Intracranial EWSR1::CREM fusion sarcoma presenting as a paraneoplastic inflammatory syndrome: illustrative case

BACKGROUND: Intracranial mesenchymal tumors with EWSR1::CREM fusion are rare neoplasms that can mimic common dural-based lesions like meningiomas and may present with atypical systemic features driven by tumor-associated inflammatory signaling. OBSERVATIONS: The authors report the case of a 31-year-old female who initially presented with unexplained anemia, systemic inflammatory symptoms, and difficulties with conception. Despite extensive hematological and rheumatological evaluation, no unifying diagnosis was identified. Imaging ultimately revealed a right frontal dural-based mass initially suspected to represent meningioma. She underwent gross-total resection, and pathological analysis demonstrated a high-grade sarcoma with EWSR1::CREM fusion. Notably, her systemic symptoms resolved completely following tumor removal, and the patient conceived approximately 1 month after resection. LESSONS: This case illustrates a rare intracranial EWSR1::CREM-fused tumor presenting with a paraneoplastic inflammatory syndrome that may have impaired conception in a reproduction-aged female. These lesions can radiographically mimic benign dural-based tumors such as meningioma while producing systemic inflammatory effects. Accurate diagnosis is critical, as tumor-directed therapy may result in resolution of both systemic symptoms and associated reproductive dysfunction. https://thejns.org/doi/10.3171/CASE26694.