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The increasing prevalence of chronic lymphocytic thyroiditis in papillary microcarcinoma

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Abstract

Although the incidence of some malignancy has decreased over the recent years, this is not the case of papillary thyroid microcarcinoma (PTMC), whose incidence has increased worldwide. Most PTMC are found incidentally after histological examination of specimens from surgery for benign thyroid disease. Hashimoto’s thyroiditis, whose incidence has also increased, coexists in about one in three PTMC patients. Three different mechanisms have been proposed to clarify the association between chronic lymphocytic thyroiditis and PTMC, namely tumor development/growth by: (i) TSH stimulation, (ii) expression of certain proto-oncogenes, (iii) chemokines and other molecules produced by the lymphocytic infiltrate. Whether Hashimoto’s thyroiditis protects against lymph node metastasis is debated. Overall, autommune thyroiditis seems to contribute to the favorable prognosis of PTMC. Major limitations of the studies so far performed include: (i) retrospective design, (ii) limited statistical power, (iii) high risk of selection bias, (iv) and predominant Asian ethnicity of patients. Full genetic profiling of both diseases and identification of environmental factors capable to trigger them, as well as well-powered prospective studies on different ethnical groups, may help understand their causal association and why their frequencies are continuing raising.

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References

  1. Bircan HY, Koc B, Akarsu C, Demiralay E, Demirag A, Adas M, et al. Is Hashimoto's thyroiditis a prognostic factor for thyroid papillary microcarcinoma? Eur Rev Med Pharmacol Sci. 2014;18(13):1910–5.

    CAS  PubMed  Google Scholar 

  2. Slijepcevic N, Zivaljevic V, Marinkovic J, Sipetic S, Diklic A, Paunovic I. Retrospective evaluation of the incidental finding of 403 papillary thyroid microcarcinomas in 2466 patients undergoing thyroid surgery for presumed benign thyroid disease. BMC Cancer. 2015;15:330. https://doi.org/10.1186/s12885-015-1352-4.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rizzo M, Sindoni A, Talamo Rossi R, Bonaffini O, Panetta S, Scisca C, et al. Annual increase in the frequency of papillary thyroid carcinoma as diagnosed by fine-needle aspiration at a cytology unit in Sicily. Hormones. 2013;12(1):46–57.

    Article  Google Scholar 

  4. Latina A, Gullo D, Trimarchi F, Benvenga S. Hashimoto's thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer. PloS One. 2013;8(3):e55450. https://doi.org/10.1371/journal.pone.0055450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hay ID, Hutchinson ME, Gonzalez-Losada T, McIver B, Reinalda ME, Grant CS, et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery. 2008;144(6):980–7; discussion 7–8. https://doi.org/10.1016/j.surg.2008.08.035.

    Article  PubMed  Google Scholar 

  6. Lin JD, Kuo SF, Chao TC, Hsueh C. Incidental and nonincidental papillary thyroid microcarcinoma. Ann Surg Oncol. 2008;15(8):2287–92. https://doi.org/10.1245/s10434-008-9958-2.

    Article  PubMed  Google Scholar 

  7. Baser H, Ozdemir D, Cuhaci N, Aydin C, Ersoy R, Kilicarslan A, et al. Hashimoto's thyroiditis does not affect ultrasonographical, cytological, and histopathological features in patients with papillary thyroid carcinoma. Endocr Pathol. 2015;26(4):356–64. https://doi.org/10.1007/s12022-015-9401-8.

    Article  PubMed  Google Scholar 

  8. Yu XM, Wan Y, Sippel RS, Chen H. Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18,445 cases. Ann Surg. 2011;254(4):653–60. https://doi.org/10.1097/SLA.0b013e318230036d.

    Article  PubMed  Google Scholar 

  9. Lin JD. Increased incidence of papillary thyroid microcarcinoma with decreased tumor size of thyroid cancer. Med Oncol. 2010;27(2):510–8. https://doi.org/10.1007/s12032-009-9242-8.

