Pathogenesis of Thyroid Carcinoma

  • Massimo SantoroEmail author
  • Francesca Carlomagno
Reference work entry
Part of the Endocrinology book series (ENDOCR)


This chapter summarizes our current knowledge about molecular lesions driving the most common subtypes of thyroid carcinoma. Genetic lesions in the RET receptor tyrosine kinase and in RAS family GTPases are present in a large proportion of sporadic medullary thyroid carcinomas (MTC). RAS mutations are also common in well-differentiated thyroid carcinomas of the papillary (PTC) and follicular (FTC) type. Genetic lesions, most commonly the V600E point mutation, in the BRAF serine/threonine kinase are common in PTC; the PAX8-PPARG gene fusion is present in FTC. Finally, aggressive thyroid cancer types are enriched in several additional mutations including those targeting the TP53 tumor suppressor and the TERT (telomerase-reverse transcriptase) gene promoter. This knowledge is being translated into novel diagnostic and prognostic markers as well as molecular targets for novel therapeutic options.


Kinase Neoplastic progression Differentiation MAPK TP53 TERT 



4E-binding protein 1


AKR mice tyhymoma oncogene


Anaplastic lymphoma kinase


Adenomatous polyposis coli


AT-rich interaction domain




Anaplastic thyroid carcinoma


ATP-dependent helicase X


B-type rapidly accelerated fibrosarcoma oncogene


Coiled coil domain containing protein 6


Carcinoembryonic antigen


Cutaneous lichen amyloidosis


Cadherin like domain


Cysteine rich domain


Cyclic AMP responsive element binding binding protein


Catenin beta 1


Classical variant-papillary thyroid carcinoma


DNA damage response


Dicer 1 ribonuclease III


Differentiated thyroid carcinoma


Eukaryotic translation initiation factor 1A, X-linked


Extracellular regulated kinase


E-twenty six


Familial adenomatous polyposis of colon


Familial non medullary thyroid carcinoma


Forkhead box E1


Follicular thyroid adenoma


Follicular thyroid carcinoma


Familial thyroid epithelial neoplasia


Follicular variant-papillary thyroid carcinoma


GA binding protein


GTPase activating protein


Glial cell-derived neurotrophic factor


Guanine nucleotide exchange factor


Guanosine triphosphate


Hürthle cell carcinoma


Hirschsprung's disease




Kinase domain


Lysine methyltransferase 2 A/C/D


Mitogen-activated protein kinase


Multiple endocrine neoplasia syndrome


Mut L homolog 1


Mut L homolog 3


Mismatch repair


Multinodular goiter 1


Mut S homolog 2


Mut S homolog 6


Medullary thyroid carcinoma


mammalian target of rapamycin


mammalian target of rapamycin complex


Nuclear coactivator 4


Neurofibromatosis 1


Neurofibromatosis 2


Non invasive follicular thyroid neoplasm with papillary like nuclear features


NK2 homeobox 1


Non-medullary thyroid carcinoma


Non-medullary thyroid carcinoma 1




Neurotrophic tyrosine kinase


Paired box gene 8


Polybromo-1, BRG1-associated factor


Phosphoinositide-dependent kinase 1


Poorly differentiated thyroid carcinoma


Phosphatidylinositol 3 kinase


Phosphatidylinositol 3 kinase catalytic subunit


Phosphatidylinositol (3,4,5)-trisphosphate


Protein kinase B


Peroxisome proliferator-activated receptor gamma


PAX8-PPARG fusion protein




Papillary thyroid carcinoma


Phosphatase and tensin homolog


Rat sarcoma oncogene


Ras binding domain


Rearranged during transfection


Ribosomal protein S6 kinase


Receptor tyrosine kinase


Single base substitution


SET domain containing 2 protein


SWI/SNF related matrix associated actin dependent regulator of chromatin B1


Son of sevenless


SwItch/sucrose non-fermentable


Thyroid carcinoma


The cancer genome atlas


Thyroid tumors with cell oxyphilia


Tall cell variant-papillary thyroid carcinoma


Telomerase reverse transcriptase


