Poorly differentiated and undifferentiated thyroid carcinomas

Turk Patoloji Dergisi

Volumn 31, Issue , 2015, Pages 48-59

  Eloy, Catarina ^a   Fereira, Luciana ^a   Salgado, Catarina ^a,b   Soares, Paula ^a,b   Sobrinho Simões, Manuel ^a,b,c  

^a UNIVERSITY OF PORTO   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

^c Unit of Reproductive Medicine Department of Gynecology Hospital Centre of S John Porto   (Portugal)

Author keywords

Anaplastic thyroid carcinoma; Molecular medicine; Non medullary thyroid carcinoma; Poorly differentiated thyroid carcinoma; Small cell carcinomas

Indexed keywords

ALISERTIB; ANAPLASTIC LYMPHOMA KINASE; AURORA KINASE; B RAF KINASE; BARASERTIB; BETA CATENIN; CALCITONIN; CARCINOEMBRYONIC ANTIGEN; CD31 ANTIGEN; CD34 ANTIGEN; CHROMOGRANIN; CYCLIN D1; CYTOKERATIN; KI 67 ANTIGEN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; MICRORNA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN P53; PROTEIN P63; RADIOACTIVE IODINE; SYNAPTOPHYSIN; THYROGLOBULIN; THYROID TRANSCRIPTION FACTOR 1; TRANSCRIPTION FACTOR PAX8; UNCLASSIFIED DRUG; UNINDEXED DRUG; UVOMORULIN; VIMENTIN; TUMOR MARKER;

CELL PROLIFERATION; DOWN REGULATION; GENE MUTATION; HUMAN; IMMUNOHISTOCHEMISTRY; LYMPHOMA; ONCOGENE RAS; POORLY DIFFERENTIATED THYROID CANCER; REVIEW; SQUAMOUS CELL CARCINOMA; THYROID CARCINOMA; THYROID FOLLICULAR CARCINOMA; THYROID MEDULLARY CARCINOMA; UNDIFFERENTIATED CARCINOMA; UPREGULATION; WNT SIGNALING PATHWAY; BIOPSY; CARCINOMA; CELL DIFFERENTIATION; CHEMISTRY; CLASSIFICATION; FLUORESCENCE IN SITU HYBRIDIZATION; GENETICS; MOLECULAR DIAGNOSIS; PATHOLOGY; PREDICTIVE VALUE; PROGNOSIS; THYROID NEOPLASMS;

BIOMARKERS, TUMOR; BIOPSY; CARCINOMA; CELL DIFFERENTIATION; HUMANS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION, FLUORESCENCE; MOLECULAR DIAGNOSTIC TECHNIQUES; PREDICTIVE VALUE OF TESTS; PROGNOSIS; THYROID NEOPLASMS;

EID: 84940187162     PISSN: 10185615     EISSN: 13095730     Source Type: Journal    
DOI: 10.5146/tjpath.2015.01314     Document Type: Review

References (86)

