Primary Central Nervous System Melanoma (pCNSM) and Treatment Protocols

Primary central nervous system melanoma (pCNSM) is an exceptionally rare malignancy arising from melanocytes of neural crest origin, with an annual incidence of just 0.005 per 100,000 individuals. Due to its rarity and the heterogeneity in tumor biology, no standardized treatment protocol currently exists. Immunotherapy has emerged as a promising approach, though its role in pCNSM remains underinvestigated. We conducted an extensive literature review spanning 1980 to 2023, analyzing data from PubMed, Google Scholar, published case reports, and the Archives of the American Institute for Radiologic Pathology. A total of 138 articles covering 148 pCNSM cases were included—77 involving primary brain melanomas and 71 involving primary spinal melanomas. Surgical resection, either gross total or partial, was performed in 95% of cases and typically followed by radiotherapy. Only 2 cases of brain melanoma received immunotherapy. Treatment approaches were largely similar between brain and spinal melanomas; however, primary spinal melanoma (PSM) cases showed better outcomes. Our review suggests that a multimodal strategy involving surgical resection followed by adjuvant radiotherapy and, where applicable, immunotherapy may offer improved outcomes, especially in spinal cases. However, the limited use of immunotherapy in brain cases and the overall rarity of pCNSM highlight the need for further multicenter research to identify more effective and tailored treatment protocols.