Isocitrate dehydrogenase (IDH)-mutant astrocytomas show a peak incidence in young and middle-aged adults and have relatively favorable outcomes. In patients with these tumors ≥55 years at diagnosis, clinical, histopathologic, and prognostic characteristics are less clear. Here, we compared histopathological, immunohistochemical, molecular, and overall survival of 34 patients aged ≥55 years with a group of 84 patients aged 19-54 years; all had IDH mutant astrocytomas. The older cohort had 14 World Health Organization (WHO) grade 2, 7 WHO grade 3, and 13 WHO grade 4 tumors versus 24, 32, and 28 WHO grade 2, 3, and 4 tumors in the younger group. Comparing equal-grade tumors in both cohorts, Kaplan-Meyer survival analysis revealed that patients ≥55 years of age showed worse prognosis despite receiving comparable treatment regimens (Stupp protocol). Roughly equal numbers of noncanonical IDH mutations were seen in both groups (11.76% in ≥55 vs 19.04% in <55). Older patients were more likely to show retention of nuclear protein alpha-thalassemia and mental retardation X-linked syndrome (ATRX) and/or absence of strong P53 staining by immunohistochemistry. Although patients ≥55 years of age with astrocytomas, IDH-mutant, had worse overall survival, many, particularly those with low-grade tumors, had 5 years or greater survival. Employing parallel treatment regimens with chemotherapy, radiation, and maximum safe resection may improve survival of older patients with IDH mutant gliomas.
Keywords: ATRX; IDH-mutant; astrocytoma; brain tumor; molecular diagnostics; outcome.
© The Author(s) 2025. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.