Thyroid adenoma associated protein


Tumor protein p53


Tuberous sclerosis 2


Thyroid stimulating hormone


Wingless-related integration site


Yes-associated protein


  1. Afkhami M, Karunamurthy A, Chiosea S, Nikiforova MN, Seethala R, Nikiforov YE, et al. Histopathologic and clinical characterization of thyroid tumors carrying the BRAF(K601E) mutation. Thyroid. 2016;26(2):242–7.CrossRefPubMedGoogle Scholar
  2. Agrawal N, Jiao Y, Sausen M, Leary R, Bettegowda C, Roberts NJ, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab. 2013;98(2):E364–9.CrossRefPubMedGoogle Scholar
  3. Akıncılar S, Khattar E, Boon PL, Unal B, Fullwood MJ, Tergaonkar V. Long-range chromatin interactions drive mutant tert promoter activation. Cancer Discov. 2016;6(11):1276–91.CrossRefPubMedGoogle Scholar
  4. Armstrong MJ, Yang H, Yip L, Ohori NP, McCoy KL, Stang MT, et al. PAX8/PPARγ rearrangement in thyroid nodules predicts follicular-pattern carcinomas, in particular the encapsulated follicular variant of papillary carcinoma. Thyroid. 2014;24(9):1369–74.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Asa SL, Giordano TJ, LiVolsi VA. Implications of the TCGA genomic characterization of papillary thyroid carcinoma for thyroid pathology: does follicular variant papillary thyroid carcinoma exist? Thyroid. 2015;25(1):1–2.CrossRefPubMedGoogle Scholar
  6. Boichard A, Croux L, Al Ghuzlan A, Broutin S, Dupuy C, Leboulleux S, et al. Somatic RAS mutations occur in a large proportion of sporadic RET-negative medullary thyroid carcinomas and extend to a previously unidentified exon. J Clin Endocrinol Metab. 2012;97(10):E2031–5.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bonora E, Tallini G, Romeo G. Genetic predisposition to familial nonmedullary thyroid cancer: an update of molecular findings and state-of-the-art studies. J Oncol. 2010;2010:385206.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016 Dec 3;388(10061):2783–2795.CrossRefGoogle Scholar
  9. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676–90.CrossRefGoogle Scholar
  10. Ciampi R, Knauf JA, Kerler R, Gandhi M, Zhu Z, Nikiforova MN, et al. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J Clin Invest. 2005;115(1):94–101.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ciampi R, Mian C, Fugazzola L, Cosci B, Romei C, Barollo S, et al. Evidence of a low prevalence of RAS mutations in a large medullary thyroid cancer series. Thyroid. 2013;23(1):50–7.CrossRefPubMedGoogle Scholar
  12. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–90.CrossRefGoogle Scholar
  13. Dillon LW, Pierce LC, Lehman CE, Nikiforov YE, Wang YH. DNA topoisomerases participate in fragility of the oncogene RET. PLoS One. 2013;8(9):e75741.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Dralle H, Machens A, Basa J, Fatourechi V, Franceschi S, Hay ID, et al. Follicular cell-derived thyroid cancer. Nat Rev Dis Primers. 2015;1:15077.CrossRefPubMedGoogle Scholar
  15. Drieschner N, Kerschling S, Soller JT, Rippe V, Belge G, Bullerdiek J, Nimzyk R. A domain of the thyroid adenoma associated gene (THADA) conserved in vertebrates becomes destroyed by chromosomal rearrangements observed in thyroid adenomas. Gene. 2007;403(1–2):110–7.CrossRefPubMedGoogle Scholar
  16. Dunn L, Fagin JA. Therapy: lenvatinib and radioiodine-refractory thyroid cancers. Nat Rev Endocrinol. 2015;11(6):325–7.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Duntas LH, Doumas C. The ‘rings of fire’ and thyroid cancer. Hormones (Athens). 2009;8(4):249–53.CrossRefGoogle Scholar
  18. Eberhardt NL, Grebe SK, McIver B, Reddi HV. The role of the PAX8/PPARgamma fusion oncogene in the pathogenesis of follicular thyroid cancer. Mol Cell Endocrinol. 2010;321(1):50–6.CrossRefPubMedGoogle Scholar
  19. Elisei R, Romei C, Cosci B, Agate L, Bottici V, Molinaro E, et al. RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab. 2007;92(12):4725–9.CrossRefPubMedGoogle Scholar
