Atypical clear cell sarcoma of the pleura presenting as large pleural effusion with 22q12 abnormality: A challenging case with twists and turns

Primary clear cell sarcoma of soft tissue (CCSST) arising from the pleura is an infrequent occurrence, with only two cases reported in the English literature. We report a rare case of pleural CCSST with unusual clinical features and unconventional morphology. A 68-year-old man presented with a large right pleural effusion that developed following a dental abscess. He was treated with thoracentesis and antibiotics for suspected empyema without significant improvement. A CT-guided biopsy was performed and showed a malignant epithelioid neoplasm with significant pleomorphism and melanocytic differentiation, highly suggestive of a melanoma. The diagnosis was subsequently amended to CCSST based on the combined genetic findings (i.e., chromosome 22 abnormality, microsatellite stable status, no evidence of ultraviolet mutational signature, and lack of BRAF or any other mutations commonly identified in melanoma). Apart from the peculiar location, the present case showed several atypical features, such as older age at onset, unusual clinical presentations mimicking an infection, and unconventional morphology with significant pleomorphism and brisk mitotic activity. As such, it may be better classified as atypical CCSST. This case highlights the challenges in diagnosing CCSST and emphasizes the importance of including CCSST in the differential diagnosis of an epithelioid tumor with melanocytic differentiation.