ganglioneuromatosis

Ganglioneuromatosis is a rare, benign condition characterized by proliferation of mature ganglion cells, Schwann cells, and neural fibers within the enteric nervous system and/or surrounding tissues. It can occur as a localized lesion or as a diffuse, multifocal process that involves segment(s) of the gastrointestinal tract. The diffuse form is sometimes referred to as diffuse ganglioneuromatosis and can be associated with systemic syndromes, most notably MEN2B.

The condition may appear as isolated intestinal ganglioneuromas or as widespread thickening of the myenteric and submucosal nerve plexuses. When associated with MEN2B, it often accompanies mucosal neuromas of the lips, tongue, and oral or ocular surfaces, and carries implications for surveillance of medullary thyroid carcinoma and pheochromocytoma due to underlying RET gene mutations.

Histologically, ganglioneuromatosis shows mature ganglion cells embedded in a Schwannian stroma with fibrous and neural components, typically lacking immature neuroblasts. Immunohistochemistry can aid diagnosis, with markers such as S-100 highlighting Schwann cells and neurofilament or synaptophysin labeling mature neurons.

Clinical features vary by extent and location. GI involvement can cause constipation, abdominal pain, distension, or intestinal obstruction, especially in diffuse disease. Mucosal neuromas and other MEN2B features may predominate in other patients. Diagnosis relies on clinical suspicion, endoscopic or radiologic assessment, and confirmatory biopsy with histology and genetic testing for RET mutations.

Management focuses on symptom relief and addressing associated syndromes. Localized lesions may be surgically excised; diffuse disease requires multidisciplinary care, with screening for MEN2B–related tumors. The prognosis is generally favorable for the neural proliferation itself, but overall outcomes depend on associated conditions and complications.