EANO - EURACAN - SNO Guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors

Abstract

In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents, and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, a molecular workup is important for differential diagnosis, in particular, DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasing of prognostic and predictive importance. MRI finding are non-specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas. Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies.

Keywords: circumscribed astrocytic gliomas; glioneuronal tumors; guideline; neuronal tumors.

Fig. 1

Suggested pathological processing of tumors of circumscribed astrocytic gliomas, glioneuronal and neuronal tumors. Diagnostic workup typically starts with histological evaluation of an H&E slide (example of a PXA, (a), followed by immunohistochemical analyses of proliferation markers (b), differentiation markers (eg, GFAP; c) and mutation specific immunohistochemistry (e.g. IDH1 R132H; d). For many tumor types the histological evaluation will guide further molecular testing that may either be desirable or essential for diagnosis (e). In this example the tumor was tested for BRAF because histology represented PXA that frequently harbor BRAF V600E mutation. For cases that are not resolvable by histology (eg, histological features compatible with more than one tumor type) and targeted molecular testing (eg, testing result not clear or testing not established) DNA methylation profiling and consecutive copy number analysis may aid for the classification (f).

Fig. 2

A. Pilocytic astrocytoma, T1 post-contrast MRI image. B. Pleomorphic xanthoastrocytoma, T1 post-contrast MRI image. C. Subependymal giant cell astrocytoma, T1 post-contrast MRI image. D. Ganglioglioma, T1 post-contrast MRI image. E. DNT, T2-weighted MRI image. F. Central neurocytoma, T1 post-contrast MRI image. G. Extraventricular neurocytoma, T1 post-contrast MRI image.