CIC::DUX4 Sarcoma With Preferentially Expressed Antigen in Melanoma (PRAME) Immunopositivity

CIC-rearranged sarcomas are rare, high-grade, undifferentiated, small round cell sarcomas of bone and soft tissue classified by gene fusions involving the CIC gene with other gene partners, most commonly the DUX4 gene. These tumors tend to affect a wide age range, with a predilection for adult males, with the most common anatomical location being the deep soft tissues of the limbs or trunk. CIC-rearranged sarcomas have proven not only to be challenging to diagnose but also to treat due to their high resistance to conventional therapies. Preferentially expressed antigen in melanoma (PRAME) is an immunohistochemical stain that was developed primarily for the diagnosis of melanoma and has been shown to also be expressed in other epithelial and mesenchymal tumors. To date, PRAME immunopositivity has not been reported in CIC-rearranged sarcomas. Here, we report a 51-year-old male with a large gluteal undifferentiated small round cell sarcoma and bilateral lung metastases, whereby RNA sequencing confirmed the tumor as CIC::DUX4 sarcoma. Interestingly, the sarcoma demonstrated very strong PRAME immunohistochemical positivity, a diagnostic finding that has not yet been reported on CIC::DUX4 sarcomas and has potential use as a beneficial tool in the workup of a diagnostically challenging disease.