An integrative radiological, histopathological and molecular analysis of pediatric pontine histone-wildtype glioma with MYCN amplification (HGG-MYCN)

A. Tauziède-EspariatEmail author,
M-A Debily,
D. Castel,
J. Grill,
S. Puget,
M. Sabel,
K. Blomgren,
A. Gareton,
V. Dangouloff-Ros,
E. Lechapt,
N. Boddaert and
P. Varlet

Acta Neuropathologica Communications20197:10

https://doi.org/10.1186/s40478-019-0738-y

Received: 16 April 2019
Accepted: 14 May 2019
Published: 10 June 2019

The 2016 WHO Classification of tumours of the central nervous system has introduced a new histomolecular entity, the midline diffuse glioma, H3K27 M-mutant [8]. This entity represents an infiltrative high-grade glioma (HGG) (grade IV) of the pons and the brainstem, which mainly effects children. It harbors K27 M mutations of H3F3A, HIST1H3B/C or HIST2H3A/C genes. In the pons, morphological differential diagnoses are numerous with a large spectrum of tumours ranging from benign such as pilocytic astrocytoma to malignant such as embryonal tumour with multilayered rosettes (ETMR). From the reclassification of CNS-PNETs in the study by Sturm et al., HGG-MYCN was described in 28/323 cases (9%), mainly located in the cerebral hemispheres. Moreover, in a recent series of pontine gliomas, three molecular subgroups were defined: H3K27 M-mutant, MYCN-amplified and silent [1]. The MYCN subgroup was the least frequent, with only 8% of cases (4/47) [1]. This corresponds to a very rare tumour and very few radiological, clinical and histopathological data are available in the literature. In our center, six cases of HGG-MYCN were diagnosed by whole exome sequencing (WES) based on the co-amplification of MYCN and ID2 (2 cases from BIOMEDE cohort) [3]. Herein, our aim is to describe the clinical, imaging, histopathological, immunohistochemical and molecular features of these cases to better characterize them.