Cutaneous Rhabdomyosarcoma With FUS::TFCP2 Fusion: An Emerging Entity That Expands the Differential Diagnosis of ALK-Positive Spindle Cell Neoplasm of the Skin

Abstract: Rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion is an emerging subtype of rhabdomyosarcoma that rarely arises in skin. It is characterized by spindle and epithelioid morphology, and frequent expression of cytokeratin and anaplastic lymphoma kinase (ALK). We report a case of primary cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion in a 59-year-old man who initially presented with an erythematous lesion on the chest that progressed to a mass-forming lesion 6 months before his hospital visit. On examination, an irregularly shaped 12-cm indurated erythematous plaque with a 2-cm multinodular solid mass was observed. Histologic examination revealed sparse infiltration of round cells with minimal atypia within the thickened dermis of the erythematous area, while the mass exhibited fascicular or sheet-like proliferation of atypical spindle and epithelioid cells. Diffuse expression of ALK and cytokeratin, along with partial expression of alpha smooth muscle actin and desmin, raised suspicion of ALK -rearranged mesenchymal neoplasms, including inflammatory myofibroblastic tumor. However, fluorescence in situ hybridization (FISH) failed to detect ALK rearrangements. FUS::TFCP2 fusion was identified by RNA sequencing and confirmed by FISH. Additional immunohistochemistry for myogenin and MyoD1 demonstrated myogenic differentiation, leading to the final diagnosis. The patient underwent chemotherapy and surgical resection, followed by radiotherapy, and remains disease free for 8 months postoperatively. This case highlights the diagnostic challenges posed by aberrant ALK expression and the indolent appearance of early stage lesions. Awareness of this rare entity combined with molecular testing is crucial for accurate diagnosis and appropriate management.