Usefulness of SS18-SSX antibody as a diagnostic marker for pulmonary metastatic synovial sarcoma

Abstract

Background The novel SS18-SSX fusion-specific antibody is reported to have high sensitivity and specificity for the diagnosis of primary synovial sarcoma (SS), which often metastasizes to the lung. Thus far, no study has validated the diagnostic efficacy of SS18-SSX antibody for pulmonary metastatic SS. Therefore, we aimed to investigate the usefulness of the SS18-SSX antibody in the diagnosis of pulmonary metastatic SS. Methods We evaluated the immunohistochemistry of SS18-SSX fusion-specific antibody (E9X9V) in 10 pulmonary metastatic SS cases and the corresponding five primary sites (four limbs and one mediastinum) in five patients, for whom SS was already diagnosed and confirmed by fluorescence in-situ hybridization in the metastatic and primary sites, and in 93 clinical and histologic mimics including 49 non-SS, pulmonary metastatic sarcomas, 39 primary lung cancers, and five intrathoracic solitary fibrotic tumors. All specimens were surgically resected at Shinshu University Hospital during 2001–2019. For primary and metastatic SS, we also evaluated SS18-SSX immunohistochemistry using needle biopsy and touch imprint cytology specimens from the primary site. Results SS18-SSX staining was diffusely-strongly positive in all 10 pulmonary metastatic SS cases and the corresponding five primary sites; whereas, it was negative in all 93 clinical and histologic mimics (100% sensitivity and 100% specificity). Further, SS18-SSX staining was also sufficiently positive in the biopsy and cytology specimens. Conclusions Immunohistochemistry of the SS18-SSX fusion-specific antibody is useful for the differential diagnosis of pulmonary metastatic SS in clinical practice. This simple and reliable method has the potential to replace traditional genomic tests. However, further studies are warranted in this regard.

Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma

“…Our study included 70 synovial sarcoma samples, 64 of which were positive cases (91%) by SS18-SSX IHC. This is concordant with published literature across 8 studies, which have recorded a total of 303 positive IHC results from 326 (93%) synovial sarcoma samples, with sensitivity ranging from 86 to 100% in their respective studies 14,20–26. Only one study attributed negative samples to a rare alternative fusion splice site, 23 while others alluded to technical factors arising from tissue handling 20,22,24.…”

“…This is concordant with published literature across 8 studies, which have recorded a total of 303 positive IHC results from 326 (93%) synovial sarcoma samples, with sensitivity ranging from 86 to 100% in their respective studies. 14,[20][21][22][23][24][25][26] Only one study attributed negative samples to a rare alternative fusion splice site, 23 while others alluded to technical factors arising from tissue handling. 20,22,24 Although we identified one technical false negative attributable to a freezing artifact, we were able to demonstrate that most cases are biological true negatives, where the fusion epitope is different from the one recognized by the diagnostic antibody.…”

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

“…The first goal we aimed at in this study was to confirm the high sensitivity and specificity of the SS18-SSX antibody in the diagnosis of SS in a retrospective cohort of SSs and its histological mimickers. Our results report a sensitivity of 95% and a specificity of 100% and are thus in perfect agreement with recently published data 13,17,19,22 –27 . In the largest reported series (400 tumors including 100 SSs and 300 mimics), Baranov et al who suggested for the first time that the IHC approach could replace molecular investigations to support SS morphological diagnosis 19 have obtained values perfectly overlapping with those presently reported.…”

SS18-SSX Expression in a Contemporary Cohort of Primary Renal Synovial Sarcoma: A Multi-Institutional Experience of Fourteen Patients

“…[14][15][16][17]19 TLE1 is usually focal and weak in LMS; however, can be diffuse in rare cases. 31 SS18-SSX IHC positivity is never reported in LMS . 26,31 Rhabdomyosarcoma has a myoD1 + /myogenin + /SS18-SSX-immunoprofile differentiating it from primary renal synovial sarcomas.…”