H3F3A mutations define the entity of Diffuse Midline Glioma, which was added to the WHO 2016 classification. There have been several reports describing the clinical, prognostic, and histopathological implications of this mutation in children. It is unclear, however, what proportion of adults with gliomas occurring in the midline have an H3 K27M mutation. We set out to define this in a single-institution, retrospective cohort study.

From 850 consecutive gliomas in adults we identified 163 cases with midline gliomas on MRI (parasaggital cortex, corpus callosum, basal ganglia, thalamus, brainstem, spinal cord, or cerebellum). Clinical cases were reviewed in accordance with IRB guidelines. FFPE tissue was obtained from 123 cases and stained for H3 K27M, IDH1, and ATRX.

A H3 K27M mutation was identified in 18 of 123 cases (15%). As compared to non-H3 K27M mutated tumors, there were no difference in age at diagnosis, sex, tumor grade at diagnosis, contrast enhancement on MRI, extent of resection, or treatment received. All H3 K27M mutant tumors were WHO grade III or IV on histology, while non-mutant tumors encompassed all four grades (p = 0.13). The most common locations to have H3 K27M-mutated tumors were midbrain (2/3; 67%), pons (4/11; 36%), cerebellum (6/24; 25%), spinal cord (2/14; 14%), and thalamus (3/31; 10%). Median survival was significantly longer for patients with H3 K27M-mutated tumors (17.6 months) than high grade non-mutated tumors (7.7 months, p = 0.03).