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Molecular Pathology of Non-familial Follicular Epithelial–Derived Thyroid Cancer in Adults: From RAS/BRAF-like Tumor Designations to Molecular Risk Stratification

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Abstract

This review addresses the impact of molecular alterations on the diagnosis and prognosis of differentiated thyroid carcinoma (DTC), including papillary, follicular, and well-differentiated carcinoma NOS, as well as oncocytic neoplasms. The molecular characterization of DTC is based upon the well-established dichotomy of BRAF-like and RAS-like designations, together with a remaining third group, less homogeneous, composed of non-BRAF-/non-RAS-like tumors. The role of BRAF V600E mutation in risk stratification is discussed in the clinico-pathological context, namely, staging and invasive features of classic papillary thyroid carcinoma (PTC) and histopathological variants carrying an excellent prognosis (microPTC) or a guarded prognosis, including the aggressive variants tall cell and hobnail cell PTCs. In follicular patterned tumors, namely, follicular thyroid carcinoma (FTC), with or without oncocytic features, the most prevalent molecular alteration are RAS mutations that do not carry prognostic significance. The only genetic alteration that has been proven to play a role in risk stratification of PTC and FTC is TERT promoter (TERTp) mutation.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68: 394-424, 2018.

    Article  PubMed  Google Scholar 

  2. Lang BH, Lo CY, Chan WF, Lam KY, Wan KY, Staging systems for papillary thyroid carcinoma: A review and comparison. Ann Surg 245: 366-378, 2007.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tuttle M, Morris L, Haugen Bet al., Thyroid-differentiated and anaplastic carcinoma (Chapter 73) In: Amin MB, Edge SB, Greene F, et al., editors. AJCC Cancer Staging Manual. 8th., New York City: Springer International Publishing, 2017.

  4. Trovisco V, Soares P, Preto A, Castro P, Maximo V, Sobrinho-Simões M, Molecular genetics of papillary thyroid carcinoma: Great expectations. Arq Bras Endocrinol Metabol 51: 643-653, 2007.

    Article  PubMed  Google Scholar 

  5. Soares P, Fonseca E, Wynford-Thomas D, Sobrinho-Simões M, Sporadicret-rearranged papillary carcinoma of the thyroid: A subset of slow growing, less aggressive thyroid neoplasms? The Journal of Pathology 185: 71-78, 1998.

    Article  CAS  PubMed  Google Scholar 

  6. Tallini G, Santoro M, Helie Met al., RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res 4: 287-294, 1998.

    CAS  PubMed  Google Scholar 

  7. Soares P, Sobrinho-Simoes M, Cancer: Small papillary thyroid cancers--is BRAF of prognostic value? Nat Rev Endocrinol 7: 9-10, 2011.

    Article  PubMed  Google Scholar 

  8. Soares P, Trovisco V, Rocha ASet al., BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 22: 4578-4580, 2003.

    Article  CAS  PubMed  Google Scholar 

  9. Melo M, da Rocha AG, Vinagre J, Sobrinho-Simoes M, Soares P, Coexistence of TERT promoter and BRAF mutations in papillary thyroid carcinoma: Added value in patient prognosis? J Clin Oncol 33: 667-668, 2015.

    Article  PubMed  Google Scholar 

  10. Xing M, Liu R, Liu Xet al., BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol 32: 2718-2726, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shi X, Liu R, Basolo Fet al., Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants. J Clin Endocrinol Metab 101: 264-274, 2016.

    Article  CAS  PubMed  Google Scholar 

  12. Cancer Genome Atlas Research Network, Integrated genomic characterization of papillary thyroid carcinoma. Cell 159: 676-690, 2014.

    Article  Google Scholar 

  13. Yoo SK, Lee S, Kim SJet al., Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers. PLoS Genet 12: e1006239, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Huang Y, Qu S, Zhu Get al., BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment. J Natl Cancer Inst 110: 362-370, 2018.

    Article  PubMed  Google Scholar 

  15. Prescott JD, Sadow PM, Hodin RAet al., BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence. Surgery 152: 984-990, 2012.

    Article  PubMed  Google Scholar 

  16. Yip L, Nikiforova MN, Yoo JYet al., Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: A study of 1510 patients. Ann Surg 262: 519–525; discussion 524–515, 2015.

  17. Soares P, Celestino R, Melo M, Fonseca E, Sobrinho-Simões M, Prognostic biomarkers in thyroid cancer. Virchows Arch 464: 333-346, 2014.

    Article  CAS  PubMed  Google Scholar 

  18. Tavares C, Melo M, Cameselle-Teijeiro JM, Soares P, Sobrinho-Simoes M, ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome. Eur J Endocrinol 174: R117-126, 2016.

    Article  CAS  PubMed  Google Scholar 

  19. Patel KN, Yip L, Lubitz CCet al., The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg 271, 2020.

  20. Melo M, da Rocha AG, Vinagre J, Sobrinho-Simões M, Soares P, Coexistence of TERT promoter and BRAF mutations in papillary thyroid carcinoma: Added value in patient prognosis? J Clin Oncol 33: 667-668, 2015.

    Article  PubMed  Google Scholar 

  21. Xing M, Alzahrani AS, Carson KAet al., Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol 33: 42-50, 2015.

    Article  PubMed  Google Scholar 

  22. Vuong HG, Duong UN, Altibi AMet al., A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma. Endocr Connect 6: R8-r17, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Trovisco V, Soares P, Preto Aet al., Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients' age but not with tumour aggressiveness. Virchows Arch 446: 589-595, 2005.

