Anaplastic ganglioglioma - a diagnosis comprising several distinct tumour types

Anaplastic ganglioglioma is a rare tumour and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications AIM: We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities METHODS: Samples were subjected to histological review, DNA methylation profiling and next generation sequencing. Morphologic and molecular data were summarised to an integrated diagnosis RESULTS: The majority of histologically diagnosed anaplastic gangliogliomas resolved into CNS WHO diagnoses of glial tumours, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, IDH wildtype and diffuse paediatric-type high-grade glioma, H3 wildtype and IDH wildtype (11 and 2/54) followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis and common molecular profiles pointing to a separate entity were not evident CONCLUSION: In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.