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Sample records for occult papillary thyroid

  1. Occult Papillary Thyroid Carcinoma Metastasis to the Sacrum and the Skull: An Unusual Presentation

    PubMed Central

    Jouhar, Fatima S.; Quadri, Asif; Afandi, Bachar; Al Rawi, Sadir

    2014-01-01

    This case represents occult follicular variant of papillary thyroid carcinoma (FVPTC) with large metastasis to the sacrum. The patient, a 42-year-old female, presented after hemithyroidectomy for benign follicular adenoma with lower back pain associated with fever and sweating. A lytic lesion of the left sacral bone was found on the CT with biopsy showing metastatic carcinoma with morphology and immunophenotype of thyroid gland primary tumor proven to be FVPTC. The patient had completion thyroidectomy with benign pathology. PMID:25544844

  2. Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.

    PubMed

    Gordon, Michael S; Gordon, Murray B

    2016-01-01

    Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.

  3. Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report

    PubMed Central

    K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

    2014-01-01

    Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039

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

    ClinicalTrials.gov

    2016-12-02

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

  5. Low risk papillary thyroid cancer.

    PubMed

    Brito, Juan P; Hay, Ian D; Morris, John C

    2014-06-16

    Thyroid cancer is one of the fastest growing diagnoses; more cases of thyroid cancer are found every year than all leukemias and cancers of the liver, pancreas, and stomach. Most of these incident cases are papillary in origin and are both small and localized. Patients with these small localized papillary thyroid cancers have a 99% survival rate at 20 years. In view of the excellent prognosis of these tumors, they have been denoted as low risk. The incidence of these low risk thyroid cancers is growing, probably because of the use of imaging technologies capable of exposing a large reservoir of subclinical disease. Despite their excellent prognosis, these subclinical low risk cancers are often treated aggressively. Although surgery is traditionally viewed as the cornerstone treatment for these tumors, there is less agreement about the extent of surgery (lobectomy v near total thyroidectomy) and whether prophylactic central neck dissection for removal of lymph nodes is needed. Many of these tumors are treated with radioactive iodine ablation and thyrotropin suppressive therapy, which-although effective for more aggressive forms of thyroid cancer-have not been shown to be of benefit in the management of these lesions. This review offers an evidence based approach to managing low risk papillary thyroid cancer. It also looks at the future of promising alternative surgical techniques, non-surgical minimally localized invasive therapies (ethanol ablation and laser ablation), and active surveillance, all of which form part of a more individualized treatment approach for low risk papillary thyroid tumors.

  6. 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.

  7. Coexistence of papillary carcinoma and Hashimoto's thyroiditis.

    PubMed

    Matesa-Anić, Dubravka; Matesa, Neven; Dabelić, Nina; Kusić, Zvonko

    2009-03-01

    The aim of the study was to determine the incidence of coexistence of papillary carcinoma and Hashimoto's thyroiditis in cytologic material. Cytologic findings were collected from 10508 patients that underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the thyroid. Hashimoto's thyroiditis was found in 2156 (20.5%) and papillary carcinoma in 269 (2.6%) of 10508 patients with FNAC, whereas both Hashimoto's thyroiditis and papillary carcinoma were present in 42 (0.4%) patients. Among patients with FNAC diagnosis of Hashimoto's thyroiditis, the prevalence of papillary carcinoma was 1.9%. Among patients with FNAC diagnosis of papillary carcinoma, the prevalence of Hashimoto's thyroiditis was 15.6%. There was no statistically significant association between the presence of papillary carcinoma and Hashimoto's thyroiditis in patients undergoing FNAC (p=0.0522). In conclusion, in a large series of patients, the incidence of Hashimoto's thyroiditis and papillary carcinoma coexistence in cytologic material was 0.4%. There was no statistically significant relationship between Hashimoto's thyroiditis and papillary carcinoma in cytologic material.

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

    ClinicalTrials.gov

    2014-08-20

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

  9. Thyroid Langerhans cell histiocytosis and papillary thyroid carcinoma

    PubMed Central

    Algarni, Mohammed; Alhakami, Hadi; AlSubayea, Haia; Alfattani, Naif; Guler, Mohammet; Satti, Mohamed

    2016-01-01

    A 27-year-old female, married with two children, presented to our clinic with a 1-year history of thyroid swelling and pressure symptoms on lying backward and bilateral cervical lymphadenopathy. The patient was a known case of panhypopituitarism for 5 years. Comprehensive patient evaluation including FNAC with papillary thyroid cancer result then she underwent total thyroidectomy and bilateral neck dissection and final histologic examination confirmed papillary thyroid carcinoma in the background of lymphocytic thyroiditis, associated with Langerhans cell histiocytosis (LCH). The draining cervical lymph nodes were also involved by LCH and metastatic papillary thyroid carcinoma. Although the association of LCH with papillary thyroid carcinoma in the thyroid has been reported, their co-existence with LCH in the draining lymph nodes is very uncommon. PMID:27867869

  10. Ultrasonographic imaging of papillary thyroid carcinoma variants

    PubMed Central

    2017-01-01

    Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC. PMID:28222584

  11. Occult carcinoma of the thyroid gland.

    PubMed

    Arellano, L; Ibarra, A

    1984-09-01

    Ten occult carcinomas of the thyroid gland were found in 274 unselected autopsies at the Pathology Service, Hospital José Joaquín Aguirre, between December 1980 and March 1983. This is the lowest incidence among the most recent published series. The present results suggest that environmental factors play an important role in the etiology of this type of carcinoma.

  12. Expression of obestatin and ghrelin in papillary thyroid carcinoma.

    PubMed

    Karaoglu, Aziz; Aydin, Suleyman; Dagli, Adile F; Cummings, David E; Ozercan, Ibrahim H; Canatan, Halit; Ozkan, Yusuf

    2009-03-01

    Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto's thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto's disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.

  13. Pediatric papillary thyroid cancer: current management challenges

    PubMed Central

    Verburg, Frederik A; Van Santen, Hanneke M; Luster, Markus

    2017-01-01

    Although with a standardized incidence of 0.54 cases per 100,000 persons, differentiated thyroid cancer (DTC) is a rare disease in children and adolescents, it nonetheless concerns ~1.4% of all pediatric malignancies. Furthermore, its incidence is rising. Due to the rarity and long survival of pediatric DTC patients, in most areas of treatment little evidence exists. Treatment of pediatric DTC is therefore littered with controversies, many questions therefore remain open regarding the optimal management of pediatric papillary thyroid cancer (PTC), and many challenges remain unsolved. In the present review, we aim to provide an overview of these challenging areas of patient and disease management in pediatric PTC patients. Data on diagnosis, surgery, radionuclide, and endocrine therapy are discussed, and the controversies therein are highlighted. PMID:28096684

  14. Determinants of papillary cancer of the thyroid

    SciTech Connect

    Wingren, G.; Hatschek, T.; Axelson, O. )

    1993-10-01

    Determinants of papillary thyroid cancer were evaluated in a questionnaire-based case-control study from southeastern Sweden. A total of 104 cases, diagnosed from 1977 to 1987, and 387 randomly selected controls were included in the analyses. Female subjects with papillary cancer reported a work history as dentists/dental assistants, telephone operators, teachers, and day nursery personnel, and an occupational contact with chemicals and video display terminals more often than did controls. The 11 male cases more often reported working as mechanics and metal workers and having occupational contact with solvents. Other factors associated with increased risk for female papillary cancer were having private well water at the birth address; leisure time exposure to combustion smoke; low intake of cruciferous vegetables and seafood; and a family history of goiter, heart disease, biliary disorder, or female genital cancer. Diagnostic radiographic examinations, especially to the head, neck, or upper back/chest area, or repeated dental examinations, were also found to be associated with this form of cancer. With regard to the possible influence from hormonal factors among women less than age 50 years at time of diagnosis, an increased risk was found for a pregnancy soon after puberty. Tendencies toward a decreasing risk with increasing age at first pregnancy as well as an increasing risk with increasing number of pregnancies were found as well. Multiparity seemed to potentiate the effect from prior radiographic examinations.

  15. 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

  16. 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

  17. Metastatic papillary thyroid carcinoma to the nose: report and review of cutaneous metastases of papillary thyroid cancer

    PubMed Central

    Cohen, Philip R.

    2015-01-01

    Background: Metastatic papillary thyroid carcinoma typically appears in local lymph nodes. Skin metastases are rare. Purpose: A man with progressive metastatic papillary thyroid carcinoma who developed a cutaneous metastasis on his nose is described. The clinical manifestations of metastatic papillary thyroid carcinoma to skin are reviewed. Methods: PubMed was used to search the following terms, separately and in combination: basal, cancer, carcinoma, cell, cutaneous, kinase, inhibitor, metastases, nose, papillary, rearranged during transfection, receptor, RET, thyroid, tyrosine, vandetanib. Results: Pathologic changes observed on the biopsy of the man’s nose lesion were similar to those of his original cancer. Genomic evaluation of the tumor revealed an aberration involving the rearranged during transfection (RET) receptor tyrosine kinase. The residual tumor was excised. Treatment with vandetanib, a RET inhibitor was initiated; his metastatic disease has been stable, without symptoms or recurrent cutaneous metastasis, for 2 years following the discovery of his metastatic nose tumor. Conclusions: Papillary thyroid carcinoma with skin metastases is rare. Nodules usually appear on the scalp or neck; the thyroidectomy scar is also a common site. Metastatic tumor, albeit infrequently, can present as a nose lesion. The prognosis for patients with cutaneous metastases from papillary thyroid carcinoma is poor. However, with the ability to test the tumor for genomic aberrations, molecular targeted therapies—such as tyrosine kinase inhibitors—may provide extended survival in these individuals. PMID:26693082

  18. [Kartagener syndrome and papillary thyroid carcinoma: an unusual combination].

    PubMed

    Ren, Jingyuan; Wang, Xurui; He, Zhongyin

    2015-11-01

    A case of a papillary thyroid carcinoma in a patient with situs inversus with associated bronchiectasis and chronic sinusitis (Kartagener's syndrome) is reported. A 61-year-old male patient has the symptoms of nasal obstruction. nasal purulent discharge and headache for 2 years. Physical examination: right nasal purulent in right nasal cavity and multiple lychee-like opaque mass in right middle meatus. A nodule, one centimeter in diameter, locates in the upper pole of right thyroid. Evidence of full situs inversus viscerum can be confirmmed by chest radiographs and ultrasound doppler. Pathology: right nasal polyps, the right small papillary thyroid cancer. TEM Tip primary ciliary dyskinesia. Clinical diagnosis: Kartagener syndrome, papillary thyroid carcinoma (T1a N0 M0, I period), chronic sinusitis-nasal polyps.

  19. Papillary thyroid microcarcinoma in Graves' disease presenting as a cystic neck mass.

    PubMed

    Patil, Milind; Kamalanathan, Sadishkumar; Sahoo, JayaPrakash; Vivekanandan, Muthupillai; Kate, Vikram; Pandit, Nandini; Badhe, Bhawana

    2015-01-01

    The presentation of papillary thyroid microcarcinoma (PTMC) as a solitary cystic neck mass is uncommon. Additionally, its association with Graves' disease is very rare. We report a case of occult PTMC, who presented with a cystic neck mass in the background of Graves' disease without any goiter. Imaging like ultrasound of neck, single photon emission computed tomography-CT (SPECT-CT), and technetium scan failed to detect any lesion in the thyroid, which was picked up only by the contrast-enhanced computed tomography (CECT) of neck. The patient underwent total thyroidectomy with right modified lymph node dissection. Our case highlights the presentation of metastatic PTMC as a differential diagnosis of a cystic neck mass even in a patient with Graves' disease without any thyroid enlargement.

  20. Papillary carcinoma thyroid with anastomosing channels: An unusual morphology

    PubMed Central

    Dalal, Varsha; Kaur, Manveen; Bansal, Anju

    2017-01-01

    Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, accounting for 70%–80% of all thyroid malignancies. It is biologically indolent and has an excellent prognosis. Variations in histopathologic patterns are known to influence prognosis and often result in a diagnostic dilemma. We report an unusual case of a 35-year-old female with papillary carcinoma of a thyroid isthmus showing anastomosing channels on histopathology, a distinctive pattern that has not been described in PTC. Similar to tumor cells, the lining cells of these channels were also positive for thyroid transcription factor 1, thyroglobulin, and cytokeratin-19 and negative for CD34 and CD31. The diagnosis of PTC should rely on nuclear morphology rather than architecture. Pathologists should be aware of different variants because some of these variants show aggressive behavior and poor outcome. The present report highlights the distinctive pattern of PTC, recognition of which is important to avoid any diagnostic pitfall. PMID:28367032

  1. Simultaneous Papillary Carcinoma in Thyroglossal Duct Cyst and Thyroid

    PubMed Central

    Kraft, Adele O.; Berenstein, Cynthia Koeppel; Fonseca, Bernardo; Martorina, Wagner José; de Souza, Andreise Laurian N. R.; Meyer de Moraes, Gustavo; Rajão, Kamilla Maria Araújo Brandão; Sousa, Bárbara Érika Caldeira Araújo

    2017-01-01

    Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options. PMID:28270939

  2. Is papillary thyroid microcarcinoma an indolent tumor?

    PubMed Central

    Gao, Xuemei; Zhang, Xiao; Zhang, Yajing; Hua, Wenjuan; Maimaiti, Yusufu; Gao, Zairong

    2016-01-01

    Abstract The increasing detection of papillary thyroid microcarcinoma (PTMC) has created management dilemmas. To clarify the clinical significance of postsurgery stimulated thyroglobulin (ps-Tg) in PTMC who undergo thyroidectomy and radioactive iodine (RAI), we retrospectively reviewed the 358 PTMC patients who were treated with RAI and followed up in our hospital. Those with an excessive anti-Tg antibody, ultrasound-detected residual were excluded, thereby resulting in the inclusion of 280 cases. Their clinical and histopathological information and clinical outcomes were collected and summarized. Tumor stages were classified according to the tumor, node, metastasis (TNM) staging system and the consensus of the European Thyroid Association (ETA) risk stratification system, respectively. Kaplan–Meier curves were constructed to compare the disease-free survival (DFS) rates of different risk-staging systems. By the end of follow-up, none of the patients died of the disease or relapsed. The 8-year DFS rate was 76.9%. Kaplan–Meier curves showed different DFS rates in TNM stages I versus IV, III versus IV, very low risk versus high risk, low risk versus high risk, respectively (P < 0.05), while they were not significantly different in stage I versus stage III, very low risk versus low risk (P > 0.05). Finally, 40 (14.3%) cases got a persistent disease. Five variables (male sex, nonconcurrent benign pathology, initial tumor size >5 mm, lymph node metastasis, and ps-Tg ≥ 10 μg/L) were associated with disease persistence by univariate regression analysis. Ps-Tg ≥ 10 μg/L was the only independent prognostic variable that predicted disease persistence by multivariate regression analysis (odds ratio: 36.057, P = 0.000). Therefore, PTMC with a small size of ≤1 cm does not always act as an indolent tumor. In conclusion, ps-Tg ≥ 10 μg/L is associated with increased odds of disease persistence. ETA risk stratification is more

  3. Papillary thyroid microcarcinoma in thalassaemia: an emerging concern for physicians?

    PubMed

    De Sanctis, V; Campisi, S; Fiscina, B; Soliman, A

    2012-09-01

    The occurrence of malignancies in thalassaemic patients is an emerging concern for physicians. In the last five years, in a single Thalassaemia Unit following 195 thalassaemic patients, eleven cases of carcinoma were diagnosed: 4 cases of liver, 1 of lung, 1 of adrenal gland and 5 cases of papillary thyroid carcinoma (patient mean age 42.6 years).Therefore, we decided to perform a thyroid ultrasonography (US) in addition to the periodic (6-12 months) assessment of FT4 and TSH in all adult patients with thalassaemia followed at the Thalassaemia Unit of Siracusa and at the Outpatient Clinic of Quisisana Hospital of Ferrara. Thyroid nodules were found in 8.6% of 58 examined thalassaemia major or intermedia patients. To exclude thyroid malignancy, fine needle biopsy (FNAC) under US guidance was performed. A diagnosis of incidental papillary thyroid microcarcinoma (PTMC) was made in 3 female patients with iron overload. According to the World Health Organization, PTMC is defined as papillary thyroid carcinoma measuring < or = 10 mm in the greatest dimension. Two patients were HCV positive. All underwent a total or subtotal thyroidectomy with histological confirmation of the FNAC cytology diagnosis. In conclusion, it seems that patients with thalassaemia have a substantial risk for malignancies. Further studies are needed in these patients to clarify the possible link between cellular iron content, hepatitis C virus infection and cancer development. A thyroid ultrasonography is recommended for all adult thalassaemic patients in addition to the annual FT4 and TSH assessment.

  4. Collision tumor of the thyroid gland: primary squamous cell and papillary thyroid carcinoma.

    PubMed

    Warman, Meir; Lipschitz, Noga; Ikher, Sergey; Halperin, Doron

    2011-01-01

    Introduction. Collision tumor of the thyroid gland is defined when independent and histologically distinct tumors coexist within the gland. The presence of both papillary and squamous cell carcinoma in the thyroid gland is unusual. Suggested etiologies include embryonic remanents of squamous epithelium, chronic inflammation, or thyroid malignancies promoting squamous metaplasia. Case Presentation. An elderly patient presented with a rapid enlargement of a long-standing right thyroid nodule. The tumor was locally invasive and unresectable. Pathology revealed the diagnosis of papillary and squamous cell carcinoma of the thyroid gland. Possible primary sites for squamous cell carcinoma in upper aerodigestive tract were excluded. The patient outcome was fatal although palliative chemoradiotherapy. Discussion. Collision tumor of papillary and squamous cell carcinoma of the thyroid gland is a rare entity that may imply bad prognosis, as to the presence of the squamous portion. The best treatment includes resection of the tumor; unfortunately it is not possible in most cases.

  5. Primary papillary thyroid carcinoma previously treated incompletely with radiofrequency ablation.

    PubMed

    Kim, Hoon Yub; Ryu, Woo Sang; Woo, Sang Uk; Son, Gil Soo; Lee, Eun Sook; Lee, Jae Bok; Bae, Jeoung Won

    2010-01-01

    Radiofrequency ablation (RFA) recently has been applied to benign thyroid nodules, mainly for the cosmetic reasons, and limited cases of local recurrences or focal distant metastases of well-differentiated thyroid cancer, in the high-risk reoperative condition or for the palliative purpose. But no report has been made on the RFA for primary thyroid cancer to date. We report on a patient with primary papillary carcinoma of thyroid gland who had undergone RFA before the cytological diagnosis of malignancy, later referred and treated with robotic surgery successfully. We can learn the following lessons from our case; (1) the RFA for operable primary thyroid malignancy should be avoided, because of the possibility of remnant viable cancer and undetectable nodal metastasis, and (2) robotic or endoscopic thyroid surgery may be a feasible operative method for benign or malignant thyroid nodules previously treated with RFA.

  6. Thyroid pathologies accompanying primary hyperparathyroidism: a high rate of papillary thyroid microcarcinoma

    PubMed Central

    Kutlutürk, Koray; Otan, Emrah; Yağcı, Mehmet Ali; Usta, Sertaç; Aydın, Cemalettin; Ünal, Bülent

    2014-01-01

    Objective: Thyroid pathologies and non-medullary thyroid cancer often accompany primary hyperparathyroidism (PHPT). The purpose of this study was to examine the association between thyroid diseases, especially micropapillary thyroid cancer, with PHPT. Material and Methods: Data regarding 46 patients who were operated on with a diagnosis of PHPT at Inonu University Faculty of Medicine, General Surgery Clinic between June 2009 and March 2013 were retrospectively analyzed. Age, gender, levels of preoperative calcium, parathyroid hormone and phosphorus, and the histopathological results of the removed parathyroid and thyroid tissues were evaluated. All of the patients had a preoperative diagnosis of PHPT and there was no history of radiation to the head and neck region in any of the patients. Results: Out of the 46 patients who were operated on for PHPT, 39 were female and 7 were male. The mean age was 52.8 years (25–76). Simultaneous thyroidectomy was performed in 35 patients (76.1%) due to an accompanying thyroid disorder. Papillary microcarcinoma was detected in 5 of these 35 (10.9%) patients who underwent thyroidectomy, two of which (40%) were multifocal tumors. The benign thyroid pathologies detected in the remaining 30 (65.2%) cases included lymphocytic thyroiditis in 3, Hashimoto thyroiditis in 1, follicular adenoma in 3 (two of which was Hurtle cell), and nodular colloidal goiter in 23 patients. The preoperative serum phosphate level was significantly higher in the group with papillary thyroid microcarcinoma (p=0.013). Conclusion: In regions where goiter is endemic, thyroid diseases and thyroid papillary microcarcinoma occur in association with PHPT at a higher rate compared to the normal population. Therefore, we believe that patients who are planned for surgery due to PHPT should be thoroughly investigated for the presence of any concomitant malignant thyroid pathologies in the preoperative period. It should also be kept in mind that patients with high

  7. Follicular variant of papillary carcinoma in submandibular ectopic thyroid with no orthotopic thyroid gland.

    PubMed

    Guerrissi, Jorge O

    2012-01-01

    Ectopic thyroid tissue with no orthotopic gland is extremely rare; malign transformation of ectopic thyroid is also an uncommon event, and rarer is the follicular variant of papillary carcinoma. In this clinical report, a case with submandibular ectopic thyroid without orthotropic thyroid gland is presented. Treatment was a complete resection of tumor, and histologic findings reveal follicular variant of papillary carcinoma. The patient had an uneventful postoperative recovery, and a substitution treatment with thyroxine was maintained. Physicians should be aware of the possibility that a lingual, submandibular, or lateral neck swelling could be an ectopic thyroid gland. This entity poses specific diagnostic and therapeutic difficulties, and definitive diagnosis is histologic. Computed tomographic scan, radioactive scan, and ultrasonography are necessary in revealing the presence of normal thyroid gland. Recommended treatment is primarily surgical, sometimes associated with radioiodine I 131 therapy and a substitution treatment with thyroxine.

  8. Synchronous papillary thyroid carcinoma and breast ductal carcinoma

    PubMed Central

    Zhong, Jinjing; Lei, Jianyong; Jiang, Ke; Li, Zhihui; Gong, Rixiang; Zhu, Jingqiang

    2017-01-01

    Abstract Background: The incidences of both thyroid cancer and breast cancer have been rising in recent years; however, it is very rare to find a single person with both of these cancers. Only a few cases of synchronous thyroid and breast cancer have been published, and even fewer cases have been reported in older patients (>60 years). Case summary: The current study presents a case of synchronous papillary thyroid carcinoma and breast ductal carcinoma in an elderly patient. The patient first underwent a mastectomy and axillary lymphadenectomy in our department, followed by a total thyroidectomy and lymphadenectomy of the left lateral region of the neck 1 month later. Postoperative pathological examination identified invasive ductal carcinoma of the breast and papillary carcinoma of the thyroid. Over almost half a year of follow-up, the patient has exhibited no evidence of recurrence or metastasis, as demonstrated by careful ultrasound examinations. Herein, we not only report this case but also present a systematic review of the causes, diagnosis, and treatment of synchronous breast and thyroid cancer. Conclusion: Although synchronous primary tumors of the thyroid and breast are very rare, they remain a possibility; therefore, more attention should be paid to these cases. PMID:28207532

  9. Concurrent papillary thyroid cancer with pituitary ACTH-secreting tumor.

    PubMed

    Kuo, Sheng-Fong; Chen, Jeng-Yeou; Chuang, Wen-Yu; Jung, Shih-Ming; Chang, Yu-Chen; Lin, Jen-Der

    2007-04-01

    Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide ((131)I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer, (201)thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi (131)I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer.

  10. [Genetic factors predisposing to the development of papillary thyroid cancer].

    PubMed

    Puzianowska-Kuźnicka, Monika; Pietrzak, Maciej

    2005-01-01

    According to classic theory of neogenesis, cancer arises from well-differentiated cell that in response to variety of factors de-differentiates, becomes able to proliferate without control and/or loses its ability to undergo apoptosis. According to another theory, cancers (at least cancers of some organs) originate from stem cells, which "by definition" are poorly differentiated and able to proliferate indefinitely. Therefore a lower number of abnormal events is necessary for these cells to escape proliferation-controlling mechanisms. With regard to papillary thyroid cancers it is still thought that it arises from well-differentiated thyreocyte. One of the characteristic features of cancer cell is chromosomal instability. Lowest number of such abnormalities is observed in well-differentiated thyroid cancers (including papillary cancer), intermediate - in poorly-differentiated cancers, while highest - in anaplastic cancers. Microarray analysis shows that despite of clinical heterogeneity, gene expression profiles of papillary cancers are very similar. Genetic anomalies predisposing to the development of papillary cancer most commonly regard proteins that possess kinase activity. Kinases phosphorylate other proteins, and play an extremely important role in signal transduction from outside the cell as well as inside the cell. Constitutive activation of some kinases may lead to the excessive and/or permanent activation of some transduction pathways specific for mitogens or growth factors. This results in excessive proliferation. The best known protein of such type which function is altered in papillary thyroid cancers is RET - a membrane-located growth factor-receptor with kinase activity. RET gene undergoes different rearrangements in this type of cancer. There are approximately 10 RET rearrangements known, with RET/PTC3 and RET/PTC1 being most common. In this anomaly kinase domain-encoding 3' end of RET gene is aberrantly bound to 5' end of another gene. Fusion

  11. Is familial papillary thyroid microcarcinoma more aggressive than sporadic form?

    PubMed Central

    Lee, Cho Rok; Park, Seulkee; Kang, Sang-Wook; Lee, Jandee; Jeong, Jong Ju; Chung, Woong Youn; Park, Cheong Soo

    2017-01-01

    Purpose With the increasing incidence of papillary thyroid microcarcinoma (PTMC), familial papillary thyroid microcarcinoma (FPTMC) is now recognized more frequently. However, the biological behavior of FPTMC is poorly understood. The aim of this study was to investigate the prevalence of FPTMC and its biological aggressiveness. Methods Between March 2006 and July 2010, 2,414 patients underwent primary surgical therapy for PTMC and 149 (6.2%) were further classified as FPTMC. To determine the biological aggressiveness of FPTMC, we compared the clinicopathological features and prognosis between FPTMC and sporadic PTMC (SPTMC). Results The male-to-female ratio was higher in FPTMC than in sporadic papillary thyroid microcarcinoma (SPTMC: 1:4.5 vs. 1:7.2, P = 0.041). The central lymph node (LN) metastasis rate was significantly higher in FPTMC than in SPTMC (36.2% vs. 24.2%, P = 0.002). The local recurrence rate was also higher in FPTMC than in SPTMC (4.5% vs. 0.6%, P < 0.001). We identified familial occurrence in 6.2% of cases of PTMC. FPTMC is associated with a high rate of central LN metastasis and local recurrence. Conclusion These findings suggest that close follow-up can be beneficial in FPTMC patients to detect local recurrence. PMID:28289666

  12. Clinical and Pathological Implications of Concurrent Autoimmune Thyroid Disorders and Papillary Thyroid Cancer

    PubMed Central

    Cunha, L. L.; Ferreira, R. C.; Marcello, M. A.; Vassallo, J.; Ward, L. S.

    2011-01-01

    Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance. PMID:21403889

  13. Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

    PubMed

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

    2016-01-01

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

  14. Hyponatremia after thyroid hormone withdrawal in a patient with papillary thyroid carcinoma.

    PubMed

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

    2014-03-01

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

  15. Papillary thyroid carcinoma with an uncommon spread of hematogenous metastases to the choroid and the skin.

    PubMed

    Bucerius, Jan; Meyka, Susanne; Michael, Bangard; Biersack, Hans-Jürgen; Eter, Nicole

    2008-01-01

    Papillary carcinoma is the most common malignancy of the thyroid gland with initial lymphogenic metastatic spread in many cases. Hematogenous spread may affect the lung, bone and brain. We present a case of hematogenous metastases of papillary thyroid carcinoma both in the choroid and the skin, which are reported in the literature to be rare sites of metastases in primary differentiated thyroid carcinoma. This finding is even more remarkable, as the reported patient presented without any other disseminated hematogenous metastases at the time of diagnosis of both of these metastases. With this background, papillary carcinoma of the thyroid should be considered in the differential diagnosis of choroidal or skin metastasis of unknown origin.

  16. Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate.

    PubMed

    Rakheja, Dinesh; Boriack, Richard L; Mitui, Midori; Khokhar, Shama; Holt, Shelby A; Kapur, Payal

    2011-04-01

    Elevated levels of D: -2-hydroxyglutarate (D: -2-HG) occur in gliomas and myeloid leukemias associated with mutations of IDH1 and IDH2. L: -2-Hydroxyglutaric aciduria, an inherited metabolic disorder, predisposes to brain tumors. Therefore, we asked whether sporadic cancers, without IDH1 or IDH2 hot-spot mutations, show elevated 2-hydroxyglutarate levels. We retrieved 15 pairs of frozen papillary thyroid carcinoma (PTC) and adjacent non-neoplastic thyroid, and 14 pairs of hyperplastic nodule (HN) and adjacent non-hyperplastic thyroid. In all lesions, exon 4 sequencing confirmed the absence of known mutations of IDH1 and IDH2. We measured 2-hydroxyglutarate by liquid chromatography-tandem mass spectrometry. Compared to normal thyroid, PTCs had significantly higher D: -2-HG and L: -2-hydroxyglutarate (L: -2-HG) levels, and compared to HNs, PTCs had significantly higher D: -2-HG levels. D: -2-HG/L: -2-HG levels were not significantly different between HNs and normal thyroid. Further studies should clarify if elevated 2-hydroxyglutarate in PTC may be useful as cancer biomarker and evaluate the role of 2-hydroxyglutarate in cancer biology.

  17. Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma

    PubMed Central

    Rosignolo, Francesca; Sponziello, Marialuisa; Durante, Cosimo; Puppin, Cinzia; Mio, Catia; Baldan, Federica; Di Loreto, Carla; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2016-01-01

    PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis. PMID:27249794

  18. Clinical characteristics of papillary thyroid carcinoma arising from the pyramidal lobe

    PubMed Central

    Yoon, Sang Gab; Yi, Jin Wook; Seong, Chan-Yong; Kim, Jong-Kyu; Kim, Su-Jin; Chai, Young Jun; Choi, June Young

    2017-01-01

    Purpose Papillary thyroid carcinoma (PTC) arising from the pyramidal lobe is rare; therefore, clinicopathologic evaluation is lacking. In addition, the rate of occult malignancy in the pyramidal lobe after thyroid surgery is unclear. This study is to evaluate the clinical characteristics of PTCs that involve the pyramidal lobe. Methods The study enrolled 1,107 patients who underwent thyroid surgery for PTC at Seoul National University Hospital from 2006 to 2015. Pyramidal lobe status in pathologic reports was clear in all cases. “Pyramidal lobe-dominant PTC” was defined as single pyramidal lobe cancer or multifocal cancer with larger pyramidal lobe tumor. “Incidental pyramidal lobe PTC” was defined as occult cancer identified after thyroidectomy or as multifocal cancer with smaller pyramidal lobe tumor. Results Ten patients were included in the pyramidal lobe-dominant PTC group. The mean age was 58 ± 12.5 years, and the mean tumor size was 0.7 ± 0.7 cm. Cervical lymph node metastasis was found in 5 patients (50%). Three patients had microscopic lymphatic invasion, and 7 had advanced American Joint Comitee on Cancer (AJCC) stage disease (5 with stage III and 2 with stage IV). Compared with conventional PTC (n = 1,058), pyramidal lobe-dominant PTC was significantly associated with lymphatic invasion (P = 0.031) and advanced AJCC stage (P = 0.022). The prevalence of incidental pyramidal lobe PTC was 3.56%. Conclusion Pyramidal lobe PTC is relatively small in size; however, the rate of extrathyroidal extension and lymph node metastasis is high. Preoperative evaluation of nodal status is important, and the extent of surgery should be determined in accordance with the preoperative diagnosis. PMID:28289665

  19. 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

  20. Co-expression and clinical utility of Snail and N-cadherin in papillary thyroid carcinoma.

    PubMed

    Yang, Xiangshan; Shi, Ranran; Zhang, Jing

    2016-01-01

    Papillary thyroid carcinoma is one of the most common subtypes of thyroid cancer and portends a good prognosis. N-cadherin (neural cadherin) is a member of the classical cadherin family and is often overexpressed in many types of cancers. Snail, a kind of zinc finger protein, is a transcriptional repressor which has been intensively studied in mammals. We investigate the immunohistochemical expression of Snail and N-cadherin in papillary thyroid carcinoma tissues and cells and then discuss the clinical value of Snail and N-cadherin expression. Immunohistochemical technique was performed to detect Snail and N-cadherin in 60 cases of papillary thyroid carcinoma and analyzed the relationship between the expression of Snail, N-cadherin, and clinicopathological indicators. Western blot was used to investigate the constitutive and inducible expression of Snail and N-cadherin. In our study, the expression rate of Snail and N-cadherin was 85.0 % (51/60) and 78.3 % (47/60), respectively, in papillary thyroid carcinoma. The expression rate of Snail and N-cadherin in thyroid papillary carcinoma with metastatic lymph nodes was 93.3 and 86.7 %, respectively, while in papillary thyroid carcinoma tissue without lymph node metastasis, the expression rate was 60.0 and 53.3 %, respectively. The positive correlation of Snail and N-cadherin was observed (r = 0.721, p < 0.01). In addition, Western blot further identified the constitutive and inducible expression of Snail and N-cadherin in papillary thyroid carcinoma tissues and cell lines. In conclusion, Snail and N-cadherin are constitutively and inducibly expressed in papillary thyroid carcinoma and may play important roles in the development and metastasis of papillary thyroid carcinoma. Snail and N-cadherin may be used as an effective indicator.

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

    PubMed Central

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

    2014-01-01

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

  2. Resistance of papillary thyroid cancer stem cells to chemotherapy

    PubMed Central

    GIUFFRIDA, RAFFAELLA; ADAMO, LUANA; IANNOLO, GIOACCHIN; VICARI, LUISA; GIUFFRIDA, DARIO; ERAMO, ADRIANA; GULISANO, MASSIMO; MEMEO, LORENZO; CONTICELLO, CONCETTA

    2016-01-01

    Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitely in vitro and give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies. PMID:27347201

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Cribiform variant of papillary thyroid cancer and familial adenomatous polyposis

    PubMed Central

    Perea del Pozo, E.; Ramirez Plaza, C.; Padillo Ruiz, J.; Martos Martínez, J.M.

    2015-01-01

    Background Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterised by the progressive development of multiple colorectal adenomatous polyps and an increased incidence of colorectal carcinoma. It is often accompanied by other benign or malignant extracolonic manifestations, including gastric and duodenal tumours, osteomas, desmoid tumours, retinal pigmentation, and thyroid and adrenocortical tumours Methods and results We report the case of a 42-year-old white female with FAP who was referred to our Endocrine Surgery Unit for surgery because of a palpable mass in the left side of the neck. An ultrasound-guided fine needle aspiration biopsy showed a cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC). The incidence, clinical presentation, histology and treatment options for this rare histological subtype are discussed. Conclusions The diagnosis of CMV of PTC is very strongly related to the FAP syndrome and must be suspected when a thyroid node appears in FAP patients. Likewise, any patient without known FAP who presents this histology in a surgically biopsied or resected thyroid node should undergo total colonoscopy for screening of colonic polyposis and genetic study of the APC gene sequence. PMID:26521198

  6. 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

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

    PubMed

    Dong, Li-Qun; Sun, Xiao-Mei; Xiang, Cheng-Fa; Wu, Jin; Yu, Ping

    2016-07-01

    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.

  8. Columnar cell variant of papillary thyroid carcinoma: A diagnostic dilemma in fine-needle aspiration cytology.

    PubMed

    Verma, Ritu; Paul, Paramita

    2016-10-01

    Columnar cell variant of papillary thyroid carcinoma (PTC) is an uncommon variant with an aggressive course as compared to classic papillary carcinoma. Cytologic diagnosis of these tumors is difficult due to absence of characteristic nuclear features of classic pattern of papillary carcinoma. We present a case of columnar cell variant in a young female misdiagnosed on aspiration cytology. A 21-year-old female presented with solitary nodule in the left aspect of thyroid. A diagnosis of medullary thyroid carcinoma was rendered. The resected thyoroidectomy specimen revealed a columnar cell variant of PTC which was further supported by immunohistochemical staining. Diagn. Cytopathol. 2016;44:816-819. © 2016 Wiley Periodicals, Inc.

  9. The Diffuse Sclerosing Variant of Papillary Thyroid Cancer Presenting as Innumerable Diffuse Microcalcifications in Underlying Adolescent Hashimoto's Thyroiditis: A Case Report.

    PubMed

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

    2016-03-01

    Hashimoto's thyroiditis is the most common diffuse thyroid disease and is characterized by diffuse lymphocytic infiltration. However, the ultrasonographic findings of papillary thyroid carcinomas that arise from Hashimoto's thyroiditis in the pediatric and adolescent population are not well known.We report a rare ultrasonographic finding in a 22-year-old woman diagnosed with the diffuse sclerosing variant of papillary thyroid carcinoma that arose from underlying Hashimoto's thyroiditis: innumerable diffuse microcalcifications instead of a typical malignant-appearing nodule.

  10. Ultrasonic features of papillary thyroid microcarcinoma coexisting with a thyroid abnormality

    PubMed Central

    Li, Bo; Zhang, Yaqiong; Yin, Ping; Zhou, Jian; Jiang, Tian'an

    2016-01-01

    The present study aimed to investigate the value of ultrasonography in the diagnosis of papillary thyroid microcarcinoma (PTMC) coexisting with a thyroid abnormality, and to improve the accuracy of PTMC diagnosis. The ultrasonic features of 38 PTMC nodules coexisting with a thyroid abnormality and 56 thyroid benign nodules, obtained by surgical resection and confirmed by pathological analysis, were retrospectively analyzed. All masses were ≤ 1.0 cm in diameter. Ultrasonic features that were analyzed included the shape, aspect ratio, boundary, margin, echo, uniformity, presence or absence of microcalcification and enlargement of the lymph nodes, as well as the blood flow of the nodules. Furthermore, the sensitivity, specificity and accuracy of ultrasonography for the diagnosis of PTMC were obtained. The following ultrasonic features of thyroid nodules were significantly (P<0.05) associated with PTMC coexisting with a thyroid abnormality: An irregular shape; an aspect ratio of ≥ 1; an unclear boundary; blurred margins; internal heterogeneous hypoechogenicity; and microcalcification. Therefore, thyroid nodules with these ultrasonic characteristics coexisting with a thyroid abnormality may be suspected as malignant PTMC. The present study demonstrated that ultrasound-guided biopsies are necessary to prevent misdiagnosis of PTMC. The sensitivities of enlarged neck lymph nodes and abundant blood flow are so low that they may be considered as references for the differentiation of PTMC from benign nodules. PMID:27698812

  11. TROP-2 expression in papillary thyroid carcinoma: Potential Diagnostic Utility.

    PubMed

    Simms, Anthony; Jacob, Reuben P; Cohen, Cynthia; Siddiqui, Momin T

    2016-01-01

    TROP-2 is a type I transmembrane glycoprotein which is over-expressed in various malignancies, and is related to epithelial cell adhesion molecule (EpCAM), also called TROP-1, gp40, and KSA. In this study, we evaluated TROP-2 expression in papillary thyroid carcinoma (PTC) and compared it to other thyroid neoplastic and non-neoplastic lesions. Immunohistochemical (IHC) evaluation for TROP-2 was performed on 137 thyroid fine needle aspiration (FNA) cell blocks (CB) which included classic PTC (64), follicular variant PTC (FVPTC) (10), anaplastic thyroid carcinoma (AC) (2), medullary carcinoma (MC) (8), follicular neoplasms (FN) (8), Hurthle cell neoplasms (HCN) (9), follicular lesion of uncertain significance (FLUS) (12), and benign thyroid nodule (BTN) (24). IHC for TROP-2 expression was also performed on 331 BTN and malignant tumor tissue sections in tissue microarray (TMA). Membranous staining in >5% of tumor cells was considered positive. TROP-2 stained 61 of 64 PTC CB, 7 of 10 FVPTC CB, and 9 of 12 FLUS CB. All other cases were negative for TROP-2. TROP-2 showed a sensitivity of 95.31% and specificity of 89% for classic PTC in FNA CB. In TMA samples, TROP-2 stained 54 of 60 classic PTC cases and hence showed a high sensitivity and specificity. All BTN in CB and TMA were negative. We conclude that TROP-2 is a highly sensitive and specific IHC marker for identifying classic PTC. TROP-2 may play an important role in diagnosing classic PTC, especially in equivocal cases. This study also identifies a strong role for TROP-2 in separating PTC from BTN.

  12. Diffuse Follicular Variant of Papillary Thyroid Carcinoma: A Case Report with a Revision of Literature

    PubMed Central

    Vinciguerra, Gian Luca Rampioni; Noccioli, Niccolò; Bartolazzi, Armando

    2016-01-01

    The diffuse follicular variant of papillary thyroid carcinoma (DFV-PTC) is a rare malignant thyroid condition. It represents an uncommon variant of papillary carcinoma characterized by a diffuse involvement of thyroid parenchyma, follicular architecture and nuclear features of PTC in absence of a surrounding capsule. Up to date few data have been collected about this entity and, at the best of our knowledge, only 24 cases have been reported in the literature. According to these reports DFV-PTC seems to occur preferentially in young women and shows more aggressive behavior than other papillary thyroid tumors. Herein we present an unusual case of DFV-PTC occurring in an 83 years old woman, involving the entire thyroid gland, without distinct or prevalent thyroid nodules. The tumor was clinically misdiagnosed as obstructive goiter. PMID:28191291

  13. Encapsulated follicular variant of papillary thyroid carcinoma/noninvasive follicular thyroid neoplasm with papillary-like nuclear features with Spindle Cell Metaplasia: Case report and review of literature.

    PubMed

    Haroon Al Rasheed, Mohamed Rizwan; Acosta, Andres; Tarjan, Gabor

    2017-04-01

    Spindle cell lesions of the thyroid are rare overall, and span a wide clinical spectrum that ranges from spindle cell metaplasia (SCM(1)) to anaplastic carcinoma. Their differentiation is only seldom straightforward, and usually requires the integration of the clinical, histological and immunohistochemical data. Only a handful of publications have described cases of SCM in the thyroid and we add to that literature by reporting a unique case of encapsulated follicular variant of papillary thyroid carcinoma/noninvasive follicular thyroid neoplasm with papillary-like nuclear features with SCM. In addition, we review the literature on the relationship between SCM and different thyroid lesions, summarizing the morphological and immunohistochemical features that aid in its differentiation from more aggressive spindle cell proliferations.

  14. [Cryptogenic and iatrogenic papillary thyroid carcinoma in children and adolescences: comparative study].

    PubMed

    Fridman, M V; Demidchik, Iu E; Papok, V E; Savva, N N; Zborovskaia, A A; Spivak, L V; Schmid, K W

    2011-01-01

    The clinico-morphological investigations of 117 children and adolescences with papillary thyroid carcinoma, surgically treated in the Republic Centre for Thyroid Tumors, Minsk, Belarus in 1995-2009 and dutifully followed-up have been studied. Ninety -five observations of all cases were sporadic, but 22 patients had been treated earlier from other neoplasm (Hodgkin's diseases, malignant lymphoma, leukemia, sarcoma, medulloblastoma). Epidemiologic, clinical and pathological peculiarities of thyroid carcinoma in Belarus were analyzed. A number of features distinguished "cryptogenic" and "iatrogenic" papillary thyroid carcinoma in children and adolescents were found out.

  15. Cross-talk between NO and HMGB1 in lymphocytic thyroiditis and papillary thyroid cancer.

    PubMed

    Mardente, Stefania; Zicari, Alessandra; Consorti, Fabrizio; Mari, Emanuela; Di Vito, Maura; Leopizzi, Martina; Della Rocca, Carlo; Antonaci, Alfredo

    2010-12-01

    The controversy on whether or not inflammatory infiltrates in chronic lymphocytic thyroiditis predispose to cancer, has now merged into a debate over the role of the inflammatory infiltrates. The question is how and why some cells become transformed and what factors allow them to spread and in some cases become invasive. Here, we show that the amount of inflammatory mediators such as nitric oxide (NO) and high mobility group Box 1 protein (HMGB1) produced in thyroiditis microenvironment increases in tumors and could be involved in the cellular transformation process. NO and HMGB1 are known to attract macrophages that would promote angiogenesis, matrix remodelling and suppression of an efficient immune response. Inflammatory infiltrates could increase the risk of papillary cancer in patients with autoimmune lymphocytic thyroiditis. Cytokines and soluble inflammatory mediators involved in cancer-related inflammation are not only a target for innovative diagnostic and therapeutic strategies but they also represent a future challenge for oncologists.

  16. Molecular Pathways Associated with Aggressiveness of Papillary Thyroid Cancer

    PubMed Central

    Benvenga, Salvatore; Koch, Christian A

    2014-01-01

    The most common thyroid malignancy is papillary thyroid cancer (PTC). Mortality rates from PTC mainly depend on its aggressiveness. Geno- and phenotyping of aggressive PTC has advanced our understanding of treatment failures and of potential future therapies. Unraveling molecular signaling pathways of PTC including its aggressive forms will hopefully pave the road to reduce mortality but also morbidity from this cancer. The mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathway as well as the family of RAS oncogenes and BRAF as a member of the RAF protein family and the aberrant expression of microRNAs miR-221, miR-222, and miR-146b all play major roles in tumor initiation and progression of aggressive PTC. Small molecule tyrosine kinase inhibitors targeting BRAF-mediated events, vascular endothelial growth factor receptors, RET/PTC rearrangements, and other molecular targets, show promising results to improve treatment of radioiodine resistant, recurrent, and aggressive PTC. PMID:24955023

  17. Orbital metastasis as initial manifestation of a widespread papillary thyroid microcarcinoma

    PubMed Central

    Pagsisihan, Daveric Ablis; Aguilar, Anthony Harvey Isabelo; Maningat, Ma Patricia Deanna Delfin

    2015-01-01

    Papillary thyroid carcinomas (PTCs), particularly microcarcinomas, rarely metastasise to the orbit. We report a case of a 49-year-old woman with a right supraorbital mass and unremarkable physical examination of the thyroid gland region. Orbital CT scan showed an expansile lytic lesion in the orbital plate of the frontal bone with a soft tissue component. An incision biopsy revealed metastatic well-differentiated thyroid carcinoma. Thyroid ultrasound was normal except for a subcentimetre nodule in the right lobe. The patient underwent total thyroidectomy where histopathology showed a subcentimetre follicular variant PTC. She subsequently received radioactive iodine therapy. Post-therapy whole body scan revealed metastatic thyroid tissues in the right orbital and posterior parietal, and left shoulder and hip areas. Although infrequent, metastatic thyroid carcinoma should be considered in patients with orbital metastasis even when neck examination is normal. In rare cases, this may be the initial manifestation of a widely metastatic papillary thyroid microcarcinoma. PMID:25819821

  18. Microarray profiling of circular RNAs in human papillary thyroid carcinoma

    PubMed Central

    Peng, Nianchun; Shi, Lixin; Zhang, Qiao; Hu, Ying; Wang, Nanpeng; Ye, Hui

    2017-01-01

    Background Non-coding circular RNAs (circRNAs) have displayed dysregulated expression in several human cancers. Here, we profiled the circRNA expression of papillary thyroid carcinoma (PTC) tumors to improve our understanding of PTC pathogenesis. Methods Microarray profiling was performed on 18 thyroid samples, consisting of six PTC tumors, six matching contralateral normal samples, and six benign thyroid lesions. After low-intensity filtering, hierarchical clustering revealed the circRNA expression patterns. Statistical analysis followed by qRT-PCR validation identified the differential circRNAs. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a network map of circRNA-miRNA interactions for the differential circRNAs. Bioinformatics platforms predicted cancer-related circRNA-miRNA associations and putative downstream target genes, respectively. Results A total of 88 circRNAs and 10 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to normal thyroid tissue, while 129 circRNAs and 226 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to benign thyroid lesions. A total of 12 upregulated and four downregulated circRNAs were overlapping between the foregoing comparisons. One downregulated circRNA (hsa_circRNA_100395) showed interactive potential with two cancer-related miRNAs (miR-141-3p and miR-200a-3p). From this analysis, we identified several promising cancer-related genes that may be targets of the dysregulated hsa_circRNA_100395/miR-141-3p/miR-200a-3p axis in PTC tumors. Conclusions circRNA dysregulation may play a role in PTC pathogenesis, and several key circRNAs show promise as candidate biomarkers for PTC. The hsa_circRNA_100395/miR-141-3p/ miR-200a-3p axis may be involved in the pathogenesis of PTC. PMID:28288173

  19. Expression of papillary thyroid carcinoma-associated molecular markers and their significance in follicular epithelial dysplasia with papillary thyroid carcinoma-like nuclear alterations in Hashimoto's thyroiditis.

    PubMed

    Ma, Heng; Yan, Jin; Zhang, Chao; Qin, Shenghui; Qin, Lingzhi; Liu, Liwei; Wang, Xi; Li, Naping

    2014-01-01

    The aim of this study was to evaluate the expression of papillary thyroid carcinoma (PTC)-associated tumor markers in follicular epithelial dysplasia showing PTC-like nuclear alterations (FED) in Hashimoto's thyroiditis (HT) and to explore the relationship between HT and PTC. In this study, 43 PTC, 18 HT with FED and 16 peritumoral benign thyroid tissues were immunohistochemically analyzed for CK19, galectin-3, HBME-1, CD56, claudin-1 and NGAL expression. Our research revealed that in HT, the expression of CK19, galectin-3, HBME-1, claudin-1 and NGAL was focal and limited to FED, while CD56 was strongly positive in FED and most Hürthle cells. The stain intensity of CK19, claudin-1 and NGAL in FED decreased compared with PTC, but were significantly higher than that in peritumoral benign thyroid tissues (all P < 0.0125). For galectin-3, HBME-1 and CD56, no statistically significant difference was detected between HT and peritumoral benign thyroid tissues (all P > 0.05). In conclusion, In HT, FED might be a precancerous condition closely associated with PTC development as they have overlaps in cytological and immunomarker profiles, indicating that in patients with HT, under prolonged stimuli from chronic inflammation, part of follicular epithelia may show regeneration, hyperplasia, Hürthle cell metaplasia and dysplasia, eventually malignant transformation. Hence, long term follow-up and regular inspection would be necessary for Hashimoto's thyroiditis with FED.

  20. 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

  1. Risk prediction and clinical model building for lymph node metastasis in papillary thyroid microcarcinoma.

    PubMed

    Lin, Dao-Zhe; Qu, Ning; Shi, Rong-Liang; Lu, Zhong-Wu; Ji, Qing-Hai; Wu, Wei-Li

    2016-01-01

    The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central/lateral lymph node dissection, remains controversial. This study investigated the clinicopathologic factors predictive of lymph node metastasis (LNM) in patients diagnosed with PTMC. Multivariate logistic regression analysis was used for PTMC patients identified from the Surveillance, Epidemiology, and End Results database who were treated by surgery between 2002 and 2012, to determine the association of clinicopathologic factors with LNM. According to the results, a total of 31,017 patients met the inclusion criteria of the study. Final histology confirmed 2,135 (6.9%) cases of N1a disease and 1,684 cases (5.4%) of N1b disease. Our multivariate logistic regression analysis identified variables associated with both central LNM and lateral lymph node metastasis (LLNM), including a younger age (<45 years), male sex, non-Hispanic white and other race, classical papillary histology, larger tumor size, multifocality, and extrathyroidal extension; distant metastasis was also significantly associated with LLNM. The significant predictors identified from multivariable logistic regression were integrated into a statistical model that showed that extrathyroidal extension had maximum weight in the predictive role for LNM. LLNM was validated to be a significant risk factor for cancer-specific death in Cox regression analyses, whereas central LNM failed to predict a worse cancer-specific survival according to our data. Therefore, we suggested that central lymph node dissection could be performed in certain patients with risk factors. Given the prevalence of LLNM in PTMC, a thorough inspection of the lateral compartment is recommended in PTMC patients with risk factors for precise staging; from the viewpoint of a radical treatment for tumors, prophylactic lateral lymph node dissection that aims to remove the occult lateral lymph nodes may be an option for PTMC with

  2. Features of papillary thyroid microcarcinoma in the presence and absence of lymphocytic thyroiditis.

    PubMed

    Kim, Hee Sung; Choi, Yoon Jung; Yun, Ji-Sup

    2010-09-01

    It is known that the prevalence of lymphocytic thyroiditis (LT) is higher in patients with papillary thyroid carcinoma (PTC), that gender influences this association, and that certain features of PTC occur more frequently in patients who also have LT. These relationships have not been studied in patients with papillary thyroid microcarcinomas (PTMC), however. Therefore, we performed a study to compare the clinical and pathological features of patients with PTMC who did and did not have LT. We collected the 323 consecutive patients following excision of PTMC diagnosed as papillary carcinoma on preoperative needle aspiration cytology. We analyzed the demographic, serologic, and pathologic data of those cases with categorization into four groups based on presence of LT and neck lymph node metastasis. In all PTMC, the presence of LT did not influence the frequency of lymph node metastasis (27 of 105 [25.7%] vs. 48 of 218 [22.0%]). Among the patients with metastatic PTMC, LT was noted significantly more often in female than male patients (95.2% vs. 79.8%). In metastatic PTMC, multifocality and bilaterality was more frequent in with LT than without LT (44.4% vs. 29.2%; 29.6% vs. 14.6%). Both the presence of serum thyroglobulin antibody (TgAb; p = 0.016) and serum microsomal antibody (p = 0.013) were highly correlated with the presence of LT. Twenty-seven of 105 patients (25.7%) with PTMC with LT had nodal metastasis. Co-existing LT was noted predominantly in women, influenced more often multifocality and bilaterality of tumors, and higher frequency of metastasis to lateral compartment lymph nodes.

  3. Relationship of hemoxygenase-1 and prolidase enzyme activity with oxidative stress in papillary thyroid cancer

    PubMed Central

    Terzioglu, D; Teksoz, S; Arikan, AE; Uslu, E; Yılmaz, E; Eren, B

    2016-01-01

    Aim: Recent studies associate thyroid cancer with oxidative stress. We aim to clarify the relation between papillary thyroid cancer, oxidative stress, hemoxygenase-1, prolidase enzymes and investigate the availability of these enzymes as markers for diagnosis, success of treatment, and follow-up. Methods: Thirty-one patients with papillary thyroid carcinoma and 25 healthy control subjects were included in this study. Hemoxygenase-1, prolidase (oxidant stress indicator), malondialdehyde, protein carbonyl, and superoxide dismutase (an indicator of antioxidant defense system) were measured pre-operatively and 30 days after thyroidectomy. Results: There was a significant decrease in serum levels of malondialdehyde and superoxide dismutase (p <0.001 for both) after thyroidectomy in papillary thyroid carcinoma group. In addition, there was a significant difference in the postoperative serum levels of prolidase, malondialdehyde, protein carbonyl, and superoxide dismutase between papillary thyroid carcinoma and control groups (p =0.024, p <0.001, p =0.002, and p =0.016, respectively) beside significant difference of malondialdehyde, protein carbonyl, hemoxygenase-1, and superoxide dismutase pre-operative serum levels (p <0.001, p =0.003, p =0.006, and p =0.025, respectively). Conclusion: When the unquestionable role of oxidative stress in the pathogenesis of cancer is considered, in the future it is expected to associate parametric changes in the serum of patients caused by oxidative stress to papillary thyroid cancer. Hippokratia 2016, 20(1): 55-59 PMID:27895444

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

    PubMed

    Chruścik, Anna; Lam, Alfred King-yin

    2015-12-01

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

  5. Predictive Factors of Superior Mediastinal Nodal Metastasis from Papillary Thyroid Carcinoma—A Prospective Observational Study

    PubMed Central

    Woo, Joo Hyun; Park, Ki Nam; Lee, Jae Yong; Lee, Seung Won

    2016-01-01

    Objectives The purpose of this study was to demonstrate the incidence rates and predictive factors of superior mediastinal lymph node (SMLN) metastasis in PTC (papillary thyroid carcinoma) patients. Methods A prospective observational study was performed between January 2009 and January 2011. PTC patients who had tumors with a maximal diameter greater than 1 cm and clinically negative SMLNs were included in this study. Finally, a total of 217 patients who underwent total thyroidectomy with central compartment neck dissection (CND) and elective superior mediastinal lymph node dissection (SMLND), with or without modified radical neck dissection (MRND) and revisional CND, were included. Results Occult SMLN metastasis was present in 15.7% (34/217). Cytological classifications of tumor, BRAFV600E mutation, Tumor size, T-stage, perithyroidal extension, lymphovascular invasion, multifocality, and paratracheal pN(+) were not predictive of SMLN metastasis (P > .05), while revision surgery, pretracheal pN(+), and multiple lateral pN(+) were associated with SMLN metastasis. There were no major complications related to SMLND. Transient and permanent hypoparathyroidism was observed in 69 cases (31.8%) and 8 cases (3.6%), respectively. Conclusions Despite clinically negative SMLN in preoperative evaluation, SMLN metastasis can be predicted for patients with a PTC tumor size larger than 1 cm, pretracheal LN metastasis, multiple lateral metastasis, and revisional surgery. PMID:26848952

  6. Association of tuberculous thyroiditis and papillary carcinoma of the thyroid: a rare coincidence.

    PubMed

    Errami, Noureddine; Benjellounb, Amine; Hemmaouia, Bouchaib; Nadoura, Karim; Benariba, Fouad

    2014-01-01

    We report the case of a 25 year-old patient with no medical history, admitted to our unit for nodular goiter of the right lobe without clinical or laboratory signs of hyperthyroidism. We carried out a right lobo-isthmectomy revealing the association of tuberculosis and thyroid papillary carcinoma. A left lobectomy has, therefore, been performed in a second stage. The patient underwent a six-month antituberculosis treatment with a good clinical outcome. We discuss this rare association and its best diagnostic and therapeutic support, with a review of the literature.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

  9. Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.