    Article  CAS  PubMed  Google Scholar 

  24. Yip L, Nikiforova MN, Yoo JYet al., Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: A study of 1510 patients 262: 519, 2015.

  25. Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing M, BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: A systematic review and meta-analysis. Medicine 91: 274-286, 2012.

    Article  CAS  PubMed  Google Scholar 

  26. Melo M, Gaspar da Rocha A, Batista Ret al., TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease. The Journal of Clinical Endocrinology & Metabolism 102: 1898–1907, 2017.

  27. Rodrigues AC, Penna G, Rodrigues E, Castro P, Sobrinho-Simoes M, Soares P, The Genetics of Papillary Microcarcinomas of the Thyroid: Diagnostic and Prognostic Implications. Curr Genomics 18: 244-254, 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Patel KN, Yip L, Lubitz CCet al., The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg 271: e21-e93, 2020.

    Article  PubMed  Google Scholar 

  29. Liu R, Xing M, TERT promoter mutations in thyroid cancer. Endocr Relat Cancer 23: R143-R155, 2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gandolfi G, Ragazzi M, Frasoldati A, Piana S, Ciarrocchi A, Sancisi V, TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma. Eur J Endocrinol 172: 403-413, 2015.

    Article  CAS  PubMed  Google Scholar 

  31. Melo M, Gaspar da Rocha A, Cancela EPG, Sobrinho-Simões M, Soares P, Age-Associated Mortality Risk in Papillary Thyroid Cancer: Does BRAF Make a Real Difference? J Clin Oncol 36: 1455-1456, 2018.

    Article  PubMed  Google Scholar 

  32. Liu R, Bishop J, Zhu G, Zhang T, Ladenson PW, Xing M, Mortality Risk Stratification by Combining BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Cancer: Genetic Duet of BRAF and TERT Promoter Mutations in Thyroid Cancer Mortality. JAMA Oncol 3: 202-208, 2017.

    Article  PubMed  Google Scholar 

  33. Yang J, Gong Y, Yan S, Chen H, Qin S, Gong R, Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis. Endocrine 67: 44-57, 2020.

    Article  CAS  PubMed  Google Scholar 

  34. Melo M, da Rocha AG, Vinagre Jet al., TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 99: E754-E765, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Moon S, Song YS, Kim YAet al., Effects of Coexistent BRAF(V600E) and TERT Promoter Mutations on Poor Clinical Outcomes in Papillary Thyroid Cancer: A Meta-Analysis. Thyroid 27: 651-660, 2017.

    Article  CAS  PubMed  Google Scholar 

  36. Prescott JD, Sadow PM, Hodin RA et al., BRAFV600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence 152: 984–990, 2012.

  37. Rosai J, LiVolsi VA, Sobrinho-Simoes M, Williams ED, Renaming papillary microcarcinoma of the thyroid gland: The Porto proposal. Int J Surg Pathol 11: 249-251, 2003.

    Article  PubMed  Google Scholar 

  38. Aliyev E, Ladra-Gonzalez MJ, Sanchez-Ares Met al., The Authors Reply PMC and PMT: Real Medicine and Not Just Biology. Am J Surg Pathol Publish Ahead of Print, 2020.

  39. Rosai J, Albores Saavedra J, Asioli Set al. : WHO Classification of Tumours of Endocrine Organs. 4th ed., Lyon: IARC, 2017.

    Google Scholar 

  40. Furuya-Kanamori L, Bell KJL, Clark J, Glasziou P, Doi SAR, Prevalence of Differentiated Thyroid Cancer in Autopsy Studies Over Six Decades: A Meta-Analysis. J Clin Oncol 34: 3672–3679, 2016.

  41. Miyauchi A, Kudo T, Ito Yet al., Natural history of papillary thyroid microcarcinoma: Kinetic analyses on tumor volume during active surveillance and before presentation. Surgery 165: 25-30, 2019

    Article  PubMed  Google Scholar 

  42. Paparodis RD, Karvounis E, Bantouna Det al., Incidentally Discovered Papillary Thyroid Microcarcinomas Are More Frequently Found in Patients with Chronic Lymphocytic Thyroiditis Than with Multinodular Goiter or Graves' Disease. Thyroid 30: 531-535, 2020.

    Article  PubMed  Google Scholar 

  43. Rego-Iraeta A, Perez-Mendez LF, Mantinan B, Garcia-Mayor RV, Time trends for thyroid cancer in northwestern Spain: True rise in the incidence of micro and larger forms of papillary thyroid carcinoma. Thyroid 19: 333-340, 2009.

    Article  PubMed  Google Scholar 

  44. Soares P, Celestino R, Gaspar da Rocha A, Sobrinho-Simoes M, Papillary thyroid microcarcinoma: how to diagnose and manage this epidemic? Int J Surg Pathol 22: 113-119, 2014.

    Article  PubMed  Google Scholar 

  45. Sobrinho-Simoes MA, Sambade MC, Gonçalves V, Latent thyroid carcinoma at autopsy:A study from Oporto, Portugal. Cancer 43: 1702-1706, 1979.

    CAS  PubMed  Google Scholar 

  46. Wartofsky L, Management of papillary microcarcinoma: primum non nocere? J Clin Endocrinol Metab 97: 1169-1172, 2012.

    Article  CAS  PubMed  Google Scholar 

  47. Sugitani I, Fujimoto Y, Symptomatic versus asymptomatic papillary thyroid microcarcinoma: A retrospective analysis of surgical outcome and prognostic factors. Endocr J 46: 209-216, 1999.

