Melanoma Arising in Blue Nevus: A Case Report Demonstrating the Primary Site in Disseminated Disease

Blue nevus is a benign dermal lesion occasionally associated with malignant transformation into melanoma arising in a blue nevus, a rare and aggressive form of melanoma with different molecular features. Fewer than 200 cases have been reported worldwide. In this case study, a 78-year-old woman presented with a congenital bluish nodular lesion on the left buttock that enlarged over the years. Magnetic resonance imaging suggested a malignant soft tissue tumor. Surgical excision was performed, accompanied by an intraoperative histopathological study, reporting a melanoma with no dermoepidermal junction involvement. Immunohistochemistry confirmed the melanocytic origin; molecular analysis ruled out a BRAF gene mutation but identified a GNAQ exon 5 mutation in the melanoma and blue nevus components, confirming the precursor lesion. Despite multiple therapies, the disease progressed with metastases to the liver, lungs, and brain, ultimately resulting in the patient’s death. Melanoma arising in a blue nevus represents an aggressive neoplasm, highlighting the importance of early biopsy and multidisciplinary evaluation. The application of immunohistochemistry and molecular profiling in atypical presentations that mimic other neoplasms represents a valuable tool for diagnosis, prognosis, and treatment planning in rare melanoma subtypes.