Susceptibility Genes and Chromosomal Regions Associated With Non-Syndromic Familial Non-Medullary Thyroid Carcinoma: Some Pathogenetic and Diagnostic Keys

Front Endocrinol (Lausanne). 2022 Feb 28;13:829103. doi: 10.3389/fendo.2022.829103. eCollection 2022.


Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic alterations involved in the pathogenesis of sporadic follicular cell derived tumors are well recognized, while the predisposing alterations implicated in hereditary follicular tumors are less well known. Since the genetic background of syndromic familial non-medullary carcinoma has been well established, here we review the pathogenesis of non-syndromic familial non-medullary carcinoma emphasizing those aspects that may be useful in clinical and pathological diagnosis. Non-syndromic familial non-medullary carcinoma has a complex and heterogeneous genetic basis involving several genes and loci with a monogenic or polygenic inheritance model. Most cases are papillary thyroid carcinoma (classic and follicular variant), usually accompanied by benign thyroid nodules (follicular thyroid adenoma and/or multinodular goiter). The possible diagnostic and prognostic usefulness of the changes in the expression and/or translocation of various proteins secondary to several mutations reported in this setting requires further confirmation. Given that non-syndromic familial non-medullary carcinoma and sporadic non-medullary thyroid carcinoma share the same morphology and somatic mutations, the same targeted therapies could be used at present, if necessary, until more specific targeted treatments become available.

Keywords: cancer diagnosis; cancer risk; familial non-medullary thyroid carcinoma; familial thyroid cancer; papillary thyroid carcinoma; susceptibility genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Medullary / congenital
  • Carcinoma, Neuroendocrine
  • Humans
  • Multiple Endocrine Neoplasia Type 2a*
  • Neoplastic Syndromes, Hereditary* / diagnosis
  • Neoplastic Syndromes, Hereditary* / genetics
  • Neoplastic Syndromes, Hereditary* / pathology
  • Thyroid Cancer, Papillary / diagnosis
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Neoplasms* / diagnosis
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology

Supplementary concepts

  • Familial medullary thyroid carcinoma
  • Thyroid cancer, medullary