1. ¹Santa Casa School of Medical Sciences and University of Sao Paulo, Sao Paulo, Brazil
2. ²Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK
3. ³Histopathology Department, St Thomas' Hospital, London, UK
4. ⁴The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
5. ⁵Department of Histopathology, Royal Marsden Hospital, London, UK
6. ⁶Department of Histopathology, Royal Brompton Hospital, London, UK
7. ⁷Institute of Orthopaedics and Musculoskeletal Science, University College London, Stanmore, Middlesex, UK
8. ⁸Department of Histopathology, University College Hospital, London, UK

Correspondence: Professor AM Flanagan, MD, FRC Path, PhD, Institute of Orthopaedics and Musculoskeletal Science, University College London, Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP, UK. E-mail: a.flanagan@ucl.ac.uk

Received 11 December 2006; Revised 11 January 2007; Accepted 16 January 2007; Published online 2 March 2007.

Abstract

Synovial Sarcoma consistently harbors t(X;18) resulting in SS18-SSX1, SS18-SSX2 and rarely SS18-SSX4 fusion transcripts. Of 328 cases included in our study, synovial sarcoma was either the primary diagnosis or was very high in the differential diagnosis in 134 cases: of these, amplifiable cDNA was obtained from 131. SS18-SSX fusion products were found in 126 (96%) cases (74 SS18-SSX1, 52 SS18-SSX2), using quantitative and 120 by conventional reverse transcriptase–polymerase chain reaction (RT-PCR). One hundred and one cases in a tissue microarray, analyzed by fluorescence in situ hybridization (FISH), revealed that 87 (86%) showed SS18 rearrangement: four RT-PCR positive cases, reported as negative for FISH, showed loss of one spectrum green signal, and 15 cases had multiple copies of the SS18 gene: both findings are potentially problematic when interpreting results. One of three cases, not analyzed by RT-PCR reaction owing to poor quality RNA, was positive by FISH. SS18-SSX1 was present in 56 monophasic and 18 biphasic synovial sarcoma: SS18-SSX2 was detected in 41 monophasic and 11 biphasic synovial sarcoma. Poorly differentiated areas were identified in 44 cases (31%). There was no statistically significant association between biphasic, monophasic and fusion type. Five cases were negative for SS18 rearrangement by all methods, three of which were pleural-sited neoplasms. Following clinical input, a diagnosis of mesothelioma was favored in one case, a sarcoma, not otherwise specified in another and a solitary fibrous tumor in the third case. The possibility of a malignant peripheral nerve sheath tumor could not be excluded in the other two cases. We concluded that the employment of a combination of molecular approaches is a powerful aid to diagnosing synovial sarcoma giving at least 96% sensitivity and 100% specificity but results must be interpreted in the light of other modalities such as clinical findings and immunohistochemical data.