GNAQ mutation in primary spinal melanoma: illustrative case

Primary melanoma in the spine is a rare tumor characterized by lack of primary dermal or uveal lesions. The infrequency of this tumor significantly obfuscates both its diagnosis and treatment.

The authors describe the case of a 74-year-old male who presented with back pain, lower extremity weakness, and numbness. MRI revealed a contrast-enhancing intradural, extramedullary lesion at T11-12 with a hypointense signal on T2-weighted imaging. The patient underwent resection of the lesion. The diagnosis of primary spinal melanoma was confirmed by histopathology, immunohistochemical studies, and lack of primary lesions on dermatological and ophthalmological examination. Next-generation sequencing also revealed a guanine-nucleotide binding protein (GNAQ) mutation.

The authors present a potential mechanism of primary spinal melanoma tumorigenesis associated with GNAQ. GNAQ mutations lead to abnormal β-catenin activation in neural crest cells, resulting in differentiation into melanoblasts and migration to the spinal cord. Over time, GNAQ mutations can lead to aberrant proliferation of ectopic melanocytes due to downstream activation of the RAS/RAF signaling pathway. Understanding this pathomechanism and its role in primary CNS melanoma may provide a route for potential targeted therapy. https://thejns.org/doi/10.3171/CASE25183.