Gliosarcoma of the craniovertebral junction with loss of H3K27me3: a case report with molecular profiling.

Gliosarcoma is a rare and aggressive variant of glioblastoma characterized by biphasic glial and sarcomatous components. Lesions arising from the craniovertebral junction or brainstem are extremely uncommon, and their molecular pathogenesis remains poorly understood. A 69-year-old woman presented with rapidly progressive quadriparesis. Magnetic resonance imaging demonstrated an enhancing mass extending from the clivus to the medulla and an additional lesion in the ventricular trigone. Partial resection via an endoscopic transpharyngeal transclival approach achieved decompression. Histologically, the tumor exhibited distinct glial and sarcomatous components, with loss of H3K27me3 expression restricted to the sarcomatous areas. Comprehensive molecular profiling revealed mutations in PTEN, SUZ12, TERT, and EPHB1. Despite adjuvant radiation therapy, temozolomide, and bevacizumab, leptomeningeal dissemination occurred, and the patient died five months postoperatively. This rare case of gliosarcoma arising at the craniovertebral junction exhibited distinctive molecular and epigenetic features, including a SUZ12 mutation potentially associated with loss of H3K27me3. To our knowledge, gliosarcoma harboring these molecular abnormalities has not been previously reported. These findings may be associated with PRC2 dysfunction; however, their biological significance remains to be clarified. Comprehensive molecular profiling may contribute to improved diagnostic characterization of such rare entities.