Test ID: 86177
Synovial Sarcoma (SS), 18q11.2 (SS18 or SYT) Rearrangement, FISH, Tissue

As an aid in the diagnosis of synovial sarcoma when RT-PCR results are equivocal or do not support the clinical picture

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 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 (IHC) markers can be helpful in the correct diagnosis of these various tumor types, recent molecular studies have shown the superior specificity of molecular markers 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) (#83361 Synovial Sarcoma by Reverse Transcriptase PCR, Paraffin), 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 18q11.2 SS18 gene rearrangements in these tumors, which supports the diagnosis of SS.

An interpretive report will be provided.

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the SYT FISH probe.

A positive result suggests rearrangement of the SYT gene region at 18q11.2 and supports the diagnosis of synovial sarcoma (SS).

A negative result suggests no rearrangement of the SYT gene region at 18q11.2. However, this result does not exclude the diagnosis of SS.

This test is not approved by the U.S. Food and Drug Administration (FDA) and it is best used as an adjunct to existing clinical and pathologic information.

A blinded investigation was performed on 36 formalin-fixed, paraffin-embedded tissues including 14 synovial sarcoma (SS) tumors and 22 normal tissues or non-SS tumors. Each SS specimen had been previously characterized to carry the t(X;18) via RT-PCR analysis. Eleven tumors had the SSX1 translocation partner and 3 tumors had the SSX2 translocation partner. Two technologists each scored 100 interphase nuclei for each specimen. Once unblinded, the results showed that all 22 normal tissues and non-SS tumors yielded normal results, while all 14 SS specimens were correctly identified as abnormal. The expected break-apart signal pattern was observed in 10 patients, while 4 patients demonstrated atypical break-apart signal patterns.

1. Sandberg AA, Bridge JA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Synovial sarcoma. Cancer Genet Cytogenet 2002 Feb;133(1):1-23

2. Kokovic I, Bracko M, Golouh R, et al: Are there geographical differences in the frequency of SYT-SSX1 and SYT-SSX2 chimeric transcripts in synovial sarcoma? Cancer Detect Prev 2004;28(4):294-301