    Article  CAS  PubMed  Google Scholar 

  48. Ahn HS, Kim HJ, Welch HG, Korea's thyroid-cancer "epidemic"--screening and overdiagnosis. N Engl J Med 371: 1765-1767, 2014.

    Article  PubMed  Google Scholar 

  49. Barbaro D, Simi U, Meucci G, Lapi P, Orsini P, Pasquini C, Thyroid papillary cancers: microcarcinoma and carcinoma, incidental cancers and non-incidental cancers - are they different diseases? Clin Endocrinol (Oxf) 63: 577-581, 2005.

    Article  CAS  Google Scholar 

  50. Karatzas T, Vasileiadis I, Kapetanakis S, Karakostas E, Chrousos G, Kouraklis G, Risk factors contributing to the difference in prognosis for papillary versus micropapillary thyroid carcinoma. Am J Surg 206: 586-593, 2013.

    Article  PubMed  Google Scholar 

  51. Pazaitou-Panayiotou K, Capezzone M, Pacini F, Clinical features and therapeutic implication of papillary thyroid microcarcinoma. Thyroid 17: 1085-1092, 2007.

    Article  PubMed  Google Scholar 

  52. Song YS, Kang BH, Lee Set al., Genomic and Transcriptomic Characteristics According to Size of Papillary Thyroid Microcarcinoma. Cancers (Basel) 12: 1345, 2020.

  53. de Biase D, Gandolfi G, Ragazzi Met al., TERT Promoter Mutations in Papillary Thyroid Microcarcinomas. Thyroid 25: 1013–1019, 2015.

  54. Rosario PW, Ward LS, Graf H, Vaisman F, Mourao GF, Vaisman M, Thyroid nodules </= 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion. Arch Endocrinol Metab 63: 456-461, 2019.

    PubMed  Google Scholar 

  55. Melo M, Gaspar da Rocha A, Batista Ret al., TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease. J Clin Endocrinol Metab 102: 1898–1907, 2017.

  56. Penna GC, Pestana A, Cameselle JMet al., TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma. Endocrine 61: 489-498, 2018.

    Article  CAS  PubMed  Google Scholar 

  57. Perera D, Ghossein R, Camacho Net al., Genomic and Transcriptomic Characterization of Papillary Microcarcinomas With Lateral Neck Lymph Node Metastases. J Clin Endocrinol Metab 104: 4889-4899, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Yabuta T, Matsuse M, Hirokawa M, Yamashita S, Mitsutake N, Miyauchi A, TERT Promoter Mutations Were Not Found in Papillary Thyroid Microcarcinomas That Showed Disease Progression on Active Surveillance. Thyroid 27: 1206-1207, 2017.

    Article  PubMed  Google Scholar 

  59. Vinagre J, Almeida A, Populo Het al., Frequency of TERT promoter mutations in human cancers. Nat Commun 4: 2185, 2013.

    Article  PubMed  Google Scholar 

  60. Sama MT, Grosso E, Mele Cet al., Molecular characterisation and clinical correlation of papillary thyroid microcarcinoma. Endocrine, 2020.

  61. Yu FX, Hu MX, Zhao HXet al., Precise Detection of Gene Mutations in Fine-Needle Aspiration Specimens of the Papillary Thyroid Microcarcinoma Using Next-Generation Sequencing. Int J Endocrinol 2019: 4723958, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kim SY, Kim T, Kim K, Bae JS, Kim JS, Jung CK, Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans. J Pathol Transl Med 54: 310-317, 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Liu J, Liu R, Shen X, Zhu G, Li B, Xing M, The Genetic Duet of BRAF V600E and TERT Promoter Mutations Robustly Predicts Loss of Radioiodine Avidity in Recurrent Papillary Thyroid Cancer. J Nucl Med 61: 177-182, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Xing M, Alzahrani AS, Carson KAet al., Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 309: 1493-1501, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Niemeier LA, Kuffner Akatsu H, Song Cet al., A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma. Cancer 118: 2069-2077, 2012.

    Article  CAS  PubMed  Google Scholar 

  66. Bernstein J, Virk RK, Hui Pet al., Tall cell variant of papillary thyroid microcarcinoma: clinicopathologic features with BRAF(V600E) mutational analysis. Thyroid 23: 1525-1531, 2013.

    Article  CAS  PubMed  Google Scholar 

  67. Piana S, Ragazzi M, Tallini Get al., Papillary thyroid microcarcinoma with fatal outcome: Evidence of tumor progression in lymph node metastases: Report of 3 cases, with morphological and molecular analysis. Hum Pathol 44: 556-565, 2013.

    Article  PubMed  Google Scholar 

  68. Mitsutake N, Fukushima T, Matsuse Met al., BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: A different oncogenic profile from Chernobyl. Sci Rep 5: 16976, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tallini G, De Leo A, Repaci Aet al., Does the Site of Origin of the Microcarcinoma with Respect to the Thyroid Surface Matter? A Multicenter Pathologic and Clinical Study for Risk Stratification. Cancers (Basel) 12: 246, 2020.

  70. Medas F, Canu GL, Cappellacci Fet al., Predictive Factors of Lymph Node Metastasis in Patients With Papillary Microcarcinoma of the Thyroid: Retrospective Analysis on 293 Cases. Front Endocrinol (Lausanne) 11: 551, 2020.

