Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation.

Abstract

Pediatric glioblastoma (GBM) can be sub-classified into several molecular subgroups, including a group defined by a mutation in histone H3 at position amino acid 27 resulting in the replacement of lysine by methionine (K27M) [1]. K27M GBMs are located in the midline, often occur in children, and have been shown to have worse prognosis than other GBM subgroups, with a median survival of 6 months [2–5]. The 2016 revision of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System now recognizes “diffuse midline glioma, H3 K27M-mutant” as a distinct clinic-pathological entity and recommends grading as Grade 4 [5]. A robust immunohistochemical stain has been recently developed to specifically detect the K27M mutation. It can be used to help diagnose these high-grade tumors, particularly in the setting of a small biopsy where the amount of tissue is insufficient for molecular studies [6]. Here we report two patients with midline pilocytic astrocytoma and a glioneuronal tumor, respectively, harboring a K27M mutation. Our findings show that K27M mutations may be present in a spectrum of brain tumors with less aggressive clinical behavior and prolonged survival. Our data indicates that the entity of H3 K27M-mutant tumors may represent a spectrum including not only diffuse gliomas [5] but also less aggressive tumors than previously recognized, and that histone H3 K27M mutation should not be used as the sole criterion for the diagnosis of WHO Grade IV and to imply a dismal prognosis and aggressive management.