1. DeLellis RA LR HP, Eng C Tumours of endocrine Organs-WHO classification of tumours. 3rd ed. 2004.
2. C. Hedinger EDWLHS. Histological typing of thyroid tumours. 2nd ed. Berlin; 1988.
3. Maximo V, Lima J, Prazeres H, Soares P, Sobrinho-Simoes M. The biology and the genetics of Hurthle cell tumors of the thyroid. Endocr Relat Cancer. 2012;19:R131-47.
4. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7:569-80.
5. G arcia-Rostan G, Tallini G, Salvatore G. Anaplastic thyroid carcinoma: Molecular tools for diagnosis and therapy. Int J Endocrinol. 2015;2015:341725.
6. G arcia-Rostan G, Sobrinho-Simoes M. Poorly differentiated thyroid carcinoma: An evolving entity. Diagn. Histopathol. 2011; 17: 114-23.
7. Soares P, Lima J, Preto A, Castro P, Vinagre J, Celestino R, Couto JP, Prazeres H, Eloy C, Máximo V, Sobrinho-Simões M. Genetic alterations in poorly differentiated and undifferentiated thyroid carcinomas. Curr Genomics. 2011;12:609-17.
8. Rosai J DRA CM, Frable WJ, Tallini G. Tumors of the thyroid & parathyroid glands. 4th ed; 2015.
9. Cruz J, Eloy C, Aragues JM, Vinagre J, Sobrinho-Simoes M. Small-cell (basaloid) thyroid carcinoma: A neoplasm with a solid cell nest histogenesis? Int J Surg Pathol. 2011;19:620-6.
10. Eloy C, Cameselle-Teijeiro J, Vieira J, Teixeira MR, Cruz J, Sobrinho-Simoes M. Carcinoma of the thyroid with Ewing/ PNET family tumor elements: A tumor of unknown histogenesis. Int J Surg Pathol. 2014;22:579-81.
11. Eloy C, Oliveira M, Vieira J, Teixeira MR, Cruz J, Sobrinho-Simoes M. Carcinoma of the thyroid with ewing family tumor elements and favorable prognosis: Report of a second case. Int J Surg Pathol. 2014;22:260-5.
12. Eloy C, Cameselle-Teijeiro JM, Rousseau E, Sobrinho-Simoes M. Small cell tumors of the thyroid gland: A review. Int J Surg Pathol. 2014;22:197-201.
13. Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J. Poorly differentiated thyroid carcinoma: The Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol. 2007;31:1256-64.
14. Sobrinho-Simoes M, Sambade C, Fonseca E, Soares P. Poorly differentiated carcinomas of the thyroid gland: A review of the clinicopathologic features of a series of 28 cases of a heterogeneous, clinically aggressive group of thyroid tumors. Int J Surg Pathol. 2002;10:123-31.
15. Sobrinho-Simoes M, Eloy C, Magalhaes J, Lobo C, Amaro T. Follicular thyroid carcinoma. Mod Pathol. 2011;24 Suppl 2:S10-8.
16. Nakazawa T, Celestino R, Machado JC, Cameselle-Teijeiro JM, Vinagre J, Eloy C, Benserai F, Lameche S, Soares P, Sobrinho-Simões M. Cribriform-morular variant of papillary thyroid carcinoma displaying poorly differentiated features. Int J Surg Pathol. 2013;21:379-89.
17. Bongiovanni M, Mazzucchelli L, Giovanella L, Frattini M, Pusztaszeri M. Well-differentiated follicular patterned tumors of the thyroid with high-grade features can metastasize in the absence of capsular or vascular invasion: Report of a case. Int J Surg Pathol. 2014;22:749-56.
18. Hiltzik D, Carlson DL, Tuttle RM, Chuai S, Ishill N, Shaha A, Shah JP, Singh B, Ghossein RA. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: A clinicopathologic study of 58 patients. Cancer. 2006;106:1286-95.
19. Sobrinho-Simoes M, Máximo V, Rocha AS, Trovisco V, Castro P, Preto A, Lima J, Soares P. Intragenic mutations in thyroid cancer. Endocrinol Metab Clin North Am. 2008;37:333-62, viii.
20. Volante M, Rapa I, Gandhi M, Bussolati G, Giachino D, Papotti M, Nikiforov YE. RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab. 2009;94:4735-41.
21. Wang Y, Hou P, Yu H, Wang W, Ji M, Zhao S, Yan S, Sun X, Liu D, Shi B, Zhu G, Condouris S, Xing M. High prevalence and mutual exclusivity of genetic alterations in the phosphatidylinositol-3-kinase/akt pathway in thyroid tumors. J Clin Endocrinol Metab. 2007;92:2387-90.
22. Hou P, Liu D, Shan Y, Hu S, Studeman K, Condouris S, Wang Y, Trink A, El-Naggar AK, Tallini G, Vasko V, Xing M. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res. 2007;13:1161-70.