    PubMed

    Ringel, Matthew D; Hardy, Elena; Bernet, Victor J; Burch, Henry B; Schuppert, Frank; Burman, Kenneth D; Saji, Motoyasu

    2002-05-01

    The development of distant metastasis is the most important predictor of death from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene whose product, metastin, was recently identified as the endogenous agonist for a novel Gq/11 coupled receptor (metastin receptor). The expression and functional consequences of metastin and the metastin receptor have not been evaluated in thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Paired normal and tumor samples were available for 4 PC and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA, 2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not expressed in any normal thyroid or benign FA samples, and was expressed in only a minority (2/10) of FC samples. However, the receptor was expressed in the majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. Taken together, these data suggest a potential role for metastin and/or metastin receptors in modulating the biological behavior of thyroid cancers.

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

    PubMed Central

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

    2016-01-01

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

  11. A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer

    PubMed Central

    Su, Xingyun; Wang, Weibin; Ruan, Guodong; Liang, Min; Zheng, Jing; Chen, Ye; Wu, Huiling; Fahey, Thomas J.; Guan, Minxin; Teng, Lisong

    2016-01-01

    Nuclear genetic alterations have been widely investigated in papillary thyroid cancer (PTC), however, the characteristics of the mitochondrial genome remain uncertain. We sequenced the entire mitochondrial genome of 66 PTCs, 16 normal thyroid tissues and 376 blood samples of healthy individuals. There were 2508 variations (543 sites) detected in PTCs, among which 33 variations were novel. Nearly half of the PTCs (31/66) had heteroplasmic variations. Among the 31 PTCs, 28 specimens harbored a total of 52 somatic mutations distributed in 44 sites. Thirty-three variations including seven nonsense, 11 frameshift and 15 non-synonymous variations selected by bioinformatic software were regarded as pathogenic. These 33 pathogenic mutations were associated with older age (p = 0.0176) and advanced tumor stage (p = 0.0218). In addition, they tended to be novel (p = 0.0003), heteroplasmic (p = 0.0343) and somatic (p = 0.0018). The mtDNA copy number increased in more than two-third (46/66) of PTCs, and the average content in tumors was nearly four times higher than that in adjacent normal tissues (p < 0.0001). Three sub-haplogroups of N (A4, B4a and B4g) and eight single-nucleotide polymorphisms (mtSNPs) (A16164G, C16266T, G5460A, T6680C, G9123A, A14587G, T16362C, and G709A) were associated with the occurrence of PTC. Here we report a comprehensive characterization of the mitochondrial genome and demonstrate its significance in pathogenesis and progression of PTC. This can help to clarify the molecular mechanisms underlying PTC and offer potential biomarkers or therapeutic targets for future clinical practice. PMID:27735863

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-09-01

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

  14. Clinicopathological Features of Low-Grade Thyroid-like Nasopharyngeal Papillary Adenocarcinoma

    PubMed Central

    Li, Minhua; Wei, Jiangguo; Yao, Xiaofei; Wang, Cheng

    2017-01-01

    Purpose Primary low-grade thyroid-like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx. Here, we describe a novel case of a 15-year-old Chinese girl who was diagnosed with low-grade thyroid-like papillary adenocarcinoma, including a brief review of the literature to reveal the clinicopathological features of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma. Materials and Methods Immunohistochemistry was used to evaluate the expression of pan-cytokeratin (CKpan), cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), vimentin, epithelial membrane antigen (EMA), thyroglobulin, CD15, S100, P40, CK20, CDX-2, glial fibrillary acidic protein (GFAP), and Ki-67. Additionally, in situ hybridization investigation was utilized to identify the presence of small Epstein-Barr virus (EBV)–encoded RNA. Results Histopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores. Immunohistochemically, the neoplastic cells were positive for CKpan, CK7, TTF-1, vimentin, and EMA, but negative for thyroglobulin, CD15, S100, P40, CK20, CDX-2, and GFAP. The Ki-67–labeling index reached 5% in the most concentrated spot. In situ hybridization for EBV was negative. Conclusion Due to the distinct rarity of low-grade thyroid-like papillary adenocarcinomaswith a favorable clinical outcome, a nationwide effort to raise public awareness of this neoplasm is required. PMID:27384157

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

    PubMed Central

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

    2016-01-01

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

  16. Multifocal fibrosing thyroiditis and its association with papillary thyroid carcinoma using BRAF pyrosequencing.

    PubMed

    Frank, Renee; Baloch, Zubair W; Gentile, Caren; Watt, Christopher D; LiVolsi, Virginia A

    2014-09-01

    Multifocal fibrosing thyroiditis (MFT) is characterized by numerous foci of fibrosis in a stellate configuration with fibroelastotic and fibroblastic centers entrapping epithelial structures. MFT has been proposed as a risk factor for papillary thyroid carcinoma (PTC) development. We attempted to identify whether MFT showed such molecular changes and could possibly be related to PTC. We identified seven cases of PTC with MFT in our institutional pathology database and personal consult service of one of the authors (VAL) for the years 1999 to 2012. Areas of PTC, MFT, and normal tissue were selected for BRAF analysis. Macro-dissection, DNA extraction and PCR amplification, and pyrosequencing were performed to detect BRAF mutations in codon 600. All of the MFT lesions and normal thyroid tissue were negative for BRAF mutations. Of the seven PTCs analyzed, five (71 %) were negative for BRAF mutations, while two cases were positive. In our study, none of the MFT lesions harbored BRAF mutations, whereas 29 % (two of seven) PTCs in the same gland were positive. Hence, in this small study, we found no evidence that the MFT lesion is a direct precursor to PTC. It is likely an incidental bystander in the process and a reflection of the background thyroiditis.

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

    PubMed

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

    2016-10-01

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

  18. Fibronectin 1 promotes migration and invasion of papillary thyroid cancer and predicts papillary thyroid cancer lymph node metastasis

    PubMed Central

    Xia, Shujun; Wang, Chuandong; Postma, Emily Louise; Yang, Yanhua; Ni, Xiaofeng; Zhan, Weiwei

    2017-01-01

    Lymph node metastasis (LNM) is common in papillary thyroid cancer (PTC), and is an indicator of recurrence. The detailed molecular mechanism of LNM in PTC has not been well described. This study aimed to investigate the role of fibronectin 1 in PTC LNM and its clinical relevance. The expression of fibronectin 1 was confirmed in PTC tissues and cell lines. A correlation analysis was conducted and a receiver-operating characteristic curve obtained. The effect of fibronectin 1 on the proliferation of PTC cell lines was performed using a colony-formation assay and Cell Counting Kit 8. Cell-cycle analysis was performed with a flow-cytometry assay. Migration and invasion ability were evaluated by transwell and wound-healing assays. Fibronectin 1 was overexpressed in metastasized PTC. Overexpressed fibronectin 1 was positively correlated with PTC LNM. Receiver-operating characteristic analysis showed that the diagnostic accuracy of fibronectin 1 was 81.1%, with sensitivity of 80% and specificity of 82%. Overexpression of fibronectin 1 promoted proliferation, migration, and invasion in PTC. Fibronectin 1 plays a critical role in PTC metastasis by modulating the proliferation, migration, and invasion ability of PTC cells, and it is a valuable diagnostic biomarker for predicting PTC LNM. PMID:28367057

  19. The impact of coexistent Hashimoto's thyroiditis on lymph node metastasis and prognosis in papillary thyroid microcarcinoma.

    PubMed

    Qu, Ning; Zhang, Ling; Lin, Dao-Zhe; Ji, Qing-Hai; Zhu, Yong-Xue; Wang, Yu

    2016-06-01

    The impact of coexistent Hashimoto's thyroiditis (HT) on lymph node metastasis (LNM) and prognosis in papillary thyroid microcarcinoma (PTMC) remains controversial. We evaluated the association of coexistent HT with clinicopathologic parameters, LNM, and prognosis by retrospectively reviewing a series of consecutive patients treated for PTMC at Fudan University Cancer Center from January 2005 to December 2010. Of all 1,250 patients with complete data for analysis, 364 (29.1 %) had coexistent HT (HT group) and 886 patients (70.9 %) had no evidence of HT (control group). The HT group had higher proportion of female (87.9 vs 70.1 %) patients, higher mean level of thyroid-stimulating hormone (TSH) (2.39 vs 2.00 mIU/L), and lower incidence of extrathyroidal extension (7.4 vs 11.7 %) than those in the control group. However, the incidence of LNM and recurrence was similar between the two groups, and HT was not associated with LNM and recurrence. A series of clinicopathologic factors identified for predicting LNM and recurrence in the control group did not show any prediction in the HT group. In summary, this study suggested that coexistent HT had insignificant protective effect on LNM and prognosis in PTMC, which was inconsistent with prior studies. Further studies aiming to determine novel predictors are recommended in PTMC patients with coexistent HT.

  20. 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.

  1. The clinicopathologic differences in papillary thyroid carcinoma with or without co-existing chronic lymphocytic thyroiditis.

    PubMed

    Yoon, Yeo-Hoon; Kim, Hak Joon; Lee, Jin Woo; Kim, Jin Man; Koo, Bon Seok

    2012-03-01

    The goal of this study is to determine the clinicopathologic differences in patients with papillary thyroid carcinoma (PTC) with or without chronic lymphocytic thyroiditis (CLT). We reviewed the medical records of 195 consecutive PTC patients who underwent total thyroidectomy and bilateral central lymph node dissection from April 2008 to March 2010. The differences in clinicopathologic factors, such as age, gender, size of primary tumor, perithyroidal invasion, lymphovascular invasion, capsular invasion, and central lymph node (CLN) metastasis, were analyzed in PTC patients with or without CLT. Among 195 patients, 56 (28.7%) had co-existing CLT. Patients with CLT had the following characteristics as compared to patients without CLT: significantly younger, female predominance, smaller tumor size, and lower incidence of capsular invasion (p = 0.038, 0.006, 0.037, and 0.026, respectively). Also, patients with CLT (12.5%) had a significantly lower incidence of CLN metastases than patients without CLT (28.1%; p = 0.025) based on univariate analysis. Moreover, multivariate analysis showed that younger age (p = 0.042, odds ratio = 1.033) and female gender (p = 0.012, odds ratio = 6.865) are independent clinical factors in patients with CLT compared to patients without CLT. CLT was shown to be commonly associated with PTC. Compared to patients with PTC without CLT, patients with CLT were younger with a female predominance, which are the most important and well-known prognostic variables for thyroid cancer mortality.

  2. Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome.

    PubMed

    Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

    2012-08-01

    The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence.

  3. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases.

    PubMed

    Eusebi, V; Damiani, S; Ellis, I O; Azzopardi, J G; Rosai, J

    2003-08-01

    Five cases of a hitherto undescribed breast tumor having histologic features similar to those of the tall cell variant papillary thyroid carcinoma are described. They were composed of columnar mitochondrion-rich to oxyphilic cells arranged in nests, papillae, and follicle-like structures. In addition, the neoplastic cells showed numerous nuclear grooves and, in two cases, nuclear pseudo-inclusions. None of the patients had previous concomitant or subsequent evidence of a thyroid tumor. Immunohistochemistry further excluded a metastasis from the thyroid in the four cases tested, as they were consistently thyroglobulin and thyroid transcription factor 1 negative.

  4. Frontal bone metastasis from an occult follicular thyroid carcinoma: Diagnosed by FNAC

    PubMed Central

    Kalra, Rajnish; Pawar, Richa; Hasija, Sonia; Chandna, Abha; Sankla, Manoj; Malhotra, Chanchal

    2017-01-01

    Metastatic deposits in skull bones from follicular thyroid carcinoma is rare, and metastatic disease in skull being the presenting symptom without obvious thyroid lesion (occult primary) is even rarer. A 60-year-old female patient presented with a mass in the frontal region of the skull. Fine needle aspiration cytology was done which revealed an adenocarcinoma with repeated follicular pattern, reminiscent of follicular neoplasm of thyroid, which on immunocytochemistry revealed positivity for thyroglobulin. Patient was investigated further for primary thyroid malignancy, and imaging revealed a nodule in the left lobe of thyroid. Neuroimaging showed osteolytic lesion involving the cranium. PMID:28182063

  5. A Papillary Thyroid Microcarcinoma Revealed by a Single Bone Lesion with No Poor Prognostic Factors

    PubMed Central

    Godbert, Yann; Henriques-Figueiredo, Benedicte; Cazeau, Anne-Laure; Carrat, Xavier; Stegen, Marc; Soubeyran, Isabelle; Bonichon, Francoise

    2013-01-01

    Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT) found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg). The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis. PMID:23509641

  6. Combined Endonasal-Transcervical Approach to a Metastatic Parapharyngeal Space Papillary Thyroid Carcinoma

    PubMed Central

    Benet, Arnau; El-Sayed, Ivan

    2015-01-01

    Purpose: Although papillary thyroid carcinoma metastases to the parapharyngeal space are rare, the high amount of fat tissue allows tumors to grow clinically undetectable until they invade most of the parapharyngeal space. We describe for the first time a combined endonasal and transcervical approach for a parapharyngeal metastasis from a papillary thyroid carcinoma. Materials and Methods: A 51-year-old male with a previous history of papillary thyroid carcinoma presented with left ear fullness and left-sided facial numbness. Imaging revealed a 4x3 cm pre-styloid parapharyngeal space mass invading the foramen ovale and extending below the palate. Needle biopsy confirmed metastatic papillary thyroid carcinoma. Results: The lesion was resected with a combined endoscopic endonasal and transcervical approach. Postoperative MRI revealed gross total resection, and the patient recovered from his symptoms. Conclusion: This novel approach provides access to pre-styloid parapharyngeal tumors with superior extension to the skull base, avoiding more extensive traditional open approaches. PMID:26203403

  7. Current Management of Low Risk Differentiated Thyroid Cancer and Papillary Microcarcinoma.

    PubMed

    Tarasova, V D; Tuttle, R M

    2017-01-10

    Each year, the proportion of thyroid cancer patients presenting with low risk disease is increasing. Moreover, the definition of low risk thyroid cancer is expanding and several histological subtypes beyond papillary microcarcinomas are now classified as low risk disease. This shift in the landscape of thyroid cancer presentation is forcing clinicians to critically re-evaluate whether or not traditional management paradigms that were effective in treating intermediate and high risk disease are applicable to these low risk patients. Here we review the definition of low risk disease, examine the various histological subtypes that are considered low risk in the 2015 American Thyroid Association guidelines for the management of thyroid nodules and thyroid cancer, and review our current approach to the management of these low risk tumours.

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

    SciTech Connect

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

    1986-10-01

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

  9. Familial Papillary Thyroid Carcinoma (FPTC): a Retrospective Analysis in a Sample of the Bulgarian Population for a 10-Year Period.

    PubMed

    Vidinov, Kalin; Nikolova, Dragomira

    2017-03-01

    In recent years, there are numerous reports indicating the presence of familial papillary carcinoma. Unfortunately, no genetic defect can be linked directly to the disease. In this study, we set the goal to make a retrospective analysis of the cases with papillary carcinoma in the Department of Endocrine Surgery for the past 10 years, to compare the characteristics of sporadic and familial forms of the disease and to find families with hereditary papillary carcinoma. The study included 810 patients treated for thyroid cancer in the Department of Endocrine Surgery, USBALE "Acad. Iv. Penchev" Hospital, between January 1, 2006 and December 31, 2015. We used chi square test to determine statistical significant difference. The data analysis and interpretation was performed on SPSS 20.0. Both groups had similar demographic distribution. We found that 587 patients have sporadic papillary carcinoma, while 147 have a relative with thyroid pathology in the first degree of kinship. In 8 patients, there was a blood relative with thyroid cancer. When we compared the two groups, we found statistically significant difference only in tumor size. There was no significant difference in aggressiveness of the thyroid cancer (multifocality and lymph node metastasis). When analyzing the results, we identified 147 patients with a family history of thyroid disease (20%). In 8 patients (5.44%), we found at least one relative with papillary thyroid carcinoma. However, our study does not demonstrate any difference in the aggressiveness of familial and sporadic papillary thyroid carcinoma.

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

    PubMed Central

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

    2016-01-01

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

  11. Cribriform variant papillary thyroid cancer: a characteristic of familial adenomatous polyposis.

    PubMed

    Fenton, P A; Clarke, S E; Owen, W; Hibbert, J; Hodgson, S V

    2001-02-01

    Inherited cancer syndromes may predispose to more than one type of cancer, and these characteristically develop at an earlier age than their sporadic counterparts. The occurrence in a single individual of multiple, early onset primary cancers may indicate an inherited cancer susceptibility. Familial adenomatous polyposis (FAP), an autosomal, dominantly inherited susceptibility to colorectal adenomas and cancer also predisposes to childhood medulloblastomas and to a specific rare histologic type (cribriform variant) of papillary thyroid cancer. We describe a patient who developed a childhood medulloblastoma of the cerebellum, and subsequently a cribriform papillary thyroid cancer. These cancers predated the diagnosis of FAP in this patient, who was later found to have several relatives with FAP. The adenomatous polyposis coli (APC) mutation delineated in this family was in the region associated with those causing an increased risk of thyroid cancer. We submit that the diagnosis of the cribriform variant of papillary thyroid cancer in a young individual, especially after a previous cancer diagnosis, should alert the physician to the possibility of a diagnosis of FAP.

  12. Long-term follow-up of papillary and follicular thyroid carcinomas with bone metastasis

    PubMed Central

    Chen, Szu-Tah; Hsueh, Chuen; Li, Chia-Lin; Chao, Tzu-Chieh

    2017-01-01

    The aims of this study were to investigate papillary and follicular thyroid carcinomas with bone metastasis in various clinical presentations and to determine the prognostic factors after multimodality treatment. A retrospective analysis was performed of 3,120 patients with papillary and follicular thyroid carcinoma. Of these patients, 131 (including 97 women, 71.8%) were diagnosed with bone metastasis and underwent follow-up at the Chang Gung Medical Center. Patients with bone metastasis were categorized into two groups. Group A was comprised of patients who were diagnosed with bone metastasis either before thyroidectomy or within 6 months of the initial thyroidectomy (90 patients, 68.7%). Group B was comprised of patients with bone metastasis who received a diagnosis 6 months post-thyroidectomy in the follow-up period (41 patients, 31.3%). After a mean follow-up period of 8.4 ± 7.0 years, there were 88 deaths (67.2%) attributed to thyroid cancer and 13 patients (9.9%) achieved disease-free status. A multivariate analysis showed that older age, early diagnosis, and brain metastasis were each associated with a poor prognosis. The difference in disease-specific mortality rates between groups A and B was significant (p < 0.0001). In conclusion, papillary and follicular thyroid cancers with bone metastasis have a high rate of mortality. Despite this high mortality, 9.9% patients still had an excellent response to treatment. PMID:28278295

  13. Papillary thyroid microcarcinoma co-exists with Hashimoto's thyroiditis: Is strain elastography still useful?

    PubMed

    Li, Yi; Wang, Yan; Wu, Qiong; Hu, Bing

    2016-05-01

    To study the performance of strain elastography in differentiating papillary thyroid microcarcinoma (PTMC) combined with Hashimoto's thyroiditis (HT), conventional ultrasound scan (US) and strain elastography (SE) were performed on 558 nodules smaller than 10 mm by one examiner before surgeries. Serum concentrations of thyroid peroxidase antibody (TPO-Ab) (normal range: 0-60 U/ml) were measured. Continuous variables were analyzed by independent t test. Receiver operating characteristics (ROC) curve analysis was applied to calculate the cut-off values of strain ratio (SR) and elastography score (ES). The comparison of AUCs is performed by Z test. 482 nodules were diagnosed as PTMC and there were 181 nodules co-existed with HT. SR measurements were lower in PTMC co-existed with HT when comparing to those without HT. (7.292±6.581 vs 11.319±13.155, p<0.000). Taking the data from all of the 558 nodules, the best cut-off of diagnosing PTMC was SR>2.58. When taking the data from 181 PTMC with HT, the best cut-off was SR>2.10. The diagnostic value of SR>2.1 were higher than ES>3, conventional US and combining US and SE (z=3.595, 4.876, 4.420, p<0.001), but cut-off of SR>2.1 did not show significant enhancement of diagnostic value compared to SR>2.58 (z=0.439, p=0.8903>0.001) in PTMC with HT. There is a negative relation between SR and titer of TPO-Ab (r=-0.650, p<0.0001). PTMC with high TPO-Ab (>1000) titer presented lower SR (5.972±4.118 vs 8.379±9.172, p=0.009). Although SR measurements were lower in nodules co-existed with HT when comparing those without HT, using a regular ES and cut-off of SR measurement would not influence the diagnosing performance. SE is still very useful for diagnosing PTMC with HT. PTMC with high TPO-Ab titer might require a lower cut-off of SR.

  14. Mouse Models of Follicular and Papillary Thyroid Cancer Progression

    PubMed Central

    Russo, Marika A.; Arciuch, Valeria G. Antico; Di Cristofano, Antonio

    2011-01-01

    A significant number of well-differentiated thyroid cancers progress or recur, becoming resistant to current therapeutic options. Mouse models recapitulating the genetic and histological features of advanced thyroid cancer have been an invaluable tool to dissect the mechanisms involved in the progression from indolent, well differentiated tumors to aggressive, poorly differentiated carcinomas, and to identify novel therapeutic targets. In this review, we focus on the lessons learned from models of epithelial cell-derived thyroid cancer showing progression from hyperplastic lesions to locally invasive and metastatic carcinomas. PMID:22654848

  15. Papillary and follicular thyroid cancer: impact of treatment in 1578 patients

    SciTech Connect

    Simpson, W.J.; Panzarella, T.; Carruthers, J.S.; Gospodarowicz, M.K.; Sutcliffe, S.B.

    1988-06-01

    We report the experience from 13 Canadian radiotherapy centers concerning the treatment and outcome for 1074 papillary and 504 follicular thyroid cancer patients followed for 4-24 years. Surgical resection was carried out in almost all patients; there was no correlation between the type of operation and recurrence or survival. Treatment with external irradiation (201 patients) radioiodine (214 patients), or both (107 patients) was used more often in poor prognosis patients than in those with good prognostic factors, and was effective in reducing local recurrences and improving survival, especially in patients with microscopic residual disease postoperatively. Treatment complications were common but rarely fatal. Thyroid cancer was the cause of death in over half of the papillary cancer deaths and in two-thirds of the follicular cancer deaths.

  16. An unusual manifestation: Papillary thyroid carcinoma in a patient with ataxia-telengiectasia.

    PubMed

    Ulusoy, Ezgi; Edeer-Karaca, Neslihan; Özen, Samim; Ertan, Yeşim; Gökşen, Damla; Aksu, Güzide; Darcan, Şükran; Kütükçüler, Necil

    2016-01-01

    Ataxia-telangiectasia (A-T) is a rare autosomal recessive, multisystem, neurodegenerative disorder, characterized by oculocutaneous telangiectasias, variable immunodeficiency and progressive neurological impairment. Definitive diagnosis is made by revealing a disease causing mutation on ATM gene. Missense mutations and polymorphisms of ATM gene can play a role in the development of thyroid papillary carcinoma. A 13-year-old Turkish girl was diagnosed with ataxia telengiectasia at the age of 8 years. When she was 12 years old, multi-nodular goiter was detected by physical examination and ultrasonography. She underwent thyroidectomy and histopathologic investigation revealed a papillary carcinoma with follicular variant. The patient received post-operative radioiodine therapy as well as L-thyroxine treatment because she had residual lesions. Up until now, she is the first Turkish child wit A-T and thyroid carcinoma described in the literature.

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

    PubMed

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

    2012-08-01

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

  18. Diffuse sclerosing variant of papillary thyroid carcinoma--an update of its clinicopathological features and molecular biology.

    PubMed

    Pillai, Suja; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y

    2015-04-01

    Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is an uncommon variant of papillary thyroid carcinoma. The aim of this review is to critically analyse the features of this entity. A search of the literature revealed 25 clinicopathological studies with in-depth analysis of features of DSVPTC. Overall, the prevalence of DSVPTC varies from 0.7-6.6% of all papillary thyroid carcinoma. Higher prevalence of DSVPTC was noted in paediatric patients and in patients affected by irradiation. DSVPTC tends to occur more frequently in women and in patients in the third decade of life. Macroscopically, DSVPTC can involve the thyroid gland extensively without forming a dominant mass. Microscopic examination of DSVPTC revealed extensive fibrosis, squamous metaplasia and numerous psammoma bodies. The latter pathological feature can aid in the pre-operative diagnosis of the entity by fine needle aspiration and ultrasound. Compared to conventional papillary thyroid carcinoma, DSVPTC had a higher incidence of lymph node metastases at presentation. Distant metastases were noted in approximately 5% of the cases. Patients with DSVPTC were recommended to be managed by aggressive treatment protocols. It is likely that as a result of this, the prognosis of the patients with DSVPTC was noted to be similar to conventional papillary thyroid carcinoma. Overall, cancer recurrence and cancer related mortality have been reported in 14% and 3%, respectively, of patients with DSVPTC. In immunohistochemical studies, DSVPTC showed different expression patterns of epithelial membrane antigen, galectin 3, cell adhesion molecules, p53 and p63 when compared to conventional papillary thyroid carcinoma. On genetic analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC and activation of RET/PTC rearrangements are common. To conclude, DSVPTC has different clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

  19. Severe hyponatremia: a comorbidity with I131 therapy in a patient with papillary thyroid cancer.

    PubMed

    Kaewput, Chalermrat; Pusuwan, Pawana

    2014-08-01

    Hyponatremia is the most common electrolyte disorder in hospitalized patients, especially in elderly patients, in which morbidity varies widely in severity. A 64-year-old Thai woman with papillary thyroid cancer who developed hypothyroid state after thyroid hormone withdrawal for preparation of 1-131 treatment, had severe hyponatremia within the day of 1-131 administration. It is possible that the combination of old age, hypothyroidism, severe nausea and vomiting, and inappropriate secretion of antidiuretic hormone (SIADH) may all have precipitated the severe hyponatremia in the presented case.

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

    SciTech Connect

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

    1994-02-01

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

  1. 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.

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

    PubMed

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

    2014-05-01

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

  3. Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells.

    PubMed

    Zhang, Li; Cheng, Xian; Gao, Yanyan; Zheng, Jie; Xu, Qiang; Sun, Yang; Guan, Haixia; Yu, Huixin; Sun, Zhen

    2015-11-01

    Apigenin, abundantly present in fruits and vegetables, is recognized as a flavonoid with anti-inflammatory, antioxidant and anticancer properties. In this study, we first investigated the anti-neoplastic effects of apigenin on papillary thyroid carcinoma (PTC) cell line BCPAP cells. Our results show that apigenin inhibited the viability of BCPAP cells in a dose-dependent manner. A large body of evidence demonstrates that autophagy contributes to cell death in certain contexts. In the present study, autophagy was induced by apigenin treatment in BCPAP cells, as evidenced by Beclin-1 accumulation, conversion of LC3 protein, p62 degradation as well as the significantly increased formation of acidic vesicular organelles (AVOs) compared to the control group. 3-MA, an autophagy inhibitor, rescued the cells from apigenin-induced cell death. Notably, apigenin enhanced production of reactive oxygen species (ROS), and subsequent induction of significant DNA damage as monitored by the TUNEL assay. In addition, apigenin treatment caused a significant accumulation of cells in the G2/M phase via down-regulation of Cdc25C expression. Our findings reveal that apigenin inhibits papillary thyroid cancer cell viability by the stimulation of reactive oxygen species (ROS) production, induction of DNA damage, leading to G2/M cell cycle arrest followed by autophagic cell death. Thus, our results provide new insights into the molecular mechanisms underlying apigenin-mediated autophagic cell death and suggest apigenin as a potential chemotherapeutic agent which is able to fight against papillary thyroid cancer.

  4. Minimally-invasive endoscopically-assisted neck dissection for lateral cervical metastases of thyroid papillary carcinoma.

    PubMed

    Zhang, Zongmin; Xu, Zhengang; Li, Zhengjiang; An, Changming; Liu, Jie; Zhu, Yiming; Ni, Song; Tang, Pingzhang; Sayan, Anna; Ilankovan, Velupillai

    2014-11-01

    Traditional open operations for lateral neck dissection in patients with papillary thyroid carcinoma leave an unsightly scar. We report complete lateral neck dissection and thyroidectomy for papillary thyroid carcinoma using an endoscopically-assisted approach through a small incision, and evaluate its feasibility and safety. Between March 2010 and January 2013, 6 patients with no definite metastases to the lymph nodes at levels II-IV, and 20 with definite metastases to the lymph nodes at levels II-V were selected. Thyroidectomy, dissection of the central compartment (level VI), and ipsilateral level II-IV and II-V neck dissections were done through a small incision in the neck. The steps of endoscopic lateral neck dissection were similar to those of conventional operations. The mean operating time for the whole procedure was 3.57 hours (range 2.5 - 5.0). It was successful in all patients and there were no serious complications or serious blood loss. A total of 21 patients had lymph node metastases in the central and lateral zones. The mean yield of lymph nodes was 38.6 (range 16-61). There was no evidence of residual or recurrent disease at follow-up, and the cosmetic result was excellent. Minimally invasive, video-assisted comprehensive neck dissection for metastatic papillary thyroid carcinoma is feasible and safe, and has excellent cosmetic results. Further studies with a larger number of patients and long-term follow-up are needed to verify its oncological validity.

  5. MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer.

    PubMed

    Sondermann, Adriana; Andreghetto, Flavia Maziero; Moulatlet, Ana Carolina Bernardini; da Silva Victor, Elivane; de Castro, Marilia Germanos; Nunes, Fábio Daumas; Brandão, Lenine Garcia; Severino, Patricia

    2015-08-01

    Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.

  6. Prognosis of papillary thyroid carcinoma in elderly patients after thyroid resection

    PubMed Central

    Chereau, Nathalie; Trésallet, Christophe; Noullet, Severine; Godiris-Petit, Gaelle; Tissier, Frederique; Leenhardt, Laurence; Menegaux, Fabrice

    2016-01-01

    Abstract The size of the elderly population and the incidence of papillary thyroid carcinoma (PTC) in this group appear to be rapidly increasing, although published information based on more detailed older age groupings are lacking. This study aimed to determine the clinical features and outcomes of elderly patients in PTC. All consecutive patients who received surgery for PTC in our Department from 1978 to 2014 were included. We compared 3 patient groups: young (<65 years), older (65–75 years), and very old patients (>75 years). Total thyroidectomy was performed with lymph node (LN) dissection in most cases, and radioiodine therapy was administered as needed. A total of 3835 patients (3257 young patients, 450 older patients, and 128 very old patients) were identified. Very old patients were more likely to have advanced (III/IV) tumor, nodes, metastases (TNM) stage, greater tumor size, number of tumors, and extracapsular invasion compared with young and older patients. For the 2289 patients with LN dissection (60%), metastatic LNs were more frequent in the very old group (44%) than in the other groups (34% young and 33% older patients) (P = 0.01). Very old patients had more frequent distant metastases (5%) than the older (2%) and young groups (1%) (P < 0.001). The overall postoperative morbidity was not significantly different between the 3 age groups. Recurrence was documented in 202 (6.2%) young, 29 (6.4%) older, and 15 (11.7%) very old PTC patients (P = 0.04). The 5-year disease-free survival was 81.3% for very old, 92.9% for older, and 94.7% for young group (P < 0.001). Very old patients should be considered high-risk PTC patients and their therapeutic strategy may benefit from aggressive treatment. PMID:27893690

  7. Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma

    PubMed Central

    Lee, Hyekyung; Baek, Tae Hwa; Park, Meeja; Lee, Seung Yun; Son, Hyun Jin; Kang, Dong Wook; Kim, Joo Heon; Kim, Soo Young

    2016-01-01

    Background There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. Methods We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. Results From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. Conclusions Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma. PMID:27550048

  8. The Effect of Levothyroxine Discontinuation Timing on Postoperative Hypothyroidism after Hemithyroidectomy for Papillary Thyroid Microcarcinoma.

    PubMed

    Ha, Tae Kwun; Kim, Dong Wook; Park, Ha Kyoung; Baek, Jin Wook; Lee, Yoo Jin; Park, Young Mi; Kim, Do Hun; Jung, Soo Jin; Ahn, Ki Jung

    2016-01-01

    Objective. No previous studies regarding the appropriate timing of thyroid hormone discontinuation after hemithyroidectomy have been published. This study aimed to identify the appropriate timing for levothyroxine discontinuation after hemithyroidectomy among patients with papillary thyroid microcarcinoma (PTMC). Methods. This study retrospectively evaluated 304 patients who underwent ≥1 attempt to discontinue levothyroxine after hemithyroidectomy for treating PTMC between January 2008 and December 2013. Fifty-three patients were excluded because of preoperative hypothyroidism or hyperthyroidism, a history of thyroid hormone or antithyroid therapy, no available serological data, or a postoperative follow-up of <24 months. We evaluated the associations of successful levothyroxine discontinuation with patient age, sex, preoperative serological data, underlying thyroid gland histopathology, anteroposterior diameter of the residual thyroid gland, number of discontinuation attempts, and initial discontinuation timing. Results. Among the 251 included patients, 125 patients (49.8%) achieved successful levothyroxine discontinuation during the follow-up period after hemithyroidectomy. There was a significant difference in the outcomes for patients who underwent an initial discontinuation attempt at ≤3 months and ≥4 months after hemithyroidectomy (p < 0.001). There were significant differences in the discontinuation outcomes according to underlying thyroid histopathology (p = 0.001), preoperative thyroid-stimulating hormone levels (p < 0.001), and number of discontinuation attempts (p < 0.001). Conclusions. Among patients with PTMC, the initial levothyroxine discontinuation attempt is recommended at ≥4 months after hemithyroidectomy.

  9. Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity.

    PubMed

    Maimaiti, Yusufu; Jie, Tan; Jing, Zhou; Changwen, Wang; Pan, Yu; Chen, Chen; Tao, Huang

    2016-04-22

    Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

  10. Non-invasive diagnosis of papillary thyroid microcarcinoma: a NMR-based metabolomics approach

    PubMed Central

    Lu, Jinghui; Hu, Sanyuan; Miccoli, Paolo; Zeng, Qingdong; Liu, Shaozhuang; Ran, Lin; Hu, Chunxiao

    2016-01-01

    Papillary thyroid microcarcinoma (PTMC) is a subtype of papillary thyroid carcinoma (PTC). Because its diameter is less than 10 mm, diagnosing it accurately is difficult with traditional methods such as image examinations and FNA (Fine Needle Aspiration). Investigating the metabolic changes induced by PTMC may enhance the understanding of its pathogenesis and provide important information for a new diagnosis method and treatment plan. In this study, high resolution magic angle spin (HRMAS) spectroscopy and 1H-nuclear magnetic resonance (1H-NMR) spectroscopy were used to screen metabolic changes in thyroid tissues and plasma from PTMC patients respectively. The results revealed reduced levels of fatty acids and elevated levels of several amino acids (phenylalanine, tyrosine, lactate, serine, cystine, lysine, glutamine/glutamate, taurine, leucine, alanine, isoleucine and valine) in thyroid tissues, as well as reduced levels of amino acids such as valine, tyrosine, proline, lysine, leucine and elevated levels of glucose, mannose, pyruvate and 3-hydroxybutyrate in plasma, are involved in the metabolic alterations in PTMC. In addition, a receiver operating characteristic (ROC) curve model for PTMC prediction was able to classify cases with good sensitivity and specificity using 9 significant changed metabolites in plasma. This work illustrates that the NMR-based metabolomics approach is capable of providing more sensitive diagnostic results and more systematic therapeutic information for PTMC. PMID:27835583

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-03-06

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

  13. Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration

    PubMed Central

    Parascandolo, Alessia; Rappa, Francesca; Cappello, Francesco; Kim, Jaehyup; Cantu, David A.; Chen, Herbert; Mazzoccoli, Gianluigi; Hematti, Peiman; Castellone, Maria Domenica; Salvatore, Marco; Laukkanen, Mikko O.

    2017-01-01

    Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stromal cells (MSCs) in non-carcinogenic thyroids and papillary thyroid cancer (PTC). The phenotypic and differentiation characteristics of Thyroid MSCs and PTC MSCs were comparable with bone marrow MSCs. A molecular level analysis showed increased FIBROBLAST ACTIVATING PROTEIN, COLLAGEN 1 TYPE A1, TENASCIN, and SOD3 expression in PTC MSCs compared to Thyroid MSCs, suggesting the presence of MSCs with a fibrotic fingerprint in papillary thyroid cancer tumors and the autocrine-paracrine conversion of SOD3 expression, which was enhanced by cancer cells. Stromal SOD3 had a stimulatory effect on cancer cell growth and an inhibitory effect on cancer cell migration, thus indicating that SOD3 might be a novel player in thyroid tumor stroma. PMID:28216675

  14. Overexpression of NOTCH-regulated Ankyrin Repeat Protein is associated with papillary thyroid carcinoma progression

    PubMed Central

    Zhang, Mingdi; Qin, Yiyu; Zuo, Bin; Gong, Wei; Zhang, Shenglai; Gong, Yurong; Quan, Zhiwei; Chu, Bingfeng

    2017-01-01

    Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes. Therefore, these results indicate that NRARP is an important clinical biomarker in thyroid carcinoma and it promotes EMT induction as well as the progression of PTCs via NOTCH signaling activation. PMID:28207739

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

    NASA Astrophysics Data System (ADS)

    Kim, Edward; Baloch, Zubair; Kim, Caroline

    2015-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  18. MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors.

    PubMed

    Mancikova, Veronika; Castelblanco, Esmeralda; Pineiro-Yanez, Elena; Perales-Paton, Javier; de Cubas, Aguirre A; Inglada-Perez, Lucia; Matias-Guiu, Xavier; Capel, Ismael; Bella, Maria; Lerma, Enrique; Riesco-Eizaguirre, Garcilaso; Santisteban, Pilar; Maravall, Francisco; Mauricio, Didac; Al-Shahrour, Fatima; Robledo, Mercedes

    2015-06-01

    MicroRNA deregulation could be a crucial event in thyroid carcinogenesis. However, current knowledge is based on studies that have used inherently biased methods. Thus, we aimed to define in an unbiased way a list of deregulated microRNAs in well-differentiated thyroid cancer in order to identify diagnostic and prognostic markers. We performed a microRNA deep-sequencing study using the largest well-differentiated thyroid tumor collection reported to date, comprising 127 molecularly characterized tumors with follicular or papillary patterns of growth and available clinical follow-up data, and 17 normal tissue samples. Furthermore, we integrated microRNA and gene expression data for the same tumors to propose targets for the novel molecules identified. Two main microRNA expression profiles were identified: one common for follicular-pattern tumors, and a second for papillary tumors. Follicular tumors showed a notable overexpression of several members of miR-515 family, and downregulation of the novel microRNA miR-1247. Among papillary tumors, top upregulated microRNAs were miR-146b and the miR-221~222 cluster, while miR-1179 was downregulated. BRAF-positive samples displayed extreme downregulation of miR-7 and -204. The identification of the predicted targets for the novel molecules gave insights into the proliferative potential of the transformed follicular cell. Finally, by integrating clinical follow-up information with microRNA expression, we propose a prediction model for disease relapse based on expression of two miRNAs (miR-192 and let-7a) and several other clinicopathological features. This comprehensive study complements the existing knowledge about deregulated microRNAs in the development of well-differentiated thyroid cancer and identifies novel markers associated with recurrence-free survival.

  19. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: An Evidence-Based Nomenclature Change.

    PubMed

    Jug, Rachel; Jiang, Xiaoyin

    2017-01-01

    A consensus panel recently used clinical evidence and pathologic parameters to rename noninvasive encapsulated follicular variant of papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to better reflect the indolent course of this tumor. NIFTP has stringent histopathologic diagnostic criteria established by the panel, including papillary-like nuclear features, and submission of the entire tumor capsule to exclude invasion. From a molecular standpoint, NIFTP is often characterized by RAS-type mutations, similar to other follicular-patterned lesions. While there has been prior evidence in the literature for the low malignant potential of these tumors, projects moving forward will help to independently reinforce the reliability of these criteria and nomenclature. With planned inclusion of NIFTP into the latest World Health Organization endocrine tumor classification scheme, this nomenclature shift provides a model for pathology efforts to refine diagnostic classifications to better guide treatment. In this review we discuss this nomenclature change and review the current literature.

  20. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: An Evidence-Based Nomenclature Change

    PubMed Central

    2017-01-01

    A consensus panel recently used clinical evidence and pathologic parameters to rename noninvasive encapsulated follicular variant of papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to better reflect the indolent course of this tumor. NIFTP has stringent histopathologic diagnostic criteria established by the panel, including papillary-like nuclear features, and submission of the entire tumor capsule to exclude invasion. From a molecular standpoint, NIFTP is often characterized by RAS-type mutations, similar to other follicular-patterned lesions. While there has been prior evidence in the literature for the low malignant potential of these tumors, projects moving forward will help to independently reinforce the reliability of these criteria and nomenclature. With planned inclusion of NIFTP into the latest World Health Organization endocrine tumor classification scheme, this nomenclature shift provides a model for pathology efforts to refine diagnostic classifications to better guide treatment. In this review we discuss this nomenclature change and review the current literature. PMID:28280647

  1. Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. Report of three cases.

    PubMed

    Chan, J K; Carcangiu, M L; Rosai, J

    1991-03-01

    Three examples of an unusual morphologic variant of papillary thyroid carcinoma (PTC) are reported. The presence of a prominent stromal component resulted in low-power microscopic appearances resembling fibroadenoma, phyllodes tumor, or fibrocystic disease of the breast in two cases. The carcinomatous component grew in the form of anastomosing narrow tubules, clustered glands, solid sheets with or without squamous differentiation, and/or papillae, and exhibited the typical nuclear features of PTC. The abundant stroma had a nodular fasciitis-like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix, collagen, and extravasated red blood cells; this was interpreted as an exuberant mesenchymal reaction to the carcinoma. The importance of recognizing this variant of PTC is that, when one encounters a fibroproliferative lesion of the thyroid, a diligent search should be made for papillary carcinoma. This variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so-called carcinosarcomas.

  2. RET/PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose.

    PubMed

    Hamatani, Kiyohiro; Eguchi, Hidetaka; Ito, Reiko; Mukai, Mayumi; Takahashi, Keiko; Taga, Masataka; Imai, Kazue; Cologne, John; Soda, Midori; Arihiro, Koji; Fujihara, Megumu; Abe, Kuniko; Hayashi, Tomayoshi; Nakashima, Masahiro; Sekine, Ichiro; Yasui, Wataru; Hayashi, Yuzo; Nakachi, Kei

    2008-09-01

    A major early event in papillary thyroid carcinogenesis is constitutive activation of the mitogen-activated protein kinase signaling pathway caused by alterations of a single gene, typically rearrangements of the RET and NTRK1 genes or point mutations in the BRAF and RAS genes. In childhood papillary thyroid cancer, regardless of history of radiation exposure, RET/PTC rearrangements are a major event. Conversely, in adult-onset papillary thyroid cancer among the general population, the most common molecular event is BRAF(V600E) point mutation, not RET/PTC rearrangements. To clarify which gene alteration, chromosome aberration, or point mutation preferentially occurs in radiation-associated adult-onset papillary thyroid cancer, we have performed molecular analyses on RET/PTC rearrangements and BRAF(V600E) mutation in 71 papillary thyroid cancer cases among atomic bomb survivors (including 21 cases not exposed to atomic bomb radiation), in relation to radiation dose as well as time elapsed since atomic bomb radiation exposure. RET/PTC rearrangements showed significantly increased frequency with increased radiation dose (P(trend) = 0.002). In contrast, BRAF(V600E) mutation was less frequent in cases exposed to higher radiation dose (P(trend) < 0.001). Papillary thyroid cancer subjects harboring RET/PTC rearrangements developed this cancer earlier than did cases with BRAF(V600E) mutation (P = 0.03). These findings were confirmed by multivariate logistic regression analysis. These results suggest that RET/PTC rearrangements play an important role in radiation-associated thyroid carcinogenesis.

  3. [Morphological features of papillary thyroid carcinoma with a focal tall-cell component].

    PubMed

    Abrosimov, A Iu; Kozhushnaia, S M

    2012-01-01

    The morphological features of papillary thyroid macro- and microcarcinomas of classical structure with the focal presence or absence of a tall-cell component were comparatively studied. Histological specimens of 55 neoplasms were examined in 53 patients. A trend was seen for the higher rate of regional metastasis in a group of tall-cell tumors. Additional studies of groups of patients matched for sex, age, and extrathyroid tumor extension are required to make a final conclusion on the metastatic potential and prognostic features of tumors with a tall-cell component. To solve this task, it is expedient to separate neoplasms with a focal tall-cell component from the bulk of classical papillary carcinomas.

  4. Ultrasonography and cytology as predictors of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Importance of the differential diagnosis with the invasive encapsulated follicular variant of papillary thyroid cancer.

    PubMed

    Rosario, Pedro Weslley

    2017-03-02

    The noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has an excellent prognosis even if treated only by lobectomy.(1-3) Recently, it was proposed that this tumor should no longer be considered "cancer" and be given the denomination "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP).(2) There is great interest in knowing the preoperative characteristics of NIFTP since, in view of a high probability of this diagnosis (higher than that of malignancy), less extensive surgery would be more indicated. This article is protected by copyright. All rights reserved.

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

    PubMed Central

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

    2016-01-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis. PMID:27616592

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  7. Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

    PubMed Central

    Caria, Paola; Cantara, Silvia; Frau, Daniela Virginia; Pacini, Furio; Vanni, Roberta; Dettori, Tinuccia

    2016-01-01

    Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of HER2 (Human Epidermal Growth Factor Receptor 2) amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL and BRAF mutational status. We analyzed HER2 gene amplification and the integrity of ALK, ETV6, RET, and BRAF genes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzed BRAFV600E mutation and RTL by qRT-PCR. Significant HER2 amplification (p = 0.0076), which was restricted to scattered groups of cells, was found in fPTC samples. HER2 amplification in fPTCs was invariably associated with BRAFV600E mutation. RTL was shorter in fPTCs than sPTCs (p < 0.001). No rearrangements of other tested genes were observed. These findings suggest that the association of HER2 amplification with BRAFV600E mutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy. PMID:27775641

  8. Correlation between Ultrasound Elastography and Histologic Characteristics of Papillary Thyroid Carcinoma

    PubMed Central

    Yi, Li; Qiong, Wu; Yan, Wang; Youben, Fan; Bing, Hu

    2017-01-01

    The aim of this study was to investigate the correlation between elastography and histologic characteristics including fibrosis and calcification. We also wanted to investigate whether other clinicopathologic indexes influence the strain ratio (SR) of papillary thyroid carcinomas (PTCs). We retrospectively reviewed 126 papillary thyroid carcinomas (PTCs) from 103 patients who underwent ultrasonography and elastography before surgery. The histologic characteristics and clinicopathologic indexes were compared with the SR of ultrasound elastography (UE). The results showed that there was a significantly positive correlation between fibrosis degree and SR measurements (r = 0.754, p = 0.000); the SR was significantly different between the groups with and without calcification (11.34 ± 10.08 vs. 6.81 ± 7.33, p = 0.000). The standard coefficients of collagen and stromal calcification were 0.684 and 0.194, respectively. There was no significant correlation between SR and indices such as size, position, co-existence with Hashimoto’s thyroiditis (HT), multifocality or cervical lymph node (CLN) metastasis. In conclusion, we found that the SR of UE is positively correlated with the fibrosis of PTC. Stromal calcification will elevate the SR dramatically, but psammoma bodies will not when they exist in the absence of stromal calcification. PMID:28327620

  9. Curcumin inhibits hypoxia-induced migration in K1 papillary thyroid cancer cells

    PubMed Central

    Tan, Cheng; Zhang, Li; Cheng, Xian; Lin, Xiu-Feng; Lu, Rong-Rong; Bao, Jian-Dong

    2014-01-01

    Curcumin, traditionally used as food and medicinal purposes, has recently been reported to have protective efficacy against hypoxia. Hypoxia is one of the important reactive factors in tumor metastasis, which is a key problem in clinical thyroid cancer therapy. In present study, we investigate the anti-metastatic effect of curcumin on the K1 papillary thyroid cancer cells as well as its potential mechanisms. The results show that curcumin effectively inhibits hypoxia-induced reactive oxygen species (ROS) upregulation and significantly decreases the mRNA and protein expression levels of hypoxia-inducible factor-1α (HIF-1α) in K1 cells. Curcumin also decreases the DNA binding ability of HIF-1α to hypoxia response element (HRE). Furthermore, curcumin enhances E-cadherin expression, inhibits metalloproteinase-9 (MMP-9) enzyme activity, and weakens K1 cells migration under hypoxic conditions. In summary, these results indicate that curcumin possesses a potent anti-metastatic effect and might be an effective tumoristatic agent for the treatment of aggressive papillary thyroid cancers. PMID:25349216

  10. Radioactive Iodine Therapy Decreases Recurrence in Thyroid Papillary Microcarcinoma

    PubMed Central

    Creach, Kimberly M.; Siegel, Barry A.; Nussenbaum, Brian; Grigsby, Perry W.

    2012-01-01

    Background. The most appropriate therapy for papillary microcarcinoma (PMC) is controversial. Methods. We reviewed the therapy and outcome of 407 patients with PMC. Results. Three hundred-eighty patients underwent total thyroidectomy, and 349 patients received I-131 therapy. The median followup was 5.3 years. Forty patients developed recurrent disease. On univariate analysis, development of disease recurrence was correlated with histological tumor size > 0.8 cm (P = 0.0104), age < 45 years (P = 0.043), and no I-131 therapy (P < 0.0001). On multivariate analysis, histological tumor size > 0.8 cm, positive lymph nodes, and no I-131 therapy were significant. The 5-year RFS for patients treated with I-131 was 95.0% versus 78.6% (P < 0.0001) for patients not treated with I-131. Patients with lymph node metastasis who did not receive I-131 had a 5-year RFS of 42.9% versus 93.2% (P < 0.0001) for patients who received I-131. Conclusions. Recommend I-131 remnant ablation for patients with PMC, particularly patients with lymph node metastasis. PMID:22462017

  11. Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects

    PubMed Central

    Accordi, Elen Dias; Xekouki, Paraskevi; Azevedo, Bruna; de Alexandre, Rodrigo Bertollo; Frasson, Carla; Gantzel, Siliane Marie; Papadakis, Georgios Z.; Angelousi, Anna; Stratakis, Constantine A.; Sotomaior, Vanessa Santos; Faucz, Fabio R.

    2016-01-01

    Background Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA, SDHB, SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA, SDHB, SDHC, and SDHD genes and familiar PTC in a large Brazilian family. Method Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing. Results Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST. Conclusion Familiar PTC and a GIST were not associated with SDHx mutations; additional genetic defects, yet unknown, may be responsible for the development of tumor. PMID:27493882

  12. Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis.

    PubMed

    Chitikova, Zhanna; Pusztaszeri, Marc; Makhlouf, Anne-Marie; Berczy, Margaret; Delucinge-Vivier, Celine; Triponez, Frederic; Meyer, Patrick; Philippe, Jacques; Dibner, Charna

    2015-05-10

    We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-frozen and FFPE samples. NanoString analysis of 51 transcripts in 17 PTC and 17 benign nodule samples obtained from different donors and in 24 pairs of benign and PTC nodules, obtained from the same donor (multinodular goiters), confirmed significant alterations in the levels of BMAL1, c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was established for each sample, based on the combined expression levels of BMAL1, CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this predictive score closely correlated with the clinicopathological characteristics of the analyzed thyroid nodules. Our study identified new thyroid transcripts with altered levels in PTC using the NanoString approach. A predictive score correlation coefficient might contribute to improve the preoperative diagnosis of thyroid nodules.

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

    PubMed Central

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

    2016-01-01

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

  14. Increased Expression of Phosphatidylcholine (16:0/18:1) and (16:0/18:2) in Thyroid Papillary Cancer

    PubMed Central

    Ishikawa, Seiji; Tateya, Ichiro; Hayasaka, Takahiro; Masaki, Noritaka; Takizawa, Yoshinori; Ohno, Satoshi; Kojima, Tsuyoshi; Kitani, Yoshiharu; Kitamura, Morimasa; Hirano, Shigeru; Setou, Mitsutoshi; Ito, Juichi

    2012-01-01

    A good prognosis can be expected for most, but not all, cases of thyroid papillary cancer. Numerous molecular studies have demonstrated beneficial treatment and prognostic factors in various molecular markers. Whereas most previous reports have focused on genomics and proteomics, few have focused on lipidomics. With the advent of mass spectrometry (MS), it has become possible to identify many types of molecules, and this analytical tool has become critical in the field of omics. Recently, imaging mass spectrometry (IMS) was developed. After a simple pretreatment process, IMS can be used to examine tissue sections on glass slides with location information. Here, we conducted an IMS analysis of seven cases of thyroid papillary cancer by comparison of cancerous with normal tissues, focusing on the distribution of phospholipids. We identified that phosphatidylcholine (16:0/18:1) and (16:0/18:2) and sphingomyelin (d18:0/16:1) are significantly higher in thyroid papillary cancer than in normal thyroid tissue as determined by tandem mass (MS/MS) analysis. These distributional differences may be associated with the biological behavior of thyroid papillary cancer. PMID:23139822

  15. Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2015-09-28

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

  16. Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells

    PubMed Central

    Paliouras, Miltiadis; Mitmaker, Elliot J.; Trifiro, Mark A.

    2016-01-01

    Background The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. Methods Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. Results TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. Conclusion A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam

  17. Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis.

    PubMed

    Chui, Michael Herman; Cassol, Clarissa A; Asa, Sylvia L; Mete, Ozgur

    2013-05-01

    In chronic lymphocytic thyroiditis (CLT), the follicular epithelial cells display cytological atypia resembling papillary thyroid carcinoma (PTC), and epidemiological studies have suggested an increased risk of PTC in patients with this condition. While reactive atypia is observed diffusely in CLT-affected thyroid parenchyma, it is not unusual to find microscopic foci morphologically distinct from the surrounding parenchyma, exhibiting more pronounced cytological and architectural atypia. These small atypical lesions, which we term "follicular epithelial dysplasia" (FED), are particularly prominent in cases of severe CLT, yet lack invasive growth, papillary architecture, or intranuclear pseudoinclusions. To gain further insight into their biological significance, we constructed a tissue microarray of 70 cases of CLT, comprised of morphologically normal thyroid, thyroid with reactive atypia, FED, follicular nodular disease (nodular hyperplasia or follicular adenoma), and PTC. Immunohistochemical staining was performed for a marker panel including PTC (HBME-1, cytokeratin 19, galectin-3, and cyclin-D1) as well as TTF-1, thyroglobulin, and p63. Slides were digitally scanned and immunohistochemical staining evaluated using automated image analysis software. FED lesions were positive for TTF-1 and thyroglobulin (50/50, 100 %), though some (13/50, 26 %) also expressed p63. Similar to PTC, strong diffuse staining was observed for HBME-1 (43/50, 86 %), cytokeratin 19 (48/50, 96 %), galectin-3 (20/50, 40 %) and cyclin-D1 (38/50, 76 %). In contrast, normal thyroid, reactive atypia, and follicular nodular disease were negative, or at most, exhibited focal weak staining for HBME-1, cytokeratin 19, and galectin-3. The results of this study demonstrate the presence of atypical microscopic lesions in CLT with an immunohistochemical profile similar to PTC, supporting the concept of a premalignant lesion preceding PTC, arising in the context of severe chronic inflammation.

