SS18::SSX fusion (synovial sarcoma)

What is measured: the SS18::SSX fusion from t(X;18)(p11;q11). How: FISH with an SS18 break-apart probe, RT-PCR or targeted RNA sequencing naming the partner (SSX1 in about two-thirds, SSX2 in a third, SSX4 rarely), or immunohistochemistry with the fusion-specific SS18-SSX antibody (about 95 percent sensitive and near 100 percent specific) and the SSX C-terminus antibody; TLE1 staining is a sensitive but less specific screen. The fusion protein hijacks the BAF (SWI/SNF) chromatin-remodelling complex and displaces SMARCB1, which is why the tumours are partly INI1-deficient; a poorly differentiated component and size over 5 cm worsen the outlook. About 70 percent express MAGE-A4 and 80 percent NY-ESO-1, cancer-testis antigens. What a result changes: it settles the diagnosis against MPNST, solitary fibrous tumour, Ewing sarcoma and poorly differentiated carcinoma; synovial sarcoma is more chemosensitive than most sarcomas (ifosfamide with doxorubicin); with MAGE-A4 immunohistochemistry and HLA-A*02 typing it qualifies patients for afamitresgene autoleucel (approved 2024) and NY-ESO-1-directed letetresgene autoleucel; BRD9 degraders and other BAF-directed drugs are in trials. Where it matters: synovial sarcoma.