) suppression, 346 patients had received conventional external irradiation to the neck before referral to our institutions, whereas 586 patients had not received radiotherapy. From the follow-up data of these patients, survival rates were calculated separately for tumor Stages T1 (n = 203), T2 (n = 552), and T3/T4 (n = 277) using life-table analysis. Distribution of risk factors (histologic type of tumor, grading of malignancy, presence of distant metastases, age and sex) was similar in all groups with the one exception, that the radiotherapy patients with Stage T3/T4 were older. There was no significant difference in the life expectancy of irradiated and not irradiated patients by Breslow and Mantel-Cox tests. In Stages T1, T2, and T3/T4, 75% of the radiotherapy patients survived for 10.6 +/- 0.32, 11.5 +/- 0.61, and 6.71 +/- 0.85 years, respectively; the figures for the nonirradiated patients were 9.4 +/- 0.17, 10.8 +/- 0.37, and 6.26 +/- 0.51 years, respectively. When survival rates were calculated separately for patients with Stage T3/T4 older and younger than 40 years, there was no obvious effect of radiotherapy in the younger group, whereas in the older patients, improvement of survival by radiation just failed to reach statistical significance. In conclusion, this retrospective analysis failed to prove that survival is prolonged in patients with differentiated carcinoma by administration of conventional external radiotherapy after surgery. A benefit to older patients with locally advanced tumors has still to be demonstrated.

  20. Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: the EPIC study.

    PubMed

    Zamora-Ros, Raul; Rinaldi, Sabina; Biessy, Carine; Tjønneland, Anne; Halkjaer, Jytte; Fournier, Agnes; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Tikk, Kaja; Fortner, Reneé T; Boeing, Heiner; Förster, Jana; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Papatesta, Eleni-Maria; Masala, Giovanna; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Polidoro, Silvia; Peeters, Petra H M; Bueno-de-Mesquita, H Bas; Weiderpass, Elisabete; Lund, Eiliv; Argüelles, Marcial; Agudo, Antonio; Molina-Montes, Esther; Navarro, Carmen; Barricarte, Aurelio; Larrañaga, Nerea; Manjer, Jonas; Almquist, Martin; Sandström, Maria; Hennings, Joakim; Tsilidis, Konstantinos K; Schmidt, Julie A; Khaw, Kay-Thee; Wareham, Nicholas J; Romieu, Isabelle; Byrnes, Graham; Gunter, Marc J; Riboli, Elio; Franceschi, Silvia

    2015-03-01

    Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for ≤ 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for ≥ 9 vs. ≤ 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR = 1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR = 1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause. PMID:25041790

  1. 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

  2. Differential miRNA expression defines migration and reduced apoptosis in follicular thyroid carcinomas.

    PubMed

    Wojtas, Bartosz; Ferraz, Carolina; Stokowy, Tomasz; Hauptmann, Steffen; Lange, Dariusz; Dralle, Henning; Musholt, Thomas; Jarzab, Barbara; Paschke, Ralf; Eszlinger, Markus

    2014-05-01

    The objective of the study was to identify microRNAs (miRs) characteristic for follicular thyroid carcinoma (FTC) and to define their role in tumorigenesis. A miR-microarray study was conducted to identify miRs differentially expressed between FTCs and their surrounding tissues. Selection was further reinforced by a literature review. Four miRs were selected and confirmed by RT-qPCR: miR-146b, -183, -221 were up-regulated, whereas miR-199b down-regulated in FTCs. The influence of these miRs on cell proliferation, cell cycle, apoptosis and migration was studied in HTori and FTC-133 cells. Functional characterization suggests an impact of miR-183 and miR-146b in FTC development. Overexpression of both miRs significantly induces migration. Moreover, overexpression of miR-183 significantly represses apoptosis. MiR-199b and -221 do not have significant effects on proliferation, cell cycle, apoptosis or migration in HTori and FTC-133 cells. Our data suggest that miR-146b and miR-183 may influence FTC development through the induction of migration and apoptosis inhibition. PMID:24631480

  3. 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.

  4. Impaired Vitamin D Activation and Association with CYP24A1 Haplotypes in Differentiated Thyroid Carcinoma

    PubMed Central

    Penna-Martinez, Marissa; Ramos-Lopez, Elizabeth; Stern, Julienne; Kahles, Heinrich; Hinsch, Nora; Hansmann, Martin-Leo; Selkinski, Ivan; Grünwald, Frank; Vorländer, Christian; Bechstein, Wolf O.; Zeuzem, Stefan; Holzer, Katharina

    2012-01-01

    Background Common polymorphisms of the vitamin D receptor gene have been reported to affect the risk of breast, colon, prostate, and differentiated thyroid cancer (DTC), but polymorphisms within the genes of vitamin D metabolizing enzymes have not been studied in DTC. The aim of the present study was to investigate the genes for vitamin D enzymes in patients with DTC and healthy controls (HC) as well as the vitamin D (25-hydroxyvitamin D3, and 1,25-hydroxyvitamin) status. Methods German patients (n=253) with DTC (papillary thyroid carcinoma [PTC] and follicular thyroid carcinoma [FTC]) and HC (n=302) were genotyped for polymorphisms within the vitamin D metabolizing enzymes such as 25-hydroxylase (CYP2R1[rs12794714, rs10741657]), 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1[rs10877012, rs4646536]), and 25-hydroxyvitamin D 24-hydrolase (CYP24A1[rs927650, rs2248137, rs2296241]). Furthermore, the 25-hydroxyvitamin D3 [25(OH)D3] and 1,25-hydroxyvitamin [1,25(OH)2D3] plasma levels were measured by a radioimmunoassay. Results There was no difference in the genotypes; however, the CYP24A1 haplotype analysis showed that rs2248137C/rs2296241A (13.1% vs. 19.1%; corrected p [pc]=0.04) was less frequent in the PTC, whereas the haplotypes rs2248137C/rs2296241G (56.0% vs. 41.9%; pc=0.03), rs927650C/rs2296241G (22.5% vs. 8.4%; pc=1.6×10−3), and rs927650C/rs2248137C/rs2296241G (21.1% vs. 7.3%; pc=1.5×10−3) were more frequent in the FTC compared with HC. Furthermore, if patients and controls were grouped according to four 25(OH)D3 categories (severely deficient, deficient, insufficient, and sufficient), then the patients with both DTC subtypes had significantly lower levels of circulating 1,25(OH)2D3, especially in the group with a deficient 25(OH)D3 status compared with the controls. Although the polymorphisms showed no differences stratified for the four 25(OH)D3 categories, the activation status by 1,25(OH)2D3 differed significantly depending on the genotypes of the

  5. The limit of detection in scintigraphic imaging with I-131 in patients with differentiated thyroid carcinoma

    NASA Astrophysics Data System (ADS)

    Hänscheid, H.; Lassmann, M.; Buck, A. K.; Reiners, C.; Verburg, F. A.

    2014-05-01

    Radioiodine scintigraphy influences staging and treatment in patients with differentiated thyroid carcinoma. The limit of detection for fractional uptake in an iodine avid focus in a scintigraphic image was determined from the number of lesion net counts and the count density of the tissue background. The count statistics were used to calculate the diagnostic activity required to elevate the signal from a lesion with a given uptake significantly above a homogeneous background with randomly distributed counts per area. The dependences of the minimal uptake and the minimal size of lesions visible in a scan on several parameters of influence were determined by linking the typical biokinetics observed in iodine avid tissue to the lesion mass and to the absorbed dose received in a radioiodine therapy. The detection limits for fractional uptake in a neck lesion of a typical patient are about 0.001% after therapy with 7000 MBq, 0.01% for activities typically administered in diagnostic assessments (74-185 MBq), and 0.1% after the administration of 10 MBq I-131. Lesions at the limit of detection in a diagnostic scan with biokinetics eligible for radioiodine therapy are small with diameters of a few millimeters. Increasing the diagnostic activity by a factor of 4 reduces the diameter of visible lesions by 25% or about 1 mm. Several other determinants have a comparable or higher influence on the limit of detection than the administered activity; most important are the biokinetics in both blood pool and target tissue and the time of measurement. A generally valid recommendation for the timing of the scan is impossible as the time of the highest probability to detect iodine avid tissue depends on the administered activity as well as on the biokinetics in the lesion and background in the individual patient.

  6. 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

  7. Follicular thyroid carcinoma.

    PubMed

    Haigh, Philip I

    2002-08-01

    Follicular carcinomas are rare thyroid malignancies that are difficult to diagnose preoperatively. Fine needle aspiration is an excellent diagnostic tool and should be the initial step in managing the solitary thyroid nodule. Follicular carcinoma cannot be diagnosed with certainty by cytologic features alone; the diagnosis rests on the histologic findings of blood vessel or tumor capsule invasion. Surgical resection is the primary option for treatment. The extent of thyroidectomy for optimal survival outcome has not been determined scientifically. The outcome is excellent in minimally invasive follicular carcinoma with lobectomy and isthmusectomy; it is difficult to argue that total thyroidectomy is necessary. In a low risk prognostic group, for tumors other than minimally invasive carcinoma, lobectomy and isthmusectomy or total thyroidectomy can be justified. However, if total thyroidectomy can be done safely with a minimum of complications, then it has definite advantages for staging, postoperative surveillance, treatment, and possibly a lower recurrence rate and better survival rate. For all patients at high risk of recurrence, total thyroidectomy is preferred. PMID:12074771

  8. [Treatment of patients with radioiodine refractory, differentiated thyroid carcinoma. A Consensus Statement].

    PubMed

    Lindner, Christina; Dierneder, J; Pall, G; Pirich, C; Hoffmann, M; Raderer, M; Becherer, A; Niederle, B; Lipp, R; Lind, P; Gallowitsch, H; Romeder, F; Virgolini, I

    2015-01-01

    There is no clear standard therapy for patients with radioactive iodine (131I)-refractory locally advanced or metastatic differentiated thyroid cancer. The therapeutic options for this indication have expanded with the recently approved multiple kinase inhibitor sorafenib. Recommendations for the definition and the management of iodine refractory patients were worked up by an interdisciplinary expert panel, consisting of endocrine surgeons, medical oncologists and nuclear medicine specialists. PMID:25421138

  9. Interest of somatostatin receptors scintigraphy for imaging differentiated thyroid carcinoma tumor sites

    SciTech Connect

    Giammarile, F.; Lumbroso, J.; Schlumberger, M.

    1995-05-01

    Despite the fact that differentiated thyroid carcinoma (DTC) is not classified as a neuroendocrine tumor, there is an increasing interest for the use of somatostatin receptors scintigraphy (SRS) in this disease. We evaluated SRS in DTC patients having no or a poor radioiodine uptake at the level of their tumor sites. Nine patients (pts) (7 men, 2 women; aged from 52 to 65 years) were previously treated (surgery of the primary: 9/9pts; followed by cervical radiotherapy: 4/9pts; radioiodine therapy: 8/9pts; surgery or radiotherapy to bone metastases: 2/9 pts) for DTC (papillary form: 6 pts; follicular; 1 pts; insular: 2 pts). They were explored by conventional imaging modalities (CIM) including Tc-99m MDP bone scans. High activity radioiodine scans were obtained 5 days after I-131 therapy. SRS was carried out during thyroxine therapy using Indium-111 pentetreotide (120 MBq) with imaging at 4 and 24 hours after injection (whole body scans and, when necessary, SPECT). Thyroglobulin blood level ranged from 120 to 60,000ng/ml. SRS was positive at the level of all tumor sites in 8/9 pts; radioiodine scans were negative in 4 pts (1pt with an insular DTC, 3 pt with a papillary DTC), slightly positive in 2 pts (papillary DTC), positive only on part of tumor sites in 1 pts (insular DTC), positive in 1 pt (follicular DTC) and not done in 1 pt. SRS demonstrated 3 new tumor sites (1 to bone, 1 to lung and 1 to mediastinal lymph nodes) in 2 pts; in an other pt, SRS clarified out a doubtful Tc-99m bone scan result and led to definitive confirmation of bone metastases. We had only 1 false negative result in 1 pt having pulmonary metastases (slightly positive radioiodine scan) which had been stable in size on CT for 6 years. These results indicate that, when radioiodine scans are ineffective, SRS is a powerful modality for imaging DTC tumor sites.

  10. Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma.

    PubMed

    Reverter, J L; Holgado, S; Alonso, N; Salinas, I; Granada, M L; Sanmartí, A

    2005-12-01

    The effect of subclinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine (LT4). To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and/or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women (mean +/- SD age: 51 +/- 12 years) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women (51 +/- 11 years) matched for body mass index and menopausal status. We determined calcium metabolism parameters, bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry. No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH, which was significantly increased in controls. No differences were found between groups in bone mineral density in femoral neck (0.971 +/- 0.148 gr/cm(2) vs 0.956 +/- 0.130 gr/cm(2) in patients and controls respectively, P = 0.5). In lumbar spine, bone mineral density values were lower in controls than in patients (1.058 +/- 0.329 gr/cm(2) vs 1.155 +/- 0.224 gr/cm(2) respectively, P < 0.05). When premenopausal (n = 44) and postmenopausal (n = 44) patients were compared with their respective controls, bone mineral density was similar both in femoral neck and lumbar spine. The proportion of women with normal bone mass density, osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women. In conclusion, long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma. PMID:16322336

  11. [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

  12. Tyrosine-kinase inhibitors to treat radioiodine-refracted, metastatic, or recurred and progressive differentiated thyroid carcinoma [Review].

    PubMed

    Ito, Yasuhiro; Suzuki, Shinichi; Ito, Ken-Ichi; Imai, Tsuneo; Okamoto, Takahiro; Kitano, Hiroya; Sugitani, Iwao; Sugino, Kiminori; Tsutsui, Hidemitsu; Hara, Hisato; Yoshida, Akira; Shimizu, Kazuo

    2016-07-30

    Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients' quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs. PMID:27210070

  13. Pediatric Medullary Thyroid Carcinoma

    PubMed Central

    Starenki, Dmytro; Park, Jong-In

    2016-01-01

    Medullary thyroid carcinoma (MTC), which originates from thyroid parafollicular C cells, accounts for 3 to 5% of thyroid malignancies. MTC occurs either sporadically or in an inherited autosomal dominant manner. Hereditary MTC occurs as a familial MTC or as a part of multiple endocrine neoplasia (MEN) type 2A and B syndromes. A strong genotype-phenotype correlation has been observed between hereditary MTC and germ-line “gain of function” mutations of the RET proto-oncogene. Most cases of pediatric MTC are hereditary whereas sporadic MTC is rare in children and is usually diagnosed in adults. Therefore, MTC in children is most often diagnosed in the course of a familial genetic investigation. The standard treatment of MTC mainly requires surgery involving total thyroidectomy and central neck node dissection before extrathyroidal extension occurs. To prevent MTC development in hereditary syndromes, prophylactic thyroidectomy is performed in presymptomatic patients. An appropriate age at which the surgery should take place is determined based upon the data from genotyping, serum calcitonin measurements, and ultrasonography. For the treatment of advanced MTC cases, the broad spectrum receptor tyrosine kinase inhibitors vandetanib and cabozantinib, which also inhibit RET, are used although they are not always effective. PMID:27014708

  14. Medullary Thyroid Carcinoma: Imaging.

    PubMed

    Delorme, Stefan; Raue, Friedhelm

    2015-01-01

    Imaging plays an important role in early detection and staging of medullary thyroid carcinoma (MTC) as well as in follow-up to localize early recurrence. MTC is a rare, calcitonin-secreting thyroid malignancy often diagnosed by ultrasound and calcitonin screening as part of the routine workup for any thyroid nodule. If calcitonin is elevated, imaging studies are needed for preoperative staging, which dictates surgical management. This can be done by ultrasound of the neck and abdomen. Computed tomography (CT) or magnetic resonance imaging (MRI) studies for more distant disease are done preoperatively if calcitonin levels are higher than 500 pg/ml. Neither FDG-PET/CT nor F-DOPA-PET/CT are used routinely for preoperative staging but may contribute in doubtful individual cases. Postoperative elevated calcitonin is related to persistence or recurrence of MTC. Imaging studies to localize tumor tissue during postoperative follow-up include ultrasound, CT, MRI as well as PET studies. They should be used wisely, however, since treatment consequences are often limited, and even patients with persistent disease may survive long enough to accumulate significant radiation doses. Imaging studies are also useful for diagnosis of associated components of the hereditary MTC such as pheochromocytoma and primary hyperparathyroidism (pHPT). PMID:26494385

  15. Differential gene expression of medullary thyroid carcinoma reveals specific markers associated with genetic conditions.

