Diagnostic accuracy of neuropathological assessment across different diagnostic settings for high-grade gliomas: the added value of DNA methylation profiling
4 affiliations
- 1Department of Neurosurgery, Vivantes Klinikum Im Friedrichshain, Berlin, Germany
- 2Department of Neurosurgery, Helios Klinikum Erfurt, Erfurt, Germany
- 3Department of Neuropathology, Charité – Universitätsmedizin Berlin, Berlin, Germany
- 4Department for Continuing Education, University of Oxford, Oxford, UK
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.
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BibTeX
@article{christoforou2026diagnostic,
title = {{Diagnostic accuracy of neuropathological assessment across different diagnostic settings for high-grade gliomas: the added value of DNA methylation profiling}},
author = {Timotheos Christoforou and Umida Elmuradova and Stefanie Hammersen and Arend Koch and Sven Kantelhardt and Ali Mulhem},
journal = {Acta Neurochirurgica},
year = {2026},
month = oct,
doi = {10.1007/s00701-026-07078-w},
url = {https://doi.org/10.1007/s00701-026-07078-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Diagnostic accuracy of neuropathological assessment across different diagnostic settings for high-grade gliomas: the added value of DNA methylation profiling
AU - Timotheos Christoforou
AU - Umida Elmuradova
AU - Stefanie Hammersen
AU - Arend Koch
AU - Sven Kantelhardt
AU - Ali Mulhem
PY - 2026
DA - 2026/10/24
JO - Acta Neurochirurgica
DO - 10.1007/s00701-026-07078-w
UR - https://doi.org/10.1007/s00701-026-07078-w
AB - 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.
SN - 0001-6268
SN - 0942-0940
ER -