Contribution of molecular profiling in primary cervical intramedullary melanoma: case report and literature review

Primary spinal cord melanoma (PSCM) is an exceptionally rare tumor. While primary central nervous system (CNS) melanomas account for approximately 1% of all diagnosed melanomas, strictly intramedullary localizations are even more unusual. Differentiating PSCM from a spinal metastasis is a diagnostic challenge, particularly in patients with a history of cutaneous melanoma. We report a case where molecular profiling proved decisive in establishing the diagnosis and guiding therapy.

An 80-year-old man presented with progressive cervical myelopathy. MRI revealed a C1-C2 intramedullary lesion, initially suspected as a metastasis given his history of cutaneous melanoma. Surgical biopsy confirmed a melanocytic tumor. While standard histology inherently cannot differentiate a primary lesion from a metastasis, in our specific case, heavy pigmentation and small sample size also prevented the assessment of the mitotic index and cellular pleomorphism. An initial immunohistochemical suspicion of a BRAF mutation, resulting from a misinterpretation caused by heavy melanin pigment hindering the analysis, was ruled out by molecular biology (NGS). NGS revealed a GNAQ mutation and a BRAF wild-type status. Following a negative extension workup excluding other GNAQ-mutated primaries, and given the patient's clinical deterioration, the diagnosis of primary intramedullary melanoma was confirmed. The therapeutic strategy shifted to adjuvant immunotherapy combined with focal radiotherapy, later discontinued due to severe immune-mediated myocarditis.

This case highlights the crucial role of molecular profiling in the diagnostic workup of intramedullary melanocytic lesions. The identification of GNAQ mutations, after the exclusion of other GNAQ-mutated primaries, supports a primary CNS origin, whereas BRAF mutations suggest a metastatic origin. Accurate diagnosis drastically alters the oncological management.