Clinical Information

Synovial sarcoma (SS) is a malignant soft tissue tumor that predominantly occurs in the lower limbs of children and young adults. This tumor accounts for approximately 5% to 10% of soft tissue tumors, has a poor prognosis, and may occur in other areas of the body such as the head and neck, heart, abdominal wall, mediastinum, and lung, in addition to the extremities. Histologically, SS is grouped either into the monophasic subtype consisting of mostly spindle cells or the biphasic subtype consisting of epithelial and spindle cells. Depending on the site of origin, the differential diagnosis of SS can include mesothelioma, fibrosarcoma, solitary fibrous tumor, leiomyosarcoma, malignant peripheral nerve sheath tumors, epithelioid sarcoma, and clear cell sarcoma. In addition, when the SS is poorly differentiated, the differential diagnosis broadens to include the small round-blue cell tumors (Ewing sarcoma, alveolar rhabdomyosarcoma, and neuroblastoma). Accurate diagnosis of SS is important for appropriate clinical management of patients. Although immunohistochemical markers can be helpful in the correct diagnosis of these various tumor types, recent molecular studies have shown the superior specificity of molecular makers in differentiating SS from other tumors.

A recurrent, tumor-specific translocation t(X;18)(p11.2;q11.2) is observed in approximately 90% of synovial sarcomas. A single gene, SS18 (SYT), has been implicated on 18q11.2, while 1 of 3 related genes, SSX1, SSX2, or infrequently SSX4, is usually involved on Xp11.2. The prevalence of SS18-SSX1 is about twice that of SS18-SSX2 in most studies. Detection of these transcripts is usually performed by reverse transcriptase-PCR (RT-PCR) (SYT / Synovial Sarcoma RT-PCR), which allows specific identification of SS18-SSX1 or SS18-SSX2. Identification of the SS18-SSX1 fusion is associated with an unfavorable outcome with significantly shorter overall survival when compared to the SS18-SSX2 fusion. Unfortunately, RT-PCR results may be equivocal or falsely negative due to many reasons such as when the available RNA is of poor quality or if a rare translocation partner is present. In these cases, FISH testing can be used to identify SS18 gene rearrangements in these tumors, which supports the diagnosis of SS.