  20. Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang SH, Koeffler HP. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest. 1993;91(1):179–84.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Fagin JA, Wells Jr SA. Biologic and clinical perspectives on thyroid cancer. N Engl J Med. 2016;375(11):1054–67.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Frank-Raue K, Rybicki LA, Erlic Z, Schweizer H, Winter A, Milos I, et al. Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. Hum Mutat. 2011;32(1):51–8.CrossRefPubMedGoogle Scholar
  23. Gandhi M, Evdokimova V, Nikiforov YE. Mechanisms of chromosomal rearrangements in solid tumors: the model of papillary thyroid carcinoma. Mol Cell Endocrinol. 2010;321(1):36–43.CrossRefPubMedGoogle Scholar
  24. Ganly I, Ricarte Filho J, Eng S, Ghossein R, Morris LG, Liang Y, et al. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy. J Clin Endocrinol Metab. 2013;98(5):E962–72.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Garcia-Rendueles ME, Ricarte-Filho JC, Untch BR, Landa I, Knauf JA, Voza F, et al. NF2 loss promotes oncogenic RAS-induced thyroid cancers via YAP-dependent transactivation of RAS proteins and sensitizes them to MEK inhibition. Cancer Discov. 2015;5(11):1178–93.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Garcia-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(8):1811–5.PubMedGoogle Scholar
  27. Gasparre G, Porcelli AM, Bonora E, Pennisi LF, Toller M, Iommarini L, et al. Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci U S A. 2007;104(21):9001–6.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Giordano TJ. Follicular cell thyroid neoplasia: insights from genomics and the cancer genome atlas research network. Curr Opin Oncol. 2016;28(1):1–4.CrossRefPubMedGoogle Scholar
  29. Grubbs EG, Ng PK, Bui J, Busaidy NL, Chen K, Lee JE, et al. RET fusion as a novel driver of medullary thyroid carcinoma. J Clin Endocrinol Metab. 2015;100(3):788–93.CrossRefPubMedGoogle Scholar
  30. Gudmundsson J, Sulem P, Gudbjartsson DF, Jonasson JG, Sigurdsson A, Bergthorsson JT, et al. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet. 2009;41(4):460–4.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Haraldsdottir S, Shah MH. New era for treatment in differentiated thyroid cancer. Lancet. 2014;384(9940):286–8.CrossRefPubMedGoogle Scholar
  32. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004;18(16):1926–45.CrossRefPubMedGoogle Scholar
  33. Hodak S, Tuttle RM, Maytal G, Nikiforov YE, Randolph G. Changing the cancer diagnosis: the case of follicular variant of papillary thyroid cancer-primum non nocere and NIFTP. Thyroid. 2016;26(7):869–71.CrossRefPubMedGoogle Scholar
  34. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER cancer statistics review, 1975–2013. Bethesda: National Cancer Institute., based on November 2015 SEER data submission, posted to the SEER web site. 2016.
  35. Hsiao SJ, Nikiforov YE. Molecular approaches to thyroid cancer diagnosis. Endocr Relat Cancer. 2014;21(5):T301–13.PubMedPubMedCentralGoogle Scholar
  36. Ito T, Seyama T, Iwamoto KS, Hayashi T, Mizuno T, Tsuyama N, et al. In vitro irradiation is able to cause RET oncogene rearrangement. Cancer Res. 1993;53(13):2940–3.PubMedGoogle Scholar
  37. Ji JH, Oh YL, Hong M, Yun JW, Lee HW, Kim D, et al. Identification of driving ALK fusion genes and genomic landscape of medullary thyroid cancer. PLoS Genet. 2015;11(8):e1005467.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Johansson E, Andersson L, Örnros J, Carlsson T, Ingeson-Carlsson C, Liang S, et al. Revising the embryonic origin of thyroid C cells in mice and humans. Development. 2015;142(20):3519–28.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Kasaian K, Wiseman SM, Walker BA, Schein JE, Hirst M, Moore RA, et al. Putative BRAF activating fusion in a medullary thyroid cancer. Cold Spring Harb Mol Case Stud. 2016;2(2):a000729.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Krishnan A, Nair SA, Pillai MR. Biology of PPAR gamma in cancer: a critical review on existing lacunae. Curr Mol Med. 2007;7(6):532–40.CrossRefPubMedGoogle Scholar
