Two Diseases That Share a Name — Defining Glioblastoma and Diffuse Midline Glioma Under the 2021 WHO Classification

In this opening episode, Dr. Shonka and Dr. Chong frame the conversation around two diseases that share the name glioma but differ fundamentally in biology, demographics, and treatment. Dr. Shonka introduces glioblastoma, IDH wild-type, the most common malignant brain tumor in adults, with an incidence of about 3.2 per 100,000, median age at diagnosis of approximately 65 years, and median survival under 2 years despite surgery, radiation, and temozolomide. Dr. Chong contrasts this with diffuse midline glioma (DMG), H3 K27-altered: less common but disproportionately devastating, the leading cause of brain tumor–associated death in children, with median survival of about 9 to 11 months. Diffuse intrinsic pontine glioma (DIPG) alone affects roughly 300 US children per year. Dr. Chong notes that nearly half of H3 K27M-altered tumors are diagnosed in adults, where tumors more often arise in the thalamus and median survival approaches 2 to 2.5 years. Dr. Shonka then flags the August 2025 US Food and Dr.ug Administration (FDA) accelerated approval of dordaviprone for H3 K27M-mutant DMG in patients 1 year of age and older with progressive disease following prior therapy. Dr. Chong walks through how the 2021 World Health Organization (WHO) classification reorganized these tumors by molecular features rather than histology alone: glioblastoma defined by IDH wild-type status plus hallmark alterations including EGFR amplification, chromosome 7 gain or 10 loss, and TERT promoter mutation; DMG defined by an H3 K27 histone mutation with global loss of H3K27 trimethylation.

In the next episode, “Imaging Clues That Raise Suspicion for DMG,” Dr. Shonka details the MRI findings that should prompt molecular testing.