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

    PubMed Central

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

    2016-01-01

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

  19. Brain metastases with exceptional features from papillary thyroid carcinoma: report of three cases.

    PubMed

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

    2011-01-01

    We present three papillary thyroid carcinoma PTC patients with brain metastases who are unusual in many aspects. The first case is a unique 3mm papillary thyroid microcarcinoma (PTMC) patient with metastases to the cerebrum and lung. The solitary cerebral lesion was identified by iodine-131 whole- body scan ((131)I-WBS) and (131)I single photon emission tomography/computed tomography (SPET/CT). Almost complete response achieved after radiosurgery. The second case is a unique PTC patient with coexistent (131)I-negative cerebrum, adrenal gland and ilium metastases, which were identified by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI). Partial response achieved after radiosurgery. The third case is a patient with an incident solitary cystic cerebellar mass as a primary presentation of follicular variant of PTC and absent other distant metastases. In conclusion, widespread metastases from small PTMC may occur. Concomitant brain and adrenal metastases may occur in a same PTC patient. Brain metastasis may present as a cystic lesion.

  20. Down-regulation of miR-181b promotes apoptosis by targeting CYLD in thyroid papillary cancer.

    PubMed

    Li, Dengfeng; Jian, Wei; Wei, Chuankui; Song, Hongming; Gu, Yifan; Luo, Yi; Fang, Lin

    2014-01-01

    MicroRNAs (miRNAs) are a small class of non-coding RNAs that are widely deregulated in various cancers. They act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to examine the potential role of miR-181b in human thyroid papillary cancer. The expression levels of different miRNAs were measured by micro array analysis in 10 thyroid papillary cancer specimens and adjacent normal thyroid cancer tissues. MTT assays, colony formation assays, apoptosis assays were used to explore the potential function of miR-181b inhibitor in TPC1 human thyroid papillary cancer cells. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-181b, in corroboration with qPCR and western blot assays. We found that the expression of miR-181b was higher in thyroid papillary cancer specimens compared with adjacent normal tissues (P < 0.05). Downregulation of miR-181b inhibited cellular growth and promoted cellular apoptosis. Luciferase assays indicated that miR-181b can bind with its putative target site in the 3'-untranslated region (3'-UTR) of CYLD, suggesting that CYLD is a direct target of miR-181b. Western blot analysis indicated that downregulation of miR-181b results in the upregulation of CYLD at protein levels. Taken together, downregulation of miR-181b expression causes cellular growth inhibition, promoting cellular apoptosis by targeting CYLD. These findings suggest that downregulation of the expression of miR-181b may be a therapeutic target for the treatment of human thyroid papillary cancer.

  1. rs965513 polymorphism as a common risk marker is associated with papillary thyroid cancer

    PubMed Central

    Han, Jun; Chen, Meijun; Qiao, Hong; Zhang, Shaojun

    2016-01-01

    Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. With the rapid development of genome-wide association studies (GWAS), many genome variants associated with susceptibility to PTC have been identified, including the single nucleotide polymorphism rs965513 (9q22.33) near FOXE1. To evaluate the association between rs965513 and PTC in different ethnicities and countries, we conducted a meta-analysis using relatively large-scale samples from 23 studies (N = 163,136; 20,736 cases and 142,400 controls) by searching the PubMed and Google Scholar databases. Significant heterogeneity caused by different populations among the selected studies was observed. The A allele of rs965513 polymorphism was shown to be highly associated with risk of thyroid cancer, with odds ratios of 1.58 (95% CI 1.32–1.90) in all populations, 1.65 (95% CI 1.31–2.07)) in Caucasian populations and 1.49 in Asian populations. Compared to the dominant and recessive models, we observed the highest odds ratio (OR = 2.80, 95% CI 2.12–3.69) in the homozygous model. These results revealed that the rs965513 polymorphism is a risk factor for thyroid cancer PMID:27191655

  2. Aggressive Disease Course of Papillary Thyroid Carcinoma with Focal Undifferentiated Component: A Case Report.

    PubMed

    Riaz, Saima; Bashir, Humayun; Hassan, Aamna; Mushtaq, Sajid; Jamshed, Arif; Murtaza, Ahmad

    2016-10-05

    We report an aggressive papillary thyroid carcinoma (PTC) with focal undifferentiated component in a 32-year-old female. She had limited disease confined within the thyroid gland at diagnosis. Within 12 months of thyroidectomy and radioiodine ablation, thyroglobulin (Tg) levels were elevated. Second radioiodine ablative dose was given, however, stimulated Tg levels showed an upward trend with negative iodine scan within 12 months. An 18F fludeoxyglucose-avid solitary pulmonary nodule that was detected on positron emission tomography/computed tomography scan was resected followed by empiric radioiodine therapy. Within the next 10 months she developed multifocal bone metastases. The multifocal disease was rendered inoperable and treated with external beam radiation. The patient is on follow-up, and the Tg level continues to rise with local disease progression. In a small percentage of patients, PTC behaves as a very aggressive disease despite treatment. Focally undifferentiated thyroid carcinoma is an expression of the extreme end of the spectrum of differentiated thyroid carcinoma.

  3. Aggressive Disease Course of Papillary Thyroid Carcinoma with Focal Undifferentiated Component: A Case Report

    PubMed Central

    Riaz, Saima; Bashir, Humayun; Hassan, Aamna; Mushtaq, Sajid; Jamshed, Arif; Murtaza, Ahmad

    2016-01-01

    We report an aggressive papillary thyroid carcinoma (PTC) with focal undifferentiated component in a 32-year-old female. She had limited disease confined within the thyroid gland at diagnosis. Within 12 months of thyroidectomy and radioiodine ablation, thyroglobulin (Tg) levels were elevated. Second radioiodine ablative dose was given, however, stimulated Tg levels showed an upward trend with negative iodine scan within 12 months. An 18F fludeoxyglucose-avid solitary pulmonary nodule that was detected on positron emission tomography/computed tomography scan was resected followed by empiric radioiodine therapy. Within the next 10 months she developed multifocal bone metastases. The multifocal disease was rendered inoperable and treated with external beam radiation. The patient is on follow-up, and the Tg level continues to rise with local disease progression. In a small percentage of patients, PTC behaves as a very aggressive disease despite treatment. Focally undifferentiated thyroid carcinoma is an expression of the extreme end of the spectrum of differentiated thyroid carcinoma. PMID:27751976

  4. Interactive role of miR-126 on VEGF-A and progression of papillary and undifferentiated thyroid carcinoma.

    PubMed

    Salajegheh, Ali; Vosgha, Haleh; Rahman, Md Atiqur; Amin, Moein; Smith, Robert Anthony; Lam, Alfred King-Yin

    2016-05-01

    MicroRNA-126 (miR-126) expression has been shown to be associated with angiogenesis. The aim of the current study is to evaluate the functional roles of miR-126 in dysregulation of VEGF expression and cancer progression in thyroid carcinomas. The expression of VEGF-A and miR-126 were measured in 101 thyroid carcinomas tissues (including 51 conventional papillary thyroid carcinoma, 37 follicular variant of papillary thyroid carcinoma, and 13 undifferentiated thyroid carcinomas), 13 matched lymph nodes with metastatic thyroid carcinoma, 21 benign thyroid tissues, and 5 thyroid carcinoma cell lines (both papillary and undifferentiated carcinomas). Then, exogenous miR-126 was transfected, and the expressions of VEGF-A were determined (Western blot technique). Proliferation assay, cell cycle analysis, and apoptosis assays were used to evaluate the role of miR-126 in these events. Significant underexpression of miR-126 levels in thyroid cancer tissues and cell lines was detected using real-time polymerase chain reaction. Introducing exogenous miR-126 into the cancer cell lines resulted in a significant reduction of VEGF-A protein expression. Marked inhibition in proliferation, cell cycle arrest in G0-G1, and promotion of total apoptosis were also noted. The modulatory role of miR-126 on expression of VEGF-A and its tumor suppressive roles were demonstrated for the first time in thyroid cancer. The current experiments provided specific information on the functional consequences of VEGF manipulation via microRNA on cancer.

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

    PubMed

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

    2014-12-01

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

  6. Papillary thyroid carcinoma involving cervical neck lymph nodes: correlations with lymphangiogenesis and ultrasound features.

    PubMed

    Choi, Yoonjung; Park, Kyung Joo; Ryu, Seungho; Kim, Dong-Hoon; Yun, Jisup; Kang, Doo Kyoung; Chun, Mison

    2012-01-01

    Stratification of risk factors for cervical lymph node metastasis (LNM) in thyroid papillary carcinoma is important for providing standards for post-operative adjuvant radio-iodine therapy and for patient prognosis. We investigated pathological factors based on the lymphatic vessel system and radiological features associated with tumor with cervical neck LNM. Among patients who had undergone thyroidectomy confirmed to be papillary thyroid carcinoma, we selected 126 age-sex matched paired patients without cervical LNM (group 1) and with LNM (group 2) to evaluate risk factors. Pathological factors evaluated were size, multiplicity, and extra thyroid extension state, based on the pathological reports using stored data. The lymphatic vessel density (LVD) of each tumor was evaluated by staining for VEGFR-3 and D2-40 and correlated with cervical LNM state. Malignant ultrasound features were evaluated to compare the differences between these two groups. Larger tumor size, multiplicity, extrathyroid extension were more common in group 2 (p<0.05). The median percentage of VEGFR-3 for group 1 was 20 (range 0-30) and D2-40 was 13 (range 7-23) while for group 2, VEGFR-3 was 80 (70-90) and D2-40 was 78 (54-114). LVD measured by intratumoral D2-40 staining was 20.6% and 79.4% for group 1 and group 2, respectively. Intra-tumoral lymphatics measured by D2-40 stain had a strong correlation with cervical LNM (Odds 1.230, CI 1.01.-1.499 p value 0.040). Ultrasound (US) features had no significant differences between the two groups although calcifications tended to be higher in group 2 (84% vs. 76% p=0.264). Lymphatic vessel density and nodule echogenicity were not associated with LNM. Intratumoral lymphangiogenesis was most strongly associated with LNM and thus, could be a useful predictive marker for cervical LNM.

  7. Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features.

    PubMed

    Cho, Uiju; Mete, Ozgur; Kim, Min-Hee; Bae, Ja Seong; Jung, Chan Kwon

    2017-03-10

    Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features'. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae. Of a total of 6,269 papillary thyroid carcinomas, 152 tumors fulfilled the criteria for encapsulated follicular variant. The results were stratified according to two different diagnostic cutoff criteria with respect to the extent of papillae. When the cutoff of 1% papillae was used, the rates of lymph node metastasis and BRAF(V600E) mutation were 3% and 10% in non-invasive tumors and 9% and 4% in invasive tumors, respectively. Despite the lack of invasive growth, one patient with BRAF(V600E) mutant-tumor displaying predominant follicular growth and subtle papillae developed a bone metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAF(V600E) mutation was found in all tumors. However, central lymph node micrometastasis still occurred in 3% of non-invasive tumors. Non-V600E BRAF and RAS mutations were detected in 4% and 47% of non-invasive tumors, respectively. Our findings suggest that non-invasive follicular thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign thyroid neoplasm as it can present with lymph node micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk thyroid cancers. Clinical surveillance similar to

  8. Cystic thyroid mass following I-131 treatment of papillary thyroid carcinoma: An unusual complication

    SciTech Connect

    Morrish, D.W.; Jackson, F.I.; Lalani, Z.H.; Catz, Z.; Sloboda, R. )

    1989-12-01

    Several unusual complications of I-131 therapy for thyroid carcinoma are known. Two patients who developed a further unusual event that consisted of a palpable mass and cystic degeneration are described.

  9. Associations between body mass index and lymph node metastases of patients with papillary thyroid cancer

    PubMed Central

    Wu, Changhua; Wang, Liang; Chen, Wanjun; Zou, Shujuan; Yang, Aiju

    2017-01-01

    Abstract Epidemiological studies suggest that obesity is a risk of thyroid cancer, especially papillary thyroid cancer (PTC). However, the associations of obesity and clinic–pathological features, especially the association of body mass index (BMI) and lymph node metastasis of thyroid cancer are unclear. Seven hundred ninety-six primary patients with PTC were enrolled in this retrospective cohort study. The relationships between BMI and clinic-pathological features of PTC were evaluated by logistic regression models based on the 5-point increase in BMI and BMI quartiles (underweight, normal weight, overweight, and obesity). The 5-point increase in BMI was strongly associated with extra-thyroidal invasion [odds ratio (OR) 2.201, P < 0.001], primary tumor size larger than 1 cm (OR 1.267, P = 0.027), advanced tumor node metastasis (TNM) staging (OR 1.479, P = 0.004), and multifocality (OR 1.31, P = 0.01) in multivariable-adjusted models. The relationships between BMI and lymph node metastasis of PTC were evaluated by Mann–Whitney U test. The mean number of positive central lymph nodes and lateral nodes were increased with the increase of BMI when BMI ≥18.5 kg/m2. It was not shown in underweight group. The present study found that increased BMI was associated with the lymph node metastases (LNMs) of patients with PTC, and other invasive features, including large tumor size, extra-thyroidal invasion, advanced TNM staging, and multifocality. Further studies with long-term follow-up are needed to confirm this finding. PMID:28248875

  10. TERT Promoter Mutation in an Aggressive Cribriform Morular Variant of Papillary Thyroid Carcinoma.

    PubMed

    Oh, Eun Ji; Lee, Sohee; Bae, Ja Seong; Kim, Yourha; Jeon, Sora; Jung, Chan Kwon

    2017-03-01

    The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare thyroid neoplasm characterized by unique morphologic findings and association with familial adenomatous polyposis. The biologic behavior of this variant has been reported to behave similarly to classic PTC. We report a rare sporadic case of CMV-PTC occurring in a 45-year-old female with multiple lymph nodes and bone metastases, which were detected after total thyroidectomy and radioactive iodine remnant ablation. Molecular analyses of primary thyroid and metastatic tumor tissues revealed a telomerase reverse transcriptase (TERT) promoter mutation, but absence of BRAF, KRAS, NRAS, HRAS, and PIK3CA mutations. Over a 4-year follow-up period, structurally identifiable bone metastases were persistent, but serial post-operative serum thyroglobulin levels remained undetectable in the absence of thyroglobulin antibody. The literature was reviewed. This is the first case of aggressive CMV-PTC showing TERT promoter mutation. TERT promoter mutations may help in predicting aggressive clinical behavior in CMV-PTC. Postoperative serum thyroglobulin measurement may have no impact on clinical decision-making in this type of tumor.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells.

    PubMed

    Xu, Jimin; Capezzone, Marco; Xu, Xiao; Hershman, Jerome M

    2005-02-01

    We previously demonstrated that the human nicotinamide N-methytransferase (NNMT) gene was highly expressed in many papillary thyroid cancers and cell lines. The expression in other papillary and follicular cancers or cell lines and normal thyroid cells was low or undetectable. To gain an understanding of the molecular mechanism of this cell-specific expression, the NNMT promoter was cloned and studied by luciferase reporter gene assay. The promoter construct was expressed highly in papillary cancer cell lines, including those with higher (e.g. BHP 2-7) and lower (e.g. BHP 14-9) NNMT gene expression, and expressed weakly in follicular thyroid cancer cell lines. Further study with 5'-deletion promoter construct suggested that the NNMT promoter was regulated differently in BHP 2-7 and BHP 14-9 cells. In BHP 2-7 cells, promoter activity was dependent on an upstream sequence. In BHP 14-9 cells, sequence in the basal promoter region contributed notably to the overall promoter activity. RT-PCR or Western blot analysis indicated that hepatocyte nuclear factor-1beta (HNF-1beta) was expressed in only papillary cancer cell lines with high NNMT gene expression. HNF-1beta was not expressed or expressed very weakly in other papillary, follicular, and Hurthle cancer cell lines and primary cultures of normal thyroid cells and benign thyroid conditions. A HNF-1 binding site was identified in the NNMT basal promoter region. Mutations in this site decreased NNMT promoter activity in the HNF-1beta-positive BHP 2-7 cells, but not in the HNF-1beta-negative BHP 14-9 cells. HNF-1beta bound to the HNF-1 site specifically as a homodimer as determined by gel retardation assays with HNF-1beta-specific antibody. Cotransfection of a HNF-1beta expression plasmid increased NNMT promoter activity significantly in both HNF-1beta-positive and -negative thyroid cancer cell lines and Hep G2 liver cancer cells. Furthermore, transient expression of HNF-1beta in BHP 14-9 cells increased endogenous NNMT

  14. Thyroid cancer

    MedlinePlus

    ... a family history of thyroid cancer and chronic goiter (enlarged thyroid). There are several types of thyroid ... Read More Anaplastic thyroid cancer Breathing difficulty Cancer Goiter - simple Metastasis Radiation therapy Thyroid cancer - papillary carcinoma ...

  15. DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells.

    PubMed

    Degl'Innocenti, Debora; Romeo, Paola; Tarantino, Eva; Sensi, Marialuisa; Cassinelli, Giuliana; Catalano, Veronica; Lanzi, Cinzia; Perrone, Federica; Pilotti, Silvana; Seregni, Ettore; Pierotti, Marco A; Greco, Angela; Borrello, Maria Grazia

    2013-02-01

    Thyroid carcinomas derived from follicular cells comprise papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC) and undifferentiated anaplastic thyroid carcinoma (ATC). PTC, the most frequent thyroid carcinoma histotype, is associated with gene rearrangements that generate RET/PTC and TRK oncogenes and with BRAF-V600E and RAS gene mutations. These last two genetic lesions are also present in a fraction of PDTCs. The ERK1/2 pathway, downstream of the known oncogenes activated in PTC, has a central role in thyroid carcinogenesis. In this study, we demonstrate that the BRAF-V600E, RET/PTC, and TRK oncogenes upregulate the ERK1/2 pathway's attenuator cytoplasmic dual-phase phosphatase DUSP6/MKP3 in thyroid cells. We also show DUSP6 overexpression at the mRNA and protein levels in all the analysed PTC cell lines. Furthermore, DUSP6 mRNA was significantly higher in PTC and PDTC in comparison with normal thyroid tissues both in expression profile datasets and in patients' surgical samples analysed by real-time RT-PCR. Immunohistochemical and western blot analyses showed that DUSP6 was also overexpressed at the protein level in most PTC and PDTC surgical samples tested, but not in ATC, and revealed a positive correlation trend with ERK1/2 pathway activation. Finally, DUSP6 silencing reduced the neoplastic properties of four PTC cell lines, thus suggesting that DUSP6 may have a pro-tumorigenic role in thyroid carcinogenesis.

  16. miR-101 inhibits cell proliferation by targeting Rac1 in papillary thyroid carcinoma

    PubMed Central

    LIN, XIAOJIE; GUAN, HONGYU; LI, HAI; LIU, LIEHUA; LIU, JUAN; WEI, GUOHONG; HUANG, ZHIMIN; LIAO, ZHIHONG; LI, YANBING

    2014-01-01

    Accumulating evidence suggests that some microRNAs (miRNAs) are involved in papillary thyroid carcinoma (PTC) progression. However, it remains necessary to elucidate the underlying molecular mechanisms involved. In the present study, we investigated the role of microRNA-101 (miR-101) in PTC via targeting of Ras-related C3 botulinum toxin substrate 1 (Rac1). The results showed that miR-101 was significantly downregulated in PTC tissues compared with adjacent normal tissues. Restoration of miR-101 expression significantly inhibited cell proliferation in the K1 PTC cell line. Moreover, algorithm-based and experimental strategies verified Rac1 as a direct target of miR-101 in the K1 cell line. Taken together, these findings suggest that miR-101 inhibited PTC growth via the downregulation of Rac1 expression, providing a better understanding of miRNA-modulated signaling networks for future cancer therapeutics. PMID:24649082

  17. Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers

    PubMed Central

    Jee, Hyeon-Gun; Kim, Byoung-Ae; Cho, Hyesun; Song, Young Shin; Cho, Sun Wook; Shin, Jong-Yeon; Kim, Jong-Il; Lee, Kyu Eun; Seo, Jeong-Sun

    2016-01-01

    Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8–PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non–BRAF–Non–RAS (NBNR), as well as BRAF–like and RAS–like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8–PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease. PMID:27494611

  18. The role of external beam radiotherapy in the treatment of papillary thyroid cancer.

    PubMed

    Lee, Nancy; Tuttle, Michael

    2006-12-01

    The role of external beam radiotherapy (EBRT) in treating thyroid cancer has brought forth controversy. Due to various histologic presentations and different natural histories, there is no uniform approach/recommendation among centers and/or authorities regarding the role of EBRT for thyroid cancer. This is particularly true for papillary thyroid carcinoma (PTC) where the clinical course can range from a disease that is cured with simple surgery to an aggressive form of poorly differentiated thyroid cancer with high rates of recurrence/death from disease. In addition, because the majority of the patients with PTC undergo postoperative radioactive iodine (RAI) treatment, the question remains as to what is the exact role of EBRT for PTC in the setting of RAI treatment? In this issue of Endocrine-Related Cancer, Chow and colleagues identified indications for EBRT and RAI therapy for PTC based on a retrospective review of 1300 patients. The authors concluded that postoperative RAI treatment is indicated in patients with pT2-pT4, pN0-pN1b while postoperative EBRT is recommended for patients with gross residual, positive margin, pT4, pN1b, and lymph nodes>2 cm disease. Other centers have also published their experience on the value of EBRT for PTC but with different indications. The reasons for the variations from different centers are complex. However, when all published results are taken together, the findings confirm the added value of EBRT to the present management of PTC in a select group of patients, particularly those with high risk features. In this commentary, these issues will be discussed and recommendations regarding the role of EBRT will be given.

  19. 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

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

    PubMed

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

    2015-01-01

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

  1. 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

  2. American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

    PubMed

    Haugen, Bryan R; Sawka, Anna M; Alexander, Erik K; Bible, Keith C; Caturegli, Patrizio; Doherty, Gerard M; Mandel, Susan J; Morris, John C; Nassar, Aziza; Pacini, Furio; Schlumberger, Martin; Schuff, Kathryn; Sherman, Steven I; Somerset, Hilary; Sosa, Julie Ann; Steward, David L; Wartofsky, Leonard; Williams, Michelle D

    2017-04-01

    American Thyroid Association (ATA) leadership asked the ATA Thyroid Nodules and Differentiated Thyroid Cancer Guidelines Task Force to review, comment on, and make recommendations related to the suggested new classification of encapsulated follicular variant papillary thyroid carcinoma (eFVPTC) without capsular or vascular invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The task force consists of members from the 2015 guidelines task force with the recusal of three members who were authors on the paper under review. Four pathologists and one endocrinologist were added for this specific review. The manuscript proposing the new classification and related literature were assessed. It is recommended that the histopathologic nomenclature for eFVPTC without invasion be reclassified as a NIFTP, given the excellent prognosis of this neoplastic variant. This is a weak recommendation based on moderate-quality evidence. It is also noted that prospective studies are needed to validate the observed patient outcomes (and test performance in predicting thyroid cancer outcomes), as well as implications on patients' psychosocial health and economics.

  3. MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer

    PubMed Central

    Chou, Chen-Kai; Liu, Rue-Tsuan; Kang, Hong-Yo

    2017-01-01

    Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies. PMID:28294980

  4. MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma

    NASA Astrophysics Data System (ADS)

    Huang, Chen-Tsung; Oyang, Yen-Jen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2014-09-01

    Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA-target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.

  5. CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma.

    PubMed

    Zhang, Sijia; Wang, Yihan; Chen, Meijun; Sun, Lulu; Han, Jun; Elena, V Kazakova; Qiao, Hong

    2017-03-08

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence rate is rapidly growing. It is necessary to understand the pathogenesis of PTC to develop effective diagnosis methods. Promoter methylation has been recognized to contribute to the alterations in gene expression observed in tumorigenesis. Our RNA-seq data identified 1191 differentially expressed mRNAs and 147 differentially expressed lncRNAs in PTC. Next, promoter methylation of these genes was detected by reduced representation bisulfite sequencing (RRBS) technology and comprehensively analyzed to identify differential methylation. In total, 14 genes (13 mRNAs and 1 lncRNA), in which methylation was intimately involved in regulating gene expression, were proposed as novel diagnostic biomarkers. To gain insights into the relationships among these 14 genes, a core co-function network was constructed based on co-expression, co-function and co-methylation data. Notably, CXCL12 was identified as an essential gene in the network that was closely connected with the other genes. These data suggested that CXCL12 down-regulation in PTC may be caused by promoter hypermethylation. Our study was the first to perform an RRBS analysis for PTC and suggested that CXCL12 may contribute to PTC development by methylation-mediated epigenetic regulation of gene expression.

  6. CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma

    PubMed Central

    Zhang, Sijia; Wang, Yihan; Chen, Meijun; Sun, Lulu; Han, Jun; Elena, V. Kazakova; Qiao, Hong

    2017-01-01

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence rate is rapidly growing. It is necessary to understand the pathogenesis of PTC to develop effective diagnosis methods. Promoter methylation has been recognized to contribute to the alterations in gene expression observed in tumorigenesis. Our RNA-seq data identified 1191 differentially expressed mRNAs and 147 differentially expressed lncRNAs in PTC. Next, promoter methylation of these genes was detected by reduced representation bisulfite sequencing (RRBS) technology and comprehensively analyzed to identify differential methylation. In total, 14 genes (13 mRNAs and 1 lncRNA), in which methylation was intimately involved in regulating gene expression, were proposed as novel diagnostic biomarkers. To gain insights into the relationships among these 14 genes, a core co-function network was constructed based on co-expression, co-function and co-methylation data. Notably, CXCL12 was identified as an essential gene in the network that was closely connected with the other genes. These data suggested that CXCL12 down-regulation in PTC may be caused by promoter hypermethylation. Our study was the first to perform an RRBS analysis for PTC and suggested that CXCL12 may contribute to PTC development by methylation-mediated epigenetic regulation of gene expression. PMID:28272462

  7. BRAF-activated LncRNA functions as a tumor suppressor in papillary thyroid cancer

    PubMed Central

    Guo, Kai; Ma, Ben; Cao, Yi-Ming; Xiang, Jun; Lu, Zhong-Wu; Zhu, Yong-Xue; Li, Duan-Shu; Ji, Qing-Hai

    2017-01-01

    Long non-coding RNAs (lncRNAs) participate in cancer cell tumorigenesis, cell cycle control, migration, proliferation, apoptosis, metastasis and drug resistance. The BRAF-activated non-coding RNA (BANCR) functions as both an oncogene and a tumor suppressor. Here, we investigated BANCR's role in papillary thyroid carcinoma (PTC) by assessing BANCR levels in PTC and matched normal thyroid epithelial tissues from 92 patients using qRT-PCR. We also used lentiviral vectors to establish PTC cell lines to investigate the effects of BANCR overexpression on cancer cell proliferation, apoptosis, migration and invasion. Our results indicate BANCR levels are lower in PTC tumor tissues than control tissues. Decreased BANCR levels correlate with tumor size, the presence of multifocal lesions and advanced PTC stage. BANCR overexpression reduced PTC cell proliferation and promoted apoptosis, which inhibited metastasis. It also inactivated ERK1/2 and p38, and this effect was enhanced by treatment with the MEK inhibitor U0126. Finally, BANCR overexpression dramatically inhibited tumor growth from PTC cells in xenograft mouse models. These results suggest BANCR inhibits tumorigenesis in PTC and that BANCR levels may be used as a novel prognostic marker. PMID:27462868

  8. The Roles of the Epithelial-Mesenchymal Transition Marker PRRX1 and miR-146b-5p in Papillary Thyroid Carcinoma Progression

    PubMed Central

    Hardin, Heather; Guo, Zhenying; Shan, Weihua; Montemayor-Garcia, Celina; Asioli, Sofia; Yu, Xiao-Min; Harrison, April D.; Chen, Herbert; Lloyd, Ricardo V.

    2015-01-01

    Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial–mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-β1–induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-β1–induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression. PMID:24946010

  9. Multiple HABP2 variants in familial papillary thyroid carcinoma: Contribution of a group of "thyroid-checked" controls.

    PubMed

    Kern, Benjamin; Coppin, Lucie; Romanet, Pauline; Crépin, Michel; Szuster, Isabelle; Renaud, Florence; Leteurtre, Emmanuelle; Frénois, Frédéric; Wemeau, Jean-Louis; Carnaille, Bruno; Cardot-Bauters, Catherine; Cao, Christine Do; Pigny, Pascal

    2017-03-01

    A heterozygous germline variant in the HABP2 gene c.1601G > A (p.Gly534Glu), which negatively impacts its tumor suppressive activity in vitro, has been described in 4-14% of kindreds of European-American ancestry with familial papillary thyroid carcinoma (fPTC). But it is also found in ≈4% of Europeans and European/Americans from public databases that, however, did not provide information on the thyroid function of the controls. To get unbiased results, we decided to compare HABP2 genotypes of patients with fPTC with those of "thyroid-checked" controls. A control group consisting of 136 European patients who were thyroidectomised for medullary thyroid carcinoma and devoid of any histologically detectable PTC or follicular-deriving carcinoma was built. In parallel we recruited 20 patients with fPTC from eleven independent European kindreds. The entire coding region of HABP2 was analyzed by Sanger sequencing the germline DNAs of patients. Nucleotide variants were searched for by Snap Shot analysis in the controls. Two variants, c.1601G > A (p.Gly534Glu) and c.364C > T (p.Arg122Trp), were found in 2 and 3 patients at the heterozygous level respectively (minor allele frequency (MAF): 5.0% and 7.5%, respectively). In controls, the MAF was either similar for the c.1601G > A HABP2 variant (2.94%, ns) or significantly lower for the c.364C > T variant (0.73%, p = 0.016). The Arg122 residue lies in the EGF-3 domain of HABP2 which is important for its activation but, however, superposition of the predicted 3D structures of the wild type and mutated proteins suggests that this variant is tolerated at the protein level. In conclusion, our data do not support the pathogenicity of the HABP2 c.1601G > A variant but highlight the existence of a new one that should be more extensively searched for in fPTC patients and its pathogenicity more carefully evaluated.

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

    ClinicalTrials.gov

    2017-01-24

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

  11. Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

    PubMed Central

    Rebuffat, S A; Morin, M; Nguyen, B; Castex, F; Robert, B; Péraldi-Roux, S

    2010-01-01

    Background: Thyroid cancers are difficult to treat due to their limited responsiveness to chemo- and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches. Results: We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4′) or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial destruction of NPA cell line by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and exhibited an anti-proliferative activity. Comparison of the cytotoxic activity of anti-TPO aAbs shows that B4′ induced an anti-proliferative effect and a better ADCC than B4, but a lower one than anti-TPO aAbs from patients' sera. Antibody-dependent cell-mediated cytotoxicity was increased when human peripheral blood mononuclear cells were used as effector cells, suggesting that FcγRs, CD64, CD32 and CD16 are involved. Indeed, anti-TPO aAbs from patients' sera, but not B4 and B4′, exhibited CDC activity. Conclusions: These data indicate that anti-TPO aAbs display moderate ADCC and anti-proliferative activities on NPA cells; IgG glycosylation appears to be important for cytotoxic activity and ADCC efficiency depends on FcγR-bearing cells. Finally, recombinant human anti-TPO aAbs cannot yet be considered as an optimal tool for the development of a novel therapeutic approach for thyroid cancer. PMID:20145622

  12. Tumorigenesis of Papillary Thyroid Cancer Is Not BRAF-Dependent in Patients with Acromegaly

    PubMed Central

    Kim, Hee Kyung; Lee, Ji Shin; Park, Min Ho; Cho, Jin Seong; Yoon, Jee Hee; Kim, Soo Jeong; Kang, Ho-Cheol

    2014-01-01

    Introduction Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly. Materials and Methods We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor β (IGF-1Rβ). Results Thyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p = 0.030). The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007). IGF-1Rβ immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rβ was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014). Conclusion The prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC

  13. Combined papillary and mucoepidermoid carcinoma of the thyroid gland: a possible collision tumor diagnosed on fine-needle cytology. Report of a case with immunocytochemical and molecular correlations.

    PubMed

    Fulciniti, Franco; Vuttariello, Emilia; Calise, Celeste; Monaco, Mario; Pezzullo, Luciano; Chiofalo, Maria Grazia; Di Gennaro, Francesca; Malzone, Maria Gabriella; Campanile, Anna Cipolletta; Losito, Nunzia Simona; Botti, Gerardo; Chiappetta, Gennaro

    2015-05-01

    Fine-needle cytology (FNC) is frequently used to diagnose thyroid nodules discovered by palpation or imaging studies. Molecular tests on FNC material may increase its diagnostic accuracy. We report a case of a classic papillary thyroid carcinoma combined with a mucoepidermoid carcinoma correctly identified on FNC. The papillary component had a classic immunophenotype (CK19+, TTF1+), while the mucoepidermoid one was only focally CK19+. Point mutations (BRAF and RAS) and rearrangements (RET/PTC) of the papillary component have been also investigated on FNC samples, with resulting concurrent rearrangements of RET/PTC1 and RET/PTC3, but no point mutations. The histogenesis of combined papillary and mucoepidermoid carcinoma of the thyroid still remains partly unsettled, and further genomic studies are needed to shed some more light on this peculiar neoplasm.

  14. Both gender and concurrent chronic lymphocytic thyroiditis may influence the nuclear texture of papillary thyroid carcinomas cells.

    PubMed

    Cunha, Lucas Leite; Ferreira, Rita de Cássia; de Matos, Patricia Sabino; da Assumpção, Ligia Vera Montalli; Ward, Laura Sterian

    2014-01-01

    A disparity in gender incidence has been reported in both papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) diseases frequently associated and whose incidence has been increasing in parallel. We aimed to analyze differences in morphometric variables between male and female PTC patients and their relationship with the presence of concurrent CLT. The nuclear texture features of 100 hematoxylin-eosin stained nuclei from 100 consecutive classic PTC patients enrolled in our service were compared with their clinical and pathological features, including the presence of CLT. All patients were submitted to a standard management protocol and followed-up for 13-248 months (Mo = 117 months). Chromatin in women tended to present a denser and more homogeneous structure, in a less mottled pattern, with higher values of energy (p = 0.008) and diagonal moment (p = 0.032) than men. Concurrent CLT was more prevalent in women (41.42%) than in men (13.33%, p = 0.04) and was associated with higher cluster prominence values (p = 0.027), a parameter that indicates a predominance of high nuclear contrasted heterochromatin. A multivariate logistic regression analysis showed that higher cluster prominence was independently correlated with chromatin in patients who presented CLT but did not demonstrate any association between concurrent CLT and gender. We were unable to demonstrate any association between gender and any characteristic of tumor aggressiveness or patients outcome. Our results suggest that chromatin texture of hematoxylin-eosin stained nuclei in paraffin sections of PTC cells is related to both gender and concurrent CLT.

  15. Thyroid gland removal

    MedlinePlus

    Total thyroidectomy; Partial thyroidectomy; Thyroidectomy; Subtotal thyroidectomy; Thyroid cancer - thyroidectomy; Papillary cancer - thyroidectomy; Goiter - thyroidectomy; Thyroid nodules - thyroidectomy

  16. BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma

    PubMed Central

    Henke, Lauren E; Pfeifer, John D; Ma, Changquing; Perkins, Stephanie M; DeWees, Todd; El-Mofty, Samir; Moley, Jeffrey F; Nussenbaum, Brian; Haughey, Bruce H; Baranski, Thomas J; Schwarz, Julie K; Grigsby, Perry W

    2015-01-01

    The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1–2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1–2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1–2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan–Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy. PMID:25712893

  17. BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma.

    PubMed

    Henke, Lauren E; Pfeifer, John D; Ma, Changquing; Perkins, Stephanie M; DeWees, Todd; El-Mofty, Samir; Moley, Jeffrey F; Nussenbaum, Brian; Haughey, Bruce H; Baranski, Thomas J; Schwarz, Julie K; Grigsby, Perry W

    2015-06-01

    The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1-2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1-2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1-2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan-Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy.

  18. Hashimoto's thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with L-thyroxine.

    PubMed

    Fiore, E; Rago, T; Latrofa, F; Provenzale, M A; Piaggi, P; Delitala, A; Scutari, M; Basolo, F; Di Coscio, G; Grasso, L; Pinchera, A; Vitti, P

    2011-08-01

    The possible association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a still debated issue. We analyzed the frequency of PTC, TSH levels and thyroid autoantibodies (TAb) in 13 738 patients (9824 untreated and 3914 under l-thyroxine, l-T(4)). Patients with nodular-HT (n=1593) had high titer of TAb and/or hypothyroidism. Patients with nodular goiter (NG) were subdivided in TAb-NG (n=8812) with undetectable TAb and TAb+NG (n=3395) with positive TAb. Among untreated patients, those with nodular-HT showed higher frequency of PTC (9.4%) compared with both TAb-NG (6.4%; P=0.002) and TAb+NG (6.5%; P=0.009) and presented also higher serum TSH (median 1.30 vs 0.71 μU/ml, P<0.001 and 0.70 μU/ml, P<0.001 respectively). Independently of clinical diagnosis, patients with high titer of TAb showed a higher frequency of PTC (9.3%) compared to patients with low titer (6.8%, P<0.001) or negative TAb (6.3%, P<0.001) and presented also higher serum TSH (median 1.16 vs 0.75 μU/ml, P<0.001 and 0.72 μU/ml, P<0.001 respectively). PTC frequency was strongly related with serum TSH (odds ratio (OR)=1.111), slightly related with anti-thyroglobulin antibodies (OR=1.001), and unrelated with anti-thyroperoxidase antibodies. In the l-T(4)-treated group, when only patients with serum TSH levels below the median value (0.90 μU/ml) were considered, no significant difference in PTC frequency was found between nodular-HT, TAb-NG and TAb+NG. In conclusion, the frequency of PTC is significantly higher in nodular-HT than in NG and is associated with increased levels of serum TSH. Treatment with l-T(4) reduces TSH levels and decreases the occurrence of clinically detectable PTC.

  19. Significance of TNF-α and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma

    PubMed Central

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

    2016-01-01

    Circulating levels of TNF-α and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-α and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-α and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-α levels significantly positively correlated with the levels of L-Selectin, while TNF-α immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-α was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-α and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer. PMID:26881177

  20. A pregnant woman with metastatic papillary thyroid carcinoma and paraplegia: Multiple considerations involved in the management.

    PubMed

    Basu, Sandip; Kand, Purushottam

    2011-01-01

    A 35 years old primigravida hailing from a humble, rural background with no previous history related to thyroid carcinoma, presented with acute paraparesis at the last trimester of pregnancy and was diagnosed to harbor metastatic papillary thyroid carcinoma (PTC) following magnetic resonance imaging (MRI) of the spine with guided biopsy, which demonstrated near complete collapse of D5 and D10 vertebral bodies with altered signal on the D4 to D6 and D9 to D11 vertebral bodies, in addition to a gravid uterus and a large goiter. There was also evidence of bilateral nodular lesions in the lung parenchyma and a fairly large hepatic lesion in segment 8 of the liver . Histopathology revealed metastatic follicular variant of thyroid papillary carcinoma. This case with challenging presentation had multiple issues to be resolved during its management: a) acute paraparesis and the requirement of radioiodine ((131)I) treatment soon after total thyroidectomy, b) her first valuable pregnancy that required to be managed successfully, c) the poor general condition, d) the abstinence from iodine containing medications, in relation to the Cesarean section planned, e) the timing of total thyroidectomy, f) postnatal care of the newborn and g) radioprotective measures. All were important considerations in the management of this patient. Iodine restricted diet and medications were recommended and were communicated to the obstetricians involved in the patient. The patient underwent Cesarean section and total thyroidectomy at the same sitting. The newborn baby was healthy and was started on artificial feeding. Recombinant TSH primed protocol was not considered immediately in view of a major surgery being undertaken and the poor general condition, so that the patient would not require frequent support during the isolation period. In the first 3 weeks of the postoperative period, she was put on T3 substitution and after a 2 weeks gap was given (131)I and whole body diagnostic scan was

  1. Thyroid Nodules and Thyroid Cancer: Surgical Aspects

    PubMed Central

    Clark, Orlo H.

    1980-01-01

    Patients with thyroid nodules must be treated selectively because these nodules develop far more frequently than does thyroid cancer. A thorough clinical history, family history and history of radiation, as well as an accurate physical examination, are very important in determining whether surgical treatment is indicated. Thyroid function tests, a radioactive isotope scan, a thyroid echogram and fine-needle biopsy are also useful. Although there is considerable debate concerning the amount of thyroid tissue that should be removed at operation, the minimal procedure for a “cold,” solid thyroid nodule is a total thyroid lobectomy and isthmectomy. This is the treatment of choice for patients with occult papillary thyroid carcinoma. Partial lobectomy is to be discouraged. Near total or total thyroidectomy should be considered for all other patients with differentiated thyroid cancer. Many factors influence the prognosis of patients with thyroid cancer including age, sex, type of thyroid cancer, invasion, symptoms, lymph node metastasis, metastasis to distant sites, extent of the surgical procedure, and use of radioactive iodine and thyroid hormone. With adequate treatment, the prognosis for differentiated thyroid carcinoma is excellent. PMID:7222643

  2. Variants in microRNA genes in familial papillary thyroid carcinoma.

    PubMed

    Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya; Genutis, Luke K; Wang, Yanqiang; Li, Wei; Volinia, Stefano; Jazdzewski, Krystian; He, Huiling; Wakely, Paul E; Senter, Leigha; de la Chapelle, Albert

    2017-01-24

    Papillary Thyroid Carcinoma (PTC) displays one of the highest familiality scores of all cancers as measured by case-control studies, yet only a handful of genes have been implicated until now. Variants in microRNAs have been associated with the risk of several cancers including PTC but the magnitude of this involvement is unclear. This study was designed to test to what extent genomic variants in microRNAs contribute to PTC risk. We used SOLiD technology to sequence 321 genomic regions encoding 427 miRNAs in one affected individual from each of 80 PTC families. After excluding variants with frequency ≥ 1% in 1000 Genomes Phase 1 (n = 1092) we detected 1978 variants. After further functional filtering steps 25 variants in pre-miRs remained. Co-segregation was observed for six out of 16 tested miRNA variants with PTC in the families, namely let-7e, miR-181b, miR-135a, miR-15b, miR-320, and miR-484. Expression of miR-135a and miR-181b was tested in normal thyroid and tumor tissue from patients that carry the variants and a decrease in expression was observed. In vitro assays were applied to measure the effect of the variants on microRNAs' maturation. Four out of six variants were tested. Only the let-7e and miR-181b variants showed an effect on processing leading to lower levels of mature miRNA. These two variants were not detected in 1170 sporadic PTC cases nor in 1404 controls. Taken together, our data show that high penetrance germline sequence variants of miRNAs potentially predispose to a fraction of all PTC but are not common.

  3. BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence

    PubMed Central

    Oczko-Wojciechowska, Małgorzata; Barczyński, Marcin

    2016-01-01

    Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. BRAF V600E mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinico-pathological risk factors were reported but with controversial conclusions. The prognostic significance of BRAF mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using BRAF mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30–80%). At present it seems that BRAF mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors. The most recent ATA recommendations do not indicate a routine application of BRAF status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering BRAF and/or TERT status. At present, researchers are working on determining the role of BRAF mutation in patients from a low-risk group and its correlations with others molecular events. Currently, BRAF mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and

  4. Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas.

    PubMed

    Selmansberger, Martin; Kaiser, Jan Christian; Hess, Julia; Güthlin, Denise; Likhtarev, I; Shpak, Victor; Tronko, Mykola; Brenner, Alina; Abend, Michael; Blettner, Maria; Unger, Kristian; Jacob, Peter; Zitzelsberger, Horst

    2015-07-01

    A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to (131)iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The 'Genrisk-T' cohort consisted of 45 PTCs and the 'UkrAm' cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation.

  5. Risk factor analysis for central nodal metastasis in papillary thyroid carcinoma.

    PubMed

    Mao, Ling-Na; Wang, Ping; Li, Zhi-Yu; Wang, Yong; Song, Zheng-Ya

    2015-01-01

    Lymph node involvement is associated with recurrence in papillary thyroid carcinoma (PTC). The central neck compartment (level VI) lymph nodes are at the greatest risk of metastases from PTC, but the role of central neck dissection (CND) remains controversial, particularly in PTC without clinical cervical lymph node metastasis (cN0). The present study aimed to identify risk factors of central cervical nodal metastasis and the safety of CND in patients with cN0 PTC. The current study retrospectively investigated 389 patients who had been followed up for 12.0-25.5 months after surgery, and were divided into positive or negative lymph node involvement groups according to the pathological results subsequent to this surgery. Univariate and multivariate analyses were used to study the risk factor of central node involvement. The mean tumor size was 0.71±0.35 cm (range, 0.1-2.0 cm). There was no significant difference in the rate of central lymph node involvement based on age (<45 or ≥45 years) or tumor focality (unifocal or multifocal). However, there were significant differences based on gender, extra-thyroid invasion and tumor size (P<0.05). The incidence of transient hypoparathyroidism and transient vocal cord paralysis following CND was 12.34 and 4.11%, respectively. No patient experienced permanent hypoparathyroidism or vocal cord paralysis. One patient (1/389; 0.23%) experienced disease recurrence during the follow-up. A larger tumor size and the male gender were significantly associated with the central nodal metastasis rate for cN0 PTC with a tumor size of <2.0 cm. CND for cN0 PTC patients was safe and the tumor-associated recurrence rate following CND plus total thyroidectomy was low. The present study suggests that CND should be conducted for male cN0 PTC patients with a larger tumor size (≥0.5 cm).

  6. Variants in microRNA genes in familial papillary thyroid carcinoma

    PubMed Central

    Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya; Genutis, Luke K; Wang, Yanqiang; Li, Wei; Volinia, Stefano; Jazdzewski, Krystian; He, Huiling; Wakely, Paul E; Senter, Leigha; de Chapelle la, Albert

    2017-01-01

    Papillary Thyroid Carcinoma (PTC) displays one of the highest familiality scores of all cancers as measured by case-control studies, yet only a handful of genes have been implicated until now. Variants in microRNAs have been associated with the risk of several cancers including PTC but the magnitude of this involvement is unclear. This study was designed to test to what extent genomic variants in microRNAs contribute to PTC risk. We used SOLiD technology to sequence 321 genomic regions encoding 427 miRNAs in one affected individual from each of 80 PTC families. After excluding variants with frequency ≥ 1% in 1000 Genomes Phase 1 (n = 1092) we detected 1978 variants. After further functional filtering steps 25 variants in pre-miRs remained. Co-segregation was observed for six out of 16 tested miRNA variants with PTC in the families, namely let-7e, miR-181b, miR-135a, miR-15b, miR-320, and miR-484. Expression of miR-135a and miR-181b was tested in normal thyroid and tumor tissue from patients that carry the variants and a decrease in expression was observed. In vitro assays were applied to measure the effect of the variants on microRNAs’ maturation. Four out of six variants were tested. Only the let-7e and miR-181b variants showed an effect on processing leading to lower levels of mature miRNA. These two variants were not detected in 1170 sporadic PTC cases nor in 1404 controls. Taken together, our data show that high penetrance germline sequence variants of miRNAs potentially predispose to a fraction of all PTC but are not common. PMID:28031538

  7. SRGAP1 Is a Candidate Gene for Papillary Thyroid Carcinoma Susceptibility

    PubMed Central

    He, Huiling; Bronisz, Agnieszka; Liyanarachchi, Sandya; Nagy, Rebecca; Li, Wei; Huang, Yungui; Akagi, Keiko; Saji, Motoyasu; Kula, Dorota; Wojcicka, Anna; Sebastian, Nikhil; Wen, Bernard; Puch, Zbigniew; Kalemba, Michal; Stachlewska, Elzbieta; Czetwertynska, Malgorzata; Dlugosinska, Joanna; Dymecka, Kinga; Ploski, Rafal; Krawczyk, Marek; Morrison, Patrick J.; Ringel, Matthew D.; Kloos, Richard T.; Jazdzewski, Krystian; Symer, David E.; Vieland, Veronica J.; Ostrowski, Michael; Jarząb, Barbara

    2013-01-01

    Background: Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative. Objectives: The objective of this study was to identify susceptibility genes for PTC. Methods: A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies. Results: Linkage analysis and association studies identified the Slit-Robo Rho GTPase activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain segregated with the disease in 1 family each. One missense variant, R617C, located in the RhoGAP domain occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was severely impaired by the Q149H and R617C variants. Conclusions: Our findings suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a low-penetrant gene, possibly of a modifier type. PMID:23539728

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

    PubMed Central

    Zhang, Huairong

    2016-01-01

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

  9. BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Carcinoma in Chinese Patients

    PubMed Central

    Gao, Jie; Ren, Xinyu; Teng, Lianghong; Duan, Huanli; Lin, Yansong; Li, Xiaoyi; Zhang, Bo; Liang, Zhiyong

    2016-01-01

    Background The BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations have been reported in papillary thyroid carcinoma (PTC). The aim of this retrospective cross-sectional study was to add further information regarding the prevalence of the BRAF V600E and TERT promoter mutations in Chinese PTC and their clinicopathological associations. Methods We detected the BRAF V600E mutation and TERT promoter mutations in 455 Chinese PTC patients and analyzed the association of these mutations with several clinicopathological features. Results The BRAF V600E mutation was detected in 343 (75.4%) of 455 cases and was significantly associated with older age (p<0.001) and conventional subtype (p = 0.003). TERT promoter mutations were detected in 19 (4.4%) of 434 PTCs and were associated with older age (p<0.001), larger tumor size (p = 0.024), and advanced TNM stage(p<0.001). Of the 19 patients that were positive for TERT promoter mutations, 18 (94.7%) also harbored the BRAF V600E mutation. Conclusion We determined the prevalence and clinicopathological associations of BRAF V600E and TERT promoter mutations in Chinese PTC patients. TERT promoter mutations but not the BRAF V600E mutation were associated with more advanced TNM stage upon diagnosis. PMID:27064992

  10. Significance of micrometastases in the calculation of the lymph node ratio for papillary thyroid cancer

    PubMed Central

    Chang, Young Woo; Kim, Hwan Soo; Jung, Seung Pil; Kim, Hoon Yub; Lee, Jae Bok; Bae, Jeoung Won

    2017-01-01

    Purpose The lymph node ratio (LNR) is an important prognostic factor in papillary thyroid carcinoma (PTC), but micrometastases in cervical lymph nodes (LNs) are not of great clinical importance. In this study, we analyzed the accuracy of prediction of the prognosis depending on whether micrometastases were included in the number of metastatic LNs when calculating LNR. Methods The study included 353 PTC patients who underwent total thyroidectomy with neck LN dissection, and calculated LNR by 2 methods according to whether micrometastases were included in the number of metastatic LNs: Method 1 did not and method 2 did include. To compare the predictive values of LNR by the 2 methods, correlation coefficients and receiver operating characteristic (ROC) curves were analyzed. Results Positive correlations were found between LNR and preablation stimulated thyroglobulin (sTg) levels in both methods, but the correlation between method 1 LNR and preablation sTg level was significantly stronger than that for method 2 (Fisher z = 1.7, P = 0.045). The areas under these 2 independent ROC curves were analyzed; the prognostic efficacy of method 1 LNR was more accurate than that of method 2 LNR, and the difference was statistically significant (P = 0.0001). Conclusion Regional recurrence of PTC can be predicted more accurately by not including micrometastases in the number of metastatic LNs when calculating LNR. PMID:28289664

  11. Individualized optimal surgical extent of the lateral neck in papillary thyroid cancer with lateral cervical metastasis.

    PubMed

    Park, Jae-Yong; Koo, Bon Seok

    2014-06-01

    Despite an excellent prognosis, cervical lymph node (LN) metastases are common in patients with papillary thyroid cancer (PTC). The presence of metastasis is associated with an increased risk of locoregional recurrence, which significantly impairs quality of life and may decrease survival. Therefore, it has been an important determinant of the extent of lateral LN dissection in the initial treatment of PTC patients with lateral cervical metastasis. However, the optimal extent of therapeutic lateral neck dissection (ND) remains controversial. Optimizing the surgical extent of LN dissection is fundamental for balancing the surgical morbidity and oncological benefits of ND in PTC patients with lateral neck metastasis. We reviewed the currently available literature regarding the optimal extent of lateral LN dissection in PTC patients with lateral neck metastasis. Even in cases with suspicion of metastatic LN at the single lateral level or isolated metastatic lateral LN, the application of ND including all sublevels from IIa and IIb to Va and Vb may be overtreatment, due to the surgical morbidity. When there is no suspicion of LN metastasis at levels II and V, or when multilevel aggressive neck metastasis is not found, sublevel IIb and Va dissection may not be necessary in PTC patients with lateral neck metastasis. Thus consideration of the individualized optimal surgical extent of lateral ND is important when treating PTC patients with lateral cervical metastasis.

