Mucosal Neuroma Syndrome without mutations of the RET-protooncogene: A histologic study on a case, supported by molecular genetic analysis.

Mucosal neuromas are nerve hamartomas of the digestive tract and larynx, usually observed in the setting of Multiple Endocrine Neoplasia type 2b (MEN2b), i.e. in the presence of typical mutations and in association with medullary thyroid carcinoma, pheochromocytoma and marfanoid habitus. Exceptionally, they arise without the accompanying mutations and endocrine tumors, and in this paper we are reporting on a case of mucosal neuromas lacking the specific mutations. The patient was an adolescent girl with marfanoid habitus, with a left-sided epidermal nevus of the neck, and a bulging left upper lip and cheek. The left side of her tongue was considerably enlarged and studded with multiple protrusions. The histologic examination of the tongue showed a proliferation of tortuous gigantic nerve trunks, composed of multiple small bundles of argyrophylic and fully mylinated axons, invested by extremely hyperplasic perineurium and epineurium. These architectural distortions and disproportions, in the absence of disorders of polarity, imparted to the picture a dysmorphic, rather than neoplastic imprint. Although the required follow-up procedures were hindered by the patient's unavailability, DNA sequencing, performed on the paraffin specimen, demonstrated that none of the RET mutations reported to date in MEN 2b were present in our case. Therefore, this syndrome could be reasonably excluded and a final diagnosis of Multiple Neuroma Syndrome was assessed. Awareness of mucosal neuroma can be critical for the patient's survival, since this rare and often underrated neoplasm is likely to be an early marker of MEN2b, a life-threatening syndrome which requires early prophylactic surgery.