    PubMed

    Maliszewska, Agnieszka; Leandro-Garcia, Luis J; Castelblanco, Esmeralda; Macià, Anna; de Cubas, Aguirre; Goméz-López, Gonzalo; Inglada-Pérez, Lucía; Álvarez-Escolá, Cristina; De la Vega, Leticia; Letón, Rocío; Gómez-Graña, Álvaro; Landa, Iñigo; Cascón, Alberto; Rodríguez-Antona, Cristina; Borrego, Salud; Zane, Mariangela; Schiavi, Francesca; Merante-Boschin, Isabella; Pelizzo, Maria R; Pisano, David G; Opocher, Giuseppe; Matias-Guiu, Xavier; Encinas, Mario; Robledo, Mercedes

    2013-02-01

    Medullary thyroid carcinoma accounts for 2% to 5% of thyroid malignancies, of which 75% are sporadic and the remaining 25% are hereditary and related to multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RET mutations, knowledge of pathways specifically associated with each mutation and with non-RET-mutated sporadic MTC remains lacking. Gene expression patterns have provided a tool for identifying molecular events related to specific tumor types and to different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling of 49 frozen MTC specimens classified as RET mutation, we identified PROM1, LOXL2, GFRA1, and DKK4 as related to RET(M918T) and GAL as related to RET(634) mutation. An independent series of 19 frozen and 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used for validation by RT-qPCR. Two tissue microarrays containing 69 MTCs were available for IHC assays. According to pathway enrichment analysis and gene ontology biological processes, genes associated with the MTC(M918T) group were involved mainly in proliferative, cell adhesion, and general malignant metastatic effects and with Wnt, Notch, NFκB, JAK/Stat, and MAPK signaling pathways. Assays based on silencing of PROM1 by siRNAs performed in the MZ-CRC-1 cell line, harboring RET(M918T), caused an increase in apoptotic nuclei, suggesting that PROM1 is necessary for survival of these cells. This is the first report of PROM1 overexpression among primary tumors. PMID:23201134

  16. 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

  17. Pulmonary metastases in differentiated thyroid carcinoma. Study of 58 cases with implications for the primary tumor treatment

    SciTech Connect

    Massin, J.P.; Savoie, J.C.; Garnier, H.; Guiraudon, G.; Leger, F.A.; Bacourt, F.

    1984-02-15

    Fifty-eight cases of pulmonary metastases (PM) from 831 cases of differentiated thyroid carcinoma (DTC) were studied. PM were found in about 10% of follicular and 5% of papillary tumors. /sup 131/I uptake was found in 55% of the cases, irrespective of histology. Twenty-one patients were treated by /sup 131/I only and 12 were cured. Micronodular metastases, 92% papillary, with 86% positive /sup 131/I uptake and 77% 8-year survival rate, are the most favorable forms. In others the influence of PM size/age, uptake, delay of appearance, presence of cervical or mediastinal lymph nodes is discussed. Occurrence of late PM according to treatment of the primary tumor was 1.3% thyroidectomy + /sup 131/I; 3% thyroidectomy; 5% partial thyroidectomy + /sup 131/I; 11% partial thyroidectomy only. Thus prevention in DTC of severe PM (28% 8-year survival rate) can best be achieved by complete thyroidectomy + /sup 131/I ablation dose.

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

    PubMed

    Heemstra, K A; Hamdy, N A T; Romijn, J A; Smit, J W A

    2006-06-01

    Patients with differentiated thyroid carcinoma (DTC) are commonly treated long-term with thyrotropin (TSH)- suppressive thyroxine replacement therapy resolving in a state of subclinical hyperthyroidism. The relationship between subclinical hyperthyroidism and osteoporosis is not clear. In this review, we systematically selected and analyzed 21 studies addressing this issue. Although multiple methodological differences between studies prevented a structured meta-analysis, our data suggest that postmenopausal women with subclinical hyperthyroidism are most at risk, whereas no increased risk was observed in men and premenopausal women. Based on these findings we believe that measurement of bone mineral density is recommended in postmenopausal women with DTC starting TSH suppressive therapy. This should be subsequently regularly measured to enable timely intervention with bone protective agents. PMID:16839260

  19. 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.

  20. Thyroid metastasis of bladder transitional cell carcinoma.

    PubMed

    Mirjalili, S M M; Hashemipour, S; Salehi, S; Kazemifar, A M; Madani, P S

    2016-04-01

    The thyroid gland is a rare site for cancer metastasis. We report a 75-year-old man who was referred with a history of hematuria and generalized bone pain for the past few months. He had a past history of partial left lobe thyroidectomy for follicular adenoma. Subsequently he was referred for a thyroid mass and a subtotal thyroidectomy showed a poorly-differentiated carcinoma. On the latest admission, the patient underwent resection of a bladder tumour with malignant histology and an immunohistochemical profile of CK7+/CK20+/34 Beta E12+/CEA-/PSA-. Re-examination of thyroid sections with immunohistochemical stains revealed the malignant cells to be CK7+/CK20+/34 Beta E12+/CEA-/TTF1-. The findings were compatible with metastasis of the bladder transitional cell carcinoma to the thyroid gland.Scans revealed multiple liver and bone metastases. The patient died 2 months after the diagnosis. PMID:27126668

  1. 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.

  2. 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

  3. Iodine-131 treatment and high-resolution CT: results in patients with lung metastases from differentiated thyroid carcinoma.

    PubMed

    Ilgan, Seyfettin; Karacalioglu, A Ozgur; Pabuscu, Yuksel; Atac, G Kaan; Arslan, Nuri; Ozturk, Emel; Gunalp, Bengul; Ozguven, M Ali

    2004-06-01

    Between 1984 and 2002, pulmonary metastases were detected in 42 (4%) out of 1,023 patients with differentiated thyroid carcinoma (DTC) in our department. The age at diagnosis ranged from 6 to 77 years. Lung metastases were diagnosed by both increased thyroglobulin (Tg) levels and positive uptake of iodine-131 on scans, and/or positive radiological findings. The primary tumours were histologically classified as papillary (30 patients), follicular (nine patients) and poorly differentiated (two tall cell, one insular carcinoma). The duration of follow-up ranged from 24 to 228 months. The end-results of the (131)I therapy were evaluated. The treatment of choice was (131)I therapy of metastases after total thyroidectomy plus lymph node dissection (if lymph node metastases were present). Applied single and total (131)I activities were 1.8-10.4 GBq and 5.5-43.7 GBq, respectively. Lung metastases were present at the time of diagnosis in 30 patients and developed during the follow-up period in the remaining 12. Twelve patients with extensive metastases died of thyroid carcinoma and another died due to secondary malignancy (malignant mesothelioma). Ten patients with lung metastases remain completely free of disease and are probably cured, while another seven were stable at the time of study. Three- and five-year survival rates were 86% (36/42) and 76% (32/42), respectively. To define the diagnostic value of high-resolution computed tomography (HRCT) and identify the distinctive features of lung metastases from DTC, 22 patients were further examined with HRCT within 2 weeks of the initial diagnosis of lung metastases and the results were compared with chest X-ray findings. HRCT detected metastases in 10 out of 14 patients with a normal chest X-ray and confirmed metastases in all patients with positive (n=5) and suspicious (n=3) chest X-ray. HRCT did not show any abnormalities in four patients with positive lung uptake on (131)I whole-body images. Stage of disease, existence

  4. 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

  5. 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

  6. Polymorphisms within base and nucleotide excision repair pathways and risk of differentiated thyroid carcinoma.

    PubMed

    Cipollini, Monica; Figlioli, Gisella; Maccari, Giuseppe; Garritano, Sonia; De Santi, Chiara; Melaiu, Ombretta; Barone, Elisa; Bambi, Franco; Ermini, Stefano; Pellegrini, Giovanni; Cristaudo, Alfonso; Foddis, Rudy; Bonotti, Alessandra; Romei, Cristina; Vivaldi, Agnese; Agate, Laura; Molinari, Eleonora; Barale, Roberto; Forsti, Asta; Hemminki, Kari; Elisei, Rossella; Gemignani, Federica; Landi, Stefano

    2016-05-01

    The thyrocytes are exposed to high levels of oxidative stress which could induce DNA damages. Base excision repair (BER) is one of the principal mechanisms of defense against oxidative DNA damage, however recent evidences suggest that also nucleotide excision repair (NER) could be involved. The aim of present work was to identify novel differentiated thyroid cancer (DTC) risk variants in BER and NER genes. For this purpose, the most strongly associated SNPs within NER and BER genes found in our previous GWAS on DTC were selected and replicated in an independent series of samples for a new case-control study. Although a positive signal was detected at the nominal level of 0.05 for rs7689099 (encoding for an aminoacid change proline to arginine at codon 117 within NEIL3), none of the considered SNPs (i.e. rs7990340 and rs690860 within RFC3, rs3744767 and rs1131636 within RPA1, rs16962916 and rs3136166 in ERCC4, and rs17739370 and rs7689099 in NEIL3) was associated with the risk of DTC when the correction of multiple testing was applied. In conclusion, a role of NER and BER pathways was evoked in the susceptibility to DTC. However, this seemed to be limited to few polymorphic genes and the overall effect size appeared weak. PMID:27062014

  7. Well-Differentiated Thyroid Carcinomas: Management of the Central Lymph Node Compartment and Emerging Biochemical Markers

    PubMed Central

    Yeung, Meei J.; Pasieka, Janice L.

    2011-01-01

    Well-differentiated thyroid cancers (WDTCs) are generally indolent cancers that are associated with a low mortality. Although the incidence of these tumors is increasing, there has not been an associated increase in the mortality rates. As we gain a greater understanding and more experience with these good prognosis cancers, the way in which we treat these tumors is evolving. The definition of persistent or recurrent disease has seen a shift from being a clinical and/or radiological diagnosis to now one based on a biochemical blood marker, thyroglobulin. Central lymph node metastases are a very common problem in WDTC, being present in up to 90% of patients. The optimal surgical management of the central lymph node compartment remains a hotly debated topic. This paper identifies these controversies and presents available data surrounding these issues. Biochemical tumor markers are gaining wider use in practice and in time hopefully provide more specific information with which surgical decision-making can be based. A summary of the clinically available markers is presented. PMID:21969828

  8. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  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. 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

  11. 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

  12. 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

  13. Detection and treatment of lung metastases of differentiated thyroid carcinoma in patients with normal chest X-rays

    SciTech Connect

    Schlumberger, M.; Arcangioli, O.; Piekarski, J.D.; Tubiana, M.; Parmentier, C.

    1988-11-01

    Lung metastases were demonstrated by total-body /sup 131/I scans in 23 patients with differentiated thyroid carcinoma, at a time when chest x-ray was normal. This total-body /sup 131/I scan was performed after the administration of 2 mCi (in 11 patients) or 100 mCi (in 12 patients). Overall uptake of 131I in lungs was less than 1% of the administered dose in 11 patients. All patients were treated with radioiodine. No lung uptake was found in 20 patients at the last 100 mCi post-therapy scan. Among them, Tg level became undetectable during T4 treatment in eight, lung CT scan showed the disappearance of the micronodules in seven, and lung biopsy did not show evidence of disease in two patients. No patient developed radiation lung fibrosis. In conclusion, favorable responses to radioiodine treatment were observed despite relatively low overall uptake, in relation to the small size of lung metastases. This provides high concentrations of radioiodine and therefore high radiation doses.

  14. 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

  15. 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. PMID:26018699

  16. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... non-cancerous 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.

  17. 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.

  18. Targeted molecular therapies in thyroid carcinoma.

    PubMed

    Romagnoli, Serena; Moretti, Sonia; Voce, Pasquale; Puxeddu, Efisio

    2009-12-01

    Thyroid cancer incidence has significantly increased in the last three decades and many patients seek medical attention for its treatment every year. Among follicular cell-derived tumors, the majority are differentiated thyroid carcinomas (DTC), whose prognosis is very good with only 15% of the cases presenting disease persistence or recurrence after initial treatment. Medullary thyroid carcinoma has a worse prognosis, especially in patients with diffused cancers at the time of initial surgery. Traditional treatment options for persistent or recurrent disease include additional surgery, radioiodine treatment and TSH-suppression in DTC patients; external beam radiotherapy, and cytotoxic chemotherapy, often have low efficacy and many patients with advanced disease ultimately die. In the last two decades many of the molecular events involved in cancer formation have been uncovered. This knowledge has prompted the development of novel therapeutic strategies mainly based on the inhibition of key molecular mediators of the tumorigenic process. In particular the class of small-molecule tyrosine kinase inhibitors was enriched by many compounds that have reached clinical trials and in some cases have had approval for clinical use in specific cancers. Many of these compounds entered clinical trials also for locally advanced or metastatic thyroid carcinomas showing very promising results. PMID:20126863

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

    ClinicalTrials.gov

    2016-06-30

    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

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

    ClinicalTrials.gov

    2016-07-12

    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

  1. Diagnosis and management of carcinoma of the thyroid

    SciTech Connect

    Block, M.A.

    1987-06-01

    Thyroid nodules are a frequent finding but engender concern primarily because of a large size or, occasionally, as a manifestation of a carcinoma. Needle biopsy permits a definite diagnosis in the majority of cases. Well-differentiated thyroid carcinoma is treated by surgery, the extent of which would be based on the gross evidence of the extent of the disease, the histologic features of the lesion, the patient's age and overall medical status, and the need to avoid postoperative complications. The appropriate care after surgery is also based on the individual patient. Medullary thyroid carcinoma is best treated by total thyroidectomy with cervical lymph node dissection on the side of a palpable nodule. Serum calcitonin determinations provide diagnostic and some prognostic data. Anaplastic carcinoma is usually best treated by radiation therapy. The outlook is good for most thyroid carcinoma recognized reasonably early.

  2. Undetectable Thyroglobulin Levels in Poorly Differentiated Thyroid Carcinoma Patients Free of Macroscopic Disease After Initial Treatment: Are They Useful?

    PubMed Central

    Ibrahimpasic, Tihana; Ghossein, Ronald; Carlson, Diane L.; Nixon, Iain J.; Palmer, Frank L.; Patel, Snehal G.; Tuttle, Robert M.; Shaha, Ashok; Shah, Jatin P.; Ganly, Ian

    2016-01-01

    Background Predictive role of undetectable thyroglobulin (Tg) in patients with poorly differentiated thyroid carcinoma (PDTC) is unclear. Our goal was to report on Tg levels following total thyroidectomy and adjuvant RAI in PDTC patients and to correlate Tg levels with recurrence. Methods Forty patients with PDTC with no distant metastases at presentation (M0) and managed by total thyroidectomy and adjuvant RAI were identified from a database of 91 PDTC patients. Of these, 31 patients had Tg values recorded and formed the basis of our analysis. A nonstimulated Tg level <1 ng/ml was used as a cutoff point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ2 test. Recurrence-free survival (RFS) stratified by postop Tg level was calculated by Kaplan–Meier method and compared by log-rank test. Results Twenty patients had undetectable Tg (<1 ng/ml) and 11 had detectable Tg (≥1 ng/ml; range 2–129 ng/ml) following surgery. After adjuvant RAI, 24 patients had undetectable Tg (<1 ng/ml) and 7 had detectable Tg (≥1 ng/ml; range 1–57 ng/ml). Patients with undetectable Tg were less likely to have pathologically positive margins compared to those with detectable Tg (33 vs. 72 % respectively; p = 0.03). Patients with undetectable Tg levels had better 5-year regional control and distant control than patients with detectable Tg level (5-year regional recurrence- free survival 96 vs. 69 %; p = 0.03; 5-year distant recurrence-free survival 96 vs. 46 %, p = 0.11). Conclusion Postoperative thyroglobulin levels in subset of patients with PDTC appear to have predictive value for recurrence. Patients with undetectable Tg have a low rate of recurrence. PMID:25893415

  3. The long term effect of levothyroxine on bone mineral density in patients with well differentiated thyroid carcinoma after treatment.

    PubMed

    Eftekhari, Mohammad; Asadollahi, Abolfazl; Beiki, Davood; Izadyar, Sina; Gholamrezanezhad, Ali; Assadi, Majid; Fard-Esfahani, Armaghan; Fallahi, Babak; Takavar, Abbas; Saghari, Mohsen

    2008-01-01

    To date a few studies have focused on the possible effects of subclinical hyperthyroidism on bone metabolism, showing conflicting results. This study was designed to evaluate this possibility. Sixty-six patients, 22 pre-menopausal women, 33 post-menopausal women and 11 men, who had received iodine-131 ((131)I) ablation postoperatively for well differentiated thyroid carcinoma (WDTC) and were treated for a long term with levothyroxine (T(4)), entered the study and were compared with sixty-six healthy controls individually matched to the patients for age, gender and menopausal status. The bone mineral density (BMD) of lumbar and hip regions of the patients was measured, while on the T(4) suppressive treatment, with average duration of 14.93+/-2.17 months after initiation of the T(4) suppressive treatment and was compared with the BMD of healthy controls. All patients were in the subclinical hyperthyroid state, while all controls were serologically and clinically euthyroid. Our results show that there was no significant difference in BMD measured at the lumbar spine of patients and controls in any subgroup (P>0.05). Analysis of the data of BMD from the hips in men, premenopausal women and controls, also revealed no difference. It was noted that the mean BMD of the femur in the postmenopausal women were at the statistical limit of significance as compared to the control group (P=0.05). In conclusion, our findings indicate that the replacement dose of T(4) in WDTC patients after (131)I ablation, does not have a significant effect on BMD in men, in pre and post-menopausal women and hence on the risk of osteoporosis. In post-menopausal women, the mean femoral BMD was at the limit of statistical significance. PMID:19081859

  4. 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

  5. Integrated genomic characterization of papillary thyroid carcinoma.

    PubMed

    2014-10-23

    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

  6. 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

  7. Change of Bone Mineral Density and Biochemical Markers of Bone Turnover in Patients on Suppressive Levothyroxine Therapy for Differentiated Thyroid Carcinoma

    PubMed Central

    Kim, Chei Won; Hong, Seokbo; Oh, Se Hwan; Lee, Jung Jin; Han, Joo Young; Kim, So Hun; Nam, Moonsuk; Kim, Yong Seong

    2015-01-01

    Untreated hyperthyroidism and high-dose thyroid hormone are associated with osteoporosis, and increased bone mineral density (BMD) has been demonstrated in postmenopausal females with hypoparathyroidism. Studies on the effect of suppressive levothyroxine (LT4) therapy on BMD and bone metabolism after total thyroidectomy in patients with differentiated thyroid carcinoma have presented conflicting results, and few studies in relation to the status of hypoparathyroidism have been studied. One hundred postmenopausal women and 24 premenopausal women on LT4 suppression therapy were included in this study. BMD of lumbar spine and femur and bone turnover markers were measured at the baseline and during the follow-up period up to 18 months using dual energy X-ray absorptiometry. Biochemical marker of bone resorption was measured by urine deoxypyridinoline and bone formation by serum osteocalcin. The age ranged from 36 to 64 years old. Thyroid stimulating hormone (TSH) was suppressed during the study. The results showed that BMD of femur and lumbar spine were not significantly changed in both pre- and postmenopausal women except femur neck in postmenopausal women without hypoparathyroidism. Patients with hypoparathyroidism had higher BMD gain than those without hypoparathyroidism in total hip (1.25 vs. -1.18%, P=0.015). Biochemical markers of bone turnover, serum osteocalcin, and urine deoxypyridinoline did not show significant change. In conclusion, patients with well differentiated thyroid carcinoma are not at a great risk of bone loss after LT4 suppressive therapy. The state of hypoparathyroidism is associated with increased BMD, particularly in postmenopausal women. PMID:26389089

  8. 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

  9. [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

  10. Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

    PubMed Central

    Sohn, Seo Young; Joung, Ji Young; Cho, Yoon Young; Park, Sun Mi; Jin, Sang Man; Chung, Jae Hoon

    2015-01-01

    Background There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH). Methods We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up. Results Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods. Conclusion Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT. PMID:26248858

  11. RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.

    PubMed Central

    Thiagalingam, A; De Bustros, A; Borges, M; Jasti, R; Compton, D; Diamond, L; Mabry, M; Ball, D W; Baylin, S B; Nelkin, B D

    1996-01-01

    An activated ras oncogene induces a program of differentiation in the human medullary thyroid cancer cell line TT. This differentiation process is accompanied by a marked increase in the transcription of the human calcitonin (CT) gene. We have localized a unique Ras-responsive transcriptional element (RRE) in the CT gene promoter. DNase I protection indicates two domains of protein-DNA interaction, and each domain separately can confer Ras-mediated transcriptional inducibility. This bipartite RRE was also found to be Raf responsive. By affinity screening, we have cloned a cDNA coding for a zinc finger transcription factor (RREB-1) that binds to the distal RRE. The consensus binding site for this factor is CCCCAAACCACCCC. RREB-1 is expressed ubiquitously in human tissues outside the adult brain. Overexpression of RREB-1 protein in TT cells confers the ability to mediate increased transactivation of the CT gene promoter-reporter construct during Ras- or Raf-induced differentiation. These data suggest that RREB-1 may play a role in Ras and Raf signal transduction in medullary thyroid cancer and other cells. PMID:8816445

  12. 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.

