Molecular Characterization of a Rare Glioblastoma Case With Atypical Histopathologic Features

A 76-year-old man presented with a subtle, non-mass-like right insular and temporal opercular T2 FLAIR hyperintensity that remained stable for over 2 years before showing interval progression. Resection revealed mildly hypercellular atypical glial cells with a Ki-67 index of approximately 1% and no necrosis or microvascular proliferation. Immunohistochemistry was negative for IDH1 R132H. Next-generation sequencing identified a TERT promoter mutation, EGFR amplification, and CDKN2A deletion. Methylation profiling confirmed glioblastoma, IDH wild-type, World Health Organization grade 4. Despite lacking classic histologic features, the integrated molecular findings established the diagnosis. The patient underwent near-total resection, followed by hypofractionated radiotherapy with concurrent temozolomide, maintenance temozolomide, and tumor treating fields therapy. This case highlights the essential role of molecular diagnostics in accurately classifying diffuse gliomas with atypical histology.