Superficial CIC::DUX4 Sarcoma With Focal WT1 Expression: Histomorphologic Clues and Immunohistochemical Pitfalls

CIC::DUX4 sarcoma (CDS) is a rare cutaneous and deep soft tissue tumor in the differential diagnosis of small round blue cell sarcomas. CDS, by definition, is negative for rearrangements in EWSR1, and has been reported to have strong nuclear WT1 expression and ETV4 expression in most published cases so far. We herein report a case of challenging CDS diagnosed by genomic profiling, with weak, focal cytoplasmic WT-1 positivity, positive staining for CD56, CD138 (subset), and CD4 (subset). This case highlights the challenges involved in evaluating cutaneous small round blue cell tumors based on morphology and immunohistochemistry alone, especially in the presence of an atypical immunophenotype.