Abstract:

CIC-DUX4 Sarcoma (CDS) is a rare entity with fewer than 150 cases reported, characterized by gene fusion between CIC (19q13) and one of the two DUX4 retrogenes (4q35 or 10q26). It has an aggressive clinical course with a poor prognosis. Bearing a strong histologic resemblance to Ewing sarcoma, it is a major diagnostic consideration in the differential diagnosis of small round blue cell sarcomas negative for rearrangements in EWSR1, comprising approximately two thirds of such cases. By immunohistochemistry, strong nuclear WT1 expression–reported in 70-100% of CDS–along with ETV4 expression has been used to distinguish these entities. We present the case of a 23-year-old woman with a chest lesion that had been present for 2 years with rapid growth over the last two months. A biopsy was performed, which revealed a dermal proliferation of atypical small round cells with vesicular nuclei, variably prominent nucleoli, and amphophilic to slightly eosinophilic cytoplasm. Brisk mitotic activity, occasional multinucleation, and background myxoid stromal changes with ectatic vessels were present. An immunohistochemical work-up was performed, the results of which included expression of CD56, CD138 (subset), CD4 (subset), CD99 (patchy), and CD68 (subset), with no nuclear WT1 . Only upon detection of the CIC-DUX4 fusion by genomic profiling was the definitive diagnosis achieved. This case emphasizes the need to exercise caution when evaluating small round blue cell tumors based on morphology and immunohistochemistry alone. The minimal WT1 staining is highly unusual in CIC-DUX4 sarcoma, particularly in a cutaneous location. Additionally, the CD56 and patchy CD138 positivity could quickly lead to diagnostic confusion, raising the possibility of hematolymphoid malignancies. Given the rarity and imperfect characterization of cutaneous CDS, molecular studies can prove invaluable in the accurate diagnosis of this aggressive entity and other small round blue cell tumors in the skin.

Financial Disclosure:
No current or relevant financial relationships exist.

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Brandon Say, MD