Paediatric-type diffuse high-grade gliomas in the 5th CNS WHO Classification

Abstract

As a relevant element of novelty, the fifth CNS WHO Classification highlights the distinctive pathobiology underlying gliomas arising primarily in children by recognizing for the first time the families of paediatric-type diffuse gliomas, both high-grade and low-grade. This review will focus on the family of paediatric-type diffuse high-grade gliomas, which includes four tumour types: 1) Diffuse midline glioma H3 K27-altered; 2) Diffuse hemispheric glioma H3 G34-mutant; 3) Diffuse paediatric-type high-grade glioma H3-wildtype and IDH-wildtype; and 4) Infant-type hemispheric glioma. The essential and desirable diagnostic criteria as well as the entities entering in the differential will be discussed for each tumour type. A special focus will be given on the issues encountered in the daily practice, especially regarding the diagnosis of the diffuse paediatric-type high-grade glioma H3-wildtype and IDH-wildtype. The advantages and the limits of the multiple molecular tests which may be utilised to define the entities of this tumour family will be evaluated in each diagnostic context.

Keywords: DMG with EZHIP overexpression; ETV6-NTRK3; MEF2D-NTRK1; MYC amplification; MYCN amplification; PDGFRA amplification; RTK fusions; ZCCHC8-ROS1; diffuse hemispheric glioma H3 G34-mutant; diffuse midline glioma K27M-altered; diffuse paediatric-type high grade glioma H3-wildtype and IDH-wildtype; infant-type hemispheric glioma; infant-type hemispheric glioma with atypical location; pHGG MYCN; pHGG RTK1; pHGG RTK2; paediatric high-grade glioma; radiation-induced gliomas.