What is the fuss about FUS fused rhabdomyosarcoma?

Abstract Introduction/Objective Rhabdomyosarcoma (RMS) is a rare and aggressive soft tissue sarcoma that primarily affects children and adolescents. It arises from primitive mesenchymal cells committed to skeletal muscle differentiation. Understanding the molecular drivers and genetic alterations underlying RMS is crucial for developing targeted therapies and improving patient outcomes. Recently, a novel fusion event involving the transcription factor CP2-like protein 2 (TFCP2) and fused in sarcoma (FUS) has emerged as a potential oncogenic driver in a subset of RMS cases. This fusion event represents a novel genetic alteration with implications for RMS pathogenesis, diagnosis, and therapeutic strategies. Methods/Case Report A 58-year-old female presented with a tender fullness along the right mandibular body. A biopsy performed at an outside institution was notable for a spindle cell neoplasm. She underwent resection of the lesion with pathology demonstrating a predominantly monomorphic spindle cell sarcoma with focal areas of pleomorphism. The lesion was diffusely positive for MyoD1. SOX10, S100, H-caldesmon, SMA, and pan-cytokeratin were negative. H3K27me3 was retained, arguing against malignant peripheral nerve sheath tumor with extensive rhabdomyoblastic differentiation. Break-apart FISH studies for FUS gene were positive. Overall, the findings were those of a recently described RMS variant with rearranged TFCP2 gene with FUS or EWSR1 as the partner gene. The patient later received adjuvant chemotherapy and radiotherapy. Despite that, her restaging scan 12 months later showed rapid progression with involvement of lungs, bone, and local recurrence in the jaw bilaterally. Results (if a Case Study enter NA) NA Conclusion TFCP2-FUS gene fusion drives an emerging family of RMS with a predilection for the jaws. Recognition of this rare entity can guide personalized therapeutic approaches and improve the prognostic stratification of RMS patients