  12. Cooccurrence of Metastatic Papillary Thyroid Carcinoma and Salmonella Induced Neck Abscess in a Cervical Lymph Node

    PubMed Central

    Kim, Jae-Myung; Jung, Eun Jung; Song, Eun Jin; Kim, Dong Chul; Jeong, Chi-Young; Ju, Young-Tae; Lee, Young-Joon; Hong, Soon-Chan; Choi, Sang-Kyung; Ha, Woo-Song

    2017-01-01

    Cervical lymph node metastasis is common in patients with papillary thyroid carcinoma (PTC). Salmonella species are rarely reported as causative agents in focal infections of the head and neck. The cooccurrence of lymph node metastasis from PTC and a bacterial infection is rare. This report describes a 76-year-old woman with a cervical lymph node metastasis from PTC and Salmonella infection of the same lymph node. The patient presented with painful swelling in her left lateral neck region for 15 days, and neck ultrasonography and computed tomography showed a cystic mass along left levels II–IV. The cystic mass was suspected of being a metastatic lymph node; modified radical neck dissection was performed. Histopathological examination confirmed the presence of PTC in the resected node and laboratory examination of the combined abscess cavity confirmed the presence of Salmonella Typhi. Following antibiotic sensitivity testing of the cultured Salmonella Typhi, she was treated with proper antibiotics. Cystic lesions in lymph nodes with metastatic cancer may indicate the presence of cooccurring bacterial infection. Thus, culturing of specimen can be option to make accurate diagnosis and to provide proper postoperative management. PMID:28261270

  13. Sparing Surgery for the Successful Treatment of Thyroid Papillary Carcinoma Invading the Trachea: A Case Report

    PubMed Central

    Kulbakin, Denis; Chekalkin, Timofey; Muhamedov, Marat; Choynzonov, Evgeniy; Kang, Ji-hoon; Kang, Seung-baik; Gunther, Victor

    2016-01-01

    Published reports on salvage treatment for trachea reconstruction after total thyroidectomy or partial tracheotomy are available, some of them using structures of the trachea itself, auricular cartilage, a musculocutaneous flap, or other methods. In our report, we emphasize the importance of a search for a new material and approach for sparing surgery. The purpose of this article is to describe a case of a successful sparing surgery in a patient with advanced thyroid papillary carcinoma invading the trachea. After total thyroidectomy in 2012, partial resection of the trachea was performed in 2014. The lesion defect was 5.5 × 2.3 cm in size, located between 4 (2nd–6th) tracheal cartilaginous rings and involving about a semicircumference. It was reconstructed with the aid of the knitted TiNi-based mesh endograft, which has been prefabricated in the sternocleidomastoid muscle and further covered with the skin draped over the wound. The tracheostoma was fully closed 6 weeks after the surgery. There were neither side effects nor complications. This kind of tracheal surgery for extensive lesions demonstrates good functional and cosmetic outcomes. PMID:27990114

  14. Preoperative predictors of lateral neck lymph node metastasis in papillary thyroid microcarcinoma

    PubMed Central

    Liu, Zheng; Lei, Jianyong; Liu, Yang; Fan, Yuxia; Wang, Xiaoming; Lu, Xiubo

    2017-01-01

    Abstract Lateral lymph node metastasis (LNM) is not uncommon in papillary thyroid microcarcinoma (PTMC). Our present study aimed to investigate the risk factors associated with lateral LNM in PTMC. We retrospectively collected data pertaining to 366 patients with PTMC who underwent surgery at our center from 2010 to 2015. These patients were divided into the following 2 groups: a lateral LNM-positive group and a lateral LNM-negative group. Clinical and ultrasound data were compared between the 2 groups to determine the risk factors associated with lateral LNM. Univariate and multivariate analyses indicated that capsule invasion (OR = 3.995, 95% CI, 2.148–7.430) and upper portion location (OR = 4.541, 95% CI, 2.444–8.438) were significant risk factors for lateral LNM of PTMC and that capsule invasion (AUC = 0.666) and upper portion location (AUC = 0.678) could be used to predict lateral LNM of PTMC. Moreover, the patients in lateral LNM positive group exhibited significantly higher rates of tumor recurrence or metastasis than the patients in lateral LNM negative group (P = 0.027). Patients with PTMC located in the upper portion or exhibiting capsule invasion should receive meticulous preoperative evaluations for lateral LNM, prophylactic lateral LND may be considered. PMID:28272218

  15. Pattern of nodal involvement in papillary thyroid cancer: a challenge of quantitative analysis

    PubMed Central

    Fama, Fausto; Cicciù, Marco; Giudice, Giuseppe Lo; Sindoni, Alessandro; Palella, Jessica; Piquard, Arnaud; Saint-Marc, Olivier; Benvenga, Salvatore; Bramanti, Ennio; Cervino, Gabriele; Florio, Maria Gioffre

    2015-01-01

    Introduction: Backgrounds of this study were to examine and analyse the relationship among the number of lymph nodes with metastases harvested in central and lateral compartments, the characteristics of tumours and patients, and the recurrences rate. Methods: A retrospective review of 118 patients treated for a papillary thyroid cancer and underwent to neck dissection, including in all cases both central and lateral compartment, was realised. A quantitative analysis, on this homogeneous cohort of patients, was performed to hypothesize the minimum number of cervical lymph nodes to be necessarily excised in order to obtain an adequate management of these patients. Results: The mean follow-up time was 75.9 months. Five-year overall survival was 96.6%. The correlation among the metastatic lymph node number of the ipsilateral central compartment, isolated or pooled with those of the ipsilateral lateral compartment, age of patient and tumour size revealed a statistical significance (P=0.01); both parameters, tumour size and age, may be considered as dependent predictor variables. Conclusion: We suppose, notwithstanding the limited number of patients, that the number of lymph nodes harvested to achieve an optimal cervical dissection may be superior to 8 and 11 in central and lateral compartments, and 6 and 10 in contralateral ones, respectively. Moreover we recommend the bilateral dissection of central nodes compartment in presence of tumour localised in the isthmus. PMID:26617901

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

    PubMed

    Zhang, Huairong; Gao, Bo; Shi, Bingyin

    2016-01-01

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

  17. Outcomes for patients with papillary thyroid cancer who do not undergo prophylactic central neck dissection

    PubMed Central

    Nixon, I. J.; Wang, L. Y.; Ganly, I.; Patel, S. G.; Morris, L. G.; Migliacci, J. C.; Tuttle, R. M.; Shah, J. P.; Shaha, A. R.

    2016-01-01

    Background The role of prophylactic central neck dissection (CND) in the management of papillary thyroid cancer (PTC) is controversial. This report describes outcomes of an observational approach in patients without clinical evidence of nodal disease in PTC. Methods All patients who had surgery between 1986 and 2010 without CND for PTC were identified. All patients had careful clinical assessment of the central neck during preoperative and perioperative evaluation, with any suspicious nodal tissue excised for analysis. The cohort included patients in whom lymph nodes had been removed, but no patient had undergone a formal neck dissection. Recurrence-free survival (RFS), central neck RFS and disease-specific survival (DSS) were calculated using the Kaplan–Meier method. Results Of 1798 patients, 397 (22·1 per cent) were men, 1088 (60·5 per cent) were aged 45 years or more, and 539 (30·0 per cent) had pT3 or pT4 disease. Some 742 patients (41·3 per cent) received adjuvant treatment with radioactive iodine. At a median follow-up of 46 months the 5-year DSS rate was 100 per cent. Five-year RFS and central neck RFS rates were 96·6 and 99·1 per cent respectively. Conclusion Observation of the central neck is safe and should be recommended for all patients with PTC considered before and during surgery to be free of central neck metastasis. PMID:26511531

  18. The Benefits and Risks of Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma: Prospective Cohort Study.

    PubMed

    Lee, Doh Young; Oh, Kyoung Ho; Cho, Jae-Gu; Kwon, Soon-Young; Woo, Jeong-Soo; Baek, Seung-Kuk; Jung, Kwang-Yoon

    2015-01-01

    Objectives. This study evaluated the benefits of performing prophylactic central neck dissection (CND) with total thyroidectomy (TT) in management of papillary thyroid carcinoma (PTC) patients who were clinically node-negative at presentation. Methods. A total of 257 patients with stage T1 or T2 PTC and without preoperative evidence of lymph node involvement (N0) were enrolled in this prospective study. The patients were randomly assigned to two groups: (1) a total thyroidectomy (TT) group (n = 104) or (2) a TT plus CND group (n = 153). The two groups were compared for their perioperative data, complication rates, disease recurrence rates, and clinical outcomes. Results. The two groups of patients were similar in age, sex ratio, follow-up duration, and tumor size (P = 0.227, 0.359, 0.214, and 0.878, resp.). The two groups showed similar rates of disease recurrence (3.9% in the TT group versus 3.3% in the TT plus CND group); however, complications occurred more frequently in the TT plus CND group; especially transient hypocalcemia (P = 0.043). Conclusions. Patients treated with TT plus CND had a higher rate of complications with similar recurrence rate. We believe that CND may not be routinely recommended when treating patients with PTC.

  19. MiR-101 targets USP22 to inhibit the tumorigenesis of papillary thyroid carcinoma

    PubMed Central

    Zhao, Huadong; Tang, Haili; Huang, Qike; Qiu, Bo; Liu, Xiaomin; Fan, Dong; Gong, Li; Guo, Hang; Chen, Chong; Lei, Shixiong; Yang, Lu; Lu, Jianguo; Bao, Guoqiang

    2016-01-01

    Increasing evidence suggests that microRNA-101 (miR-101) is involved in the progression of various human cancers, including papillary thyroid carcinoma (PTC). However, the biological functions of miR-101 and underlying molecular mechanisms in PTC remain largely unknown. In this study, we demonstrated that miR-101 underexpression in PTC tissue was associated with lymph node metastasis and poor prognosis of PTC patients. MiR-101 reduced PTC cell proliferation, apoptosis resistance, and invasion. Ubiquitin-specific protease 22 (USP22) was confirmed as a direct target of miR-101. USP22 restoration attenuated the inhibitory effects of miR-101 on PTC malignant traits in vitro. In vivo, miR-101 overexpression or USP22 depletion reduced the tumorigenesis of PTC. Overall, our findings provide new insight into the mechanism of PTC inhibition by miR-101, suggesting the potential of miR-101 as a therapeutic target in PTC patients. PMID:27904772

  20. Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report

    PubMed Central

    Pyo, Ju Yeon; Kim, Jisup; Choi, Sung-eun; Shin, Eunah; Yang, Seok-Woo; Park, Cheong Soo; Kim, Seok-Mo

    2017-01-01

    We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study. PMID:27873522

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

    ClinicalTrials.gov

    2017-01-31

    BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV 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

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

    ClinicalTrials.gov

    2015-11-04

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

  3. Papillary Thyroid Cancer and Lung Adenocarcinoma Presenting as Two Primary Malignancies in a Patient with Symptomatic Goiter

    PubMed Central

    Daniel, Deepu; Delumpa, Leah; Bray, Natasha

    2015-01-01

    In rare instances, patients may be diagnosed with two different primary malignancies. Though such synchronous malignancies have been documented in sporadic case reports, the overwhelming majority of malignancies involving multiple organs can be attributed to a primary source. Papillary thyroid carcinoma and lung adenocarcinoma are rarely diagnosed within the same year. Our case report presents a patient who was diagnosed with these two malignancies during her same hospital visit. Biopsies results proved that the two malignancies were in fact separate entities and not a consequence of metastasis from a primary source. PMID:26290667

  4. The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family

    PubMed Central

    Perdas, Ewelina; Stawski, Robert; Nowak, Dariusz; Zubrzycka, Maria

    2016-01-01

    Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC. PMID:27314338

  5. [Anatomo-clinical prognostic factors of papillary carcinoma of the thyroid. Multivariate analysis: report of a series of 52 cases].

    PubMed

    Patey, M; Menzies, D; Theobald, S; Delisle, M J; Flament, J B; Pluot, M

    1998-02-01

    A retrospective study about 52 cases of papillary thyroid carcinomas was carried out with emphasis on histopathological features. The mean follow up period was 10 years. The survival curves were estimated using the Kaplan-Meier method and compared using the log rank test. The multivariate analysis was performed using the Cox's regression model. In univariate analysis, age, Tp (histopathological extension of the tumor), histological differentiation, VAN score (Vascular invasion nuclear Atypia tumor Necrosis) of Akslen and the LeuM1 expression were significant prognostic factors. In multivariate analysis, the Tp and histological differentiation were associated with high risks of poor outcome.

  6. Bioinformatics analyses of significant prognostic risk markers for thyroid papillary carcinoma.

    PubMed

    Min, Xiao-Shan; Huang, Peng; Liu, Xu; Dong, Chao; Jiang, Xiao-Lin; Yuan, Zheng-Tai; Mao, Lin-Feng; Chang, Shi

    2015-09-01

    This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention.

  7. Deregulated expression of VHL mRNA variants in papillary thyroid cancer.

    PubMed

    Baldini, Enke; Tuccilli, Chiara; Arlot-Bonnemains, Yannick; Chesnel, Frank; Sorrenti, Salvatore; De Vito, Corrado; Catania, Antonio; D'Armiento, Eleonora; Antonelli, Alessandro; Fallahi, Poupak; Watutantrige-Fernando, Sara; Tartaglia, Francesco; Barollo, Susi; Mian, Caterina; Bononi, Marco; Arceri, Stefano; Mascagni, Domenico; Vergine, Massimo; Pironi, Daniele; Monti, Massimo; Filippini, Angelo; Ulisse, Salvatore

    2017-03-05

    Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences.

  8. Common genetic variants in metabolism and detoxification pathways and the risk of papillary thyroid cancer

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Neta, Gila; Brenner, Alina V; Hutchinson, Amy; Pfeiffer, Ruth M; Sturgis, Erich M; Xu, Li; Wheeler, William; Doody, Michele M; Chanock, Stephen J; Sigurdson, Alice J

    2012-01-01

    Relationships are unclear between polymorphisms in genes involved in metabolism and detoxification of various chemicals and papillary thyroid cancer (PTC) risk as well as their potential modification by alcohol or tobacco intake. We evaluated associations between 1647 tagging single nucleotide polymorphisms (SNPs) in 132 candidate genes/regions involved in metabolism of exogenous and endogenous compounds (Phase I/II, oxidative stress, and metal binding pathways) and PTC risk in 344 PTC cases and 452 controls. For 15 selected regions and their respective SNPs, we also assessed interaction with alcohol and tobacco use. Logistic regression models were used to evaluate the main effect of SNPs (Ptrend) and interaction with alcohol/tobacco intake. Gene- and pathway-level associations and interactions (Pgene interaction) were evaluated by combining Ptrend values using the adaptive rank-truncated product method. While we found associations between PTC risk and nine SNPs (Ptrend≤0.01) and seven genes/regions (Pregion<0.05), none remained significant after correction for the false discovery rate. We found a significant interaction between UGT2B7 and NAT1 genes and alcohol intake (Pgene interaction=0.01 and 0.02 respectively) and between the CYP26B1 gene and tobacco intake (Pgene interaction=0.02). Our results are suggestive of interaction between the genetic polymorphisms in several detoxification genes and alcohol or tobacco intake on risk of PTC. Larger studies with improved exposure assessment should address potential modification of PTC risk by alcohol and tobacco intake to confirm or refute our findings. PMID:22389382

  9. Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer

    PubMed Central

    McNamara, William F.; Wang, Laura Y.; Palmer, Frank L.; Nixon, Iain J.; Shah, Jatin P.; Patel, Snehal G.; Ganly, Ian

    2016-01-01

    Background The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence. Methods A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method. Results A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001). Conclusion Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease. PMID:26994486

  10. Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma

    PubMed Central

    Kim, Yourha; Kim, Min-Hee; Jeon, Sora; Kim, Jeeyoon; Kim, Chankyung; Bae, Ja Seong

    2017-01-01

    Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients. PMID:28358874

  11. Intracellular Signal Transduction and Modification of the Tumor Microenvironment Induced by RET/PTCs in Papillary Thyroid Carcinoma

    PubMed Central

    Menicali, Elisa; Moretti, Sonia; Voce, Pasquale; Romagnoli, Serena; Avenia, Nicola; Puxeddu, Efisio

    2012-01-01

    RET gene rearrangements (RET/PTCs) represent together with BRAF point mutations the two major groups of mutations involved in papillary thyroid carcinoma (PTC) initiation and progression. In this review, we will examine the mechanisms involved in RET/PTC-induced thyroid cell transformation. In detail, we will summarize the data on the molecular mechanisms involved in RET/PTC formation and in its function as a dominant oncogene, on the activated signal transduction pathways and on the induced gene expression modifications. Moreover, we will report on the effects of RET/PTCs on the tumor microenvironment. Finally, a short review of the literature on RET/PTC prognostic significance will be presented. PMID:22661970

  12. Papillary thyroid carcinoma and laryngeal squamous cell carcinoma manifesting as a collision tumor of the neck: A case report

    PubMed Central

    WANG, XIN; CUI, XIANG-YAN; FANG, NING; CHEN, WEI-LUN; YU, HONG; ZHU, WEI

    2013-01-01

    A 55-year-old male presented with a rapidly expanding mass on the right side of the neck and progressive hoarseness. An electronic laryngoscopy and a computed tomography scan were performed, and the patient was subsequently diagnosed with tumors of the larynx and the thyroid gland. An en bloc near-total thyroidectomy combined with a total laryngectomy was performed. The final pathological analysis revealed a collision tumor that was derived from a laryngeal squamous cell carcinoma and a papillary thyroid carcinoma. Collision tumors of the head and neck are rare. The therapy for a collision tumor should consist of a combination of the treatments that are normally used for each focus. PMID:24260054

  13. Tumor size measured by preoperative ultrasonography and postoperative pathologic examination in papillary thyroid carcinoma: relative differences according to size, calcification and coexisting thyroiditis.

    PubMed

    Yoon, Young Hoon; Kwon, Ki Ryun; Kwak, Seo Young; Ryu, Kyeung A; Choi, Bobae; Kim, Jin-Man; Koo, Bon Seok

    2014-05-01

    Ultrasonography (US) is a useful diagnostic modality for evaluation of the size and features of thyroid nodules. Tumor size is a key indicator of the surgical extent of thyroid cancer. We evaluated the difference in tumor sizes measured by preoperative US and postoperative pathologic examination in papillary thyroid carcinoma (PTC). We reviewed the medical records of 172 consecutive patients, who underwent thyroidectomy for PTC treatment. We compared tumor size, as measured by preoperative US, with that in postoperative specimens. And we analyzed a number of factors potentially influencing the size measurement, including cancer size, calcification and coexisting thyroiditis. The mean size of the tumor measured by preoperative US was 11.4, and 10.2 mm by postoperative pathologic examination. The mean percentage difference (US-pathology/US) of tumor sizes measured by preoperative US and postoperative pathologic examination was 9.9 ± 19.3%, which was statistically significant (p < 0.001). When the effect of tumor size (≤10.0 vs. 10.1-20.0 vs. >20.0 mm) and the presence of calcification or coexisting thyroiditis on the tumor size discrepancy between the two measurements was analyzed, the mean percentage differences according to tumor size (9.1 vs. 11.2% vs. 9.8%, p = 0.842), calcification (9.2 vs. 10.2%, p = 0.756) and coexisting thyroiditis (17.6 vs. 9.5%, p = 0.223) did not show statistical significance. Tumor sizes measured in postoperative pathology were ~90% of those measured by preoperative US in PTC; this was not affected by tumor size, the presence of calcification or coexisting thyroiditis. When the surgical extent of PTC treatment according to tumor size measured by US is determined, the relative difference between tumor sizes measured by preoperative US and postoperative pathologic examination should be considered.

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

    PubMed

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

    2016-08-01

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

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

    ClinicalTrials.gov

    2017-01-31

    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

  16. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    SciTech Connect

    Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

    2009-07-07

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  17. An Epistatic Interaction between the PAX8 and STK17B Genes in Papillary Thyroid Cancer Susceptibility

    PubMed Central

    Inglada-Pérez, Lucía; Sastre-Perona, Ana; Pastor, Susana; Velázquez, Antonia; Mancikova, Veronika; Ruiz-Llorente, Sergio; Schiavi, Francesca; Marcos, Ricard; Malats, Nuria; Opocher, Giuseppe; Diaz-Uriarte, Ramon; Santisteban, Pilar; Valencia, Alfonso; Robledo, Mercedes

    2013-01-01

    Papillary Thyroid Cancer (PTC) is a heterogeneous and complex disease; susceptibility to PTC is influenced by the joint effects of multiple common, low-penetrance genes, although relatively few have been identified to date. Here we applied a rigorous combined approach to assess both the individual and epistatic contributions of genetic factors to PTC susceptibility, based on one of the largest series of thyroid cancer cases described to date. In addition to identifying the involvement of TSHR variation in classic PTC, our pioneer study of epistasis revealed a significant interaction between variants in STK17B and PAX8. The interaction was detected by MD-MBR (p = 0.00010) and confirmed by other methods, and then replicated in a second independent series of patients (MD-MBR p = 0.017). Furthermore, we demonstrated an inverse correlation between expression of PAX8 and STK17B in a set of cell lines derived from human thyroid carcinomas. Overall, our work sheds additional light on the genetic basis of thyroid cancer susceptibility, and suggests a new direction for the exploration of the inherited genetic contribution to disease using association studies. PMID:24086368

  18. Clinical and Morphologic Features of ETV6-NTRK3 Translocated Papillary Thyroid Carcinoma in an Adult Population Without Radiation Exposure.

    PubMed

    Seethala, Raja R; Chiosea, Simion I; Liu, Cheng Z; Nikiforova, Marina; Nikiforov, Yuri E

    2017-04-01

    The ETV6-NTRK3 translocation characterizes a subset of radiation associated and pediatric papillary thyroid carcinomas (PTCs). We now describe the clinicopathologic features of ETV6-NTRK3 translocated PTC in an adult population without radiation exposure. Twelve cases were identified by next-generation sequencing (ThyroSeq version 2). The mean patient age was 37 years with a female predilection (10:2). Preoperative fine needle aspiration was performed on 6 patients of which 4 were classified as "malignant," whereas 2 were classified as "follicular lesion of undetermined significance." One third (4/12) of patients demonstrated extrathyroidal extension and one half of patients (5/10) demonstrated lymph node metastases. One patient presented with brain metastasis. Tumors typically (8/12) demonstrated an admixture of follicular and papillary patterns and were usually infiltrative and multinodular (6/12 cases). Tumors often showed clear cell or oncocytic foci and demonstrated overt nuclear features of PTC, though characteristically, interspersed bland areas were common, even in metastases. Cytoplasmic vacuolization resembling that of mammary analog secretory carcinoma was also common but focal. TTF-1 was positive and S100 was negative in all tested cases confirming a thyroid phenotype. Unique morphologies included glomeruloid follicles, reverse polarization of nuclei. Survey of the TCGA datasets revealed similar findings. Thus, ETV6-NTRK3 translocated PTC are locoregionally aggressive and can metastasize distantly. They are characterized by mixture of papillary and follicular architecture and may show cytoplasmic vacuolization akin to other ETV6 translocated carcinomas. Although nuclear features are typically overt, interspersed bland regions may cause diagnostic difficulty in metastatic sites, and may explain discordance on fine needle aspiration.

  19. Intercellular adhesion molecule 1 is a sensitive and diagnostically useful immunohistochemical marker of papillary thyroid cancer (PTC) and of PTC-like nuclear alterations in Hashimoto's thyroiditis

    PubMed Central

    ZHANG, KE; GE, SHU-JIAN; LIN, XIAO-YAN; LV, BEI-BEI; CAO, ZHI-XIN; LI, JIA-MEI; XU, JIA-WEN; WANG, QIANG-XIU

    2016-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is important in the progression of inflammatory responses. Recently, increased levels of ICAM-1 have been reported in a number of types of malignancy. The present study aimed to investigate ICAM-1 expression in papillary thyroid cancer (PTC) and in Hashimoto's thyroiditis (HT) with PTC-like nuclear alterations, and to assess the predictive value of ICAM-1 in thyroid lesions. ICAM-1 expression was retrospectively investigated in 132 consecutive cases of PTC, 72 cases of HT, 10 of follicular cancer, 15 of follicular adenoma, 16 of nodular goiter and 8 samples of normal thyroid tissue using immunohistochemical analyses, and in 42 PTC patients using western blotting. ICAM-1 expression was not detected in normal follicular cells, follicular lesions (adenoma and cancer) and benign nodular hyperplasia, but was frequently overexpressed in PTC cells. ICAM-1 overexpression was associated with extra-thyroidal invasion and lymph node metastasis; no association was found with age, gender, tumor size, multifocality, pathological stage, recurrence or distant metastasis. ICAM-1 expression in HT patients with PTC-like nuclear alterations was significantly higher than that in HT cases with non-PTC-like features. Compared with antibodies against cytokeratin 19, galectin-3 and Hector Battifora mesothelial-1, ICAM-1 was the most sensitive marker for the detection of PTC-like features in HT. These findings demonstrate that ICAM-1 expression is upregulated in PTC and in HT with PTC-like nuclear alterations. This feature may be an important factor in the progression of cancer of the thyroid gland. PMID:26998068

  20. Association between the KRAS Gene Polymorphisms and Papillary Thyroid Carcinoma in a Chinese Han Population

    PubMed Central

    Ning, Lifeng; Rao, Wenwang; Yu, Yaqin; Liu, Xiaoli; Pan, Yuchen; Ma, Yuan; Liu, Rui; Zhang, Shangchao; Sun, Hui; Yu, Qiong

    2016-01-01

    Several studies have reported the association between MAPK signaling pathway gene polymorphisms and papillary thyroid carcinoma (PTC). KRAS gene, an oncogene from the mammalian RAS gene family plays an important role in the MAPK pathway. This study aimed to identify the potential association of KRAS gene polymorphisms with susceptibility to PTC in a Han Chinese population. A total of 861 patients with PTC, 562 disease controls with nodular goiter and 897 healthy controls were recruited. Four tagSNP polymorphisms (rs12427141, rs712, rs7315339 and rs7960917) of KRAS gene were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Statistical analyses and haplotype estimations were conducted using Haploview and Unphased softwares. Only significant differences were observed in genotypic frequencies of the rs7315339 polymorphism (χ2 =7.234, df=2, p=0.027) between PTC and disease controls. Statistically significant differences in both allelic and genotypic genotypes frequencies for rs712 (Genotype, χ2=8.258, p=0.016) and rs12427141 (Allele, χ2=3.992, p=0.046; Genotype, χ2=8.140, p=0.017) were observed between PTC patients and controls. Haplotype analyses revealed higher frequencies of GA and TA haplotypes (p=0.039 and p=0.003, respectively) from rs712- rs12427141 (two-SNP) or TGA and TTG haplotype containing the alleles from rs7960917, rs712 and rs12427141, as well as the GAT haplotype containing the alleles from rs712, rs12427141 and rs7315339 in PTC patients than in healthy controls (p=0.042, p=0.037, p=0.027, respectively). Inversely, the haplotype TTA from rs7960917, rs712 and rs12427141 or the haplotype TAC from rs712, rs12427141 and rs7315339 was significantly less frequent in the PTC patients than in normal control (p=0.003, p=0.003, respectively). These findings suggest the role of these KRAS gene variants in susceptibility to PTC. Moreover, significant differences of the KRAS gene polymorphisms may occur

  1. Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker.

    PubMed

    Wreesmann, Volkert B; Sieczka, Elizabeth M; Socci, Nicholas D; Hezel, Michael; Belbin, Thomas J; Childs, Geoffrey; Patel, Snehal G; Patel, Kepal N; Tallini, Giovanni; Prystowsky, Michael; Shaha, Ashok R; Kraus, Dennis; Shah, Jatin P; Rao, Pulivarthi H; Ghossein, Ronald; Singh, Bhuvanesh

    2004-06-01

    Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0

  2. Radioguided sentinel lymph node biopsy in patients with papillary thyroid carcinoma

    PubMed Central

    Carcoforo, Paolo

    2016-01-01

    Background The ATA guidelines do not recommend prophylactic central compartment neck dissection in patients with T1–T2 papillary thyroid carcinoma (PTC) with no clinical evidence of lymph node metastasis, however patients’ staging is recommended. Lymph node metastasis may be present also in small PTC, but preoperative ultrasound identifies suspicious cervical lymphadenopathy in 20–30% of patients. The role of sentinel lymph node biopsy (SLNB) remain open to debate. It has been shown that the identification rate of SLN in PTC patients is improved using a radiotracer compared to a dye technique. The aim of this systematic review was to evaluate the role of radioguided SLNB (rSLNB) in the treatment of PTC patients. Methods A systematic search was performed in the PubMed and Embase database to identify all original articles regarding the application of rSLNB in PTC patients. The primary outcome was false negative rate (FNR) of the rSLNB; the secondary outcomes were SLN intraoperative identification rate (IIR), site of lymph node metastasis, and persistent disease during follow up. Results Twelve studies were included. Most of PTC patients were T1–T2. The overall SLN IIR, SLN metastatic rate, and FNR were 92.1%, 33.6%, and 25.4%, respectively. Overall, lymph node metastasis were found in the central compartment (23.0%) and in the lateral compartments (10.6%). The persistent disease in patients who underwent SLNB associated to lymph node dissection (LND) in the same compartment of the SLN regardless of the SLN status was 0.6%. Conclusions In all PTC patients, also in T1–T2 stage, due to the high FNR the SLNB performed alone should be abandoned and converted into a technique to guide the lymphadenectomy in a specific neck compartment (i.e., central or lateral) based on the radioactivity, regardless of the SLN status, for better lymph node staging and selection of patients for postoperative radioiodine ablation. PMID:28149805

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

    ClinicalTrials.gov

    2017-02-17

    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 IV Thyroid Gland Follicular Carcinoma; Stage IV 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

  4. Papillary thyroid cancer and inflammatory bowel disease: Is there a relationship?

    PubMed Central

    Sonu, Irene S; Blonski, Wojciech; Lin, Ming Valerie; Lewis, James; Aberra, Faten; Lichtenstein, Gary R

    2013-01-01

    AIM: To formally study age of diagnosis of papillary thyroid cancer (PTC) in inflammatory bowel disease (IBD) patients and evaluate the prevalence of PTC in IBD patients compared to a control population. METHODS: We were interested in testing the hypothesis that patients with IBD are more likely to be diagnosed with PTC than a control population. A retrospective cohort analysis was performed using the University of Pennsylvania Health System’s electronic database. Outpatients from 1998-2009 were included in the search, and patients in the cohort were selected based on ICD-9 codes. Inclusion criteria included the diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) and the concurrent diagnosis of thyroid cancer in comparison to a control population. Using these methods 912 patients with CD and 1774 with UC were compared to 1638 diverticulitis and 19 447 asthma controls. Statistics were performed using corrected chi-square analysis. The primary outcome for this study was the diagnosis of PTC. Approval to conduct this study was obtained by the Institutional Review Board at the University of Pennsylvania. RESULTS: The mean age was 47.5 years (range: 18-102 years) and 66% patients were female. An analysis of variance model was used to compare the age of PTC diagnosis between the CD, UC, asthma and diverticulitis groups, and a statistically significant difference in age at PTC diagnosis was noted across all groups (F = 6.35, df = 3, P = 0.0006). The age of PTC diagnosis in CD patients was statistically significantly lower than UC, asthma, and diverticulitis patients (average PTC diagnosis age for CD 25, UC 49, asthma 45, diverticulitis 63). After covarying for sex and age in 2009, the difference in age at PTC diagnosis remained statistically significant (F = 4.13, df = 3, P = 0.0089). A total of 86 patients were diagnosed with PTC. Nine patients (0.5%) with UC were diagnosed with PTC. Patients with UC were not shown to be more likely to develop PTC [odds

  5. The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma

    PubMed Central

    Moncayo, Roy; Kroiss, Alexander; Oberwinkler, Manfred; Karakolcu, Fatih; Starzinger, Matthias; Kapelari, Klaus; Talasz, Heribert; Moncayo, Helga

    2008-01-01

    Background Thyroid physiology is closely related to oxidative changes. The aim of this controlled study was to evaluate the levels of nutritional anti-oxidants such as vitamin C, zinc (Zn) and selenium (Se), and to investigate any association of them with parameters of thyroid function and pathology including benign and malignant thyroid diseases. Methods This controlled evaluation of Se included a total of 1401 subjects (1186 adults and 215 children) distributed as follows: control group (n = 687), benign thyroid disease (85 children and 465 adults); malignant thyroid disease (2 children and 79 adults). Clinical evaluation of patients with benign thyroid disease included sonography, scintigraphy, as well as the determination of fT3, fT4, TSH, thyroid antibodies levels, Se, Zn, and vitamin C. Besides the routine oncological parameters (TG, TSH, fT4, ultrasound) Se was also determined in the cases of malignant disease. The local control groups for the evaluation of Se levels were taken from a general practice (WOMED) as well as from healthy active athletes. Blood samples were collected between 8:00 and 10:30 a.m. All patients lived in Innsbruck. Statistical analysis was done using SPSS 14.0. The Ho stated that there should be no differences in the levels of antioxidants between controls and thyroid disease patients. Results Among the thyroid disease patients neither vitamin C, nor Zn nor Se correlated with any of the following parameters: age, sex, BMI, body weight, thyroid scintigraphy, ultrasound pattern, thyroid function, or thyroid antibodies. The proportion of patients with benign thyroid diseases having analyte concentrations below external reference cut off levels were 8.7% of cases for vitamin C; 7.8% for Zn, and 20.3% for Se. Low Se levels in the control group were found in 12%. Se levels were significantly decreased in cases of sub-acute and silent thyroiditis (66.4 ± 23.1 μg/l and 59.3 ± 20.1 μg/l, respectively) as well as in follicular and papillary

  6. Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted papillary thyroid cancer aggressiveness

    PubMed Central

    Zhang, Tao; Shen, Xiaopei; Liu, Rengyun; Zhu, Guangwu; Bishop, Justin; Xing, Mingzhao

    2017-01-01

    How the BRAF V600E mutation promotes the pathogenesis and aggressiveness of papillary thyroid cancer (PTC) is not completely understood. Here we explored a novel mechanism involving WASP interacting protein family member 1 (WIPF1). In PTC tumors, compared with the wild-type BRAF, BRAF V600E was associated with over-expression and hypomethylation of the WIPF1 gene. In thyroid cancer cell lines with wild-type BRAF, WIPF1 expression was robustly upregulated upon introduced expression of BRAF V600E (P=0.03) whereas the opposite was seen upon BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E. Methylation of a functionally critical region of the WIPF1 promoter was decreased by expressing BRAF V600E in cells harboring the wild-type BRAF and increased by BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E mutation. Under-expression and hypermethylation of WIPF1 induced by stable BRAF knockdown was reversed by DNA demethylating agent 5′-azadeoxycytidine. Knockdown of WIPF1 robustly inhibited anchorage-independent colony formation, migration, and invasion of thyroid cancer cells and suppressed xenograft thyroid cancer tumor growth and vascular invasion, mimicking the effects of BRAF knockdown. In human PTC tumors, WIPF1 expression was associated with extrathyroidal invasion (P=0.01) and lymph node metastasis (P=2.64E-05). In summary, BRAF V600E-activated MAP kinase pathway causes hypomethylation and overexpression of WIPF1; WIPF1 then functions like an oncoprotein to robustly promote aggressive cellular and tumor behaviors of PTC. This represents a novel mechanism in BRAF V600E-promoted PTC aggressiveness and identifies WIPF1 as a novel therapeutic target for thyroid cancer. PMID:27863429

  7. Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer

    ClinicalTrials.gov

    2014-07-23

    Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage II Follicular Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  8. Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma.

    PubMed

    Fang, Zejun; Song, Rui; Gong, Chaoju; Zhang, Xiaomin; Ren, Guoping; Li, Jinfan; Chen, Yuexia; Qiu, Lanlan; Mei, Lingming; Zhang, Ronghui; Xiang, Xueping; Chen, Xiang; Shao, Jimin

    2016-03-01

    Ribonucleotide reductase (RR) has been reported to be associated with several types of cancer while the expression and role of RR in thyroid carcinoma (TC) has not been investigated. Here, we first examined the expression level of three RR subunit proteins (RRM1, RRM2, and RRM2B) in papillary thyroid carcinoma (PTC) and undifferentiated thyroid carcinoma (UTC) patient samples by immunohistochemistry. The results showed that RRM1 was higher expressed in 95.2 % cancer tissues compared with their adjacent normal tissues in 146 PTC samples. The expression level of RRM1 was positively correlated with T stage, lymph node metastasis (LNM), extrathyroidal invasion (ETI), and TNM stage in PTC patients. However, in 12 UTC samples, RRM1 expression was negatively expressed in six cases. To further determine the biological role of RRM1 in TC, ectopic expression or siRNA-mediated knockdown of RRM1 were carried out in the high-differentiated thyroid carcinoma cell line TPC-1 and the poor-differentiated thyroid carcinoma cell line SW579, respectively. In TPC-1 and SW579 cells, overexpression and siRNA knockdown of RRM1 demonstrated that RRM1 promoted DNA synthesis and proliferation in both cell lines as shown by EdU incorporation and cell viability assays. However, RRM1 enhanced cell migration and invasion in TPC-1 cells but inhibited that in SW579 cells as shown by wound healing and transwell assays. Moreover, we also found that RRM1 promoted PTEN expression and reduced Akt phosphorylation in a RR-activity-independent manner in the low-differentiated TC cells but not in the high-differentiated TC cells. In contrast, RRM2 expression was higher expressed in both PTC and UTC patient samples, consisting with its oncogenic role in other cancers. Therefore, we suggest that RRM1 promotes thyroid carcinoma proliferation as a component of RR but may play a different role in the invasion and metastasis of differently differentiated thyroid carcinomas through a non-RR pathway, which could

  9. Expression microarray analysis of papillary thyroid carcinoma and benign thyroid tissue: emphasis on the follicular variant and potential markers of malignancy

    PubMed Central

    Finn, S. P.; Smyth, P.; Cahill, S.; Streck, C.; O’Regan, E. M.; Flavin, R.; Sherlock, J.; Howells, D.; Henfrey, R.; Cullen, M.; Toner, M.; Timon, C.; O’Leary, J. J.

    2007-01-01

    The most common sub-variant of papillary thyroid carcinoma (PTC) is the so-called follicular variant (FVPTC), which is a particularly problematic lesion and can be challenging from a diagnostic viewpoint even in resected lesions. Although fine needle aspiration cytology is very useful in the diagnosis of PTC, its accuracy and utility would be greatly facilitated by the development of specific markers for PTC and its common variants. We used the recently developed Applied Biosystems 1700 microarray system to interrogate a series of 11 benign thyroid lesions and conditions and 14 samples of PTC (six with classic morphology and eight with follicular variant morphology). TaqMan® reverse transcriptase-polymerase chain reaction was used to validate the expression portfolios of 50 selected transcripts. Our data corroborates potential biomarkers previously identified in the literature, such as LGALS3, S100A11, LYN, BAX, and cluster of differentiation 44 (CD44). However, we have also identified numerous transcripts never previously implicated in thyroid carcinogenesis, and many of which are not represented on other microarray platforms. Diminished expression of metallothioneins featured strongly among these and suggests a possible role for this family as tumour suppressors in PTC. Fifteen transcripts were significantly associated with FVPTC morphology. Surprisingly, these genes were associated with an extremely narrow repertoire of functions, including the major histocompatibility complex and cathepsin families. PMID:17252232

  10. Recurrent Papillary Thyroid Carcinoma with Pleural Metastasis Diagnosed by Effusion Cytology: A Report of Cases with Clinicopathologic Correlation

    PubMed Central

    Sakamoto, Reid I; Sumida, Lauren C; Lum, Christopher AK

    2015-01-01

    Papillary thyroid carcinoma (PTC) is typically an indolent disease characterized by slow growth and a favorable prognosis. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion. We report 3 female patients of Japanese/Okinawan ancestry with a history of PTC who presented with hydrothorax. Cytologic examination in conjunction with immunohistochemical staining enabled a definitive diagnosis of metastatic PTC. Molecular analysis of the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways demonstrated the presence of the v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation in 2 of our 3 patients, with the absence of any other clinically significant mutations in all cases. Further investigation is necessary to elucidate the molecular and environmental mechanisms involved in this aggressive manifestation of PTC. PMID:25755913

  11. Low VHL mRNA expression is associated with more aggressive tumor features of papillary thyroid carcinoma.

    PubMed

    Stanojevic, Boban; Saenko, Vladimir; Todorovic, Lidija; Petrovic, Nina; Nikolic, Dragan; Zivaljevic, Vladan; Paunovic, Ivan; Nakashima, Masahiro; Yamashita, Shunichi; Dzodic, Radan

    2014-01-01

    Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR = 5.78, 95% CI 3.17-10.53, P<0.0001), classical papillary morphology of the tumor (OR = 2.92, 95% CI 1.33-6.44, P = 0.008) and multifocality (OR = 1.96, 95% CI 1.06-3.62, P = 0.031). In disease-free survival analysis, low VHL expression had marginal significance (P = 0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.

  12. Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma

    PubMed Central

    Stanojevic, Boban; Saenko, Vladimir; Todorovic, Lidija; Petrovic, Nina; Nikolic, Dragan; Zivaljevic, Vladan; Paunovic, Ivan; Nakashima, Masahiro; Yamashita, Shunichi; Dzodic, Radan

    2014-01-01

    Alterations of the von Hippel–Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR = 5.78, 95% CI 3.17–10.53, P<0.0001), classical papillary morphology of the tumor (OR = 2.92, 95% CI 1.33–6.44, P = 0.008) and multifocality (OR = 1.96, 95% CI 1.06–3.62, P = 0.031). In disease-free survival analysis, low VHL expression had marginal significance (P = 0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated. PMID:25490036

  13. Relation Between F-18 FDG Uptake of PET/CT and BRAFV600E Mutation in Papillary Thyroid Cancer.

    PubMed

    Yoon, Seokho; An, Young-Sil; Lee, Su Jin; So, Eu Young; Kim, Jang-Hee; Chung, Yoon-Sok; Yoon, Joon-Kee

    2015-12-01

    BRAFV600E mutation and F-18 fluorodeoxyglucose (FDG) uptake are potential prognostic factors of papillary thyroid cancer (PTC). This study was performed to investigate the relationship between the BRAFV600E mutation and F-18 FDG uptake in PTC.We retrospectively included 169 PTC patients who underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) before thyroidectomy from May 2009 to August 2012. Subjects were classified into overt PTC (>1 cm, n = 76) and papillary thyroid microcarcinoma (PTMC, n = 93) groups. Univariate and multivariate analyses were performed to assess the relationship between maximum standardized uptake value (SUVmax) of the primary tumors and clinicopathologic variables.The BRAFV600E mutation was detected in 82.2% (139/169). In all subjects, the BRAFV600E mutation and tumor size were independently related to SUVmax by multivariate analysis (P = 0.048 and P < 0.001, respectively). SUVmax was significantly higher in tumors with the BRAFV600E mutation than in those with wild-type BRAF (9.4 ± 10.9 vs 5.0 ± 4.1, P < 0.001). Similarly, in overt PTC group, the BRAFV600E mutation and tumor size were independently correlated with SUVmax (P = 0.032 and P = 0.001, respectively). By contrast, in PTMC group, only tumor size was significantly associated with SUVmax (P = 0.010). The presence of the BRAFV600E mutation is independently associated with high F-18 FDG uptake on preoperative PET/CT in patients with overt PTC, but this relationship was not evident in PTMC. This study provides a better understanding of the relationship between F-18 FDG uptake and BRAFV600E mutation in patients with PTC.

  14. The correlation of sodium iodide symporter and BRAF(V600E) mutation in classical variant papillary thyroid carcinoma.

    PubMed

    Yazgan, Aylin; Yıldırım, Nilüfer; Gözalan, Ayşegül; Gümüştaş, Sinem; Kılıçarslan, Aydan; Balci, Serdar; Aydın, Cevdet; Ersoy, Reyhan; Cakir, Bekir; Güler, Gülnur

    2016-06-01

    BRAF(V600E) mutation was analyzed by real-time polymerase chain reaction in 96 consecutive cases with classical variant papillary thyroid cancer, and immunohistochemical staining of Na+/I- symporter (NIS) protein was evaluated. Localization (intracellular or membranous), density, and the intensity of cytoplasmic staining were characterized semiquantitatively. Extrathyroidal invasion, surgical margin positivity, and lymph node metastasis were compared with BRAF(V600E) mutation and NIS expression. Eighty-eight patients who had at least 24-month follow-up were also included in survival analysis. BRAF(V600E) mutation was determined in 78.1% (75/96) and functional NIS activity in 74% (71/96) of the cases. There were statistically significant differences in mean ages between BRAF(V600E) mutation-positive (48.6) and BRAF(V600E) mutation-negative cases (37.3; Levene test, P=.419; Student t test, P=.001). The surgical margin positivity (46.7%) and extrathyroidal extension percentage (54.7%) in the BRAF(V600E) mutation-positive group were higher than the negative (28.6% and 33.3%, respectively) group, without statistical significance (P=.138 and P=.084, respectively). Functional NIS activity was higher in BRAF(V600E) mutation-positive cases (78.1%) than mutation-negative ones (57.1%; P=.047). The possibility of moderate and intense cytoplasmic staining in BRAF(V600E) mutation-positive cases (72%) was 6.3 times higher than the possibility of weak staining (28%) in the mutation-positive cases (95% confidence interval, 2.2-18.8; P=.001). Functional NIS expression is higher in patients with classical variant papillary thyroid cancer with BRAF(V600E) mutation. However, the clinical features were not found to be associated with NIS expression. There may be different mechanisms determining the outcome of therapy.

  15. Platelet derived growth factor receptor alpha mediates nodal metastases in papillary thyroid cancer by driving the epithelial-mesenchymal transition

    PubMed Central

    Ekpe-Adewuyi, Esther; Lopez-Campistrous, Ana; Tang, Xiaoyun; Brindley, David N.; McMullen, Todd P. W.

    2016-01-01

    Recently platelet derived growth factor receptor-alpha (PDGFRα) was recognized as a potential target to treat aggressive papillary thyroid cancer given its strong association with lymph node metastases. However, it is unclear how PDGFRα potentiates metastases and if it works through the canonical MAPK pathway traditionally linked to PTC oncogenesis. We explored the phenotypic changes driven by PDGFRα activation in human papillary thyroid cancer (PTC) cells and the downstream signalling cascades through which they are effected. We demonstrate that PDGFRα drives an impressive phenotypic change in PTC cell lines as documented by significant cytoskeletal rearrangement, increased migratory potential, and the formation of invadopodia. Cells lacking PDGFRα formed compact and dense spheroids, whereas cells expressing active PDGFRα exhibited invadopodia in three-dimensional culture. To achieve this, active PDGFRα provoked downstream activation of the MAPK/Erk, PI3K/Akt and STAT3 pathways. We further confirmed the role of PDGFRα as a transformative agent promoting the epithelial to mesenchymal transition of PTC cells, through the augmentation of Snail and Slug expression. Crenolanib, a small molecule inhibitor of PDGFRα, suppressed the levels of Snail and Slug and almost completely reversed all the phenotypic changes. We demonstrate that PDGFRα activation is an essential component that drives aggressiveness in PTC cells, and that the signaling pathways are complex, involving not only the MAPK/Erk but also the PI3K/Akt and STAT3 pathways. This argues for upstream targeting of the PDGFRα given the redundancy of oncogenic pathways in PTC, especially in patients whose tumors over-express this tyrosine kinase receptor. PMID:27845909

  16. Peroperative diagnosis and treatment of metastases to the regional lymph nodes in papillary carcinoma of the thyroid gland

    SciTech Connect

    Hamming, J.F.; van de Velde, C.J.; Goslings, B.M.; Fleuren, G.J.; Hermans, J.; Delemarre, J.F.; van Slooten, E.A. )

    1989-08-01

    The management of two groups of patients with papillary carcinoma of the thyroid gland (n = 165) was evaluated retrospectively. Total thyroidectomy was the standard procedure in both groups, but the peroperative diagnosis and treatment of metastases to the regional lymph nodes differed. In group 1 (n = 84), only clinically positive lymph nodes were resected, and if residual postoperative 131I uptake was found, an ablation dose of {sup 131}I was given. In group 2 (n = 81), all of the tissue in the tracheoesophageal groove was removed routinely at total thyroidectomy and frozen section was done of the lymph nodes lying along the internal jugular vein. If metastases were found, a modified radical dissection of the neck was performed on the affected side. The two patient groups were comparable with regard to risk factors--local tumor stage, age and sex. Almost twice as many patients were found to have metastases to the lymph nodes in group 2. There was no significant difference in the ten year over-all or recurrence free survival time between the two groups. In group 1, there were more recurrences on the explored side of the neck but fewer distant metastases; however, both findings were not significant. In group 2, significantly more instances of hypoparathyroidism and palsy of the accessory nerve were found (p less than 0.05). Thus, when a more extensive search was carried out, more metastases to the lymph node were discovered and treated, but this did not prevent recurrences in the neck nor did it improve survival time. This approach resulted in more postoperative morbidity. There seems to be no justification for prophylactic removal of regional lymph nodes in instances of papillary carcinoma of the thyroid gland, but modified radical neck dissection may be beneficial if clinically suspect regional lymph nodes are present in the lateral part of the neck. 52 references.

  17. Renal Metastasis and Dual (18F-Fluorodeoxyglucose and 131I) Avid Skeletal Metastasis in a Patient with Papillary Thyroid Cancer

    PubMed Central

    Kulkarni, Prashanth; Rekha, Pobbi Setty Radhakrishna Gupta; Prabhu, Meghana; Venkataramarao, Sunil Hejjaji; Raju, Nalini; Chandrasekhar, Naveen Hedne; Kannan, Subramanian

    2017-01-01

    Differentiated thyroid carcinoma (DTC) though usually behaves in an indolent manner, can have unusual metastatic presentation. Initial presentation of metastatic disease has been reported in 1–12% of DTC being less frequent in papillary (~2%) than in follicular (~10%) thyroid carcinoma. Renal metastasis from DTC is very rare. To our knowledge, only about 30 cases have been reported in the English literature to date. To make clinicians aware that management of such high-risk thyroid cancer frequently requires novel multimodality imaging and therapeutic techniques. A 72-year-old female is described who presented with abdominal pain and bilateral lower limbs swelling. Initial contrast enhanced computed tomography (CT) scan of abdomen showed a well-encapsulated mass in the upper pole of right kidney favoring a renal cell carcinoma. Postright sided radical nephrectomy, histopathology, and immunohistochemistry reports suggested metastatic deposits from thyroid malignancy. 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT demonstrated hypermetabolic nodule in the left lobe of thyroid and a lytic lesion involving left acetabulum suggestive of skeletal metastasis. Subsequently, ultrasound-guided fine needle aspiration cytology of the thyroid nodules in bilateral lobes confirmed thyroid malignancy (Bethesda 6/6). Total thyroidectomy revealed papillary thyroid cancer (PTC) (follicular variant-PTC [FV-PTC]). After surgery, 131I-whole body scan showed iodine avid lytic lesion in the left acetabulum. The present case is a rare scenario of a renal metastasis as the presenting feature of an FV-PTC. Dual avidity in metastatic thyroid cancers (iodine and FDG) is rare and based on the degree of dedifferentiation of the DTC. PMID:28242987

  18. Extent of surgery for papillary thyroid cancer: preoperative imaging and role of prophylactic and therapeutic neck dissection.

    PubMed

    Cisco, Robin M; Shen, Wen T; Gosnell, Jessica E

    2012-03-01

    Papillary thyroid cancer (PTC) has an excellent prognosis, yet lymph node metastases are common. Most authors agree that central and/or lateral lymph node dissection should be undertaken in patients with abnormal lymph nodes detected on ultrasound, physical examination or intraoperative inspection. However the appropriate extent of prophylactic lymph node dissection for clinically node-negative patients remains the subject of controversy. There have been no randomized trials to date to offer guidance on this issue. The 2006 guidelines of the American Thyroid Association recommended consideration of prophylactic bilateral central lymph node dissection (CLND) for all patients undergoing thyroidectomy for PTC. However, the absence of compelling evidence for a benefit in terms of recurrence or survival, and the potential for increased morbidity, have led many, including our institution, to take an approach of selective central lymph node dissection. This approach is guided by the detection of abnormal lymph nodes on preoperative ultrasound, on physical examination, or during surgery. Postoperatively, ultrasound by an experienced ultrasonographer is the mainstay of evaluation for lymph node recurrence and is combined with monitoring of thyroglobulin and antithyroglobulin antibody levels. Reoperative lymph node dissection is typically undertaken upon detection and fine needle aspiration (FNA) of involved lymph nodes 0.8 cm or greater in size.

  19. Molecular Analysis of TTF-1 and TTF-2 Genes in Patients with Early Onset Papillary Thyroid Carcinoma

    PubMed Central

    Espadinha, Carla; Silva, Ana Luísa; Cabrera, Rafael; Bugalho, Maria João

    2012-01-01

    Two common variants, close from TTF-1 and TTF-2, were shown to predispose to thyroid cancer (TC) in European populations. We aimed to investigate whether TTF-1 and TTF-2 variants might contribute to TC early onset (EO). Tumor samples from eighteen patients with papillary TC (PTC), who underwent total thyroidectomy at an age of ≤21, were screened for TTF-1 and TTF-2 variants. No TTF-1 variants were documented; two novel germinal TTF-2 variants, c.200C>G (p.A67G) and c.510C>A (p.A170A), were identified in two patients. Two already described TTF-2 variants were also documented; the allelic frequency among patients was not different from that observed among controls. Moreover, RET/PTC rearrangements and the BRAFV600E mutation were identified in 5/18 and 2/18 PTCs, respectively. Thyroglobulin (TG) and thyroid peroxidase (TPO) expression was found to be significantly decreased in tumors, and the lowest level of TPO expression occurred in a tumor harboring both the p.A67GTTF-2 variant and a RET/PTC3 rearrangement. PMID:22481925

  20. Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

    PubMed Central

    Hieber, Ludwig; Huber, Reinhard; Bauer, Verena; Schäffner, Quirin; Braselmann, Herbert; Thomas, Geraldine; Bogdanova, Tatjana; Zitzelsberger, Horst

    2011-01-01

    Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs) were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY). In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH) for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22) of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87%) indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis. PMID:21436994

  1. The clinicopathologic differences of central lymph node metastasis in predicting lateral lymph node metastasis and prognosis in papillary thyroid cancer associated with or without Hashimoto's thyroiditis.

    PubMed

    Zhu, Youzhi; Zheng, Ke; Zhang, Huihao; Chen, Ling; Xue, Jiajie; Ding, Mingji; Wu, Kunlin; Wang, Zongcai; Kong, Lingjun; Chen, Xiangjin

    2016-06-01

    This study aims to evaluate the difference of central lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) associated with or without Hashimoto's thyroiditis (HT) in predicting lateral node metastasis. A retrospective case control study was performed. Patients (1276) with PTC who underwent a total or near-total thyroidectomy with at least one lymph node dissection in our institution were retrospectively reviewed. All patients were divided into two groups (HT-group and non-HT group) according to the pathological diagnosis. In HT-group, the incidence of both central and lateral LNM was lower compared with non-HT group. The average of central metastatic lymph node radio (LNR) was also lower than that in Non-HT group. The multivariate analysis showed that the number of metastatic central LNs (HT ≥ 4, Non-HT ≥ 2) and the central LNR (HT ≥ 0.4, Non-HT ≥ 0.6) were independently associated with lateral LNM. Patients with HT need larger primary tumor size, more positive central LN and higher LNR to predict the presence of lateral LNM. HT may protect against central and lateral LNM in PTC. The number of positive central LNs and central LNR in PTC could be used to determine the presence of lateral LNM and inform postoperative follow-up.

  2. Prediction of thyroid extracapsular extension with cervical lymph node metastases (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma.

    PubMed

    Wei, Xi; Li, Ying; Zhang, Sheng; Gao, Ming

    2014-09-01

    The aim of our study was to find a specific imaging (contrast-enhanced ultrasound, CEUS) to detect extracapsular extension and cervical lymph node metastases (ECE-LNM) that associated with BRAF protein expression in papillary thyroid carcinoma (PTC). Preoperative utrasonography (US) or CEUS was performed in the diagnosis of extracapsular extension (ECE) in 317 patients with 369 PTC. BRAF protein status was tested on the primary tumor and lymph node involvement. The diagnostic accuracy of CEUS and US was evaluated after thyroid surgery. The association between CEUS and BRAF expression were then analyzed to investigate the diagnostic value of ECE-LNM in PTC. The sensitivity and specificity of CEUS were higher than those in US in the diagnosis of ECE in patients with PTC (91.1, 86.5 vs 49, 55 %). BRAF protein overexpression were significantly associated with ECE (P = 0.0003) and lymph node metastasis (LNM) positive cases (P = 0.0014). The results of CEUS, not US, have a significant correlation with BRAF expression status in PTC samples (P < 0.0001). Associated with BRAF protein expression status, the routine preoperative CEUS could have a good value in the diagnosis of ECE-LNM in PTC and facilitate a surgeon to improve further clinical management.

  3. Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma.

    PubMed

    Wu, Wenyi; Zhang, Liting; Lin, Jianqing; Huang, Hanwei; Shi, Bai; Lin, Xingong; Huang, Zhongxin; Wang, Chaoyang; Qiu, Jianlong; Wei, Xiaolong

    2016-12-20

    Hypermethylation leading to the loss of hypermethylated in cancer-1 (HIC1) gene expression occurs in many different types of human cancer. HIC1 is a transcriptional repressor that directly binds to the promoter region of NAD-dependent deacetylase sirtuin-1 (SIRT1). SIRT1 functions in cell growth, is anti-apoptotic, protect neurons, functions in senescence, and regulates energy restriction. Epigenetic modification and dysregulation affecting the HIC1/SIRT1 axis is potentially important for the development of malignancies. However, the importance of HIC1 expression in the development of papillary thyroid carcinoma, especially in Chinese patients, is uncertain. Therefore, we assessed the level of methylation in the HIC1 promoter and the mRNA and protein expression levels of HIC1 and SIRT1 in human thyroid papillary carcinoma and tumor adjacent control tissues. The demethylation reagent 5-aza-2'-deoxyctidine (5-aza-dc) and an HIC1 overexpression plasmid were used to manipulate the HIC1/SIRT1 pathway, and the effects on cell senescence, apoptosis, and cell cycle progression were assessed. Compared to normal thyroid tissue, thyroid tumors had lower expression of HIC1 and higher SIRT1 expression. The level of HIC1 methylation was also higher in thyroid carcinoma tissues than adjacent tissues. HIC1 expression was closely correlated with patient age and tumor progression. Restoration of HIC1 expression through an overexpression plasmid or 5-aza-dC treatment reduced SIRT1 expression and cell proliferation, and led to senescence, cell cycle arrest, and apoptosis. Aberrant expression of HIC1/SIRT1 and hypermethylation of the HIC1 promoter may be critical for the development and progression of papillary thyroid cancer.

