ID #1020 Primary Intracranial Sarcoma With DICER1 Mutation Mimicking Chronic Subdural Disease in a Young Child

Abstract Intro We describe a rare case of DICER1-associated primary intracranial sarcoma presenting with atypical clinical and pathological features, underscoring diagnostic challenges and the importance of molecular testing. The DICER1 gene encodes an RNase III enzyme essential for microRNA processing and gene regulation. Pathogenic DICER1 alterations predispose children to rare and aggressive central nervous system tumors, including pituitary blastoma, embryonal tumor with multilayered rosettes, and primary intracranial sarcoma. Case Presentation A 3-year-old male with a history of bilateral subdural hematomas from non-accidental trauma in infancy presented with several months of red eye and was found to have bilateral papilledema. MRI demonstrated complex bilateral subdural fluid collections, right greater than left, with interval progression compared with imaging two years earlier. Bilateral burr holes evacuated thick, clear gelatinous fluid, and subdural drains were placed. Six weeks later, the patient re-presented with headache, vomiting, fatigue, and decreased appetite. Imaging showed worsening extra-axial collections, prompting bilateral craniotomies with biopsy. Pathology revealed a poorly differentiated neoplasm with epithelioid and myxoid spindle cell components, positive for TLE, actin, and desmin, raising concern for aggressive sarcoma. The diagnosis remained uncertain, and tissue was submitted for molecular analysis. During this period, the patient experienced rapid clinical decline, leading to initiation of vincristine, irinotecan, and temozolomide, with symptomatic improvement. Results Copy number variation analysis demonstrated amplification of MET and MYC, and further DNA sequence analysis identified a pathogenic DICER1 mutation. Therapy was transitioned to ICE chemotherapy (ifosfamide, carboplatin, etoposide) for seven cycles, followed by adjuvant intensity-modulated radiation therapy to 60.2 Gy. The patient achieved clinical remission and remains disease-free six months after completing therapy. Conclusion This case highlights the essential role of molecular diagnostics in accurately classifying rare pediatric CNS tumors and guiding risk-adapted treatment in aggressive disease.