MEDULLARY THYROID CARCINOMA

Abstract

Medullary thyroid carcinoma (MTC) represents 4–10 % of all thyroid carcinomas; MTCs arise from the parafollicular cells (C cells). Around 20–25 % of MTCs are part of inherited multiple endocrine neoplasia type 2 (MEN2) syndromes, while the rest are sporadic. Most are MEN2 syndromes that are divided in MEN2A and MEN2B. MEN2A represents 95 % of all MEN2 cases and is subdivided in 4 variants: classical MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung’s disease (HD), and familial medullary thyroid carcinoma (FMTC). Codon 634 in exon 11 is found mutated in 80–93 % of MEN2A patients. MEN2B are 5 % of all patients with MEN2 syndromes. MEN2B is characterized by the presence of MTC, pheochromocytoma, ganglioneuromatosis of the intestine and oral mucosa, neuromas of the tongue, marfanoid habitus, and medullated corneal nerve fibers. The mutation M918T in exon 16 is found in 95–100 % of MEN2B cases. Two thirds of sporadic MTCs have somatic mutations in RET: M918T in exon 16, the most common mutation; 8–68 % of the RET mutation-negative cases have somatic mutations in HRAS and KRAS. RET germline mutations should be offered to all patients with C-cell hyperplasia, familial MTC, and apparently sporadic MTC. These molecular studies are very helpful in characterizing these tumors.