H3F3A-G34R mutant high grade neuroepithelial neoplasms with glial and dysplastic ganglion cell components

Felipe AndreiuoloEmail author View ORCID ID profile,
Tomo Lisner,
Jozef Zlocha,
Christof Kramm,
Arend Koch,
Brigitte Bison,
Albane Gareton,
Marc Zanello,
Andreas Waha,
Pascale Varlet and
Torsten Pietsch

Acta Neuropathologica Communications20197:78

https://doi.org/10.1186/s40478-019-0731-5

Received: 8 March 2019
Accepted: 29 April 2019
Published: 20 May 2019

Abstract

The recently described malignant neuro-epithelial tumors with histone H3F3Apoint mutations at G34 (NET-H3-G34) occur most often in cerebral hemispheres of teenagers and young adults, and have a generally adverse prognosis. These tumors have been histologically classified as glioblastoma or primitive neuroectodermal tumor (PNET) in the past, and have not been defined as a separate entity in the revised WHO classification of tumors of the CNS 2016. Here, we report two cases of NET-H3-G34 with glial and dysplastic ganglion cell components affecting teenagers. Patients were treated with surgery and radiochemotherapy with temozolomide. One patient underwent partial resection and deceased 21 months after diagnosis, while the other patient is alive without evidence of disease 15 months after total resection. So far, a dysplastic ganglion cell component has not been described in NET-H-G34, and its presence raises a possible relation to (anaplastic) gangliogliomas. Genome-wide copy number analysis did not provide unequivocal evidence that these tumors represent anaplastic variants of gangliogliomas, as opposed to NET-H3-G34. Our observations expand the morphologic spectrum of NET-H3-G34. Further cases of NET-H3-G34 with dysplastic ganglion cells should be clinically followed to find differences or similarities in their biological behavior, as compared to NET-H3-G34 and anaplastic gangliogliomas.