Imaging features associated with H3 K27-altered and H3 G34-mutant gliomas: a narrative systematic review

Abstract

Background Advances in molecular diagnostics accomplished the discovery of two malignant glioma entities harboring alterations in the H3 histone: diffuse midline glioma, H3 K27-altered and diffuse hemispheric glioma, H3 G34-mutant. Radiogenomics research, which aims to correlate tumor imaging features with genotypes, has not comprehensively examined histone-altered gliomas (HAG). The aim of this research was to synthesize the current published data on imaging features associated with HAG. Methods A systematic search was performed in March 2022 using PubMed and the Cochrane Library, identifying studies on the imaging features associated with H3 K27-altered and/or H3 G34-mutant gliomas. Results Forty-seven studies fulfilled the inclusion criteria, the majority on H3 K27-altered gliomas. Just under half (21/47) were case reports or short series, the remainder being diagnostic accuracy studies. Despite heterogeneous methodology, some themes emerged. In particular, enhancement of H3 K27M-altered gliomas is variable and can be less than expected given their highly malignant behavior. Low apparent diffusion coefficient values have been suggested as a biomarker of H3 K27-alteration, but high values do not exclude this genotype. Promising correlations between high relative cerebral blood volume values and H3 K27-alteration require further validation. Limited data on H3 G34-mutant gliomas suggest some morphologic overlap with 1p/19q-codeleted oligodendrogliomas. Conclusions The existing data are limited, especially for H3 G34-mutant gliomas and artificial intelligence techniques. Current evidence indicates that imaging-based predictions of HAG are insufficient to replace histological assessment. In particular, H3 K27-altered gliomas should be considered when occurring in typical midline locations irrespective of enhancement characteristics.

A case of adult‐onset diffuse midline glioma diagnosed by histone H3K27M immunostaining after death, which required differentiation from brainstem encephalitis and myelitis

“…The lesions usually occur in the pons in cases of pediatric patients. However, in adults, the tumor site is mainly in the thalamus and less frequently in the medulla oblongata and spinal cord 1,3 …”

“…On imaging examinations, DMG usually demonstrates a non‐uniform hyperintensity on T2‐weighted images. The characteristics of gadolinium enhancement vary from ring enhancement to the absence of enhancement 3 …”

Editorial for “Deep Learning for Noninvasive Assessment of H3 K27M Mutation Status in Diffuse Midline Gliomas Using MR Imaging”

“…2 Apparent diffusion coefficient values of the lesion are likewise variable, but usually low to slightly low. 2 There have been some promising results with cerebral blood flow values, but data are currently limited and further research is warranted. 2 Recent work has demonstrated the applicability of artificial intelligence (AI) techniques for improving H3 K27 mutation status definition, based on conventional MRI sequences.…”

“…2 There have been some promising results with cerebral blood flow values, but data are currently limited and further research is warranted. 2 Recent work has demonstrated the applicability of artificial intelligence (AI) techniques for improving H3 K27 mutation status definition, based on conventional MRI sequences. Most studies have used machine learning (ML) techniques, which are capable of learning complex tasks and developing predictive models through sample data.…”

“…From an MRI point of view, H3 K27‐mutant gliomas are remarkably variable, with a spectrum of presentations spanning between contrast‐enhancing mass‐forming lesions with central necrosis and infiltrative processes without contrast enhancement 2 . Apparent diffusion coefficient values of the lesion are likewise variable, but usually low to slightly low 2 . There have been some promising results with cerebral blood flow values, but data are currently limited and further research is warranted 2 …”