Metastatic Vaginal Melanoma: A Case Report

Background Primary vaginal melanoma is a rare malignancy, accounting for less than 1% of all melanomas in women. In contrast to cutaneous melanomas, mucosal tumors are not associated with ultraviolet (UV) radiation, have distinct clinical courses and biological/mutational profiles, rarely harbor B-Raf proto oncogene (BRAF) mutations, and ultimately respond poorly to standard therapy regimens. Here, we present the case of metastatic primary vaginal mucosal melanoma harboring co-occurring sensitizing and resistance-associated mutations in the KIT gene. Case Presentation A 68-year-old postmenopausal woman presented with pelvic pain and a vaginal mass. Biopsy confirmed a diagnosis of mucosal melanoma and concurrent vulvar melanoma in situ. Positron emission topography (PET)/computed tomography (CT) revealed widely metastatic disease, and she was transferred to our care. A liver biopsy was performed to confirm metastatic disease and obtain tissue for molecular profiling. Next-generation sequencing (OmniSeq INSIGHT, Labcorp; Buffalo, NY) demonstrated co-occurring KIT mutations (L576P and V654A), low tumor mutational burden (7.1 mut/Mb), and no evidence of BRAF mutation. She was treated with nivolumab plus relatlimab-rmbw. The patient experienced disease progression and received palliative radiation, which failed to provide symptomatic relief. The patient expired less than six months after diagnosis. Conclusion This case demonstrates the unique features and care limitations of mucosal melanomas. To our knowledge, co-occurring KIT L576P AND V654A mutations in a treatment-naïve primary vaginal melanoma have not been described in previous reports. This finding underscores the complexity of molecular profiling in guiding treatment decisions.