Ganglioneuromas across age groups: Systematic review of individual patient data.

Background: Ganglioneuromas are very rare tumours of the sympathetic nervous system. Clinical and pathological knowledge is currently based on largely incomparable registries and case series that focus on paediatric or adrenal cases. To comprehensively characterize the full clinical spectrum across ages and locations, a meta-analysis was performed where amenable and complemented by systematic literature review of individual patient data (IPD).

Design: Articles containing "ganglioneuroma" in English on humans, published from 1/1/1995-6/27/2018, were identified from PubMed. Aggregate data from 10 eligible patient series on 19 variables were considerably inhomogeneous, restricting meta-analysis to age and gender distribution. To determine basic disease characteristics across ages and locations, IPD were retrieved from case reports and small case series (PROSPERO CRD42018010247).

Results: Individual patient data representing 364 cases revealed that 65.7% (60.6%-70.4%) were diagnosed in adults, more frequently in females (62%, 56.9%-66.9%). 24.5% (20.3%-39.1%) were discovered incidentally. Most often, ganglioneuromas developed in abdomen/pelvis (66.2, 32.1% adrenal). With age, the proportion of ganglioneuroma localizations with high post-surgical complication rate (35.6% head/neck and 16.3% thorax) decreased. Contrarily, the diagnosis of adrenal ganglioneuromas (<1% post-surgical complications) increased with age. Hormone production, hypertension or coincidence with another non-neuroblastic neural-crest-derived tumour component was more common for adrenal location. Recurrence and metastatic spread have not been reported for ganglioneuromas without secondary tumour component.

Conclusions: This work summarizes characteristics of the currently largest number of international GN patients across all ages. The data confirm a benign nature of GN, independent of age. Age-related differences in predominant tumour location, associated post-surgical complications and hormone production suggest case-centred management strategies.