An Emerging Pediatric CNS Tumor: Imaging Evaluation of H3K27M and BRAF V600E Comutated Midline Tumors.

Abstract

Background and purpose: Diffuse midline gliomas (DMG) with concurrent H3K27M and BRAF V600E mutations represent a rare and poorly studied subset of pediatric central nervous system tumors. While traditionally associated with poor prognosis, recent evidence suggests that MAPK pathway alterations may confer improved outcomes in select cases. This study aims to explore the imaging characteristics of H3K27M/BRAF V600E coaltered midline gliomas.

Materials and methods: Eight pediatric patients (6 males, 2 females; age range: 3-18 years, mean: 11 years) with H3K27M/BRAFV600E-mutant midline tumors were retrospectively reviewed. Data collected included MR imaging features, histopathologic and molecular data, treatment, and follow-up outcomes.

Results: Of the eight patients identified, six (n=6/8; 75%) were thalamic, with the remainder involving the hypothalamus/optic pathway and cervical spine. Tumors demonstrated heterogeneous histology: pediatric-type low-grade glioma-like (n=3), ganglioglioma-like (n=3), and high-grade glioma-like (n=2).All tumors were midline in location. Thalamic tumors were well-demarcated but demonstrated infiltrative and exophytic components, with frequent involvement of the third ventricle (n=4/6;66.7%) and internal capsule (n=4/6;66.7%). Imaging demonstrated heterogeneous T1/T2 signal with coarse calcifications in five of thalamic tumors. Hydrocephalus was present in all patients with thalamic lesions. These tumors demonstrated varied diffusion characteristics with areas of intermediate and reduced diffusivity. Enhancement was present but heterogeneous across tumor types. Both HGG-like tumors presented with cranial and spinal leptomeningeal metastases.

Conclusions: DMGs harboring both H3K27M and BRAFV600E mutations may represent a distinct subtype, with radiologic, histopathologic, and molecular features that appear different from those of non-MAPK-altered H3K27M DMGs.

Abbreviations: World Health Organization = WHO, Diffuse midline glioma = DMG, Mitogen-activated protein kinase = MAPK, Formalin-fixed paraffin-embedded = FFPE, Wild-type = WT, Overall survival = OS, Contrast-enhanced = CE, High-grade gliomas = HGGs, Long-term survival = LTS, Short-term survival= STS.