Case Report: Synovial sarcoma with diffuse myxoid stroma and complete absence of epithelial differentiation in the...

Synovial sarcoma is a translocation-associated soft-tissue sarcoma defined by the SS18-SSX fusion gene and typically exhibits biphasic or monophasic histology with at least focal epithelial marker expression. However, rare cases with diffuse myxoid stroma may closely mimic other myxoid sarcomas, which can pose a diagnostic challenge. A 61-year-old woman presented with a gradually enlarging mass on the posterior aspect of the right thigh. Magnetic resonance imaging revealed a 55-mm soft tissue tumor with heterogeneous high signal intensity on T2-weighted images and partial contrast enhancement. Core needle biopsy demonstrated atypical spindle to round cells within a prominent myxoid background. Immunohistochemically, cytokeratin was negative and SOX9 was diffusely positive, raising suspicion for extraskeletal myxoid chondrosarcoma. The patient underwent marginal excision followed by postoperative radiotherapy; however, lung metastasis and local recurrence subsequently developed. Comprehensive genomic profiling identified an SS18-SSX1 fusion gene, and the diagnosis of synovial sarcoma was confirmed by fluorescence in situ hybridization and reverse transcription polymerase chain reaction in both the primary and recurrent tumors. RNA sequencing further verified the SS18-SSX1 fusion and demonstrated no additional pathogenic or clinically relevant fusion transcripts. Histologically, the tumor consistently exhibited a diffuse myxoid stroma with a focal reticular pattern, closely resembling extraskeletal myxoid chondrosarcoma. It lacked epithelial marker expression, including cytokeratin and epithelial membrane antigen (EMA), throughout the disease course. To our knowledge, this case represents a rare presentation of synovial sarcoma arising in the extremity with diffuse myxoid stroma and complete absence of epithelial marker expression, with the diagnosis confirmed by molecular identification of the specific fusion transcript. This case highlights that synovial sarcoma can exhibit a myxoid phenotype and may lack epithelial marker expression, both of which can complicate the diagnosis. It also underscores the importance of integrating molecular analyses, particularly fusion-oriented genomic testing, for accurate diagnosis in challenging soft-tissue tumors.