  41. Kumar M, Lechel A, Güneş Ç. Telomerase: the devil inside. Genes (Basel). 2016;7(8).CrossRefPubMedCentralGoogle Scholar
  42. Kunstman JW, Juhlin CC, Goh G, Brown TC, Stenman A, Healy JM, et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet. 2015;24(8):2318–29.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Landa I, Ganly I, Chan TA, Mitsutake N, Matsuse M, Ibrahimpasic T, et al. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab. 2013;98(9):E1562–6.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016;126(3):1052–66.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Liebner DA, Shah MH. Thyroid cancer: pathogenesis and targeted therapy. Ther Adv Endocrinol Metab. 2011;2(5):173–95.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Liu T, Yuan X, Xu D. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications. Genes (Basel). 2016a Jul 18;7(7). pii: E38.CrossRefPubMedCentralGoogle Scholar
  47. Liu T, Yuan X, Xu D. Cancer-specific telomerase reverse transcriptase (TERT) promoter mutations: biological and clinical implications. Genes (Basel). 2016b;7(7):38.CrossRefGoogle Scholar
  48. Machens A, Niccoli-Sire P, Hoegel J, Frank-Raue K, van Vroonhoven TJ, Roeher HD, et al. Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med. 2003;349(16):1517–25.CrossRefPubMedGoogle Scholar
  49. Maenhaut C, Christophe D, Vassart G, Dumont J, Roger PP, Opitz R. Ontogeny, Anatomy, Metabolism and Physiology of the Thyroid. [Updated 2015 Jul 15]. In: De Groot LJ, Chrousos G, Dungan K, et al., Editors. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000.
  50. Malandrino P, Russo M, Ronchi A, Minoia C, Cataldo D, Regalbuto C, et al. Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination. Endocrine. 2016;53(2):471–9.CrossRefPubMedGoogle Scholar
  51. Máximo V, Botelho T, Capela J, Soares P, Lima J, Taveira A, et al. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer. 2005;92(10):1892–8.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Mazeh H, Sippel RS. Familial nonmedullary thyroid carcinoma. Thyroid. 2013;23(9):1049–56.CrossRefPubMedGoogle Scholar
  53. Mazzaferri EL. An overview of the management of papillary and follicular thyroid carcinoma. Thyroid. 1999;9(5):421–7.CrossRefPubMedGoogle Scholar
  54. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014;99(5):E754–65.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Mendoza MC, Er EE, Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci. 2011;36(6):320–8.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Moritz A, Li Y, Guo A, Villén J, Wang Y, MacNeill J, et al. Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. Sci Signal. 2010;3(136):ra64.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Moura MM, Cavaco BM, Pinto AE, Leite V. High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab. 2011;96(5):E863–8.CrossRefPubMedGoogle Scholar
  58. Mulligan LM. RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer. 2014;14(3):173–86.CrossRefPubMedGoogle Scholar
  59. Navas-Carrillo D, Ríos A, Rodríguez JM, Parrilla P, Orenes-Piñero E. Familial nonmedullary thyroid cancer: screening, clinical, molecular and genetic findings. Biochim Biophys Acta. 2014;1846(2):468–76.PubMedGoogle Scholar
  60. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569–80.CrossRefPubMedGoogle Scholar
  61. Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2016;2(8):1023–9.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn 2nd GW, Tallini G, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318–26.CrossRefPubMedGoogle Scholar