    Article  PubMed  Google Scholar 

  10. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295(18):2164–7. https://doi.org/10.1001/jama.295.18.2164.

    Article  CAS  Google Scholar 

  11. Londero SC, Krogdahl A, Bastholt L, Overgaard J, Trolle W, Pedersen HB, et al. Papillary thyroid microcarcinoma in Denmark 1996–2008: a national study of epidemiology and clinical significance. Thyroid : official journal of the American Thyroid Association. 2013;23(9):1159–64. https://doi.org/10.1089/thy.2012.0595.

    Article  Google Scholar 

  12. Du L, Wang Y, Sun X, Li H, Geng X, Ge M, et al. Thyroid cancer: trends in incidence, mortality and clinical-pathological patterns in Zhejiang Province, Southeast China. BMC Cancer. 2018;18(1):291. https://doi.org/10.1186/s12885-018-4081-7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Benvenga S, Trimarchi F. Changed presentation of Hashimoto's thyroiditis in North-Eastern Sicily and Calabria (Southern Italy) based on a 31-year experience. Thyroid : official journal of the American Thyroid Association. 2008;18(4):429–41. https://doi.org/10.1089/thy.2007.0234.

    Article  CAS  Google Scholar 

  14. Rizzo M, Rossi RT, Bonaffini O, Scisca C, Altavilla G, Calbo L, et al. Increased annual frequency of Hashimoto's thyroiditis between years 1988 and 2007 at a cytological unit of Sicily. Ann Endocrinol. 2010;71(6):525–34. https://doi.org/10.1016/j.ando.2010.06.006.

    Article  CAS  Google Scholar 

  15. Liu Y, Li C, Zhao W, Wang Y. Hashimoto's thyroiditis is an important risk factor of papillary thyroid microcarcinoma in younger adults. Horm Metab Res = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;49(10):732–8. https://doi.org/10.1055/s-0043-117892.

    Article  CAS  PubMed  Google Scholar 

  16. Chen YK, Lin CL, Cheng FT, Sung FC, Kao CH. Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study. Br J Cancer. 2013;109(9):2496–501. https://doi.org/10.1038/bjc.2013.597.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Guarino V, Castellone MD, Avilla E, Melillo RM. Thyroid cancer and inflammation. Mol Cell Endocrinol. 2010;321(1):94–102. https://doi.org/10.1016/j.mce.2009.10.003.

    Article  CAS  PubMed  Google Scholar 

  18. Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP. Coexistent Hashimoto's thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery. 1999;126(6):1070–6 discussion 6–7.

    Article  CAS  Google Scholar 

  19. Resende de Paiva C, Gronhoj C, Feldt-Rasmussen U, von Buchwald C. Association between Hashimoto's thyroiditis and thyroid cancer in 64,628 patients. Front Oncol. 2017;7:53. https://doi.org/10.3389/fonc.2017.00053.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg. 1955;70(2):291–7.

    Article  CAS  Google Scholar 

  21. Tamimi DM. The association between chronic lymphocytic thyroiditis and thyroid tumors. Int J Surg Pathol. 2002;10(2):141–6. https://doi.org/10.1177/106689690201000207.

    Article  PubMed  Google Scholar 

  22. Melcescu E, Horton WB, Pitman KT, Vijayakumar V, Koch CA. Euthyroid Graves' orbitopathy and incidental papillary thyroid microcarcinoma. Hormones. 2013;12(2):298–304.

    Article  Google Scholar 

  23. Ieni A, Vita R, Magliolo E, Santarpia M, Di Bari F, Benvenga S, et al. One-third of an archivial series of papillary thyroid cancer (years 2007–2015) has coexistent chronic lymphocytic thyroiditis, which is associated with a more favorable tumor-node-metastasis staging. Front Endocrinol. 2017;8:337. https://doi.org/10.3389/fendo.2017.00337.

    Article  Google Scholar 

  24. Akin S, Yazgan Aksoy D, Akin S, Kilic M, Yetisir F, Bayraktar M. Prediction of central lymph node metastasis in patientswith thyroid papillary microcarcinoma. Turk J Med Sci. 2017;47(6):1723–7. https://doi.org/10.3906/sag-1702-99.

