Medullary thyroid cancers (MTC) are rare tumors of neuroendocrine origin that arise from parafollicular C cells which secrete calcitonin and other peptides and hormones.  Sporadic MTC accounts for 75% of cases, and inherited MTC constitutes the rest.  Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occurs.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant syndrome, characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, in one variant, primary hyperparathyroidism (PHPT).  MEN2 can be classified into three forms: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC).  MEN 2B syndrome accounts for 5% of all MEN2 cases.

MTC typically occurs in childhood in MEN 2B.  The diagnosis of MTC is based on history, physical examination, calcitonin and CEA levels, imaging, and fine needle aspiration biopsy.  MEN 2B is diagnosed clinically by the presence of additional features including mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and an asthenic ‘marfanoid’ body habitus.  Every patient with MTC should undergo DNA analysis for the presence of the RET mutation.

The best treatment for MEN 2B is surgery.  A prophylactic thyroidectomy is recommended for all patients with an identified RET mutation at the first year of life.  Also, lifelong thyroid hormone supplementation is needed.  The prognosis of MTC depends on the stage at which it is diagnosed and the quality of initial surgical treatment.

Mutations in the RET proto-oncogene, at the chromosomal region 10q11.2, account for the clinical subtypes of MEN2.  The RET protein is a receptor tyrosine kinase.  About 98% of individuals with MEN 2B are identifiable through RET testing.  FMTC, including families with fewer than four cases, is more accurately considered a matter of penetrance.