EWSR1::NFATC2-rearranged sarcoma in bone-case report and review of the literature

Round cell sarcomas with EWSR1-non-ETS fusions are rare and entirely distinct from Ewing sarcoma with canonical fusion. Of these, EWSR1::NFATC2-rearranged sarcoma (ENS) has emerged as a distinct entity. Whereas few cases of ENS have been reported, clinical data regarding biologic behavior remain limited. In order to further characterize this rare sarcoma, we herein report a case of ENS arising in the tibia of a 21-year-old male, who initially presented with a several-year history of lower leg pain. Imaging showed a large, expansile and marrow-replacing lesion with focal cortical breakthrough. Biopsy showed monomorphic epithelioid and spindle cells with clear cell change, mimicking several entities including a myoepithelial tumor and perivascular epithelioid cell tumor (PEComa). Fluorescence in situ hybridization (FISH) was positive for EWSR1 gene rearrangement with selective amplification of the 5′ probe, and next-generation sequencing confirmed the presence of a EWSR1::NFATC2 translocation. The patient underwent radical resection of the tibial mass and showed no evidence of local recurrence or metastatic disease at 8 months post resection. Given the fully malignant potential of this tumor, knowledge of this rare entity is essential to ensure proper management and prevent misdiagnosis.