Clinicopathologic and Molecular Features of H3 K27M-Mutant Diffuse Midline Glioma Across the Age Spectrum

Background and Objectives: Diffuse midline glioma (DMG), H3 K27-altered, occurs in children and adults, but age-group differences and their prognostic significance remain uncertain. We examined clinicopathologic and molecular features and survival in H3 K27M-mutant DMG across age groups. Materials and Methods: This retrospective single-center study included 53 patients (18 children and 35 adults). Histologic features, treatment, targeted sequencing results (28 tumors), and overall survival (OS) were analyzed. Results: Thalamic tumors predominated in adults (77.1%) and brainstem tumors in children (66.7%; p < 0.001). Median Ki-67 labeling index (LI) was higher in children (39% vs. 20%; p = 0.032); the estimated age-group difference remained similar after adjustment for location. Treatment regimens differed by age, but no significant age-group differences were found in other histologic features or the genomic alterations examined. At the data cutoff, 48 patients (90.6%) had died. Median OS was 20.3 months, without a significant difference between children and adults (15.2 vs. 21.7 months; p = 0.124). Higher Ki-67 LI remained associated with shorter OS after adjustment for age group, brainstem involvement, necrosis, and upfront radiotherapy (hazard ratio (HR) 1.37 per 10-percentage-point increment; 95% confidence interval (CI), 1.16–1.63; p < 0.001). Necrosis was also independently associated with shorter OS (HR 2.54; 95% CI, 1.29–5.00; p = 0.007). TP53 alteration was associated with shorter OS in univariable analysis but not after adjustment. Conclusions: Age groups differed in anatomical distribution and proliferative activity, but age was not independently associated with OS. Ki-67 LI and necrosis may provide accessible prognostic information, whereas the association of TP53 alteration with outcome requires validation.