  63. Papp S, Asa SL. When thyroid carcinoma goes bad: a morphological and molecular analysis. Head Neck Pathol. 2015;9(1):16–23.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Pasca di Magliano M, Di Lauro R, Zannini M. Pax8 has a key role in thyroid cell differentiation. Proc Natl Acad Sci U S A. 2000;97(24):13144–9.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Radkay LA, Chiosea SI, Seethala RR, Hodak SP, LeBeau SO, Yip L, et al. Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics. Cancer Cytopathol. 2014;122(12):873–82.CrossRefPubMedGoogle Scholar
  66. Raman P, Koenig RJ. Pax-8-PPAR-γ fusion protein in thyroid carcinoma. Nat Rev Endocrinol. 2014;10(10):616–23.CrossRefPubMedPubMedCentralGoogle Scholar
  67. Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, et al. 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(11):4885–93.CrossRefPubMedPubMedCentralGoogle Scholar
  68. Ricarte-Filho JC, Li S, Garcia-Rendueles ME, Montero-Conde C, Voza F, Knauf JA, et al. Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest. 2013;123(11):4935–44.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, et al. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA. 2011;305(1):68–77.CrossRefPubMedGoogle Scholar
  70. Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 2007;26(22):3291–310.CrossRefGoogle Scholar
  71. Santoro M, Carlomagno F. Targeting the Raf-MEK-ERK mit. Cold Spring Harb Perspect Biol. 2013;5(12):a009233.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7(4):295–308.CrossRefPubMedGoogle Scholar
  73. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefPubMedPubMedCentralGoogle Scholar
  74. Smallridge RC, Copland JA. Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol (R Coll Radiol). 2010;22(6):486–97. doi:10.1016/j.clon.2010.03.013.CrossRefGoogle Scholar
  75. Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer. 2009;16(1):17–44.CrossRefPubMedGoogle Scholar
  76. Tuttle RM, Haddad RI, Ball DW, Byrd D, Dickson P, Duh QY, et al. Thyroid carcinoma, version 2.2014. J Natl Compr Canc Netw. 2014;12(12):1671–80.CrossRefPubMedGoogle Scholar
  77. Vinagre J, Almeida A, Pópulo H, Batista R, Lyra J, Pinto V, et al. Frequency of TERT promoter mutations in human cancers. Nat Commun. 2013;4:2185.CrossRefPubMedGoogle Scholar
  78. Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, et al. 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(8):1256–64.CrossRefPubMedGoogle Scholar
  79. Wells Jr SA, Pacini F, Robinson BG, Santoro M. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013;98(8):3149–64.CrossRefPubMedPubMedCentralGoogle Scholar
  80. Wells Jr SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. American thyroid association guidelines task force on medullary thyroid carcinoma. revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Williams D. Radiation carcinogenesis: lessons from Chernobyl. Oncogene. 2008;27(Suppl 2):S9–18.CrossRefPubMedGoogle Scholar
  82. Williams D. Thyroid growth and cancer. Eur Thyroid J. 2015;4(3):164–73.CrossRefPubMedPubMedCentralGoogle Scholar
  83. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 2013;381(9871):1058–69.CrossRefPubMedPubMedCentralGoogle Scholar
  84. Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015;33(1):42–50.CrossRefPubMedGoogle Scholar
  85. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol. 2003;120(1):71–7.CrossRefPubMedGoogle Scholar
  86. Zimmermann MB, Galetti V. Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies. Thyroid Res. 2015;8:8.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dipartimento di Medicina Molecolare e Biotecnologie MedicheUniversità di Napoli Federico IINaplesItaly

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