Molecular pathology of hereditary and sporadic medullary thyroid carcinomas

Am J Clin Pathol. 2015 Jun;143(6):768-77. doi: 10.1309/AJCPHWACTTUYJ7DD.


Objectives: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy, with unique histologic features and molecular pathology. It is important to recognize, because its management, which is in part driven by the genetic basis of this disease, is different from follicular-derived thyroid tumors. The aim of this article is to briefly review the histopathologic features of MTC and then explore its molecular pathology, including the role of molecular diagnostic testing and the use of targeted therapy for advanced disease.

Methods: A review of published literature was performed.

Results: A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors.

Conclusions: Molecular genetic testing is routinely performed to identify hereditary cases. In addition, understanding the molecular basis of both hereditary and sporadic MTC has led to the development of targeted therapy with tyrosine kinase inhibitors. Although additional data are needed, tumor mutation status may affect response to targeted therapy. Therefore, it is possible that genetic testing of tumor tissue to predict treatment response, as is currently done for other cancer types, may come into practice in the future.

Keywords: Familial medullary thyroid carcinoma; Medullary thyroid carcinoma; Multiple endocrine neoplasia; RAS; RET; Tyrosine kinase.

Publication types

  • Review

MeSH terms

  • Carcinoma, Medullary / genetics*
  • Carcinoma, Medullary / pathology*
  • Humans
  • Pathology, Molecular / methods*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*