Melanoma in an Unlikely Guise: Diagnostic Challenges of a Solid–cystic Popliteal Mass in Neurofibromatosis Type 1

Malignant melanoma (MM) uncommonly presents as a solid-cystic soft tissue mass, posing a significant diagnostic challenge. We report a rare case in a 63-year-old woman with neurofibromatosis type 1 (NF-1) who presented with a painful, rapidly progressive swelling on the posterior aspect of her right lower thigh. Imaging revealed a large, well-defined solid-cystic lesion suggestive of a soft tissue sarcoma or malignant peripheral nerve sheath tumor. Initial fine-needle aspiration cytology was nondiagnostic. Definitive diagnosis was achieved following wide surgical excision, with histopathological and immunohistochemical analysis confirming MM (strongly positive for S100, Melan-A, and SOX10). This case highlights that MM must be considered in the differential diagnosis of atypical cystic soft tissue lesions, even in anatomically unexpected locations, especially in patients with predisposing conditions such as NF-1 and affirms the indispensable integration of multimodality imaging with histopathological and immunohistochemical correlation in resolving diagnostically challenging soft tissue masses.