  13. 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

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

    PubMed Central

    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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Heart Failure as First Sign of Development of Cardiac Metastases in a Patient with Diagnosis of Papillary Thyroid Carcinoma on Treatment with Tyrosine-Kinase Inhibitors: Differential Diagnoses and Clinical Management

    PubMed Central

    Bruixola, Gema; Segura, Ángel; Caballero, Javier; Andrés, Ana; Reche, Encarnación; Escoín, Corina; Díaz-Beveridge, Roberto

    2014-01-01

    Background Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer. Patient A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases. Results After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels. Conclusions We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation. PMID:25298765

  20. 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

  1. 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

  2. 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.

  3. Insular carcinoma: A distinct thyroid carcinoma with associated iodine-131 localization

    SciTech Connect

    Justin, E.P.; Seabold, J.E.; Robinson, R.A.; Walker, W.P.; Gurll, N.J.; Hawes, D.R. )

    1991-07-01

    Insular carcinoma, once considered a poorly-differentiated thyroid cancer, has been reclassified as a distinct thyroid neoplasm. Since this neoplasm is composed of follicular epithelial cells, it may concentrate radioiodide (131I) making postoperative 131I imaging for detection of metastases and radiotherapy possible. A 20-yr review of 35 cases diagnosed as anaplastic or undifferentiated thyroid carcinoma at this medical center revealed five patients with insular carcinoma. Four patients showed postoperative 131I localization and received therapeutic doses of 131I. Three of the four showed extrathyroidal 131I localization in neoplastic lesions. In one patient, the resolution of metastatic lesions by magnetic resonance and 131I imaging suggests that 131I may have an important therapeutic role in this aggressive neoplasm.

  4. 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

  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. 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

  7. Primary thyroid paraganglioma mimicking medullary thyroid carcinoma: A case report

    PubMed Central

    YU, XING; WANG, YONG; WANG, PING; JI, CAI-HONG; MIAO, CHUN-DI; ZHENG, SHU

    2015-01-01

    Primary thyroid paraganglioma (TP) is an uncommon tumor, and in rare cases, this disease tends to mimic medullary thyroid carcinoma (MTC). The present study reports a rare case of primary TP mimicking thyroid carcinoma, accompanied by hyperthyroidism. A 30-year-old female presented with an anterior cervical mass. Pre-operative radiological studies and operative frozen section analysis indicated an atypical MTC. Primary TP was finally diagnosed by pathology and immunohistochemical staining. Laboratory examinations (thyroid hormones tests) and Tc99m emission computed tomography revealed hyperthyroidism. Gene analysis of TP-associated gene mutations was negative. Surgical resection was performed as a curative approach and there is currently no metastasis after 36 months of follow-up. Surgeons must be aware of this disease in order to ensure a correct diagnosis and to prevent them from performing unnecessary procedures. The current study presents a case of primary TP mimicking MTC, discusses the radiographic results and histological characteristics, and provides a review of the associated literature. PMID:26622613

  8. Proteomic Profiling of Thyroid Papillary Carcinoma

    PubMed Central

    Ban, Yoshiyuki; Yamamoto, Gou; Takada, Michiya; Hayashi, Shigeo; Ban, Yoshio; Shimizu, Kazuo; Akasu, Haruki; Igarashi, Takehito; Bando, Yasuhiko; Tachikawa, Tetsuhiko; Hirano, Tsutomu

    2012-01-01

    Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. We performed shotgun liquid chromatography (LC)/tandem mass spectrometry (MS/MS) analysis on pooled protein extracts from patients with PTC and compared the results with those from normal thyroid tissue validated by real-time (RT) PCR and immunohistochemistry (IHC). We detected 524 types of protein in PTC and 432 in normal thyroid gland. Among these proteins, 145 were specific to PTC and 53 were specific to normal thyroid gland. We have also identified two important new markers, nephronectin (NPNT) and malectin (MLEC). Reproducibility was confirmed with several known markers, but the one of two new candidate markers such as MLEC did not show large variations in expression levels. Furthermore, IHC confirmed the overexpression of both those markers in PTCs compared with normal surrounding tissues. Our protein data suggest that NPNT and MLEC could be a characteristic marker for PTC. PMID:22518348

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

    PubMed

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

    2016-04-01

    Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus. PMID:26421671

  10. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: A cytological dilemma.

    PubMed

    Pantola, Chayanika; Kala, Sanjay; Athar, Mohd; Thakur, Sudeep

    2016-01-01

    Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid is a rare primary thyroid tumor arising in a background of Hashimoto's/lymphocytic thyroiditis and has been recently introduced in the World Health Organization (WHO) classification of thyroid tumors. It is characterized by extensive sclerosis, squamous and glandular differentiation, and inflammatory infiltrate rich in eosinophil. Here, we are discussing the cytological features of this rare case in a 35-year-old female presented with thyroid swelling and lymph-node enlargement. PMID:27011441

  11. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: A cytological dilemma

    PubMed Central

    Pantola, Chayanika; Kala, Sanjay; Athar, Mohd.; Thakur, Sudeep

    2016-01-01

    Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid is a rare primary thyroid tumor arising in a background of Hashimoto's/lymphocytic thyroiditis and has been recently introduced in the World Health Organization (WHO) classification of thyroid tumors. It is characterized by extensive sclerosis, squamous and glandular differentiation, and inflammatory infiltrate rich in eosinophil. Here, we are discussing the cytological features of this rare case in a 35-year-old female presented with thyroid swelling and lymph-node enlargement. PMID:27011441

  12. Unusual Thyroid Carcinoma Metastases: a Case Series and Literature Review.

    PubMed

    Farina, Eleonora; Monari, Fabio; Tallini, Giovanni; Repaci, Andrea; Mazzarotto, Renzo; Giunchi, Francesca; Panzacchi, Riccardo; Cammelli, Silvia; Padula, Gilbert D A; Deodato, Francesco; Pasquali, Renato; Fanti, Stefano; Fiorentino, Michelangelo; Morganti, Alessio G

    2016-03-01

    The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission. PMID:26662609

  13. Re-ablation I-131 activity does not predict treatment success in low- and intermediate-risk patients with differentiated thyroid carcinoma.

    PubMed

    Prpic, Marin; Kruljac, Ivan; Kust, Davor; Kirigin, Lora S; Jukic, Tomislav; Dabelic, Nina; Bolanca, Ante; Kusic, Zvonko

    2016-06-01

    The aim of this study was to evaluate the efficacy of different radioactive iodine (I-131) activities used for re-ablation, to compare various combinations of treatment activities, and to identify predictors of re-ablation failure in low- and intermediate-risk differentiated thyroid carcinoma (DTC) patients. The study included 128 consecutive low- and intermediate-risk patients with DTC with ablation failure after total thyroidectomy. Patient characteristics, T status, tumor size, lymph node involvement, postoperative remnant size on whole-body scintigraphy, serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-Tg antibody (TgAb), and Tg/TSH ratio were analyzed as potential predictors of the re-ablation success. Re-ablation was successful in 113 out of 128 patients (88.3 %). Mean first I-131 activity was 2868 ± 914 MBq (77.5 ± 24.7 mCi) and mean second I-131 activity 3004 ± 699 MBq (81.2 ± 18.9 mCi). There was no association between the first, second, and cumulative activity with re-ablation treatment outcome. Treatment failure was associated with higher Tg levels prior to re-ablation (Tg2) (OR 1.16, 95 % CI 1.05-1.29, P = 0.003) and N1a status (OR 3.89, 95 % CI 1.13-13.41, P = 0.032). After excluding patients with positive-to-negative TgAb conversion, Tg2 level of 3.7 ng/mL predicted treatment failure with a sensitivity of 75.0 %, specificity of 80.5 %, and a negative predictive value of 97.1 %. Patients with positive-to-negative TgAb conversion had higher failure rates (OR 2.96, 95 % CI 0.94-9.29). Re-ablation success was high in all subgroups of patients and I-131 activity did not influence treatment outcome. Tg may serve as a good predictor of re-ablation failure. Patients with positive-to-negative TgAb conversion represent a specific group, in whom Tg level should not be used as a predictive marker of treatment outcome. PMID:26732041

  14. Bone mineral density and bone microarchitecture after long-term suppressive levothyroxine treatment of differentiated thyroid carcinoma in young adult patients.

    PubMed

    Mendonça Monteiro de Barros, Graziella; Madeira, Miguel; Vieira Neto, Leonardo; de Paula Paranhos Neto, Francisco; Carvalho Mendonça, Laura Maria; Corrêa Barbosa Lima, Inayá; Corbo, Rossana; Fleiuss Farias, Maria Lucia

    2016-07-01

    Bone mineral density (BMD) seems not to be decreased in young patients given long-term suppressive doses of levothyroxine (LT4), but information regarding the bone microstructure in these patients is lacking. The aim of this study was to determine whether supraphysiologic doses of LT4, initiated during childhood or adolescence for treatment of differentiated thyroid carcinoma (DTC), have any detrimental effects on bone microarchitecture as evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Seventeen patients (27.3 ± 7.1 years old) with DTC with subclinical hyperthyroidism since adolescence and 34 healthy volunteers matched for age, sex, and body mass index were studied by dual-energy X-ray absorptiometry (DXA) to determine the areal BMD at the lumbar spine, hip, and proximal third of the radius. Volumetric BMD and structural parameters of the trabecular and cortical bone were assessed by HR-pQCT of the distal radius and distal tibia. DTC patients were given suppressive doses of LT4 starting at a mean age of 12.6 years, and the mean duration of treatment was 14.2 years. In DTC patients, clinical parameters did not correlate with DXA or HR-pQCT parameters. No differences were found between the patients and controls with respect to BMD and Z scores at any site evaluated by DXA, and no differences were found in the bone microstructure parameters evaluated by HR-pQCT. This cross-sectional study suggests that long-standing suppressive therapy with LT4 during the attainment of peak bone mass may have no significant adverse effects on bone density or microarchitecture. PMID:26056020

  15. [Thyroid's metastasis of tonsillar squamous cell carcinoma].

    PubMed

    Scanelli, Giovanni; Aimoni, Claudia; Marchetti, Elisabetta; Geminiani, Matteo; Pastore, Antonio

    2005-09-01

    The authors describe the case of a 58 years old man, affected by squamous cell carcinoma of the tonsil, who underwent left tonsillectomy with bilateral neck dissection, followed by radiotherapy. After a 6 months period, the patient began to suffer from dysphonia, dysphagia and loss of weight: a painless neoformation was detected at the right lobe of the tyhroid, resulted a metastasis of the tonsillar neoplasm. The search for intranodular thyroglobulin was negative; the patient underwent thyroidectomy which showed a massive infiltration of the right cricothyroid space, cricoid and thyroid wing cartilage necrosis and intralaryngeal tumor infiltration. The authors describe the thyroid metastasis treatment, present an up-to-date review of the literature and suggest a thyroid careful clinical evaluation in every patient with a previous history of oropharyngeal cancer. PMID:16229323

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Somatostatin receptors and somatostatin content in medullary thyroid carcinomas

    SciTech Connect

    Reubi, J.C.; Chayvialle, J.A.; Franc, B.; Cohen, R.; Calmettes, C.; Modigliani, E. )

    1991-04-01

    Human medullary thyroid carcinomas from 19 patients were analyzed for their content in somatostatin (SRIF) receptors using receptor autoradiography with a SRIF-28 analogue and the SRIF octapeptide (Tyr3)-SMS 201-995 as iodinated radioligands. Four out of 19 cases were SRIF receptor positive with the SRIF octapeptide radioligand. These cases as well as four additional tumors were also positive with the SRIF-28 radioligand 125I-(Leu8, D-Trp22, Tyr25)-SRIF-28. High affinity binding sites pharmacologically specific for bioactive SRIF analogues, specifically located on tumor tissue, were identified. In some cases the SRIF receptors were distributed in a non-homogeneous pattern, with labelling occurring preferentially in highly differentiated tumor regions. Numerous cases were shown to have a high tumoral SRIF content measured by radioimmunoassay or immunohistochemical technique. However, there was no correlation between SRIF receptor status and tumor levels of endogenous SRIF. No correlation was seen between the clinical outcome or the survival of the patients and their tumoral SRIF receptor content. Whereas some medullary thyroid carcinomas seem to be a target for SRIF, the SRIF function in these tumors remains unclear. SRIF receptors in a group of medullary thyroid carcinomas may be useful morphological marker of these tumors and of potential interest for their in vivo localization.

  1. Thyroid carcinoma: presentation of a clinical material with special aspects on the classification and operative treatment.

    PubMed

    Grimelius, L; Johansson, H; Nilsson, F; Wicklund, H; Akerström, G

    1978-01-01

    During the years 1969-1975, 58 patients were treated for thyroid carcinoma. 48 patients had differentiated and 10 had anaplastic carcinomas. The material is presented with special attention given to diagnostic methods and treatment for the differentiated forms. The value of cytological examination of fine needle biopsy is clearly documented. 40 patients with differentiated carcinomas were treated with total thyroidectomy, with low complication rate. Accidental persistent recurrent nerve paralysis as well as persistent hypoparathyroidism occurred in less than 3%, Subdivision of papillary and follicular carcinomas on the basis of their local growth pattern is emphasized as being of value in the determination of subsequent therapy. PMID:705971

  2. Treatment rationale in thyroid carcinoma. Effect of scan dose

    SciTech Connect

    Ramanna, L.; Waxman, A.D.; Brachman, M.B.; Tanasescu, D.E.; Chapman, N.; Braunstein, G.D.

    1985-10-01

    The authors have previously shown that the definition of ablation of thyroid tissue in patients treated with thyroidectomy and radioiodine (I-131) for thyroid carcinoma depends upon the dose of I-131 used to scan the patient. The therapeutic response to I-131 therapy was evaluated in a group of ten differentiated thyroid cancer patients who had a negative 2-mCi (-2 mCi) diagnostic study, but had a positive 10-mCi (+10 mCi) diagnostic study (group 1) during their follow-up evaluation. These results were compared to another group of ten differentiated thyroid cancer patients who received I-131 ablation therapy based on a positive 2-mCi (+2 mCi) I-131 scan (group 2). Six patients in group 1 and eight in group 2 had improvement or ablation of residual tissue based on the 10-mCi scan following therapy. The difference in response between the two groups was not statistically significant (P = 0.63) by two-tailed Fisher's exact test, indicating that even patients with -2-mCi, but +10-mCi scans may respond to I-131 therapy. Whether the large dose therapy makes any impact on the clinical outcome has not been answered by this study.

  3. Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

    SciTech Connect

    Michigishi, T.; Mizukami, Y.; Mura, T.; Nomura, T.; Watanabe, K.; Tonami, N.; Hisada, K. )

    1991-05-01

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

  4. Paraneoplastic hypercalcemia in a dog with thyroid carcinoma

    PubMed Central

    Lane, Amy E.; Wyatt, Kenneth M.

