INSP-02. WHO 2021 classification of CNS tumors

Abstract

In line with recommendations of the cIMPACT-NOW consortium, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5 classification) is substantially different from the previous (revised 4th) edition. Salient changes include the separation of pediatric-type low- and high-grade diffuse gliomas from adult-type diffuse gliomas, refinement of the classification of ependymal tumors, and the addition of a newly recognized embryonal CNS tumors. Furthermore, for some tumors the name was changed. For example, diffuse midline glioma (DMG), H3K27M-mutant is now DMG, H3K27-altered (because there are H3-wildtype DMGs that do show loss of nuclear H3K27me3 staining and with a similar prognosis as DMGs, H3K27M-mutant), and supratentorial ependymoma, RELA fusion-positive was changed into ZFTA fusion-positive (as ZFTA (‘zinc finger translocation associated’, the new name for c11orf95) is the more frequent fusion partner in these tumors). The WHO CNS5 tumor classification certainly is an improvement, but it brings several (new) challenges as well. For example, for more CNS tumors it is now impossible to reach a state-of-the-art ‘histomolecular’ diagnosis in case molecular tools for assessment of essential diagnostic characteristics are not available. In those situations, adding NOS (not otherwise specified) to the histology-based diagnosis is the way to go. Furthermore, designing the optimal therapeutic management for newly defined tumor types is challenging. And while a more precise classification facilitates enrollment of more homogeneous populations of patients in clinical studies, the higher granularity of CNS tumor taxonomy makes it more difficult to perform studies on a large number of patients for particular tumor types. Still, one would like to think that patients suffering from a CNS tumor are better served by a more precise diagnosis because this allows for a better estimation of prognosis and, hopefully sooner than later, for a more tailored and effective therapeutic approach.