  4. New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase.

    PubMed

    Quagliariello, Vincenzo; Armenia, Emilia; Aurilio, Caterina; Rosso, Francesco; Clemente, Ottavia; de Sena, Gabriele; Barbarisi, Manlio; Barbarisi, Alfonso

    2016-08-01

    The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc.

  5. Pediatric Thyroid Cancer

    MedlinePlus

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

  6. [Diffuse sclerosing papillary carcinoma mimicking chronic lymphocytic thyroiditis. A unusual neoplasm variant].

    PubMed

    Pino Rivero, V; Pardo Romero, G; González Palomino, A; Pantoja Hernández, C G; Trinidad Ramos, G; Marcos García, M; Blasco Huelva, A

    2006-01-01

    We report the clinical case of a 39 years old female diagnosed as a chronic lymphocytic tiroiditis by F.N.A.B. with multinodular goiter of long evolution. The patient was operated by total thyroidectomy and her final anatomopathologic result was papillary carcinoma diffuse sclerosing variant. During the surgical act several cervical nodes were detected and removed being informed the most of them as metastasic. A review of the literature at respect of this malignant neoplasm is performed.

  7. miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma

    PubMed Central

    Minna, Emanuela; Romeo, Paola; Dugo, Matteo; De Cecco, Loris; Todoerti, Katia; Pilotti, Silvana; Perrone, Federica; Seregni, Ettore; Agnelli, Luca; Neri, Antonino; Greco, Angela; Borrello, Maria Grazia

    2016-01-01

    Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta-analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation. Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia. PMID:26871295

  8. Papillary thyroid carcinoma (PTC) in Lynch syndrome: Report of two cases and discussion on Lynch syndrome behaviour and genetics.

    PubMed

    Pelizzo, M R; Pennelli, G; Zane, M; Galuppini, F; Colletti, P M; Merante Boschin, I; Rubello, D

    2015-08-01

    We present here two cases of papillary thyroid carcinoma (PTC) in patients affected by Lynch syndrome (LS). The first case is a 47-year-old woman with typical hereditary non-polyposis colorectal cancer (HNPCC) syndrome, reported with endometrial and ovarian carcinoma at age 43, and colon cancer at age 45. The patient underwent total thyroidectomy and central node dissection in 2007, at 47years old, with a histological diagnosis of PTC (T1aN1a). Molecular genetics showed a germ-line mutation of the MLH1 gene, 1858 G>T(E620X), with substitution of glycine with a stop codon at position 620. This mutation has pathogenetic significance and was considered responsible for the various tumours of the HNPCC spectrum. In particular, in the same kindred, spanning 5 generations, there were 5 members with colorectal cancer, 4 with endometrial cancer, 3 with gastric and 2 with breast cancer. The second case is a 34-year-old man with typical HNPCC syndrome with colonic resection for colon cancer at age 21. The patient underwent total thyroidectomy with central and lateral node dissection in 2010, at age 34, with a histological diagnosis of PTC with nodal metastases (pT4N1b). Molecular genetic analysis showed a germ-line mutation of the MSH2 gene (thymine insertion at position 907). This mutation had pathogenetic significance and was considered responsible for HNPCC development. Two similar cases have been reported: a 39-year-old woman, and a 44-year-old woman, affected by HNPCC syndrome, with anaplastic thyroid carcinoma and undifferentiated thyroid carcinoma, respectively. We reviewed the Lynch syndrome literature on the history, genetics and expanding tumour spectrum of this condition.

  9. Risk factors associated with high thyroglobulin level following radioactive iodine ablation, measured 12 months after treatment for papillary thyroid carcinoma

    PubMed Central

    Kim, Eun Young; Hyun, Kee Hoon; Park, Yong Lai; Park, Chan Heun

    2017-01-01

    Purpose The measurement of serum thyroglobulin (Tg) of papillary thyroid carcinoma patients, 12 months after total thyroidectomy and radioactive iodine (RAI) ablation following thyroxine hormone withdrawal (T4-off Tg) or recombinant human thyroid-stimulating hormone stimulation (rhTSH-Tg), is standard method for monitoring disease status. The aim of this study was to find predictive factors for detectable T4-off Tg during follow-up. Methods A retrospective review was conducted of 329 patients who underwent total thyroidectomy and RAI ablation between October 2008 and August 2012. Subjects were assigned to high (>1 ng/mL, n = 53) and low (≤1 ng/mL, n = 276) groups, based on T4-off Tg measured 12 months postoperatively. Demographic and clinicopathological characteristics at diagnosis and follow-up were compared between the 2 groups. Results The low and high T4-off Tg groups differed with respect to tumor size, preoperative Tg, ablative Tg, cervical lymph node metastasis, thyroglobulinemia out of proportion to results of diagnostic whole body scan, and American Thyroid Association 3-level stratification and restratification. Multivariate analysis confirmed that ablative Tg > 1.0 ng/mL (odds ratio [OR], 10.801; P = 0.001), more than 5 cervical lymph node metastasis (OR, 6.491; P = 0.003), and thyroglobulinemia out of proportion (OR, 9.221; P = 0.000) were risk factors. Conclusion Ablative Tg >1.0 ng/mL, more than 5 cervical lymph node metastasis, and thyroglobulinemia out of proportion were independent factors for T4-off Tg >1 ng/mL 12 months postoperative. In low-risk patients without these risk factors, the possible omission of Tg measurements could be considered during follow-up. PMID:28090499

  10. [Expression of microRNA-221 and IL-17 in papillary thyroid carcinoma and correlation with clinicopathologic features].

    PubMed

    Jiang, X L; Zhang, H; Chen, Y L; Peng, L

    2017-03-08

    Objective: To study the expression of microRNA-221(miR-221) and IL-17 in papillary thyroid carcinoma (PTC) and their roles in the carcinogenesis of PTC. Methods: Real-time RT-PCR, Western blot and immunohistochemistry (IHC) were used to detect the expression of miR-221 and IL-17 in 40 cases of PTC, 20 adjacent normal thyroid tissues and 20 cases of nodular goiter, and the correlation with clinicopathologic features was analyzed. Results: (1)The expression level of miR-221 was significantly higher in PTC compared with nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). The expression of miR-221 was related to TNM staging, capsular invasion and lymph node metastasis (P<0.05) but not to patients' age, sex, tumor size, multifocality, tumor spread and vascular invasion.(2)Real-time RT-PCR and Western blot showed that higher levels of IL-17 mRNA and IL-17 protein in PTC than nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). IHC assay showed positive expression of IL-17 in PTC but not in nodular goiter and adjacent normal thyroid tissue. IL-17 expression was related to TNM staging, capsular invasion and lymph node metastasis, but not to patients' age, sex, tumor size, tumor spread and vascular invasion.(3) Expression analysis revealed a significant correlation between the miR-221 and IL-17 expression (r=0.524, P=0.001). Conclusions: The expressions of miR-221 and IL-17 are significantly higher and positively correlated in PTC, suggesting that miR-221 may regulate IL-17 expression by interacting with a variety of cytokines and inflammatory cells to participate in the development of PTC. miR-221 may be a potential novel prognostic indicator and therapeutic target for PTC.

  11. Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumour: report of three cases with molecular analysis and review of the literature.

    PubMed

    Rossi, S; Fugazzola, L; De Pasquale, L; Braidotti, P; Cirello, V; Beck-Peccoz, P; Bosari, S; Bastagli, A

    2005-06-01

    We report the simultaneous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC), presenting as spatially distinct and well-defined tumour components, in three cases. In the first patient, histology, immunohistochemistry and electron microscopy demonstrated an MTC in the one nodule and PTC in two additional lesions. Non-neoplastic thyroid parenchyma separated the three nodules. Metastasis from PTC was diagnosed in a regional lymph node. Genetic analysis of both tumour components showed a distinctive mutational pattern: in the MTC a Cys634Arg substitution in exon 11 of the RET gene and in the two PTC foci a Val600Glu substitution in exon 15 of the BRAF gene. The other two patients are members of a large multigenerational family affected with familial MTC due to a germline mutation of the RET gene (Ala891Ser). Both patients harboured, besides medullary cancer and C-cell hyperplasia, distinct foci of papillary thyroid cancer, which was positive for Val600Glu BRAF mutation. Review of the literature disclosed 18 similar lesions reported and allowed the identification of different patterns of clinical presentation and biological behaviour. So far, the pathogenesis of these peculiar cases of thyroid malignancy has been completely unknown, but an underlying common genetic drive has been hypothesised. This is the first report in which two mutations, in the RET and BRAF genes, have been identified in three cases of MTC/PTC collision tumour, thus documenting the different genetic origin of these two coexisting carcinomas.

  12. AHR Over-Expression in Papillary Thyroid Carcinoma: Clinical and Molecular Assessments in a Series of Italian Acromegalic Patients with a Long-Term Follow-Up

    PubMed Central

    Mian, Caterina; Ceccato, Filippo; Barollo, Susi; Watutantrige-Fernando, Sara; Albiger, Nora; Regazzo, Daniela; de Lazzari, Paola; Pennelli, Gianmaria; Rotondi, Sandra; Nacamulli, Davide; Pelizzo, Maria Rosa; Jaffrain-Rea, Marie-Lise; Grimaldi, Franco; Occhi, Gianluca; Scaroni, Carla

    2014-01-01

    Aim Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3–7%. Germline mutations in the aryl-hydrocarbon receptor (AHR) interacting protein (AIP) have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC) in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer. Methods Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied. Results 12 DTCs (10 papillary and 2 follicular carcinomas) were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status. Conclusions The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma. PMID:25019383

  13. Mutant-specific BRAF and CD117 immunocytochemistry potentially facilitate risk stratification for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens.

    PubMed

    Meng, Zhilan; Lu, Junliang; Wu, Huanwen; Zhao, Yu; Luo, Yufeng; Gao, Jie; Zhu, Qingli; Jiang, Yuxin; Li, Wenbo; Liang, Zhiyong

    2016-01-01

    The study aims to test whether combination of mutant-specific BRAF and CD117 immunocytochemical (ICC) staining stratifies probability for papillary thyroid carcinoma (PTC) in thyroid fine-needle aspiration biopsy (FNAB) specimens. A consecutive cohort of cases diagnosed as atypia of undetermined significance (AUS) or suspicious for malignancy-suspicious for papillary thyroid carcinoma (SM-SPTC) from 30 December, 2011 to 23 October, 2014 in a single institute was enrolled. Forty cytologically benign and 50 cytologically diagnosed PTC within the same time span were also included. CD117 and mutant-specific BRAF (BRAF VE1) ICC staining was performed. Association of BRAF VE1 and CD117 expression with final diagnosis was analyzed. Both BRAF VE1 and CD117 showed good performance in distinguishing PTC from benign nodules. Combination of BRAF VE1 and CD117 stratified 180 cases into three categories: BRAF VE1 positive regardless of CD117 expression (ICC-malignant), BRAF VE1 negative plus low level of CD117 expression (ICC-intermediate), and BRAF VE1 negative plus high level of CD117 expression (ICC-benign), which was associated with 100, 75.6, and 0 % of malignancy. Combination of mutant-specific BRAF and CD117 ICC may potentially facilitate the PTC risk stratification in FNAB thyroid nodule specimens.

  14. Elevated Concentrations of SERPINE2/Protease Nexin-1 and Secretory Leukocyte Protease Inhibitor in the Serum of Patients with Papillary Thyroid Cancer

    PubMed Central

    Stępień, Tomasz; Brożyna, Mateusz; Kuzdak, Krzysztof; Komorowski, Jan

    2017-01-01

    Introduction. SERPINE2 and secretory leukocyte protease inhibitor (SLPI) are proteins with anticoagulant properties which could promote solid tumor growth. However, their role in the pathogenesis of thyroid cancer has not been determined. Materials and Methods. The aim of this study was to assess serum SERPINE2 and SLPI concentrations in a group of 36 patients with papillary thyroid cancer (PTC) and a group of 19 subjects with multinodular nontoxic goiter (MNG). The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum SERPINE2 and SLPI concentrations were measured using specific ELISA methods. Results. Significantly higher concentrations of SERPINE2 and SLPI were found in patients with PTC as compared with MNG and controls. Positive correlation was found between SERPINE2 and SLPI concentrations in PTC patients. The levels of SERPINE2 and SLPI did not differ significantly between MNG and healthy controls. Conclusions. Our results indicate that SERPINE2 and SLPI play a significant role in the development of papillary thyroid cancer and imply that the evaluation of serum concentrations of both anticoagulant molecules may be considered as additional marker for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors. PMID:28255192

  15. DUSP4/MKP2 overexpression is associated with BRAFV600E mutation and aggressive behavior of papillary thyroid cancer

    PubMed Central

    Ma, Ben; Shi, Rongliang; Yang, Shuwen; Zhou, Li; Qu, Ning; Liao, Tian; Wang, Yu; Wang, Yulong; Ji, Qinghai

    2016-01-01

    The study was performed to retrospectively analyze the correlation of dual specificity phosphatase 4 (DUSP4) expression with clinicopathological variables and BRAFV600E mutation to better characterize the potential role of DUSP4 as a biomarker in papillary thyroid cancer (PTC). Patients (n=120) who underwent surgery for PTC at Fudan University Shanghai Cancer Center (FUSCC) were enrolled in this study, and a validation cohort from The Cancer Genome Atlas (TCGA) database was identified to confirm the preliminary findings in our study. We investigated DUSP4 expression at the mRNA level in PTC tissues and adjacent normal tissues using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). BRAFV600E mutation analysis was also performed in PTC tissues using Sanger sequencing. Initially, we compared PTC tissues with paired normal tissues in DUSP4 expression using Student’s t-test, and then analyzed the correlation of DUSP4 with clinicopathological variables and BRAFV600E mutation in PTC using Mann–Whitney U, Kruskal–Wallis, χ2, and Fisher’s exact tests. Human-derived thyroid cell lines were also used to verify our findings. DUSP4 was significantly overexpressed in PTC tissues compared with the adjacent normal tissues (P<0.001). High DUSP4 expression showed a significant association with lymph node metastasis and extrathyroidal extension in both FUSCC and TCGA cohorts, and DUSP4 overexpression was an independent risk factor for lymph node metastasis in multivariate analysis. Additionally, DUSP4 expression was associated with BRAFV600E mutation in both the cohorts (FUSCC: P=0.002, TCGA: P<0.001) and PTC cell lines (P=0.023). In conclusion, DUSP4 was identified as a potential biomarker for aggressive behavior in PTC, and its overexpression was BRAFV600E mutation-related. PMID:27143921

  16. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    PubMed Central

    Cohn, Allen L; Day, Bann-Mo; Abhyankar, Sarang; McKenna, Edward; Riehl, Todd; Puzanov, Igor

    2017-01-01

    Background Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study. Methods Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing. Results Overall incidence of BRAFV600E mutation in evaluable patients (n=548) was 3% (95% confidence interval [CI], 1.7–4.7): 11% in colorectal tumors (n=75), 6% in biliary tract tumors (n=16), 3% in non-small cell lung cancers (n=71), 2% in other types of solid tumors (n=180), and 3% in multiple myeloma (n=31). There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68), breast cancer (n=86), or prostate cancer (n=21). Conclusion This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. PMID:28255242

  17. Frequent BRAF (V600E) and Absence of TERT Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan.

    PubMed

    Oishi, Naoki; Kondo, Tetsuo; Nakazawa, Tadao; Mochizuki, Kunio; Inoue, Tomohiro; Kasai, Kazunari; Tahara, Ippei; Yabuta, Tomonori; Hirokawa, Mitsuyoshi; Miyauchi, Akira; Katoh, Ryohei

    2017-02-07

    Pediatric papillary thyroid carcinoma (PTC) has unique features but requires further genetic investigation. Moreover, there has been increasing concern about the risk for pediatric PTC in Japan after the Fukushima accident. This study aims to evaluate the frequencies of BRAF and TERT promoter mutations and to examine their significance in non-radiation-associated pediatric PTCs in Japan. We enrolled 81 pediatric PTC patients aged ≤20 years. The control group included 91 adult PTCs from patients >20 years old. BRAF and TERT mutations were analyzed by allele-specific-PCR and/or Sanger sequencing. Compared with adult PTCs, pediatric PTCs exhibited larger tumor size, more frequent lymph node metastasis, and less classical histology. The prevalence of BRAF (V600E) in pediatric PTCs was 54% and significantly lower than that in adults of 85%. In the pediatric PTCs, BRAF (V600E) was positively associated with older age, classical histology, and the lymph node metastasis but independent from other clinicopathological factors. TERT mutations were identified in 13% of adults and in none of the pediatric PTCs. In conclusion, pediatric PTCs are characterized by more advanced clinicopathological features, lower BRAF (V600E) frequency, and absence of TERT mutation. The BRAF (V600E) frequency in this study is similar to the reported BRAF (V600E) frequency in the ultrasonographically screened pediatric PTCs in Fukushima.

  18. Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

    PubMed Central

    Detours, V; Delys, L; Libert, F; Weiss Solís, D; Bogdanova, T; Dumont, J E; Franc, B; Thomas, G; Maenhaut, C

    2007-01-01

    Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, γ-radiation and H2O2. On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to γ-radiation and H2O2 are similar. On a finer scale, a 118 genes signature discriminated the γ-radiation and H2O2 responses. This signature could be used to classify the tumours as CTB or French with an error of 15–27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to γ-radiation and H2O2. These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test. PMID:17712314

  19. Long intergenic non-coding RNA 271 is predictive of a poorer prognosis of papillary thyroid cancer

    PubMed Central

    Ma, Ben; Liao, Tian; Wen, Duo; Dong, Chuanpeng; Zhou, Li; Yang, Shuwen; Wang, Yu; Ji, Qinghai

    2016-01-01

    A number of long non-coding RNAs (lncRNAs) have been found to play critical roles in oncogenesis and tumor progression. We aimed to investigate whether lncRNAs could act as prognostic biomarkers for papillary thyroid cancer (PTC) that may assist us in evaluating disease status and prognosis for patients. We found 220 lncRNAs with expression alteration from the annotated 2773 lncRNAs approved by the HUGO gene nomenclature committee in The Cancer Genome Atlas (TCGA) dataset, of which FAM41C, CTBP1-AS2, LINC00271, HAR1A, LINC00310 and HAS2-AS1 were associated with recurrence. After adjusting classical clinicopathogical factors and BRAFV600E mutation, LINC00271 was found to be an independent risk factor for extrathyroidal extension, lymph node metastasis, advanced tumor stage III/IV and recurrence in multivariate analyses. Additionally, LINC00271 expression was significantly downregulated in PTCs versus adjacent normal tissues (P < 0.001). The Gene Set Enrichment Analysis (GSEA) revealed that genes associated with cell adhesion molecules, cell cycle, P53 signaling pathway and JAK/STAT signaling pathway were remarkably enriched in lower-LINC00271 versus higher-LINC00271 tumors. In conclusion, LINC00271 was identified as a possible suppressor gene in PTC in our study, and it may serve as a potential predictor of poor prognoses in PTC. PMID:27833134

  20. miR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma

    SciTech Connect

    Liu, Lianyong; Wang, Jingnan; Li, Xiangqi; Ma, Junhua; Shi, Chao; Zhu, Hongling; Xi, Qian; Zhang, Jichen; Zhao, Xuemei; Gu, Mingjun

    2015-02-20

    microRNAs (miRNAs) are frequently dysregulated in human malignancies. It was recently shown that miR-204-5p is downregulated in papillary thyroid carcinoma (PTC); however, the functional significance of this observation is not known. This study investigated the role of miR-204-5p in PTC. Overexpressing miR-204-5p suppressed PTC cell proliferation and induced cell cycle arrest and apoptosis. The results of a luciferase reporter assay showed that miR-204-5p can directly bind to the 3′ untranslated region (UTR) of insulin-like growth factor-binding protein 5 (IGFBP5) mRNA, and IGFBP5 overexpression partially reversed the growth-inhibitory effects of miR-204-5p. These results indicate that miR-204-5p acts as a tumor suppressor in PTC by regulating IGFBP5 expression and that miR-204-5p can potentially serve as an antitumorigenic agent in the treatment of PTC. - Highlights: • miR-204-5p expression is downregulated in PTC tissues and cell lines. • miR-204-5p suppresses proliferation and promotes apoptosis in PTC cells. • miR-204-5p suppresses IGFBP5 expression by direct binding to the 3′-UTR. • IGFBP5 overexpression reverses the effects of miR-204-5p.

  1. A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition

    PubMed Central

    Tomsic, Jerneja; He, Huiling; Akagi, Keiko; Liyanarachchi, Sandya; Pan, Qun; Bertani, Blake; Nagy, Rebecca; Symer, David E.; Blencowe, Benjamin J.; Chapelle, Albert de la

    2015-01-01

    Papillary thyroid carcinoma (PTC) displays strong but so far largely uncharacterized heritability. Here we studied genetic predisposition in a family with six affected individuals. We genotyped all available family members and conducted whole exome sequencing of blood DNA from two affected individuals. Haplotype analysis and other genetic criteria narrowed our list of candidates to a germline variant in the serine/arginine repetitive matrix 2 gene (SRRM2). This heterozygous variant, c.1037C > T (Ser346Phe or S346F; rs149019598) cosegregated with PTC in the family. It was not found in 138 other PTC families. It was found in 7/1,170 sporadic PTC cases and in 0/1,404 controls (p = 0.004). The encoded protein SRRM2 (also called SRm300) is part of the RNA splicing machinery. To evaluate the possibility that the S346F missense mutation affects alternative splicing, we compared RNA-Seq data in leukocytes from three mutation carriers and three controls. Significant differences in alternative splicing were identified for 1,642 exons, of which a subset of 7 exons was verified experimentally. The results confirmed a higher ratio of inclusion of exons in mutation carriers. These data suggest that the S346F mutation in SRRM2 predisposes to PTC by affecting alternative splicing of unidentified downstream target genes. PMID:26135620

  2. Pathologic features of metastatic lymph nodes identified from prophylactic central neck dissection in patients with papillary thyroid carcinoma.

    PubMed

    Lee, Hyoung Shin; Park, Chanwoo; Kim, Sung Won; Noh, Woong Jae; Lim, Soo Jin; Chun, Bong Kwon; Kim, Beom Su; Hong, Jong Chul; Lee, Kang Dae

    2016-10-01

    The importance of pathologic features of metastatic lymph nodes (LNs), such as size, number, and extranodal extension, has been recently emphasized in patients with papillary thyroid carcinoma (PTC). We evaluated the characteristics of metastatic LNs identified after prophylactic central neck dissection (CND) in patients with PTC. We performed a retrospective review of 1,046 patients who underwent unilateral or bilateral thyroidectomy with ipsilateral prophylactic CND. We reviewed the characteristics of the metastatic LNs and analyzed their correlation to the clinicopathologic characteristics of the primary tumor. Cervical LN metastasis after prophylactic CND was identified in 280 out of 1046 patients (26.8 %). The size of metastatic foci (≥2 mm) was independently correlated with primary tumor size (≥1 cm) (p = 0.016, OR = 1.88). Primary tumor size (≥1 cm) was also correlated to the number of metastatic LNs (≥5) (p = 0.004, OR = 3.14) and extranodal extension (p = 0.021, OR = 2.41) in univariate analysis. The size of the primary tumor affects pathologic features of subclinical LN metastasis in patients with PTC. Patients with primary tumors ≥1 cm have an increased risk of larger LN metastases (≥2 mm), an increased number of LN metastases (≥5), and a higher incidence of ENE, which should be considered in decision for prophylactic CND.

  3. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma

    SciTech Connect

    Zhu, Hongling; Fang, Jin; Zhang, Jichen; Zhao, Zefei; Liu, Lianyong; Wang, Jingnan; Xi, Qian; Gu, Mingjun

    2014-07-18

    Highlights: • miR-182 and CHL1 expression patterns are negatively correlated. • CHL1 is a direct target of miR-182 in PTC cells. • miR-182 suppression inhibits PTC cell growth and invasion. • CHL1 is involved in miR-182-mediated cell behavior. - Abstract: In this study, we investigated the role and underlying mechanism of action of miR-182 in papillary thyroid carcinoma (PTC). Bioinformatics analysis revealed close homolog of LI (CHL1) as a potential target of miR-182. Upregulation of miR-182 was significantly correlated with CHL1 downregulation in human PTC tissues and cell lines. miR-182 suppressed the expression of CHL1 mRNA through direct targeting of the 3′-untranslated region (3′-UTR). Downregulation of miR-182 suppressed growth and invasion of PTC cells. Silencing of CHL1 counteracted the effects of miR-182 suppression, while its overexpression mimicked these effects. Our data collectively indicate that miR-182 in PTC promotes cell proliferation and invasion through direct suppression of CHL1, supporting the potential utility of miR-182 inhibition as a novel therapeutic strategy against PTC.

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

    ClinicalTrials.gov

    2017-03-15

    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

  5. Clinicopathological Features and Prognosis of Papillary Thyroid Microcarcinoma for Surgery and Relationships with the BRAFV600E Mutational Status and Expression of Angiogenic Factors

    PubMed Central

    Shi, Chenlei; Guo, Yong; Lv, Yichen; Nanding, Abiyasi; Shi, Tiefeng; Qin, Huadong; He, Jianjun

    2016-01-01

    Objective To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) for surgery by comparing the difference between PTMC and larger papillary thyroid carcinoma (LPTC). Methods We analyzed the differences in the clinicopathological characteristics, prognosis, B-type RAF kinase (BRAF)V600E mutational status and expression of angiogenic factors, including pigment epithelium-derived factor (PEDF), Vascular Endothelial Growth Factor (VEGF), and hypoxia-inducible factor alpha subunit (HIF-1α), between PTMC and LPTC by retrospectively reviewing the records of 251 patients with papillary thyroid carcinoma, 169 with PTMC, and 82 with LPTC (diameter >1 cm). Results There were no significant differences in the gender, age, multifocality, Hashimoto’s thyroiditis, TNM stage, PEDF protein expression, rate of recurrence, or mean follow-up duration between patients with PTMC or LPTC. The prevalence of extrathyroidal invasion (EI), lymph node metastasis (LNM), and BRAF mutation in patients with PTMC was significantly lower than in patients with LPTC. In addition, in PTMC patients with EI and/or LNM and/or positive BRAF (high-risk PTMC patients), the prevalence of extrathyroidal invasion, Hashimoto's disease, lymph node metastasis, tumor TNM stage, PEDF positive protein expression, the rate of recurrent disease, and the mRNA expression of anti-angiogenic factors was almost as high as in patients with larger PTC, but with no significant difference. Conclusions Extrathyroid invasion, lymph node metastases, and BRAFV600E mutation were the high risk factors of PTMC. PTMC should be considered for the same treatment strategy as LPTC when any of these factors is found. Particularly, PTMC with BRAFV600E gene mutations needed earlier surgical treatment. In addition, the high cell subtype of PTMC with BRAFV600E gene mutation is recommended for total thyroidectomy in primary surgery to reduce the risk of recurrence. PMID:27936049

  6. Is Every Patient Followed up as a Papillary Thyroid Cancer Patient Really That?

    PubMed Central

    Abdulrezzak, Ummuhan; Tutus, Ahmet; Kula, Mustafa; Öztürk, Figen; Soyuer, Işın

    2012-01-01

    We report the case of a 64-year-old man followed up for two years as suffering from differentiated thyroid cancer (DTC). In the patient’s follow up, despite thyroglobulin level and I-131 whole body scan results being normal, metastases were identified at the 4th thoracic vertebra corpus by MR. Histopathological findings were carcinoma metastases. F-18 FDG PET/CT showed increased metabolic activity in the right renal mass, bilaterally in the surrenal gland, multiple lymph nodes in the thoracic and abdominal para-aortic region and in multiple vertebral and pelvic bones. An excisional biopsy of the right renal mass was reported as renal cell carcinoma. Immunohistochemical staining performed retrospectively to the first thyroid preparation showed renal cell carcinoma metastases. Consequently, any patient who presents with a thyroid nodule can also be considered as possibly suffering from metastatic disease. F-18 FDG PET/CT can provide valuable information in finding the primary focus and metastases. Conflict of interest:None declared. PMID:23487501

  7. Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis

    PubMed Central

    Mohamad Yusof, Azliana; Abdullah Suhaimi, Shahrun Niza; Muhammad, Rohaizak; Jamal, Rahman

    2016-01-01

    Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19–24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine–cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E−06) involving downregulation

  8. A comparison of the clinicopathological features and prognoses of the classical and the tall cell variant of papillary thyroid cancer: a meta-analysis

    PubMed Central

    Chen, Tianwen; Guo, Yawen; Zhang, Chao

    2017-01-01

    Papillary thyroid cancer (PTC) accounts for 80–90% of all thyroid malignancies. The tall cell variant (TCV) is a rare aggressive histotype of PTC. We performed a meta-analysis to compare the clinicopathological characteristics and prognostic factors of TCV with those of classical papillary thyroid carcinoma (cPTC). A literature search was performed using the PubMed and EMBASE databases using Medical Subject Headings and keywords. Twenty studies that included 1871 patients with TCV and 75323 patients with cPTC were included in our meta-analysis. Odds ratios and confidence intervals were calculated for each study. Patients with TCV were associated with multifocality, higher TNM stage, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, BRAF mutation, disease-specific survival, and overall survival. We found that TCV cases were associated with more aggressive clinicopathological characteristics and poorer prognoses than cPTC cases were. Our results suggest that TCV is a high-risk PTC that warrants aggressive treatment and follow-up strategies. PMID:28009980

  9. Pembrolizumab and Lenvatinib in Treating Metastatic or Recurrent Differentiated Thyroid Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-01-24

    Columnar Cell Variant Thyroid Gland Papillary Carcinoma; Follicular Variant Thyroid Gland Papillary Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage III Differentiated 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; Stage IVA Differentiated Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Differentiated Thyroid Gland Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Differentiated Thyroid Gland 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

  10. Utility of SPECT/CT as an adjunct to planar whole body I-131 imaging: liver metastasis from papillary thyroid cancer.

    PubMed

    Agriantonis, Demetrios J; Hall, Lance; Wilson, Michael A

    2009-04-01

    One of the major limitations of planar I-131 imaging is its lack of anatomic precision. SPECT/CT offers the benefit of precise anatomic localization that planar imaging lacks. Whether for confirmation of physiologic uptake or true pathology, SPECT/CT has an important role to play in clarifying equivocal findings. We present a case of papillary thyroid cancer metastatic to the liver, a relatively rare scenario. SPECT/CT allowed definitive lesion characterization at the time of the patient's visit to the nuclear medicine department.

  11. Comparative Study between Robotic Total Thyroidectomy with Central Lymph Node Dissection via Bilateral Axillo-breast Approach and Conventional Open Procedure for Papillary Thyroid Microcarcinoma

    PubMed Central

    He, Qing-Qing; Zhu, Jian; Zhuang, Da-Yong; Fan, Zi-Yi; Zheng, Lu-Ming; Zhou, Peng; Hou, Lei; Yu, Fang; Li, Yan-Ning; Xiao, Lei; Dong, Xue-Feng; Ni, Gao-Feng

    2016-01-01

    Background: A large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection (CND) emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach (BABA), compared with conventional open procedure in papillary thyroid microcarcinoma. Methods: One-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People's Liberation Army (PLA) were randomly assigned to robotic group or conventional open approach group (n = 50 in each group). The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale (VAS), postoperative hospital stay time, complications, and numerical scoring system (NSS, used to assess cosmetic effect) were analyzed. Results: The robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group (118.8 ± 16.5 min vs. 90.7 ± 10.3 min, P < 0.05). The study showed significant differences between the two groups in terms of the VASs (2.1 ± 1.0 vs. 3.8 ± 1.2, P < 0.05) and NSS (8.9 ± 0.8 vs. 4.8 ± 1.7, P < 0.05). The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant (all P > 0.05). Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups

  12. miR-219–5p Modulates Cell Growth of Papillary Thyroid Carcinoma by Targeting Estrogen Receptor α

    PubMed Central

    Huang, Chen; Cai, Zhaogeng; Huang, Mingzhu; Mao, Chaoming; Zhang, Qifa; Lin, Yi; Zhang, Xiaomei; Tang, Bi; Chen, Yuqing; Wang, Xiaojing; Qian, Zhongqing; Ye, Lei

    2015-01-01

    Context: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. It has been demonstrated that micro-RNAs (miRNAs) are involved in the development of PTC. The miRNA-chromatin immunoprecipitation microarray assay revealed down-regulation of miR-219–5p; however, the effect of miR-219–5p on PTC cell growth remains unknown. This result implied the critical role of miR-219–5p in the development of PTC. Methods: We investigated the association between miR-219–5p and PTC development. Expression of miR-219–5p was monitored in 30 PTC tissue specimens and compared with that in 30 normal thyroid tissue specimens. The effect of miR-219–5p on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanism was clarified by a reporter assay and rescue experiment. Results: The current study confirmed that miR-219–5p expression was inhibited in PTC tissue samples. There were statistically significant differences in the expression of miR-219–5p with regard to sex, tumor size, and lymph node metastasis in patients with PTC. Forced expression of miR-219–5p suppressed PTC cell proliferation and migration and promoted apoptosis. Further study showed that estrogen receptor (ER) α was the direct target of miR-219–5p and mediated the effect of miR-219–5p on PTC occurrence. Expression of miR-219–5p was inversely correlated with that of ERα. Importantly, ERα overexpression in PTC cells rescued the inhibitory effect of miR-219–5p on PTC cell proliferation and migration. Thus, our results indicated that miR-219–5p played a critical role in PTC growth by inhibiting ERα. Conclusion: Our investigation identified miR-219–5p as a negative regulator of PTC development through targeting of ERα. PMID:25423566

  13. TERT promoter Mutation and Its Association with Clinicopathological Features and Prognosis of Papillary Thyroid Cancer: A Meta-analysis

    PubMed Central

    Liu, Chunping; Liu, Zeming; Chen, Tianwen; Zeng, Wen; Guo, Yawen; Huang, Tao

    2016-01-01

    We performed a meta-analysis to elucidate the associations of the clinicopathological characteristics and prognostic factors of papillary thyroid cancer (PTC) with TERT promoter mutations. A literature search was performed of the PubMed and EMBASE databases using Medical Subject Headings and keywords. Individual study-specific odds ratios (ORs) and confidence intervals (CIs) were calculated. The average prevalence rate of TERT promoter mutations was 10.1%. TERT promoter mutations occurred more frequently in patients with larger tumors (p = 0.003). TERT promoter mutations were associated with advanced stage (OR = 3.11, 95% CI = 2.22–4.36), lymph node metastasis (OR = 1.82, 95% CI = 1.12–2.96), distant metastasis (OR = 4.18, 95% CI = 1.61–10.81), BRAF mutation positivity (OR = 2.71, 95% CI = 1.45–3.24), recurrence (OR = 3.91, 95% CI = 1.83–8.34), and mortality (OR = 8.13, 95% CI = 3.77–17.53). The associations of TERT promoter mutations with extrathyroidal invasion (OR = 1.98, 95% CI = 0.96–4.07), unifocality (OR = 1.36, 95% CI = 0.90–2.07), and vascular invasion (OR = 1.45, 95% CI = 0.92–2.30) were not significant. TERT promoter mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in PTC. PMID:27833153

  14. Improvement in the Detection of Cystic Metastatic Papillary Thyroid Carcinoma by Measurement of Thyroglobulin in Aspirated Fluid.

    PubMed

    Wang, Yong; Zhao, Huan; Wang, Yi-Xiang J; Wang, Min-Jie; Zhang, Zhi-Hui; Zhang, Li; Zhang, Bin; Ahuja, Anil T; Zhou, Chun-Wu; Jiang, Yu-Xin; Guo, Hui-Qin

    2016-01-01

    Cystic change in metastatic lymph nodes of papillary thyroid carcinoma (PTC) is a diagnostic challenge for fine needle aspiration (FNA) because of the scant cellularity. The aim of this study was to evaluate the measurement of thyroglobulin in fine needle aspirate (Tg-FNA) for detecting metastatic PTC in patients with cystic neck lesions and to validate the optimal cutoff value of Tg-FNA. A total of 75 FNA specimens of cystic lesions were identified, including 40 of metastatic PTC. Predetermined threshold levels of 0.04 (minimum detection level), 0.9, 10.0, and 77.0 ng/mL (maximum normal serum-Tg level) were used to evaluate the diagnostic accuracy of Tg-FNA for metastatic PTC detection. The areas under the receiver operating characteristic curve for diagnosing metastatic PTC of Tg-FNA values of 0.04, 0.9, 10.0, and 77.0 ng/mL were 0.5 (95% confidence interval [CI], 0.382-0.618), 0.645 (95% CI, 0.526-0.752), 0.945 (95% CI, 0.866-0.984), and 0.973 (95% CI, 0.907-0.996), respectively. With a cutoff value of 77.0 ng/mL, the combination of Tg-FNA and FNA cytology showed superior diagnostic power (97.5% sensitivity and 100% specificity) compared to FNA cytology alone (80% sensitivity and 100% specificity). We recommend a Tg-FNA cutoff of 77.0 ng/mL, the maximum normal serum-Tg level, for cystic neck lesions.

  15. Immunohistochemistry is highly sensitive and specific for detecting the BRAF V600E mutation in papillary thyroid carcinoma.

    PubMed

    Sun, Jian; Zhang, Jing; Lu, Junliang; Gao, Jie; Lu, Tao; Ren, Xinyu; Duan, Huanli; Liang, Zhiyong

    2015-01-01

    The V600E mutation in the B-type Raf kinase (BRAF) gene is a common genetic change in cases of papillary thyroid carcinoma (PTC) that appears to play a key role in the development and progression of this disease. We sought to assess the sensitivity and specificity of immunohistochemical detection of this mutation with a V600E mutated BRAF antibody in a Chinese PTC cohort. In this study, we used fully automated immunohistochemistry (IHC) assay with a BRAF V600E (VE1) mouse monoclonal primary antibody to screen for the BRAF V600E mutation in 556 cases of PTC. Moreover, to verify the IHC staining results, real-time PCR was applied to detect this mutation in the same patient cohort. Among the 556 cases in the examined primary PTC cohort, 414 (74.5%) cases and 419 (75.4%) cases were positive for the BRAF V600E mutation by IHC staining and by real-time PCR, respectively. The real-time PCR results indicated that the sensitivity and specificity of IHC staining for the BRAF V600E mutation were 98.8% and 100%, respectively. The BRAF V600E mutation was common among Chinese patients with primary PTC, and was strongly correlated with older patient age and the conventional subtype of PTC but was not associated with parameters of clinicopathological aggressiveness. The fully automated IHC is a reliable technique that can serve as an alternative to molecular biological approaches for the routine detection of the BRAF V600E mutation in PTC patients.

  16. A meta-analysis on the effect of operation modes on the recurrence of papillary thyroid microcarcinoma

    PubMed Central

    Tang, Xiaoqiao; Sang, Jianfeng

    2017-01-01

    Whether total thyroidectomy reduces the recurrence rate in patients with papillary thyroid microcarcinoma (PTMC) is currently controversy. Conclusions of sporadic, inconsistent, and mono-institutional studies need a meta-analysis to evaluate. 525 relevant studies were obtained from initial search on PubMed, 511 studies were excluded by inclusion and exclusion criteria. Eligible data were extracted from each included study. The Odds ratios (ORs) and 95% confidence interval (CI) were used to assess the difference in the recurrence rates between PTMC patients treated with total thyroidectomy and non-total thyroidectomy. OR and 95% CI were calculated using a fixed-effects or a random-effects model. The Q statistic was used to evaluate homogeneity and Beggs test was used to assess publication bias. 14 studies meeting the inclusion criteria were included in this meta-analysis. The over all recurrence rates of pooled patients with total thyroidectomy and non-total thyroidectomy were 2.83% and 2.84% respectively. Primary random-effects model analysis showed, no significant difference of recurrence rates existed between two operation modes (OR = 0.732, 95% CI: 0.444 - 1.208), while, high heterogeneity among studies was found, I-squared index (I2) = 40.2%. After remove one study with high heterogeneity, the OR of the pooled recurrence rates of the total thyroidectomy and the non-total thyroidectomy groups was 0.786 (95% CI: 0.363 - 1.701), further suggesting no significant difference of the recurrence rate exists between two operation modes. Our meta-analysis demonstrated postoperative recurrence of PTMC is not reduced by total thyroidectomy, non-total thyroidectomy is also a good choice to treat PTMC patients. PMID:27756889

  17. Selective inhibitors of aurora kinases inhibit proliferation, reduce cell viability and impair cell cycle progression in papillary thyroid carcinoma cells.

    PubMed

    Baldini, E; Tuccilli, C; Prinzi, N; Sorrenti, S; Antonelli, A; Fallahi, P; Mian, C; Barollo, S; Catania, A; Morrone, S; Tartaglia, F; Mascagni, D; Coccaro, C; Pepe, M; Filippini, A; D'Armiento, M; Ulisse, S

    2015-01-01

    The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC₅₀ comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC.

  18. Preoperative ultrasound-guided carbon nanoparticles localization for metastatic lymph nodes in papillary thyroid carcinoma during reoperation

    PubMed Central

    Zhao, Wan-jun; Luo, Han; Zhou, Yi-mei; Gou, Ze-hui; Wang, Bin; Zhu, Jing-qiang

    2017-01-01

    Abstract Due to the damaged anatomical structure and a large amount of fibrous and scar tissues in the surgical field, reoperation of papillary thyroid carcinoma is difficult. This study introduces a new method of locating metastatic lymph nodes during reoperation and evaluates the effectiveness and safety of the preoperative ultrasound-guided carbon nanoparticles (CNs) localization. This retrospective cohort study enrolled 52 patients who were diagnosed with lymph node metastasis by histopathology and underwent reoperation from October 2015 to February 2016. The modified radical neck dissection or selective neck node dissection was performed. A total of 26 patients underwent preoperative ultrasound-guided CNs injection, and other 26 patients did not. Tolerance, the result of injection, the number of resected metastatic lymph nodes, and postoperative complications were recorded and analyzed. In CNs group, 102 suspicious nonpalpable lesions in 26 patients were injected with CNs, and 99 of the 102 lesions were successfully identified by surgeon in the reoperation. The positive rate of resected lymph nodes in total, in the central compartment, and in the lateral compartment were 31.6%, 31.2%, and 32.8%, respectively, which was significantly higher than that in the control group (P < 0.001, P < 0.001, and P = 0.041). In addition, the positive rates of levels III, IV, and V in the CNs group were 35.6%, 21.9%, and 30.5%, respectively, which was significantly higher than that in the control group (P < 0.001, P = 0.005, and P = 0.01). In additional, in the CNs group, the rate of temporary hypoparathyroidism was significantly lower compared with the control group (0% vs 26.9%, P = 0.021). Preoperative ultrasound-guided CNs injection is a safe and effective method for localization of the metastatic lymph nodes during reoperation. PMID:28272249

  19. To Identify Predictors of Central Lymph Node Metastasis in Patients with Clinically Node-Negative Conventional Papillary Thyroid Carcinoma

    PubMed Central

    Zhao, Gang; Du, Jialin; Chen, Xiaoyi; Lin, Xiaodong; Chen, Zhengbo

    2016-01-01

    Objective. The aim of this study was to identify the risk factors associated with central lymph node metastasis (CLNM) in patients with clinically node-negative conventional papillary thyroid carcinoma (cN0 CPTC). Methods. A total of 190 cN0 CPTC patients who underwent thyroidectomy with prophylactic central neck dissection (pCND) in the Department of General Surgery at Guangdong General Hospital between March 2014 and December 2015 were assessed retrospectively. The relations of CLNM with clinicopathologic characteristics of cN0 CPTC were analyzed by univariate and multivariate logistic regression. Results. The incidence of CLNM in patients with cN0 CPTC was 63.2% (120 of 190 cases). Univariate analysis showed that age <45 years (P = 0.000), tumor size >2 cm (P = 0.009), multifocality (P = 0.001), and bilaterality (P = 0.000) were significantly associated with the increased incidence of CLNM in cN0 CPTC. No significant correlations were found between CLNM and other variables such as gender (P = 0.150), capsular invasion (P = 0.973), extrathyroidal invasion (P = 0.616), and lymphadenectomy (P = 0.062). Multivariate logistic regression analysis revealed that age <45 years (P = 0.000), tumor size >2 cm (P = 0.025), and bilaterality (P = 0.000) were independent risk factors of CLNM in patients with cN0 CPTC. Conclusions. Metastatic disease to central compartment lymph nodes is prevalent in patients with cN0 CPTC. Age <45 years, tumor size >2 cm, and bilaterality are independent risk factors of CLNM, which allow for selective CND in patients with cN0 CPTC. PMID:28074094

  20. MicroRNA-363-3p inhibits papillary thyroid carcinoma progression by targeting PIK3CA

    PubMed Central

    Liu, Jia; Li, Qun; Li, Rui; Ren, Peiyou; Dong, Su

    2017-01-01

    MicroRNA-363-3p (miR-363-3p) reportedly plays crucial roles in tumor development and progression in many types of cancers. However, its role in papillary thyroid carcinoma (PTC) remain largely unclear. We therefore investigated the function and underlying mechanism of miR-363-3p in PTC. Here, we found that miR-363-3p was significantly downregulated in human PTC tissue samples and cell lines, and that miR-363-3p levels are negatively correlated with advanced clinical stage and lymph node metastasis. In addition to suppressing tumor growth in vivo, restoration of miR-363-3p in TPC-1 cells significantly inhibits proliferation, migration, and invasion and induced apoptosis in vitro. Mechanistically, miR-363-3p was verified to directly bind to 3’UTR of the phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) mRNA, and reduce its expression at both mRNA and protein levels, which further inhibits phosphatidylinositol 3-kinase/Akt signaling pathway. PIK3CA expression was also found to be increased in human PTC tissues, and were inversely correlated with miR-363-3p. Furthermore, restoration of PIK3CA partially rescued the miR-363-3p-induced inhibition effect on TPC-1 cell proliferation, migration and invasion. Taken together, these findings indicated for the first time that miR-363-3p functions as a tumor suppressor in PTC, and its suppressive effect is mediated by repressing PIK3CA. PMID:28123856

  1. Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer

    PubMed Central

    Kwong, Norra; Marqusee, Ellen; Gordon, Michael S; Larsen, P Reed; Garber, Jeffrey R; Kim, Matthew I; Alexander, Erik K

    2014-01-01

    Well-differentiated thyroid carcinoma (WDTC) generally has a favorable prognosis. However, patients with distant metastatic disease experience progression of disease with a higher mortality. A subset of patients not previously described may challenge the conventional dogma regarding the progressive nature of all metastatic WDTC. Through analysis of our database, we identified patients with distant metastatic WDTC and persistent, minimally progressive disease. In all patients, persistent metastatic disease was confirmed via tissue biopsy, abnormal PET scan, and/or biochemical elevations in thyroglobulin or antibody levels. Progression of disease was monitored clinically and with repeat imaging. We describe five patients with WDTC and pulmonary metastases, aged 8–43 years at diagnosis. All patients underwent initial surgery and radioactive iodine (RAI) ablation, with some receiving multiple treatments. Persistent pulmonary metastatic disease was confirmed over decades (mean 22 years, range 8–42 years) with minimal progression despite no further treatment beyond thyroid hormone suppression. Persistent disease was biopsy-proven in all patients at a mean of 9.6 years from last RAI treatment. All patients had elevated thyroglobulin or anti-thyroglobulin antibody levels, while three demonstrated metabolically active disease with positive FDG uptake on PET scan, and one patient with persistent radioactive iodine avid pulmonary metastasis 36 years after her last RAI treatment. This case series demonstrates that some patients with distant metastases, even if metabolically active and radioactive iodine resistant, remain stable for decades without further treatment. Clinical awareness of such patients and continual reassessment of disease risk following initial therapy are crucial as aggressive treatment may not be necessary. PMID:25316293

  2. Study of Immunohistochemical Markers (CK-19, CD-56, Ki-67, p53) in Differentiating Benign and Malignant Solitary Thyroid Nodules with special Reference to Papillary Thyroid Carcinomas

    PubMed Central

    Dwivedi, Smriti Sudhanshu; Joshi, Avinash R; Kulkarni, Maithili Mandar; Bhayekar, Pallavi; Jadhav, Amruta; Nayar, Musphera; Kambale, Neelam S

    2016-01-01

    Introduction Solitary Thyroid Nodule (STN) has provoked increased concern owing to higher incidence of malignancy. The inter and intra observer variation in the histomorphological diagnosis of Papillary Thyroid Carcinomas (PTC) may sometimes pose a diagnostic difficulty. Aim This study was undertaken to analyse immunohistochemical (IHC) markers (CK-19, CD-56, p53, Ki-67) to differentiate between benign and malignant surgically resected STN along with their utility in the identification of PTC. Materials and Methods The present cross sectional study was conducted over a period of 4 years. A technique of manual tissue array was employed for cases subjected to IHC. The primary antibodies used were CK-19, CD-56, p53 and Ki-67. Analysis of the expression of IHC markers (p53, Ki-67) to distinguish between benign and malignant STN was done. Evaluation and correlation of expression of IHC markers (CK-19, CD-56) to determine its utility in reaching definitive diagnosis and assessing prognosis of PTC was tried. Results were subjected to statistical analysis. The results were considered to be significant when the p-value <0.05. Results Out of the 160 cases of surgically resected STN specimens, 68 cases were non-neoplastic, 24 cases were benign and 68 cases were of malignant tumours (7 cases of follicular carcinoma (FCa), 61 cases of PTC). CK-19 was found to be a sensitive (83.61%) and a highly specific positive marker (100%) for the diagnosis of PTC. The difference in CD-56 expression between PTC and non-PTC group was found to be highly statistically significant. CD-56 was found to be a sensitive (85.86%) and specific (82.25%) negative marker in differentiating PTC from follicular lesions/neoplasms. The difference in p53 expression between the malignant and non-malignant STN cases was found to be highly statistically significant with a sensitivity and specificity 85.29% and 70.65% respectively. The statistical difference in mean Ki-67 Labeling Index (LI) was found to be

  3. BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma

    PubMed Central

    Rusinek, Dagmara; Swierniak, Michal; Chmielik, Ewa; Kowal, Monika; Kowalska, Malgorzata; Cyplinska, Renata; Czarniecka, Agnieszka; Piglowski, Wojciech; Korfanty, Joanna; Chekan, Mykola; Krajewska, Jolanta; Szpak-Ulczok, Sylwia; Jarzab, Michal; Widlak, Wieslawa; Jarzab, Barbara

    2015-01-01

    Background The molecular mechanisms driving the papillary thyroid carcinoma (PTC) are still poorly understood. The most frequent genetic alteration in PTC is the BRAFV600E mutation–its impact may extend even beyond PTC genomic profile and influence the tumor characteristics and even clinical behavior. Methods In order to identify BRAF-dependent signature of early carcinogenesis in PTC, a transgenic mouse model with BRAFV600E-induced PTC was developed. Mice thyroid samples were used in microarray analysis and the data were referred to a human thyroid dataset. Results Most of BRAF(+) mice developed malignant lesions. Nevertheless, 16% of BRAF(+) mice displayed only benign hyperplastic lesions or apparently asymptomatic thyroids. After comparison of non-malignant BRAF(+) thyroids to BRAF(−) ones, we selected 862 significantly deregulated genes. When the mouse BRAF-dependent signature was transposed to the human HG-U133A microarray, we identified 532 genes, potentially indicating the BRAF signature (representing early changes, not related to developed malignant tumor). Comparing BRAF(+) PTCs to healthy human thyroids, PTCs without BRAF and RET alterations and RET(+), RAS(+) PTCs, 18 of these 532 genes displayed significantly deregulated expression in all subgroups. All 18 genes, among them 7 novel and previously not reported, were validated as BRAFV600E-specific in the dataset of independent PTC samples, made available by The Cancer Genome Atlas Project. Conclusion The study identified 7 BRAF-induced genes that are specific for BRAF V600E-driven PTC and not previously reported as related to BRAF mutation or thyroid carcinoma: MMD, ITPR3, AACS, LAD1, PVRL3, ALDH3B1, and RASA1. The full signature of BRAF-related 532 genes may encompass other BRAF-related important transcripts and require further study. PMID:26625260

  4. Rearranged Anaplastic Lymphoma Kinase (ALK) Gene in Adult-Onset Papillary Thyroid Cancer Amongst Atomic Bomb Survivors

    PubMed Central

    Mukai, Mayumi; Takahashi, Keiko; Hayashi, Yuzo; Nakachi, Kei; Kusunoki, Yoichiro

    2012-01-01

    Background We previously noted that among atomic bomb survivors (ABS), the relative frequency of cases of adult papillary thyroid cancer (PTC) with chromosomal rearrangements (mainly RET/PTC) was significantly greater in those with relatively higher radiation exposure than those with lower radiation exposure. In contrast, the frequency of PTC cases with point mutations (mainly BRAFV600E) was significantly lower in patients with relatively higher radiation exposure than those with lower radiation exposure. We also found that among ABS, the frequency of PTC cases with no detectable gene alterations in RET, neurotrophic tyrosine kinase receptor 1 (NTRK1), BRAF, or RAS was significantly higher in patients with relatively higher radiation exposure than those with lower radiation exposure. However, in ABS with PTC, the relationship between the presence of the anaplastic lymphoma kinase (ALK) gene fused with other gene partners and radiation exposure has received little study. In this study, we tested the hypothesis that the relative frequency of rearranged ALK in ABS with PTC, and with no detectable gene alterations in RET, NTRK1, BRAF, or RAS, would be greater in those having relatively higher radiation exposures. Methods The 105 subjects in the study were drawn from the Life Span Study cohort of ABS of Hiroshima and Nagasaki who were diagnosed with PTC between 1956 and 1993. Seventy-nine were exposed (>0 mGy), and 26 were not exposed to A-bomb radiation. In the 25 ABS with PTC, and with no detectable gene alterations in RET, NTRK1, BRAF, or RAS, we examined archival, formalin-fixed, paraffin-embedded PTC specimens for rearrangement of ALK using reverse transcription–polymerase chain reaction and 5′ rapid amplification of cDNA ends (5′ RACE). Results We found rearranged ALK in 10 of 19 radiation-exposed PTC cases, but none among 6 patients with PTC with no radiation exposure. In addition, solid/trabecular-like architecture in PTC was closely associated with ALK

  5. Analysis of predictability of F-18 fluorodeoxyglucose-PET/CT in the recurrence of papillary thyroid carcinoma.

    PubMed

    Kim, Suk Kyeong; So, Young; Chung, Hyun Woo; Yoo, Young Bum; Park, Kyung Sik; Hwang, Tae Sook; Kim, Bokyung; Lee, Won Woo

    2016-10-01

    Whether preoperative F-18 fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) can predict recurrence of papillary thyroid carcinoma (PTC) remains unclear. Herein, we evaluated the potential of primary tumor FDG avidity for the prediction of tumor recurrence in PTC patients. A total of 412 PTC patients (72 males, 340 females; age: 47.2 ± 12.2 years; range: 17-84 years) who underwent FDG-PET/CT prior to total thyroidectomy (n = 350), subtotal thyroidectomy (n = 2), or lobectomy (n = 60) from 2007 to 2011 were analyzed. The predictive ability for recurrence was investigated among various clinicopathological factors, BRAF(V)(600E) mutation, and preoperative FDG avidity of the primary tumor using Kaplan-Meier (univariate) and Cox proportional hazards regression (multivariate) analyses. Of the 412 patients, 19 (4.6%) experienced recurrence, which was confirmed either by pathology (n = 17) or high serum thyroglobulin level (n = 2), during a mean follow-up period of 43.9 ± 16.6 months. Of the 412 patients, 237 (57.5%) had FDG-avid tumors (maximum standardized uptake value, 7.1 ± 7.0; range: 1.6-50.5). Kaplan-Meier analysis revealed that tumor size (P = 0.0054), FDG avidity of the tumor (P = 0.0049), extrathyroidal extension (P = 0.0212), and lymph node (LN) stage (P < 0.0001) were significant predictors for recurrence. However, only LN stage remained a significant predictor in the multivariate analysis (P < 0.0001). Patients with FDG-avid tumors had higher LN stage (P < 0.0001), larger tumor size (P < 0.0001), and more frequent extrathyroidal extension (P < 0.0001). In conclusion, FDG avidity of the primary tumor in preoperative FDG-PET/CT could not predict the recurrence of PTC. LN stage was the only identified predictor of PTC recurrence.