23. L iu Z, Hou P, Ji M, Guan H, Studeman K, Jensen K, Vasko V, El-Naggar AK, Xing M. Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. J Clin Endocrinol Metab. 2008;93:3106-16.
24. Santarpia L, El-Naggar AK, Cote GJ, Myers JN, Sherman SI. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab. 2008;93:278-84.
25. Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A, Santoro M, Fagin JA, Nikiforov YE. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003;88:5399-404.
26. Begum S, Rosenbaum E, Henrique R, Cohen Y, Sidransky D, Westra WH. BRAF mutations in anaplastic thyroid carcinoma: Implications for tumor origin, diagnosis and treatment. Mod Pathol. 2004;17:1359-63.
27. Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res. 2009;69:4885-93.
28. G arcia-Rostan G, Tallini G, Herrero A, D’Aquila TG, Carcangiu ML, Rimm DL. Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma. Cancer Res. 1999;59:1811-5.
29. G arcia-Rostan G, Camp RL, Herrero A, Carcangiu ML, Rimm DL, Tallini G. Beta-catenin dysregulation in thyroid neoplasms: Down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis. Am J Pathol. 2001;158:987-96.
30. Rocha AS, Soares P, Fonseca E, Cameselle-Teijeiro J, Oliveira MC, Sobrinho-Simoes M. E-cadherin loss rather than beta-catenin alterations is a common feature of poorly differentiated thyroid carcinomas. Histopathology. 2003;42:580-7.
31. Pita JM, Figueiredo IF, Moura MM, Leite V, Cavaco BM. Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014;99:E497-507.
32. G arcia-Rostan G, Costa AM, Pereira-Castro I, Salvatore G, Hernandez R, Hermsem MJ, Herrero A, Fusco A, Cameselle-Teijeiro J, Santoro M. Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res. 2005;65:10199-207.
33. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R, Almeida A, Salgado C, Eloy C, Castro P, Prazeres H, Lima J, Amaro T, Lobo C, Martins MJ, Moura M, Cavaco B, Leite V, Cameselle-Teijeiro JM, Carrilho F, Carvalheiro M, Máximo V, Sobrinho-Simões M, Soares P. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014;99:E754-65.
34. Vinagre J, Pinto V, Celestino R, Reis M, Pópulo H, Boaventura P, Melo M, Catarino T, Lima J, Lopes JM, Máximo V, Sobrinho-Simões M, Soares P. Telomerase promoter mutations in cancer: An emerging molecular biomarker? Virchows Arch. 2014;465:119-33.
35. L iu X, Wu G, Shan Y, Hartmann C, von Deimling A, Xing M. Highly prevalent TERT promoter mutations in bladder cancer and glioblastoma. Cell Cycle. 2013;12:1637-8.
36. Vinagre J, Almeida A, Pópulo H, Batista R, Lyra J, Pinto V, Coelho R, Celestino R, Prazeres H, Lima L, Melo M, da Rocha AG, Preto A, Castro P, Castro L, Pardal F, Lopes JM, Santos LL, Reis RM, Cameselle-Teijeiro J, Sobrinho-Simões M, Lima J, Máximo V, Soares P. Frequency of TERT promoter mutations in human cancers. Nat Commun. 2013;4:2185.
37. L anda I, Ganly I, Chan TA, Mitsutake N, Matsuse M, Ibrahimpasic T, Ghossein RA, Fagin JA. Frequent somatic TERT promoter mutations in thyroid cancer: Higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab. 2013;98:E1562-6.
38. L iu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El-Naggar AK, Xing M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013;20:603-10.
39. Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93:1600-8.
40. Somerman MJ, Berry JE, Khalkhali-Ellis Z, Osdoby P, Simpson RU. Enhanced expression of alpha v integrin subunit and osteopontin during differentiation of HL-60 cells along the monocytic pathway. Exp Cell Res. 1995;216:335-41.
41. Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, Gandhi M, Carty SE, Hodak SP, Luo J, Dacic S, Yu YP, Nikiforova MN, Ferris RL, Altschuler DL, Nikiforov YE. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci U S A. 2014;111:4233-8.
42. G iordano TJ, Kuick R, Thomas DG, Misek DE, Vinco M, Sanders D, Zhu Z, Ciampi R, Roh M, Shedden K, Gauger P, Doherty G, Thompson NW, Hanash S, Koenig RJ, Nikiforov YE. Molecular classification of papillary thyroid carcinoma: Distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene. 2005;24:6646-56.
