Diagnostic accuracy of neuropathological assessment across different diagnostic settings for high-grade gliomas: the added value of DNA methylation profiling
In brief
Specialist review detected all high-grade gliomas; general pathology missed 1 in 5
In 130 selected cases, specialist neuropathology identified every high-grade glioma classified by DNA methylation profiling, while general pathology missed 20 of them, often labeling tumors low-grade or non-neoplastic. Specialist review matched the reference classification in 99% of cases, but this retrospective, selected cohort cannot establish performance across all settings; methylation profiling also refined some diagnoses.
- Journal
- Acta neurochirurgica (Q1)
- Published
- 24 October 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 4, Very Low (CEBM 4)
- Authors
- Timotheos Christoforou, Umida Elmuradova, Stefanie Hammersen, Arend Koch, Sven Kantelhardt, Ali Mulhem
- PMID
- 42931851
- DOI
- 10.1007/s00701-026-07078-w
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 30 October 2026): Compares diagnostic accuracy across pathology settings against methylation profiling
Abstract
BACKGROUND: Accurate histopathological diagnosis is essential for the management of patients undergoing surgery for suspected high-grade glioma (HGG). We evaluated the diagnostic accuracy of pathological assessment performed in a general pathology department and a specialist neuropathology department, using EPIC-based DNA methylation classification as the operational reference standard. METHODS: This retrospective diagnostic accuracy study included 130 patients with complete results from three diagnostic assessments (selected from 173 screened records) with intracranial space-occupying lesions who underwent surgical biopsy or resection between May 2019 and February 2025. Tissue specimens were assessed in a general pathology department and subsequently evaluated independently in a specialist neuropathology department, followed by DNA methylation profiling using the Illumina Infinium MethylationEPIC BeadChip. HGGs (CNS WHO grades 3-4) were classified as positive and all other lesions as negative. RESULTS: Assessment in the general pathology department yielded 20 HGG classifications discordant with the EPIC reference (false negatives), including 13 tumors initially classified as low-grade gliomas, two as other intracranial lesions, and five as non-neoplastic brain tissue. Sensitivity was 79%, specificity 100%, positive predictive value 100%, negative predictive value 62%, and overall accuracy 84%. Specialist neuropathological assessment achieved a sensitivity of 100%, specificity of 97%, positive predictive value of 99%, negative predictive value of 100%, and overall accuracy of 99%. Three cases differed in specific classification or binary status: two HGG diagnoses were further refined as glioblastoma, IDH-wildtype, CNS WHO grade 4, while one specimen interpreted histopathologically as showing proliferative and mitotic activity was classified as tumor-free brain tissue by DNA methylation profiling. CONCLUSIONS: Specialist neuropathological assessment showed high agreement with the EPIC-based reference classification for HGGs, whereas assessment outside a specialized neuropathology setting showed lower sensitivity for HGG identification in this selected cohort. DNA methylation profiling provides complementary diagnostic value by refining tumour classification.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.