These findings suggest that focal radiation may be inadequate for some of these patients. Further, diffuse invasion of the brainstem, spinal cord and thalamus was common with some cases showing spread as distant as the frontal lobes. Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype were only found in WHO grade III–IV astrocytomas, while PIK3CA mutations and PDGFRA gains/amplifications were found in WHO grade II–IV astrocytomas. K27M-H3 mutations were exclusively found in tumours with WHO grade II–IV astrocytoma histology. Upon histological review, 62 patients had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour (PNET). Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were pre-treatment biopsy/surgical specimens. Here, we review 72 DIPG cases with well documented clinical history and molecular data and describe the pathological features of this disease in relation to clinical and genetic features. This has also allowed us to investigate the terminal pattern of disease and gain a better understanding of what challenges we are facing in treating DIPG.

Our group has developed an autopsy-based protocol to investigate the histologic and biologic spectrum of DIPG. In the majority of cases diagnosis is based on clinical and MRI findings, resulting in the scarcity of pre-treatment specimens available to study. Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children.

Typestatus 2 a12