Anaplastic ganglioglioma—A diagnosis comprising several distinct tumour types

Abstract

Aims 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. 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, desoxyribonucleic acid (DNA) methylation profiling and next‐generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis. Results The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric‐type high‐grade glioma, H3 wild type and IDH wild type (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. Conclusions 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.

Primary spinal intramedullary anaplastic ganglioglioma in a pediatric patient

“…However, diagnostic criteria for AGG continues to be challenging, with attempts to categorize tumors by their molecular profiles. [12] A recent study by Reinhardt et al, 2022, showed that this diagnosis may be resolved into several distinct tumor types based on molecular characteristics which may carry different prognostic and therapeutic implications. [22] For example, the authors suggest AGGs with H3 mutations could be classified as diffuse midline gliomas (DMGs).…”

“…[12] A recent study by Reinhardt et al, 2022, showed that this diagnosis may be resolved into several distinct tumor types based on molecular characteristics which may carry different prognostic and therapeutic implications. [22] For example, the authors suggest AGGs with H3 mutations could be classified as diffuse midline gliomas (DMGs). However, AGGs do not have a separate methylation class, suggesting that the histological criteria used for diagnosis may represent a heterogeneous group of tumor entities.…”

Brain Tumors in Adolescents and Young Adults: A Review

“…76 However, the true existence of anaplastic ganglioglioma is currently debated, and some previously reported cases have now been reclassified using DNA methylation profiling. 54 77 For the majority of patients, management consists of antiseizure medications and surgical resection for patients with refractory epilepsy, hydrocephalus, or focal neurological deficits. MSR is usually recommended, and a higher extent of resection is associated with improved recurrence-free survival and seizure control.…”

Neuropil‐like islands are a possible pathogenetic link between glioblastoma and gangliocytoma/ganglioglioma in a case of synchronous bilateral brain tumors

“…Among the genetic alterations investigated, the TERT promoter mutation was the only difference between the two tumors (i.e., it was mutated (C250T) in the former (left parietal tumor), while it was wild type in the latter (right medial temporal tumor)). A systematic analysis using DNA methylation profiling and next-generation sequencing, 11,17 which would have been helpful to delineate further the pathogenetic relationship between the two tumors, was not available in this study.…”

“…Based on genetic analyses, the former tumor was a telomerase reverse transcriptase promoter gene (TERT) mutated tumor, and the latter a non-TERT mutated tumor. In a systematic analysis, Reinhardt et al (2022) described anaplastic GGs using DNA methylation profiling and next-generation sequencing, 11 where a histologically diagnosed cohort of anaplastic GG was mostly resolved into other established central nervous system (CNS) WHO brain tumors, including GBM. Here, we describe the patient's clinicopathological and genetic features and examine the pathogenetic relationship between the two tumors.…”