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Low-grade epilepsy-associated neuroepithelial tumours with a prominent oligodendroglioma-like component: the diagnostic challenges
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International audience. AIM: We searched for recurrent pathological features and molecular alterations in a retrospective series of 72 low-grade epilepsy-associated neuroepithelial tumours (LEATs) with a prominent oligodendroglioma-like component, in order to classify them according to the 2021 WHO classification of CNS tumours. MATERIAL AND METHODS: Centralized pathological examination was performed as well as targeted molecular analysis of BRAF and FGFR1 by multiplexed digital PCR (mdPCR). DNA-methylation profiling was performed in cases with sufficient DNA. In cases with no genetic alteration by mdPCR and sufficient material, RNA sequencing was done. RESULTS: We first reclassified our cohort into 3 groups: ganglioglioma (GG, n=14), dysembryoplastic neuroepithelial tumours (DNT, n=19) and glioneuronal tumours/paediatric-type low grade glioma not otherwise specified (GNT/PLGG NOS, n=39). mdPCR found an alteration in 38/72 cases. Subsequent RNA sequencing revealed a fusion transcript involving BRAF, FGFR1/2/3 or NTRK2 in 9/25 cases. DNA-methylation profiling found 12/46 cases with a calibrated score ≥0.9. Unsupervised hierarchical clustering revealed 2 clusters: cluster 1 was enriched with cases classified as DNT at histology, belonging to the LGG-DNT methylation class (MC), with CD34 negativity and FGRF1 alterations; cluster 2 was enriched with cases classified at histology as GG, belonging to the LGG-GG MC methylation class, with BRAF V600E mutation and CD34 positivity. The tumours reclassified as GNT/PLGG NOS were equally distributed across both clusters. Interestingly, all polymorphous low grade neuroepithelial tumour of the young belonged to cluster 2 whereas diffuse LGG MAPK pathway-altered were equally distributed among the two clusters. This led us to build an algorithm to classify LEATs with a prominent oligodendroglioma-like component. CONCLUSIONS: Integrated histomolecular diagnosis of LEATs with a prominent oligodendroglioma-like component remains challenging. Because these tumours can be split into two major clusters of biological significance, the clinico-pathological relevance of the four types recognized by the WHO CNS5 within this spectrum of tumours is questionable.
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