Spindle cell/sclerosing rhabdomyosarcoma is an infrequent subtype of rhabdomyosarcoma according to the World Health Organization Classification of Soft Tissue and Bone Tumours, which includes a novel category of intraosseous spindle-cell rhabdomyosarcomas (ISCRMS) with EWSR1:: or FUS::TFCP2 fusions. We report a case of ISCRMS with EWSR1::TFCP2 fusion presenting in the femur mimicking osteosarcoma in this unusual primary location. We present an 18-year-old male with relapsed widely metastatic sarcoma, morphologically identical to osteosarcoma responding poorly to chemotherapy, initially presenting in the distal femur. Sections showed a high-grade malignant neoplasm with sheets of epithelioid and spindled cells without obvious rhabdomyoblastic differentiation morphologically containing focal areas resembling new bone/osteoid formation. Molecular sequencing identified t(12;22) EWSR1::TFCP2. The tumor cells were diffusely positive for pancytokeratin, MyoD1, and ALK by retrospective immunohistochemistry. Desmin and SATB2 were focally positive. Myogenin was negative, and INI-1 expression was retained. ISCRMS commonly involves craniofacial and pelvic bones, but rarely originates in long bones, as in this case. Initially, osteosarcoma was the primary diagnostic consideration based on distal long bone location, patient age, and evidence of osteoid formation. Distinction between the two entities may be nearly impossible on morphologic grounds alone, which presents a diagnostic pitfall without molecular or extensive immunoprofiling data.
Keywords: EWSR1::TFCP2; bone tumor; intraosseous spindle cell rhabdomyosarcoma; pediatric.