  71. Aliyev E, Ladra-Gonzalez MJ, Sanchez-Ares Met al., Thyroid Papillary Microtumor: Validation of the (Updated) Porto Proposal Assessing Sex Hormone Receptor Expression and Mutational BRAF Gene Status. Am J Surg Pathol 44: 1161-1172, 2020.

    Article  PubMed  Google Scholar 

  72. Coca-Pelaz A, Shah JP, Hernandez-Prera JCet al., Papillary Thyroid Cancer-Aggressive Variants and Impact on Management: A Narrative Review. Adv Ther 37: 3112-3128, 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Trovisco V, Vieira de Castro I, Soares Pet al., BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 202: 247–251, 2004.

  74. Trovisco V, Soares P, Soares R, Magalhaes J, Sa-Couto P, Sobrinho-Simoes M, A new BRAF gene mutation detected in a case of a solid variant of papillary thyroid carcinoma. Hum Pathol 36: 694-697, 2005.

    Article  CAS  PubMed  Google Scholar 

  75. Baloch ZW, LiVolsi VA, Special types of thyroid carcinoma. Histopathology 72: 40-52, 2018.

    Article  PubMed  Google Scholar 

  76. Rivera M, Ricarte-Filho J, Patel Set al., Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): A clinicopathologic and molecular study. Hum Pathol 41: 172-180, 2010.

    Article  CAS  PubMed  Google Scholar 

  77. Lu Z, Zhang Y, Feng D, Sheng J, Yang W, Liu B, Targeted next generation sequencing identifies somatic mutations and gene fusions in papillary thyroid carcinoma. Oncotarget 8: 45784-45792, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Chou A, Fraser S, Toon CW et al., A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol 39: 652–659, 2015

    Article  PubMed  PubMed Central  Google Scholar 

  79. Perot G, Soubeyran I, Ribeiro Aet al., Identification of a recurrent STRN/ALK fusion in thyroid carcinomas. PLoS One 9: e87170, 2014

    Article  PubMed  PubMed Central  Google Scholar 

  80. Ritterhouse LL, Wirth LJ, Randolph GW et al., ROS1 Rearrangement in Thyroid Cancer. Thyroid 26: 794–797, 2016.

    Article  CAS  PubMed  Google Scholar 

  81. Chen J-H, Faquin WC, Lloyd RV, Nosé V, Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma. Modern Pathology 24: 739-749, 2011.

    Article  CAS  PubMed  Google Scholar 

  82. Evans HL, Columnar-Cell Carcinoma of the Thyroid: A Report of Two Cases of an Aggressive Variant of Thyroid Carcinoma. American Journal of Clinical Pathology 85: 77-80, 1986.

    Article  CAS  PubMed  Google Scholar 

  83. Wenig BM, Thompson LDR, Adair CF, Shmookler B, Heffess CS, Thyroid papillary carcinoma of columnar cell type. Cancer 82: 740-753, 1998.

    Article  CAS  PubMed  Google Scholar 

  84. Asioli S, Erickson LA, Sebo TJet al., Papillary thyroid carcinoma with prominent hobnail features: A new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of eight cases. Am J Surg Pathol 34: 44–52, 2010.

  85. Lee YS, Kim Y, Jeon S, Bae JS, Jung SL, Jung CK, Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review. Int J Clin Exp Pathol 8: 7988-7997, 2015.

    PubMed  PubMed Central  Google Scholar 

  86. Donaldson LB, Yan F, Morgan PF et al., Hobnail variant of papillary thyroid carcinoma: A systematic review and meta-analysis. Endocrine, 2020.

  87. Ieni A, Barresi V, Cardia Ret al., The micropapillary/hobnail variant of papillary thyroid carcinoma: A review of series described in the literature compared to a series from one southern Italy pathology institution. Rev Endocr Metab Disord 17: 521-527, 2016.

    Article  CAS  PubMed  Google Scholar 

  88. Teng L, Deng W, Lu Jet al., Hobnail variant of papillary thyroid carcinoma: Molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. Oncotarget 8: 22023-22033, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Albores-Saavedra J, Papillary thyroid carcinoma with prominent hobnail features: A new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of 8 cases. Am J Surg Pathol 34: 913; author reply 914, 2010.

  90. Asioli S, Erickson LA, Righi A, Lloyd RV, Papillary thyroid carcinoma with hobnail features: Histopathologic criteria to predict aggressive behavior. Hum Pathol 44: 320-328, 2013.

    Article  PubMed  Google Scholar 

  91. Cameselle-Teijeiro JM, Rodriguez-Perez I, Celestino Ret al., Hobnail Variant of Papillary Thyroid Carcinoma: Clinicopathologic and Molecular Evidence of Progression to Undifferentiated Carcinoma in 2 Cases. Am J Surg Pathol 41: 854-860, 2017.

    Article  PubMed  Google Scholar 

  92. Lubitz CC, Economopoulos KP, Pawlak AC et al., Hobnail variant of papillary thyroid carcinoma: An institutional case series and molecular profile. Thyroid 24: 958-965, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Motosugi U, Murata S, Nagata K, Yasuda M, Shimizu M, Thyroid papillary carcinoma with micropapillary and hobnail growth pattern: A histological variant with intermediate malignancy? Thyroid 19: 535-537, 2009.