  6. Thyroid malignancy presenting with visual loss: an unusual case of paraneoplastic retinopathy.

    PubMed

    Hughes, Emily; Moran, Sarah; Flitcroft, Ian; Logan, Patricia

    2016-10-19

    Paraneoplastic retinopathy is a rare cause of painless vision loss, associated with an underlying (and often occult) systemic malignancy. Ocular examination findings are subtle, and the diagnosis is often made on the basis of electrophysiology findings. This report describes the case of a 48-year-old Caucasian man with paraneoplastic retinopathy presenting as visual disturbance, central scotomata and abnormal electrophysiology. He was subsequently diagnosed with papillary thyroid malignancy.

  7. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.

    PubMed

    Bartolome, Aleksandar; Boskovic, Srdjan; Paunovic, Ivan; Bozic, Vesna; Cvejic, Dubravka

    2016-04-01

    Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.

  8. Fine-needle aspiration of the diffuse sclerosing variant of papillary thyroid carcinoma masked by florid lymphocytic thyroiditis; A potential pitfall: A case report and review of the literature.

    PubMed

    Bongiovanni, Massimo; Triponez, Frederic; McKee, Thomas A; Kumar, Neeta; Matthes, Thomas; Meyer, Patrick

    2009-09-01

    The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare tumor with aggressive behavior that requires aggressive treatment. Despite characteristic clinical and histological features that easily permit diagnosis, pre-operative fine-needle aspiration cytology (FNAC) diagnosis is often challenging and thus delays diagnosis. We describe the cytological features of a case of DSV-PTC diagnosed by FNAC in a 30-year-old woman presenting with an ill-defined mass in her neck lasting for 2 months. Ultrasonograpy revealed a heterogeneous enlargement of both thyroid lobes suspicious for a lymphoproliferative syndrome. Flow cytometry showed a suspect B-lymphocyte population. FNAC showed in five out of six slides an overwhelming presence of slightly atypical monomorphic small lymphocytes. The remaining slide showed syncytial tissue fragments of follicular cells with nuclear enlargement and pleomorphism, irregular nuclear membrane, grooves with scattered intranuclear inclusions, squamous metaplastic epithelium, and abundant psammoma bodies. A diagnosis of DSV-PTC was rendered and confirmed by total thyroidectomy and lymph node dissection. Our report supports the possibility of obtaining a preoperative diagnosis of DSV-PTC by FNAC. In the case of diffuse thyroid enlargement, adequate sampling of the thyroid and the presence of the combination of features described in our case permitted the diagnosis of this PTC variant.

  9. Pri-Mir-34b/C and Tp-53 Polymorphisms are Associated With The Susceptibility of Papillary Thyroid Carcinoma

    PubMed Central

    Chen, Peng; Sun, Ruifen; Pu, Yan; Bai, Peng; Yuan, Fang; Liang, Yundan; Zhou, Bin; Wang, Yanyun; Sun, Yinghe; Zhu, Jingqiang; Zhang, Lin; Gao, Linbo

    2015-01-01

    Abstract Tumor suppressor p53 directly regulated the abundance of the miR-34b/c. The interaction might contribute to certain cancer. We hypothesized that rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72Pro may be related to the risk of papillary thyroid carcinoma (PTC). A total of 784 patients with PTC and 1006 healthy controls were recruited to participate in this study. The variants were discriminated using a polymerase chain reaction–restriction fragment length polymorphism method (PCR-RFLP). Additionally, the relative expression levels of miR-34b/c and TP-53 in 44 paired samples were revealed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A significantly increased risk of PTC was observed in the miR-34b/c rs4938723 CT, CC, and CT/CC genotypes compared with the TT genotype (CT vs TT: adjusted odds ratio [OR] = 1.51, 95%confidence interval [CI] = 1.23–1.85; CC vs TT: adjusted OR = 1.89, 95%CI = 1.39–2.63; CT/CC vs TT: adjusted OR = 1.59, 95%CI = 1.30–1.92, respectively). Significantly increased PTC susceptibility was also associated with the TP-53 Arg72Pro CC and CG/CC genotypes compared with the GG genotype (CC vs GG: adjusted OR = 2.04, 95%CI = 1.54–2.70; CG/CC vs GG: adjusted OR = 1.35, 95%CI = 1.11–1.67, respectively). Stratification analysis revealed that patients carrying the TP-53 Arg72Pro C allele and CC genotype had a significantly increased risk for developing N1 (C vs. G: OR = 1.27, 95%CI = 1.03–1.56; CC vs. GG: OR = 1.62, 95%CI = 1.07–2.46, respectively). Combined analysis showed that the genotypes of rs4938723 CT/CC + TP-53CG/CC increased the risk of PTC compared with rs4938723TT + TP-53GG (OR = 2.25, 95%CI = 1.67–3.03). Additionally, level of miR-34b was significantly upregulated in PTC patients. These findings indicate that the miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may contribute to the

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

    ClinicalTrials.gov

    2017-03-20

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

  11. ABCG2/BCRP gene expression is related to epithelial-mesenchymal transition inducer genes in a papillary thyroid carcinoma cell line (TPC-1).

    PubMed

    Mato, E; González, C; Moral, A; Pérez, J I; Bell, O; Lerma, E; de Leiva, A

    2014-06-01

    Tumor malignancy is associated with the epithelial-mesenchymal transition (EMT) process and resistance to chemotherapy. However, little is known about the relationship between the EMT and the multidrug-resistance gene in thyroid tumor progression. We investigated whether the expression of the ABCG2/BCRP gene is associated with ZEB1 and other EMT inducer genes involved in tumor dedifferentiation. We established a subpopulation of cells that express the ABCG2/BCRP gene derived from the thyroid papillary carcinoma cell line (TPC-1), the so-called TPC-1 MITO-resistant subline. The most relevant findings in these TPC-1 selected cells were a statistically significant upregulation of ZEB1 and TWIST1 (35- and 15-fold change respectively), no changes in the relative expression of vimentin and SNAIL1, and no expression of E-cadherin. The TPC-1 MITO-resistant subline displayed a faster migration and greater invasive ability than parental cells in correlation with a significant upregulation of the survivin (BIRC5) gene (twofold change, P<0.05). The knockdown of ZEB1 promoted nuclear re-expression of E-cadherin, reduced expression of vimentin, N-cadherin, and BIRC5 genes, and reduced cell migration (P<0.05). Analysis of human thyroid carcinoma showed a slight overexpression of the ABCG2/BCRP at stages I and II (P<0.01), and a higher overexpression at stages III and IV (P<0.01). SNAIL1, TWIST1, and ZEB1 genes showed higher expression at stages III and IV than at stages I and II. E- and N-cadherin genes were upregulated at stages I and II of the disease (ninefold and tenfold change, respectively, P<0.01) but downregulated at stages III and IV (fourfold lower, P<0.01). These results could be a promising starting point for further study of the role of the ABCG2/BCRP gene in the progression of thyroid tumor.

  12. Integrated Ligand-Receptor Bioinformatic and In Vitro Functional Analysis Identifies Active TGFA/EGFR Signaling Loop in Papillary Thyroid Carcinomas

    PubMed Central

    Degl'Innocenti, Debora; Alberti, Chiara; Castellano, Giancarlo; Greco, Angela; Miranda, Claudia; Pierotti, Marco A.; Seregni, Ettore; Borrello, Maria Grazia; Canevari, Silvana; Tomassetti, Antonella

    2010-01-01

    Background Papillary thyroid carcinoma (PTCs), the most frequent thyroid cancer, is usually not life threatening, but may recur or progress to aggressive forms resistant to conventional therapies. A more detailed understanding of the signaling pathways activated in PTCs may help to identify novel therapeutic approaches against these tumors. The aim of this study is to identify signaling pathways activated in PTCs. Methodology/Principal Findings We examined coordinated gene expression patterns of ligand/receptor (L/R) pairs using the L/R database DRLP-rev1 and five publicly available thyroid cancer datasets of gene expression on a total of 41 paired PTC/normal thyroid tissues. We identified 26 (up) and 13 (down) L/R pairs coordinately and differentially expressed. The relevance of these L/R pairs was confirmed by performing the same analysis on REarranged during Transfection (RET)/PTC1-infected thyrocytes with respect to normal thyrocytes. TGFA/EGFR emerged as one of the most tightly regulated L/R pair. Furthermore, PTC clinical samples analyzed by real-time RT-PCR expressed EGFR transcript levels similar to those of 5 normal thyroid tissues from patients with pathologies other than thyroid cancer, whereas significantly elevated levels of TGFA transcripts were only present in PTCs. Biochemical analysis of PTC cell lines demonstrated the presence of EGFR on the cell membrane and TGFA in conditioned media. Moreover, conditioned medium of the PTC cell line NIM-1 activated EGFR expressed on HeLa cells, culminating in both ERK and AKT phosphorylation. In NIM-1 cells harboring BRAF mutation, TGFA stimulated proliferation, contributing to PI3K/AKT activation independent of MEK/ERK signaling. Conclusions/Significance We compiled a reliable list of L/R pairs associated with PTC and validated the biological role of one of the emerged L/R pair, the TGFA/EGFR, in this cancer, in vitro. These data provide a better understanding of the factors involved in the biology of PTCs and

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

    PubMed

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

    2016-12-01

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

  14. Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression.

    PubMed

    Zhang, You-Yuan; Liu, Ze-Bing; Ye, Xuan-Guang; Ren, Wei-Min

    2016-10-01

    Treatment with high iodine concentrations can delay oncogenic activation effects, reduce cell growth and return thyroid-specific gene and protein expression levels to normal. During rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) 3 activation, excess iodine can act as a protective agent in thyroid follicular cells. The chemokine receptor CCR7 serves a critical role in lymphocyte trafficking into and within lymph nodes, the preferential metastatic site for PTC. However, the potential associations between chemokine (C‑C motif) ligand 21 (CCL21)/C‑C chemokine receptor type 7 (CCR7) interaction and iodine concentrations in primary cultures of PTC with RET/PTC expression remain unclear. Proliferation assays of primary cultures of PTC cells with RET/PTC1 and RET/PTC3 expression indicated that CCR7 activation by its specific ligand, CCL21, was associated with significantly increased cell proliferation. Flow cytometry data indicated that CCL21/CCR7 interaction significantly increased the fraction of cells in the G2/M phase of the cell cycle. Western blotting indicated that CCL21/CCR7 interaction significantly upregulated cyclin A, cyclin B1 and cyclin‑dependent kinase 1 (CDK1) expression. Western blotting determined that CCL21/CCR7 interaction significantly enhanced the levels of phosphorylated extracellular signal‑regulated kinase (P‑ERK). Co-immunoprecipitation confirmed that there was interaction between P‑ERK and cyclin A, cyclin B1 or CDK1, particularly in the presence of CCL21. Sodium iodide (NaI, 10-5 M) significantly abolished the effects of exogenous CCL21. These results suggest that CCL21/CCR7 interaction contributes to G2/M progression of RET/PTC‑expressing cells via the ERK pathway in association with 10‑5 M NaI.

  15. [Thyroiditis].

    PubMed

    Buffet, Camille; Groussin, Lionel

    2013-02-01

    The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

  16. Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins

    PubMed Central

    Abdullah, Mardiaty Iryani; Lee, Ching Chin; Mat Junit, Sarni; Ng, Khoon Leong

    2016-01-01

    Background Papillary thyroid cancer (PTC) is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG). Methods In the present study, a gel-based proteomics analysis was performed to analyse the expression of proteins in tissue and serum samples of PTC patients with (PTCb; n = 6) and without a history of BTG (PTCa; n = 8) relative to patients with BTG (n = 20). This was followed by confirmation of the levels of proteins which showed significant altered abundances of more than two-fold difference (p < 0.01) in the tissue and serum samples of the same subjects using ELISA. Results The data of our study showed that PTCa and PTCb distinguish themselves from BTG in the types of tissue and serum proteins of altered abundance. While higher levels of alpha-1 antitrypsin (A1AT) and heat shock 70 kDa protein were associated with PTCa, lower levels of A1AT, protein disulfide isomerase and ubiquitin-conjugating enzyme E2 N seemed apparent in the PTCb. In case of the serum proteins, higher abundances of A1AT and alpha 1-beta glycoprotein were detected in PTCa, while PTCb was associated with enhanced apolipoprotein A-IV and alpha 2-HS glycoprotein (AHSG). The different altered expression of tissue and serum A1AT as well as serum AHSG between PTCa and PTCb patients were also validated by ELISA. Discussion The distinctive altered abundances of the tissue and serum proteins form preliminary indications that PTCa and PTCb are two distinct cancers of the thyroid that are etiologically and mechanistically different although it is currently not possible to rule out that they may also be due other reasons such as the different stages of the malignant disease. These proteins stand to have a potential use as tissue or serum biomarkers to discriminate the three different thyroid neoplasms although this requires further validation in clinically representative

  17. Comparison of proliferating cell nuclear antigen, thyroid transcription factor-1, Ki-67, p63, p53 and high-molecular weight cytokeratin expressions in papillary thyroid carcinoma, follicular carcinoma, and follicular adenoma.

    PubMed

    Tan, Ayca; Etit, Demet; Bayol, Umit; Altinel, Deniz; Tan, Sedat

    2011-04-01

    The searching of the reliable and repeatable immunohistochemical markers in the differential diagnosis of the thyroid's differentiated follicular epithelial neoplasms has been continuing. Recently, the studies have majored on immunohistochemical markers such as high-molecular weight cytokeratin (HMW-CK), galectin-3, cytokeratin 19, and p27. We aimed to evaluate the differences of the expressions of the proliferating cell nuclear antigen (PCNA), thyroid transcription factor-1 (TTF-1), Ki-67, p63, p53, and HMW-CK among the papillary thyroid carcinomas (PTCs), follicular carcinomas (FCs), and follicular adenomas (FAs). Thirty-nine patients with the diagnoses of the PTC, FC, and FA in the archives of the Izmir Tepecik Training and Research Hospital Pathology Laboratory registries in between 2004 and 2009 were included in the study. Immunohistochemical stains for PCNA, TTF-1, Ki-67, p63, p53, and HMW-CK were applied. The results were analyzed statistically by using Statistical Package for the Social Sciences (SPSS) for Windows 16.0 program (SPSS Inc., IBM, Somers, New York, USA). In all 3 groups, all tumors showed PCNA and TTF-1 positivity. Ki-67 proliferation index varied in a wide range in all groups. Although it was not statistically significant, 19 of 39 tumors (7 PTCs, 2 FCs, and 10 FAs) were stained with p63. The results of the immunoreactivity seen in PTCs with p53 (41.2%) and HMW-CK (52.9%) were statistically significant. The tumors in the other 2 groups (FC and FA) showed no reactivity with HMW-CK. Although the differential diagnosis of the thyroid follicular neoplasms are based on the histologic and cytomorphological criteria, p53 and HMW-CK positivity might be undertaken in favor of the diagnosis of the PTC.

  18. The association between chronic lymphocytic thyroiditis and thyroid tumors.

    PubMed

    Tamimi, Dalal M

    2002-04-01

    An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To assess the relationship, a histopathologic analysis of surgically resected thyroid tumors together with the frequency and severity of chronic lymphocytic infiltration of the thyroid among patients with follicular adenoma, follicular carcinoma, and papillary carcinoma was performed. The prevalence of lymphocytic infiltrate, which is indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma (58%) than in patients with follicular carcinoma (20%) or follicular adenoma (14%). The lymphocytic infiltration within the tumor compared with the severity of thyroiditis in the nontumorous tissue. Therefore, the association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed. The possibility that an immunologic mechanism involved in the pathogenesis of papillary carcinoma stimulates lymphocytic infiltration in the thyroid tissue through an autoimmune mechanism is suggested.

  19. Thyroiditis

    MedlinePlus

    ... Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the United States. Postpartum thyroiditis, which causes ... hormone levels in the blood) followed by temporary hypothyroidism, is a common cause of thyroid problems after ...

  20. Thyroid

    MedlinePlus

    Thyroid is used to treat the symptoms of hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, ...

  1. Thyroid Growth and Cancer

    PubMed Central

    Williams, Dillwyn

    2015-01-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term ‘cancer’ to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID

  2. MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway

    SciTech Connect

    Ma, Yanfei; Qin, Huadong; Cui, Yunfu

    2013-11-29

    Highlights: •MiR-34a is up- and GAS1 is down-regulated in papillary thyroid carcinoma. •GAS1 is a direct target for miR-34a. •MiR-34a promotes PTC cells proliferation and inhibits apoptosis through PI3K/Akt/Bad pathway. -- Abstract: MicroRNAs (miRNAs) are fundamental regulators of cell proliferation, differentiation, and apoptosis, and are implicated in tumorigenesis of many cancers. MiR-34a is best known as a tumor suppressor through repression of growth factors and oncogenes. Growth arrest specific1 (GAS1) protein is a tumor suppressor that inhibits cancer cell proliferation and induces apoptosis through inhibition of RET receptor tyrosine kinase. Both miR-34a and GAS1 are frequently down-regulated in various tumors. However, it has been reported that while GAS1 is down-regulated in papillary thyroid carcinoma (PTC), miR-34a is up-regulated in this specific type of cancer, although their potential roles in PTC tumorigenesis have not been examined to date. A computational search revealed that miR-34a putatively binds to the 3′-UTR of GAS1 gene. In the present study, we confirmed previous findings that miR-34a is up-regulated and GAS1 down-regulated in PTC tissues. Further studies indicated that GAS1 is directly targeted by miR-34a. Overexpression of miR-34a promoted PTC cell proliferation and colony formation and inhibited apoptosis, whereas knockdown of miR-34a showed the opposite effects. Silencing of GAS1 had similar growth-promoting effects as overexpression of miR-34a. Furthermore, miR-34a overexpression led to activation of PI3K/Akt/Bad signaling pathway in PTC cells, and depletion of Akt reversed the pro-growth, anti-apoptotic effects of miR-34a. Taken together, our results demonstrate that miR-34a regulates GAS1 expression to promote proliferation and suppress apoptosis in PTC cells via PI3K/Akt/Bad pathway. MiR-34a functions as an oncogene in PTC.

  3. 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

  4. Association between x-ray repair cross-complementing group 3 (XRCC3) genetic polymorphisms and papillary thyroid cancer susceptibility in a Chinese Han population.

    PubMed

    Yuan, Kai; Huo, Meiling; Sun, Yong; Wu, Hongyan; Chen, Hongqiang; Wang, Yulong; Fu, Rongzhan

    2016-01-01

    Papillary thyroid cancer (PTC) is a predominant type of thyroid cancer. Ionizing radiation is the only well-established risk factor and may result in double-strand breaks. The x-ray repair cross-complementing group 3 (XRCC3) gene plays a vital role in DNA repair through homologous recombination. We aimed at investigating the association between XRCC3 genetic polymorphisms and PTC susceptibility. Eighty-three PTC patients and 367 controls in a Chinese population were enrolled in the study. Tag single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of XRCC3 SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between XRCC3 SNPs and PTC susceptibility. The statistical analyses were conducted by using SPSS 13.0 software. Four tag-SNPs were initially identified by HaploView 4.2 software. Only one SNP (rs861539) was shown to be significantly associated with increased risk of PTC. There was a significant difference in smoking and drinking status between PTC cases and controls. And the stratified analysis suggested that the polymorphisms of rs861539 in XRCC3 were correlated with PTC risk in the four subgroups of smokers (ex-smokers included), non-smokers, drinkers (ex-drinkers included), and non-drinkers. The meta-analysis showed that only two studies reported a significant association between XRCC3 polymorphisms and PTC risk. In this study, we find a significant association between rs861539 polymorphisms and PTC susceptibility. However, there were inconsistent results in previous published studies. Therefore, further studies in a large population are required to gain insights into the PTC risk conferred by XRCC3 SNPs.

  5. Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis.

    PubMed

    Acosta, Andres M; Pins, Michael R

    2016-02-01

    Tumors containing elements of both papillary thyroid carcinoma (PTC) and squamous cell carcinoma (SCC) are rare but well documented. When they present initially as metastatic disease in an organ that can harbor a primary SCC, the possibility of a tumor to tumor metastasis (TTM) must be considered. The aim of this case study is to illustrate how BRAF mutational analysis can be used to help differentiate between these two diagnoses. We report a 63-year-old male with a longstanding history of PTC metastatic to the brain and lymph nodes who presented to our institution with a right lower lobe lung mass after a 2-year recurrence-free interval. Histopathologic and immunohistochemical analysis revealed a composite neoplasm with distinct elements of both PTC and SCC. We performed BRAF (V600E) (c.1799 T > A) mutational analysis to help elucidate the origin of each component. This is the first time that BRAF sequencing has been used to discriminate between dedifferentiated PTC and TTM, to the best of our knowledge. In the context of metastatic PTC with SCC dedifferentiation, the presence of the identical BRAF (V600E) (c.1799 T > A) mutation in both components might help rule out tumor to tumor metastasis.

  6. A Functional Insertion/Deletion Polymorphism in the Promoter Region of the NFKB1 Gene Increases the Risk of Papillary Thyroid Carcinoma

    PubMed Central

    Wang, Xunli; Peng, Hong; Liang, Yundan; Sun, Ruifen; Wei, Tao; Li, Zhihui; Gong, Yanping; Gong, Rixiang; Liu, Feng; Zhang, Lin

    2015-01-01

    This study aimed to assess whether an insertion/deletion polymorphic variation rs28362491 in the NFKB1 promoter region was related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was extracted from the peripheral venous blood of 352 patients with PTC and 459 controls. The NFKB1 rs28362491 polymorphism was genotyped by using a polymerase chain reaction assay. We found that the frequency of the heterozygous genotype ATTG1/ATTG2 was significantly higher in the cases compared to the controls (odds ratios [OR]=1.44, 95% confidence intervals [CI]=1.05–1.96, p=0.02). Moreover, the frequency of ATTG1/ATTG2+ATTG1/ATTG1 genotypes was significantly elevated in the cases compared to the controls (OR=1.38, 95% CI=1.03–1.85, p=0.03). These findings suggest that the −94 insertion/deletion ATTG polymorphism in the NFKB1 promoter might be associated with an increased risk of PTC. PMID:25692306

  7. Image-guided high-dose-rate interstitial brachytherapy – a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer

    PubMed Central

    Wu, Ning; Zhao, Hongfu; Han, Dongmei; Zhao, Zhipeng; Ge, Yuxin

    2016-01-01

    Purpose To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). Case report This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive 131I, the lesion expanded as 3.7 × 3.0 × 2.3 cm3 and 2.0 × 1.5 × 1.5 cm3. The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. Results Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. Conclusions The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC. PMID:27257420

  8. Changes in serum thyroglobulin antibody levels as a dynamic prognostic factor for early-phase recurrence of thyroglobulin antibody-positive papillary thyroid carcinoma after total thyroidectomy.

    PubMed

    Yamada, Osamu; Miyauchi, Akira; Ito, Yasuhiro; Nakayama, Ayako; Yabuta, Tomonori; Masuoka, Hiroo; Fukushima, Mitsuhiro; Higashiyama, Takuya; Kihara, Minoru; Kobayashi, Kaoru; Miya, Akihiro

    2014-01-01

    We demonstrated previously that dynamic prognostic markers such as the thyroglobulin (Tg)-doubling time in thyroglobulin antibody (TgAb)-negative papillary thyroid carcinoma (PTC) and changes in pre- and postoperative TgAb levels in TgAb-positive PTC patients more keenly reflect patients' prognosis than conventional static prognostic factors. Here we investigated periodic changes in TgAb levels in 513 TgAb-positive PTC patients who underwent total thyroidectomy. The TgAb levels at 1 year after surgery decreased to <50% of the preoperative values in 407 (79%) patients, and the remaining 106 (21%) patients showed no decrease in TgAb. In 426 patients, TgAb was also measured more than 1 year after surgery. Compared with their TgAb levels 1 year after surgery, 59 patients (14%) showed an increase in TgAb levels of >20% during the follow-up. The postoperative Tg levels at 1 year after surgery remained positive in 44 (9%) patients despite their TgAb positivity. To date (median follow-up period 35 months), 12 of the 426 patients (3%) showed PTC recurrence, and 11 of these patients showed either or both a TgAb elevation later than 1 year after surgery and postoperative Tg positivity. Although further studies with longer follow-ups are necessary, we can conclude that changes in postoperative TgAb levels may be usable as a surrogate tumor marker for TgAb-positive PTC patients after total thyroidectomy.

  9. TERT promoter mutations and Ki-67 labeling index as a prognostic marker of papillary thyroid carcinomas: combination of two independent factors

    PubMed Central

    Matsuse, Michiko; Yabuta, Tomonori; Saenko, Vladimir; Hirokawa, Mitsuyoshi; Nishihara, Eijun; Suzuki, Keiji; Yamashita, Shunichi; Miyauchi, Akira; Mitsutake, Norisato

    2017-01-01

    Although most papillary thyroid carcinomas (PTCs) have a good prognosis, a small but certain fraction shows aggressive behavior. Therefore, a novel and well-performing molecular marker is needed. In the present study, we assessed the impact of the combination of the TERT promoter/BRAF mutations and Ki-67 labeling index (LI) as a prognostic marker in PTC patients. Of 400 PTC samples, 354 were successfully genotyped for both TERT promoter/BRAF and analyzed for Ki-67 LI. Based on the combination of the mutational status and Ki-67 LI, the cases were categorized into three groups: high-, middle-, and low-risk. The recurrence rates of low-, middle-, and high-risk group were 1.9% (6 of 323), 18.2% (4 of 22), and 44.4% (4 of 9), respectively. The Kaplan-Meier curve and log-rank analyses demonstrated that there were statistical differences between any two groups. The hazard ratios for recurrence remained significant after adjustment for age, sex, tumor size, and extrathyroidal extension (low vs. middle: 8.80, 95% CI: 2.35–32.92, p = 0.001; middle vs. high: 6.255, 95% CI: 1.13–34.51, p = 0.035). In conclusion, the combination of the TERT promoter/BRAFV600E mutations and Ki-67 LI performed excellent in predicting PTC recurrence and may be clinically useful. PMID:28150740

  10. Clinicopathological Characteristics and Prognosis of Papillary Thyroid Carcinoma in Naturally Menopausal Women with Various Durations of Premenarche, Reproductive Periods, and Postmenopausal Stages

    PubMed Central

    Zhu, Xuhang; Yu, Bin; Huang, Yu-qing; Zhou, Jing-nan

    2017-01-01

    Background. Papillary thyroid cancer (PTC) exhibits a higher incidence in women. Due to various ages at menarche and menopause, estrogen levels vary, which may account for the differences in the occurrence, development, and prognosis of female patients with PTC. Objective. The aim of this study was to investigate the association between various durations in different estrogen levels and PTC and to provide important information to guide clinical management and treatment of this disease. Methods. First, we selected naturally menopausal female study subjects diagnosed with PTC at Zhejiang Cancer Hospital from 2007 to 2012 and then compared the differences in clinicopathological characteristics and prognosis among subjects with various lengths of premenarche, reproductive periods, and postmenopausal stages. Results. We found that all patients showed a significantly higher incidence of tumor multicentricity and intrathyroidal dissemination as the time after menopause increased. Additionally, women with shorter (<30) or longer (>38) reproductive lives had increased recurrence rates of PTC. Conclusions. In this study, we did not find any relationship of self-reported menarche and menopausal ages with the prognosis of PTC patients. More importantly, natural postmenopausal PTC patients with shorter or longer reproductive life, compared to the normal groups, had a higher rate of cancer recurrence and the patients with these characteristics could be recommended a more aggressive surgical treatment. PMID:28356910

  11. [Clinical and morphological features of papillary thyroid cancer in children and adolescents in the Republic of Belarus: analysis of 936 post-Chernobyl carcinomas].

    PubMed

    Fridman, M V; Man'kovskaia, S V; Kras'ko, O V; Demidchik, Iu E

    2014-01-01

    There is presented clinical and morphological characteristics of post-Chernobyl papillary thyroid cancer in 936 children and adolescents. In general, carcinoma of these patients featured by locally advanced growth - 57.4% (387 of 674 patients with this sign could be assessed), metastases in regional lymph nodes - 73,7% (N1b in 40.7%) and internal organs - 11.1%. The mean duration of follow-up was 12,4 +/- 3,5 years (range 4.3 to 19.6 years) including children 14,6 +/- 2,7 years (range 8.8 to 19.6 years) and adolescents - 10,1 +/- 3,1 years (range 4.3 to 18.8 years). Overall survival for the 20-year period was 96,6% +/- 1,2%. The causes of death were suicide (7), injuries and accidents (5), secondary malignancies (1), somatic diseases (2). Only in two patients the death was related to the main disease - lung metastases. Free-recurrence survival for the cohort of post-Chernobyl carcinomas was 92,7% +/- 1,0%.

  12. Clinical impact of cervical lymph node involvement and central neck dissection in patients with papillary thyroid carcinoma: a retrospective analysis of 368 cases.

    PubMed

    Bozec, Alexandre; Dassonville, Olivier; Chamorey, Emmanuel; Poissonnet, Gilles; Sudaka, Anne; Peyrottes, Isabelle; Ettore, Francette; Haudebourg, Juliette; Bussière, Françoise; Benisvy, Danielle; Marcy, Pierre-Yves; Sadoul, Jean Louis; Hofman, Paul; Lassale, Sandra; Vallicioni, Jacques; Demard, François; Santini, José

    2011-08-01

    The impact of cervical lymph node metastases and the optimal surgical management of the neck in patients with papillary thyroid carcinoma (PTC) remain controversial. The objectives of this retrospective study were to determine, in patients with PTC, the predictive factors and the impact on tumor recurrence rate of cervical lymph node involvement, and to evaluate the oncologic results and the morbidity of central neck dissection (CND). We reviewed the records of patients who had undergone surgical treatment for PTC at our institution between 1990 and 2000. A total of 368 patients (86 men and 282 women) were included in this study. Young age (p = 0.02), tumor size (p = 0.001) and extrathyroidal tumor extension (p = 0.003) were significant predictive factors of cervical lymph node metastatic involvement (multivariate analysis). Initial metastatic cervical lymph node involvement was identified as an independent risk factor of tumor recurrence (multivariate analysis, p = 0.01). Metastatic lymph node(s) were found in prophylactic CND specimens in 31% of the patients. CND increased the risk of postoperative hypocalcemia (p = 0.008) and of permanent hypoparathyroidism (p = 0.002). In conclusion, cervical lymph node metastatic involvement at the time of initial surgery is an independent risk factor of tumor recurrence. CND provided an up-staging of more than 30% of patients with a clinically N0 neck, but was associated with significant morbidity regarding parathyroid function.

  13. [Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

    PubMed

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

    2016-01-01

    On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly

  14. The role of postoperative external-beam radiotherapy in the management of patients with papillary thyroid cancer invading the trachea

    SciTech Connect

    Keum, Ki Chang; Suh, Yang Gun; Koom, Woong Sub; Cho, Jae Ho; Shim, Su Jung; Lee, Chang Geol; Park, Chung Soo; Chung, Woong Youn; Kim, Gwi Eon . E-mail: gekim@yumc.yonsei.ac.kr

    2006-06-01

    Purpose: To determine the role of adjuvant external-beam radiotherapy (EBRT) in the management of patients with well-differentiated thyroid cancer invading the trachea. Methods and Materials: Of 1,098 thyroid cancer patients, 68 (6%) were found to have tracheal invasion, and they all received 'shave' excision of the tracheal cartilage. Among them, 12 patients had no postoperative residuum, 43 patients had microscopic residuum, and 13 patients had macroscopic residuum. All patients were divided into two groups according to treatment modality with or without EBRT; (1) the control group (n = 43) and (2) the EBRT group (n = 25). Results: The locoregional recurrence rate for EBRT patients was much lower than that of control patients (51% for the control group vs. 8% for the EBRT group) (p < 0.01). The 10-year local progression-free survival rate for the EBRT group was significantly better than that of the control group (89% in the EBRT group vs. 38% in the control group) (log-rank, p < 0.01). The use of adjuvant EBRT after conservative surgery was an independent prognostic factor in univariate and multivariate analyses. Conclusions: External-beam radiotherapy was found to be effective, particularly in patients with thyroid cancer invading the trachea with microscopic or gross residuum after conservative surgery.

  15. Thyroid gland morphology in young adults: normal subjects versus those with prior low-dose neck irradiation in childhood

    SciTech Connect

    Hanson, G.A.; Komorowski, R.A.; Cerletty, J.M.; Wilson, S.D.

    1983-12-01

    Thyroid glands obtained at autopsy from young adults were studied to establish more accurately the ''normal'' morphology in the groups 20 to 40 years of age. A total of 56 autopsy specimens (many obtained from trauma victims) were examined in detail by totally embedding and sectioning the thyroid glands. The morphology of these thyroid glands also was compared to that of surgically removed thyroid glands from 47 young adult patients with prior low-dose neck irradiation. The ''normal'' thyroid specimens frequently showed morphologic features, such as thyroid tissue outside the recognizable capsule of the gland (40 of 56 patients) and in the strap muscles of the neck (six of 56 patients), which are conditions commonly considered as evidence for invasive thyroid carcinoma. The thyroid glands from the ''normal'' young adult population were significantly different from those thyroid glands surgically removed from patients who had received irradiation. The irradiated thyroid glands invariably showed multiple nodules of a wide variety of histologic types, extensive lymphocytic infiltrates, and distorting fibrosis as well as a high incidence of malignancy (27 of 47 patients). A single 0.1 cm focus of papillary carcinoma was found in one specimen in the nonirradiated thyroid group. This study suggests that ''occult'' thyroid carcinomas in the group 20 to 40 years of age are rare and are significantly fewer in number than in the older population (P less than 0.02).

  16. A rare case report of very low thyroglobulin and a negative whole-body scan in a patient with a solid variant of papillary thyroid carcinoma with distant metastases

    PubMed Central

    Li, Wei; Sun, Danyang; Ming, Hui; Zhang, Guizhi; Tan, Jian

    2017-01-01

    Abstract Rationale: The early detection of recurrent differentiated thyroid carcinoma (DTC) cells in postsurgery DTC patients relies on the sensitivity of measuring both the level of thyroglobulin (Tg) and 131-iodine distribution on a whole-body scan (WBS). Recent studies have defined patients who subsequently have no evidence of disease as those who have a stimulated Tg level <1 ng/mL with no other radiological or clinical evidence of disease. Patient Concerns: A woman patient with solid variant papillary thyroid carcinoma (SVPTC) had undergone twice thyroidectomy with lymph node dissection and radioactive therapy. Recently, she was found to have lung and brain metastases despite a very low serum Tg level and a negative WBS. Nowadays, the patients have suggested targeted treatment, such as tyrosine kinase inhibitors, may be worthy of consideration to prevent the related events. Diagnoses: She was diagnosed as PTC. Interventions: She had undergone twice thyroidectomy with lymph node dissection and radioactive therapy. Outcomes: She was found to have lung and brain metastases despite a very low serum Tg level and a negative WBS. Lessons: We aim to suggest that patients with SVPTC should be treated cautiously because they may have a higher frequency of distant metastases and a less favorable prognosis compared with patients with classical papillary thyroid cancer. PMID:28207517

  17. Post-operative stimulated thyroglobulin and neck ultrasound as personalized criteria for risk stratification and radioactive iodine selection in low- and intermediate-risk papillary thyroid cancer.

    PubMed

    Orlov, Steven; Salari, Farnaz; Kashat, Lawrence; Freeman, Jeremy L; Vescan, Allan; Witterick, Ian J; Walfish, Paul G

    2015-09-01

    The purpose of this study was to demonstrate the utility of a personalized risk stratification and radioactive iodine (RAI) selection protocol (PRSP) using post-operative stimulated thyroglobulin (Stim-Tg) and neck ultrasound in low- and intermediate-risk papillary thyroid carcinoma (PTC) patients. Patients with PTC tumors ≥1 cm were prospectively followed after total thyroidectomy and selective therapeutic central compartment neck dissection. Low/intermediate risk was defined as PTC confined to the thyroid or central (level VI) lymph nodes. Stim-Tg and neck ultrasound were performed approximately 3 months after surgery and used to guide RAI selection. Patients with Stim-Tg < 1 µg/L did not receive RAI, while those with Stim-Tg >5 µg/L routinely did. Those with Stim-Tg 1-5 µg/L received RAI on the basis of several clinical risk factors. Patients were followed for >6 years with serial neck ultrasound and basal/stimulated thyroglobulin. Among the 129 patients, 84 (65 %) had undetectable Stim-Tg after initial surgery, 40 (31 %) had Stim-Tg of 1-5 µg/L, and 5 (4 %) had Stim-Tg >5 µg/L. RAI was administered to 8 (20 %) patients with Stim-Tg 1-5 µg/L and 5 (100 %) with Stim-Tg >5 µg/L. Using this approach, RAI therapy was avoided in 17/20 (85 %) patients with tumors >4 cm, in 72/81 (89 %) patients older than 45 years, and in 6/9 (67 %) patients with central lymph node involvement. To date, 116 (90 %) patients in this cohort have not received RAI therapy with no evidence of residual/recurrent disease, whereas among the 13 patients who received RAI, 1 (8 %) had pathologic residual/recurrence disease. Using the proposed PRSP, RAI can be avoided in the majority of low/intermediate-risk PTC patients. Moreover, traditional risk factors considered to favor RAI treatment were not always concordant with the PRSP and may lead to overtreatment.

  18. Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model

    PubMed Central

    Duquette, Mark; Sadow, Peter M.; Fischer, Andrew H.; Song, Chen; Castellanos-Rizaldos, Elena; Makrigiorgos, G. Mike; Kurebayashi, Junichi; Nose, Vania; Van Hummelen, Paul; Bronson, Roderick T.; Vinco, Michelle; Giordano, Thomas J.; Dias-Santagata, Dora; Pandolfi, Pier Paolo; Nucera, Carmelo

    2015-01-01

    BRAFV600E mutation exerts an essential oncogenic function in many tumors, including papillary thyroid carcinoma (PTC). Although BRAFV600E inhibitors are available, lack of response has been frequently observed. To study the mechanism underlying intrinsic resistance to the mutant BRAFV600E selective inhibitor vemurafenib, we established short-term primary cell cultures of human metastatic/recurrent BRAFV600E-PTC, intrathyroidal BRAFV600E-PTC, and normal thyroid (NT). We also generated an early intervention model of human BRAFV600E-PTC orthotopic mouse. We find that metastatic BRAFV600E-PTC cells elicit paracrine-signaling which trigger migration of pericytes, blood endothelial cells and lymphatic endothelial cells as compared to BRAFWT-PTC cells, and show a higher rate of invasion. We further show that vemurafenib therapy significantly suppresses these aberrant functions in non-metastatic BRAFV600E-PTC cells but lesser in metastatic BRAFV600E-PTC cells as compared to vehicle treatment. These results concur with similar folds of down-regulation of tumor microenvironment–associated pro-metastatic molecules, with no effects in BRAFWT-PTC and NT cells. Our early intervention preclinical trial shows that vemurafenib delays tumor growth in the orthotopic BRAFWT/V600E-PTC mice. Importantly, we identify high copy number gain of MCL1 (chromosome 1q) and loss of CDKN2A (P16, chromosome 9p) in metastatic BRAFV600E-PTC cells which are associated with resistance to vemurafenib treatment. Critically, we demonstrate that combined vemurafenib therapy with BCL2/MCL1 inhibitor increases metastatic BRAFV600E-PTC cell death and ameliorates response to vemurafenib treatment as compared to single agent treatment. In conclusion, short-term PTC and NT cultures offer a predictive model for evaluating therapeutic response in patients with PTC. Our PTC pre-clinical model suggests that combined targeted therapy might be an important therapeutic strategy for metastatic and refractory BRAFV600

  19. Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma.

    PubMed

    Schulten, Hans-Juergen; Hussein, Deema; Al-Adwani, Fatima; Karim, Sajjad; Al-Maghrabi, Jaudah; Al-Sharif, Mona; Jamal, Awatif; Bakhashab, Sherin; Weaver, Jolanta; Al-Ghamdi, Fahad; Baeesa, Saleh S; Bangash, Mohammed; Chaudhary, Adeel; Al-Qahtani, Mohammed

    2016-01-01

    Brain metastatic papillary thyroid carcinomas (PTCs) are afflicted with unfavorable prognosis; however, the underlying molecular genetics of these rare metastases are virtually unknown. In this study, we compared whole transcript microarray expression profiles of a BRAF mutant, brain metastasis from a PTC, including its technical replicate (TR), with eight non-brain metastatic PTCs and eight primary brain tumors. The top 95 probe sets (false discovery rate (FDR) p-value < 0.05 and fold change (FC) > 2) that were differentially expressed between the brain metastatic PTC, including the TR, and both, non-brain metastatic PTCs and primary brain tumors were in the vast majority upregulated and comprise, e.g. ROS1, MYBPH, SLC18A3, HP, SAA2-SAA4, CP, CCL20, GFAP, RNU1-120P, DMBT1, XDH, CXCL1, PI3, and NAPSA. Cytokines were represented by 10 members in the top 95 probe sets. Pathway and network analysis (p-value < 0.05 and FC > 2) identified granulocytes adhesion and diapedesis as top canonical pathway. Most significant upstream regulators were lipopolysaccharide, TNF, NKkB (complex), IL1A, and CSF2. Top networks categorized under diseases & functions were entitled migration of cells, cell movement, cell survival, apoptosis, and proliferation of cells. Probe sets that were significantly shared between the brain metastatic PTC, the TR, and primary brain tumors include CASP1, CASP4, C1R, CC2D2B, RNY1P16, WDR72, LRRC2, ZHX2, CITED1, and the noncoding transcript AK128523. Taken together, this study identified a set of candidate genes and biofunctions implicated in, so far nearly uncharacterized, molecular processes of a brain metastasis from a PTC.

  20. Association Between Expression of X-Linked Inhibitor of Apoptosis Protein and the Clinical Outcome in a BRAFV600E-Prevalent Papillary Thyroid Cancer Population

    PubMed Central

    Yim, Ji Hye; Kim, Won Gu; Jeon, Min Ji; Han, Ji Min; Kim, Tae Yong; Yoon, Jong Ho; Hong, Suck Joon; Song, Dong Eun; Gong, Gyungyub; Shong, Young Kee

    2014-01-01

    Background: The X-linked inhibitor of apoptosis protein (XIAP) is associated with carcinogenesis, cancer progression, and metastasis through inhibition of the caspase-mediated apoptotic pathway. The BRAFV600E mutation is the most common genetic alteration and an established prognostic marker in papillary thyroid cancer (PTC). The prevalence of the BRAF mutation is very high and is up to 80% in Korean PTC patients. In the present study, we evaluated the potential role of XIAP expression as a novel prognostic marker to predict recurrence, in combination with the BRAFV600E mutational status. Methods: The study enrolled 164 patients with conventional PTC who underwent bilateral thyroidectomy followed by immediate 131I ablation. The presence of the BRAFV600E mutation was evaluated by direct sequencing. The degree of XIAP expression was evaluated by immunohistochemical (IHC) staining using a monoclonal antibody. Results: The BRAFV600E mutation was found in 123 of 164 patients (75%) with classical PTC. XIAP expression was positive in 128 of 164 patients (75%), and positive XIAP expression was significantly associated with the presence of lateral cervical lymph node metastases (p=0.01). XIAP expression was more frequent in BRAFV600E mutated PTCs than in BRAF wild type PTCs (p=0.048). The BRAFV600E mutation was significantly associated with cancer recurrence in study subjects (hazard ratio=2.98, p=0.039). PTCs positive for the BRAFV600E mutation but negative for XIAP expression had a significantly higher rate of recurrent PTC (hazard ratio=4.53, p=0.012). Conclusion: The evaluation of XIAP expression and BRAF mutational analysis was more useful for the prediction of cancer recurrence in patients with PTC than BRAF genotype alone. PMID:24124924

  1. Concordance study between one-step nucleic acid amplification and morphologic techniques to detect lymph node metastasis in papillary carcinoma of the thyroid.

    PubMed

    del Carmen, Sofía; Gatius, Sonia; Franch-Arcas, Guzmán; Baena, José Antonio; Gonzalez, Oscar; Zafon, Carlos; Cuevas, Dolors; Valls, Joan; Pérez, Angustias; Martinez, Mercedes; Ros, Susana; Macías, Carmen García; Iglesias, Carmela; Matías-Guiu, Xavier; de Álava, Enrique

    2016-02-01

    Tumor resection in papillary thyroid carcinoma (PTC) is often accompanied by lymph node (LN) removal of the central and lateral cervical compartments. One-step nucleic acid amplification (OSNA) is a polymerase chain reaction-based technique that quantifies cytokeratin 19 (CK19) messenger RNA copies. Our aim is to assess the value of OSNA in detection of LN metastases in PTC, in comparison with imprints and microscopic analysis of formalin-fixed, paraffin-embedded (FFPE) tissue. A total of 387 LNs from 37 patients were studied. From each half LN, 2 imprints were taken and analyzed with hematoxylin and eosin (H&E) and CK19 immunostaining. One half of the LN was submitted to OSNA and one half to FFPE processing and H&E and CK19 staining. For concordance analysis, every single LN was considered as a case. A group of 11 cases with discordant results between OSNA and H&E/CK19 FFPE sections were subjected to additional FFPE serial sectioning and H&E and CK19 staining. We found a high degree of concordance between the assays used, with sensitivities ranging from 0.81 to 0.95, and specificities ranging from 0.87 and 0.98. OSNA allowed upstaging of patients from pN0 to pN1, in comparison with standard pathologic analysis. Identification of a metastatic LN with more than 15000 CK19 messenger RNA copies predicted the presence of a second LN with macrometastasis (<5000 copies). In summary, the study shows that OSNA application in sentinel or suspicious LN may be helpful in assessing nodal status in PTC patients.

  2. Interleukin 27 -964A > G genetic polymorphism and serum IL-27p28 levels in Chinese patients with papillary thyroid cancer.

    PubMed

    Zhang, Shulong; Gao, Xueren; Wang, Yong; Jia, Jianguang; Zhang, Qiang; Ji, Zhenling

    2015-09-01

    The aim of this study was to investigate the association between a potentially functional polymorphism (rs153109, -964A > G) in the promoter region of interleukin-27 (IL-27) gene and the risk of papillary thyroid cancer (PTC) in a Chinese population. Genotype of IL-27 -964A > G polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum IL-27p28 levels were determined using enzyme-linked immunosorbent assay (ELISA). No significant difference was noticed in IL-27 -964A > G polymorphism between PTC patients and healthy controls in the overall analysis. However, analysis of clinical features showed that PTC patients carrying the GG genotype or G allele had significantly decreased risks for developing lymph node metastasis compared with those carrying the AA genotype or A allele (GG vs. AA: OR = 0.38, 95 % CI, 0.20-0.72; G vs. A: OR = 0.63, 95 % CI, 0.44-0.86). Furthermore, ELISA results demonstrated that serum IL-27p28 levels were significantly decreased in PTC patients compared with those in controls (P < 0.05). Serum IL-27p28 levels in healthy controls with the GG genotype were significantly high compared with those carrying AA genotype or the AG genotype (P < 0.05). In conclusion, our results suggest that IL-27 -964A > G polymorphism may be associated with the decreased risk for lymph node metastasis of PTC.

  3. Expression characteristics of proteins of IGF-1R, p-Akt, and survivin in papillary thyroid carcinoma patients with type 2 diabetes mellitus

    PubMed Central

    Yan, Yuerong; Hu, Fengqiu; Wu, Weilu; Ma, Ruiting; Huang, Hui

    2017-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is related to increased risk of papillary thyroid carcinoma (PTC). Insulin-like growth factor-1 receptor (IGF-1R) is increased in patients with T2DM. The increased IGF-1R may be responsible for the development of PTC. In this study, we investigated the expression of phosphorylation of Akt (p-Akt)/survivin pathway activated by IGF-1R in PTC subjects with and without diabetes. Clinicopathological data of 20 PTC patients with T2DM were retrospectively analyzed and compared with those of 21 PTC subjects without diabetes. Meanwhile, IGF-1R, p-Akt, and survivin expressions of PTC tissues were detected by immunohistochemical staining. The immunohistochemical results found that the expression level of IGF-1R was significantly higher in diabetic PTC patients than that in nondiabetic PTC patients (P < 0.05). However, no significant differences of p-Akt and survivin expression were found between PTC patients with T2DM and PTC patients without T2DM. In addition, among 20 PTC patients with T2DM, subgroup analysis showed that the ratio of tumor size >10 mm was significantly higher in IGF-1R moderate to strong expression group than that in IGF-1R negative to weak expression group (P < 0.05). IGF-1R expression level was higher in PTC patients with T2DM, and the increased IGF-1R expression was associated with lager tumor size. IGF-1R may play an important role in carcinogenesis and tumor growth in PTC patients with T2DM. PMID:28328831

  4. Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements

    PubMed Central

    Hayes, D. Neil; Lucas, Amy S.; Tanvetyanon, Tawee; Krzyzanowska, Monika K.; Chung, Christine H.; Murphy, Barbara A.; Gilbert, Jill; Mehra, Ranee; Moore, Dominic T.; Sheikh, Arif; Hoskins, Janelle; Hayward, Michele C.; Zhao, Ni; O’Connor, Wendi; Weck, Karen E.; Cohen, Roger B.; Cohen, Ezra E.W.

    2015-01-01

    Purpose A multicenter, open-label, phase II trial was conducted to evaluate the efficacy, safety, and tolerability of selumetinib in iodine-refractory papillary thyroid cancer (IRPTC). Experimental Design Patients with advanced IRPTC with or without follicular elements and documented disease progression within the preceding 12 months were eligible to receive selumetinib at a dose of 100 mg twice daily. The primary endpoint was objective response rate using Response Evaluation Criteria in Solid Tumors. Secondary endpoints were safety, overall survival, and progression-free survival (PFS). Tumor genotype including mutations in BRAF, NRAS, and HRAS was assessed. Results Best responses in 32 evaluable patients out of 39 enrolled were 1 partial response (3%), 21 stable disease (54%), and 11 progressive disease (28%). Disease stability maintenance occurred for 16 weeks in 49%, 24 weeks in 36%. Median PFS was 32 weeks. BRAF V600E mutants (12 of 26 evaluated, 46%) had a longer median PFS compared with patients with BRAF wild-type (WT) tumors (33 versus 11 weeks, respectively, HR = 0.6, not significant, P = 0.3). The most common adverse events and grades 3 to 4 toxicities included rash, fatigue, diarrhea, and peripheral edema. Two pulmonary deaths occurred in the study and were judged unlikely to be related to the study drug. Conclusions Selumetinib was well tolerated but the study was negative with regard to the primary outcome. Secondary analyses suggest that future studies of selumetinib and other mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) inhibitors in IRPTC should consider BRAF V600E mutation status in the trial design based on differential trends in outcome. PMID:22241789

  5. Pigment epithelium-derived factor has a role in the progression of papillary thyroid carcinoma by affecting the HIF1α-VEGF signaling pathway

    PubMed Central

    Lv, Yichen; Sun, Yu; Shi, Tiefeng; Shi, Chenlei; Qin, Huadong; Li, Zhaozhu

    2016-01-01

    The progression mechanism of papillary thyroid carcinoma (PTC) remains largely unknown. Accumulating evidence has suggested that various targets of pigment epithelium-derived factor (PEDF) are able to inhibit cancer progression. The aim of the present study was to examine PEDF expression in PTC patients and to investigate its relationship with aggressive clinicopathological features, as well as to explore whether PEDF affects the progression of PTC via the hypoxia-inducible factor 1α (HIF1α)-vascular endothelial growth factor (VEGF) pathway. A total of 271 patients with PTC, including 24 men and 247 women, were enrolled in the present study. Relevant patient data, including demographic features, preoperative clinical features and pathological features, were collected for analysis. The protein expression levels of PEDF in PTC tissues were detected using immunohistochemical staining, and the mRNA expression levels of PEDF, VEGF and HIF1α in 15 PTC tissues with lymph node metastasis (LNM) and 10 tissues without LNM were detected using reverse transcription-quantitative polymerase chain reaction. Immunohistochemical staining with an anti-PEDF antibody detected PEDF expression in 74.5% of the PTC tissues. PEDF expression levels were significantly correlated with LNM, extrathyroid invasion, a high TNM stage, the presence of the BRAFV600E mutation and tumor size. PEDF mRNA expression levels were significantly decreased in PTC tissues with LNM, as compared with PTC tissues without LNM, while the mRNA expression levels of HIF1α and VEGF were markedly increased in PTC tissues with LNM. Taken together, the results of the present study suggested that PEDF plays a role in the progression of PTC, and that PEDF may exert an anti-angiogenesis role by affecting the HIF1α-VEGF pathway, eventually inhibiting the metastasis of PTC. PMID:28105231

  6. Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma

    PubMed Central

    Schulten, Hans-Juergen; Hussein, Deema; Al-Adwani, Fatima; Karim, Sajjad; Al-Maghrabi, Jaudah; Al-Sharif, Mona; Jamal, Awatif; Bakhashab, Sherin; Weaver, Jolanta; Al-Ghamdi, Fahad; Baeesa, Saleh S; Bangash, Mohammed; Chaudhary, Adeel; Al-Qahtani, Mohammed

    2016-01-01

    Brain metastatic papillary thyroid carcinomas (PTCs) are afflicted with unfavorable prognosis; however, the underlying molecular genetics of these rare metastases are virtually unknown. In this study, we compared whole transcript microarray expression profiles of a BRAF mutant, brain metastasis from a PTC, including its technical replicate (TR), with eight non-brain metastatic PTCs and eight primary brain tumors. The top 95 probe sets (false discovery rate (FDR) p-value < 0.05 and fold change (FC) > 2) that were differentially expressed between the brain metastatic PTC, including the TR, and both, non-brain metastatic PTCs and primary brain tumors were in the vast majority upregulated and comprise, e.g. ROS1, MYBPH, SLC18A3, HP, SAA2-SAA4, CP, CCL20, GFAP, RNU1-120P, DMBT1, XDH, CXCL1, PI3, and NAPSA. Cytokines were represented by 10 members in the top 95 probe sets. Pathway and network analysis (p-value < 0.05 and FC > 2) identified granulocytes adhesion and diapedesis as top canonical pathway. Most significant upstream regulators were lipopolysaccharide, TNF, NKkB (complex), IL1A, and CSF2. Top networks categorized under diseases & functions were entitled migration of cells, cell movement, cell survival, apoptosis, and proliferation of cells. Probe sets that were significantly shared between the brain metastatic PTC, the TR, and primary brain tumors include CASP1, CASP4, C1R, CC2D2B, RNY1P16, WDR72, LRRC2, ZHX2, CITED1, and the noncoding transcript AK128523. Taken together, this study identified a set of candidate genes and biofunctions implicated in, so far nearly uncharacterized, molecular processes of a brain metastasis from a PTC. PMID:27822408

  7. Clinicopathological features for predicting central and lateral lymph node metastasis in papillary thyroid microcarcinoma: Analysis of 66 cases that underwent central and lateral lymph node dissection

    PubMed Central

    Tao, Yang; Wang, Chongjie; Li, Liye; Xing, Haijun; Bai, Yun; Han, Bing; Liu, Zhiyan; Yang, Xiangshan; Zhu, Shourong

    2017-01-01

    Currently the surgical approach for papillary thyroid microcarcinoma (PTMC), particularly the range of lymph node dissection, remains controversial. The present study aims to evaluate the risk factors for central and lateral lymph node metastasis (CLNM and LLNM) for appropriate clinical decision of neck lymph node dissection in PTMC. A total of 66 cases of PTMC that underwent unilateral or bilateral lobectomy plus prophylactic cervical lymph node dissection were collected for clinicopathological evaluation, including age, gender, tumor size, subtypes, extrathyroidal invasion, multifocality, calcifications, loss of cellular polarity/cohesiveness (LOP/C) in the invasive front, CLNM and LLNM, and retrospectively analysis. Univariate analysis revealed that LOP/C was significantly associated with CLNM (P=0.001) and LLNM (P<0.0001). The male gender was a risk factor of CLNM (P=0.04), while the age <45 years, tumor size >0.5 cm and multifocality were high-risk factors of LLNM (P=0.022, 0.044 and 0.005, respectively). Multivariable analysis revealed that LOP/C was significantly associated with CLNM [P=0.007, odds ratio (OR)=7.765, 95% confidence interval (CI)=1.773–33.996] and LLNM [P=0.029, OR=5.717, 95% CI=1.190–27.470]. Both multivariable analysis and χ2 test revealed that CLNM was another important high-risk factor of LLNM (P=0.021, OR=5.444, 95% CI=1.290–22.969, χ2=17.867, P<0.001). The present study revealed that prophylactic central lymph node dissection is essential for PTMC surgery and that prophylactic lateral lymph node dissection is recommend for patients with LOP/C and CLNM, which can be performed by intraoperative frozen section pathological examination. This must be considered discreetly in the case of patients with age <45 years, tumor size >0.5 cm and multifocal lesions. PMID:28123728

  8. Impact of lymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer: potential role of BRAFV600E mutation in defining CND.

