A multifocal IDH-mutant glioma with differential response to IDH inhibition: Role of quantitative neuroimaging

We present a rare case of concurrent, spatially distinct 1p/19q-intact IDH-mutant astrocytoma and 1p/19q-codeleted IDH-mutant oligodendroglioma in the same patient with divergent responses to IDH inhibitor therapy. A 40-year-old male presented to the emergency room following a seizure and was found to have 2 distinct left hemisphere tumors. Both lesions underwent biopsy and resection, with updated molecular diagnosis 4 years later revealing IDH-mutant 1p/19q-intact astrocytoma and IDH-mutant 1p/19q-codeleted oligodendroglioma. Tumor volumes, T2-FLAIR mismatch percentage, and normalized apparent diffusion coefficient (nADC) were quantified from serial MRIs. At initial presentation, quantitative analysis revealed the posterior lesion (IDH-mutant 1p/19q-intact astrocytoma) exhibited 60.6% T2-FLAIR mismatch volume and elevated median nADC of 2.72, while the anterior lesion (IDH-mutant 1p/19q-codeleted oligodendroglioma) showed minimal T2-FLAIR mismatch (1.8%) and lower median nADC (1.94). Volumetric analysis during IDH inhibitor (ivosidenib) therapy revealed differential response: the oligodendroglioma decreased in volume by 32.6% over 19 months, while the astrocytoma demonstrated progressive growth with a 77.3% volume increase over 19 months. This case demonstrates the utility of quantitative neuroimaging for accurate characterization of concurrent IDH-mutant gliomas with distinct molecular profiles. The observed differential response to IDH inhibition supports emerging evidence of molecular subtype-specific treatment sensitivities in IDH-mutant gliomas.