A case report of FUS::TFCP2 fusion sarcoma lacking myogenic and epithelial markers

Abstract Background FUS::TFCP2 fusion sarcoma is a rare, aggressive rhabdomyosarcoma subtype typically co-expressing myogenic (MyoD1, Myogenin) and epithelial (CKpan, EMA) markers together with ALK protein. Cases with complete lack of these markers are exceptionally uncommon and pose diagnostic challenges. Case presentation A 38-year-old woman presented with a painless mass in the right abdominal wall. Histological examination revealed a predominantly epithelioid tumor admixed with spindle cells. Immunohistochemistry showed positivity for ALK, Vimentin, and BCL-2, with retained SMARCA4 expression; p53 showed wild-type staining pattern; the Ki-67 proliferation index was approximately 10%. The tumor was completely negative for myogenic (MyoD1, Myogenin, Desmin) and epithelial (CKpan, EMA) markers. Molecular testing at Fudan University Shanghai Cancer Center using targeted RNA-based next-generation sequencing detected a FUS::TFCP2 gene fusion ( FUS exon 6 fused to TFCP2 exon 2) . No CDKN2A deletion was identified. The final diagnosis was confirmed as FUS::TFCP2 fusion sarcoma of the right abdominal wall. Unlike previously reported cases that show co-expression of myogenic and epithelial markers, this case demonstrated complete absence of both myogenic and epithelial marker expression—an extreme deviation from the classic immunophenotype. The patient underwent complete surgical excision and remained recurrence-free at 8 months of follow-up. Conclusion This case expands the immunophenotypic spectrum of FUS::TFCP2 fusion sarcoma and highlights that molecular testing is essential for definitive diagnosis when immunohistochemical findings are atypical.