MRI features of pleomorphic xanthoastrocytoma defined by DNA methylation profile.

Introduction: Pleomorphic xanthoastrocytomas (PXA) are primary brain tumors challenging to diagnose due to their morphological and molecular overlap with other tumors. While DNA methylation profiling (MP) aids pathological classification, it alone may be inconclusive. Magnetic resonance imaging (MRI), routinely performed for lesion assessment, provides valuable information. Combining histo-molecular features, MP, and MRI is thus beneficial, particularly in cases of diagnostic uncertainty. In this study, we retrospectively analyzed MRI features of methylation-confirmed PXAs (mcPXAs) versus tumors with PXA-like histology using WHO 2021 criteria.

Methods: We included 29 adult patients with tumors displaying PXA-suggestive histology, completed MP, and preoperative MRI. Tumors were classified into three groups: mcPXA, histological PXA with methylation-confirmed glioblastoma (mcGBM), and other MP-confirmed diagnoses (mcMimic). Clinical and molecular data were recorded.

Results: All tumors were supratentorial with heterogeneous enhancement. The mcGBM group showed significantly more peritumoral edema and hypercellularity than mcPXA (P=0.002 and P=0.023). No significant differences were found in tumor location, cystic components, or hemorrhagic content. The BRAF^V600E mutation appeared in 89% of mcPXA, 8% of mcGBM, and 29% of mcMimic cases (P<0.05). Our composite MRI and molecular score for PXA diagnosis achieved an area under the curve of 0.95, with 95% specificity and 77% sensitivity.

Conclusion: In cases of histological uncertainty, lack of peritumoral edema and hypercellularity supports a PXA epigenetic profile. Our specific score could aid in challenging cases, though further validation in larger cohorts is warranted.