SS18

The cancer-specific fusion oncoprotein SS18-SSX1 disturbs chromatin accessibility by hijacking the BAF complex from the promoters and enhancers to the Polycomb-repressed chromatin regions. This process relies on the selective recognition of H2AK119Ub nucleosomes by synovial sarcoma X breakpoint 1 (SSX1). However, the mechanism underlying the selective recognition of H2AK119Ub nucleosomes by SSX1 in the absence of ubiquitin (Ub)-binding capacity remains unknown. Here we report the cryo-EM structure of SSX1 bound to H2AK119Ub nucleosomes at 3.1-Å resolution. Combined in vitro biochemical and cellular assays revealed that the Ub recognition by SSX1 is unique and depends on a cryptic basic groove formed by H3 and the Ub motif on the H2AK119 site. Moreover, this unorthodox binding mode of SSX1 induces DNA unwrapping at the entry/exit sites. Together, our results describe a unique mode of site-specific ubiquitinated nucleosome recognition that underlies the specific hijacking of the BAF complex to Polycomb regions by SS18-SSX1 in synovial sarcoma.

Most cases of synovial sarcoma (SS) are aggressive and large-sized; only few show indolent behavior, having a small size. Nerves are rare sites of SS occurrence. An atypical case of SS can lead to its misdiagnosis as a benign tumor and delay its treatment.

Here, we report a case of primary SS of indolent multinodular synovial sarcoma of peripheral nerves. Considering the clinical and imaging findings at the first visit, we suspected a benign tumor and continued careful follow-up. Three years later, marginal resection was performed and SS was suspected. We then performed an additional wide resection using a free flap. Histopathologically, the proximal tumor showed a diffuse proliferation of spindle cells without pleomorphism, whereas the distal tumor showed a similar histology with more hypercellularity. Additional wide-resection specimens showed remnant tumors derived from the peripheral nerve. Immunohistochemistry (IHC) showed positive staining for SS18:SSX and SSX in both tumors and fluorescence in situ hybridization showed positive staining for the SS18 split in both tumors. Finally, SS of the peripheral nerve was diagnosed. Owing to FNCLCC grade 2 tumor and tumor size, adjuvant chemotherapy was not performed.

In cases of SS or other sarcomas with atypical clinical courses, with imaging findings mimicking benign tumors, we recommend marginal resection along with pathological examination for correct diagnosis.

We report a case of small gastric synovial sarcoma (SS) finally diagnosed after laparoscopic-endoscopic cooperative surgery (LECS). A 50 year-old male underwent medical examination for a chief complaint of epigastric pain. Endoscopic examination showed a 20 mm submucosal tumor (SMT) located in the anterior wall which extended to the lesser curvature of the middle stomach. The biopsy tissue did not yield a definitive diagnosis. During 6 months of follow-up for this lesion suspected to be an inflammatory tumor, neither the shape nor the size of the tumor changed. We performed LECS for both diagnosis and treatment. Histologically, the tumor was composed of fascicles of spindle cells. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen, cytokeratin (AE1/AE3) and S100 protein, while being negative for desmin, α-smooth muscle actin, CD34, c-kit and DOG1. The expression of INI1 was reduced. Fluorescence in situ hybridization (FISH) detected SS18 rearrangement. The SMT was diagnosed as primary SS. A SMT measuring < 20 mm might be malignant potential tumor such as SS even if there are no typical malignant findings by endoscopy. Surgical resection should be considered for SMT measuring < 20 mm with atypical findings even in the absence of definitive high-risk features.