10162-RC-4 A Case of Pleomorphic Xanthoastrocytoma with BRAFV600E Mutation, CDKN2A Deletion, and TERT Promoter Mutation Presenting with Leptomeningeal Dissemination and Pulmonary Metastasis

Abstract Background Pleomorphic xanthoastrocytoma (PXA) is a WHO grade 2 or 3 astrocytic tumor typically seen in children and young adults, with generally favorable outcomes. However, cases harboring BRAFV600E mutation, CDKN2A/B homozygous deletion, and TERT promoter mutations may show aggressive behavior with early recurrence and leptomeningeal dissemination. We report a rare case of PXA with all three alterations, showing rapid leptomeningeal spread and pulmonary metastasis. Case A man in his 40s presented with right-hand sensory disturbance and fine motor dysfunction. MRI revealed a tumor in the left parietal lobe. Awake craniotomy with gross total resection was performed. Histology showed spindle cell fascicles, rhabdoid cell sheets, calcification, and necrosis. Molecular testing revealed BRAFV600E mutation, TERT C228T mutation, and CDKN2A homozygous deletion. Methylation profiling classified the tumor as MC PXA (score 0. 99). The patient received radiotherapy with temozolomide and was discharged. Three months later, he developed neuropathic pain, motor impairment, and dysphagia. CSF cytology and MRI confirmed carcinomatous meningitis. He developed aspiration pneumonia and required ventilatory support. MRI showed multiple infarctions in the left hemisphere and right temporal lobe. He died four months postoperatively. Autopsy revealed BRAFV600E-positive atypical glial cell clusters with vascular invasion in both lungs and pleura, consistent with distant metastases. Discussion Although PXAs are generally indolent, this case exhibited rapid progression with leptomeningeal and systemic dissemination, likely due to the high-risk molecular profile. For such cases, early detection of dissemination and more intensive therapeutic strategies are warranted. Conclusion PXA with BRAFV600E, CDKN2A deletion, and TERT promoter mutation can follow an exceptionally aggressive course. This case underscores the importance of molecular risk stratification and individualized treatment planning.