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Impact of DNA Methylation Profiling on Central Nervous System Tumor Diagnosis and Management: A Pediatric Cohort
Mehmet Arda Inan1, Ayça ERşEN Danyeli, Figen Soylemezoglu
1Acibadem University School of Medicine, Department of Pathology, Istanbul, Türkiye.
Aim:
To present a single-center experience, and to highlight the urgent need for multi-institutional collaboration in Türkiye and surrounding regions lacking access to methylation platforms, with the aim of enhancing diagnostic precision and neuropathological practice.
Material And Methods:
All pediatric patients who underwent methylation?based tumor classification (MBTC) between November 2023 and July 2025 were retrospectively identified. Clinical, histological, and molecular data were extracted and correlated with methylation results. Concordance between histopathology and MBTC was categorized as concordant, minor discordance, major discordance, novel classification, or un-classifiable.
Results:
A total of 48 tumors were profiled (26 females [54%]; 22 males [46%]; median age, 6.5 years; range, 0?17). The most frequent localization was supratentorial (n=18, 36%). Of the entire cohort, concordance was 58%. Excluding unclassifiable cases, concordance among evaluable tumors was 67%. Discordance occurred in 11 cases (23%), including 6 (13%) with major discrepancies. Concordance was significantly associated with tumor localization (p=0.028) but not WHO grade (p=0.17) and classifier confidence (p=0.73).
Conclusion:
MBTC is a valuable complementary tool in the diagnostic workup of pediatric central nervous system (CNS) tumors, particularly in morphologically ambiguous and ultra-rare cases. It should be integrated with conventional histopathology rather than viewed as a replacement, as it may prevent prognostic misclassification and inappropriate treatment in selected patients.