Abstract
BACKGROUND: Primary melanocytic neoplasms of the central nervous system (PMN-CNS) are rare lesions of variable aggressiveness originating from leptomeningeal melanocytes. They present as either circumscribed or diffuse lesions within the CNS. Given the limited number of reported cases, survival and recurrence outcomes are poorly understood. METHODS: A retrospective chart review of all local adult (≥18 years) cases of PMN-CNS across four centres in Canada, the United States and Germany (1993-present). RESULTS: Forty-eight cases were identified, with median age at diagnosis of 58 years (IQR: 38-68), 52% female. Tumour locations included cerebrum (30, 63%), spine (10, 21%), multifocal (6, 13%) and diffuse (1, 2%). Twelve (25%) tumours had confirmed GNAQ/GNA11, five (10%) NRAS, two (4%) BRAF V600E and one (2%) BRAF V600K mutations. BAP1 deletions were identified in two (4%) cases. Operative outcomes were: gross total resection (22, 46%), subtotal resection (18, 38%) and biopsy-only (5, 10%). Surgery was followed by adjuvant radiotherapy in 31 (65%) cases and adjuvant chemotherapy and/or immunotherapy in 26 (54%) cases, with various combinations of nivolumab/ipilimumab, pembrolizumab, temozolomide, dabrafenib, trametinib, encorafenib and binimetinib. Radiographic recurrence was observed in 24 (50%) cases at a median of 14 (95% CI: 11, —) months postoperatively. Median overall survival time was 26 months (95% CI: 18, —). CONCLUSIONS: There is substantial heterogeneity in the molecular and clinical characteristics of PMN-CNS. As the largest multicenter cohort study of this tumour class, our findings will help to define the natural history of the disease, assist in prognostication and guide treatment.