43. Chevillard S, Ugolin N, Vielh P, Ory K, Levalois C, Elliott D, Clayman GL, El-Naggar AK. Gene expression profiling of differentiated thyroid neoplasms: Diagnostic and clinical implications. Clin Cancer Res. 2004;10:6586-97.
44. Huang Y, Prasad M, Lemon WJ, Hampel H, Wright FA, Kornacker K, LiVolsi V, Frankel W, Kloos RT, Eng C, Pellegata NS, de la Chapelle A. Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci U S A. 2001;98:15044-9.
45. L ubitz CC, Fahey TJ, 3rd. The differentiation of benign and malignant thyroid nodules. Adv Surg. 2005;39:355-77.
46. Prasad NB, Somervell H, Tufano RP, Dackiw AP, Marohn MR, Califano JA, Wang Y, Westra WH, Clark DP, Umbricht CB, Libutti SK, Zeiger MA. Identification of genes differentially expressed in benign versus malignant thyroid tumors. Clin Cancer Res. 2008;14:3327-37.
47. Nikiforov YE. Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas. Endocr Pathol. 2004;15:319-27.
48. Papp S, Asa SL. When thyroid carcinoma goes bad: A morphological and molecular analysis. Head Neck Pathol. 2015;9:16-23.
49. Arends JW. Molecular interactions in the Vogelstein model of colorectal carcinoma. J Pathol. 2000;190:412-6.
50. Donghi R, Longoni A, Pilotti S, Michieli P, Della Porta G, Pierotti MA. Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest. 1993;91:1753-60.
51. Nakamura T, Yana I, Kobayashi T, Shin E, Karakawa K, Fujita S, Miya A, Mori T, Nishisho I, Takai S. p53 gene mutations associated with anaplastic transformation of human thyroid carcinomas. Jpn J Cancer Res. 1992;83:1293-8.
52. Takeuchi Y, Daa T, Kashima K, Yokoyama S, Nakayama I, Noguchi S. Mutations of p53 in thyroid carcinoma with an insular component. Thyroid. 1999;9:377-81.
53. Pilotti S, Collini P, Del Bo R, Cattoretti G, Pierotti MA, Rilke F. A novel panel of antibodies that segregates immunocytochemically poorly differentiated carcinoma from undifferentiated carcinoma of the thyroid gland. Am J Surg Pathol. 1994;18:1054-64.
54. Asakawa H, Kobayashi T. Multistep carcinogenesis in anaplastic thyroid carcinoma: A case report. Pathology. 2002;34:94-7.
55. Ragazzi M, Ciarrocchi A, Sancisi V, Gandolfi G, Bisagni A, Piana S. Update on anaplastic thyroid carcinoma: Morphological, molecular, and genetic features of the most aggressive thyroid cancer. Int J Endocrinol. 2014;2014:790834.
56. Shi X, Liu R, Qu S, Zhu G, Bishop J, Liu X, Sun H, Shan Z, Wang E, Luo Y, Yang X, Zhao J, Du J, El-Naggar AK, Teng W, Xing M. Association of TERT promoter mutation 1,295,228 C|T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer. J Clin Endocrinol Metab. 2015;100:E632-7.
57. Hannallah J, Rose J, Guerrero MA. Comprehensive literature review: Recent advances in diagnosing and managing patients with poorly differentiated thyroid carcinoma. Int J Endocrinol. 2013;2013:317487.
58. Asioli S, Erickson LA, Righi A, Jin L, Volante M, Jenkins S, Papotti M, Bussolati G, Lloyd RV. Poorly differentiated carcinoma of the thyroid: Validation of the Turin proposal and analysis of IMP3 expression. Mod Pathol. 2010;23:1269-78.
59. Bond JA, Wyllie FS, Rowson J, Radulescu A, Wynford-Thomas D. In vitro reconstruction of tumour initiation in a human epithelium. Oncogene. 1994;9:281-90.
60. Monaco C, Califano D, Chiappetta G, Mineo A, De Franciscis V, Vecchio G, Santelli G. Mutated human Kirsten ras, driven by a thyroglobulin promoter, induces a growth advantage and partially dedifferentiates rat thyroid epithelial cells in vitro. Int J Cancer. 1995;63:757-60.
61. Portella G, Vitagliano D, Borselli C, Melillo RM, Salvatore D, Rothstein JL, Vecchio G, Fusco A, Santoro M. Human N-ras, TRK-T1, and RET/PTC3 oncogenes, driven by a thyroglobulin promoter, differently affect the expression of differentiation markers and the proliferation of thyroid epithelial cells. Oncol Res. 1999;11:421-7.
62. Cancer Genome Atlas Research N. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159:676-90.
63. Namba H, Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, Ohtsuru A, Saenko VA, Kanematsu T, Yamashita S. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003;88:4393-7.
