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

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.

Case Report: Five Adult Cases of H3K27-Altered Diffuse Midline Glioma in the Spinal Cord

“…It was worth noting, however, that the initial MRI presentation of the five patients all resembled a low-grade CNS tumor, which easily led to being misdiagnosed as benign tumors at the initial diagnosis, potentially delaying treatment. In case of a 25-year-old women ( 22 ) and a 28-year-old man ( 23 ), the DMG-H3K27m tumors were located in the cervical medulla, mimicking the manifestations of meningioma and ganglioneuroma on the images respectively. Other studies have suggested that patients with suspected gliomas at midline sites on MR should first undergo immunohistochemistry testing for H3K27M mutations, especially if tissues were difficult to collect and malignancy is difficult to diagnose based on histological examination alone ( 13 ).…”

A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature

“…Molecular genetic analysis was performed by extracting DNA from FFPE material using the Maxwell system (Promega) according to the manufacturer’s protocol and subsequent application of the Illumina Focus Panel (Illumina) on an Illumina MiniSeq device (Illumina) according to the manufacturer’s protocols enabling us to analyze 41 genes in parallel, including IDH1 and IDH2 hot spot regions (the complete gene list can be found in Table 1 ). Hot spot loci of TERT promoter were analyzed by Sanger sequencing [ 4 , 7 ]. DNA-methylation profiling was performed using Illumina EPIC bead chips that were scanned on an Illumina NextSeq 550DX device.…”

Genotypical glioblastoma of the frontal lobe mimicking ganglioglioma: A case report and review of the literature

“…Molecular genetic analysis was performed as previously described. 10 Analysis showed a mutation of the TERT promoter region (C228T) and a PTPN11 p.G60R mutation (Figure 3A). There was no mutation at the further analyzed 52 genes (Figure 3B).…”