Synovial Sarcoma (SS), 18q11.2 (SS18 or SYT) Rearrangement, FISH, Tissue
Supporting the diagnosis of synovial sarcoma when used in conjunction with an anatomic pathology consultation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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)(p11.2q11.2) 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 [RT-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 SS18 gene rearrangements in these tumors, which supports the diagnosis of SS.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
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 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA and is best used as an adjunct to existing clinical and pathologic information.
Fixatives other than formalin (eg, Prefer, Bouin's) may not be successful for FISH assays. Although FISH testing will not be rejected due to nonformalin fixation results may be compromised.
Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.
FISH analysis was performed on 36 formalin-fixed, paraffin-embedded tissue samples including 14 synovial sarcoma (SS) tumors and 22 noncancerous controls or non-SS tumors. The normal controls were used to generate a normal cutoff for this assay. Each SS specimen had been previously characterized to carry the t(X;18) via reverse transcriptase-PCR analysis. Eleven tumors had the SSX1 translocation partner and 3 tumors had the SSX2 translocation partner. Rearrangement of SS18 was identified in all 14 SS specimens with the expected break-apart signal pattern observed in 10 patients and 4 patients demonstrated atypical break-apart signal patterns.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Fisher C, de Brujin DRH, Guerts van Kessel A: Chapter IX: Synovial sarcoma. In World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Soft Tissue and Bone. Edited by CDM Fletcher, KK Unni, F Mertens. Lyon, IARC Press, 2002, pp 200-204
2. Sandberg AA, Bridge JA: Updates on the cytogenetics and tissue tumors. Synovial sarcoma. Cancer Genet Cytogenet 2002 Feb;133(1):1-23
3. Kokovic I, Bracko M, Golouh R, et al: Are there geographical chimeric transcripts in synovial sarcoma? Cancer Detect Prev 2004;28(4):294-301