    2012-01-01

    This case report describes a dog with thyroid carcinoma and paraneoplastic hypercalcemia. Following thyroidectomy the dog became hypocalcemic and required supplementation with calcitriol and calcium carbonate. During the following 2 years, attempts to reduce the supplementation resulted in hypocalcemia. The dog died from renal failure with no evidence of thyroid carcinoma. PMID:23543930

  5. Mandibular metastasis in a patient with follicular carcinoma of thyroid

    PubMed Central

    Bhadage, Chetan J.; Vaishampayan, Sagar; Umarji, Hemant

    2012-01-01

    Mandibular metastasis due to thyroid carcinoma is not very frequent and the cases described in the literature are few. Due to its bloodstream dissemination, most of them are a consequence of the follicular variant of thyroid carcinomas. We are presenting a case in which the metastatic lesion of mandible was detected before diagnosis of primary malignancy. PMID:22919227

  6. The Role of Epithelial Mesenchymal Transition Markers in Thyroid Carcinoma Progression

    PubMed Central

    Montemayor-Garcia, Celina; Hardin, Heather; Guo, Zhenying; Larrain, Carolina; Buehler, Darya; Asioli, Sofia; Chen, Herbert; Lloyd, Ricardo V.

    2013-01-01

    Understanding the molecular mechanisms involved in thyroid cancer progression may provide targets for more effective treatment of aggressive thyroid cancers. Epithelial-mesenchymal transition (EMT) is a major pathologic mechanism in tumor progression and is linked to the acquisition of stem-like properties of cancer cells. We examined expression of ZEB1 which activates EMT by binding to the E-box elements in the E-cadherin promoter, and expression of E-cadherin in normal and neoplastic thyroid tissues in a tissue microarray (TMA) which included 127 neoplasms and 10 normal thyroid specimens. Thyroid follicular adenomas (FA, n=32), follicular thyroid carcinomas (FTC, n=28), and papillary thyroid carcinomas (PTC, n=57) all expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic thyroid carcinomas (ATC, n=10) were negative for E-cadherin, but positive for ZEB1. A validation set of 10 whole sections of ATCs showed 90% of cases positive for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines (normal thyroid, NTHY-OR13-1; PTC, TPC-1 and ATC, THJ-21T) showed that the ATC cell line expressed the highest levels of ZEB1 while the normal thyroid cell line expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed that Smad7 mRNA was significantly higher in ATC than in any other group (p<0.05). These results indicate that ATCs show evidence of EMT including decreased expression of E-cadherin and increased expression of ZEB1 compared to well differentiated thyroid carcinomas and that increased expression of Smad7 may be associated with thyroid tumor progression. PMID:24126800

  7. Cutaneous metastasis from anaplastic thyroid carcinoma exhibiting exclusively a spindle cell morphology. A case report and review of literature.

    PubMed

    Danialan, Richard; Tetzlaff, Michael T; Torres-Cabala, Carlos A; Mays, Stephen R; Prieto, Victor G; Bell, Diana; Curry, Jonathan L

    2016-03-01

    Anaplastic thyroid carcinoma is a highly aggressive cancer accounting for 1-2% of thyroid malignancies. Cutaneous metastases from anaplastic thyroid carcinoma are exceedingly rare. We report a 65-year-old woman with anaplastic thyroid carcinoma (BRAF V600E mutation) who had lymph node metastases (pT4 N1b) treated by total thyroidectomy, postoperative radiotherapy, adjuvant chemotherapy (paclitaxel and pazopanib) and targeted therapy (vemurafenib). Nine months after initial diagnosis, radiographic studies revealed multiple pulmonary metastases. A dermatologic examination showed a solitary 1.2-cm chest nodule. Skin biopsy from this nodule revealed infiltrative dermal spindle cells arranged in poorly formed fascicles. Immunohistochemical studies demonstrated the tumor cells to be PAX-8 (+), pancytokeratin (+, focally), TTF-1 (-) and SOX-10 (-). Comparison with the patient's primary anaplastic thyroid carcinoma revealed focal areas of poorly differentiated spindle cells morphologically similar to the malignant spindle cells in the skin biopsy. Together, these findings confirmed the diagnosis of anaplastic thyroid carcinoma metastatic to skin. Cutaneous metastasis of anaplastic thyroid carcinoma composed exclusively of spindle cells broadens the histologic differential diagnosis of cutaneous spindle cell malignancies and presents further diagnostic challenges. PAX-8 may be useful in discerning the spindle cell component of anaplastic thyroid carcinoma from other spindle cell malignancies in the skin. PMID:26347145

  8. Soft tissue invasion of papillary thyroid carcinoma.

    PubMed

    Lin, Jen-Der; Hsueh, Chuen; Chao, Tzu-Chieh

    2016-08-01

    Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is common and clinical presentation can vary from minimal to extensive locoregional involvement. Although PTC is generally considered the most benign among all thyroid carcinomas, it may present with local invasion with poor prognosis. Our retrospective study involved 3267 PTC patients undergoing regular follow-up at Chang Gung Medical Center in Linkou, Taiwan. Among them, 269 were PTC cases with ETE, having tumors greater than 1 cm in size and treated with total or complete thyroidectomy with or without lymph node dissection for which the follow-up period was over 10 years. The mean age of 269 cases was 46.8 ± 15.1 (range 11-83 years) years. The number of females was 204 (75.8 %). Patients were categorized into minimal ETE (175 cases) and extensive ETE (94 cases) groups according to surgical findings and pathological reports. Mean follow-up period was 13.3 ± 5.5 (range 0.2-29.3) years, during which 28 (10.4 %) patients died of thyroid cancer; and 63 (23.4 %) of all-cause mortality. Multivariate analysis showed that age, gender, extensive ETE, and lymph node metastasis had a statistically significant effect on thyroid cancer mortality. Survival rates were significantly different between minimal ETE and extensive ETE groups (p < 0.0001). In conclusion, perithyroidal soft tissue involvement by PTC is an important factor that determines patient prognosis and a closer follow-up and more aggressive treatment is necessary for patients who are old, male, extensive ETE, and with lymph node involvement. PMID:27154220

  9. A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

    PubMed Central

    Nucera, Carmelo; Nehs, Matthew A.; Mekel, Michal; Zhang, Xuefeng; Hodin, Richard; Lawler, Jack; Nose, Vânia

    2009-01-01

    Background Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line. Methods We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein–positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice. Results Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins. Conclusions Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers. PMID:19772429

  10. Esophageal recurrence of medullary thyroid carcinoma.

    PubMed

    Muñoz de Nova, Jose Luis; Dworzynska, Agnieszka; Lorente-Poch, Leyre; Sancho, Juan Jose; Sitges-Serra, Antonio

    2015-12-01

    Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall. PMID:26645011

  11. Esophageal recurrence of medullary thyroid carcinoma

    PubMed Central

    Dworzynska, Agnieszka; Lorente-Poch, Leyre; Sancho, Juan Jose; Sitges-Serra, Antonio

    2015-01-01

    Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall. PMID:26645011

  12. 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

  13. Molecular differential diagnosis of follicular thyroid carcinoma and adenoma based on gene expression profiling by using formalin-fixed paraffin-embedded tissues

    PubMed Central

    2013-01-01

    Background Differential diagnosis between malignant follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. Molecular markers may potentially support a differential diagnosis between FTC and FTA in postoperative specimens. The purpose of this study was to derive molecular support for differential post-operative diagnosis, in the form of a simple multigene mRNA-based classifier that would differentiate between FTC and FTA tissue samples. Methods A molecular classifier was created based on a combined analysis of two microarray datasets (using 66 thyroid samples). The performance of the classifier was assessed using an independent dataset comprising 71 formalin-fixed paraffin-embedded (FFPE) samples (31 FTC and 40 FTA), which were analysed by quantitative real-time PCR (qPCR). In addition, three other microarray datasets (62 samples) were used to confirm the utility of the classifier. Results Five of 8 genes selected from training datasets (ELMO1, EMCN, ITIH5, KCNAB1, SLCO2A1) were amplified by qPCR in FFPE material from an independent sample set. Three other genes did not amplify in FFPE material, probably due to low abundance. All 5 analysed genes were downregulated in FTC compared to FTA. The sensitivity and specificity of the 5-gene classifier tested on the FFPE dataset were 71% and 72%, respectively. Conclusions The proposed approach could support histopathological examination: 5-gene classifier may aid in molecular discrimination between FTC and FTA in FFPE material. PMID:24099521

  14. 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

  15. Management of Thyroid Nodules and Surgery for Differentiated Thyroid Cancer

    PubMed Central

    Iyer, N. Gopalakrishna; Shaha, A.R.

    2016-01-01

    The incidence of well-differentiated thyroid cancer has seen a worldwide increase in the last three decades. Whether this is due to a ‘true increase’ in incidence or simply increased detection of otherwise subclinical disease remains unclear. The treatment of thyroid cancer revolves around appropriate surgical intervention, minimising complications and the use of adjuvant therapy in select circumstances. Prognostic features and risk stratification are crucial in determining the appropriate treatment. There continues to be considerable debate in several aspects of management in these patients. Level 1 evidence is lacking, and there are limited prospective data to direct therapy, hence limiting decision-making to retrospective analyses, treatment guidelines based on expert opinion and personal philosophies. This overview focuses on the major issues associated with the investigation of thyroid nodules and the extent of surgery. As overall survival in well-differentiated thyroid cancer exceeds 95%, it is important to reduce over-treating the large majority of patients, and focus limited resources on high-risk patients who require aggressive treatment and closer attention. The onus is on the physician to avoid treatment-related complications from thyroid surgery and to offer the most efficient and cost-effective therapeutic option. PMID:20381323

  16. The RET oncogene in papillary thyroid carcinoma.

    PubMed

    Prescott, Jason D; Zeiger, Martha A

    2015-07-01

    Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto-oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium. PMID:25731779

  17. Metastatic Collision Tumour (Papillary Thyroid Carcinoma and Squamous Cell Carcinoma) in Cervical Lymph Nodes: An Immunohistochemical Analysis.

    PubMed

    Alhanafy, Alshimaa Mahmoud; Al-Sharaky, Dalia; Abdou, Asmaa Gaber; Abdallah, Rania Abdallah

    2016-02-01

    Collision tumours are a rare entity, in this report, we describe a case of 73-year-old woman presented with a rapid enlargement of left upper cervical lymph node (LN) associated with right thyroid nodular goiter. The histopathological examination of the excised LN showed definite areas of papillary thyroid carcinoma admixed with moderately differentiated squamous cell carcinoma (SCC). Thyroglobulin immunostaining was positive in papillary carcinomatous areas confirming thyroid gland as a source of metastasis. Then the patient underwent total thyroidectomy and neck dissection, which revealed multicentric classic papillary thyroid carcinoma with an absence of squamous differentiation on extensive sampling. The patient received adjuvant radioactive iodine, but the neck swelling was rapidly progressing, ulcerated and infected. Computed tomography (CT) revealed left large cervical amalgamated LN and two metastatic lung nodules, the patient received 2 cycles of chemotherapy and was planned for external beam radiotherapy but she died within 7 months of first presentation. Collision tumours pose a diagnostic as well as therapeutic challenge and carry a rapidly progressive course and a fatal outcome. SCC is considered as a dedifferentiation of papillary thyroid carcinoma, which may appear in metastatic site rather than the primary site. PMID:27042475

  18. Neuroendocrine differentiation in cervical carcinoma.

    PubMed Central

    Savargaonkar, P R; Hale, R J; Mutton, A; Manning, V; Buckley, C H

    1996-01-01

    AIMS: To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. METHODS: Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaining was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and ++ (> 5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. RESULTS: There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20.9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. CONCLUSIONS: Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour. Images PMID:8655680

  19. MicroRNA Expression Profiles in Papillary Thyroid Carcinoma, Benign Thyroid Nodules and Healthy Controls

    PubMed Central

    Yoruker, Ebru Esin; Terzioglu, Duygu; Teksoz, Serkan; Uslu, Fatma Ezel; Gezer, Ugur; Dalay, Nejat

    2016-01-01

    MicroRNAs (miRNAs) represent a class of short endogenous non-coding RNAs that negatively regulate gene expression at the post-transcriptional level in many biological processes, including proliferation, differentiation, stress response and apoptosis. In this study we analyzed a set of seven miRNA molecules in sera of patients with papillary thyroid cancer, multinodular goiter and healthy controls to identify miRNA molecules that may have utility as markers for PTC. MiR-21 serum levels in the preoperative PTC and MG groups were significantly higher than the control group. Likewise, postoperative levels of miR-151-5p, miR-221 and miR-222 were significantly lower in patients with PTC. When serum miRNA levels were evaluated according to stage, postoperative levels of miR-151-5p and miR-222 were significantly lower in patients with advanced stages of the disease. The miRNA levels were also found associated with the size of the primary tumor. Our data imply that specific miRNA molecules which are differentially expressed in thyroid tumors may play role in the development of papillary thyroid carcinoma. PMID:27162538

  20. 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

  1. 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.

  2. Systemic paraneoplastic vasculitis secondary to papillary carcinoma of the thyroid.

    PubMed

    Guerouaz, N; Alaoui, M; Raiss, M; Hassam, B; Senouci, K

    2016-08-01

    Systemic vasculitis secondary to thyroid carcinomas is exceptional. We report the case of a 55-year-old woman who presented with systemic vasculitis involving leucocytoclastic cutaneous vasculitis and renal disorders secondary to papillary thyroid carcinoma (PTC). Her symptoms resolved completely after total thyroidectomy. Other causes of vasculitis were excluded. To our knowledge, this is only the second case reported of systemic vasculitis associated with PTC in a paraneoplastic manner. PMID:27416971

  3. Skull base metastasis from papillary thyroid carcinoma: a report of three cases

    PubMed Central

    Tunio, Mutahir A; Al Asiri, Mushabbab; Al-Qahtani, Khalid Hussain; Aldandan, Sadiq; Riaz, Khalid; Bayoumi, Yasser

    2015-01-01

    Skull base metastasis from differentiated thyroid carcinoma, including papillary and follicular thyroid carcinoma, is a rare manifestation. Herein, we present three cases of skull base metastasis of papillary thyroid carcinoma. The mean age of the patients was 68.6 (65–74) years, and the mean interval between initial diagnosis and skull base metastasis was 56.3 (28–89) months. Cranial nerve palsies were seen in all patients. Intensity modulated radiation therapy to deliver 6,000–6,600 cGy to the skull base metastasis was given to all patients, in addition to partial resection in one patient. At the time of last follow-up, all skull base metastases were well controlled. PMID:26203287

  4. 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. PMID:26589365

  5. 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. PMID:25082554

  6. Isolated skeletal muscle metastatic deposit in a patient with micropapillary carcinoma thyroid identified by 18F FDG PET CT.

    PubMed

    Sarma, Manjit; Sonik, Bhavya; Subramanyam, Padma; Sundaram, Palaniswamy Shanmuga

    2015-03-01

    Micropapillary carcinoma of thyroid is said to be low risk differentiated thyroid malignancy with excellent prognosis. We report the identification of an isolated FDG avid muscle deposit in a treated case of micropapillary carcinoma of the right lobe and widely invasive follicular carcinoma of the left lobe thyroid gland. Patient was found to have an elevated thyroglobulin level with negative iodine scan (TENIS syndrome) on follow up at 6 months. An 18F FDG PET CT (18 fluorine-fluorodeoxyglucose positron emission computed tomography) whole body study revealed a solitary FDG avid deltoid muscle deposit which was histopathologically confirmed to be metastatic papillary carcinoma. While follicular carcinoma is known to have distant metastases, this may be the first reported case of solitary skeletal metastases from micropapillary carcinoma of thyroid and probably the second reported skeletal muscle deposit from DTC detected on 18F FDG PET CT done following elevated thyroglobulin level and negative 131 iodine WB scan (TENIS). This case also assumes importance because it demonstrates possibility of metastases even from a micropapillary carcinoma in contrast to American Thyroid Association guidelines (2009) which suggests that micropapillary carcinoma of thyroid does not merit further treatment after a Total Thyroidectomy. PMID:25698468

  7. 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

  8. 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

  9. Incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis and solitary cold nodules

    SciTech Connect

    Ott, R.A.; Calandra, D.B.; McCall, A.; Shah, K.H.; Lawrence, A.M.; Paloyan, E.

    1985-12-01

    The reported incidence of thyroid carcinoma in Hashimoto's thyroiditis varies widely. For this reason the specific subpopulation of patients with Hashimoto's thyroiditis and a solitary cold nodule was analyzed. Between 1972 and 1984 we operated on 146 consecutive patients with solitary cold nodules and Hashimoto's thyroiditis. There were 47 carcinomas, for an incidence of 32%. The mean age of the 146 patients was 43 1/2 years (median 44 years), with 126 females and 20 males. There was a history of prior head and neck radiation exposure in 54 patients, with a 33% incidence of thyroid carcinoma. The 92 patients without a history of radiation exposure had a 31.5% incidence of carcinoma. The frequency of multicentricity (bilateralism) was 33% in the group that underwent radiation and 24% in the group that did not. To date, with a mean follow-up of 4.7 years, there have been no deaths and no evidence of recurrence. In conclusion, we report a 32% incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis and a solitary cold nodule, with no apparent difference between the patients with or without a history of radiation exposure, although there was a higher incidence of bilateralism (33% versus 24%) in the carcinomas of the patients with a history of head and neck irradiation. We suggest that the operative management of these patients is total thyroidectomy for those with a history of head and neck radiation and thyroid lobectomy for patients with no history of radiation, followed by contralateral lobectomy if a carcinoma is demonstrated.

