Triple metachronous primary brain tumors: sequential occurrence of astrocytoma, atypical meningioma, and high-grade glioma without radiotherapy exposure. Illustrative case.

backgroundCollision tumors, characterized by the coexistence of distinct histological tumor types in adjacent regions, are rare in neuro-oncology. While meningioma-glioma collisions are documented, sequential occurrence without a history of radiotherapy is exceptionally uncommon, posing diagnostic challenges and implying elusive pathogenic mechanisms. OBSERVATIONS: A 31-year-old female underwent resection of a left frontal WHO grade I-II astrocytoma (2000) without radiotherapy. Eighteen years later, she developed an atypical meningioma (WHO grade II) at the same site, confirmed histologically and immunohistochemically (epithelial membrane antigen positive/glial fibrillary acidic protein negative). Seven years thereafter, a high-grade glioma (WHO grade 3) with oligodendroglioma-like features and a 1p/19q co-deletion emerged. Molecular profiling revealed divergent alterations: the meningioma exhibited NCOR2/CHD4/ELP1 mutations and 22q deletion, while the glioma harbored IDH2 p.R172H, TERT promoter, NOTCH1, and CIC mutations, supporting metachronous primary tumors despite shared 1p/19q loss. LESSONS: This case underscores that metachronous collision tumors can arise without radiotherapy, necessitating histopathological and molecular integration for accurate diagnosis. Long-term vigilance is critical for detecting sequential tumors, and shared microenvironments or genetic pathways may underlie tumorigenesis. Comprehensive profiling aids in clarifying pathogenesis and guiding management. https://thejns.org/doi/10.3171/CASE26149.