MEN 3 D44.8

Rare, autosomal dominantly inherited tumor disease considered to be a variant of multiple endocrine neoplasms (MEN) with multiple mucosaneuromas and endocrine polyadenomatosis.

Autosomal dominant mutation of the RET prooncogene, a gene encoding a transmembrane tyrosine kinase mapped to chromosome 10q11.2. The mutation causes autonomous growth stimulation (see RET oncogene below). Sporadic cases are explained by new mutations.

Marfanoid habitus (in some patients), multiple skin and mucous membrane neuromas (in 100% of cases: nodular affection of the lips (tapir snout - bumpy lips), buccal mucosa, palate and pharynx), medullary thyroid carcinomas (95% of cases: aggressive course!) and pheochromocytoma (50%), skeletal anomalies, possible parathyroid dysfunction (hyperparathyroidism), lentiginosis centrofacialis, neurological disorders, hyperplastic corneal nerves. Intestinal ganglioneuromatosis may cause severe constipation and/or diarrhea.

Remarkably, this syndrome is characterized by a high incidence of total paraesthetica. The pathogenetic relationship is unclear.

The histological picture corresponds to the "palisaded and encapsulated neuroma". Well defined, smaller and larger, nodular or strand-like tumor proliferations which can penetrate the entire dermis. The tumor convolutions are encapsulated by a delicate connective tissue envelope. The tumor parenchyma consists of interwoven strands with spindle cells that are cut in different directions. The nuclei show an undulating or comma-shaped pattern. Often perinuclear halo formations are detectable, so that the cytoplasm takes on a honeycombed aspect.

Described is the development of myelodysplastic syndrome after chemotherapeutic treatment of a pat. with MEN 3 (Mull JL et al. 2016).

The designation MEN 3 has recently been introduced instead of the original designation MEN 2b.

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