Track

Abstract

The diagnosis of high-grade dermal spindle cell neoplasms presents a significant challenge due to their histologic overlap with a broad spectrum of cutaneous spindle cell malignancies, including spindle cell squamous cell carcinoma, spindle cell malignant melanoma, cutaneous leiomyosarcoma, angiosarcoma, and atypical fibroxanthoma/pleomorphic dermal sarcoma. Diagnostic complexity is further compounded by rare instances of aberrant melanocytic marker expression, such as Melan-A/MART-1, which can lead to misclassification as spindle cell or desmoplastic melanoma. We report a diagnostically challenging case of a rapidly progressive high-grade dermal spindle cell neoplasm arising on the right knee of an elderly female, characterized by aberrant Melan-A/MART-1 expression and a novel YWHAE::ERBB2 gene fusion. Histopathologic evaluation revealed a multinodular proliferation of pleomorphic spindle cells extending from the dermis into deep soft tissue, with focal epidermal involvement and no associated squamous or melanocytic lesion. The tumor exhibited brisk mitotic activity(16 mitoses/10 HPF) and necrosis. Immunohistochemistry demonstrated positivity for CD10, Melan-A, CD99(patchy), CD31(weak), and vimentin, with negativity for cytokeratins, S100, SOX10, HMB-45, and BRAF V600E. Additional testing confirmed focal expression of MITF, PRAME, and p63 without intraepidermal melanocytic component. The histologic and immunophenotypic profile closely aligned with the feature of pleomorphic dermal sarcoma exhibiting aberrant melanocytic marker expression. Next-generation sequencing identified a novel YWHAE::ERBB2 fusion, not previously reported in cutaneous sarcomas. This case underscores the diagnostic pitfalls associated with aberrant melanocytic marker expression in high-grade dermal spindle cell neoplasms and highlights the importance of comprehensive molecular testing to refine diagnostic classification of this entity and guide potential targeted therapeutic strategies.