    Article  PubMed  Google Scholar 

  94. Bai Y, Kakudo K, Li Yet al., Subclassification of non-solid-type papillary thyroid carcinoma identification of high-risk group in common type. Cancer Sci 99: 1908-1915, 2008.

    CAS  PubMed  Google Scholar 

  95. Liu Z, Kakudo K, Bai Yet al., Loss of cellular polarity/cohesiveness in the invasive front of papillary thyroid carcinoma, a novel predictor for lymph node metastasis; possible morphological indicator of epithelial mesenchymal transition. J Clin Pathol 64: 325-329, 2011.

    Article  PubMed  Google Scholar 

  96. Chung YJ, Lee JS, Park SYet al., Histomorphological factors in the risk prediction of lymph node metastasis in papillary thyroid carcinoma. Histopathology 62: 578-588, 2013.

    Article  PubMed  Google Scholar 

  97. Yue C, Zhang Y, Xing Let al., [Clinicopathological factors in risk prediction of lymph node metastasis in papillary thyroid carcinoma]. Zhonghua Yi Xue Za Zhi 94: 3637-3641, 2014.

    PubMed  Google Scholar 

  98. Lino-Silva LS, Dominguez-Malagon HR, Caro-Sanchez CH, Salcedo-Hernandez RA, Thyroid gland papillary carcinomas with "micropapillary pattern," a recently recognized poor prognostic finding: clinicopathologic and survival analysis of 7 cases. Hum Pathol 43: 1596-1600, 2012.

    Article  PubMed  Google Scholar 

  99. Wong KS, Chen TY, Higgins SE et al., A potential diagnostic pitfall for hobnail variant of papillary thyroid carcinoma. Histopathology 76: 707-713, 2020.

    Article  PubMed  Google Scholar 

  100. Ambrosi F, Righi A, Ricci C, Erickson LA, Lloyd RV, Asioli S, Hobnail Variant of Papillary Thyroid Carcinoma: A Literature Review. Endocr Pathol 28: 293-301, 2017.

    Article  CAS  PubMed  Google Scholar 

  101. Watutantrige-Fernando S, Vianello F, Barollo Set al., The Hobnail Variant of Papillary Thyroid Carcinoma: Clinical/Molecular Characteristics of a Large Monocentric Series and Comparison with Conventional Histotypes. Thyroid 28: 96-103, 2018.

    Article  CAS  PubMed  Google Scholar 

  102. Amacher AM, Goyal B, Lewis JS, Jr., El-Mofty SK, Chernock RD, Prevalence of a hobnail pattern in papillary, poorly differentiated, and anaplastic thyroid carcinoma: A possible manifestation of high-grade transformation. Am J Surg Pathol 39: 260-265, 2015.

    Article  PubMed  Google Scholar 

  103. Asioli S, Maletta F, Pagni Fet al., Cytomorphologic and molecular features of hobnail variant of papillary thyroid carcinoma: Case series and literature review. Diagn Cytopathol 42: 78-84, 2014.

    Article  PubMed  Google Scholar 

  104. Agarwal S, Sadiq Q, Ortanca I, Hobnail cells in encapsulated papillary thyroid carcinoma: Report of 2 cases with immunohistochemical and molecular findings and literature analysis. Pathol Res Pract 216: 152678, 2020.

    Article  CAS  PubMed  Google Scholar 

  105. Lilo MT, Bishop JA, Ali SZ, Hobnail variant of papillary thyroid carcinoma: A case with an unusual presentation. Diagn Cytopathol 45: 754-756, 2017.

    Article  PubMed  Google Scholar 

  106. Liu J, Brown R, Rubenfeld S, Karni R, Papillary thyroid carcinoma with prominent hobnail features diagnosed preoperatively by fine needle aspiration and demonstrating constitutive activation of mTOR signaling pathway: a case report. J Clin Exp Pathol 3: 2161–0681.10001, 2013.

  107. Mehrotra S, Lapadat R, Barkan GA, Pambuccian SE, "Teardrop," "comet," and "bowling-pin" cells in a hobnail variant of papillary thyroid carcinoma fine needle aspirate. Diagn Cytopathol 47: 839-842, 2019.

    PubMed  Google Scholar 

  108. Morandi L, Righi A, Maletta Fet al., Somatic mutation profiling of hobnail variant of papillary thyroid carcinoma. Endocr Relat Cancer 24: 107-117, 2017.

    Article  CAS  PubMed  Google Scholar 

  109. Ito Y, Hirokawa M, Hayashi Tet al., Case report: exceptionally rapid growth character of hobnail variant of papillary thyroid carcinoma: A report of four cases. Endocr J 67: 1047-1053, 2020.

    Article  PubMed  Google Scholar 

  110. Al-Yahri O, Abdelaal A, El Ansari Wet al., First ever case report of co-occurrence of hobnail variant of papillary thyroid carcinoma and intrathyroid parathyroid adenoma in the same thyroid lobe. Int J Surg Case Rep 70: 40-52, 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Bellevicine C, Cozzolino I, Malapelle U, Zeppa P, Troncone G, Cytological and molecular features of papillary thyroid carcinoma with prominent hobnail features: A case report. Acta Cytol 56: 560-564, 2012.

    Article  PubMed  Google Scholar 

  112. Ragazzi M, Torricelli F, Donati Bet al., Coexisting well-differentiated and anaplastic thyroid carcinoma in the same primary resection specimen: immunophenotypic and genetic comparison of the two components in a consecutive series of 13 cases and a review of the literature. Virchows Arch, 2020.

