Adrenal ganglioneuroma: Prognostic factors (Review)

Abstract

Ganglioneuroma, a rare neural crest‑derived tumor, exhibits a benign profile in contrast to other neuroblastic tumors (neuroblastoma/ganglioneuroblastoma). Ganglioneuromas can be found anywhere autonomic ganglia are located, mostly abdominal/pelvic sites followed by the adrenal glands (one‑third of cases), mediastinum/thorax and cervical area. Affecting especially children more than 10 years of age, Ganglioneuroma is either asymptomatic or may cause local compressive effects; rarely inducing nonspecific abdominal complains or arterial hypertension related to oversecretion of epinephrine/norepinephrine/dopamine. Despite a good prognosis, adrenalectomy is necessary in order to rule out a malignancy. Open procedure represents the standard therapeutic option; alternatively, centers with large laparoscopic pediatric experience and good stratification protocols have reported successful procedures. High uptake of I¹²³‑MIBG is associated with a more severe outcome in cases with increased mitotic index. In neuroblastic tumors, neuron‑specific enolase >33 ng/ml, age at diagnosis <49 months, and blood vessel invasion indicate a poor prognosis. Concurrent extra‑adrenal/adrenal ganglioneuroma is associated with a more severe prognosis; post‑surgical complications are more frequent in non‑adrenal vs. adrenal ganglioneuroma. Exceptionally, immune‑mediated paraneoplastic neurologic syndromes have been reported: anti‑N‑methyl‑D‑aspartate receptor encephalitis and opsoclonus‑myoclonus‑ataxia syndrome. ROHHAD syndrome is the underlying cause in 40‑56% of cases of neuroendocrine tumors including ganglioneuroma; 70% of tumors are diagnosed within the first 24 months after hypothalamic obesity onset, associated with a severe prognosis due to hypoventilation, sleep apnea, and dysautonomia. Recently, the PKB/AKT/mTOR/S6 pathway was identified as a tumorigenic pathway in pediatric ganglioneuroma, not in neuroblastoma; mTOR inhibitors are a potential option for pre‑operatory tumor shrinkage. Pediatric adrenal ganglioneuroma has a good prognosis if adequately treated; its recognition requires adrenalectomy. Further development of specific biomarkers is needed. In the present article, we aimed to introduce a review of the literature involving adrenal ganglioneuroma based on a practical, multidisciplinary perspective of prognostic factors.

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