IDH-Mutant Astrocytomas in Patients Older than 55 Years: A Retrospective Analysis

Diffuse gliomas are the most common malignant brain tumors in adults, stratified by isocitrate dehydrogenase (IDH1/IDH2) mutation status. While the median age for central nervous system (CNS) World Health Organization (WHO) grade 2 to 3 IDH-mutant astrocytomas is 38 years, older patients of >55 years predominantly exhibit IDH-wildtype gliomas and confer a poorer prognosis. To examine the clinicopathologic spectrum of IDH-mutant astrocytomas in older adults, we retrospectively reviewed all astrocytic tumors diagnosed at our institution between 2021 and 2024 in patients >55 years. Twenty-two IDH-mutant astrocytomas (median age: 63 years; range: 56-79; male:female = 9:13) were identified and compared descriptively to a historical cohort of 179 IDH-mutant astrocytomas in younger patients. Grade distribution among older patients paralleled that of younger adults: CNS WHO grade 2 (55%), grade 3 (18%), and grade 4 (27%). Magnetic resonance imaging (MRI) showed T2/FLAIR mismatch sign in 25% of grade 2 tumors and in none of the higher grades; 50% of grade 2 tumors demonstrated contrast enhancement. IDH1 p.R132H accounted for 95% of mutations, with 1 p.R132G variant. ATRX loss was seen in 71% and strong p53 immunoreactivity in 83% of evaluable tumors. Copy-number analysis (n = 10) revealed CDKN2A/B homozygous deletion in 10% and heterozygous loss in 20%. Despite their rarity, IDH-mutant astrocytomas in older adults are more prevalent than historically appreciated and maintain imaging and molecular profiles akin to tumors in younger adults. Accordingly, IDH1 p.R132H-specific immunohistochemistry remains a cost-effective first-line screening tool irrespective of age.