    Article  PubMed  Google Scholar 

  25. Lim JY, Hong SW, Lee YS, Kim BW, Park CS, Chang HS, et al. Clinicopathologic implications of the BRAF(V600E) mutation in papillary thyroid cancer: a subgroup analysis of 3130 cases in a single center. Thyroid : official journal of the American Thyroid Association. 2013;23(11):1423–30. https://doi.org/10.1089/thy.2013.0036.

    Article  CAS  Google Scholar 

  26. Qu N, Zhang L, Lin DZ, Ji QH, Zhu YX, Wang Y. The impact of coexistent Hashimoto's thyroiditis on lymph node metastasis and prognosis in papillary thyroid microcarcinoma. Tumour Biol : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(6):7685–92. https://doi.org/10.1007/s13277-015-4534-4.

    Article  CAS  Google Scholar 

  27. Zhang LY, Liu ZW, Liu YW, Gao WS, Zheng CJ. Risk factors for nodal metastasis in cN0 papillary thyroid microcarcinoma. Asian Pac J Cancer Prev : APJCP. 2015;16(8):3361–3.

    Article  Google Scholar 

  28. Yang Y, Chen C, Chen Z, Jiang J, Chen Y, Jin L, et al. Prediction of central compartment lymph node metastasis in papillary thyroid microcarcinoma. Clin Endocrinol. 2014;81(2):282–8. https://doi.org/10.1111/cen.12417.

    Article  CAS  Google Scholar 

  29. Li M, Zhu XY, Lv J, Lu K, Shen MP, Xu ZL, et al. Risk factors for predicting central lymph node metastasis in papillary thyroid microcarcinoma (CN0): a study of 273 resections. Eur Rev Med Pharmacol Sci. 2017;21(17):3801–7.

    CAS  PubMed  Google Scholar 

  30. Choi SY, Park H, Kang MK, Lee DK, Lee KD, Lee HS, et al. The relationship between the BRAF(V600E) mutation in papillary thyroid microcarcinoma and clinicopathologic factors. World J Surg Oncol. 2013;11:291. https://doi.org/10.1186/1477-7819-11-291.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kim HS, Choi YJ, Yun JS. Features of papillary thyroid microcarcinoma in the presence and absence of lymphocytic thyroiditis. Endocr Pathol. 2010;21(3):149–53. https://doi.org/10.1007/s12022-010-9124-9.

    Article  PubMed  Google Scholar 

  32. Lai X, Zhang B, Jiang Y, Li J, Zhao R, Yang X, et al. Sonographic and clinical features of papillary thyroid microcarcinoma less than or equal to five millimeters: a retrospective study. PloS One. 2016;11(2):e0148567. https://doi.org/10.1371/journal.pone.0148567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Giordano D, Gradoni P, Oretti G, Molina E, Ferri T. Treatment and prognostic factors of papillary thyroid microcarcinoma. Clin Otolaryngol : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2010;35(2):118–24. https://doi.org/10.1111/j.1749-4486.2010.02085.x.

    Article  CAS  Google Scholar 

  34. Fu X, Lou S, Shi H, Liu Q, Chen Z, Zhou Y. Clinicopathologic analysis of 254 cases of papillary thyroid microcarcinoma. Zhonghua bing li xue za zhi = Chin J Pathol. 2015;44(4):258–61.

    Google Scholar 

  35. Kim SK, Park I, Woo JW, Lee JH, Choe JH, Kim JH, et al. Predictive Factors for Lymph Node Metastasis in Papillary Thyroid Microcarcinoma. Ann Surg Oncol. 2016;23(9):2866–73. https://doi.org/10.1245/s10434-016-5225-0.

