Multiple Endocrine Neoplasia type 2B (
MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary
thyroid carcinoma,
pheochromocytoma,
gastrointestinal disorders, marphanoid face, and mucosal multiple
ganglioneuromas. Medullary
thyroid carcinoma is the major cause of mortality in
MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for
MEN 2B. The 95% of
MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at
codon 883 has been found in 2%-3% of
MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause
MEN 2A syndrome,
familial medullary thyroid carcinoma, or
Hirschsprung's disease. RET gene expression is also involved in
Neuroblastoma. The main diagnosis standards are the
acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose
MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic
thyroidectomy. The surgical treatment of
MEN 2B is total
thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of
MEN 2 and MTC will allow new treatment possibilities.