Multiple endocrine neoplasia type 2 (MEN2) is a hereditary condition associated primarily with medullary thyroid carcinoma, a specific type of thyroid cancer. MEN2 is classified into three subtypes based on symptoms.

Multiple endocrine neoplasia (MEN) 2A is associated with mutations in RET gene, especially in codons 609, 611, 618, and 620 in exon 10, as well as in codon 634 in exon 11 of the gene. Patients with MEN2A typically have MTC, pheochromocytoma, and primary hyperparathyroidism (PHPT).

MEN2B is associated with RET mutations in codons 918 in exon 16 (> 95% of cases) and codon 883 in exon 15. These patients present with the most aggressive type of MTC. They typically have pheochromocytoma but not PHPT, and, unlike in the other syndromes, also exhibit musculoskeletal abnormalities and other developmental defects.

Finally, familial medullary thyroid cancer (FMTC) is associated with mutations in codons 609, 611, 618, and 620 in exon 10, as well as codon 768 in exon 13 and codon 804 in exon 14. In these patients, MTC is often the only clinical finding, ie, patients do not necessarily have either pheochromocytoma or PHPT. The diagnosis of FMTC is therefore made after demonstrating MTC in at least 4 family members.

As in MEN2B, the most common mutation in patients with sporadic MTC is in codon 918 in exon 16. Patients with sporadic MTC typically have decreased survival compared with the inherited forms, and often demonstrate lymph node metastases at presentation.