    PubMed

    Alzahrani, Ali S; Xing, Mingzhao

    2013-02-01

    The impact of metastasized cervical lymph nodes (CLN) identified on central neck dissection (CND) on the recurrence/persistence of papillary thyroid cancer (PTC) and the extent of CND needed to reduce recurrence/persistence have not been firmly established. To assess the impact of CLN metastasis and BRAF mutation on the recurrence/persistence of PTC and the potential of BRAF mutation in assisting CND. Analyses of 379 consecutive patients with PTC who underwent thyroidectomy with (n=243) or without CND (n=136) at a tertiary-care academic hospital during the period 2001-2010 for their clinicopathological outcomes and BRAF mutation status. Increasingly aggressive tumor characteristics were found as the extent of CND was advanced following conventional risk criteria from non-CND to limited CND to formal CND. Disease recurrence/persistence rate also sharply rose from 4.7% to 15.7% and 40.5% in these CND settings respectively (P<0.0001). CLN metastasis rate rose from 18.0 to 77.3% from limited CND to formal CND (P<0.0001). An increasing rate of BRAF mutation was also found from less to more extensive CND. A strong association of CLN metastasis and BRAF mutation with disease recurrence/persistence was revealed on Kaplan-Meier analysis and BRAF mutation strongly predicted CLN metastasis. CLN metastases found on CND are closely associated with disease recurrence/persistence of PTC, which are both strongly predicted by BRAF mutation. Current selection of PTC patients for CND is appropriate but higher extent of the procedure, once selected, is needed to reduce disease recurrence, which may be defined by combination use of preoperative BRAF mutation testing and conventional risk factors of PTC.

  9. c-Met Inhibitor Synergizes with Tumor Necrosis Factor–Related Apoptosis-Induced Ligand to Induce Papillary Thyroid Carcinoma Cell Death

    PubMed Central

    Bu, Rong; Uddin, Shahab; Ahmed, Maqbool; Hussain, Azhar R; Alsobhi, Saif; Amin, Tarek; Al-Nuaim, Abdurahman; Al-Dayel, Fouad; Abubaker, Jehad; Bavi, Prashant; Al-Kuraya, Khawla S

    2012-01-01

    The Met receptor tyrosine kinase is overexpressed and/or activated in variety of human malignancies. Previously we have shown that c-Met is overexpressed in Middle Eastern papillary thyroid carcinoma (PTC) and significantly associated with an aggressive phenotype, but its role has not been fully elucidated in PTC. The aim of this study was to determine the functional link between the c-Met/AKT signaling pathway and death receptor 5 (DR5) in a large cohort of PTC in a tissue microarray format followed by functional studies using PTC cell lines and nude mice. Our data showed that high expressions of p-Met and DR5 were significantly associated with an aggressive phenotype of PTC and correlated with BRAF mutation. Treatment of PTC cell lines with PHA665752, an inhibitor of c-Met tyrosine kinase, inhibited cell proliferation and induced apoptosis via the mitochondrial pathway in PTC cell lines. PHA665752 treatment or expression of c-Met small interfering (si)RNA resulted in dephosphorylation of c-Met, AKT and its downstream effector molecules. Furthermore, PHA665752 treatment upregulated DR5 expression via generation of reactive oxygen species in PTC cell lines, and synergistically potentiated death receptor–induced apoptosis with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Finally, cotreatment with PHA665752 and TRAIL caused more pronounced effects on PTC xenograft tumor growth in nude mice. Our data suggest that the c-Met/AKT pathway may be a potential target for therapeutic intervention for treatment of PTC refractory to conventionally therapeutic modalities. PMID:22113498

  10. Molecular Targeting of Papillary Thyroid Carcinoma With Fluorescently Labeled Ratiometric Activatable Cell Penetrating Peptides in a Transgenic Murine Model

    PubMed Central

    OROSCO, RYAN K.; SAVARIAR, ELAMPRAKASH N.; WEISSBROD, PHILIP A.; DIAZ-PEREZ, JULIO A.; BOUVET, MICHAEL; TSIEN, ROGER Y.; NGUYEN, QUYEN T.

    2016-01-01

    Background and Objectives Molecularly targeted fluorescent molecules may help detect tumors that are unseen by traditional white-light surgical techniques. We sought to evaluate a fluorescent ratiometric activatable cell penetrating peptide (RACPP) for tumor detection in a transgenic model of PTC. Methods Thirteen BRAFV600E mice with PTC were studied—seven injected intravenously with RACPP, four controls with saline. Total thyroidectomy was performed with microscopic white-light visualization. Fluorescent imaging of post-thyroidectomy fields was performed, and tissue with increased signal was removed and evaluated for PTC. Final samples were analyzed by a pathologist blinded to conditions. Vocal cord function was evaluated postoperatively with video laryngoscopy. Results The average in situ ratiometric (Cy5/Cy7) thyroid tumor-to-background contrast ratio was 2.27 +/−0.91. Fluorescence-guided clean-up following thyroidectomy identified additional tumor in 2 of 7 RACPP animals (smallest dimension 1.2 mm), and decreased the number of animals with residual tumor from 4 to 3. All retained tumor foci on final pathology were smaller than 0.76 mm. Intact vocal abduction was present in all of the RACPP animals. Conclusions RACPPs successfully targeted PTC in a transgenic thyroidectomy model, and allowed for residual tumor detection that reduced positive margins beyond what was possible with white-light surgery alone. PMID:26799257

  11. Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.

    PubMed

    Dang, Shipeng; Peng, Yongde; Ye, Lei; Wang, Yanan; Qian, Zhongqing; Chen, Yuqing; Wang, Xiaojing; Lin, Yunzhi; Zhang, Xiaomei; Sun, Xiyan; Wu, Qiong; Cheng, Yiji; Nie, Hong; Jin, Min; Xu, Huanbai

    2013-01-01

    In inflammatory sites, high molecular weight hyaluronan fragments are degraded into lower molecular weight hyaluronan fragments (LMW-HA) to regulate immune responses. However, the function of LMW-HA in PTC progression remains to be elucidated. In this study, we found that receptor of LMW-HA, TLR4, was aberrantly overexpressed in PTC tissues and cell line W3. Exposure of W3 cells to LMW-HA promoted cell proliferation and migration via TLR4. Knockdown of TLR4 has provided evidence that TLR4 is essential for LMW-HA-induced CXCR7 expression, which is responsible for LMW-HA-induced proliferation and migration of W3 cells. In tumor-bearing adult nude mice, stimulation of LMW-HA on W3 cells promotes CXCR7 expression in tumor masses (P = 0.002) and tumor growth (P < 0.001). To further confirm our findings, we investigated the clinicopathologic significance of TLR4 and CXCR7 expression using immumohistochemistry in 135 human PTC tissues and 56 normal thyroid tissue samples. Higher rates of TLR4 (53%) and CXCR7 (24%) expression were found in PTC tissues than in normal tissues. Expression of TLR4 or CXCR7 is associated with tumor size and lymph node metastasis. Therefore, LMW-HA may contribute to the development of PTC via TLR4/CXCR7 pathway, which may be a novel target for PTC immunomodulatory therapy.

  12. KBO Occultation

    NASA Astrophysics Data System (ADS)

    Rijsdijk, C.

    2016-12-01

    A recommendation to astronomers to observe an occultation by the Kuiper Belt Object KBO 2014MU69. Its first predicted stellar occultation, in early June 2017, of a 15th magnitude star, will be visible from Southern Africa.

  13. Association of HLA-B*51:01 with Papillary Thyroid Carcinoma in the Chinese Han Population of the Shandong Coastal Areas

    PubMed Central

    Xiaoyun, Chi; Zhihui, Feng; Xiaohua, Liu; Zhanhui, Du; Bin, Hu; Lin, Zhao

    2014-01-01

    Background: A lot of work has been done to study the association between human leukocyte antigen (HLA) and papillary thyroid carcinoma (PTC) in various populations. But the results of the currently available studies are not consistent. The aim of this study was to evaluate the association of HLA-A, -B, -C, -DRB1, and -DQB1 with PTC in the Chinese Han population of the coastal areas of Shandong Province with respect to age and sex. Methods: A total of 154 patients diagnosed with PTC were analyzed for HLA-A, -B, -C, -DRB1, and -DQB1 alleles by using a polymerase chain reaction sequence-based typing (PCR-SBT) method. Two hundred unrelated healthy individuals were typed as controls. Results: Compared with the controls, the HLA-B*51:01 (8.8% vs. 4.5%, p=0.029, OR 2.039 [CI 1.101–3.775]) and HLA-C*07:06 (2.6% vs. 0.5%, p=0.024, OR 5.307 [CI 1.119–25.171]) allele frequencies were higher in the PTC patients, while the HLA-C*07:01 (1.3% vs. 6.0%, p=0.001, OR 0.206 [CI 0.071–0.601]) allele frequency was lower in the PTC patients that did not persist after Bonferroni correction for multiple tests. This showed no statistically significant correlation of the HLA-A, -DRB1, and -DQB1 alleles and PTC. The incidence of PTC was more frequent in females between 30 and 60 years old. There were no significant differences in the age and sex distributions between the total and the HLA-B*51:01 positive PTC patients. Conclusions: The HLA associations in this Chinese Han population differ markedly from studies done in Europeans and Caucasians. The results reveal that HLA-B*51:01 is more likely to be a susceptible allele for PTC in addition to age and sex in the coastal areas of Shandong Province. PMID:24308748

  14. Preoperative Prediction of Cervical Lymph Node Metastasis Using Primary Tumor SUVmax on 18F-FDG PET/CT in Patients with Papillary Thyroid Carcinoma

    PubMed Central

    Jung, Ji-hoon; Kim, Choon-Young; Son, Seung Hyun; Kim, Do-Hoon; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol

    2015-01-01

    Objectives The aim of the current study was to evaluate the value of preoperative 18F-FDG (FDG) PET/CT in predicting cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC). Methods One hundred and ninety-three newly diagnosed PTC patients (M: F = 25:168, age = 46.8 ± 12.2) who had undergone pretreatment FDG PET/CT and had neck node dissection were included in this study. The FDG avidity of the primary tumor and the SUVmax of the primary tumor (pSUVmax) were analyzed for prediction of LN metastasis. Detectability by ultrasonography (US) and FDG PET/CT for cervical LN metastasis were also assessed and compared with the pSUVmax. Results The FDG avidity of the primary tumor was identified in 118 patients (FDG avid group: 61.0%, M: F = 16:102, age 47.0 ± 12.7 years) and pSUVmax ranged from 1.3 to 35.6 (median 4.6) in the FDG avid group. The tumor size in the FDG avid group was bigger and there was a higher incidence of LN metastasis compared to the FDG non-avid group (0.93 vs. 0.59 cm, p <0.001 and 49.2 vs. 33.3%, p <0.05). In the FDG avid group, patients with LN metastasis had higher pSUVmax than patients without LN metastasis (8.7 ± 8.3 vs. 5.7 ± 5.1, p <0.001). The incidence of central LN metastasis in patients with a pSUVmax >4.6 was 54%; however, the detectability of central LN metastasis by US and FDG PET/CT were 10.3% and 3.6%, respectively. Conclusion A high FDG avidity of the primary tumor was related to LN metastasis in PTC patients. Therefore, patients with a high pSUVmax should be cautiously assessed for LN metastasis and might need a more comprehensive surgical approach. PMID:26636824

  15. Thyroid cancer in childhood

    SciTech Connect

    Gorlin, J.B.; Sallan, S.E. )

    1990-09-01

    The incidence, clinical presentation, and types of thyroid cancers presenting in childhood are reviewed. The role of antecedent radiation in papillary and follicular thyroid cancers and genetics of medullary thyroid carcinoma are discussed. Unique aspects of therapy and prognosis for the pediatric patient with thyroid carcinoma are addressed as well as a diagnostic approach to the child who presents with a neck mass.59 references.

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

    ClinicalTrials.gov

    2015-05-14

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

  17. A novel RET rearrangement (ACBD5/RET) by pericentric inversion, inv(10)(p12.1;q11.2), in papillary thyroid cancer from an atomic bomb survivor exposed to high-dose radiation.

    PubMed

    Hamatani, Kiyohiro; Eguchi, Hidetaka; Koyama, Kazuaki; Mukai, Mayumi; Nakachi, Kei; Kusunoki, Yoichiro

    2014-11-01

    During analysis of RET/PTC rearrangements in papillary thyroid cancer (PTC) among atomic bomb survivors, a cDNA fragment of a novel type of RET rearrangement was identified in a PTC patient exposed to a high radiation dose using the improved 5' RACE method. This gene resulted from the fusion of the 3' portion of RET containing tyrosine kinase domain to the 5' portion of the acyl-coenzyme A binding domain containing 5 (ACBD5) gene, by pericentric inversion inv(10)(p12.1;q11.2); expression of the fusion gene was confirmed by RT-PCR. ACBD5 gene is ubiquitously expressed in various human normal tissues including thyroid. Full-length cDNA of the ACBD5-RET gene was constructed and then examined for tumorigenicity. Enhanced phosphorylation of ERK proteins in the MAPK pathway was observed in NIH3T3 cells transfected with expression vector encoding the full-length ACBD5/RET cDNA, while this was not observed in the cells transfected with empty expression vector. Stable NIH3T3 transfectants with ACBD5-RET cDNA induced tumor formation after their injection into nude mice. These findings suggest that the ACBD5-RET rearrangement is causatively involved in the development of PTC.

  18. Racial Differences in Expression Levels of miRNA Machinery-Related Genes, Dicer, Drosha, DGCR8, and AGO2, in Asian Korean Papillary Thyroid Carcinoma and Comparative Validation Using the Cancer Genome Atlas

    PubMed Central

    Kim, Jaegil; Park, Woo-Jae; Jeong, Kwang-Joon; Kang, Sun Hee; Kwon, Sun Young

    2017-01-01

    Aberrant regulation of microRNA (miRNA) machinery components is associated with various human cancers, including papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer, and a higher prevalent female malignancy. The purpose of this study is to investigate racial differences in mRNA expression levels of four miRNA machinery components, Dicer, Drosha, DGCR8, and AGO2, and their correlations with clinicopathological characteristics. Forty PTC samples from female Asian Korean PTC patients were enrolled. Using qPCR, we examined mRNA expression levels of the components and next validated our results by comparison with results of female white American in the TCGA PTC project. Interestingly, mRNA expression levels of the selected factors were altered in the TCGA PTC samples. However, only Drosha showed a significantly lower expression level in Asian Korean PTC samples. Furthermore, the mRNA expression levels of the four components showed no association with clinicopathological characteristics in both groups. On the other hand, positive correlations were observed between altered mRNA expression levels of Dicer and Drosha and DGCR8 and Drosha in TCGA PTC samples. These findings collectively revealed that altered mRNA expression levels of miRNA machinery components might be responsible for racial differences in the carcinogenesis of PTC. PMID:28352639

  19. Hashimoto's Thyroiditis and Medullary Carcinoma of Thyroid.

    PubMed

    Dasgupta, S; Chakrabarti, S; Mandal, P K; Das, S

    2014-01-01

    Hashimoto's thyroiditis (HT) has been found to be associated with lymphoma, papillary carcinoma and Hürthle cell neoplasms of thyroid. In contrast, there are only a few reports of co-existence of HT with medullary carcinoma of thyroid. An overall prevalence of medullary carcinoma of only 0.35% has been reported in HT patients. Such a rare combination is being presented here. A 33 year old female presented with history of goiter for one year. Fine needle aspiration cytology (FNAC) of the swelling revealed cytological features suggestive of medullary carcinoma of thyroid. Histopathological examination of total thyroidectomy specimen revealed Hashimoto's thyroiditis along with medullary carcinoma of thyroid. Although Hashimoto's thyroiditis can uncommonly co-exist with thyroid neoplasm, its association with medullary carcinoma is extremely rare and hence being presented.

  20. 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.

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

    PubMed

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

    2012-01-01

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

  2. Grazing Occultations.

    ERIC Educational Resources Information Center

    Cunningham, Doug; Hlynialuk, John

    1983-01-01

    A "grazing occultation" occurs when a star or other astronomical body is covered up by the extreme northern or southern limb of the moon in its easterly motion about the earth. Graze phenomena, organizing a graze expedition, and the scientific/educational value of observing grazes are among the topics discussed. (JN)

  3. L-thyroxine-treated patients with nodular goiter have lower serum TSH and lower frequency of papillary thyroid cancer: results of a cross-sectional study on 27 914 patients.

    PubMed

    Fiore, E; Rago, T; Provenzale, M A; Scutari, M; Ugolini, C; Basolo, F; Di Coscio, G; Miccoli, P; Grasso, L; Pinchera, A; Vitti, P

    2010-03-01

    The risk of papillary thyroid cancer (PTC) is related to serum TSH, and the development of thyroid autonomy by reducing TSH levels decreases the frequency of PTC in patients with nodular goiter. Our aim was to investigate the effect of L-thyroxine (LT(4)) on the frequency of PTC diagnosed by cytology in a large series of patients with nodular goiter untreated (n=20 055) or treated with L-T(4) (n=7859). L-T(4)-treated patients with respect to untreated patients presented significantly lower serum TSH (median, interquartile range: 0.30 muU/ml, 0.08-0.62 microU/ml versus 0.70 muU/ml, 0.38-1.14 muU/ml; P<0.0001) and prevalence of PTC (3.2 vs 5.1%; P<0.0001). The frequency of PTC was closely related to serum TSH, with it being lowest in patients with TSH below the normal range (<0.4 muU/ml; 189/10 059, 1.9%) and highest in patients with TSH above the normal range (>3.4 muU/ml; 21/127, 16.5%), also showing a progressive increase from the lower to the upper quartile of normal range. A significantly higher proportion of L-T(4)-treated patients (6650/7859, 84.6%) had serum TSH below the median (0.90 muU/ml) with respect to untreated patients (12,599/20,055, 62.8%; chi(2) P value <0.0001), with it being included in the range of TSH associated with a lower frequency of PTC. The relationship between serum TSH and frequency of PTC was unrelated to the type of nodularity (solitary versus multinodular) and was not age dependent. In conclusion, patients with nodular goiter, treatment with L-T(4) is responsible for the reduction of serum TSH and is associated with a decreased frequency of PTC.

  4. Radiation exposure, young age, and female gender are associated with high prevalence of RET/PTC1 and RET/PTC3 in papillary thyroid cancer: a meta-analysis

    PubMed Central

    Su, Xuan; Li, Zhaoqu; He, Caiyun; Chen, Weichao; Fu, Xiaoyan; Yang, Ankui

    2016-01-01

    Background RET/PTC rearrangements have been identified as a specific genetic event in papillary thyroid cancer (PTC). We conducted this meta-analysis to identify an enriched population who were more likely to occur RET/PTC fusion genes. Methods All relevant studies in the PubMed, Web of Science, and Embase databases were searched up to June 2015. The studies found were screened according to our inclusion and exclusion criteria. All analyses were performed using STATA software. Results Eventually, 38 eligible studies comprising 2395 participants were included. Overall analysis indicated that radiation exposure contributed to increased RET/PTC risk (OR = 2.82; 95%CI: 1.38–5.78, P = 0.005). Stratified analysis according to RET/PTC subtype and geographical area showed that this association was restricted to the RET/PTC3 subtype (OR = 8.30, 95%CI: 4.32–15.96, P < 0.001) in the Western population. In addition, age < 18 years, i.e., young age, was associated with higher prevalence of RET/PTC3 (OR = 2.03, 95%CI: 1.14–3.62, P = 0.017), especially in the radiation-exposure subpopulation (OR = 2.35, 95%CI: 1.01–5.49, P = 0.048). The association between female gender and RET/PTC1 risk was more significant in the PTC patients without radiation exposure (OR = 1.69, 95%CI: 1.04–2.74, P = 0.034). Conclusion Both radiation exposure and young age are associated with increased risk of RET/PTC3 and that female gender is associated with higher prevalence of RET/PTC1 in the subpopulation without radiation exposure. The RET/PTC status in combination with radiation exposure, age, and sex should be considered in the differential diagnosis of suspicious PTC. PMID:26918339

  5. Disseminated bone metastases from occult thyroid cancer effectively treated with debulking surgery and a single dosimetry-guided administration of radioiodine.

    PubMed

    Borsò, Elisa; Boni, Giuseppe; Mazzarri, Sara; Cocciaro, Ardico; Gambacciani, Carlo; Traino, Antonio C; Manca, Giampiero; Grosso, Mariano; Scatena, Cristian; Ortenzi, Valerio; Vannozzi, Riccardo; Marzola, Maria Cristina; Rubello, Domenico; Mariani, Giuliano

    2015-01-01

    In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric (123)I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and (123)I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100 mCi (131)I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisciplinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity.

  6. [Medullary thyroid carcinoma and other rare types of thyroid carcinoma].

    PubMed

    Obara, Takao

    2007-11-01

    Among 4 major traditional groups of thyroid carcinoma, papillary and follicular carcinomas are most common, and other forms, anaplastic and medullary carcinomas, are relatively rare. The 2003 WHO histological classification of thyroid tumor separated 7 other malignant thyroid tumors into distinct pathological entities, such as poorly differentiated, squamous cell, mucinous carcinomas, carcinoma showing thymus-like differentiation (CASTLE), etc. Although they are also extremely rare, recognition of their clinicopathologic features are very important. In this review, not only diagnostic and therapeutic strategies for the rare forms of thyroid carcinomas, specifically focussed on medullary carcinoma and CASTLE, but also their histogenetic abnormalities were discussed.

  7. [BRAF V600E mutation in thyroid nodules in Argentina].

    PubMed

    Ilera, Verónica; Dourisboure, Ricardo; Colobraro, Antonio; Silva Croome, María Del Carmen; Olstein, Gustavo; Gauna, Alicia

    This prospective study analyzed the frequency of V600E mutation of oncogene BRAF in patients operated for benign thyroid nodules and for papillary thyroid cancer in an Argentine population. In patients with papillary thyroid cancer we compared clinicopathological characteristics between those harboring BRAF mutation and those without it. Twenty five consecutive patients operated for benign nodules and for papillary carcinoma were prospectively included. Fresh tissue samples of thyroid nodules and of adjacent thyroid parenchyma were obtained. DNA was extracted and amplified by amplification refractory mutation system polymerase chain reaction (ARMS PCR). Direct sequencing was performed in four samples. Of those patients operated for papillary thyroid cancer, 77% harbored BRAF mutation. All samples from adjacent thyroid parenchyma and from patients operated for benign nodules tested negative for the mutation. Direct sequencing confirmed the results obtained by ARMS PCR. Patients with BRAF mutation were significantly older at the time of diagnosis (BRAF+ 47.7 ± 12.7 years vs. BRAF- 24.7 ± 8.1 years, p < 0.01). Nine out of ten papillary carcinomas with BRAF mutation corresponded to the classic histological subtype, which was not observed in BRAF negative tumors (p < 0.02). In conclusion, we found a high frequency of BRAF V600E mutation in this population of patients operated for papillary thyroid carcinoma in Argentina. These results are consistent with those reported in the literature.

  8. Unusual primary tumors presenting as papillary carcinomas metastatic to the neck.

    PubMed

    Dupret-Bories, Agnès; Wilt, Marc; Kennel, Pierre; Charpiot, Anne; Rodier, Jean-François

    2015-01-01

    The presence of a metastatic papillary carcinoma in the neck is presumptive evidence of a primary thyroid neoplasm since neck metastases of other primary tumors are uncommon. Immunohistochemical studies may be required to diagnose these metastases. We report 2 cases in which an unrelated tumor mimicked a thyroid malignancy. Both patients had been referred for evaluation of enlarged lymph neck nodes without any other symptoms. In both cases, a lymph node biopsy identified a metastatic papillary adenocarcinoma that was believed to be consistent with a thyroid primary. Thyroidectomy was not performed in either case. Further investigations led to the diagnosis of other primary tumors that were unrelated to the thyroid; the unrelated primaries were an ovarian serous tumor in one patient and a papillary renal cell carcinoma in the other.

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

    PubMed

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

    2016-07-11

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

  10. Renal papillary necrosis

    MedlinePlus

    ... ureters. Causes Renal papillary necrosis often occurs with analgesic nephropathy . This is damage to one or both ... Treatment depends on the cause. For example, if analgesic nephropathy is the cause, your doctor will recommend ...

  11. Thyroid consequences of the Chernobyl nuclear accident.

    PubMed

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

    1999-12-01

    It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid

  12. U.S. Thyroid Cancer Cases Continue to Rise

    MedlinePlus

    ... life-threatening, the death rate for a particularly aggressive form of the disease -- advanced papillary thyroid cancer -- ... there needs to be a "renewed focus" on aggressive management of this disease, including surgery, radiation and/ ...

  13. TCGA study improves understanding of thyroid cancer genetics - TCGA

    Cancer.gov

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

  14. Thyroid ultrasound

    MedlinePlus

    ... The thyroid feels big or irregular, called a goiter . You have abnormal lymph nodes near your thyroid. ... due to: Cysts Enlargement of the thyroid gland ( goiter ) Thyroid nodules Thyroiditis, or inflammation of the thyroid ( ...

  15. Thyroid cancer incidence attributable to overdiagnosis in the United States 1981-2011.

    PubMed

    O'Grady, Thomas J; Gates, Margaret A; Boscoe, Francis P

    2015-12-01

    Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for both men and women of all ages and races. Overdiagnosis is partially responsible for this trend, although its magnitude is uncertain. This study examines papillary thyroid cancer incidence according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer incidence, 1981-2011, using the Surveillance, Epidemiology and End Results national cancer registries. Yearly changes in early and late-stage thyroid cancer incidence were calculated. We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis in 2011 was 5.5 and 45.5% in men ages 20-49 and 50+ and 41.1 and 60.1% in women ages 20-49 and 50+, respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary thyroid cancers that likely would never have caused any clinical symptoms. The detection of early-stage papillary thyroid cancer outpaced that of late-stage disease from 1981 through 2011, in part due to overdiagnosis. Further studies into the prevention, risk stratification and optimal treatment of papillary thyroid cancer are warranted in response to these trends.

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

    PubMed

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

    2007-01-01

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

  17. Deep shadow occulter

    NASA Technical Reports Server (NTRS)

    Cash, Webster (Inventor)

    2010-01-01

    Methods and apparatus are disclosed for occulting light. The occulter shape suppresses diffraction at any given size or angle and is practical to build because it can be made binary to avoid scatter. Binary structures may be fully opaque or fully transmitting at specific points. The diffraction suppression is spectrally broad so that it may be used with incoherent white light. An occulter may also include substantially opaque inner portion and an at least partially transparent outer portion. Such occulters may be used on the ground to create a deep shadow in a short distance, or may be used in space to suppress starlight and reveal exoplanets.

  18. Incidence of thyroid cancer in women in relation to previous exposure to radiation therapy and history of thyroid disease

    SciTech Connect

    McTiernan, A.M.; Weiss, N.S.; Daling, J.R.

    1984-09-01

    Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval . 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer.

  19. Peripheral papillary tumor of type-II pneumocytes: a rare neoplasm of undetermined malignant potential.

    PubMed

    Dessy, E; Braidotti, P; Del Curto, B; Falleni, M; Coggi, G; Santa Cruz, G; Carai, A; Versace, R; Pietra, G G

    2000-03-01

    Peripheral papillary adenomas of the lung are uncommon neoplasms (only ten cases have been described so far in the English literature) composed predominantly of type-II pneumocytes and generally considered benign. We describe here two additional cases of this lung tumor. In both cases histological examination revealed an encapsulated papillary neoplasm with invasion of the capsule and, in one case, invasion of the adjacent alveoli and visceral pleura too. The proliferative index (Ki67) was less than 2% and the epithelial cells were positive for cytokeratins, surfactant apoproteins (SP), and nuclear thyroid transcription factor-1 (TTF- 1). Ultrastructurally, the epithelial cells showed the characteristic surface microvilli and cytoplasmic lamellar inclusions of type-II cells. Review of the literature has revealed two other cases of peripheral papillary adenoma of type-II pneumocytes with infiltrative features. Thus, we propose replacing the term peripheral papillary adenoma with peripheral papillary tumor of undetermined malignant potential.

  20. Partial Laryngectomy with Cricoid Reconstruction: Thyroid Carcinoma Invading the Larynx

    PubMed Central

    Ozturk, Kerem; Makay, Ozer

    2014-01-01

    Laryngotracheal invasion worsens the prognosis of thyroid cancer and the surgical approach for laryngotracheal invasion is controversial. In this paper, partial full-thickness excision of the cricoid cartilage with supracricoid laryngectomy and reconstruction of existing defect with thyroid cartilage are explained in a patient with papillary thyroid carcinoma invading the thyroid cartilage and cricoid cartilage without intraluminal invasion. Surgical indication should not be established by the site of involvement in thyroid carcinomas invading the larynx, as in primary cancers of the larynx. We think that partial laryngectomy according to the involvement site and the appropriate reconstruction techniques should be used for thyroid cancer invading the larynx. PMID:24660082

  1. Clavicle metastasis from carcinoma thyroid- an atypical skeletal event and a management dilemma.

    PubMed

    Krishnamurthy, Arvind

    2015-09-01

    Bone metastases is a well described event in the natural history of thyroid cancers and has the potential to severely impact the quality of life by causing pain, fractures and spinal cord compression. Follicular thyroid carcinomas have a greater propensity for distal metastasis than papillary and anaplastic thyroid carcinomas. The most common sites of skeletal metastasis among thyroid cancer patients are femur followed by humerus, pelvis, radius, and scapula. Clavicle metastasis at initial presentation is exceedingly rare. Although many studies have examined the various prognostic factors for patients with bony metastases from thyroid cancers, very few have actually evaluated the effects of surgical management. We present an unusual case of metastatic papillary carcinoma thyroid presenting with clavicle metastasis and review the role of surgical management of bone metastases. Clavicular resection as a part of the management of metastatic papillary carcinoma thyroid has, to the best of our knowledge never been reported before.

  2. Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis

    PubMed Central

    Hardy, Robert G.; Vicente-Dueñas, Carolina; González-Herrero, Ines; Anderson, Catriona; Flores, Teresa; Hughes, Sharon; Tselepis, Chris; Ross, James A.; Sánchez-García, Isidro

    2007-01-01

    E-Cadherin (CDH1) expression is reduced in thyroid carcinomas by primarily unknown mechanisms. In several tissues, SNAIL (SNAI1) and SLUG (SNAI2) induce epithelial-mesenchymal transition by altering target gene transcription, including CDH1 repression, but these transcription factors have not been studied in thyroid carcinoma. Recently, our group has provided direct evidence that ectopic SNAI1 expression induces epithelial and mesenchymal mouse tumors. SNAI1, SNAI2, and CDH1 expression were analyzed in thyroid-derived cell lines and samples of human follicular and papillary thyroid carcinoma by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The effect of SNAI1 expression on CDH1 transcription was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting in ori-3 cells. Thyroid carcinoma development was analyzed in CombitTA-Snail mice, in which SNAI1 levels are up-regulated. SNAI1 and SNAI2 were not expressed in cells derived from normal thyroid tissue, or in normal human thyroid samples, but were highly expressed in cell lines derived from thyroid carcinomas, in human thyroid carcinoma samples, and their metastases. SNAI1 expression in ori-3 cells repressed CDH1 transcription. Combi-TA mice developed papillary thyroid carcinomas, the incidence of which was increased by concomitant radiotherapy. In conclusion, SNAI1 and SNAI2 are ectopically expressed in thyroid carcinomas, and aberrant expression in mice is associated with papillary carcinoma development. PMID:17724139

  3. Etiopathogenesis of Differentiated Thyroid Carcinomas

    PubMed Central

    Makazlieva, Tanja; Vaskova, Olivija; Majstorov, Venjamin

    2016-01-01

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

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

    PubMed

    Benvenga, Salvatore; Antonelli, Alessandro; Vita, Roberto

    2015-12-01

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

  5. Profile of Hashimoto's Thyroiditis in Sri Lankans: Is There an Increased Risk of Ancillary Pathologies in Hashimoto's Thyroiditis?

    PubMed

    Siriweera, Eranga Himalee; Ratnatunga, Neelakanthi Vajira Illangakoon

    2010-10-10

    Hashimoto's thyroiditis has been reported to be associated with many neoplastic and nonneoplastic thyroid pathologies. This retrospective study aims to determine the demographic profile of Hashimoto's thyroiditis in Sri Lankans, document ancillary pathologies in Hashimoto's thyroiditis, and determine whether there is an increased risk of occurrence of malignancies, benign neoplasms, and nonneoplastic benign lesions in Hashimoto's thyroiditis by comparing with thyroids showing multinodular goiters, follicular adenomas, and colloid nodules. The mean age of Hashimoto's thyroiditis is 43.3 years with the majority in the 41 to 60 year age group and a female to male ratio of 10.3 : 1. This study revealed a statistically significant increase of thyroid malignancies in association with Hashimoto's thyroiditis. The association of Papillary carcinoma, Non-Hodgkin's lymphoma, and Hurthle cell adenoma with Hashimoto's thyroiditis was statistically significant.

  6. Initial surgical management of thyroid cancer.

    PubMed

    Witt, Robert L

    2008-01-01

    The rapid increase in the rate of papillary thyroid cancer is likely caused by improved surveillance. A significant trend toward total thyroidectomy for low-risk differentiated thyroid cancer is present in the United States after a paradigm shift from treatment of macroscopic disease to the treatment of macroscopic and microscopic disease by increasingly sensitive tests. Compelling arguments for thyroid lobectomy and total thyroidectomy for low-risk thyroid cancer remain. The relatively small number of deaths from thyroid cancer, the small number of clinical thyroid cancers, and the huge number of incidental thyroid cancers are indicative of how little we understand the biology of this disease. Clinical medicine awaits biologic markers to refine treatment recommendations.

  7. Canadian survey of thyroid cancer

    PubMed Central

    Simpson, W. John; McKinney, Steven E.

    1985-01-01

    We report the results of a multicentre retrospective chart review of 2214 patients with thyroid cancer registered at 13 radiotherapy centres between 1958 and 1978. The data analysed included sex, age at the time of diagnosis, pathological diagnosis, extent of disease before treatment, types of treatment and their complications, and the rates of recurrence and survival up to 24 years after diagnosis. Although papillary cancers were most common, anaplastic and miscellaneous tumours were more frequent than expected, which reflects the type of patients referred by endocrinologists and surgeons to radiotherapy centres. There were marked differences in patterns of referral to the centres. Some patients with papillary and follicular thyroid cancers died of these cancers up to 20 years after diagnosis. The clinical manifestations, treatment and outcome of the rarer types of thyroid malignant tumours were of particular interest. The influence of age at the time of diagnosis on survival rates for patients with papillary or follicular thyroid cancer was highly significant, indicating much more aggressive behaviour of these cancers in older patients, particularly those beyond the age of 60 years. A more detailed analysis of tumour subtypes should provide new information on their natural history and lead to better management. PMID:3978516

  8. Occulter Starshade Technology Development

    NASA Astrophysics Data System (ADS)

    Lisman, P. D.; Thomson, M.; Kissil, A.; Walkemeyer, P.; Polanco, O.

    2010-10-01

    Imaging Earth-like exoplanets with a free flying occulter requires developing a large, lightweight, flower-shaped, deployable structure with precisely controlled edge position and profile. In-plane tolerance requirements are considerably tighter than heritage antenna systems, but the more difficult to control out-of-plane tolerances are actually much looser. This paper presents a novel occulter mechanical design that delivers the required performance with a highly reliable deployment scheme. A very compact stowed volume is an added benefit that enables launching the occulter together with a 1 to 2m class telescope, using a single, currently available launch vehicle. Demonstrating the petal deployment function and compliance with key tolerance specifications is the focus of current technology efforts. A series of prototype models of increasing fidelity are planned, starting with a proof of concept model that is currently in fabrication. The occulter design and current development status is presented herein.

  9. [Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

    PubMed

    Itoh, Mitsuyasu

    2012-11-01

    Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

  10. Serum levels of sex hormones and expression of their receptors in thyroid tissue in female patients with various types of thyroid neoplasms.

    PubMed

    Liu, Jia; Chen, Guang; Meng, Xian-Ying; Liu, Zhong-Hui; Dong, Su

    2014-12-01

    Previous studies have demonstrated the expression of estrogen receptor (ER) and progesterone receptor (PR) in thyroid cancer; however, little is known regarding the levels of estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum and the expression of ER, PR, FSH receptor (FSHR), and LH receptor (LHR) in thyroid tissues of patients with different types of thyroid neoplasms. Serum levels of estrogen, progesterone, FSH, and LH were measured by chemiluminescence, and expression of ER, PR, FSHR, and LHR in thyroid tissue was detected by immunohistochemistry in female patients with thyroid adenoma (n = 70), nodular goiter (n = 73), thyroid papillary cancer (n = 149), poorly differentiated thyroid carcinoma (n = 12), or undifferentiated thyroid carcinoma (n = 8) and in normal controls (n = 60). The positive rates of serum estrogen level and ERα expression were significantly greater in patients with various types of thyroid neoplasms than in normal controls. The positive rates of ERβ expression were significantly less in various types of thyroid neoplasms than in normal thyroid tissues, especially in poorly differentiated carcinoma and undifferentiated carcinoma. The negative rates of serum progesterone level and positive rates of PR expression in thyroid tissue were significantly greater in patients with thyroid adenoma, nodular goiter, or thyroid papillary cancer than in normal controls. The positive rates of serum FSH and LH levels and FSHR and LHR expression were significantly greater in the thyroid adenoma group than in other groups. Our findings suggest that thyroid neoplasms might be sex hormone-dependent. The positive expression of ERα and PR often indicates thyroid papillary carcinoma, and the ERβ expression status is important for the diagnosis of poorly differentiated carcinoma and undifferentiated carcinoma. In addition, thyroid adenoma is often accompanied by an increase in serum FSH and LH levels, as well as

  11. Postpartum Thyroiditis

    MedlinePlus

    ... high thyroid hormone levels in the blood) and hypothyroidism (low thyroid hormone levels in the blood). In postpartum thyroiditis, thyrotoxicosis occurs first followed by hypothyroidism. What causes postpartum thyroiditis? The exact cause is ...

  12. Thyroid Nodules

    MedlinePlus

    ... Your Body in Balance › Thyroid Nodules Fact Sheet Thyroid Nodules March 2010 Download PDFs English Espanol Hindi ... Singer, MD Leonard Wartofsky, MD What is the thyroid gland? The thyroid gland is a butterfly-shaped ...

  13. Thyroid Tests

    MedlinePlus

    ... calories and how fast your heart beats. Thyroid tests check how well your thyroid is working. They ... thyroid diseases such as hyperthyroidism and hypothyroidism. Thyroid tests include blood tests and imaging tests. Blood tests ...

  14. Occultation by (136199) Eris

    NASA Astrophysics Data System (ADS)

    Jehin, E.; Manfroid, J.; Gillon, M.; Hutsemekers, D.; Magain, P.

    2010-11-01

    E. Jehin, J. Manfroid, M. Gillon, D. Hutsemekers, and P. Magain report that they observed an occultation of a star of magnitude I about 15.2 by the dwarf planet Eris (then at V about 18.7) on Nov. 6 using the new telescope TRAPPIST at the European Southern Observatory (La Silla). A series of 3-s exposures of a field of size 3' x 3' (1".3/pixel) were secured in fast-readout mode (with a deadtime of 1.5 s), starting at 01h50m UT for one hour. Seven frames centered at 02h19m34s UT allowed them to derive the start of the occultation as 02h19m16s.75 +/- 0s.75 and the end as 02h19m47s.6 +/- 0s.2, for a total occultation time of 30.4 +/- 1.0 seconds. The predictions (see above) made by the Rio de Janeiro group (Assafin et al., Nov. 5) and by J. L. Ortiz estimated the time of the occultation around 02h18m UT for Chile, in good agreement with the observations. During the occultation, a point source is detected with a magnitude corresponding to that of Eris. A small flux increase was also seen at the middle of the occultation, which might result from refraction in Eris' atmosphere (Elliot and Olkin 1996, Ann. Rev. Earth Planet. Sci. 24, 89). Eris is by far the most-remote solar-system object observed to date via stellar occultation, with a geocentric distance of about 96 AU. TRAPPIST is a project driven by the University of Liege, in close collaboration with the Observatory of Geneva, supported by the Belgian Fund for Scientific Research and the Swiss National Science Foundation.

  15. Natural history of thyroid cancer [Review].

    PubMed

    Takano, Toru

    2017-02-02

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

  16. Occultations, past and future

    NASA Astrophysics Data System (ADS)

    Evans, David S.

    Techniques and limitations of photoelectric observations of occultations are discussed. Methods are described for allowing for fringe effects which arise from real world deviations from a uniform limb, and for using the limb measurements to derive ephemerides for the moon. Procedures employed to identify and separate out the components of multiple star systems are reviewed, and techniques are presented for improving the acuity of photoelectric angular size measurements that are complementary to interferometric measurements. Finally, sample data are provided to illustrate anomalies observed in photoelectric occultation observations of Antares and Aldebaran.

  17. Occult fractures of extremities.

    PubMed

    Ahn, Joong Mo; El-Khoury, Georges Y

    2007-05-01

    Recent advances in cross-sectional imaging, particularly in CT and MR imaging, have given these modalities a prominent role in the diagnosis of fractures of the extremities. This article describes the clinical application and imaging features of cross-sectional imaging (CT and MR imaging) in the evaluation of patients who have occult fractures of the extremities. Although CT or MR imaging is not typically required for evaluation of acute fractures, these modalities could be helpful in the evaluation of the occult osseous injuries in which radiographic findings are equivocal or inconclusive.

  18. Thyroid abnormalities after therapeutic external radiation

    SciTech Connect

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

    1995-03-30

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

  19. [Thyroglossal cyst and papillary carcinoma. Management proposals].

    PubMed

    Palomino-Martínez, Brisa Denise; Beristain-Hernández, José Luis; Piscil-Salazar, Marco Antonio; Villalpando-Mendoza, César Javier; Velázquez-García, José Arturo

    2014-01-01

    The thyroid descends through the foramen cecum leaving the thyroglossal duct, which disappears between the fifth and the tenth week of pregnancy. The lack of involution of any part of this duct results in thyroglossal cyst formation. Its diagnostic approach is made by cervical ultrasound, computed tomography and magnetic resonance imaging. Approximately 1 % of the thyroglossal cyst formation contains malignant elements, and the most reported primary tumor has been papillary carcinoma. The recommended treatment for these carcinomas is controversial and it has evolved as time goes by. From Sistrunk procedure to neck dissection with total thyroidectomy and complementary therapies, such as iodine ablation and thyroid supplements, yet there is still no consensus as to the type of surgery and postoperative management it should be used to treat this carcinoma. Therapy should be applied according to each specific case, and it should be based on histological diagnosis, the invasive character of the tumor, and the lymph node affectation. In this paper we review the literature published so far with regards to the treatment of this carcinoma.

  20. Giant papillary conjunctivitis.

    PubMed Central

    Donshik, P C

    1994-01-01

    Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low-water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 11 A FIGURE 11 B FIGURE 11 C FIGURE 11 D PMID:7886881

  1. Radioiodine and radiotherapy in the management of thyroid cancers

    SciTech Connect

    Simpson, W.J. )

    1990-06-01

    Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients. 30 references.

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

    PubMed Central

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

    2016-01-01

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

  3. All about Occultation.

    ERIC Educational Resources Information Center

    Riddle, Bob

    2001-01-01

    Describes occultation events involving the moon, when the moon blocks the view of planets or stars. Describes other events such as a partial solar eclipse, a penumbral lunar eclipse, meteor showers, and moon phases. Provides a list of internet resources related to these events. (DLH)

  4. Surgical Treatment of Hashimoto's with Thyroid Microcarcinoma.

    PubMed

    Tao, Liu; Xi-Lin, H; Xiang-Dong, M

    2015-05-01

    The aim of this study is to explore the surgical strategies for treating Hashimoto's disease complicated with thyroid microcarcinoma. We analyzed the clinical data of 25 patients with Hashimoto's disease with thyroid microcarcinoma who were treated in our hospital from January 1995 to September 2011. The incidence of Hashimoto's disease with thyroid microcarcinoma was 9.8 % (25/256) in our hospital. Amongst them, 19 patients had papillary thyroid carcinoma and six had follicular thyroid carcinoma. There were 24 cases (96 %) confirmed by the frozen section examination and one (4 %) after surgery. One patient did not undergo remedial surgery. The surgical approaches were determined based on preoperative examinations and intraoperative frozen pathology, including thyroid lobe and isthmus resection with contralateral lobe subtotal resection in 19 cases, and bilateral subtotal thyroid lobectomy in one case. Central lymph node dissection was conducted for all patients except one who was not diagnosed until after the surgery. No recurrence occurred during the follow-up (range: 6 months to 17 years) and all patients have survived to date. The preoperative diagnosis rate of Hashimoto's disease with thyroid cancer (in particular thyroid microcarcinomas) is low. Preoperative palpation, color Doppler ultrasound, fine needle aspiration, and the frozen section examination are helpful to improve the diagnosis rate of Hashimoto's disease with thyroid microcarcinoma. Surgery procedure is the most effective approach.

  5. The association between serum TSH concentration and thyroid cancer.

    PubMed

    Boelaert, Kristien

    2009-12-01

    There is mounting evidence that the serum concentration of TSH is an independent predictor for the diagnosis of thyroid malignancy in patients with nodular thyroid disease. Furthermore, preoperative serum TSH concentrations are higher in patients with more aggressive tumours, suggesting a potential role for TSH in the progression of differentiated thyroid cancer. Based on these observations, patients with higher serum TSH concentrations and borderline cytological results may require more aggressive investigation and treatment when compared with those with lower baseline TSH levels. The mechanisms underlying the finding of higher serum TSH in patients with thyroid cancer remain unexplained. In this issue of Endocrine-Related Cancer, Fiore et al. have analysed the relationship between serum TSH and diagnosis of papillary thyroid cancer in 10 178 patients with nodular thyroid disease who were investigated by fine-needle aspiration biopsy. They found significantly higher TSH concentrations in patients who were subsequently diagnosed with thyroid cancer compared with those with benign disease. In addition, they found that the development of autonomous thyroid function (TSH<0.4 muU/ml) was associated with a reduction in the risk of papillary thyroid carcinoma. In this commentary, the evidence regarding the association between serum TSH and thyroid cancer is discussed placing these new findings into context.

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

    PubMed

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

    2014-01-01

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

  7. Silent thyroiditis

    MedlinePlus

    ... gland. The disorder can cause hyperthyroidism, followed by hypothyroidism. The thyroid gland is located in the neck, ... Later symptoms may be of an underactive thyroid ( hypothyroidism ), including fatigue and cold intolerance, until the thyroid ...

  8. Thyroid scan

    MedlinePlus

    ... test is done to: Evaluate thyroid nodules or goiter Find the cause of an overactive thyroid gland ... chap 11. Read More Anaplastic thyroid cancer Cancer Goiter - simple Hyperthyroidism Multiple endocrine neoplasia (MEN) II PET ...

  9. Thyroid Disease

    MedlinePlus

    ... your menstrual period. Your thyroid helps control your menstrual cycle. Too much or too little thyroid hormone can ... Problems getting pregnant. When thyroid disease affects the menstrual cycle, it also affects ovulation. This can make it ...

  10. Thyroid neoplasia following irradiation for medulloblastoma: report of two cases.

    PubMed

    Roggli, V L; Estrada, R; Fechner, R E

    1979-06-01

    Thyroid neoplasms occurred in two patients 14 and 18 years after treatment with radiation for medulloblastoma. One patient has a papillary cancer and the other patient had multiple adenomas and a Hurthle cell adenoma. In addition, the latter case had foci of hyperplasia plus a microfollicular transformation, which has not been described in association with prior thyroid irradiation. The radiation doses delivered to the thyroid through posterior cervical spinal ports (2000--3000 roentgens) fall within the upper range of radiation dosage associated with induction of neoplastic changes within the thyroid.

  11. [Immunohistochemical profile of angiogenesis in the thyroid gland in various thyroid diseases].

    PubMed

    Rurua, N Z; Gogiashvili, L E; Tsagareli, Z G

    2013-12-01

    The purpose of the study - to determine the feature of the vascular endothelial growth factor (VEGF) and thyroid-stimulating hormone (TSH) expression in the thyroid gland (TG) in various thyroid diseases. Material - thyroid tissue (operative material) with histologically confirmed diagnosis: 10 - follicular adenoma, 17 - multinodular goiter, 8 - thyroiditis Hashimoto, 8 - papillary carcinoma, 10 - intact (normal) thyroid samples (forensic autopsy). The immunohistochemical study of the material showed the following results: the increase of the Hürtle cells population 40 % or more indicates a hyperthyroidism tendency despite TSH+ receptor status. Under the thyroid pathology TSH and VEGF expression appears in thyrocytes and also in microvascular endothelial cells. VEGF expression is below the norm in the Hashimoto thyroiditis. VEGF is involved not only in angiogenesis, but in pathophysiological shifts in thyroid tissue. Microvessel density (MVD) and TSH positive receptor status under the thyroid pathology testify the absence of the endothelial cells transformation, however, this index can not serve as a biopothential prognostic marker of thyroid disease.

  12. TERT promoter mutations in thyroid cancer.

    PubMed

    Liu, Rengyun; Xing, Mingzhao

    2016-03-01

    The 2013 discovery of Telomerase reverse transcriptase (TERT) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.

  13. A Case Report on Multiple Stones in the Thyroid Gland in Association with Sclerosing Thyroiditis: An Unusual Encounter

    PubMed Central

    Sinha, Ravish Kumar; Ekka, Nishith; Kumar, Vinod

    2017-01-01

    Stones are very frequently found in the gallbladder and urinary tract. Rarely the thyroid gland can be a site for stone formation. Few cases of calcification in thyroid gland have been described in the medical literature in association with papillary carcinoma and multinodular goiter. A unique case of a thyroid swelling studded with multiple stones in its parenchyma, in the histopathological background of sclerosing thyroiditis in an 80-year-old male is documented here. Surgical excision was undertaken with an uneventful postoperative period. PMID:28384929

  14. Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease

    PubMed Central

    Busaidy, Naifa Lamki; Cabanillas, Maria E.

    2012-01-01

    Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine. PMID:22530159

  15. Nuclear grooves in cytologic preparations. A study of the utility of this feature in the diagnosis of papillary carcinoma.

    PubMed

    Gould, E; Watzak, L; Chamizo, W; Albores-Saavedra, J

    1989-01-01

    The sensitivity and specificity of nuclear grooves and inclusions for papillary carcinoma was investigated in 32 touch preparations and 69 fine needle aspiration cytologic preparations of the thyroid. Ultrastructurally, these grooves and inclusions are cytoplasmic invaginations into the nucleus. Overall, 100% of the papillary carcinomas contained nuclear grooves while only 70% contained inclusions. Grooves, however, could be seen in 70% of nonpapillary neoplasms and in 56% of nonneoplastic conditions of the thyroid, albeit generally fewer in number and often not as distinct. Inclusions were present in 13% of nonpapillary neoplasms and were absent in nonneoplastic conditions. Some nuclei on cytologic preparations contain lines that are probably artifacts of chromatin alignment and do not represent true nuclear grooves. Since such lines may be indistinguishable from true grooves, grooves should be used cautiously and in conjunction with other criteria in the diagnosis of papillary carcinoma.

  16. Thyroid Hormone Deiodinases and Cancer

    PubMed Central

    Casula, Sabina; Bianco, Antonio C.

    2012-01-01

    Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches. PMID:22675319

  17. Gonadal damage due to radioactive iodine (I131) treatment for thyroid carcinoma.

    PubMed Central

    Ahmed, S. R.; Shalet, S. M.

    1985-01-01

    Papillary carcinoma of the thyroid is the most common type of thyroid cancer and is associated with a good prognosis. Complications of treatment with surgery and radioiodine are uncommon. We report the case of a 13 year old boy who developed testicular damage following treatment with radioactive iodine 350 mCi for a papillary carcinoma of the thyroid. Four years after radioiodine treatment there has been no suggestion of recovery of spermatogenesis. Detailed follow-up studies of similarly treated young patients are required to define the incidence of this complication and to determine its reversibility. PMID:4022871

  18. Mammary analog secretory carcinoma of thyroid: A case report.

    PubMed

    Rupp, Aaron P; Bocklage, Thèrése J

    2017-01-01

    Mammary analog secretory carcinoma (MASC) is a recently described rare neoplasm that was first reported in the salivary gland with an associated ETV6-NTRK3 fusion. We present a case of MASC involving and presumably arising in the thyroid, which was originally diagnosed as papillary thyroid carcinoma on fine needle aspiration and surgical resection. The later correct diagnosis of MASC was confirmed by immunohistochemistry and molecular studies. The cytopathological features of MASC in the salivary gland are previously described; however, we present the first cytopathological description of MASC arising in the thyroid with the unique feature of prominent nuclear grooves. Differentiating MASC from overlapping features of cytopathologic mimics such as papillary thyroid carcinoma may carry crucial therapeutic implications. Diagn. Cytopathol. 2017;45:45-50. © 2016 Wiley Periodicals, Inc.

  19. Biomarkers for the diagnosis of thyroid cancer.

    PubMed

    Sethi, Kruttibas; Sarkar, Siddik; Das, Subhasis; Mohanty, Biswanarayan; Mandal, Mahitosh

    2010-01-01

    Thyroid tumor contributes 1% of the total tumor but 90% of the endocrine related tumors. Majority of the thyroid cancers are being diagnosed by Fine needle aspiration cytology (FNAC) and histology. Although histology is considered as gold standard, it has some limitations, like variants of papillary and follicular cancer creates confusion among pathologists, where the morphological features are indistinguishable. Conventional histology and FNAC fails to provide any prognostic and therapeutic information. To address this problem, several immunohistochemical markers are proposed and their efficiency in thyroid cancer diagnosis, treatment and prognosis are being evaluated. Among the discussed immunohistochemical markers, few have potential in accurate diagnosis and prognosis of thyroid carcinoma. Hector battifora mesothelial antigen-1 (HBME-1) and Galectin-3 (GAL-3) shows highest specificity and sensitivity in the diagnosis of thyroid cancer respectively. Overexpression of EGFR in thyroid cancer is in proportionate with the severity of the advanced thyroid carcinoma, which required further evaluation and validation. Surgery and radio-iodine therapy is the main treatment modality, however; combined targeted therapeutic approach against different thyroid cancer receptor and biomarkers can reduce the side effect, and improve therapeutic efficiency. This review is oriented towards the finding of the potent thyroid cancer receptor having enhanced sensitivity and specificity, with diagnostic, prognostic and therapeutic efficiency.

  20. Thyroid cancer after external or internal ionizing irradiation.

    PubMed

    Papadopoulou, Foteini; Efthimiou, Elias

    2009-01-01

    It has been known for 50 years that thyroid exposure to high doses of ionizing radiation in childhood and adolescence induces an appreciable cancer risk. Epidemiological studies in children treated with external radiotherapy for benign or malignant lesions in the head and neck have also shown the induction of thyroid cancer. The World Health Organization (WHO) has reported that the risk for developing thyroid cancer due to the Chernobyl accident is greatest in newborns and children below the age of 5, less in adolescents and negligible in adults. As reported, during the first 15 years after the accident, the increase in thyroid cancer cases in Belarus was 87.8 fold in children, 12.7 fold in adolescents and 4.5 fold in adults more than expected. Papillary thyroid cancer with a relative risk incidence of approximately 80% per se is typical in childhood and adolescence. We refer to the differences between adult and childhood papillary thyroid cancers. Gene mutations in thyroid tumors induced after Chernobyl accident have been studied extensively. The treatment comprises thyroid surgery, suppressive doses of thyroxine and radioiodine. It is noteworthy that the thyroid gland can be protected from the intake of radioactive iodine by oral administration of potassium iodide.

