SSX1 (SSX Family Member 1)

These findings underscore the importance of integrating molecular techniques for precise diagnosis in synovial sarcoma. The results align with global patterns, emphasizing the necessity for molecular testing to enhance diagnostic accuracy and informing potential therapeutic advancements.

Sarcomas with EWSR1::SSX fusions are rare and clinically aggressive; the histologic patterns in this series and in prior reports are heterogeneous, consisting of essentially three phenotypes: 1) primitive round or epithelioid cells, 2) osteoblasts that produce bone, or 3) uniform small spindle cells arranged in tight fascicles, sometimes with a biphasic epithelioid component, as seen in synovial sarcoma. By studying 11 additional examples of these rare sarcomas, we provide an expanded view of their clinicopathologic and molecular genetic spectrum.

Discrepancies in vascular dynamics on DSA and atypical imaging features warrant suspicion for malignancy. Early histopathological validation is critical to prevent diagnostic delays, optimize multimodal therapy, and improve outcomes in this aggressive tumor.

PLK1 overexpression was closely associated with poor prognosis. Suppressing PLK1 expression significantly inhibited the growth, invasion, and migration of SS cells, promoted apoptosis, and blocked the G2/M phase of the cell cycle.

We speculate that the latter finding could have played a role in the neuroendocrine transformation and progression of this tumor. Herein, we present a rare case of epithelial-predominant SS with unusual neuroendocrine differentiation mimicking a carcinoma.

Given that SSX1 is normally expressed primarily in the testes, it is plausible that its ectopic expression leads to aberrant function within the chromatin remodeling complex. Ultimately, the C-terminal region of SSX1 was found to bind to the acidic patch within the nucleosome, and its structural details have been elucidated through cryo-electron microscopy.

Afterwards, an EWSR1::SSX1 fusion was detected by next-generation sequencing. There is scarce literature on non-SS18 fusion-driven synovial sarcomas, and no study has evaluated whether these novel molecular alterations have a relevant clinical impact on patients beyond the diagnostic value.

The patient received two cycles of neoadjuvant doxorubicin and ifosfamide, radical surgery and one cycle of adjuvant doxorubicin and ifosfamide. Mutations and fusions may be detected in patients with sarcoma using the TSO500 HT assay and total RNA sequencing. Furthermore, it is feasible to detect patient-specific TP53 ctDNA with ddPCR, and the plasma levels detected corresponded to the clinical picture observed in each patient.

Consequently, this leads to the downregulation of tumor suppressor genes occupied by SS18 physiologically, like CAV1 and DAB2. These results reveal the underlying mechanism of genomic disorder and tumorigenesis caused by the remodeling of oncoprotein SS18-SSX1 condensates at the macroscopic level.

SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost.

Atypical SS18-break apart FISH pattern with loss of green signal should be interpreted as a peculiar unbalanced rearrangement of the SS18 gene and subsequent SS18-SSX fusion (IHC or/and NGS) test should be recommended in such cases. Reseach are partially supported by grant of the The National Centre for Research and Development no. GOSPOSTRATEG-VI/0016/2021.

Our cases on atypical presentations of SS shows unusual morphological, immunophenotype, and molecular features. We consider it relevant to include SS as a differential diagnosis when faced with pseudo-vascular/alveolar patterns. Even in cases with more typical morphology of SS, there is a possibility of finding negative results in either IHC or FISH techniques due to cryptic or complex rearrangement.