    Article  PubMed  Google Scholar 

  36. Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J Surg. 2008;32(5):747–53. https://doi.org/10.1007/s00268-007-9453-0.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ferrari SM, Elia G, Virili C, Centanni M, Antonelli A, Fallahi P. Systemic lupus erythematosus and thyroid autoimmunity. Front Endocrinol. 2017;8:138. https://doi.org/10.3389/fendo.2017.00138.

    Article  Google Scholar 

  38. Antonelli A, Ferri C, Ferrari SM, Di Domenicantonio A, Giuggioli D, Galleri D, et al. Increased risk of papillary thyroid cancer in systemic sclerosis associated with autoimmune thyroiditis. Rheumatology. 2016;55(3):480–4. https://doi.org/10.1093/rheumatology/kev358.

    Article  CAS  PubMed  Google Scholar 

  39. Fallahi P, Ruffilli I, Giuggioli D, Colaci M, Ferrari SM, Antonelli A, et al. Associations between systemic sclerosis and thyroid diseases. Front Endocrinol. 2017;8:266. https://doi.org/10.3389/fendo.2017.00266.

    Article  Google Scholar 

  40. Ferri C, Colaci M, Fallahi P, Ferrari SM, Antonelli A, Giuggioli D. Thyroid involvement in hepatitis C virus-infected patients with/without mixed cryoglobulinemia. Front Endocrinol. 2017;8:159. https://doi.org/10.3389/fendo.2017.00159.

    Article  Google Scholar 

  41. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev. 2015;14(2):174–80. https://doi.org/10.1016/j.autrev.2014.10.016.

    Article  CAS  PubMed  Google Scholar 

  42. Burikhanov R, Coulonval K, Pirson I, Lamy F, Dumont JE, Roger PP. Thyrotropin via cyclic AMP induces insulin receptor expression and insulin Co-stimulation of growth and amplifies insulin and insulin-like growth factor signaling pathways in dog thyroid epithelial cells. J Biol Chem. 1996;271(46):29400–6.

    Article  CAS  Google Scholar 

  43. Westermark K, Karlsson FA, Westermark B. Thyrotropin modulates EGF receptor function in porcine thyroid follicle cells. Mol Cell Endocrinol. 1985;40(1):17–23.

    Article  CAS  Google Scholar 

  44. Boelaert K. The association between serum TSH concentration and thyroid cancer. Endocr Relat Cancer. 2009;16(4):1065–72. https://doi.org/10.1677/ERC-09-0150.

    Article  CAS  PubMed  Google Scholar 

  45. Tam AA, Ozdemir D, Aydin C, Bestepe N, Ulusoy S, Sungu N, et al. Association between preoperative thyrotrophin and clinicopathological and aggressive features of papillary thyroid cancer. Endocrine. 2018;59(3):565–72. https://doi.org/10.1007/s12020-018-1523-6.

    Article  CAS  PubMed  Google Scholar 

  46. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et 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 : official journal of the American Thyroid Association. 2016;26(1):1–133. https://doi.org/10.1089/thy.2015.0020.

    Article  Google Scholar 

  47. Shi RL, Liao T, Qu N, Liang F, Chen JY, Ji QH. The usefulness of preoperative thyroid-stimulating hormone for predicting differentiated thyroid microcarcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2016;154(2):256–62. https://doi.org/10.1177/0194599815618388.

    Article  Google Scholar 

  48. Zheng J, Li C, Lu W, Wang C, Ai Z. Quantitative assessment of preoperative serum thyrotropin level and thyroid cancer. Oncotarget. 2016;7(23):34918–29. https://doi.org/10.18632/oncotarget.9201.

    Article  PubMed  PubMed Central  Google Scholar 

  49. McLeod DS, Watters KF, Carpenter AD, Ladenson PW, Cooper DS, Ding EL. Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response meta-analysis. J Clin Endocrinol Metab. 2012;97(8):2682–92. https://doi.org/10.1210/jc.2012-1083.

    Article  CAS  PubMed  Google Scholar 

  50. Negro R, Valcavi R, Riganti F, Toulis KA, Colosimo E, Bongiovanni M, et al. Thyrotropin values in patients with micropapillary thyroid cancer versus benign nodular disease. Endocr Pract : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2013;19(4):651–5. https://doi.org/10.4158/EP12385.OR.

