Clinicoradiological differentiation of TERT promoter-mutant molecular glioblastoma versus histological glioblastoma: a single-center cohort study of 105 IDH-wildtype tumors

To compare the clinicopathological and magnetic resonance imaging (MRI) characteristics and prognostic implications between molecular glioblastoma (mol-GBM) and histological glioblastoma (hist-GBM) according to the 2021 WHO classification of central nervous system tumors (CNS5), we conducted a retrospective study of 105 patients with IDH-wildtype gliomas diagnosed between 2016 and 2022. Patients were reclassified into hist-GBM (n = 70) and mol-GBM (n = 35), with mol-GBM defined by TERT promoter mutation. Comparative analyses of clinical, molecular, and radiological features were performed. Overall survival (OS) was assessed in a subgroup of 96 patients using Kaplan–Meier and multivariable Cox regression models. Patients with mol-GBM were significantly younger (median age: 53 vs. 55.5 years, p = 0.046, median difference = − 2.5, 95% CI: −7.434 to 2.434), exhibited lower Ki-67 proliferation indices (30 vs. 40%, p = 0.002, median difference = − 10.0, 95% CI: −16.638 to − 3.362), and had lower p53 mutation rates (65.6 vs. 84.1%, p = 0.040, OR = 0.367, 95% CI: 0.138 to 0.973). MRI analysis demonstrated that mol-GBM was associated with less extensive peritumoral edema (major edema: 54.3 vs. 68.6%; p = 0.006) and lower tumor heterogeneity grades (Grade 3: 20.0% vs. 44.2%, p = 0.001, OR = 4.360, 95% CI: 1.950 to 9.746). No significant differences were observed in quantitative enhancement parameters or apparent diffusion coefficient (ADC) values. Survival analysis revealed a non-significant trend toward improved OS in the mol-GBM group (median OS: 17.0 vs. 13.0 months, log-rank p = 0.091). In multivariable analysis, GBM subtype was not an independent predictor of survival (hazard ratio [HR] = 0.829, 95% confidence interval [CI]: 0.432 to 1.591, p = 0.573). In conclusion, TERT promoter-mutant mol-GBM is characterized by a distinct clinicoradiological profile, including younger age at diagnosis and less aggressive imaging features. While these findings may aid preoperative suspicion, they do not confer independent prognostic value, underscoring the necessity of integrated molecular diagnosis to ensure appropriate treatment intensity and prevent undertreatment.