Clinicoradiological characteristics of primary spinal cord H3 K27M-mutant diffuse midline glioma

Abstract

OBJECTIVE Primary spinal cord H3 K27M-mutant diffuse midline glioma (DMG) is a rare and devastating pathological entity. However, little attention has been paid to this disease. As a result, its clinicoradiological characteristics have yet to be described. The aim of this study was to describe the clinicoradiological characteristics of primary intramedullary H3 K27M-mutant DMG and to compare this tumor with the H3 K27 wild-type to explore potential features that could differentiate the two. METHODS A total of 59 patients with pathologically confirmed intramedullary astrocytoma were included in this study. The cohort was divided into an H3 K27M-mutant group and H3 K27 wild-type group based on the status of H3 K27M according to an immunohistochemistry method. Demographic data, MRI features, and molecular information were collected. Multivariate logistic regression was conducted to investigate variables that might have a role in differentiating an H3 K27M DMG from an H3 K27 wild-type tumor. RESULTS Only symptom duration showed an independent association with the H3 K27M mutation (OR 0.82, 95% CI 0.68–0.94, p = 0.016). Patients with spinal cord H3 K27M-mutant DMG had a shorter symptom duration than patients with H3 K27 wild-type glioma. No significant difference was found in terms of MRI features between the H3 K27M-mutant and H3 K27 wild-type groups. Additionally, H3 K27M-mutant DMG frequently demonstrated overexpression of p53. Survival outcome did not show a statistical difference between the H3 K27-mutant subgroup and H3 K27 wild-type subgroup in histologically high-grade astrocytoma. CONCLUSIONS Symptom duration was associated with an H3 K27M mutation in intramedullary astrocytoma. MRI features were heterogeneous, and no imaging feature was able to predict the H3 K27M mutation. The H3 K27M mutation did not impact survival outcome in spinal histologically high-grade astrocytoma.

The H3 K27-altered, Extent of Resection and Survival in Pediatric High-grade Spinal Cord Gliomas

“…However, several reports the incidence of H3 K27-altered increases along with histological grade. [24,25] The same trend was observed in in our study, although no statistical signi cance was observed. Due to the size of the cohort, we could not perform multivariate analysis to determine whether there is collinearity between these two prognostic factors.…”

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

“…Somatic missense mutations at amino acid position 27 of the H3F3A or HIST1H3B genes are commonly seen in astrocytomas of midline structures, including the pons, thalamus, and spinal cord, resulting in the discrete entity designated diffuse midline glioma, H3 K27M-altered ( 87 ). They are estimated to account approximately between 18% and 55% of intramedullary astrocytomas ( 86 , 88 , 89 ). Originally designed in the 2016 WHO guidelines as H3 K27M-mutant lesions, the updated nomenclature reflects other mechanisms can alter the pathway beyond genetic mutations ( 7 ).…”

“…Although they can appear in several midline structures, the spinal cord is the most common site of H3 K27M-altered gliomas in adults ( 93 ). They are designated WHO Grade 4, although their underlying microscopic appearance may appear Grade 2, 3, or 4 ( 88 , 94 ). Indeed, the majority of H3 K27M-altered gliomas appear as high-grade lesions, but approximately 40% can appear as Grade 2 in histology ( 88 , 95 ).…”

“…They are designated WHO Grade 4, although their underlying microscopic appearance may appear Grade 2, 3, or 4 ( 88 , 94 ). Indeed, the majority of H3 K27M-altered gliomas appear as high-grade lesions, but approximately 40% can appear as Grade 2 in histology ( 88 , 95 ). Cheng et al.…”

“…Cheng et al. studied 59 patients with intramedullary astrocytomas, of which 28 were designated H3K27M-altered, and found that shorter symptom duration was significantly associated with the H3K27M mutation, but did not identify significant differences on MRI ( 88 ). Gu et al.…”