    Article  Google Scholar 

  51. Shi L, Li Y, Guan H, Li C, Shi L, Shan Z, et al. Usefulness of serum thyrotropin for risk prediction of differentiated thyroid cancers does not apply to microcarcinomas: results of 1,870 Chinese patients with thyroid nodules. Endocr J. 2012;59(11):973–80.

    Article  Google Scholar 

  52. Choi JS, Nam CM, Kim EK, Moon HJ, Han KH, Kwak JY. Evaluation of serum thyroid-stimulating hormone as indicator for fine-needle aspiration in patients with thyroid nodules. Head Neck. 2015;37(4):498–504. https://doi.org/10.1002/hed.23616.

    Article  PubMed  Google Scholar 

  53. Fiore E, Rago T, Provenzale MA, Scutari M, Ugolini C, Basolo F, et al. Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer. 2009;16(4):1251–60. https://doi.org/10.1677/ERC-09-0036.

    Article  CAS  PubMed  Google Scholar 

  54. Golbert L, de Cristo AP, Faccin CS, Farenzena M, Folgierini H, Graudenz MS, et al. Serum TSH levels as a predictor of malignancy in thyroid nodules: A prospective study. PloS One. 2017;12(11):e0188123. https://doi.org/10.1371/journal.pone.0188123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Moon SS, Lee YS, Lee IK, Kim JG. Serum thyrotropin as a risk factor for thyroid malignancy in euthyroid subjects with thyroid micronodule. Head Neck. 2012;34(7):949–52. https://doi.org/10.1002/hed.21828.

    Article  PubMed  Google Scholar 

  56. Arscott PL, Stokes T, Myc A, Giordano TJ, Thompson NW, Baker JR Jr. Fas (CD95) expression is up-regulated on papillary thyroid carcinoma. J Clin Endocrinol Metab. 1999;84(11):4246–52. https://doi.org/10.1210/jcem.84.11.6139.

    Article  CAS  PubMed  Google Scholar 

  57. Kimura H, Yamashita S, Namba H, Tominaga T, Tsuruta M, Yokoyama N, et al. Interleukin-1 inhibits human thyroid carcinoma cell growth. J Clin Endocrinol Metab. 1992;75(2):596–602. https://doi.org/10.1210/jcem.75.2.1322431.

    Article  CAS  PubMed  Google Scholar 

  58. Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, et al. Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. J Endocrinol Investig. 2013;36(5):313–20. https://doi.org/10.3275/8579.

    Article  CAS  Google Scholar 

  59. Koch CA. How can environmental factors contribute to the incidence of thyroid cancer? Horm Metab Res = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;49(3):229–31. https://doi.org/10.1055/s-0043-103572.

    Article  CAS  PubMed  Google Scholar 

  60. Koch CA, Diamanti-Kandarakis E. Introduction to endocrine disrupting chemicals--is it time to act? Rev Endocr Metab Disord. 2015;16(4):269–70. https://doi.org/10.1007/s11154-016-9338-3.

    Article  PubMed  Google Scholar 

  61. Lewis J, Hoover J, MacKenzie D. Mining and environmental health disparities in native american communities. Curr Environ Health Rep. 2017;4(2):130–41. https://doi.org/10.1007/s40572-017-0140-5.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Duntas LH, Stathatos N. Toxic chemicals and thyroid function: hard facts and lateral thinking. Rev Endocr Metab Disord. 2015;16(4):311–8. https://doi.org/10.1007/s11154-016-9331-x.

    Article  CAS  PubMed  Google Scholar 

  63. Franco AT, Malaguarnera R, Refetoff S, Liao XH, Lundsmith E, Kimura S, et al. Thyrotrophin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice. Proc Natl Acad Sci U S A. 2011;108(4):1615–20. https://doi.org/10.1073/pnas.1015557108.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Virk RK, Van Dyke AL, Finkelstein A, Prasad A, Gibson J, Hui P, et al. BRAFV600E mutation in papillary thyroid microcarcinoma: a genotype-phenotype correlation. Mod Pathol : an official journal of the United States and Canadian Academy of Pathology, Inc. 2013;26(1):62–70. https://doi.org/10.1038/modpathol.2012.152.

