Abstract
Background
Diffuse astrocytic and oligodendroglial gliomas are the most common neuroepithelial tumors. Their classification is based on the integration of histological and molecular findings according to the classification of tumors of the central nervous system published by the World Health Organization (WHO) in 2016.
Objectives
This review describes the different entities and variants of diffuse gliomas and summarizes the current diagnostic criteria for these tumors.
Materials and methods
Based on the 2016 WHO classification and selected other publications, the histomolecular diagnostics of diffuse gliomas is presented and illustrated.
Results
Diffuse gliomas are divided into isocitrate dehydrogenase (IDH)-mutant or IDH-wildtype gliomas by detection of mutations in the IDH1 or IDH2 genes. Among the IDH-mutant gliomas, oligodendroglial tumors are characterized by combined losses of chromosome arms 1p and 19q. Loss of nuclear expression of the ATRX protein is a marker of IDH- mutant astrocytic gliomas. Glioblastoma, IDH-wildtype, is the most common diffuse glioma. Diffuse and anaplastic astrocytic gliomas without IDH mutation should be further evaluated for molecular features of glioblastoma, IDH-wildtype. Diffuse gliomas in the thalamus, brainstem, or spinal cord carrying a histone 3 (H3)-K27M mutation are classified as diffuse midline gliomas, H3-K27M-mutant. By determining the IDH and 1p/19q status, oligoastrocytomas can be stratified into either astrocytic or oligodendroglial gliomas. Gliomatosis cerebri is no longer regarded as a distinct glioma entity.
Conclusions
Diffuse gliomas can today be classified accurately and reproducibly by means of histological, immunohistochemical, and molecular analyses.
Zusammenfassung
Hintergrund
Diffuse astrozytäre und oligodendrogliale Gliome sind die häufigsten neuroepithelialen Tumoren. Ihre diagnostische Einordnung erfolgt durch Integration histologischer und molekularer Befunde gemäß der 2016 von der Weltgesundheitsorganisation (WHO) herausgegebenen Klassifikation der Tumoren des zentralen Nervensystems.
Ziel der Arbeit
Die Arbeit beschreibt die verschiedenen Entitäten und Varianten diffuser Gliome und die diagnostischen Kriterien für diese Tumoren.
Material und Methoden
Basierend auf der WHO-Klassifikation 2016 und ausgewählten aktuellen Veröffentlichungen wird die histomolekulare Diagnostik diffuser Gliome erläutert und anhand eigener Befunde illustriert.
Ergebnisse
Diffuse Gliome werden durch Nachweis von Mutationen in den Isocitratdehydrogenase(IDH)-Genen 1 oder 2 in IDH-mutierte und IDH-Wildtyp-Gliome unterteilt. Unter den IDH-mutierten Gliomen zeigen oligodendrogliale Tumoren kombinierte Verluste der Chromosomenarme 1p und 19q. Ein Verlust der nukleären Expression des ATRX-Proteins spricht dagegen für ein IDH-mutiertes astrozytäres Gliom. Glioblastome (IDH-Wildtyp) sind insgesamt die häufigsten diffusen Gliome. Diffuse und anaplastische Astrozytome ohne IDH-Mutation sollten auf molekulare Merkmale eines Glioblastoms, IDH-Wildtyp überprüft werden. Diffuse Gliome im Thalamus, Hirnstamm oder Rückenmark, bei denen eine Histon-3(H3)-K27M-Mutation vorliegt, werden als diffuse Mittelliniengliome, H3-K27M-mutiert klassifiziert. Anhand des IDH- und 1p/19q-Status lassen sich Oligoastrozytome entweder als astrozytäre oder oligodendrogliale Gliome einordnen. Die Gliomatosis cerebri wird nicht mehr als eigene Entität betrachtet.
Diskussion
Mittels histologischer, immunhistochemischer und molekularpathologischer Untersuchungen lassen sich diffuse Gliome heutzutage präzise und reproduzierbar diagnostizieren.
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G. Reifenberger has received research funding from Roche and Merck as well as fees for lectures or consulting activities from AbbVie. B. Malzkorn declares that he has no conflicts of interest.
The tissue samples used for the histological images in Figs. 2 and 3 were retrieved from the archive of the Institute of Neuropathology at Heinrich Heine University Düsseldorf. The use of archival samples for research purposes was approved by the Ethics Commission of the Medical Faculty of the Heinrich Heine University Düsseldorf (Study No. 3562).
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Malzkorn, B., Reifenberger, G. Integrated diagnostics of diffuse astrocytic and oligodendroglial tumors. Pathologe 40 (Suppl 1), 9–17 (2019). https://doi.org/10.1007/s00292-019-0581-8
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DOI: https://doi.org/10.1007/s00292-019-0581-8