When Synovial Sarcoma Hides in Plain Sight: A Diagnostic Wake-Up Call

A case report published in Frontiers in Oncology by Miyazaki, Oike, and colleagues at Niigata University Graduate School of Medical and Dental Sciences, Japan, documents a rare synovial sarcoma presentation that defeated every standard diagnostic test – and delayed correct treatment by over three years. The case carries urgent lessons for patients, advocates, and clinicians alike.

What the Case Involved

A 61-year-old woman presented with a growing mass on the back of her right thigh. Biopsy showed atypical cells in a prominent myxoid (jelly-like) background, and standard immunohistochemical markers used to identify synovial sarcoma – cytokeratin and EMA – were completely negative. SOX9, a marker typically associated with cartilage-forming tumors, was strongly positive. The team suspected extraskeletal myxoid chondrosarcoma (EMC), a chemotherapy-resistant subtype, and proceeded with surgery and radiation – without chemotherapy.

Lung metastasis appeared 15 months later, and local recurrence developed by 40 months. Only then, when comprehensive genomic profiling (CGP) was performed on the recurrent tumor, was the SS18–SSX1 fusion gene identified – confirming synovial sarcoma. The diagnosis was further verified by RT-PCR and FISH on both the original and recurrent specimens. Doxorubicin chemotherapy was initiated but disease progressed; the patient was transitioned to pazopanib with partial stabilization.

Why This Matters

The authors note this is the first reported case of synovial sarcoma in a limb combining diffuse myxoid stroma with complete absence of epithelial markers, confirmed by molecular fusion identification. Three takeaways stand out for the SS community:

The initial incorrect diagnosis directly shaped treatment. Because EMC is generally considered chemotherapy-insensitive, neoadjuvant systemic therapy was not pursued. A correct SS diagnosis at the outset would have changed those decisions. The authors acknowledge this explicitly as a missed diagnostic opportunity.

Standard immunohistochemistry can fail in synovial sarcoma. While over 90% of SS cases show at least focal cytokeratin or EMA positivity, this tumor had neither. SOX9 – present in the vast majority of synovial sarcomas – was misread as evidence of a different diagnosis entirely.

Molecular fusion testing is the gold standard and should happen early. The SS18–SSX fusion distinguishes synovial sarcoma from EMC and every other tumor in this patient’s differential. Had FISH, RT-PCR, or CGP been part of the initial workup, the diagnosis would have been established at biopsy, not 40 months later. The authors call for broader, earlier use of fusion-oriented genomic testing in any diagnostically challenging soft tissue tumor.

Ask for Biomarker Testing – It Opens Doors to Targeted Care

Biomarker testing doesn’t only confirm diagnosis – it determines what treatments you can access. If you or a loved one has synovial sarcoma, ask your care team whether these tests have been completed:

• HLA typing – a blood test checking immune markers required for cell therapies like Tecelra, an FDA-approved personalized therapy using your own immune cells to target cancer.
• MAGE-A4 testing – a tumor test required for Tecelra eligibility and related therapies.
• NY-ESO-1 testing – a tumor test that may qualify you for clinical trials or emerging treatments like lete-cel.

If these haven’t been ordered, request them now. National labs including Caris Life Sciences and Tempus specialize in sarcoma profiling. For printable resources to share with your care team, visit www.sarcomabiomarkertesting.com.

For more information, please refer to the original publication. 

For more information about the Synovial Sarcoma Foundation, please visit our website.