  10. Nonpalpable thyroid carcinoma: clinical controversies on preoperative selection.

    PubMed

    Carpi, Angelo; Nicolini, Andrea; Casara, Dario; Rubello, Domenico; Rosa Pelizzo, Maria

    2003-06-01

    This article emphasizes some controversies concerning the preoperative selection of nonpalpable thyroid tumors. The prevalence of occult thyroid carcinoma in surgical series (1.8-10%) is not higher than in autopsy thyroid series (2.7-24%). The prevalence of occult thyroid carcinoma in thyroid glands examined in the same institution by ultrasound, for a clinical thyroid abnormality or for investigation of other neck structures without clinically evident or suspected thyroid disease, varies from 3% to 8% and is very similar independent of the fact that a thyroid abnormality is or is not the indication for ultrasonography. These data suggest that the presence of a thyroid disease is not a risk factor for harboring an occult thyroid carcinoma (except for C-cell hyperplasia in the rare case of MEN 2 syndromes). As it is not cost effective to examine all the nonpalpable lesions with fine-needle aspiration (FNA) guided by ultrasounds, it is necessary to define to which extent ultrasound is useful in selecting those lesions to be examined cytologically by FNA. The use of ultrasound to select these lesions is very controversial. Ultrasound-guided cytologic diagnosis of nonpalpable nodules is not as accurate as in the case of palpable nodules. Sampling of material adequate for cytologic analysis depends on the lesion size; it is 64% for a 0.7-cm lesion and it increases to 86.7% for a mean size of 1.1 cm. For the diagnosis of occult thyroid carcinomas (< or =1 cm), sensitivity is 35.8% and false-negative results are 49.3%. Nonpalpable nodules with a size of 1.5 cm represent an absolute indication to perform an ultrasound-guided FNA because this is the size limit for dividing thyroid nodules in probably innocuous or potentially dangerous categories and because the cytologic diagnosis of nodules of this size is sufficiently reliable. For the smaller incidentally discovered thyroid nodules following ultrasound, physicians should discuss with the patient whether and when to

  11. Nuclear cysteine cathepsin variants in thyroid carcinoma cells.

    PubMed

    Tedelind, Sofia; Poliakova, Kseniia; Valeta, Amanda; Hunegnaw, Ruth; Yemanaberhan, Eyoel Lemma; Heldin, Nils-Erik; Kurebayashi, Junichi; Weber, Ekkehard; Kopitar-Jerala, Nataša; Turk, Boris; Bogyo, Matthew; Brix, Klaudia

    2010-08-01

    The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins. PMID:20536394

  12. Occult thyroid carcinoma: a rare case report and review of literature

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2014-01-01

    Occult thyroid carcinoma is very common in the clinic and is generally divided into four groups. Here, we proposed two types of occult thyroid carcinoma as the fifth group. The first type was locoregional lymph node metastases from thyroid carcinoma, and the second type was distant organ metastases from thyroid carcinoma. The unique aspect of the fifth group was that the primary carcinoma of the fifth group was not finally found by pathological examination. To better understand the fifth group, we reported a typical case. Furthermore, we discussed the diagnostic criteria and procedures and the management of the fifth group of occult thyroid carcinoma. PMID:25197399

  13. Management of hereditary medullary thyroid carcinoma.

    PubMed

    Pappa, Theodora; Alevizaki, Maria

    2016-07-01

    Hereditary medullary thyroid carcinoma (MTC) represents up to one-third of MTC cases and includes multiple endocrine neoplasia syndrome type 2A (and its variant familial MTC) and 2B. The aim of this paper is to provide an overview of the disease focusing on the management of hereditary MTC patients, who have already developed tumor, as well as discuss the recommended approach for asymptomatic family members carrying the same mutation. A PubMed search was performed to review recent literature on diagnosis, genetic testing, and surgical and medical management of hereditary MTC. The wide use of genetic testing for RET mutations has markedly influenced the course of hereditary MTC. Prophylactic thyroidectomy of RET carriers at an early age eliminates the risk of developing MTC later in life. Pre-operative staging is a strong prognostic factor in patients, who have developed MTC. The use of recently approved tyrosine kinase inhibitors (vandetanib, cabozantinib) holds promising results for the treatment of unresectable, locally advanced, and progressive metastatic MTC. Genetic testing of the RET gene is a powerful tool in the diagnosis and prognosis of MTC. Ongoing research is expected to add novel treatment options for patients with advanced, progressive disease. PMID:26839093

  14. BRAF Testing in Multifocal Papillary Thyroid Carcinoma

    PubMed Central

    Kimbrell, Hillary Z.; Sholl, Andrew B.; Ratnayaka, Swarnamala; Japa, Shanker; Lacey, Michelle; Carpio, Gandahari; Bhatia, Parisha; Kandil, Emad

    2015-01-01

    Background. BRAF V600E mutation is associated with poor prognosis in patients with papillary thyroid carcinoma (PTC). PTC is often multifocal, and there are no guidelines on how many tumors to test for BRAF mutation in multifocal PTC. Methods. Fifty-seven separate formalin-fixed and paraffin-embedded PTCs from twenty-seven patients were manually macrodissected and tested for BRAF mutation using a commercial allele-specific real-time polymerase chain reaction-based assay (Entrogen, Woodland Hills, CA). Data related to histologic characteristics, patient demographics, and clinical outcomes were collected. Results. All mutations detected were BRAF V600E. Seventeen patients (63%) had concordant mutation status in the largest and second-largest tumors (i.e., both were positive or both were negative). The remaining ten patients (37%) had discordant mutation status. Six of the patients with discordant tumors (22% overall) had a BRAF-negative largest tumor and a BRAF-positive second-largest tumor. No histologic feature was found to help predict which cases would be discordant. Conclusions. Patients with multifocal PTC whose largest tumor is BRAF-negative can have smaller tumors that are BRAF-positive. Therefore, molecular testing of more than just the dominant tumor should be considered. Future studies are warranted to establish whether finding a BRAF mutation in a smaller tumor has clinical significance. PMID:26448939

  15. Diagnostics and Treatment of Thyroid Carcinoma.

    PubMed

    Jarząb, Barbara; Dedecjus, Marek; Handkiewicz-Junak, Daria; Lange, Dariusz; Lewiński, Andrzej; Nasierowska-Guttmejer, Anna; Ruchała, Marek; Słowińska-Klencka, Dorota; Nauman, Janusz; Adamczewski, Zbigniew; Bagłaj, Maciej; Bałdys-Waligórska, Agata; Barczyński, Marcin; Bednarczuk, Tomasz; Cichocki, Andrzej; Czarniecka, Agnieszka; Czepczyński, Rafał; Gawlik, Aneta; Hubalewska-Dydejczyk, Alicja; Jażdżewski, Krystian; Kamiński, Grzegorz; Karbownik-Lewińska, Małgorzata; Kos-Kudła, Beata; Kułakowski, Andrzej; Kuzdak, Krzysztof; Łącka, Katarzyna; Małecka-Tendera, Ewa; Niedziela, Marek; Pomorski, Lech; Sporny, Stanisław; Stojcev, Zoran; Syrenicz, Anhelli; Włoch, Jan; Krajewska, Jolanta; Szpak-Ulczok, Sylwia; Kalemba, Michal; Buziak-Bereza, Monika

    2016-01-01

    Revised Guidelines of Polish National Societies Prepared on the initiative of the Polish Group for Endocrine Tumours approved in their final version between November 16th and 28th, 2015 by the Scientific Committee of the V Conference "Thyroid Cancer and other malignancies of endocrine glands" organised between November 14th and 17th, 2015 in Wisla, Poland; called by the following Societies: Polish Endocrine Society, Polish Society of Oncology, Polish Thyroid Association, Polish Society of Pathologists, Society of Polish Surgeons, Polish Society of Surgical Oncology, Polish Society of Clinical Oncology, Polish Society of Radiation Oncology, Polish Society of Nuclear Medicine, Polish Society of Paediatric Endocrinology, Polish Society of Paediatric Surgeons, Polish Society of Ultrasonography Gliwice-Wisła, 2015 DECLARATION: These recommendations are created by the group of delegates of the National Societies, which declare their willingness to participate in the preparation of the revised version of the Polish Guidelines. The members of the Working Group have been chosen from the specialists involved in medical care of patients with thyroid carcinoma. Directly before the preparation of the Polish national recommendations the American Thyroid Association (ATA) published its own guidelines together with a wide comment fulfilling evidence-based medicine (EBM) criteria. ATA Guidelines are consistent with National Comprehensive Cancer Network (NCCN) Recommendation. According to the members of the Working Group, it is necessary to adapt them to both the specific Polish epidemiological situation as well as to the rules referring to the Polish health system. Therefore, the Polish recommendations constitute a consensus of the experts' group, based on ATA information. The experts analysed previous Polish Guidelines, published in 2010, and other available data, and after discussion summed up the results in the form of these guidelines. It should be added that Part II, which

  16. Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 9q22.33 and 14q13.3 detects novel candidate functional SNPs in Europeans from metropolitan France and Melanesians from New Caledonia.

    PubMed

    Tcheandjieu, Catherine; Lesueur, Fabienne; Sanchez, Marie; Baron-Dubourdieu, Dominique; Guizard, Anne-Valerie; Mulot, Claire; Laurent-Puig, Pierre; Schvartz, Claire; Truong, Therese; Guenel, Pascal

    2016-08-01

    Incidence of differentiated thyroid carcinoma varies considerably between countries and ethnic groups, with particularly high incidence rates in Melanesians of New Caledonia. Differentiated thyroid cancer (DTC) has a familial relative risk higher than other cancers, highlighting the contribution of inherited factors to the disease. Recently, genome-wide association studies (GWAS) identified several DTC susceptibility loci. The most robust associations were reported at loci 9q22 (rs965513 and rs1867277) and 14q13 (rs944289 and rs116909734). In this study, we performed a fine-mapping study of the two gene regions among Europeans and Melanesians from Metropolitan France and New Caledonia. We examined 81 single nucleotide polymorphisms (SNPs) at 9q22 and 561 SNPs at 14q13 in Europeans (625 cases/776 controls) and in Melanesians (244 cases/189 controls). The association with the four SNPs previously identified in GWAS was replicated in Europeans while only rs944289 was replicated in Melanesians. Among Europeans, we found that the two SNPs previously reported at 9q22 were not independently associated to DTC and that rs965513 was the predominant signal; at 14q13, we showed that the haplotype rs944289[C]-rs116909374[C]-rs999460[T] was significantly associated with DTC risk and that the association with rs116909374 differed by smoking status (p-interaction = 0.03). Among Melanesians, a new independent signal was observed at 14q13 for rs1755774 which is strongly correlated to rs2787423; this latter is potentially a functional variant. Significant interactions with parity (p < 0.05) and body mass index were observed for rs1755774 and rs2787423. This study contributed to a better characterization of the DTC loci 9q22 and 14q13 in Europeans and in Melanesians and has identified novel variants to be prioritized for further functional studies. PMID:26991144

  17. Three cases of macrofollicular variant of papillary thyroid carcinoma

    PubMed Central

    Emad, Raddaoui; Maha, Arafah; Kfoury, Hala K.; Al-Sheikh, Abdul Malik; Zaidi, Shaesta N.

    2011-01-01

    The macrofollicular variant of papillary thyroid carcinoma (MFPTC) is a well-established entity with characteristic large follicles containing pale colloid and lined by cells with nuclear features of papillary thyroid carcinoma (PTC). In this study, we present three cases of MFPTC, along with a brief review of the literature. For all three of our cases, the histology of the resected specimen showed predominantly macrofollicular structures lined by cells with nuclear characteristics of PTC. Immunohistochemically, the three cases show positivity for galactin-3, cytokeratin-19, and HBME-1. These cases will help us in understanding the distinction from other benign and malignant follicular lesions of the thyroid, which is of utmost importance. The key to diagnosis is a high-power examination of any macrofollicular lesion of the thyroid. PMID:22048513

  18. 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. PMID:26717396

  19. Serum thyroglobulin as a risk factor for thyroid carcinoma.

    PubMed

    Hrafnkelsson, J; Tulinius, H; Kjeld, M; Sigvaldason, H; Jónasson, J G

    2000-01-01

    Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin. PMID:11207005

  20. 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. PMID:26813941

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

    PubMed Central

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad

    2015-01-01

    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. PMID:26813941

  2. 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

  3. Minimally invasive follicular thyroid carcinomas: prognostic factors.

    PubMed

    Stenson, Gustav; Nilsson, Inga-Lena; Mu, Ninni; Larsson, Catharina; Lundgren, Catharina Ihre; Juhlin, C Christofer; Höög, Anders; Zedenius, Jan

    2016-08-01

    Although minimally invasive follicular thyroid carcinoma (MI-FTC) is regarded as an indolent tumour, treatment strategies remain controversial. Our aim was to investigate the outcome for patients with MI-FTC and to identify prognostic parameters to facilitate adequate treatment and follow-up. This retrospective follow-up study involved all cases of MI-FTC operated at the Karolinska University Hospital between 1986 and 2009. Outcome was analysed using death from MI-FTC as endpoint. Fifty-eight patients (41 women and 17 men) with MI-FTC were identified. The median follow-up time was 140 (range 21-308) months. Vascular invasion was observed in 36 cases and was associated with larger tumour size [median 40 (20-76) compared with 24 (10-80) mm for patients with capsular invasion only (P = 0.001)] and older patients [54 (20-92) vs. 44 (11-77) years; P = 0.019]. Patients with vascular invasion were more often treated with thyroidectomy (21/36 compared to 7/22 with capsular invasion only; P = 0.045). Five patients died from metastatic disease of FTC after a median follow-up of 114 (range 41-193) months; all were older than 50 years (51-72) at the time of the initial surgery; vascular invasion was present in all tumours and all but one were treated with thyroidectomy. Univariate analysis identified combined capsular and vascular invasion (P = 0.034), age at surgery ≥50 years (P = 0.023) and male gender (P = 0.005) as related to risk of death from MI-FTC. MI-FTC should not be considered a purely indolent disease. Age at diagnosis and the existence of combined capsular and vascular invasion were identified as important prognostic factors. PMID:26858184

  4. Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our experience.

    PubMed

    Morisod, Benoît; Monnier, Philippe; Simon, Christian; Sandu, Kishore

    2014-08-01

    Invasion of the laryngeal framework by thyroid carcinoma requires specific surgical techniques and carries a higher rate of complications that deserve to be highlighted. We reviewed our data from 1995 to 2012 and found six patients with laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy and single-stage cricotracheal resection, plus anterolateral neck dissection. Three had airway obstruction that necessitated prior endoscopic debulking. None of the patients needed a tracheotomy. There were four cases of papillary carcinoma, and two cases of undifferentiated carcinoma. One patient died of complications of the procedure (anastomotic dehiscence and tracheo-innominate artery fistula). Another died 2 months after the procedure from local recurrence and aspiration pneumonia. One case presented recurrence at 15 months, which was managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up, he has no evidence of locoregional recurrence. The three other patients are alive without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal resection for subglottic invasion by thyroid carcinoma is an effective procedure, but carries significant risks of complications. This could be attributed to the devascularisation of the tracheal wall due to the simultaneous neck dissection, sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal resection for subglottic invasion can be curative with good functional outcomes, even for the advanced stages of thyroid cancer. Endoscopic debulking of the airway prior to the procedure avoids tracheotomy. PMID:24129693

  5. Iodine-131 uptake in inflammatory lung disease: a potential pitfall in treatment of thyroid carcinoma

    SciTech Connect

    Hoeschl, R.C.; Choy, D.H.; Gandevia, B.

    1988-05-01

    A mixed differentiated thyroid carcinoma was found in a small asymptomatic nodule in a 44-yr-old woman with recurrent chest infections and bronchiectasis. After total thyroidectomy and 162 mCi (6 GBq) radioiodine ablation there was uptake in the thyroid remnant and in both lungs, interpreted as lung metastases. In 2 years she received further three 162 mCi (6 GBq) doses of /sup 131/I, as scans showed very similar lung activity. Another scan, during thyroxin suppression, showed again activity in the lungs. A 47-yr-old male patient with similar respiratory disease and no history of thyroid disorder volunteered to undergo radioiodine scan while on triiodothyronine suppression. His scan, too, showed concentration in the lungs. The female patient died 7 years after the diagnosis of lung thyroid metastases was made. No metastasis was found at autopsy. Radioiodine lung uptake may occur in patients with chronic inflammatory lung disease, presenting a potential diagnostic pitfall in patients with differentiated thyroid carcinoma.

  6. Evaluation of the VE1 Antibody in Thyroid Cytology Using Ex Vivo Papillary Thyroid Carcinoma Specimens

    PubMed Central

    Kim, Yon Hee; Yim, Hyunee; Lee, Yong-Hee; Han, Jae Ho; Lee, Kyi Beom; Lee, Jeonghun; Soh, Euy Young; Jeong, Seon-Yong; Kim, Jang-Hee

    2016-01-01

    Background: Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. Methods: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. Results: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. Conclusions: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use. PMID:26657312

  7. Unusual Granular Cell Tumor of the Trachea Coexisting With Papillary Thyroid Carcinoma and Masquerading as Tracheal Invasion of Recurred Thyroid Carcinoma

    PubMed Central

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2016-01-01

    Abstract This was an extremely rare case of unusual granular cell tumor of the trachea coexisting with recurrent papillary thyroid carcinoma. We initially misdiagnosed this patient as having tracheal invasion from recurrent thyroid carcinoma even after a computed tomography scan and fine-needle aspiration cytology. Clinicians should be aware of the possibility of granular cell tumor of the trachea occurring simultaneously with papillary thyroid carcinoma. PMID:27149467

  8. Differentiated thyroid cancer: feasibility of loboisthmectomy in an endemic region

    PubMed Central

    CALÒ, P.G.; ERDAS, E.; MEDAS, F.; GORDINI, L.; LONGHEU, A.; PISANO, G.; NICOLOSI, A.