  113. Oh WJ, Lee YS, Cho Uet al., Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features. Korean Journal of Pathology 48: 201, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Wang X, Cheng W, Liu C, Li J, Tall cell variant of papillary thyroid carcinoma: Current evidence on clinicopathologic features and molecular biology. Oncotarget 7: 40792-40799, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Villar-Taibo R, Peteiro-González D, Cabezas-Agrícola JMet al., Aggressiveness of the tall cell variant of papillary thyroid carcinoma is independent of the tumor size and patient age. Oncology Letters 13: 3501-3507, 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Leung AK-C, Chow S-M, Law SCK, Clinical Features and Outcome of the Tall Cell Variant of Papillary Thyroid Carcinoma. The Laryngoscope 118: 32–38, 2008.

  117. Morris LGT, Shaha AR, Tuttle RM, Sikora AG, Ganly I, Tall-Cell Variant of Papillary Thyroid Carcinoma: A Matched-Pair Analysis of Survival. Thyroid 20: 153-158, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Min HS, Lee C, Jung KC, Correlation of Immunohistochemical Markers and BRAF Mutation Status with Histological Variants of Papillary Thyroid Carcinoma in the Korean Population. Journal of Korean Medical Science 28: 534, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ghossein RA, Leboeuf R, Patel KNet al., Tall Cell Variant of Papillary Thyroid Carcinoma without Extrathyroid Extension: Biologic Behavior and Clinical Implications. Thyroid 17: 655-661, 2007.

    Article  PubMed  Google Scholar 

  120. Rüter A, Dreifus J, Jones M, Nishiyama R, Lennquist S, Overexpression of p53 in tall cell variants of papillary thyroid carcinoma. Surgery 120: 1046-1050, 1996.

    Article  PubMed  Google Scholar 

  121. Nikiforova MN, Kimura ET, Gandhi Met al., BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas. The Journal of Clinical Endocrinology & Metabolism 88: 5399-5404, 2003.

    Article  CAS  Google Scholar 

  122. Xing M, BRAF mutation in thyroid cancer. Endocrine Related Cancer 12: 245-262, 2005.

    Article  CAS  PubMed  Google Scholar 

  123. Basolo F, Torregrossa L, Giannini Ret al., Correlation between theBRAFV600E Mutation and Tumor Invasiveness in Papillary Thyroid Carcinomas Smaller than 20 Millimeters: Analysis of 1060 Cases. The Journal of Clinical Endocrinology & Metabolism 95: 4197-4205, 2010.

    Article  CAS  Google Scholar 

  124. Qasem E, Murugan AK, Al-Hindi Het al., TERT promoter mutations in thyroid cancer: A report from a Middle Eastern population. Endocrine-Related Cancer 22: 901-908, 2015.

    Article  CAS  PubMed  Google Scholar 

  125. Wong KS, Higgins SE, Marqusee E, Nehs MA, Angell T, Barletta JA, Tall Cell Variant of Papillary Thyroid Carcinoma: Impact of Change in WHO Definition and Molecular Analysis. Endocrine Pathology 30: 43-48, 2018.

    Article  Google Scholar 

  126. Basolo F, Giannini R, Monaco Cet al., Potent Mitogenicity of the RET/PTC3 Oncogene Correlates with Its Prevalence in Tall-Cell Variant of Papillary Thyroid Carcinoma. The American Journal of Pathology 160: 247-254, 2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Shimizu M, Hirokawa M, Manabe T, Tall cell variant of papillary thyroid carcinoma with foci of columnar cell component. Virchows Archiv 434: 173-175, 1999.

    Article  CAS  PubMed  Google Scholar 

  128. Bronner MP, LiVolsi VA, Spindle cell squamous carcinoma of the thyroid: an unusual anaplastic tumor associated with tall cell papillary cancer. Mod Pathol 4: 637-643, 1991.

    CAS  PubMed  Google Scholar 

  129. Ganly I, Ibrahimpasic T, Rivera Met al., Prognostic Implications of Papillary Thyroid Carcinoma with Tall-Cell Features. Thyroid 24: 662-670, 2014.

    Article  CAS  PubMed  Google Scholar 

  130. Vuong HG, Long NP, Anh NHet al., Papillary thyroid carcinoma with tall cell features is as aggressive as tall cell variant: A meta-analysis. Endocrine Connections 7: R286-R293, 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Wang S, Xiong Y, Zhao Q, Song H, Yi P, Liu C, Columnar cell papillary thyroid carcinoma prognosis: Findings from the SEER database using propensity score matching analysis. Am J Transl Res 11: 6262-6270, 2019.

    PubMed  PubMed Central  Google Scholar 

  132. Sobrinho-Simões M, Nesland JM, Johannessen JV, Columnar-Cell Carcinoma: Another Variant of Poorly Differentiated Carcinoma of the Thyroid. American Journal of Clinical Pathology 89: 264-267, 1988.

    Article  PubMed  Google Scholar 

  133. Enriquez ML, Baloch ZW, Montone KT, Zhang PJ, LiVolsi VA, CDX2 Expression in Columnar Cell Variant of Papillary Thyroid Carcinoma. American Journal of Clinical Pathology 137: 722-726, 2012.

    Article  PubMed  Google Scholar 

  134. Sujoy V, Pinto A, Nosé V, Columnar Cell Variant of Papillary Thyroid Carcinoma: A Study of 10 Cases with Emphasis on CDX2 Expression. Thyroid 23: 714-719, 2013.

