The diagnosis of primary renal synovial sarcoma (PRSS) is challenging due to nonspecific clinical semiology mimicking renal carcinoma and significant histologic overlap with other kidney tumors like sarcomatoid renal cell carcinoma, clear cell sarcoma of the kidney (CCSK), and BCOR-altered sarcoma, necessitating molecular confirmation via the detection of SS18::SSX gene fusion. This case report highlights a 39-year-old male patient presenting with abdominal pain and hematuria. Imaging revealed a large, heterogeneously enhancing left renal mass. Left-sided nephrectomy revealed a tumor, which on histopathology revealed a monophasic spindle cell neoplasm with areas of necrosis. Immunohistochemistry (IHC) demonstrated diffuse positivity for pan-keratin (clone AE1/AE3), EMA, CD99, BCL2, cyclin D1, SS18, and paradoxically, BCOR—a marker classically associated with BCOR-rearranged sarcoma/CCSK. Fluorescence in situ hybridization assay confirmed SS18 gene rearrangement without the presence of BCOR gene molecular alterations, establishing the diagnosis of monophasic synovial sarcoma. This case report highlights a critical diagnostic pitfall comprising of aberrant BCOR immunoreactivity, usually reported in synovial sarcomas of soft tissues, but hitherto unreported in PRSS. This aberrant immunoexpression of BCOR probably reflects epigenetic dysregulation, occurring in the absence of underlying BCOR genetic rearrangements. Coexpression of BCOR and cyclin D1 can also lead to a misdiagnosis as CCSK. Therefore, owing to overlapping IHC profiles, definitive diagnosis of PRSS warrants SS18::SSX gene molecular testing to avoid misclassification, especially given the therapeutic and prognostic implications. Integration of morphology, IHC, and molecular studies remains paramount for accurate diagnosis of such rare renal spindle cell neoplasms.