    Article  CAS  Google Scholar 

  65. Sheu SY, Schwertheim S, Worm K, Grabellus F, Schmid KW. Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements. Mod Pathol : an official journal of the United States and Canadian Academy of Pathology, Inc. 2007;20(7):779–87. https://doi.org/10.1038/modpathol.3800797.

    Article  CAS  Google Scholar 

  66. Lin KL, Wang OC, Zhang XH, Dai XX, Hu XQ, Qu JM. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma. Ann Surg Oncol. 2010;17(12):3294–300. https://doi.org/10.1245/s10434-010-1129-6.

    Article  PubMed  Google Scholar 

  67. Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA Jr, Sigurdson AJ, et al. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab. 2014;99(2):E276–85. https://doi.org/10.1210/jc.2013-2503.

    Article  CAS  PubMed  Google Scholar 

  68. Shi CL, Guo Y, Lyu YC, Nanding Z, Gao WC, Shi TF, et al. Clinical pathological characteristics of resectable papillary thyroid microcarcinoma. Zhonghua zhong liu za zhi [Chin J Oncol]. 2017;39(5):361–6. https://doi.org/10.3760/cma.j.issn.0253-3766.2017.05.008.

    Article  CAS  Google Scholar 

  69. Marotta V, Guerra A, Zatelli MC, Uberti ED, Di Stasi V, Faggiano A, et al. BRAF mutation positive papillary thyroid carcinoma is less advanced when Hashimoto's thyroiditis lymphocytic infiltration is present. Clin Endocrinol. 2013;79(5):733–8. https://doi.org/10.1111/cen.12194.

    Article  CAS  Google Scholar 

  70. Ma YJ, Deng XL, Li HQ. BRAF(V(6)(0)(0)E) mutation and its association with clinicopathological features of papillary thyroid microcarcinoma: A meta-analysis. J Huazhong Univ Sci Technolog Med Sci = Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban = Huazhong keji daxue xuebao Yixue Yingdewen ban. 2015;35(4):591–9. https://doi.org/10.1007/s11596-015-1476-4.

    Article  CAS  PubMed  Google Scholar 

  71. Ciampi R, Nikiforov YE. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology. 2007;148(3):936–41. https://doi.org/10.1210/en.2006-0921.

    Article  CAS  PubMed  Google Scholar 

  72. Tallini G, Santoro M, Helie M, Carlomagno F, Salvatore G, Chiappetta G, et 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 : an official journal of the American Association for Cancer Research. 1998;4(2):287–94.

    CAS  Google Scholar 

  73. Su X, He C, Ma J, Tang T, Zhang X, Ye Z, et al. RET/PTC rearrangements are associated with elevated postoperative TSH levels and multifocal lesions in papillary thyroid cancer without concomitant thyroid benign disease. PloS One. 2016;11(11):e0165596. https://doi.org/10.1371/journal.pone.0165596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 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. 2017;18(3):244–54. https://doi.org/10.2174/1389202918666170105094459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kuo EJ, Goffredo P, Sosa JA, Roman SA. Aggressive variants of papillary thyroid microcarcinoma are associated with extrathyroidal spread and lymph-node metastases: a population-level analysis. Thyroid : official journal of the American Thyroid Association. 2013;23(10):1305–11. https://doi.org/10.1089/thy.2012.0563.

    Article  CAS  Google Scholar 

  76. Benvenga S, Koch CA. Molecular pathways associated with aggressiveness of papillary thyroid cancer. Curr Genomics. 2014;15(3):162–70. https://doi.org/10.2174/1389202915999140404100958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kang DY, Kim KH, Kim JM, Kim SH, Kim JY, Baik HW, et al. High prevalence of RET, RAS, and ERK expression in Hashimoto's thyroiditis and in papillary thyroid carcinoma in the Korean population. Thyroid : official journal of the American Thyroid Association. 2007;17(11):1031–8. https://doi.org/10.1089/thy.2007.0035.

