Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile.

EWSR1/FUS::TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare tumor with an aggressive clinical course, a predilection for craniofacial bones, spindled and/or epithelioid histomorphology, and positive immunohistochemistry (IHC) for epithelial and myogenic markers, along with variable ALK expression. Herein, we present four additional cases of primary cutaneous TFCP2-rearranged RMS. Notably, one tumor (case 1) displayed a varied pathological spectrum, initially presenting as a low-grade spindle cell neoplasm, but progressed into a high-grade spindle/epithelioid tumor.

Expanding the molecular landscape of undifferentiated sarcomas of bone with a novel EWSR1-SSX3 gene fusion.

Undifferentiated sarcomas characterized by a primitive monomorphic round to spindle cell phenotype and often non-specific immunoprofile remain difficult to subclassify outside molecular analysis. The increased application of RNA sequencing in clinical practice led to significant advances and discoveries of novel gene fusions that furthered our understanding and refined classification of otherwise undifferentiated neoplasms. In this study, we report an undifferentiated round to spindle cell sarcoma arising in the femur of a 34-year-old female.