Diffuse midline glioma of the cervical spinal cord with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma: a case report and review of the literature

Theo F J Kraus,Johannes Pöppe,Peter A Winkler,Lukas Machegger,Barbara Zellinger,Barbara Ladisich,Hans U Schlicker,Eva Dovjak,Mathias Spendel,Christoph Schwartz,Karl Sotlar,Michael Kral,Annekathrin Reinhardt

doi:10.1007/s10014-020-00365-z

Theo F J Kraus, Johannes Pöppe + Show 11 more

Open Access

https://doi.org/10.1007/s10014-020-00365-z

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Abstract

Here, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4 cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensive molecular workup revealed H3F3A K27M, TERT C228T and PDGFRα Y849C mutations indicating poor prognosis. The H3F3A K27M mutation assigned the tumor to the molecular group of diffuse midline glioma (WHO Grade IV). Epigenome-wide methylation profiling confirmed the methylation class of diffuse midline glioma. Thus, this is a very rare case of malignant glioma with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma. This case emphasizes the importance of comprehensive morphological and molecular workup including methylome profiling for advanced patient care.

Highlights

In the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) molecular genomic and epigenomic hallmarksGangliogliomas are rare glioneuronal tumors accounting for approximately 1.3% of all primary brain tumors [1]
Molecular genetic testing revealed that the BRAF V600E mutation is frequently found in gangliogliomas [1]
Diffuse midline gliomas H3 K27M mutant are rare tumors that typically arise within midline structures and the brain stem in younger patients [1, 2, 8]

Summary

Introduction

In the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) molecular genomic and epigenomic hallmarks. Molecular genetic testing revealed that the BRAF V600E mutation is frequently found in gangliogliomas [1] Since these tumors show a relatively benign behavior and malignant progression is rare, they are assigned to WHO grade I [1]. The glial component shows signs of anaplasia, increased proliferation activity and an increased mitotic count [1, 15] These rare tumors are currently classified as anaplastic gangliogliomas and are assigned to WHO grade III. Epigenome-wide methylation profiling was performed at the Department of Neuropathology, University Hospital Heidelberg/German Cancer Research Center (DKFZ), using Illumina EPIC methylation bead chips [9] This procedure enables to assign brain tumors according to their methylome to distinct molecular entities [9]. Well in line with the detection of the H3F3A K27M mutation, the tumor was allocated to the methylation class of diffuse midline glioma H3 K27M mutant (brain tumor classifier V11b4, Fig. 3g)

Discussion

Findings

Compliance with ethical standards