252 Clinicopathological Features of Round Cell Sarcomas Harboring EWSR1::PATZ1 Fusion, CIC Rearrangement, and BCOR Genetic Alteration: A Report of Four Cases from a Single Institution

Introduction/Objective Small round cell sarcomas (SRCSs) encompass a heterogeneous group of neoplasms, some of which were previously classified as Ewing-like sarcomas. Advances in molecular diagnostics have enabled reclassification based on specific gene fusions and alterations, including EWSR1-non-ETS fusions, CIC rearrangements, and BCOR mutations. However, the clinicopathologic features of these rare entities remain poorly defined, posing diagnostic and therapeutic challenges—particularly for EWSR1::PATZ1 sarcomas. Methods/Case Report We retrospectively reviewed four genetically confirmed SRCSs at our institution. Clinical and pathological data were obtained from the electronic medical records. Results Case 1: A 30-year-old man with a left supraclavicular mass; histology was non-specific; TLE1, BCL2, and GFAP positivity raised suspicion for synovial sarcoma or ependymoma; NGS identified EWSR1::PATZ1 fusion. Case 2: A 53-year-old woman with a right gluteal mass showing high-grade tumor with rhabdoid morphology; CIC::DUX4 fusion identified. Case 3: A 14-year-old girl with an incidental abdominal spindle cell tumor; KTM2D::BCOR fusion detected. Case 4: A 15-year-old boy with recurrent abdominal mass post-rhabdomyosarcoma treated with whole abdominal radiation; showed BCOR alteration and NRAS mutation. Conclusion Genomic profiling is essential for accurately subclassifying SRCSs. While pathognomonic alterations aid diagnosis, the lack of well-described clinicopathological features continues to hinder recognition and optimal management.