A rare IDH-Mutant glioma case: insights from single-cell transcriptomic analysis of tumor recurrences.

Abstract

Background: Isocitrate dehydrogenase (IDH) mutations are associated with better prognosis and longer survival in gliomas. In contrast, multifocal glioma is a rare intracranial tumor, primarily affecting middle-aged and elderly individuals. While recurrence is common due to the complex tumor microenvironment, cellular heterogeneity, and clonal evolution, multifocal recurrence originating from an initially unifocal, low-grade glioma has been rarely reported.

Case presentation: We present the case of a 36-year-old male initially diagnosed with oligodendroglioma, IDH-mutant and 1p/19q-codeleted, CNS WHO grade 3. After gross total resection and standard chemoradiotherapy, the patient developed multifocal recurrence after three years, with new lesions in the left temporal and frontal lobes. Histopathological analysis revealed divergent progression: the distal temporal lesion demonstrated glioblastoma-like features, whereas the in situ frontal recurrence retained characteristics of oligodendroglioma. To investigate the mechanism of multifocal tumor recurrence, we performed single-cell sequencing analysis on both foci, revealing distinct cellular compositions and hidden lineage relationships among malignant cells.

Discussion and conclusion: We describe a rare case of multifocal glioma recurrence in a middle-aged adult, highlighting the cellular heterogeneity and lineage relationships between distinct tumor foci. This case contributes to the limited literature on multifocal glioma recurrence and provides a well-characterized specimen for investigating the molecular distinctions between IDH-mutant and IDH-wildtype gliomas.