Significance of H3K27M Mutation in “Nonmidline” High-Grade Gliomas of Cerebral Hemispheres

Background: “Diffuse midline glioma H3K27M-mutant” (a mutation gene encoding H3 histone variants) represents a defined pathologic entity since the 2016 World Health Organization Central Nervous System classification and includes midline structures, namely the thalamus, brainstem, and spinal cord. H3K27M-mutant glioma responds more poorly and is associated with worse clinical outcome. Mutation detection is now diagnostic for “diffused midline gliomas.” We report on a case arising in an atypical nonmidline localization with an exceedingly adverse course. The present case raises the question of the possible meaning of the H3K27M-mutation in high-grade gliomas arising from the cerebral hemispheres and its implications from prognostic and therapeutic views. Case Description: A 48-year-old woman was admitted with a mass arising from the splenium of the corpus callosum with bilateral hemispheric extension, displaying magnetic resonance imaging characteristics typical of a high-grade glioma. Needle biopsy confirmed the diagnosis of “diffuse astrocytic neoplasm, World Health Organization grade IV.” Immunostaining of the tumor revealed the H3K27M-mutant nuclear expression. The patient was referred to adjuvant therapy and died 3 months after biopsy. Conclusions: This experience highlights the possible negative prognostic impact of H3K27M-m and possibility that H3K27M-m could be a reliable prognostic indicator to be considered in not only diffuse midline gliomas but also gliomas from the cerebral hemispheres. Because of the rarity and limited knowledge of this specific mutation in this experience, reports should be encouraged.