Molecular revolution in epilepsy.

Abstract

A “long-term epilepsy-associated tumours (LEATs)” was introduced to recognise rare tumour entities in patients with drug-resistant long-term epilepsy that do not match the WHO description and nosology but are likely closer to the disease spectrum. It is the second most common after hippocampal sclerosis. The histopathological classification of LEAT remained ever challenging due to variable microscopic features, including cellular components difficult to differentiate from preexisting neurons, and multiple architectural growth patterns occurring in many LEAT entities. However, inter- and intra-rater agreement is poor for the differential diagnosis of LEAT, also affecting the WHO grading. Molecular neuropathology has revolutionised our understanding of tumour classification strategies and their impact on clinical treatment. However, these studies have focused very much on malignant tumours rather than LEAT. In addition, commonly described molecular genetic findings do not play a role in LEAT, such as IDH1R132H, 1p/19q co-deletions, TERT promoter mutations or MGMT DNA methylation. Hence, BRAF V600E, FGFR1, FGFR2, MYB/ L1 and PRKCA gene alterations have been recognised in common LEAT entities and likely translate into specific subgroups. DNA methylation array analysis has supported this notion but needs further corroboration, in particular by addressing large enough and prospectively collected patient cohorts with LEAT.