    Article  CAS  Google Scholar 

  78. Khoo ML, Ezzat S, Freeman JL, Asa SL. Cyclin D1 protein expression predicts metastatic behavior in thyroid papillary microcarcinomas but is not associated with gene amplification. J Clin Endocrinol Metab. 2002;87(4):1810–3. https://doi.org/10.1210/jcem.87.4.8352.

    Article  CAS  PubMed  Google Scholar 

  79. Ma H, Yan J, Zhang C, Qin S, Qin L, Liu L, et al. 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. Int J Clin Exp Pathol. 2014;7(11):7999–8007.

    PubMed  PubMed Central  Google Scholar 

  80. Chui MH, Cassol CA, Asa SL, Mete O. Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis. Virchows Arch : an international journal of pathology. 2013;462(5):557–63. https://doi.org/10.1007/s00428-013-1397-1.

    Article  CAS  Google Scholar 

  81. Singh S, Singh A, Khanna AK. Thyroid incidentaloma. Indian J Surg Oncol. 2012;3(3):173–81. https://doi.org/10.1007/s13193-011-0098-y.

    Article  PubMed  Google Scholar 

  82. Sakorafas GH, Giotakis J, Stafyla V. Papillary thyroid microcarcinoma: a surgical perspective. Cancer Treat Rev. 2005;31(6):423–38. https://doi.org/10.1016/j.ctrv.2005.04.009.

    Article  PubMed  Google Scholar 

  83. Sciuto R, Romano L, Rea S, Marandino F, Sperduti I, Maini CL. Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution. Ann Oncol : official journal of the European Society for Medical Oncology. 2009;20(10):1728–35. https://doi.org/10.1093/annonc/mdp050.

    Article  CAS  Google Scholar 

  84. Slijepcevic N, Zivaljevic V, Diklic A, Jovanovic M, Oluic B, Paunovic I. Risk factors associated with intrathyroid extension of thyroid microcarcinomas. Langenbeck's Arch Surg. 2018. https://doi.org/10.1007/s00423-018-1680-3.

  85. Kwak JY, Kim EK, Youk JH, Kim MJ, Son EJ, Choi SH, et al. Extrathyroid extension of well-differentiated papillary thyroid microcarcinoma on US. Thyroid : official journal of the American Thyroid Association. 2008;18(6):609–14. https://doi.org/10.1089/thy.2007.0345.

    Article  Google Scholar 

  86. Yu X, Song X, Sun W, Zhao S, Zhao J, Wang YG. Independent risk factors predicting central lymph node metastasis in papillary thyroid microcarcinoma. Horm Metab Res = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;49(3):201–7. https://doi.org/10.1055/s-0043-101917.

    Article  CAS  PubMed  Google Scholar 

  87. Qu H, Sun GR, Liu Y, He QS. Clinical risk factors for central lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. Clin Endocrinol. 2015;83(1):124–32. https://doi.org/10.1111/cen.12583.

    Article  Google Scholar 

  88. Liu LS, Liang J, Li JH, Liu X, Jiang L, Long JX, et al. The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis. Eur Arch Otorhinolaryngol : official journal of the European Federation of Oto-Rhino-Laryngological Societies. 2017;274(3):1327–38. https://doi.org/10.1007/s00405-016-4302-0.

    Article  Google Scholar 

  89. Sun W, Lan X, Zhang H, Dong W, Wang Z, He L, et al. Risk factors for central lymph node metastasis in CN0 papillary thyroid carcinoma: a systematic review and meta-analysis. PloS One. 2015;10(10):e0139021. https://doi.org/10.1371/journal.pone.0139021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bradley NL, Wiseman SM. Papillary thyroid microcarcinoma: the significance of high risk features. BMC Cancer. 2017;17(1):142. https://doi.org/10.1186/s12885-017-3120-0.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Pisanu A, Saba A, Podda M, Reccia I, Uccheddu A. Nodal metastasis and recurrence in papillary thyroid microcarcinoma. Endocrine. 2015;48(2):575–81. https://doi.org/10.1007/s12020-014-0350-7.