    2015-01-01

    Aim The aim of the present retrospective study was to assess the feasibility of loboisthmectomy for the treatment of differentiated thyroid cancer in a endemic area, evaluating the histopathological features and the results of a case series of 1154 patients. Patients and Methods The clinical records of 1154 patients submitted to total thyroidectomy in our Department were retrospectively reviewed to analyze the histopathological characters and the results. Results In 1044 cases (90.5%) a papillary cancer was observed, in 110 (9.5%) a follicular carcinoma; microcarcinomas were 399 (34.5%). Multifocality was present in 323 cases (28%), in 142 unilateral (12.3%) and in 181 bilateral (15.7%). Thyroiditis coexisted in 472 patients (40.9%), multinodular goiter in 404 (35%), Graves’ disease in 48 (4.1%), and multinodular toxic goiter in 38 (3.3%). Complications were: postoperative bleeding in 20 patients (1.7%), transient unilateral vocal cord paralysis in 20 (1.7%) definitive in 10 (0.86%), a transient bilateral paralysis in 1 (0.08%), a transient hypoparathyroidism in 351 (30.4%), and a definitive in 24 (2.07%). Nodal recurrence occurred in 25 patients (2.16%). Conclusions Total thyroidectomy remains the safest treatment in differentiated thyroid cancer, especially if performed in high volume centers in which complications can be minimized. Loboisthmectomy can be a viable and safe alternative in small (< 1 cm) unifocal tumors in patients at low risk. Loboisthmectomy is limited in endemic areas by the association with other thyroid diseases. A correct and detailed information of the patient is essential before planning surgery. PMID:26888701

  9. Dissecting Molecular Events in Thyroid Neoplasia Provides Evidence for Distinct Evolution of Follicular Thyroid Adenoma and Carcinoma

    PubMed Central

    Krause, Kerstin; Prawitt, Susanne; Eszlinger, Markus; Ihling, Christian; Sinz, Andrea; Schierle, Katrin; Gimm, Oliver; Dralle, Henning; Steinert, Frank; Sheu, Sien-Yi; Schmid, Kurt W.; Fuhrer, Dagmar

    2011-01-01

    Benign hypofunctional cold thyroid nodules (CTNs) are a frequent scintiscan finding and need to be distinguished from thyroid carcinomas. The origin of CTNs with follicular morphologic features is unresolved. The DNA damage response might act as a physiologic barrier, inhibiting the progression of preneoplastic lesions to neoplasia. We investigated the following in hypofunctional follicular adenoma (FA) and follicular thyroid cancer (FTC): i) the mutation rate of frequently activated oncogenes, ii) the activation of DNA damage response checkpoints, and iii) the differential proteomic pattern between FA and FTC. Both FTC and FA, which did not harbor RAS, phosphoinositide-3-kinase, or PAX/peroxisome proliferator activated receptor-γ mutations, express various proteins in common and others that are more distinctly expressed in FTC rather than in FA or normal thyroid tissue. This finding is in line with the finding of constitutive DNA damage checkpoint activation (p-Chk2, γ-H2AX) and evidence for replicative stress causing genomic instability (increased cyclin E, retinoblastoma, or E2F1 mRNA expression) in FTC but not FA. We discuss the findings of the increased expression of translationally controlled tumor protein, phosphatase 2A inhibitor, and DJ-1 in FTC compared with FA identified by proteomics and their potential implication in follicular thyroid carcinogenesis. Our present findings argue for the definition of FA as a truly benign entity and against progressive development of FA to FTC. PMID:21983636

  10. Diagnostic and therapeutic use of recombinant human TSH (rhTSH) in differentiated thyroid cancer.

    PubMed

    Pacini, Furio; Castagna, Maria Grazia

    2008-12-01

    Traditionally, withdrawal of thyroid hormone to increase serum levels of thyroid-stimulating hormone (TSH) has been used in patients with differentiated thyroid carcinoma (DTC) to optimize radio-iodine uptake and serum thyroglobulin (Tg) stimulation during follow-up and in preparation for radio-iodine therapy. However, this procedure is associated with signs and symptoms of hypothyroidism which negatively affect the patient's quality of life. Recombinant human thyrotropin (rhTSH) has provided an effective alternative to thyroid hormone withdrawal. After favourable experimental trials in humans, rhTSH obtained regulatory approval in North America and in Europe as a diagnostic tool, and more recently as a preparation for radio-iodine thyroid remnant ablation. Since then, rhTSH has radically changed the diagnostic and therapeutic management of DTC patients. This review will focus on the clinical application of rhTSH in the management of DTC, highlighting current indications and future perspectives. PMID:19041828

  11. 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. PMID:26932153

  12. The treatment of metastatic thyroid disease

    SciTech Connect

    Lee, K.Y.; Lore, J.M. Jr. )

    1990-06-01

    Removal of all resectable disease commensurate with reasonable morbidity and mortality is the initial treatment of all thyroid carcinoma. Patients with no evidence of recurrent metastatic well-differentiated thyroid carcinoma should be placed on suppressive doses of Synthroid. {sup 131}I is utilized for nonresectable and for distant metastatic well-differentiated thyroid carcinoma. External radiation therapy and chemotherapy are utilized in recurrent or metastatic thyroid carcinomas that do not concentrate {sup 131}I. 49 references.

  13. Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis

    PubMed Central

    Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

    2016-01-01

    Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as “MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node.” Total thyroidectomy specimen showed “MTC with coexisting HT.” At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists. PMID:27279687

  14. Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan.

    PubMed

    Hirokawa, Mitsuyoshi; Sugitani, Iwao; Kakudo, Kennichi; Sakamoto, Atsuhiko; Higashiyama, Takuya; Sugino, Kiminori; Toda, Kazuhisa; Ogasawara, Satoshi; Yoshimoto, Seiichi; Hasegawa, Yasuhisa; Imai, Tsuneo; Onoda, Naoyoshi; Orita, Yorihisa; Kammori, Makoto; Fujimori, Keisei; Yamada, Hiroyuki

    2016-05-31

    The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma. PMID:26842589

  15. 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

  16. Thyroid carcinoma masquerading as a solitary benign hyperfunctioning nodule

    SciTech Connect

    Sandler, M.P.; Fellmeth, B.; Salhany, K.E.; Patton, J.A.

    1988-06-01

    Focal hot nodules on iodine thyroid images are associated with an exceedingly low incidence of malignancy. Most previously reported hot carcinomas represent the coexistence of small malignancies in or adjacent to a benign hot lesion. Described here is a 3-cm papillary carcinoma that fulfilled the criteria for benignancy on Tc-99m and I-123 imaging. Coincidental carcinoma within a benign lesion was excluded by detailed scintigraphic-pathologic correlation of the tumor. The implications of this case on the management of the solitary hot nodule are discussed and the literature reviewed.

  17. Thyroid carcinoma and hyperthyroidism in a dog.

    PubMed

    Bezzola, Pauli

    2002-02-01

    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

  18. 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

  19. ["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

  20. Carcinoma of the thyroid in patients with autonomous nodules

    SciTech Connect

    Smith, M.; McHenry, C.; Jarosz, H.; Lawrence, A.M.; Paloyan, E.

    1988-07-01

    Over a period of 25 years (1961-1986), 30 consecutive patients were operated upon for solitary HOT nodules. The autonomy of these nodules was substantiated by cytomel nonsuppressibility on /sup 131/I or /sup 123/I scanning, or TSH stimulated enhancement of the remaining suppressed thyroid tissue (n = 24); or as a solitary toxic hot nodule with suppression of the remaining thyroid tissue (n = 6). Seventeen of these patients were euthyroid and 13 were thyrotoxic and required preoperative preparation with antithyroid medication. Five patients had a history of head and neck irradiation. The population consisted of 24 women and six men. Their ages ranged from 14 to 68 years. The tumors ranged in size from 1.5 to 7 cm. The pathologic findings consisted of colloid adenoma in nine patients, follicular adenoma in 19 patients, and a follicular carcinoma in two patients, for an incidence of 6 per cent. It is of interest that neither of the patients with thyroid carcinoma were toxic or had a history of radiation exposure. These findings support the concept that the incidence of carcinoma in truly autonomous HOT thyroid nodules is not negligible.

  1. 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

  2. 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

  3. An unusual 131I-avid adrenal metastasis from follicular thyroid carcinoma identified by 131I-SPECT/CT.

    PubMed

    Xue, Yan-Li; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2012-09-01

    The adrenal gland is an uncommon site of metastasis from differentiated thyroid carcinoma, and I-avid adrenal metastatic lesions are even rarer. Here, we describe a 54-year-old woman with I-avid adrenal metastasis from follicular thyroid carcinoma identified using I whole-body scan (I-WBS) and I-SPECT/CT. I-SPECT/CT allowed superior localization of the equivocal I uptake in the I-WBS. It provides metabolic and anatomic information about a lesion, resulting in accurate localization and improved definition of I-WBS findings. PMID:22889799

  4. Impact of prophylactic central neck dissection on oncologic outcomes of papillary thyroid carcinoma: a review

    PubMed Central

    Mamelle, Elisabeth; Borget, Isabelle; Leboulleux, Sophie; Mirghani, Haïtham; Suárez, Carlos; Pellitteri, Phillip K.; Shaha, Ashok R.; Hamoir, Marc; Robbins, K. Thomas; Khafif, Avi; Rodrigo, Juan P.; Silver, Carl E.; Rinaldo, Alessandra; Ferlito, Alfio; Hartl, Dana M.

    2016-01-01

    Prophylactic neck dissection (PND) for papillary thyroid carcinoma (PTC) is controversial. Our aim was to assess current levels of evidence (LE) according to the Oxford Centre for Evidence-based Medicine (http://www.cebm.net/?O=1025) regarding the oncologic benefits of PND. Data were analyzed via MEDLINE key-words: PTC, differentiated thyroid carcinoma, PND, central lymph node metastases, central compartment, recurrence-free survival. There was conflicting evidence regarding the rate of reoperation for recurrence, with some studies showing a lower rate after PND with increased recurrence-free survival and a higher rate of undetectable pre- and post-ablation thyroglobulin levels (LE 4), whereas other studies did not show a difference (LE 4). Only one study (LE 4) showed improved disease-specific survival with PND. PND may improve recurrence-free survival, although this is supported by only a low LE. Current recommendations can only be based on low-level evidence. PMID:25022716

  5. 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. PMID:11992375

  6. Ectopic papillary thyroid carcinoma in the mediastinum without any tumoral involvement in the thyroid gland. A Case report

    PubMed Central

    Shafiee, Susan; Sadrizade, Ali; Jafarian, Amirhosein; Zakavi, Seyed Rasoul; Ayati, Narjess

    2013-01-01

    Ectopic thyroid tissue results from abnormal embryologic development and migration of the thyroid gland. True malignant transformation in ectopic thyroid tissue is extremely rare and is always diagnosed after surgical excision of the lesion by pathology examinations. There are well-documented cases of ectopic thyroid cancer while primary tumoral lesion occurs in the orthotopic thyroid, but only rare cases of ectopic PTC without any evidence of occult thyroid cancer in the orthotopic thyroid or cervical lymph nodes have been reported. We report on a 39 year old woman who was operated for a mediastinal mass. The initial diagnosis was a malignant thymic lesion, which was later confirmed to be a papillary thyroid carcinoma. Consequently, total thyroidectomy was performed and pathology report showed normal thyroid tissue with no evidence of any neoplastic involvement. Until now, only one similar case has been reported.

  7. Malignant melanoma arising in melanin-producing medullary thyroid carcinoma

    PubMed Central

    Hirokawa, Mitsuyoshi; Miyauchi, Akira; Otsuru, Minoru; Daa, Tsutomu

    2016-01-01

    Introduction We report a case of malignant melanoma arising in medullary thyroid carcinoma that has not yet been described. Presentation of case A 66-year-old woman presented with a mass in her thyroid. The resected mass was black in color, and was composed of a mixture of classic medullary thyroid carcinoma and pleomorphic atypical cells containing melanin pigments. The pleomorphic atypical cells were morphologically consistent with malignant melanoma, and expressed Melan-A, HMB-45, and S-100 protein as determined by immunohistochemistry. Some of these cells were also positive for calcitonin and chromogranin A. Although the malignant melanoma metastasized to the lymph nodes, the patient remained free from local recurrence and distant metastasis and the primary malignant melanoma lesion was not identified for up to 11 years after the thyroidectomy. Discussion 11 melanin-producing MTC cases have been reported to date. In the reported cases, the term “malignant melanoma” was not used, likely because the melanin-containing carcinoma cells were not morphologically consistent with malignant melanoma, but with medullary carcinoma. Conclusion Malignant melanoma arising in MTC may have a favorable prognosis. PMID:26852361

  8. Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial follicular cells.

    PubMed

    Pierotti, M A; Bongarzone, I; Borello, M G; Greco, A; Pilotti, S; Sozzi, G

    1996-05-01

    Cytogenetic and molecular analyses of thyroid tumors have indicated that these neoplasms represent a good model for analyzing human epithelial cell multistep carcinogenesis. They comprise, in fact, a broad spectrum of lesions with different phenotypes and variable biological and clinical behavior. Molecular analysis has detected specific genetic alterations in the different types of thyroid tumors. In particular, the well-differentiated carcinomas of the papillary type are characterized by activation of the receptor tyrosine kinases (RTKs), RET and NTRK1 proto-oncogenes. Cytogenetic analysis of these tumors has contributed to defining the chromosomal mechanisms leading to RTK oncogenic activation. In the majority of cases, intrachromosomal inversions of chromosome 10 and chromosome 1 led to the formation of RET-derived and NTRK1-derived oncogenes, respectively. Interestingly, molecular analysis of these oncogenes revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the oncogenic rearrangements led to the identification of a breakpoint cluster region in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with papillary carcinomas and RET activation has been suggested to be related to this event. Conversely, RAS point mutations are frequently observed in tumors with follicular histology and have been associated with metastatic dissemination. Iodide-deficient areas seem to provide a higher frequency of RAS positive follicular carcinomas. Finally, a high prevalence of TPS3 point mutations has been detected only in undifferentiated or anaplastic carcinomas and found to correlate inversely with 8CL2 expression. All of these findings are contributing to the definition of genetic and environmental factors relevant for the pathogenesis of thyroid tumors. Moreover, the characterization of specific genetic lesions could provide significant molecular

  9. A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping

    PubMed Central

    Fujarewicz, Krzysztof; Jarząb, Michał; Eszlinger, Markus; Krohn, Knut; Paschke, Ralf; Oczko-Wojciechowska, Małgorzata; Wiench, Małgorzata; Kukulska, Aleksandra; Jarząb, Barbara; Świerniak, Andrzej

    2007-01-01

    Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes – potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/malignant classification, based on gene expression profiling, for PTC. We analyzed a 180-array dataset (90 HG-U95A and 90 HG-U133A oligonucleotide arrays), which included a collection of 57 PTCs, 61 benign thyroid tumors, and 62 apparently normal tissues. Gene selection was carried out by the support vector machines method with bootstrapping, which allowed us 1) ranking the genes that were most important for classification quality and appeared most frequently in the classifiers (bootstrap-based feature ranking, BBFR); 2) ranking the samples, and thus detecting cases that were most difficult to classify (bootstrap-based outlier detection). The accuracy of PTC diagnosis was 98.5% for a 20-gene classifier, its 95% confidence interval (CI) was 95.9–100%, with the lower limit of CI exceeding 95% already for five genes. Only 5 of 180 samples (2.8%) were misclassified in more than 10% of bootstrap iterations. We specified 43 genes which are most suitable as molecular markers of PTC, among them some well-known PTC markers (MET, fibronectin 1, dipeptidylpeptidase 4, or adenosine A1 receptor) and potential new ones (UDP-galactose-4-epimerase, cadherin 16, gap junction protein 3, sushi, nidogen, and EGF-like domains 1, inhibitor of DNA binding 3, RUNX1, leiomodin 1, F-box protein 9, and tripartite motif-containing 58). The highest ranking gene, metallophosphoesterase domain-containing protein 2, achieved 96.7% of the maximum BBFR score. PMID:17914110

  10. 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

  11. 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

  12. [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

  13. Langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying metastatic thyroid papillary carcinoma.

    PubMed

    Ceyran, A Bahar; Senol, Serkan; Bayraktar, Barış; Ozkanlı, Seyma; 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

  14. 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

  15. Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors

    PubMed Central

    Dima, Mariavittoria; Kang, Kristy S.; Dasrath, Florence; Liao, Xiao-Hui; Refetoff, Samuel; Montagna, Cristina; Di Cristofano, Antonio

    2011-01-01

    Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. Despite a relatively low prevalence, it accounts for a disproportionate number of thyroid cancer-related deaths, due to its resistance to any therapeutic approach. Here we describe the first mouse model of ATC, obtained by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion, and distant metastases. Expression profiling of the murine ATCs reveals a significant overlap with genes found deregulated in human ATC, including genes involved in mitosis control. Furthermore, similar to the human tumors, [Pten, p53]thyr−/− tumors and cells are highly glycolytic and remarkably sensitive to glycolysis inhibitors, which synergize with standard chemotherapy. Taken together, our results show that combined PI3K activation and p53 loss faithfully reproduce the development of thyroid anaplastic carcinomas, and provide a compelling rationale for targeting glycolysis to increase chemotherapy response in ATC patients. PMID:22190384

  16. 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

  17. 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

  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. 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

  20. Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

    PubMed

    Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

    2012-09-01

    Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. PMID:22497336

  1. Therapeutic Outcome of Second Primary Malignancies in Patients with Well-Differentiated Thyroid Cancer

    PubMed Central

    Liou, Miaw-Jene; Tsang, Ngan-Ming; Hsueh, Chuen; Chao, Tzu-Chieh; Lin, Jen-Der

    2016-01-01

    Background. The aims of this study were to analyze the clinical characteristics of SPM in patients with well-differentiated thyroid cancer and to determine the long-term prognosis in patients with double malignancies. Materials and Methods. We retrospectively analyzed 2,864 patients with well-differentiated thyroid cancer and a mean age of 44.0 ± 14.4 years. Of these, 200 (7.0%) were diagnosed with SPM, 115 of which were diagnosed with metachronous SPM. Results. Of 2,864 patients, 163 (5.7%) patients died of thyroid cancer and 301 (10.5%) died of any cause by the end of the follow-up period. Multivariate analysis identified age, SPM, external radiotherapy, TNM stage, and postoperative serum Tg level to be factors independently associated with decreased survival. Of 200 patients with SPM, 74 (37.0%) died. In comparison to the anachronous and synchronous groups, the metachronous SPM group had a higher mean age; more advanced tumor, node, and metastasis stage; lower remission rate; higher postoperative radioactive iodide (131I) accumulated dose; a higher proportion of patients who underwent external radiotherapy; and higher thyroid cancer and total mortality rates. Conclusions. Patients with well-differentiated thyroid carcinoma and metachronous SPM had worse prognoses compared to patients without SPM. PMID:27118971

  2. Thyroid nodule

    MedlinePlus

    ... 2016:chap 14. Read More Chronic thyroiditis (Hashimoto disease) Laryngeal nerve damage Multiple endocrine neoplasia (MEN) II Thyroid cancer Thyroid cancer - medullary carcinoma Thyroid gland removal Patient Instructions Thyroid gland ...

