FDG PET/CT as the Decisive Modality in Distinguishing Clear Cell Sarcoma from Melanoma When Immunohistochemistry Overlaps: A Case Report.

Clear cell sarcoma (CCS) and malignant melanoma share overlapping immunohistochemical profiles, particularly SOX10 and HMB45 positivity, making histopathological differentiation challenging. Distinguishing between these entities is clinically essential due to their differing prognoses and therapeutic approaches. This case highlights how fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) contributed decisively to establishing the diagnosis of CCS by following a pathologist-recommended diagnostic algorithm. A 70-year-old male presented with a progressively enlarging left scapular mass. Tru-cut biopsy revealed a malignant neoplasm positive for SOX10 and HMB45, with immunohistochemistry insufficient to differentiate CCS from metastatic melanoma. The pathology report recommended a search for a primary cutaneous melanoma, indicating that in the absence of such a lesion, the diagnosis should favor CCS. Whole-body 18 F-FDG PET/CT demonstrated extensive metastatic disease involving the lungs, left adrenal gland, T11 vertebra, scapula, and a large presacral mass. Critically, no hypermetabolic cutaneous, mucosal, or nodal lesions suggestive of a primary melanoma were identified. Comprehensive dermatological evaluation was also negative for suspicious melanocytic lesions. Based on the diagnostic algorithm, histopathology, plus exclusion of a primary melanoma, the PET/CT findings supported the diagnosis of metastatic CCS. This case demonstrates that 18 F-FDG PET/CT can serve as a diagnostic tool when histopathology alone is inconclusive. The absence of a primary melanoma on whole-body 18 F-FDG PET/CT and clinical examination was the decisive factor favoring CCS over melanoma of unknown primary. This case underscores the limitations of MRI, which often describes CCS as a well-defined, benign-appearing mass, potentially delaying accurate diagnosis.