    Article  CAS  PubMed  Google Scholar 

  92. Benvenga S, Guarneri F. Molecular mimicry and autoimmune thyroid disease. Rev Endocr Metab Disord. 2016;17(4):485–98. https://doi.org/10.1007/s11154-016-9363-2.

    Article  CAS  PubMed  Google Scholar 

  93. Miccoli P, Miccoli M, Antonelli A, Minuto MN. Clinicopathologic and molecular disease prognostication for papillary thyroid cancer. Expert Rev Anticancer Ther. 2009;9(9):1261–75. https://doi.org/10.1586/era.09.92.

    Article  PubMed  Google Scholar 

  94. Koibuchi H, Omoto K, Fukushima N, Toyotsuji T, Taniguchi N, Kawano M. Coexistence of papillary thyroid cancer and Hashimoto thyroiditis in children: report of 3 cases. J Ultrasound Med : official journal of the American Institute of Ultrasound in Medicine. 2014;33(7):1299–303. https://doi.org/10.7863/ultra.33.7.1299.

    Article  Google Scholar 

  95. Li Y, Wang Y, Wu Q, Hu B. Papillary thyroid microcarcinoma co-exists with Hashimoto's thyroiditis: Is strain elastography still useful? Ultrasonics. 2016;68:127–33. https://doi.org/10.1016/j.ultras.2016.02.013.

    Article  PubMed  Google Scholar 

  96. 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. 2014;22(2):113–9. https://doi.org/10.1177/1066896913517394.

    Article  PubMed  Google Scholar 

  97. Choi YJ, Yun JS, Kook SH, Jung EC, Park YL. Clinical and imaging assessment of cervical lymph node metastasis in papillary thyroid carcinomas. World J Surg. 2010;34(7):1494–9. https://doi.org/10.1007/s00268-010-0541-1.

    Article  PubMed  Google Scholar 

  98. Wu ZG, Yan XQ, Su RS, Ma ZS, Xie BJ, Cao FL. How many contralateral carcinomas in patients with unilateral papillary thyroid microcarcinoma are preoperatively misdiagnosed as benign? World J Surg. 2017;41(1):129–35. https://doi.org/10.1007/s00268-016-3701-0.

    Article  PubMed  Google Scholar 

  99. Kim D, Park JW. Clinical implications of preoperative thyrotropin serum concentrations in patients who underwent thyroidectomy for nonfunctioning nodule(s). J Korean Surg Soc. 2013;85(1):15–9. https://doi.org/10.4174/jkss.2013.85.1.15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, 98125, Messina, Italy

    Roberto Vita & Salvatore Benvenga

  2. Department of Human Pathology of Adult and Evolutive Age “Gaetano Barresi”—Section of Pathological Anatomy, University of Messina, Viale Gazzi, 98125, Messina, Italy

    Antonio Ieni & Giovanni Tuccari

  3. Master Program on Childhood, Adolescent and Women’s Endocrine Health, University of Messina, Viale Gazzi, 98125, Messina, Italy

    Salvatore Benvenga

  4. Interdepartmental Program of Molecular & Clinical Endocrinology and Women’s Endocrine Health, University Hospital, A.O.U. Policlinico G. Martino, Viale Gazzi, 98125, Messina, Italy

    Salvatore Benvenga

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  1. Roberto Vita
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  2. Antonio Ieni
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  4. Salvatore Benvenga
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Correspondence to Salvatore Benvenga.

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Vita, R., Ieni, A., Tuccari, G. et al. The increasing prevalence of chronic lymphocytic thyroiditis in papillary microcarcinoma. Rev Endocr Metab Disord 19, 301–309 (2018). https://doi.org/10.1007/s11154-018-9474-z

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