  3. Mouse models of papillary thyroid carcinoma - short review.

    PubMed

    Rusinek, Dagmara; Krajewska, Jolanta; Jarząb, Michał

    2016-01-01

    Thyroid carcinoma (TC) is the most common endocrine malignancy, and its frequency is still rising. Papillary thyroid carcinoma (PTC) accounts for 80% of all TCs and usually is related to a very good prognosis. However, the standard therapeutic approaches are not always sufficient and disease progression is sometimes observed. These data highlight the limitation of our understanding of molecular mechanisms underlying tumorigenesis and how they vary between individual patients. Over the last 19 years mouse models of thyroid cancers have been developed in order to give answers to questions about their genetic background, relations of key molecular events with pathways fundamental for cancer, and many others. Among these models genetically engineered mice were of utmost importance regarding the input of knowledge about human tumorigenesis. In the present review the most significant mouse models of PTC are described with particular emphasis on BRAFV600E-induced ones, for the sake of its frequency in PTC, relation to factors of poor prognosis, and the fact that, since its identification, it became an attractive target in novel therapies. For the presented mouse models phenotype consequences of particular genetic alterations are described as well as the limitations of the used methods. (Endokrynol Pol 2016; 67 (2): 212-223). PMID:27082155

  4. FNAC diagnosis of medullary carcinoma thyroid: A report of three cases with review of literature

    PubMed Central

    Mehdi, Ghazala; Maheshwari, Veena; Ansari, Hena A; Sadaf, Lubna; Khan, Mohammad Amanullah

    2010-01-01

    Medullary carcinoma of the thyroid is an unusual neoplasm, which is associated with specific supportive diagnostic markers. Despite this, its cytological diagnosis is often difficult. We report herewith three cases of medullary thyroid carcinoma. The diagnosis was established on fine-needle aspiration cytology. Plasmacytoid cell pattern was observed in two cases and spindle cell pattern in the third case. PMID:21157553

  5. Trace elemental analysis of adenoma and carcinoma thyroid by PIXE method

    NASA Astrophysics Data System (ADS)

    Reddy, S. Bhuloka; John Charles, M.; Ravi Kumar, M.; Reddy, B. Seetharami; Anjaneyulu, Ch.; Naga Raju, G. J.; Sundareswar, B.; Vijayan, V.

    2002-11-01

    Trace elemental analysis was carried out in the biological samples of normal, adenoma and carcinoma thyroids using particle induced X-ray emission technique (PIXE). A 2 MeV proton beam was employed to excite the samples. The elements Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, I, Hg and Pb were identified and their concentrations were estimated. The concentrations of the elements Ca, Cu, Zn, As, I and Hg are found to be much lower in carcinoma thyroid than those in the normal thyroid while the concentration of the elements K, Ti, V, Cr, Mn, Fe, Co and Sr in carcinoma thyroid are higher than the concentrations in normal thyroid. The lower and higher values of some of the elements in carcinoma thyroid may be attributed to some pathological factors.

  6. Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance

    PubMed Central

    Iype, Elizabeth Mathew; Jagad, Vijay; Varghese, Bipin T.; Sebastian, Paul

    2016-01-01

    Introduction Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. Aim The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. Materials and Methods One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Results Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. Conclusion After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement. PMID:27042568

  7. 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

  8. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy.

    PubMed

    Junor, E J; Paul, J; Reed, N S

    1992-04-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dysphagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. PMID:1582515

  9. 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

  10. [Giant mediastinal thyroid follicular carcinoma with tracheal stenosis].

    PubMed

    Ishibashi, Hironori; Ohta, S; Hirose, M; Kitano, M; Kato, T; Yokoyama, J; Muro, H; Morita, T; Takagi, A

    2008-05-01

    A 76-year-old female was admitted to the hospital with dyspnea and hypertention. She had the giant thyroid tumor which had been awared but not treated for 40 years. On a computed tomography (CT) scan and magnetic resonance imaging (MRI), the tumor was 14 x 10 cm and the tracheal stenosis was completely intrathoracic, which was 5 x 7 mm. Tracheal incubation was performed safety by using percutaneous cardiopulmonary support. A subtotal thyroidectomy was performed by midsternotomy with cervical incision. The weight of the resected specimen was 340 g and the pathological diagnosis was follicular thyroid carcinoma. The postoperative course was uneventful and the patient suffered no hoarseness and dyspnea. PMID:18464485

  11. Littoral cell angioma presenting as metastatic thyroid carcinoma to the spleen.

    PubMed

    Mohan, Vineeth; Jones, Ralph C; Drake, Almond J; Daly, Patrick L; Shakir, K M Mohamed

    2005-02-01

    Papillary thyroid carcinoma (PTC) commonly metastasizes to cervical lymph nodes. Distant metastases are unusual with the lungs most frequently involved. Well-differentiated thyroid carcinoma very rarely presents with metastases to the spleen. This is the case of a 25-year-old man with a history of PTC (1.4 cm primary; no capsular invasion and negative lymph node metastases). One year after initial surgery, recurrent disease was found in multiple neck nodes by central neck dissection. Whole body scan (WBS) following a therapeutic ablation dose of 150 mCi I(131) revealed mediastinal metastases. Computerized axial tomography (CT) of the chest one year later showed no gross mediastinal or pulmonary disease. However, multiple large splenic lesions were incidentally noted. Evaluation by ultrasound (US) showed lesions to be solid echogenic masses without remarkable Doppler characteristics to suggest vascular tumors. US-guided percutaneous fine-needle aspiration biopsy (FNAB) of one lesion was nondiagnostic. After withdrawal from Levothyroxine, serum TSH was >100 mU/L with a thyroglobulin of 9.4 ng/mL and negative anti-thyroglobulin antibodies. Diagnostic WBS revealed faint splenic uptake but was otherwise unremarkable. Following treatment with 192 mCi I(131), WBS demonstrated increased activity in the mediastinum as well as in the spleen suggesting mediastinal and splenic metastases. Contrast CT of the abdomen showed multiple low-attenuated heterogeneously enhancing splenic masses, normal liver and no intra-abdominal lymphadenopathy. The largest mass (4.5 x 3.5 cm) was exophytic and in close proximity to the splenic capsule. Despite the serum thyroglobulin of only 9.4 ng/mL, the finding of I(131) accumulation within solid splenic masses led to a preoperative diagnosis of thyroid carcinoma metastases. To establish the diagnosis and to remove the risk for splenic rupture, a laparoscopic splenectomy was performed. Histopathologic analysis showed large littoral cell angiomas

  12. A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off.

    PubMed

    Reynolds, S; Shaheen, M; Olson, G; Barry, M; Wu, J; Bocklage, T

    2016-09-01

    We present the second reported mammary analog secretory carcinoma (MASC) apparently arising in the thyroid and propose a potential close relationship to ETV6-NTRK3 fusion papillary thyroid carcinoma. The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of "papillary thyroid carcinoma". Resection revealed a 4.5 cm infiltrative tumor. Final diagnosis was "papillary thyroid carcinoma (PTC) consistent with diffuse sclerosing variant" with positive lymph nodes (2+/4) and margins. Histologic features included mixed microcystic, solid, follicular and papillary architecture, prominent nucleoli, abundant nuclear grooves and rare nuclear pseudo-inclusions. Despite radioactive iodine, radiotherapy and multiagent chemotherapy, the patient progressed over 6 years with local recurrence and additional lymph node involvement finally developing widespread distant metastases. Prompted by the breast carcinoma-like histopathology of a metastasis, immunohistochemical staining was performed and revealed strong expression of GATA3 and mammaglobin with no reactivity for thyroglobulin or TTF-1. The original tumor was then tested and showed the same immunoprofile. RT-PCR confirmed the presence of an ETV6-NTRK3 fusion consistent with a diagnosis of MASC. Our patient's clinical, imaging and morphologic features remarkably mimicked papillary thyroid carcinoma. At the molecular level, the ETV6-NTRK3 fusion in this patient involved exons reported in the rare "papillary thyroid carcinoma" with this translocation. Given the immunophenotype of this case, it is possible that at least some ETV6-NTRK3 fusion positive PTC are actually MASC masquerading as papillary thyroid carcinoma. PMID:27075025

  13. 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

  14. Serum Galectin-3: diagnostic value for papillary thyroid carcinoma

    PubMed Central

    Yılmaz, Erdem; Karşıdağ, Tamer; Tatar, Cihad; Tüzün, Sefa

    2015-01-01

    Objective: Thyroid cancer constitutes approximately 1% of all cancers, approximately 90% of the endocrine malignancies, and is responsible for 0.4% of cancer-related deaths. Additional markers are required for the accurate diagnosis of thyroid malignancies. There is no marker that can accurately facilitate pre-operative benign-malignant differentiation of thyroid nodules. The present study aims to evaluate the diagnostic value of preoperative serum Galectin-3 levels in thyroid cancer and to avoid unnecessary aggressive interventions. Material and Methods: Sixty-four patients who were operated between May 2009 and April 2011 were included in this study prospectively. Patients with toxic nodules and those with malignancies detected in preoperative fine needle aspiration biopsies (FNAB) were excluded. Patients with thyroid nodules of >3 cm in ultrasonography or having suspicious cytological findings in their preoperative FNABs regardless of the nodule size were included. Patients were divided into 2 groups, “control”and “cancer,” according to the postoperative pathology results. Results: The control group included 50 and cancer group included 14 patients. The mean age of the control group was 44.84±13.17 (19–79), while it was 44.14±15.94 (25–72) in the cancer group. A statistically significant difference was found between Galectin-3 levels in the cancer and control groups (p<0.001). Conclusion: In the present study, serum Galectin-3 levels in patients with malignant nodules were statistically significant. PMID:26668525

  15. Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine component: case report.

    PubMed

    Selvaggi, Federico; Risio, Domenico; Waku, Mathew; Simo, Daniela; Angelucci, Domenico; D'Aulerio, Alberto; Cotellese, Roberto; Innocenti, Paolo

    2012-01-01

    Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its predominant component. It is an uncommon neoplasm, usually asymptomatic with an unknown risk of malignant transformation. Due to difficulties in assessing the rare biological nature and the discrepancies in the reported cases, a consensus on the appropriate treatment has not been definitively reached. A 50-year-old female was subjected to upper gut endoscopy which showed a 30-mm mass located in the gastric antrum, suggestive of mesenchimal tumor. Incidentally, a pelvic CT scan also documented a solid mass in the right adnexa, with morphological characteristics of ovarian neoplasm. The patient underwent gastrectomy, total hysterectomy, bilateral salpingo-oophorectomy with lymph node dissection, and omentectomy. Histology documented the presence of gastric cavernous angioma, and, in the right adnexa, foci of follicular thyroid-type carcinoma arising in SO with a well-differentiated neuroendocrine component.Here we report and discuss the clinical and morphological presentation of follicular thyroid-type carcinoma arising in SO. The neoplasm was discovered incidentally and had a favorable clinical outcome at 1-year follow-up. PMID:22613573

  16. Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine component: case report

    PubMed Central

    2012-01-01

    Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its predominant component. It is an uncommon neoplasm, usually asymptomatic with an unknown risk of malignant transformation. Due to difficulties in assessing the rare biological nature and the discrepancies in the reported cases, a consensus on the appropriate treatment has not been definitively reached. A 50-year-old female was subjected to upper gut endoscopy which showed a 30-mm mass located in the gastric antrum, suggestive of mesenchimal tumor. Incidentally, a pelvic CT scan also documented a solid mass in the right adnexa, with morphological characteristics of ovarian neoplasm. The patient underwent gastrectomy, total hysterectomy, bilateral salpingo-oophorectomy with lymph node dissection, and omentectomy. Histology documented the presence of gastric cavernous angioma, and, in the right adnexa, foci of follicular thyroid-type carcinoma arising in SO with a well-differentiated neuroendocrine component. Here we report and discuss the clinical and morphological presentation of follicular thyroid-type carcinoma arising in SO. The neoplasm was discovered incidentally and had a favorable clinical outcome at 1-year follow-up. PMID:22613573

  17. A Rare Silent Killer: Right Atrial Metastasis of Thyroid Hürthle Cell Carcinoma.

    PubMed

    Luo, Hongxiu; Tulpule, Sunil; Alam, Mahmood; Patel, Reema; Sen, Shuvendu; Yousif, Abdalla

    2015-01-01

    Hürthle cell carcinoma (HCC) is a variant of a follicular carcinoma with a tendency to higher frequency of metastases and a lower survival rate. However, intracavitary cardiac metastases from thyroid HCC are extremely rare. We describe the case of a 57-year-old female with thyroid HCC, 5 years after total thyroidectomy, who presented with dyspnea associated with hypoxia and hypotension. The computed tomography angiogram showed extensive pulmonary embolism and a 6-cm right atrial mass while the lower-extremity deep vein thrombosis studies were negative. This patient received a cardiac thrombectomy using cardiopulmonary bypass support. However, intraoperatively, we found out that the mass was from the mediastinum, directly extending into the heart and clearly unresectable since it effaced at least 1/3 of the right atrial wall. The core biopsy of the mass confirmed that it was metastatic poorly differentiated HCC of thyroidal origin. The patient eventually died of respiratory failure due to a massive pulmonary embolism. For cancer patients with unexplained dyspnea, cardiac metastases should be considered regardless of anticoagulation prophylaxis, especially when there is no deep vein thrombosis in the lower limbs. Early recognition of intracavitary cardiac metastases may help in providing prompt treatment and improving the prognosis. PMID:26078743

  18. A Rare Silent Killer: Right Atrial Metastasis of Thyroid Hürthle Cell Carcinoma

    PubMed Central

    Luo, Hongxiu; Tulpule, Sunil; Alam, Mahmood; Patel, Reema; Sen, Shuvendu; Yousif, Abdalla

    2015-01-01

    Hürthle cell carcinoma (HCC) is a variant of a follicular carcinoma with a tendency to higher frequency of metastases and a lower survival rate. However, intracavitary cardiac metastases from thyroid HCC are extremely rare. We describe the case of a 57-year-old female with thyroid HCC, 5 years after total thyroidectomy, who presented with dyspnea associated with hypoxia and hypotension. The computed tomography angiogram showed extensive pulmonary embolism and a 6-cm right atrial mass while the lower-extremity deep vein thrombosis studies were negative. This patient received a cardiac thrombectomy using cardiopulmonary bypass support. However, intraoperatively, we found out that the mass was from the mediastinum, directly extending into the heart and clearly unresectable since it effaced at least 1/3 of the right atrial wall. The core biopsy of the mass confirmed that it was metastatic poorly differentiated HCC of thyroidal origin. The patient eventually died of respiratory failure due to a massive pulmonary embolism. For cancer patients with unexplained dyspnea, cardiac metastases should be considered regardless of anticoagulation prophylaxis, especially when there is no deep vein thrombosis in the lower limbs. Early recognition of intracavitary cardiac metastases may help in providing prompt treatment and improving the prognosis. PMID:26078743

  19. Anaplastic Transformation of Papillary Thyroid Cancer in the Retroperitoneum

    PubMed Central

    Solomon, James P.; Wen, Fang; Jih, Lily J.

    2015-01-01

    Anaplastic thyroid carcinoma is an aggressive variant of thyroid cancer that in most cases arises from anaplastic transformation of terminally differentiated thyroid carcinomas. This process usually occurs in the thyroid or cervical lymph nodes. Anaplastic transformation in distant metastatic sites is exceedingly rare, only previously documented in a few case reports. We report a rare case of anaplastic transformation of papillary thyroid carcinoma within a large retroperitoneal metastasis in a 64-year-old male 30 years after the initial diagnosis. PMID:26351607

  20. Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines.

