Glioneuronal Tumour With Neurocytic Differentiation (GNTN): a Molecularly Defined Tumour Type Formerly Referred to as Extraventricular Neurocytoma

Tumours historically classified as extraventricular neurocytoma (EVN), initially in comparison with central neurocytoma, are defined by location and morphology; however, emerging molecular data demonstrate that this term is outdated. We report 14 previously unpublished tumours with a robust EVN DNA methylation profile, independent of original histopathologic diagnosis or anatomic location. Integrated molecular analyses identified FGFR1 alterations, particularly FGFR1::TACC1 fusions, as the predominant molecular driver of this tumour class. A smaller number of tumours harboured FGFR1 hotspot mutations (p.N546K and p.K656E). Among these, two cases additionally showed NF1 variants, and one tumour carried a PIK3CA mutation (p.H1047L). In addition, a single case exhibited an NTRK2 fusion. Histologically, tumours exhibited neurocytic differentiation with neuropil islands and a minor glial component, while immunohistochemistry showed frequent OLIG2 expression, contrasting with the typical immunophenotype of central neurocytoma. Notably, tumours with an EVN DNA methylation profile were identified in both extraventricular and intraventricular locations, demonstrating that anatomy-based definitions are inadequate for this tumour type. Clinical follow-up (median 33.2 months) showed predominantly lower grade behaviour, with occasional recurrence. Collectively, these findings support the view that tumours previously labelled as EVN do not represent a direct counterpart of central neurocytoma but instead constitute a molecularly and epigenetically distinct glioneuronal tumour type. We propose the designation glioneuronal tumour with neurocytic differentiation (GNTN) to reflect its biological identity and to align the terminology with contemporary molecular neuropathology, and recommend DNA methylation profiling as an essential diagnostic criterion.