SS18-SSX Antibody: A Useful Tool to Save Time and Reduce Costs in Synovial Sarcoma Diagnosis. Proposal of a Novel Diagnostic Algorithm

Abstract

Synovial sarcoma is a rare malignant mesenchymal neoplasm mostly affecting young adults, characterized by a specific translocation which results in the fusion of the SS18 gene on chromosome 18 with one of the three highly homologous SSX genes on chromosome X. Its morphological diagnosis, especially in monophasic or poorly differentiated variants, can be challenging because histological features often overlap with other malignant mesenchymal tumors. Until recently, the differential diagnosis mostly relied on the use of cytogenetic or molecular analyses to detect the specific t(X;18)(p11;q11) translocation, thus virtually restricting its correct identification to referral centers with a high histological and molecular pathology workflow. The recently commercialized highly sensitive and fusion-specific SS18-SSX antibody has significantly improved the approach to these tumors, representing a relatively cheap and easy to access tool for synovial sarcoma diagnosis. Through a retrospective analysis of 79 synovial sarcomas and histological mimickers, this study confirms the usefulness of the SS18-SSX antibody in the diagnosis of synovial sarcoma, particularly focusing on its application in the pathological response evaluation after neoadjuvant treatment as well as its time- and cost-saving advantages. Finally, we here propose a new diagnostic algorithm to apply into the routine practice.

Keywords: diagnosis; fluorescent in situ hybridization; immunohistochemistry; neoadjuvant treatment response.

Figure 1.

(A–C) Monophasic SS (A: H&E, 200×, selected area 400×) with a diffuse and homogeneous strong nuclear staining for SS18-SSX antibody (B: SS18-SSX IHC, 200×) as well as a positive FISH analysis showing a typical SS18 break-apart pattern (C: FISH 1F + 1G + 1R pattern). (D–F) Monophasic SS (D: H&E, 200×, selected area 400×) with a diffuse and strong nuclear staining for SS18-SSX antibody (E: SS18-SSX IHC, 200×) but with an atypical SS18 break-apart FISH pattern (F: FISH 1F + 1R, white arrow). (G–I) Biphasic SS (G: H&E, 200×, selected area 400×) with a negative staining for SS18-SSX antibody (H: SS18-SSX IHC, 200×) and a classical SS18 break-apart FISH pattern (I: FISH 1F + 1G + 1R). Scale bar 200 µm. Abbreviations: FISH, fluorescence in situ hybridization; SS, synovial sarcoma; IHC, immunohistochemical; 1F, one fusion; 1G, one green; 1R, one red.

Figure 2.

Monophasic SS in a 7-year-old patient. (A–C) Pretreatment biopsy: a monomorphic spindle cell proliferation (A: H&E, 200×) with a diffuse and strong nuclear staining for SS18-SSX antibody (B: SS18-SSX IHC, 200×) and an atypical SS18 break-apart FISH pattern (C: FISH 1F + 1R, white arrow). (D and E) Post-treatment sample: a single and marginal focus of residual disease in a background of diffuse hyaline fibrosis is highlighted by SS18-SSX antibody (D: H&E, 200×; E: SS18-SSX IHC, 200×). Scale bar 200 µm. Abbreviations: FISH, fluorescence in situ hybridization; IHC, immunohistochemical; SS, synovial sarcoma; 1F, one fusion; 1R, one red.

Figure 3.

Proposal of a new diagnostic algorithm for cases morphologically suspicious for SS. Abbreviations: SS, synovial sarcoma; RT-PCR, reverse transcription polymerase chain reaction; IHC, immunohistochemical; EMA, epithelial membrane antigen; FISH, fluorescence in situ hybridization; NGS, next-generation sequencing.