PATH-27. Title: Osseous Extracranial Metastases in Astrocytoma IDH-Mutant Grade 4 with CDKN2A/B Homozygous Deletion: A Case Report

INTRODUCTION Glioblastomas are the most aggressive primary brain tumors in adults. Despite maximal treatment, median survival remains approximately 15 months. Extracranial metastases (ECM) from high-grade gliomas are rare, with an incidence of 0.4% to 2%, and only isolated cases have been reported in IDH-mutant gliomas. Common metastatic sites include lungs, lymph nodes, liver, and bones. Mechanisms are poorly understood but may involve surgical disruption of blood-brain barrier, hematogenous spread and aggressive molecular alterations, such as dysregulation in CDK pathway. CASE We report a case of a 65-year-old man who presented with rapidly progressive right-sided hearing loss. Brain MRI revealed a large, heterogeneously enhancing temporal lobe mass extending into the petrous bone. He underwent gross total resection, and pathology demonstrated astrocytoma, IDH-mutant, CNS WHO grade 4. Next-generation sequencing (NGS) revealed a noncanonical IDH1 mutation, CDKN2A/B homozygous deletion, MGMT promoter hypermethylation, and high PD-L1 expression. Despite IDH1 mutation, DNA methylation profiling matched the tumor to glioblastoma IDH-wildtype class. He completed chemoradiation followed by two cycles of adjuvant temozolomide, but MRI showed progression. He was then treated with a combination of bevacizumab and vorasidenib, followed by pembrolizumab with reirradiation at second progression. Immunotherapy was discontinued after grade 4 supraventricular tachycardia post-infusion. Soon after, he developed severe lower back pain; spinal MRI showed multifocal osseous lesions. Biopsy of L5 vertebral body confirmed metastatic astrocytoma, with NGS matching the primary tumor. He was started on abemaciclib due to persistent CDK pathway alteration and received spinal radiotherapy, but disease progressed rapidly. He died six weeks after ECM diagnosis. CONCLUSION This case illustrates a rare instance of osseous ECM from a high-grade IDH-mutant astrocytoma with aggressive molecular features. Persistent CDKN2A/B homozygous deletion, and particularly, bone involvement at diagnosis may portend systemic dissemination and should be considered in risk stratification and surveillance planning.