Ganglioneuromas are proliferations of neural gangion cells that occur either as sporadic solitary lesions or as multiple/diffuse lesions (ganglioneuromatosis). They can be associated with one of several genetic syndromes. Diffuse lesions may present as exophytic polyps (‘ganglioneuromatous polyposis’; associated with FAP, Cowden syndrome, tuberous sclerosis, juvenile polyposis) or poorly demarcated transmural proliferations (‘ganglioneuromatosis’; associated with MEN IIb - RET mutations and neurofibromatosis type 1 - NF1 mutations).

Solitary lesions are usually asymptomatic, have no gender predilection, and are usually found in the left side of the colon, with a mean patient age of approximately 50 years.

Diffuse lesions present with diverse GI symptoms such as crampy abdominal pain, constipation, projectile vomiting, diarrhea and/or difficulty feeding. The mean patient age is usually less than 35 years.

The major differential is neurofibroma, in which there is a lack of ganglion cells, which are present in ganglioneuromas (NSE, synaptophysin positive). Histologically, ganglioneuromas distend the lamina and show sheets of spindle cells within a fibrillary matrix and irregular nests and groups of ganglion cells. The diffuse lesions may extend into all layers of the bowel wall, including mesentery.