  1. Papillary tubular adenoma with marked tubular vacuolization.

    PubMed

    Hattori, N; Imakado, S; Kikuchi, K; Murakami, T; Furue, M

    1997-12-01

    We report a case of papillary tubular adenoma, arising on the knee joint. The overall histologic structure of the tumor is consistent with that of papillary tubular adenoma with slight interluminal papillary changes, but most of the tumor cells present vacuolization outlined by carcinoembryonic antigen staining, suggesting that this adenoma may have resulted from microlumen formation. This is, to our knowledge, the first reported case of a papillary tubular adenoma with marked tubular vacuolization.

  2. Search for NTRK1 proto-oncogene rearrangements in human thyroid tumours originated after therapeutic radiation

    PubMed Central

    Bounacer, A; Schlumberger, M; Wicker, R; Du-Villard, J A; Caillou, B; Sarasin, A; Suárez, H G

    2000-01-01

    Rearrangements of NTRK1 proto-oncogene were detected in ‘spontaneous’ papillary thyroid carcinomas with a frequency varying from 5 to 25% in different studies. These rearrangements result in the formation of chimaeric genes composed of the tyrosine kinase domain of NTRK1 fused to 5′ sequences of different genes. To investigate if the NTRK1 gene plays a role in radiation-induced thyroid carcinogenesis, we looked for the presence of NTRK1 -activating rearrangements in 32 human thyroid tumours (16 follicular adenomas, 14 papillary carcinomas and two lymph-node metastases of papillary thyroid carcinomas) from patients who had received external radiation, using the reverse transcription polymerase chain reaction, Southern blot and direct sequencing techniques. These data were compared with those obtained in a series of 28 ‘spontaneous’ benign and malignant thyroid tumours, collected from patients without a history of radiation exposure and four in vitro culture cell lines derived from ‘spontaneous’ thyroid cancers. Our results concerning the radiation-associated tumours showed that only rearrangements between NTRK1 and TPM3 genes (TRK oncogene) were detected in 2/14 papillary carcinomas and in one lymph-node metastasis of one of these papillary thyroid carcinomas. All the radiation-associated adenomas were negative. In the ‘spontaneous’ tumours, only one of the 14 papillary carcinomas and one of the four in vitro culture cell lines, derived from a papillary carcinoma, presented a NTRK1 rearrangement also with the TPM3 gene. Twenty-five of this series of radiation-associated tumours were previously studied for the ras and RET/PTC oncogenes. In conclusion, our data: (a) show that the overall frequency of NTRK1 rearrangements is similar between radiation-associated (2/31: 6%) and ‘spontaneous’ epithelial thyroid tumours (2/32: 6%). The frequency, if we consider exclusively the papillary carcinomas, is in both cases 12%; (b) show that the TRK oncogene

  3. Thyroid Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net’s Guide to Thyroid Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Introduction Statistics Medical Illustrations Risk Factors Symptoms and ...

  4. Incidental carcinoma of the thyroid.

    PubMed

    Pezzolla, Angela; Marzaioli, Rinaldo; Lattarulo, Serafina; Docimo, Giovanni; Conzo, Giovanni; Ciampolillo, Anna; Barile, Graziana; Anelli, Ferdinando Massimiliano; Madaro, Andrea

    2014-01-01

    The diagnosis of incidental thyroid carcinoma in patients submitted to thyroidectomy for a benign disease is quite frequent. A retrospective analysis was performed on 455 patients submitted to surgical intervention in order to establish the incidence of this kind of carcinoma. Two hundred fifty-six patients (56%) were affected by benign disease (176 multinodular goiter, 12 uninodular goiter, 1 Plummer disease and 67 Basedow disease) and 202 (44%) by carcinoma. In 28 of 256 patients (11%), affected by benign disease, occurred a histological diagnosis of thyroid carcinoma, (10 papillary carcinoma, 1 follicular carcinoma, 29 papillary carcinoma follicular variant). In this study it's considered incidental thyroid carcinoma the one occurred in patients who never underwent Fine Needle Aspiration (FNA) and there were no suspicious features in all exams that may suggest the presence of carcinoma. Twenty-three of the 40 incidental carcinoma (57.5%) were microcarcinomas. Ten patients had a sincronous carcinoma. Actually, these patients are still in a follow up program and no recurrency of disease is occasionally observed. This study shows that the only way to put doubts on the real benignity of the disease is the fine needle aspiration; there are no other instruments that could identify the occurrence of the carcinoma. Moreover in the majority of cases the incidental carcinoma is a microcarcinoma, it doesn't reach significant volume, may be not centered by a FNA, but in most cases it's not really biologically aggressive.

  5. Photoelectric observations of lunar occultations

    NASA Technical Reports Server (NTRS)

    Fekel, F. C.; Montemayor, T. J.; Barnes, T. G., III; Moffett, T. J.

    1980-01-01

    Photoelectric observations of 13 lunar occultation disappearances during a March 1979 Hyades passage are reported. Three double stars (SAO 93925 = Fin 342 = 70 Tau, SAO 93961 = ADS 3248, and SAO 95419 = Kui 24) and one possible double (SAO 93950 = 75 Tau) were detected. A brief description is given of the Purdue University pulse-counting photometer as modified for occultation observations.

  6. Thyroid ultrasound

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2013-01-01

    Thyroid ultrasonography has established itself as a popular and useful tool in the evaluation and management of thyroid disorders. Advanced ultrasound techniques in thyroid imaging have not only fascinated the radiologists but also attracted the surgeons and endocrinologists who are using these techniques in their daily clinical and operative practice. This review provides an overview of indications for ultrasound in various thyroid diseases, describes characteristic ultrasound findings in these diseases, and illustrates major diagnostic pitfalls of thyroid ultrasound. PMID:23776892

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

    PubMed

    Schmid, K W

    2015-11-01

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

  8. The occult urothelial cancer.

    PubMed

    Ragonese, Mauro; Racioppi, Marco; D'Agostino, Daniele; Di Gianfrancesco, Luca; Lenci, Niccolò; Bientinesi, Riccardo; Palermo, Giuseppe; Sacco, Emilio; Pinto, Francesco; Bassi, Pier Francesco

    2016-05-24

    Transitional cell carcinoma (TCC) is the tumor that most frequently affects the urinary tract. The most common location is in the bladder; the diagnosis, as the follow-up, is based on urine cytology, endoscopic, and radiological examinations. Urinary cytology is an important non invasive tool used in the diagnosis and follow-up of patients with TCC. A positive urine cytology result is highly predictive of the presence of TCC, even in the presence of normal cystoscopy, because malignant cells may appear in the urine long time before any cystoscopically visible lesion becomes apparent. The presence of a positive urinary cytology, in the absence of clinical or endoscopic evidence of a TCC, can identify an occult urothelial cancer, located in any site of the urinary tract (upper urinary tract, bladder, prostatic urethra). Most of the urothelial tumors of the renal pelvis and ureters are diagnosed by radiological examinations, but we can observe a high rate of false negatives. In order to improve the diagnostic role of urinary cytology and other conventional examinations, numerous molecular markers have been identified; however, the real clinical application remains unclear. Photodynamic diagnosis and narrow band imaging (NBI) cystoscopy increase the diagnostic accuracy of endoscopic examinations in the presence of lesions not easily detectable. The aim of this review is to analyze the current diagnostic standards in the presence of occult urothelial cancer.

  9. The Halogen Occultation Experiment

    NASA Technical Reports Server (NTRS)

    Russell, James M., III; Gordley, Larry L.; Park, Jae H.; Drayson, S. R.; Hesketh, W. D.; Cicerone, Ralph J.; Tuck, Adrian F.; Frederick, John E.; Harries, John E.; Crutzen, Paul J.

    1993-01-01

    The Halogen Occultation Experiment (HALOE) uses solar occultation to measure vertical profiles of O3, HCl, HF, CH4, H2O, NO, NO2, aerosol extinction, and temperature versus pressure with an instantaneous vertical field of view of 1.6 km at the earth limb. Latitudinal coverage is from 80 deg S to 80 deg N over the course of 1 year and includes extensive observations of the Antarctic region during spring. The altitude range of the measurements extends from about 15 km to about 60-130 km, depending on channel. Experiment operations have been essentially flawless, and all performance criteria either meet or exceed specifications. Internal data consistency checks, comparisons with correlative measurements, and qualitative comparisons with 1985 atmospheric trace molecule spectroscopy (ATMOS) results are in good agreement. Examples of pressure versus latitude cross sections and a global orthographic projection for the September 21 to October 15, 1992, period show the utility of CH4, HF, and H2O as tracers, the occurrence of dehydration in the Antarctic lower stratosphere, the presence of the water vapor hygropause in the tropics, evidence of Antarctic air in the tropics, the influence of Hadley tropical upwelling, and the first global distribution of HCl, HF, and NO throughout the stratosphere. Nitric oxide measurements extend through the lower thermosphere.

  10. MicroRNAs in Thyroid Cancer

    PubMed Central

    2011-01-01

    Context: Traditionally, factors predisposing to diseases are either genetic (“nature”) or environmental, also known as lifestyle-related (“nurture”). Papillary thyroid cancer is an example of a disease where the respective roles of these factors are surprisingly unclear. Evidence Acquisition: Original articles and reviews summarizing our current understanding of the role of microRNA in thyroid tumorigenesis are reviewed and evaluated. Conclusion: The genetic predisposition to papillary thyroid cancer appears to consist of a variety of gene mutations that are mostly either of low penetrance and common or of high penetrance but rare. Moreover, they likely interact with each other and with environmental factors. The culpable genes may not be of the traditional, protein-coding type. A limited number of noncoding candidate genes have indeed been described, and we propose here that the failure to find mutations in traditional protein-coding genes is not coincidental. Instead, a more likely hypothesis is that changes in the expression of multiple regulatory RNA genes, e.g. microRNAs, may be a major mechanism. Our review of the literature strongly supports this notion in that a polymorphism in one microRNAs (miR-146a) predisposes to thyroid carcinoma, whereas numerous other microRNAs are involved in signaling (mainly PTEN/PI3K/AKT and T3/THRB) that is central to thyroid carcinogenesis. PMID:21865360

  11. [Thyroid cancer. In search of individualized treatment].

    PubMed

    Pitoia, Fabián; Cavallo, Andrea

    2012-01-01

    The incidence of thyroid cancer has increased exponentially around the world (mostly papillary thyroid carcinoma). This growth may reflect the combined effects of increased screening practices, together with changes in risk factors for thyroid cancer. In spite of this, disease specific mortality remained stable in the last three decades. Due to the fact that patients with papillary thyroid carcinoma often have a very good prognosis, with high survival in the long term follow-up compared with other types of carcinomas, there has been no need to change the standard treatment. The mainstays of thyroid cancer treatment are surgery (total or near-total thyroidectomy) with or without the additional administration of radioiodine (131I). These approaches are now in the center of discussion in all global forums. The current trend is to ensure the most effective and less harmful treatment and the most important issue at this point is to individualize patients according to tumor stage and risk of recurrence, to define which patients will benefit of more aggressive therapy and who could be handled with a more conservative approach.

  12. Nucleophosmin is overexpressed in thyroid tumors

    SciTech Connect

    Pianta, Annalisa; Puppin, Cinzia; Franzoni, Alessandra; Fabbro, Dora; Di Loreto, Carla; Bulotta, Stefania; Deganuto, Marta; Paron, Igor; Tell, Gianluca; Puxeddu, Efisio; Filetti, Sebastiano; Russo, Diego; Damante, Giuseppe

    2010-07-02

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

  13. Multiple primary breast and thyroid cancer.

    PubMed Central

    Ron, E.; Curtis, R.; Hoffman, D. A.; Flannery, J. T.

    1984-01-01

    The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features. PMID:6691901

  14. NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

    PubMed Central

    Schneider, David F.; Chen, Herbert

    2013-01-01

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

  15. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are ... Thyroid Cancer, by Type and Stage More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  16. Papillary carcinoma of breast: Minireview

    PubMed Central

    Ingle, Sachin B; Murdeshwar, Hemant G; Siddiqui, Saleha

    2016-01-01

    The term “intracystic papillary ductal carcinoma in situ” constitutes only 0.5% to 1% of all breast cancers. It is usually seen in postmenopausal age group. Herein, we are presenting a minireview about this unusual breast malignancy usually difficult to diagnose on clinical grounds and highlighting modalities of diagnosis and management. PMID:26798627

  17. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

    PubMed Central

    Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph

    2015-01-01

    Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

  18. Occult Fungal Scleritis

    PubMed Central

    Jeang, Lauren J.; Davis, Aaron; Madow, Brian; Espana, Edgar M.; Margo, Curtis E.

    2017-01-01

    Purpose To heighten awareness of occult fungal scleritis. Method Case report and review of the literature. Results A 73-year-old woman with diabetes mellitus was diagnosed for 3 months with immune-mediated scleritis and subsequently treated with corticosteroids. On referral, the patient had a scleral nodule with contiguous corneal infiltrate and hypopyon. Culture grew Fusarium species not further classified. The infection could not be controlled with antifungal therapy, and the eye was removed. No exogenous or endogenous source for the infection could be identified by clinical history or examination. Conclusion Fungal scleritis can develop in persons without a history of foreign body injury, minor trauma, or evidence of endogenous fungemia. A high index of suspicion for infectious scleritis must be maintained in persons with presumed immune-mediated scleritis who fail to respond to conventional therapy, particularly if they present with decreased visual acuity. PMID:28275602

  19. Pinhole occulter experiment

    NASA Technical Reports Server (NTRS)

    Ring, Jeff; Pflug, John

    1987-01-01

    Viewgraphs and charts from a briefing summarize the accomplishments, results, conclusions, and recommendations of a feasibility study using the Pinhole Occulter Facility (POF). Accomplishments for 1986 include: (1) improved IPS Gimbal Model; (2) improved Crew Motion Disturbance Model; (3) use of existing shuttle on-orbit simulation to study the effects of orbiter attitude deadband size on POF performance; (4) increased understanding of maximum performance expected from current actuator/sensor set; (5) use of TREETOPS nonlinear time domain program to obtain system dynamics describing the complex multibody flexible structures; (6) use of HONEY-X design tool to design and evaluate multivariable compensator for stability, robustness, and performance; (7) application of state-of-the-art compensator design methodology Linear Quadratic Gaussian/Loop Transfer Recovery (LQG/LTR); and (8) examination of tolerance required on knowledge of the POF boom flexible mode frequencies to insure stability, using structure uncertainty analysis.

  20. Thyroid Tests

    MedlinePlus

    ... the thyroid, a computerized tomography (CT) scan, or nuclear medicine tests, to diagnose and find the cause ... is having the scan for other health problems. Nuclear medicine tests. Nuclear medicine tests of the thyroid ...

  1. Thyroid Cancer

    MedlinePlus

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  2. Thyroid Problems

    MedlinePlus

    ... treated differently. Common thyroid disorders and problems include: Hypothyroidism Hypothyroidism is a disorder in which your thyroid doesn’ ... normal after you get better. If you have hypothyroidism, however, the levels of T4 in your blood ...

  3. Thyroid Antibodies

    MedlinePlus

    ... blocking production of thyroid hormones and resulting in hypothyroidism . TBII is not routinely tested, but TSI is ... autoimmune disease . A low level of thyroid hormones ( hypothyroidism ) can cause symptoms, such as: Weight gain Fatigue ...

  4. Comparative Evaluation of β-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules.

    PubMed

    Isaeva, A V; Zima, A P; Saprina, T V; Kasoyan, K T; Popov, O S; Brynova, O V; Berezkina, I S; Vasil'eva, O A; Ryazantseva, N V; Shabalova, I P; Litvinova, L S; Pak, Yu D; Novitskii, V V

    2016-06-01

    We compared the results of gene molecular and immunocytochemical studies of β-catenin and E-cadherin in different variants of nodular thyroid disease (nodular colloid goiter, follicular thyroid adenocarcinoma, papillary thyroid cancer) and revealed changes of the function of the E-cadherin/β-catenin complex leading to switching from adhesion function of β-catenin in nodular colloid goiter to predominantly transcriptional activity in papillary carcinoma. The results confirm the important role of disturbances in E-cadherin-β-catenin interactions in the mechanisms of malignant transformation of follicular epithelium.

  5. Expression of YY1 in Differentiated Thyroid Cancer.

    PubMed

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

    2015-05-01

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

  6. KPNO LUNAR OCCULTATION SUMMARY. III

    SciTech Connect

    Schmidtke, P. C.; Africano, J. L.

    2011-01-15

    The results for 251 lunar occultation events recorded at Kitt Peak National Observatory are presented, including 20 observations of known or suspected double stars and five measurements of stars with resolved angular diameters.

  7. Evaluation of thyroid tissue by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  8. Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy

    PubMed Central

    Martínez-Aguilar, Juan; Clifton-Bligh, Roderick; Molloy, Mark P.

    2016-01-01

    Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype. PMID:27025787

  9. Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors.

    PubMed

    Gimm, O; Perren, A; Weng, L P; Marsh, D J; Yeh, J J; Ziebold, U; Gil, E; Hinze, R; Delbridge, L; Lees, J A; Mutter, G L; Robinson, B G; Komminoth, P; Dralle, H; Eng, C

    2000-05-01

    Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.

  10. Composite encapsulated papillary carcinoma and solid papillary carcinoma.

    PubMed

    Cui, Xiaoyan; Wei, Shi

    2015-03-01

    Encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC) are distinctive variants of intraductal papillary carcinomas, each accounting for <1% of breast carcinomas. Here we report a composite carcinoma consisting of EPC and SPC. A 73-year-old woman was found to have a high density mass in the left breast on mammogram. A biopsy showed intermediate to high grade ductal carcinoma in situ (DCIS). Gross examination of the lumpectomy specimen revealed a solid, multinodular mass. Microscopic examination demonstrated two morphologically distinct intraductal carcinomas intermingled with each other. One had delicate papillae in multi-cystic spaces surrounded by thick fibrous capsule, consistent with EPC. The other had solid tumor nests with delicate fibrovascular cores. The cells were monotonous with round nuclei and salt and pepper-like chromatin, characteristic of SPC. The lack of myoepithelial cells within the papillae and at the periphery of the lesion was confirmed by immunostaining for p63 and CK5/6. Neuroendocrine differentiation of SPC was demonstrated by neuron specific enolase staining. To our knowledge, this is the first reported case of composite EPC and SPC. It raises an interesting question as to a possible common pathway of carcinogenesis of these two rare variants.

  11. [Occult hepatitis C virus infection].

    PubMed

    Carreño García, Vicente; Nebreda, Javier Bartolomé; Aguilar, Inmaculada Castillo; Quiroga Estévez, Juan Antonio

    2011-03-01

    Occult hepatitis C virus (HCV) infection is characterized by the detection of HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA determined by conventional techniques. The development of a new enzyme immunoassay for the detection of antibodies against a conserved epitope in the HCV core protein, together with the detection of HCV-RNA in peripheral blood mononuclear cells and in serum after concentrating the viral particles by ultracentrifugation, allow diagnosis of more than 90% of patients with occult HCV without the need to perform a liver biopsy. Histological damage in occult HCV infection ranges from minimal changes to liver cirrhosis and hepatocellular carcinoma, although in general this disease is less severe than classical chronic hepatitis C. A significant prevalence of occult HCV infection has been identified in risk groups such as hemodialysis patients and the family members of patients with occult hepatitis C. This occult HCV infection can also be found in subjects without clinical or biochemical evidence of liver disease.

  12. Thyroid cancer with tracheal invasion: a pathological estimation.

    PubMed

    Pappalardo, Vincenzo; La Rosa, Stefano; Imperatori, Andrea; Rotolo, Nicola; Tanda, Maria Laura; Sessa, Andrea; Dominioni, Lorenzo; Dionigi, Gianlorenzo

    2016-10-01

    We review the clinical and pathologic features of seven cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy, airway resection with reconstructive surgery over an interval of 15 years. We depicted the peculiarity of invasion of well differentiated papillary thyroid carcinoma (PTC) cells is perpendicularly oriented to the tracheal lumen, in between cartilaginous rings, along blood vessels and collagen fibers. Tracheal rings appear non-infiltrated in all histological sections of well differentiated PTC infiltrating the trachea. Similar description of inter-cartilage PTC infiltration into the trachea was first provided by Shin et al. in 1993. Interestingly, our pathological revision support the estimation by Shin et al., though that cartilage rings infiltration did occur in poorly differentiated thyroid cancers with exiguous prognosis.

  13. Thyroid cancer with tracheal invasion: a pathological estimation

    PubMed Central

    Pappalardo, Vincenzo; La Rosa, Stefano; Imperatori, Andrea; Rotolo, Nicola; Tanda, Maria Laura; Sessa, Andrea; Dominioni, Lorenzo

    2016-01-01

    We review the clinical and pathologic features of seven cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy, airway resection with reconstructive surgery over an interval of 15 years. We depicted the peculiarity of invasion of well differentiated papillary thyroid carcinoma (PTC) cells is perpendicularly oriented to the tracheal lumen, in between cartilaginous rings, along blood vessels and collagen fibers. Tracheal rings appear non-infiltrated in all histological sections of well differentiated PTC infiltrating the trachea. Similar description of inter-cartilage PTC infiltration into the trachea was first provided by Shin et al. in 1993. Interestingly, our pathological revision support the estimation by Shin et al., though that cartilage rings infiltration did occur in poorly differentiated thyroid cancers with exiguous prognosis. PMID:27867870

  14. Incidental thyroid 99mTc-MDP uptake in a patient affected by differentiated thyroid cancer.

    PubMed

    Albano, Domenico; Magri, Gian Carlo; Treglia, Giorgio; Bertagna, Francesco

    2016-01-01

    We report a case of incidental uptake of 99mTc-methylene diphosphonate in the thyroid in a 62-year-old female with a history of breast cancer treated with quadrantectomy, chemotherapy and radiotherapy, who underwent total-body-bone scintigraphy during follow up. Planar scintigraphy was followed by neck SPECT-CT that demonstrated an area of increased tracer uptake in the neck at the left lobe of the thyroid. Neck ultrasonography showed a nodule corresponding to SPECT-CT finding and the ultrasound-guided fine needle aspiration documented the presence of papillary carcinoma. The patient underwent total thyroidectomy and ipsilateral lymphadenectomy; histological examination confirmed the presence of a papillary carcinoma and the patient underwent ablation therapy with iodine-131.

  15. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

    PubMed

    Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph

    2015-12-01

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target.

  16. Loss of c-KIT expression in thyroid cancer cells.

    PubMed

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

    2017-01-01

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

  17. Loss of c-KIT expression in thyroid cancer cells

    PubMed Central

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

    2017-01-01

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

  18. Potential Utility and Limitations of Thyroid Cancer Cell Lines as Models for Studying Thyroid Cancer

    PubMed Central

    Pilli, Tania; Prasad, Kanteti V.; Jayarama, Shankar; Pacini, Furio

    2009-01-01

    Background Tumor-derived cell lines are widely used to study the mechanisms involved in thyroid carcinogenesis but recent studies have reported redundancy among thyroid cancer cell lines and identification of some “thyroid cell lines” that are likely not of thyroid origin. Summary In this review, we have summarized the uses, the limitations, and the existing problems associated with the available follicular cell-derived thyroid cancer cell lines. There are some limitations to the use of cell lines as a model to “mimic” in vivo tumors. Based on the gene expression profiles of thyroid cell lines originating from tumors of different types it has become apparent that some of the cell lines are closely related to each other and to those of undifferentiated carcinomas. Further, many cell lines have lost the expression of thyroid-specific genes and have altered karyotypes, while they exhibit activation of several oncogenes (BRAF, v-raf murine sarcoma viral oncogene homolog B1; RAS, rat sarcoma; and RET/PTC, rearranged in transformation/papillary thyroid carcinoma) and inactivation of tumor suppressor gene (TP53) which is known to be important for thyroid tumorigenesis. Conclusions A careful selection of thyroid cancer cell lines that reflect the major characteristics of a particular type of thyroid cancer being investigated could be used as a good model system to analyze the signaling pathways that may be important in thyroid carcinogenesis. Further, the review of literature also suggests that some of the limitations can be overcome by using multiple cell lines derived from the same type of tumor. PMID:20001716

  19. Villoglandular papillary adenocarcinoma: case report

    PubMed Central

    Salek, Ghizlane; Lalya, Issam; Rahali, Driss Moussaoui; Dehayni, Mohamed

    2016-01-01

    Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Herein, we report a case of VPA diagnosed and managed successfully with conservative measure. This management is particularly desirable in young women to preserve reproductive capability. PMID:28293348

  20. Occult endocrine dysfunction in patients with cirrhosis of liver

    PubMed Central

    Kumar, K. V. S. Hari; Pawah, A. K.; Manrai, Manish

    2016-01-01

    Background: Liver dysfunction leads to endocrine disturbance due to the alteration in protein metabolism or synthesis. We studied the presence of occult endocrine dysfunction in liver cirrhosis and compared the same with underlying etiology. Materials and Methods: We evaluated thirty patients with liver cirrhosis in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, and gonadal function. The patients were divided into Group 1 (cirrhosis, n = 30) and Group 2 (controls, n = 15) and the data were analyzed with appropriate statistical tests. Results: The study participants (20 males, 10 females) had a mean age of 54.5 ± 12.4 years and duration of the cirrhosis 5.1 ± 2.7 years. Four patients were in Child Class A, 11 and 15 patients were in Child Classes B and C, respectively. Eleven out of thirty patients (37%) had endocrine disorders, that include subclinical hypothyroidism (n = 3), primary hypothyroidism (n = 1), Sick Euthyroid syndrome (n = 3), central hypothyroidism (n = 2), secondary hypogonadism (n = 3) and growth hormone deficiency in three patients. Two patients had partial hypopituitarism and one patient had complete hypopituitarism. Conclusion: Occult endocrine dysfunction of thyroid and gonadal axes is common in patients with cirrhosis of the liver. The hormonal abnormalities are not different based on the etiology of the cirrhosis. PMID:28217586

  1. 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

  2. Mouse Models of Thyroid Cancer: A 2015 Update

    PubMed Central

    Kirschner, Lawrence S.; Qamri, Zahida; Kari, Suresh; Ashtekar, Amruta

    2015-01-01

    Thyroid cancer is the most common endocrine neoplasm, and its rate is rising at an alarming pace. Thus, there is a compelling need to develop in vivo models which will not only enable the confirmation of the oncogenic potential of driver genes, but also point the way towards the development of new therapeutics. Over the past 20 years, techniques for the generation of mouse models of human diseases have progressed substantially, accompanied by parallel advances in the genetics and genomics of human tumors. This convergence has enabled the development of mouse lines carrying mutations in the genes that cause thyroid cancers of all subtypes, including differentiated papillary and follicular thyroid cancers, poorly differentiated/anaplastic cancers, and medullary thyroid cancers. In this review, we will discuss the state of the art of mouse modeling of thyroid cancer, with the eventual goal of providing insight into tumor biology and treatment. PMID:26123589

  3. A rare cause of hyperthyroidism: functioning thyroid metastases.

    PubMed

    Gardner, Daphne; Ho, Su Chin

    2014-10-09

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

  4. What Is Thyroid Cancer?

    MedlinePlus

    ... Treatment? Thyroid Cancer About Thyroid Cancer What Is Thyroid Cancer? Cancer starts when cells in the body begin ... cell) Medullary Anaplastic (an aggressive undifferentiated tumor) Differentiated thyroid cancers Most thyroid cancers are differentiated cancers. The cells ...

  5. Thyroid Disorders (For Kids)

    MedlinePlus

    ... Emergency Room? What Happens in the Operating Room? Thyroid Disorders KidsHealth > For Kids > Thyroid Disorders A A ... the world is a thyroid? What Is the Thyroid? The thyroid (say: THYE-royd) is a gland, ...

  6. Uterine leiomyosarcoma metastatic to thyroid shown by (18)F-FDG PET/CT imaging.

    PubMed

    Gauthé, M; Testart Dardel, N; Nascimento, C; Trassard, M; Banal, A; Alberini, J-L

    About one third of focal thyroid uptakes in a fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) study are malignant, the most frequent histological type being papillary carcinoma. Metastases to the thyroid account for approximately 7.5% of thyroid malignancies and come mainly from kidney, lung, head and neck, and breast cancers. We report the case of a 64-year-old woman presenting a fast growing thyroid nodule whose primitive or metastatic origin was not obvious, for which (18)F-FDG PET/CT helped in the diagnostic process and in the later management of the patient. Histopathologic findings finally revealed a metastasis of uterine leiomyosarcoma.

  7. Aggressive digital papillary adenoma-adenocarcinoma.

    PubMed

    Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E

    2006-01-01

    Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.

  8. Testing for Occult Heartworm Infection

    PubMed Central

    Stogdale, L.

    1984-01-01

    Heartworm infection in dogs is endemic in southern Ontario but occurs only sporadically throughout the remainder of Canada. The disease may either be associated with microfilariae in the patient's blood, a patent infection, or it may be occult. This paper describes a case of occult dirofilariasis in a dog, with emphasis on the diagnosis. A patent infection could be missed if the clinician tests an insufficient amount of blood. He should perform multiple concentration tests using either the modified Knott's technique or a filtration method. Occult infections occur in prepatent or unisexual infections, when the worms become sterile following therapy, or when the host produces antibodies that result in the destruction of the microfilariae. The recent release of a kit which detects the presence of antibodies to the adult heartworms now enables veterinarians to make an accurate diagnosis in the vast majority of dogs. PMID:17422386

  9. [Thyroid adenoma in the piriform fossa: a case report and literature review].

    PubMed

    Huang, X T; Ma, B; Liu, M B; Zhang, Y; Huang, D L; Chen, L

    2017-02-07

    Objective: To explore the clinical characteristics of case of thyroid adenoma in the piriform fossa, and review the literatures of the congentital thyroid gland abnormality. Methods: A 44-year-old male had foreign body feeling in his pharynx for 3 years. A mass in his left piriform fossa was detected by the clinical and imaging examination. Biopsy report that the mass was thyroid papillary carcinoma. The resection of tumor with partial back thyroid cartilage through lateral neck and pharyngeal approach was performed. Results: The surgical wound healed in first-stage and no any surgical complication occurred. With postoperative pathological and immunohistochemical examination, the mass was finally diagnosed as thyroid gland adenoma. Staining for cytokerantin19 was negative. Conclusion: The symptomatic and neoplastic abnormal thyroid gland should be excised, but asymptomtic, non-neoplastic and functional abnormal thyroid gland should be retained with regular follow up.

  10. [Papillary tumors of the breast].

    PubMed

    Hungermann, D; Decker, T; Bürger, H; Kersting, C; Böcker, W

    2006-09-01

    The term papilloma applies to benign proliferative epithelial breast lesions with a papillary architecture. The papillae in such lesions contain an arborizing fibrovascular core, glandular surface epithelium and a basal myoepithelial layer. A basement membrane encloses these structures. Papilloma may occur at any site in the ductal lobular system and according to its localization is subdivided into two types: solitary (central) papilloma which are located in the major nipple/subareolar ducts or large segmental ducts and multiple (peripheral) papillomas in cystically dilated terminal ductal lobular units (TDLU). Stromal changes, epithelial metaplasia and/or proliferations and neoplasia may alter the prototypical architecture. In a significant number of papillomas atypia can be identified which have to be classified as atypical proliferates of the ductal type. These lesions must be distinguished from the papillary type of ductal carcinoma in situ. Some 17% of all papilloma are associated with (synchronous) intraductal or invasive carcinoma, but these also act as an indicator for subsequent (metachronous) carcinoma. As a consequence, in minimally invasive biopsy papilloma has to be classified as B3 and usually has to be followed by surgical excision.

  11. Absent or occult pulmonary artery.

    PubMed Central

    Presbitero, P; Bull, C; Haworth, S G; de Leval, M R

    1984-01-01

    Of 12 patients with angiographically absent pulmonary artery, 11 were investigated surgically. The previously occult pulmonary artery was found in 10 patients, in five of whom a vestige of an intrapericardial artery was present and in five the artery was patent only at the hilus, a gap existing between the main pulmonary artery and the hilar vessel, and no artery was found in one. All patients with an intrapericardial artery had right ventricular outflow tract obstruction and a ductus descending vertically from underneath the aortic arch. In those without an intrapericardial vessel the occult artery was on the side opposite the aortic arch, and there was evidence of a ductus coming from the innominate artery on the side of the interruption. The occult pulmonary artery, where identified at operation, was usually joined initially to the systemic circulation. Ultimately, continuity between the hilar and main pulmonary artery may be established surgically. Where no intrapericardial vessel exists, however, a conduit may be required to bridge the gap. It seems advisable to search for the occult artery as early in life as is feasible in the hope that providing a blood supply will ensure development of the vessel and normal lung growth. Images PMID:6743435

  12. Thyroid cancer cell lines: an overview

    PubMed Central

    Saiselet, Manuel; Floor, Sébastien; Tarabichi, Maxime; Dom, Geneviève; Hébrant, Aline; van Staveren, Wilma C. G.; Maenhaut, Carine

    2012-01-01

    Human thyroid cancer cell lines are the most used models for thyroid cancer studies. They must be used with detailed knowledge of their characteristics. These in vitro cell lines originate from differentiated and dedifferentiated in vivo human thyroid tumors. However, it has been shown that mRNA expression profiles of these cell lines were closer to dedifferentiated in vivo thyroid tumors (anaplastic thyroid carcinoma, ATC) than to differentiated ones. Here an overview of the knowledge of these models was made. The mutational status of six human thyroid cancer cell lines (WRO, FTC133, BCPAP, TPC1, K1, and 8505C) was in line with previously reported findings for 10 genes frequently mutated in thyroid cancer. However, the presence of a BRAF mutation (T1799A: V600E) in WRO questions the use of this cell line as a model for follicular thyroid carcinoma (FTC). Next, to investigate the biological meaning of the modulated mRNAs in these cells, a pathway analysis on previously obtained mRNA profiles was performed on five cell lines. In five cell lines, the MHC class II pathway was down-regulated and in four of them, ribosome biosynthesis and translation pathways were up-regulated. mRNA expression profiles of the cell lines were also compared to those of the different types of thyroid cancers. Three datasets originating from different microarray platforms and derived from distinct laboratories were used. This meta-analysis showed a significant higher correlation between the profiles of the thyroid cancer cell lines and ATC, than to differentiated thyroid tumors (i.e., PTC or FTC) specifically for DNA replication. This already observed higher correlation was obtained here with an increased number of in vivo tumors and using different platforms. In summary, this would suggest that some papillary thyroid carcinoma or follicular thyroid carcinoma (PTC or FTC) cell lines (i.e., TPC-1) might have partially lost their original DNA synthesis/replication regulation mechanisms during

  13. Thyroid Cancer Metabolism: A Review.

    PubMed

    Gill, Kurren S; Tassone, Patrick; Hamilton, James; Hjelm, Nikolaus; Luginbuhl, Adam; Cognetti, David; Tuluc, Madalina; Martinez-Outschoorn, Ubaldo; Johnson, Jennifer M; Curry, Joseph M

    2016-02-01

    Metabolic dysregulation within the tumor microenvironment (TME) is critical to the process of tumorigenesis in various cancer types. Thyrocyte metabolism in papillary and anaplastic thyroid cancer, however, remains poorly characterized, and studies analyzing the role of multicompartment metabolism in thyrocyte oncogenesis are sparse. We present a review of the current knowledge on cellular metabolism in non-cancerous and cancerous thyroid tissues, focusing on the monocarboxylate transporters MCT1 and MCT4, and on a transporter of the outer mitochondrial membrane TOMM20. Understanding the metabolic phenotype of tumor cells and associated stromal cells in thyroid cancer can have profound implications on the use of biomarker staining in detecting subclinical cancer, imaging as it relates to expression of various transport proteins, and therapeutic interventions that manipulate this dysregulated tumor metabolism to halt tumorigenesis and eradicate the cancer. Future studies are required to confirm the prognostic significance of these biomarkers and their correlation with existing staging schemas such as the AGES, AMES, ATA and MACIS scoring systems.

  14. Thyroid Cancer Metabolism: A Review

    PubMed Central

    Gill, Kurren S; Tassone, Patrick; Hamilton, James; Hjelm, Nikolaus; Luginbuhl, Adam; Cognetti, David; Tuluc, Madalina; Martinez-Outschoorn, Ubaldo; Johnson, Jennifer M; Curry, Joseph M

    2016-01-01

    Metabolic dysregulation within the tumor microenvironment (TME) is critical to the process of tumorigenesis in various cancer types. Thyrocyte metabolism in papillary and anaplastic thyroid cancer, however, remains poorly characterized, and studies analyzing the role of multicompartment metabolism in thyrocyte oncogenesis are sparse. We present a review of the current knowledge on cellular metabolism in non-cancerous and cancerous thyroid tissues, focusing on the monocarboxylate transporters MCT1 and MCT4, and on a transporter of the outer mitochondrial membrane TOMM20. Understanding the metabolic phenotype of tumor cells and associated stromal cells in thyroid cancer can have profound implications on the use of biomarker staining in detecting subclinical cancer, imaging as it relates to expression of various transport proteins, and therapeutic interventions that manipulate this dysregulated tumor metabolism to halt tumorigenesis and eradicate the cancer. Future studies are required to confirm the prognostic significance of these biomarkers and their correlation with existing staging schemas such as the AGES, AMES, ATA and MACIS scoring systems. PMID:27213120

  15. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Solez, K.; Miller, M.; Quarles, P. A.; Finer, P. M.; Heptinstall, R. H.

    1974-01-01

    To test the thesis that vasoconstriction plays a significant role in the pathogenesis of papillary necrosis caused by bromoethylamine hydrobromide (BEA), medullary plasma flow was determined in rats treated with BEA. Medullary blood flow was normal ½ to 1 hour after BEA treatment, and was actually elevated 6 hours after BEA. There was no increase in plasma levels of prostaglandins A and E, which would have been expected if there had been medullary ischemia. Pretreatment with reserpine, which inhibited the development of papillary necrosis, had little effect on medullary plasma flow. These observations do not support the notion that vasoconstriction is the mechanism by which BEA causes papillary necrosis. PMID:4472110

  16. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005

    PubMed Central

    Enewold, Lindsey; Zhu, Kangmin; Ron, Elaine; Marrogi, Aizen J.; Stojadinovic, Alexander; Peoples, George E.; Devesa, Susan S.

    2009-01-01

    Thyroid cancer incidence has been rising in the United States, and this trend has often been attributed to heightened medical surveillance and use of improved diagnostics. Thyroid cancer incidence varies by sex and race/ethnicity, and these factors also influence access to and utilization of healthcare. We therefore examined thyroid cancer incidence rates by demographic and tumor characteristics, based on 48,403 thyroid cancer patients diagnosed during 1980–2005 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. Rates varied by histologic type, sex, and race/ethnicity. Papillary carcinoma was the only histologic type for which incidence rates rose consistently among all racial/ethnic groups. Subsequent analyses focused on the 39,706 papillary thyroid cancers diagnosed during this period. Papillary carcinoma rates increased most rapidly among females. Between 1992–1995 and 2003–2005, they rose nearly 100% among White Non-Hispanics and Black females, but only 20–50% among White Hispanics, Asian/Pacific Islanders and Black males. Increases were most rapid for localized stage and small tumors; however, rates also rose for large tumors and tumors of regional and distant stage. Since 1992–1995, half the overall increase in papillary carcinoma rates was due to rising rates of very small (≤1.0 cm) cancers, 30% to cancers 1.1–2 cm, and 20% to cancers >2 cm. Among White females, the rate of increase for cancers >5 cm almost equaled that for the smallest cancers. Medical surveillance and more sensitive diagnostic procedures cannot completely explain the observed rises in papillary thyroid cancer rates. Thus, other possible explanations should be explored. PMID:19240234

  17. A case of thyroid fibromatosis, a rare lesion of this gland

    PubMed Central

    Cabrera, Rafael Adame; Leite, Valeriano

    2016-01-01

    Summary Thyroid fibromatosis is a very rare lesion; to our knowledge, there are only four cases reported in the medical literature. Herein, we report the clinical case of a woman with thyroid fibromatosis with a long follow-up (11 years). A 63-year-old female patient, with an increasing multinodular goitre without compressive symptoms, was admitted to total thyroidectomy. The histology revealed a spindle-cell proliferation with fibroblastic characteristics with no atypia and thin capillary vessels. Immunohistochemistry was positive for beta-catenin, focally to desmin and alfa-actin and negative for cytokeratins and CD34. Thyroid cells did not display any features of papillary thyroid cancer. These characteristics were compatible with thyroid fibromatosis. For the past 11 years, the patient has been periodically followed up with neck CTs and she has not shown any signs of recurrence. Thyroid fibromatosis has been associated with invasion of surrounding structures in previous reported cases. However, this aggressive behaviour was not observed in our patient. The most challenging differential diagnosis is with papillary thyroid cancer with fibromatosis-like stroma, in which the malignant component is usually peripheral. Therefore, in these cases, it is mandatory to perform an extensive examination of the resected sample. Learning points: Fibromatosis is a mesenchymal lesion that consists of an infiltrative proliferation of fibroblasts without atypia. Thyroid fibromatosis is a rare entity in this gland. In previously reported cases, it has been associated with an invasive behaviour but this was not the case in our patient. When spindle-cell proliferation with fibroblastic/myofibroblastic characteristics is detected on thyroid histology, it is mandatory to exclude a papillary thyroid carcinoma with fibromatosis-like stroma. PMID:27855230

  18. [Trabecular hyalinizing adenoma of the thyroid (HAT): A report of two cases].

    PubMed

    Román-González, Alejandro; Simón-Duque, Carlos; Camilo-Pérez, Juan; Vélez-Hoyo, Alejandro

    2016-01-01

    The hyalinizing trabecular adenoma is a rare lesion of the thyroid. There is controversy in the literature about the correct name for this disease. Dr. Carney defended the benign nature of this condition and therefore continues calling it adenoma, the World Health Organization calls for the potential of tumor malignancy, and others qualify it as a variant of papillary carcinoma based on the presence of rearranged in transformation/papillary thyroid carcinoma (RET/PTC) rearrangements. In Latin America there are few reported cases. Two cases of hyalinizing trabecular adenoma are reported. The first is a 40-year-old woman with a thyroid nodule of 3x3 cm. The immunohistochemistry was positive for thyroglobulin and calcitonin and negative for cytokeratin 19 and chromogranin. The second case is a 36-year-old patient with a thyroid nodule of 4x4 cm with an immunohistochemical pattern identical to the first case. Trabecular hyalinizing adenoma is a benign disease, easily confused with papillary or medullary thyroid carcinoma. Awareness of this entity will allow a better classification and management of thyroid conditions.

  19. Renal papillary necrosis: an update.

    PubMed

    Eknoyan, G; Qunibi, W Y; Grissom, R T; Tuma, S N; Ayus, J C

    1982-03-01

    The clinical and diagnostic features of renal papillary necrosis (RPN) of 27 patients were studied. Diabetes mellitus was the most frequent (56%) condition associated with RPN. Analgesic abuse, sickle hemoglobinopathy and urinary tract obstruction were present in 4 patients each; in 6 of these 12 patients these conditions were present as a coexistent disease with diabetes mellitus. There was evidence of an acute or chronic infection of the urinary tract in 18 patients, as a coexistent condition with another underlying disease that itself can cause RPN in 14 patients and as the only cause of RPN in another 4. Thus, the presence of more than one diagnostic condition which might be implicated in the causation of RPN was present in 15 patients or 55% of the cases in this series. When infection was excluded, six patients or 22% of the cases had two coexisting diseases, each of which has been implicated as a cause of RPN. This observation underlines the multifactorial nature of this entity and might explain why RPN is not encountered more frequently in each of the various primary diseases with which it has been associated. The average age of the patients at the time of diagnosis was 53 years for women and 56 years for men. Only six of the patients were younger than 40 years, and three of these had sickle hemoglobinopathy. The diagnosis of RPN was based on x-ray findings in eight patients, on the histologic examination of papillary tissue in urine in one, and on autopsy findings in the rest. Papillary necrosis was bilateral in three-fourths of the cases. The clinical picture varied. Most of the patients (67%) presented with chills and fever. Flank pain and dysuria were present in 11 patients (41%). As a rule oliguria was rare and progressive uremia was uncommon. In cases diagnosed at post-mortem, the patients had succumbed to infection or to a primary severe extrarenal disorder with the possibility of RPN having been entertained clinically in only half these cases prior

  20. 21 CFR 864.6550 - Occult blood test.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood...

  1. 21 CFR 864.6550 - Occult blood test.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood...

  2. 21 CFR 864.6550 - Occult blood test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood...

  3. 21 CFR 864.6550 - Occult blood test.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood...

  4. 21 CFR 864.6550 - Occult blood test.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood...

  5. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    SciTech Connect

    McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

    1987-06-01

    The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.

  6. [Study of Medullary Thyroid Carcinoma from a proband].

    PubMed

    Morlán Herrador, Laura; de Arriba, Antonio; Miguel, Gloria; Ferrera, Marta; Labarta, José I

    2016-12-01

    Thyroid cancer is an uncommon type of cancer, accounting less than 1% of all cancers in adults, and 0.5-3% of all cancers in children. There are four different types: papillary carcinoma (80-90% of cases), follicular (5-10%), medullary (5%) and anaplastic cell (2-3%). Eighty per cent of cases of medullary thyroid cancer are sporadic, but 20% are associated with an inherited syndrome that is divided into three groups: multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. The inherited forms are caused by a disruption in the RET oncogene, which is located in the long arm of chromosome 10. A hereditary case of medullary thyroid carcinoma is presented. It was detected because of a familial genetic study. The purpose of the paper is emphasize the importance of the early diagnosis and the intervention of multidisciplinary teams of experts.

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

    PubMed

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

    2013-03-01

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

  8. Thyroid Hormone Treatment

    MedlinePlus

    ... THE THYROID GLAND? The thyroid gland is a butterfly-shaped endocrine gland that is normally located in ... the thyroid gland? The thyroid gland is a butterfly-shaped endocrine gland that is normally located in ...

  9. Anaplastic thyroid cancer

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...

  10. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

  11. Thyroid and Weight

    MedlinePlus

    ... Meetings ATA Publications ATA Professional Guidelines Research Grants Thyroid Cancer Trainees Corner ATA Career Link Continuing Medical Education THYROID Calculators Thyroid Cancer Staging (CEA) Doubling Time Calculator Change In Thyroid ...

  12. Thyroid gland removal - discharge

    MedlinePlus

    ... will make your scar show less. Thyroid Hormone Replacement You may need to take thyroid hormone medicine ... natural thyroid hormone. You may not need hormone replacement if only part of your thyroid was removed. ...

  13. 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

  14. 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

  15. Radiation induced thyroid neoplasms 1920 to 1987: A vanishing problem

    SciTech Connect

    Mehta, M.P.; Goetowski, P.G.; Kinsella, T.J.

    1989-06-01

    Radiation for benign diseases has been implicated as an etiologic factor in thyroid cancer. From 1930-60, over 2 million children may have been exposed to therapeutic radiation and it is estimated that up to 7% may develop thyroid cancer after a 5-40 year latency. Thyroid stimulating hormone, secondary to radioinduced hypothyroidism, has been implicated as causative in animals. Such data has led to expensive screening programs in high risk patients. Because of a decline in irradiation for benign diseases in children over the last 2 decades, we questioned whether the incidence of radiation induced thyroid neoplasms (RITN) was also decreasing. Twenty-six of 227 patients (11%) with thyroid malignancies seen at our institution from 1974-87 had a history of previous head and neck irradiation. These included 13 papillary, 3 follicular, and 7 mixed carcinomas as well as 2 lymphomas and 1 synovial cell sarcoma. None of these 26 patients had abnormal thyroid function tests at presentation. Mean latency from irradiation to the diagnosis of thyroid cancer was 25.4 years (6-55 year range). Compared to the reported increasing incidence of RITN from 1940-70, there appears to be a significant decrease since 1970. Based on our analysis, the use of expensive screening programs in high risk populations may no longer be warranted. Additionally, the routine use of thyroid replacement in previously irradiated chemically hypothyroid patients is not recommended.30 references.

  16. A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability

    PubMed Central

    Cantisani, Maria Carmela; Parascandolo, Alessia; Perälä, Merja; Allocca, Chiara; Fey, Vidal; Sahlberg, Niko; Merolla, Francesco; Basolo, Fulvio; Laukkanen, Mikko O.; Kallioniemi, Olli Pekka; Santoro, Massimo; Castellone, Maria Domenica

    2016-01-01

    RET, BRAF and other protein kinases have been identified as major molecular players in thyroid cancer. To identify novel kinases required for the viability of thyroid carcinoma cells, we performed a RNA interference screening in the RET/PTC1(CCDC6-RET)-positive papillary thyroid cancer cell line TPC1 using a library of synthetic small interfering RNAs (siRNAs) targeting the human kinome and related proteins. We identified 14 hits whose silencing was able to significantly reduce the viability and the proliferation of TPC1 cells; most of them were active also in BRAF-mutant BCPAP (papillary thyroid cancer) and 8505C (anaplastic thyroid cancer) and in RAS-mutant CAL62 (anaplastic thyroid cancer) cells. These included members of EPH receptor tyrosine kinase family as well as SRC and MAPK (mitogen activated protein kinases) families. Importantly, silencing of the identified hits did not affect significantly the viability of Nthy-ori 3-1 (hereafter referred to as NTHY) cells derived from normal thyroid tissue, suggesting cancer cell specificity. The identified proteins are worth exploring as potential novel druggable thyroid cancer targets. PMID:27058903

  17. Lymphocytes and thyroid cancer: more to it than meets the eye?

    PubMed

    Weber, Frank

    2014-06-01

    Immune responses by innate and adaptive immune cells are crucial for the suppression of carcinogenesis and tumor spread. Effector T cells such as, cytotoxic CD8(+) T (CTL), natural killer (NK), and NK T cells (NKT cells) prevent tumor growth by their ability to induce apoptosis in cancer cells. To circumvent anti-tumor immunity, tumors commonly attract regulatory T cells (Treg), which suppress the function of CTL and NKT cells in a contact- and cytokine-dependent manner. Recent findings in patients with thyroid cancer have suggested that an imbalance between immune suppressive and anti-tumor cells occurs during thyroid carcinogenesis. However, the composition and regulation of immune responses in thyroid cancer are still elusive and a comprehensive immune profile of thyroid cancer is missing. In this issue of Endocrine-Related Cancer, Imam et al. compare immune profiles between patients with papillary thyroid carcinoma and autoimmune thyroiditis. Their data suggest that an imbalance between immunosuppressive Treg cells and effector T cells occurs during papillary thyroid carcinogenesis. Their study identified double-negative T cells as a novel key factor involved in this process. Future research is required to recapitulate these findings, to elucidate the mechanisms by which the immune response is regulated and to evaluate if this process might be used for the therapeutical management of thyroid cancer.

  18. Herpes and polyoma family viruses in thyroid cancer

    PubMed Central

    STAMATIOU, DIMITRIS P.; DERDAS, STAVROS P.; ZORAS, ODYSSEAS L.; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    Thyroid cancer is considered the most common malignancy that affects the endocrine system. Generally, thyroid cancer derives from follicular epithelial cells, and thyroid cancer is divided into well-differentiated papillary (80% of cases) and follicular (15% of cases) carcinoma. Follicular thyroid cancer is further divided into the conventional and oncocytic (Hürthle cell) type, poorly differentiated carcinoma and anaplastic carcinoma. Both poorly differentiated and anaplastic carcinoma can arise either de novo, or secondarily from papillary and follicular thyroid cancer. The incidence of thyroid cancer has significantly increased for both males and females of all ages, particularly for females between 55–64 years of age, from 1999 through 2008. The increased rates refer to tumors of all stages, though they were mostly noted in localized disease. Recently, viruses have been implicated in the direct regulation of epithelial-mesenchymal transition (EMT) and the development of metastases. More specifically, Epstein-Barr virus (EBV) proteins may potentially lead to the development of metastasis through the regulation of the metastasis suppressor, Nm23, and the control of Twist expression. The significant enhancement of the metastatic potential, through the induction of angiogenesis and changes to the tumor microenvironment, subsequent to viral infection, has been documented, while EMT also contributes to cancer cell permissiveness to viruses. A number of viruses have been identified to be associated with carcinogenesis, and these include lymphotropic herpesviruses, namely EBV and Kaposi's sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus type 8 (HHV8)]; two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV); human papillomaviruses (HPVs); human T cell lymphoma virus (HTLV); and a new polyomavirus, Merkel cell polyomavirus identified in 2008. In this review, we examined the association between thyroid cancer and two oncogenic

  19. Treatment of thyroid follicular carcinoma.

    PubMed

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

    2015-12-01

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

  20. Can Thyroid Cancer Be Prevented?

    MedlinePlus

    ... Thyroid Cancer Causes, Risk Factors, and Prevention Can Thyroid Cancer Be Prevented? Most people with thyroid cancer have ... Cancer? Can Thyroid Cancer Be Prevented? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  1. Thyroid inferno.

    PubMed

    Bhargava, Amit; Kaur, Manmeet

    2014-01-01

    The key to uncovering the etiology of hyperthyroidism lies in a careful history and physical examination. Autoimmune markers provide additive information, but should not solely be used to make a diagnosis. Concern has been raised that the overzealous use of thyroid ultrasound, following abnormal thyroid function tests, diverts attention from the workup of the biochemical abnormality to the workup of an incidentally found thyroid nodule. If further imaging is needed, the use ofathyroidscanhas been suggestedbythe Endocrine Society and the American Association of Clinical Endocrinologists. However, in certain scenarios, this may be contraindicated. We present the case of a 28-year-old female with hyperthyroidism, as aplatform to discuss an important clinical sign present on Doppler ultrasound of the thyroid. By recognizing the clinical information gained from a Doppler ultrasound, physicians can avoid additional invasive workup and apply the use of ultrasound where most appropriate.

  2. Thyroid Cancer

    MedlinePlus

    ... The coming of age of ultrasound-guided percutaneous ethanol ablation of selected neck nodal metastases in well-differentiated thyroid carcinoma. Journal of Clinical Endocrinology & Metabolism. 2011;96:2717. Caprelsa (prescribing information). Wilmington, Del.: ...

  3. Thyroid Surgery

    MedlinePlus

    ... when they believe that subsequent treatment with radioactive iodine might be necessary. For patients with larger (>1. ... if there are plans for treatment with radioactive iodine. FNA Biopsy of Thyroid Nodules Goiter Graves’ Disease ...

  4. Triton stellar occultation candidates - 1992-1994

    NASA Technical Reports Server (NTRS)

    Mcdonald, S. W.; Elliot, J. T.

    1992-01-01

    A search for Triton stellar occultation candidates for the period 1992-1994 has been completed with CCD strip-scanning observations. The search reached an R magnitude of about 17.4 and found 129 candidates within 1.5 arcsec of Triton's ephemeris during this period. Of these events, around 30 occultations are expected to be visible from the earth, indicating that a number of Triton occultation events should be visible from major observatories. Even the faintest of the present candidate events could produce useful occultation data if observed with a large enough telescope. The present astrometric accuracy is inadequate to identify which of these appulse events will produce occultations on the earth; further astrometry is needed to refine the predictions for positive occultation identification. To aid in selecting candidates for additional astrometric and photometric studies, finder charts and earth-based visibility charts for each event are included.

  5. IUVS/MAVEN Stellar Occultations

    NASA Astrophysics Data System (ADS)

    Gröller, Hannes; Yelle, Roger; Montmessin, Franck; Lacombe, Gaetan; Schneider, Nicholas M.; Deighan, Justin; Jain, Sonal; Nakagawa, Hiromu; Jakosky, Bruce

    2016-10-01

    We present the latest results from stellar occultations observed with the Imaging Ultraviolet Spectrograph (IUVS) instrument on board of Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. So far 9 campaigns have been executed on average every two months since MAVEN began orbiting Mars. Approximately 50 occultations are recorded in each campaign. The IUVS instrument observes in two spectral