Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)

MEN2 is caused by germline activating mutations in the RET proto-oncogene. The American Thyroid Association guideline divides it into MEN2A, with medullary thyroid carcinoma, phaeochromocytoma and primary hyperparathyroidism (and the variants with cutaneous lichen amyloidosis or Hirschsprung disease, and familial medullary thyroid carcinoma, now classed as an MEN2A variant), and MEN2B, with earlier and more aggressive medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas and a marfanoid habitus, almost always from the RET M918T mutation (Wells 2015). The WHO endocrine classification lists MEN2 among the genetic tumour syndromes.

How it differs from its parent: MEN1 is a menin syndrome centred on parathyroid, pancreas and pituitary; MEN2 is a RET syndrome whose defining cancer is medullary thyroid carcinoma, which the corpus covers on its own page. The guideline stratifies RET mutations into highest risk (M918T), high risk (codon 634 and A883F) and moderate risk, and times prophylactic thyroidectomy accordingly: in the first year of life for the highest-risk group, at or before age five for the high-risk group, and by calcitonin surveillance for the moderate group; phaeochromocytoma is excluded before any operation (Wells 2015).

Treatment of established disease follows the medullary thyroid cancer page: total thyroidectomy with node dissection, and for advanced RET-driven disease the selective RET inhibitor selpercatinib, which beat cabozantinib or vandetanib in the LIBRETTO-531 trial linked from the parent page; phaeochromocytoma and hyperparathyroidism are treated as in sporadic disease. The genotype-phenotype rules hold in practice: a single-centre series of 158 MEN2 patients tested the guideline's predictions against observed ages of onset (Cancers 2024, PMID 38339246).