    Article  CAS  PubMed  Google Scholar 

  135. Krasner JR, Alyouha N, Pusztaszeri Met al., Molecular mutations as a possible factor for determining extent of thyroid surgery. J Otolaryngol Head Neck Surg 48: 51, 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Akslen LA, Varhaug JE, Thyroid Carcinoma with Mixed Tall-Cell and Columnar-Cell Features. American Journal of Clinical Pathology 94: 442-445, 1990.

    Article  CAS  PubMed  Google Scholar 

  137. Putti TC, Bhuiya TA, Mixed columnar cell and tall cell variant of papillary carcinoma of thyroid: A case report and review of the literature. Pathology 32: 286-289, 2000.

    Article  CAS  PubMed  Google Scholar 

  138. Tranchida P, Bernacki E, Budev H, Giorgadze T, Preoperative cytologic diagnosis of papillary thyroid carcinoma with mixed columnar cell and tall cell features. Diagnostic Cytopathology 40: E4-E7, 2011.

    Article  PubMed  Google Scholar 

  139. Tallini G, Tuttle RM, Ghossein RA, The History of the Follicular Variant of Papillary Thyroid Carcinoma. J Clin Endocrinol Metab 102: 15-22, 2017.

    Article  PubMed  Google Scholar 

  140. Lindsay S, Carcinoma of the thyroid gland: A clinical and pathologic study of 293 patients at the University of California hospital, chapter VI. Pathologic Study of Thyroid Carcinoma: Classification of Thyroid Carcinoma. Springfield, IL: Charles C Thomas: 30–65, 1960.

  141. Chen KT, Rosai J, Follicular variant of thyroid papillary carcinoma: A clinicopathologic study of six cases. Am J Surg Pathol 1: 123-130, 1977.

    Article  Google Scholar 

  142. LiVolsi VA, Asa SL, The demise of follicular carcinoma of the thyroid gland. Thyroid 4: 233-236, 1994.

    Article  CAS  PubMed  Google Scholar 

  143. Nikiforov YE, Seethala RR, Tallini Get al., Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol 2: 1023-1029, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  144. Cameselle-Teijeiro JM, Peteiro-Gonzalez D, Caneiro-Gomez Jet al., Cribriform-morular variant of thyroid carcinoma: A neoplasm with distinctive phenotype associated with the activation of the WNT/beta-catenin pathway. Mod Pathol 31: 1168-1179, 2018.

    Article  CAS  PubMed  Google Scholar 

  145. Fukahori M, Yoshida A, Hayashi Het al., The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: New insights from a single center and a large patient cohort. Thyroid 22: 683-689, 2012.

    Article  CAS  PubMed  Google Scholar 

  146. Song YS, Lim JA, Min HSet al., Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer. Eur J Endocrinol 177: 465-473, 2017.

    Article  CAS  PubMed  Google Scholar 

  147. Jang EK, Song DE, Sim SYet al., NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma. Thyroid 24: 1275-1281, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cameselle-Teijeiro JM, Sobrinho-Simoes M, Cribriform-morular variant of thyroid carcinoma. Pathologica 111: 1-3, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Cavadas B, Pereira JB, Correia Met al., Genomic and transcriptomic characterization of the mitochondrial-rich oncocytic phenotype on a thyroid carcinoma background. Mitochondrion 46: 123-133, 2019.

    Article  CAS  PubMed  Google Scholar 

  150. Ganly I, Makarov V, Deraje Set al., Integrated Genomic Analysis of Hurthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes. Cancer Cell 34: 256–270 e255, 2018.

  151. Gopal RK, Kubler K, Calvo SEet al., Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hurthle Cell Carcinoma. Cancer Cell 34: 242–255 e245, 2018.

  152. Dettmer M, Vogetseder A, Durso MBet al., MicroRNA expression array identifies novel diagnostic markers for conventional and oncocytic follicular thyroid carcinomas. J Clin Endocrinol Metab 98: E1-7, 2013.

    Article  CAS  PubMed  Google Scholar 

  153. Erickson LA, Jalal SM, Goellner JRet al., Analysis of Hurthle cell neoplasms of the thyroid by interphase fluorescence in situ hybridization. Am J Surg Pathol 25: 911-917, 2001.

    Article  CAS  PubMed  Google Scholar 

  154. Jung CK, Kim Y, Jeon S, Jo K, Lee S, Bae JS, Clinical utility of EZH1 mutations in the diagnosis of follicular-patterned thyroid tumors. Hum Pathol 81: 9-17, 2018.

    Article  CAS  PubMed  Google Scholar 

  155. Khan NE, Bauer AJ, Schultz KAPet al., Quantification of Thyroid Cancer and Multinodular Goiter Risk in the DICER1 Syndrome: A Family-Based Cohort Study. J Clin Endocrinol Metab 102: 1614-1622, 2017.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Gullo I, Batista R, Rodrigues-Pereira Pet al., Multinodular Goiter Progression Toward Malignancy in a Case of DICER1 Syndrome: Histologic and Molecular Alterations. Am J Clin Pathol 149: 379-386, 2018.

    Article  PubMed  Google Scholar 

  157. Chernock RD, Rivera B, Borrelli Net al., Poorly differentiated thyroid carcinoma of childhood and adolescence: A distinct entity characterized by DICER1 mutations. Mod Pathol 33: 1264-1274, 2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Agaimy A, Witkowski L, Stoehr Ret al., Malignant teratoid tumor of the thyroid gland: An aggressive primitive multiphenotypic malignancy showing organotypical elements and frequent DICER1 alterations-is the term "thyroblastoma" more appropriate? Virchows Arch 477: 787-798, 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Rooper LM, Bynum JP, Miller KPet al., Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas: Molecular Characterization and Proposal for a Separate Classification. Am J Surg Pathol 44: 826-833, 2020.