    PubMed

    Hoffmann, S; Maschuw, K; Hassan, I; Reckzeh, B; Wunderlich, A; Lingelbach, S; Zielke, A

    2005-09-01

    Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially among the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (beta1-4, beta7, alpha1-6, alphaV, alphaIIb, alphaL, alphaM, alphaX) and of four IRM heterodimers (alpha2beta1, alpha5beta1, alphaVbeta3, alphaVbeta5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha2, alpha3, alpha5, beta1, beta3 and low levels of alpha1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha5 and beta1. ATC mainly displayed integrins alpha2, alpha3, alpha5, alpha6, beta1 and low levels of alpha1, alpha4 and alphaV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exceptions, namely alpha4, alpha6, and beta3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of

  1. FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer

    PubMed Central

    Cetta, Francesco

    2015-01-01

    Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP. PMID:26697262

  2. 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

  3. Iodine 131 metaiodobenzylguanidine scintigraphy of medullary carcinoma of the thyroid

    SciTech Connect

    Skowsky, W.R.; Wilf, L.H. )

    1991-05-01

    We have presented a case of sporadic medullary carcinoma of the thyroid with documentation of localization of tracer {sup 131}I-MIBG within the primary neoplasm. A review of the nuclear medicine literature of localization techniques for MCT demonstrates that {sup 131}I-MIBG, while an excellent choice for diagnosis of pheochromocytoma and neuroblastoma, produces low yield and unpredictable concentration in other neural crest apudomas, including MCT. A low incidence of true-positive results with {sup 131}I-MIBG uptake and a high incidence of false-negative results make this radiopharmaceutical a suboptimal choice for diagnostic studies, but a potentially promising one as a therapeutic agent.33 references.

  4. HABP2 G534E Variant in Papillary Thyroid Carcinoma

    PubMed Central

    Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya; He, Huiling; Senter, Leigha; de la Chapelle, Albert

    2016-01-01

    The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC) that accounts for 80–90% of all thyroid malignancies. Only 3–10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536) was genotyped in blood DNA from 179 PTC families (one affected individual per family), 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant) and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain) but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized. PMID:26745718

  5. 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

  6. The Surgical Approach to Differentiated Thyroid Cancer

    PubMed Central

    Nixon, Iain

    2015-01-01

    The incidence of thyroid cancer is increasing rapidly. A large percentage of new cases identified fall into a low-risk category. As the incidence has increased, clinical experience has confirmed that the majority of patients will have excellent outcomes and that those at risk of doing badly can be reliably identified. Treatment for thyroid cancer is predominantly surgical. The decision about how aggressively this disease should be managed has remained controversial due to the excellent outcomes irrespective of the nature of surgical procedure chosen. This article reviews the developments in our understanding of the biology of thyroid cancer and the evidence that supports the approach to management. PMID:26918146

  7. Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression

    PubMed Central

    Champa, Devora; Russo, Marika A.; Liao, Xiao-Hui; Refetoff, Samuel; Ghossein, Ronald A.; Di Cristofano, Antonio

    2014-01-01

    Poorly differentiated tumors of the thyroid gland (PDTC) are generally characterized by a poor prognosis due to their resistance to available therapeutic approaches. The relative rarity of these tumors is a major obstacle to our understanding of the molecular mechanisms leading to tumor aggressiveness and drug resistance, and consequently to the development of novel therapies. By simultaneously activating Kras and deleting p53 in thyroid follicular cells, we have developed a novel mouse model that develops papillary thyroid cancer invariably progressing to PDTC. In several cases, tumors further progress to anaplastic carcinomas. The poorly differentiated tumors are morphologically and functionally similar to their human counterparts and depend on MEK/ERK signaling for proliferation. Using primary carcinomas as well as carcinoma-derived cell lines, we also demonstrate that these tumors are intrinsically resistant to apoptosis due to high levels of expression of the Bcl2 family members Bcl2a1 and Mcl1, and can be effectively targeted by Obatoclax, a small molecule pan-inhibitor of the Bcl2 family. Furthermore, we show that Bcl2 family inhibition synergizes with MEK inhibition as well as with doxorubicin in inducing cell death. Thus, our studies in a novel, relevant mouse model, uncover a promising druggable feature of aggressive thyroid cancers. PMID:25012986

  8. 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

  9. 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. PMID:26582770

  10. A case of minocycline-induced black thyroid associated with papillary carcinoma.

    PubMed

    Nishimoto, Kohei; Kumai, Yoshihiko; Murakami, Daizo; Yumoto, Eiji

    2016-03-01

    We report a rare case of black thyroid accompanied by papillary carcinoma in a patient with an extended history of minocycline treatment. A 78-year-old man was referred to our outpatient clinic with swelling in his neck. He had been taking minocycline for the previous 2 years and 7 months to treat chronic perianal pyoderma. Neck ultrasonography and computed tomography demonstrated a 3.5 × 3.7 × 5.0-cm nodule in the left thyroid lobe, and fine-needle aspiration cytology identified it as a papillary carcinoma. The patient underwent a total thyroidectomy and neck dissection. During the procedure, a distinct black discoloration of the thyroid parenchyma was observed. Histopathology confirmed both the black thyroid and the papillary carcinoma. Based on the thyroid gland's discoloration and the history of minocycline use, the patient was diagnosed with minocycline-induced black thyroid. He was symptom-free 20 months after surgery. PMID:26991226

  11. 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

  12. 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

  13. 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

  14. A Case Report of Thyroid Carcinoma Confined to Ovary and Concurrently Occult in the Thyroid: Is Conservative Treatment Always Advised?

    PubMed Central

    Brusca, Nunzia; Del Duca, Susanna Carlotta; Salvatori, Rita; D’Agostini, Antonio; Cannas, Pina; Santaguida, Maria Giulia; Virili, Camilla; Bianchi, Loredana; Gargano, Lucilla; Centanni, Marco

    2015-01-01

    Introduction: Struma ovarii is an ovarian teratoma, represented in more than 50% by thyroid tissue. Five percent of struma ovarii cases have been proven to be malignant and, as in the thyroid gland, papillary thyroid carcinoma is the most common histotype arising in struma ovarii. Because of the unusual occurrence of this tumor, its management and follow-up after pelvic surgery is still controversial. Usually, total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii, while these procedures are still controversial in non-metastatic thyroid cancer arising in struma ovarii. Case Presentation: We report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii. After pelvic surgery, thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered. The patient underwent total thyroidectomy and histological examination showed a papillary carcinoma. Radioiodine-ablation of residual thyroid tissue was performed and levothyroxine mildly-suppressive treatment was started. Conclusions: A more aggressive treatment should not be denied for malignant struma ovarii without any evidence, even when apparently confined into the ovary. However, in selected cases, aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow-up. PMID:25745492

  15. O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy

    PubMed Central

    CHENG, YU; LI, HONGLUN; LI, JIANLIN; LI, JISHENG; GAO, YAN; LIU, BAODONG

    2016-01-01

    O-linked N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), a dynamic post-translational modification of nuclear and cytoplasmic proteins, may have a critical role in the regulation of biological cell processes and human cancer. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Accumulating evidence suggests that O-GlcNAcylation is involved in a variety of types of human cancer. However, the exact role of O-GlcNAcylation in tumor pathogenesis or progression remains to be established. Computed tomography scans of patients with anaplastic thyroid carcinoma (ATC) reveal a rapid growth rate and invasion. The present study demonstrated that O-GlcNAcylation accelerates the progression of ATC. The global O-GlcNAc level of intracellular proteins was increased by overexpression of OGT or downregulation of OGA activity with the specific inhibitor Thiamet-G. By contrast, the global O-GlcNAc level was decreased by silencing of OGT. MTT assay indicated that O-GlcNAcylation significantly promotes cell proliferation. Furthermore, O-GlcNAcylation enhanced cellular biological functions, such as colony formation ability, migration and invasion, of ATC cells in vitro. The findings of the present study suggest that O-GlcNAcylation is associated with malignant properties of thyroid cancer, and may be a potential target for the diagnosis and treatment of thyroid cancer. PMID:27347182

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

    PubMed

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

    2015-01-01

    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. PMID:25948842

  17. Characterisation of thyroid medullary carcinoma TT cell line.

    PubMed

    Zabel, M; Grzeszkowiak, J

    1997-01-01

    TT cell line is the best known stabilized cell line derived from the human medullary thyroid carcinoma. The ultrastructural characteristics of these cells include well developed rough endoplasmic reticulum, a prominent Golgi apparatus and a considerable number of secretory granules. Numerous hormones were immunocytochemically demonstrated in TT cells of which calcitonin and calcitonin gene-related peptide (CGRP) are the products of the same gene but an alternative RNA processing. TT cells were found to produce some other hormones as well, namely ACTH, neurotensin, enkephalin, PTHrP, gastrin-releasing peptide (GRP), serotonin but also functional proteins of the chromogranin group, synaptophysin, NSE, calbindin and tyrosine hydroxylase. Some marker proteins have been detected in the cytosol (CEA) and in the cytoskeleton (alpha-tubulin, cytokeratin). The influence of numerous factors on the secretory activity of these cells has been demonstrated so far, including effects of 1,25-dihydroxycholecalciferol, glucocorticoids, sex steroids, cAMP, gastrin-releasing peptide, sodium butyrate, phorbol esters, ionomycin and forskolin. The investigators performed on the TT cell line demonstrate that this is the most reliable model system for the human parafollicular cells developed so far, in comparison to other cell lines derived from the medullary carcinoma of the thyroid. PMID:9046062

  18. Production of a novel monoclonal antibody, JT-95, which can detect antigen of thyroid carcinoma.

    PubMed

    Takeyama, H; Hosoya, T; Sakurai, K; Mori, Y; Watanabe, M; Kisaki, H; Ohno, T

    1996-04-15

    Monoclonal antibody (MAb) JT-95 was produced by immunization of mice with membrane fractions of a human thyroid carcinoma. Immuno-histochemical staining has demonstrated that the antigen recognized by JT-95 is strongly expressed in 95 (95%) of 100 cases of papillary carcinomas and in 3 (75%) of 4 cases of follicular carcinomas. In benign diseases of the thyroid gland, MAb JT-95 reacted with 0 (0%) of 39 adenomas, 1 (4%) of 21 adenomatous goiters, 0 (0%) of 8 hyperthyroidism specimens, and 3 (38%) of 8 chronic thyroiditis specimens. The antigen detected by MAb JT-95 has an apparent Mr 250,000 in thyroid carcinomas. Moreover, circulating antigen in thyroid carcinoma patients was detected by MAb JT-95 in an ELISA and in Western blotting. The circulating antigen has a Mr 105,000. MAb JT-95 conjugated with (131) I was administrated to nude mice bearing a human thyroid carcinoma. JT-95 131I accumulation at the transplanted tumor was visualized by autoradiography with 2.68-14.75-fold higher levels detected at the xenograft compared to that for normal organs. Based on these data, MAb JT-95 may be useful in the diagnosis detection and therapy of thyroid carcinoma. PMID:8620498

  19. Needle tract implantation of papillary thyroid carcinoma after fine-needle aspiration biopsy.

    PubMed

    Ito, Yasuhiro; Tomoda, Chisato; Uruno, Takashi; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Kuma, Kanji; Miyauchi, Akira

    2005-12-01

    Although fine-needle aspiration biopsy (FNAB) is a useful tool for diagnosing thyroid carcinoma, there are some risks of complications. In this study, we investigated tumor implantation by FNAB of papillary carcinoma. We compared the characteristics of the main tumors and implanted tumors of patients showing FNAB implantations. Between 1990 and 2002, 4912 patients underwent FNAB and were diagnosed as having papillary carcinoma. We encountered 7 cases of needle tract implantation, which account only for 0.14%. We reviewed these 7 cases as well as 3 other patients who underwent FNAB in other hospitals. The intervals between FNAB and detection of the implanted tumor ranged from 2 to 131 months. For these 10 patients, the main tumors in 6 were diagnosed as poorly differentiated carcinoma, and 7 showed extrathyroid extension. Five showed the development of implanted tumor after comparatively shorter intervals (2-68 months), and we classified these as the short interval group. The remaining 5 were classified as the long interval group, because tumor development occurred after 87-131 months. All 5 cases in the short interval group involved preoperatively detectable lymph node metastasis; those in the long interval group did not. The MIB-1 labeling index of the implanted tumor was high in 4 cases in the short interval group, but it was low in all cases in the long interval group. The implanted tumors could be surgically removed without recurrence at the focal sites. These findings indicate that, although high growth activity in the metastatic lesions may be a risk factor of FNAB, inducing the growth of implanted tumors along the needle tract within a short interval after the procedure, FNAB remains the most useful technique for diagnosing thyroid carcinoma. The incidence of implantation was low, and when it did occur, the tumors could be surgically removed without recurrence. PMID:16311845

  20. 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

  1. Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.

    PubMed

    Kim, Seo Ki; Woo, Jung-Woo; Lee, Jun Ho; Park, Inhye; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

    2016-01-01

    It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status. PMID:26598713

  2. 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. PMID:26427663

  3. 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

  4. Metastatic papillary carcinoma of the thyroid in a patient previously treated for Graves' disease.

    PubMed

    Yunusa, Garba H; Kotze, Tessa; Brink, Anita

    2014-01-01

    Incidental papillary carcinoma of the thyroid in patients treated surgically for benign thyroid diseases including Graves' disease is a known phenomenon. However, the management of these patients remains an issue of concern and controversy for those who care for them. We report a case of metastatic papillary carcinoma of the thyroid in a patient previously treated for Graves' disease. The subject of this presentation is a 50-year-old lady who was diagnosed with Graves' disease at the age of 29, for which she had a subtotal thyroidectomy following failure of medical and radioactive iodine treatment. Three years later, the patient was referred to our nuclear medicine department with a clinical diagnosis of suspected metastatic lymph nodes presumably from a thyroid malignancy.She had an 123I diagnostic whole body scan that showed 123I avid areas in the thyroid bed as well as left cervical lymph nodes, which later turned out to be metastatic papillary carcinoma of the thyroid on histology. She was treated with therapeutic doses of 131I. Follow-up radioactive iodine scans and serum thyroglobulin assays showed no evidence of malignant thyroid tissue. The occurrence of papillary carcinoma of the thyroid after a subtotal thyroidectomy for Graves' disease is hereby reported. The need for vigilance and regular follow-up in patients who receive all forms of treatment for benign thyroid diseases is emphasized. PMID:24705115

  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. PMID:25175810

  6. 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

  7. 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

  8. Identification of potential therapeutic targets for papillary thyroid carcinoma by bioinformatics analysis

    PubMed Central

    ZHAO, MING; WANG, KE-JING; TAN, ZHUO; ZHENG, CHUAN-MING; LIANG, ZHONG; ZHAO, JIAN-QIANG

    2016-01-01

    The aim of the present study was to identify potential therapeutic targets for papillary thyroid carcinoma (PTC) and to investigate the possible mechanism underlying this disease. The gene expression profile, GSE53157, was downloaded from the Gene Expression Omnibus database. Only 10 chips, including 3 specimens of normal thyroid tissues and 7 specimens of well-differentiated thyroid carcinomas, were analyzed in the present study. Differentially-expressed genes (DEGs) between PTC patients and normal individuals were identified. Next, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of DEGs were performed. Modules in the protein-protein interaction (PPI) network were identified. Significant target genes were selected from the microRNA (miRNA) regulatory network. Furthermore, the integrated network was constructed with the miRNA regulatory and PPI network modules, and key target genes were screened. A total of 668 DEGs were identified. Modules M1, M2 and M3 were identified from the PPI network. From the modules, DEGs of cyclin-dependent kinase inhibitor 1A, S100 calcium binding protein A6 (S100A6), dual specificity phosphatase 5, keratin 19, met proto-oncogene (MET) and lectin galactoside-binding soluble 3 were included in the Malacards database. In the miRNA regulatory and integrated networks, genes of cyclin-dependent kinase inhibitor 1C (CDKN1C), peroxisome proliferator-activated receptor γ, aryl hydrocarbon receptor, basic helix-loop-helix family, member e40 and reticulon 1 were the key target genes. S100A6, MET and CDKN1C may exhibit key roles in the progression and development of PTC, and may be used as specific therapeutic targets in the treatment of PTC. However, further experiments are required to confirm these results. PMID:26870166

  9. Incidental papillary thyroid carcinoma: diagnostic findings in a series of 287 carcinomas.

    PubMed

    Pagni, Fabio; Jaconi, Marta; Delitala, Alberto; Garancini, Mattia; Maternini, Matteo; Bono, Francesca; Giani, Alessandro; Smith, Andrew

    2014-09-01

    The recent increase in the detection of papillary thyroid carcinoma (PTC) has been influenced by the finding of incidental tumours. To this group, carcinomas measuring less than 1 cm (the so-called microcarcinomas) as well as those above 1 cm belong. Analyzing a case series from our own experience, this paper focuses on the current pre-operative diagnostic challenges that can lead to PTC incidental discovery. For this retrospective study, 287 patients with a PTC diagnosis were selected. For each, the following variables were analysed: sex, age, ultrasound (US) appearance, number of thyroid nodules, PTC size, PTC variants and presence of other associated pathology. Pre-operative fine needle aspiration (FNA) results were classified according to the five-tiered SIAPEC system. For 281 patients, the US-guided FNA results were available. Cytohistological correlation was evaluated in terms of FNA sensitivity and false negative rate. An incidental PTC was found in 45.2 % of patients. The majority of these were due to unsuccessful US detection of malignant nodules (103 cases); incorrect cytological diagnosis was responsible for the other 24 cases. The most powerful clinical confounding factors were: multinodular background versus single nodule presentations (p < 0.001) and histotype (follicular vs conventional variant, p < 0.05). Of course, tumour size remains a strongly influential feature on pre-operative diagnosis, with greater difficulties arising for carcinomas <5 mm. Moreover, FNA sensitivity was lower also in large PTCs (>2 cm) due to tumour heterogeneity. Although with limitations related to the tumour's intrinsic features and the thyroid background, US-guided FNA, especially if performed by a dedicated multidisciplinary team, is a powerful diagnostic tool for detecting malignant thyroid nodules. To the state of the art, we propose a practical clinical-pathological cut-off for this procedure, setting it at 5 mm. PMID:24997780

  10. 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