Anatomical Pathology Interesting Case Conference

Discussion:

Ganglioneuroma is a mature, benign neural crest cell-derived neoplasm composed predominantly of Schwannian stroma with admixed mature ganglion cells. It represents 1.5-2.9% of all adrenal tumors with an incidence of ~1 per million. Adrenal ganglioneuromas occur in a broader adult age range (mean 35-41 years) compared to extra-adrenal retroperitoneal or mediastinal counterparts which predominantly occur in children. A slight male predominance (47-69% male) has been reported in larger case series.

The majority (63-77%) are asymptomatic incidentalomas. When symptomatic, abdominal pain is the most common complaint (10-25%). A minority may secrete catecholamines causing hypertension (2.4-12%); very rarely testosterone or dopamine secretion has been reported. Biochemical screening for hormonal activity is recommended for all adrenal incidentalomas. Ganglioneuromas are not typically associated with specific genetic mutations; however, rare associations with RET mutations in MEN2A/2B, and allelic loss at chromosome 1p have been described. Composite tumors with pheochromocytoma, though rare, must be excluded by thorough tissue sampling.

The key diagnostic challenge lies in distinguishing ganglioneuroma from ganglioneuroblastoma, which requires exhaustive tissue sampling to exclude any neuroblastic foci or nodules. The WHO classification recognizes two ganglioneuroma subtypes: maturing (minor component of maturing ganglion cells, not forming discrete nests) and mature (all ganglion cells fully mature). Treatment is complete surgical resection (adrenalectomy), and prognosis is excellent with no reported malignant transformation in pure ganglioneuromas.