    Article  PubMed  Google Scholar 

  160. 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 22: 260-265, 2014.

    Article  PubMed  Google Scholar 

  161. Oliveira G, Polonia A, Cameselle-Teijeiro JMet al., EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE). Virchows Arch 470: 517-525, 2017.

    Article  CAS  PubMed  Google Scholar 

  162. Nikiforova MN, Nikitski AV, Panebianco Fet al., GLIS Rearrangement is a Genomic Hallmark of Hyalinizing Trabecular Tumor of the Thyroid Gland. Thyroid 29: 161-173, 2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Sambade C, Franssila K, Cameselle-Teijeiro J, Nesland J, Sobrinho-Simoes M, Hyalinizing trabecular adenoma: A misnomer for a peculiar tumor of the thyroid gland. Endocr Pathol 2: 83-91, 1991.

    Article  PubMed  Google Scholar 

  164. Skalova A, Vanecek T, Sima Ret al., Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34: 599-608, 2010.

    Article  PubMed  Google Scholar 

  165. Tuttle RM, Alzahrani AS, Risk Stratification in Differentiated Thyroid Cancer: From Detection to Final Follow-up. J Clin Endocrinol Metab 104: 4087-4100, 2019.

    Article  PubMed Central  Google Scholar 

  166. Haugen BR, Alexander EK, Bible KCet al., 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 26: 1-133, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  167. Filetti S, Durante C, Hartl Det al., Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol 30: 1856-1883, 2019.

    Article  CAS  PubMed  Google Scholar 

  168. Melo M, Vicente N, Ventura M, Gaspar Da Rocha A, Soares P, Carrilho F, The role of ablative treatment in differentiated thyroid cancer management. Expert Review of Endocrinology & Metabolism 12: 109-116, 2017.

    Article  CAS  Google Scholar 

  169. Chen B, Shi Y, Xu Y, Zhang J, The predictive value of coexisting BRAFV600E and TERT promoter mutations on poor outcomes and high tumour aggressiveness in papillary thyroid carcinoma: A systematic review and meta-analysis. Clin Endocrinol (Oxf), 2020.

  170. Liu R, Xing M, TERT promoter mutations in thyroid cancer. Endocrine-related cancer 23: R143-155, 2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Kim TH, Ki CS, Kim HSet al., Refining Dynamic Risk Stratification and Prognostic Groups for Differentiated Thyroid Cancer With TERT Promoter Mutations. J Clin Endocrinol Metab 102: 1757-1764, 2017.

    Article  PubMed  Google Scholar 

  172. Kowalska A, Walczyk A, Kowalik Aet al., Response to therapy of papillary thyroid cancer of known BRAF status. Clin Endocrinol (Oxf) 87: 815-824, 2017.

    Article  CAS  Google Scholar 

  173. Garcia-Rostan G, Zhao H, Camp RLet al., ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 21: 3226-3235, 2003.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization—COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumor immortalization (PDTC/MED_ONC/31438/2017). Additional funding through the Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo—Bolsa SPEDM para projecto de investigação (2017). JV is supported by FCT with a research contract (CEECIND/00201/2017). This work was supported in part (JMC-T) by Grant ISCIII-PI19/01316-FEDER from Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Paula Soares and Antónia Povoa equally contributed to this work.

Authors and Affiliations

  1. i3S - Instituto de Investigação E Inovação Em Saúde, Universidade Do Porto, 4200-135, Porto, Portugal

    Paula Soares, Antónia Afonso Póvoa, Miguel Melo, João Vinagre, Valdemar Máximo, Catarina Eloy & Manuel Sobrinho-Simões

  2. IPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4250-475, Porto, Portugal

    Paula Soares, Antónia Afonso Póvoa, Miguel Melo, João Vinagre, Valdemar Máximo, Catarina Eloy & Manuel Sobrinho-Simões

  3. Faculdade de Medicina da Universidade Do Porto, 4200-139, Porto, Portugal

    Paula Soares, Antónia Afonso Póvoa, Miguel Melo, João Vinagre, Valdemar Máximo & Manuel Sobrinho-Simões

  4. Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/E), 4400-129, Vila Nova de Gaia, Portugal

    Antónia Afonso Póvoa

  5. Centro Hospitalar E Universitário São João, 4200-139, Porto, Portugal

    Manuel Sobrinho-Simões

  6. Centro Hospitalar Universitário de Coimbra, 3004-561, Coimbra, Portugal

    Miguel Melo

  7. Department of Pathology, Clinical University Hospital, Health Research Institute of Santiago de Compostela (IDIS), Galician Healthcare Service (SERGAS), University of Santiago de Compostela, 15706, Santiago de Compostela, Spain

    José Manuel Cameselle-Teijeiro

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  1. Paula Soares
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Soares, P., Póvoa, A.A., Melo, M. et al. Molecular Pathology of Non-familial Follicular Epithelial–Derived Thyroid Cancer in Adults: From RAS/BRAF-like Tumor Designations to Molecular Risk Stratification. Endocr Pathol 32, 44–62 (2021). https://doi.org/10.1007/s12022-021-09666-1

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