64. Dahia PL, Marsh DJ, Zheng Z, Zedenius J, Komminoth P, Frisk T, Wallin G, Parsons R, Longy M, Larsson C, Eng C. Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Res. 1997;57:4710-3.
65. Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res. 2011;71:4403-11.
66. Fuziwara CS, Kimura ET. MicroRNA deregulation in anaplastic thyroid cancer biology. Int J Endocrinol. 2014;2014:743450.
67. Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, Volinia S, Coluzzi S, Leone V, Borbone E, Liu CG, Petrocca F, Troncone G, Calin GA, Scarpa A, Colato C, Tallini G, Santoro M, Croce CM, Fusco A. Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 2007;26:7590-5.
68. Prazeres H, Salgado C, Duarte C, Soares P. LRP1B (low density lipoprotein receptor-related protein 1B). Atlas Genet Cytogenet Oncol Haematol. 2014:93-101.
69. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463:899-905.
70. Ulisse S, Delcros JG, Baldini E, Toller M, Curcio F, Giacomelli L, Prigent C, Ambesi-Impiombato FS, D’Armiento M, Arlot-Bonnemains Y. Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int J Cancer. 2006;119:275-82.
71. Baldini E, Tuccilli C, Prinzi N, Sorrenti S, Antonelli A, Gnessi L, Morrone S, Moretti C, Bononi M, Arlot-Bonnemains Y, D’Armiento M, Ulisse S. Effects of selective inhibitors of Aurora kinases on anaplastic thyroid carcinoma cell lines. Endocr Relat Cancer. 2014;21:797-811.
72. Isham CR, Bossou AR, Negron V, Fisher KE, Kumar R, Marlow L, Lingle WL, Smallridge RC, Sherman EJ, Suman VJ, Copland JA, Bible KC. Pazopanib enhances paclitaxel-induced mitotic catastrophe in anaplastic thyroid cancer. Sci Transl Med. 2013;5:166ra3.
73. Arlot-Bonnemains Y, Baldini E, Martin B, Delcros JG, Toller M, Curcio F, Ambesi-Impiombato FS, D’Armiento M, Ulisse S. Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines. Endocr Relat Cancer. 2008;15:559-68.
74. Parenti R, Salvatorelli L, Magro G. Anaplastic thyroid carcinoma: Current treatments and potential new therapeutic options with emphasis on TfR1/CD71. Int J Endocrinol. 2014;2014:685396.
75. Russo D, Damante G, Puxeddu E, Durante C, Filetti S. Epigenetics of thyroid cancer and novel therapeutic targets. J Mol Endocrinol. 2011;46:R73-81.
76. Schmid KW, Kroll M, Hofstadter F, Ladurner D. Small cell carcinoma of the thyroid. A reclassification of cases originally diagnosed as small cell carcinomas of the thyroid. Pathol Res Pract. 1986;181:540-3.
77. Rosai J, Saxen EA, Woolner L. Undifferentiated and poorly differentiated carcinoma. Semin Diagn Pathol. 1985;2:123-36.
78. Meissner WA, Warren S. Tumours of the thyroid gland. 2nd ed. Washington, DC: Armed Forces Institute of Pathology; 1969.
79. Chan JM, Bilodeau E, Celin S, Nikiforov Y, Johnson JT. Ewing sarcoma of the thyroid: Report of 2 cases and review of the literature. Head Neck. 2013;35:E346-50.
80. Kumar M, Gupta P, Chaubey A. The thyroid: An extremely rare primary site of neuroblastoma. Hum Pathol. 2006;37:1357-60.
81. Eloy C, Vinagre J, Cameselle-Teijeiro J, Paiva ME, Soares P, Sobrinho-Simoes M. Tumor-in-tumor of the thyroid with basaloid differentiation: A lesion with a solid cell nest neoplastic component? Int J Surg Pathol;19:276-80.
82. Beach DF, Klump WJ, Haddad G, Reid LM, Schwarting R, Hageboutros A. Extrapulmonary small cell: A novel case of small cell carcinoma of the thyroid gland. Med Oncol. 2012;29:1405-8.
83. L una MA, Mackay B, Hill CS, Hussey DH, Hickey RC. The quarterly case: Malignant small cell tumor of the thyroid. Ultrastruct Pathol. 1980;1:265-70.
84. Maldi E, Monga G, Rossi D, Tosoni A, Mezzapelle R, Boldorini R. Extra-osseous Ewing sarcoma of the thyroid gland mimicking lymphoma recurrence: A case report. Pathol Res Pract. 2012;208:356-9.
85. Malone VS, Dobin SM, Jones KA, Donner LR. CD99-positive large cell neuroendocrine carcinoma with rearranged EWSR1 gene in an infant: A case of prognostically favorable tumor. Virchows Arch. 2010;457:389-95.
86. Jin R, Craddock KJ, Irish JC, Perez-Ordonez B, Weinreb I. Recurrent hyalinizing clear cell carcinoma of the base of tongue with high-grade transformation and EWSR1 gene rearrangement by FISH. Head Neck Pathol. 2012;6:389-94.