The 2016 WHO Classification of Tumours of the Central Nervous System: The Major Points of Revision

Abstract

The updated 2016 edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System (CNS) uses molecular parameters and the histology to define the main tumor categories for the first time. This represents a shift from the traditional principle of using neuropathological diagnoses, which are primarily based on the microscopic features, to using molecularly-oriented diagnoses. Major restructuring was made with regard to diffuse gliomas, medulloblastomas and other embryonal tumors. New entities that are defined by both the histological and molecular features include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, wingless (WNT)-activated and medulloblastoma, sonic hedgehog (SHH)-activated; and embryonal tumor with multilayered rosettes, C19MC-altered. In addition, some entities that are no longer diagnostically relevant-such as CNS-primitive neuroectodermal tumor-have been deleted from this updated edition. The WHO2016 certainly facilitates clinical and basic research to improve the diagnosis of brain tumors and patient care.

Keywords: World Health Organization (WHO); classification; genetics; histology; new entities.

Fig. 1

Anaplastic astrocytoma, WHO2016. (a) Relatively uniform oval to elongated nuclei are evident in microcystic background. (b) In a higher-powered view, some nuclei are naked without apparent cytoplasmic processes while some pose fibrillary processes, nuclei showing irregularity and hyperchromasia. Such features correspond to anaplastic oligoastrocytoma in the previous WHO classification. (c) IDH1R132H immunohistochemistry is negative. (d) p53 is diffusely positive, suggesting TP53 mutation. (e) ATRX immunoreactivity is lost in tumor cells but intact in endothelial cells. (f) Positive p53 and negative ATRX suggest the presence of IDH mutation. Sanger sequence reveals a R132L mutation in IDH1.

Fig. 2

Diffuse midline glioma, H3 K27M-mutant. (a) Axial FLAIR MRI shows an ill-defined high intensity area in the left thalamus. (b) Thalamic tumor shows diffuse astrocytic morphology with anaplasia. (c) The tumor cells show strong GFAP expression. (d) Sagittal FLAIR MRI shows a diffusely infiltrating pontine glioma expanding the pons. (e) IDH1 R132H immunohistochemistry is negative. (f) Strong nuclear staining for K27M-mutant H3 is present.

Fig. 3

Diffuse leptomeningial glioneuronal tumor (DLGNT) (a–d) and vacuolating neuronal tumor (MVNT) (e–j). (a) Expansion by tumor tissue of the cerebellar leptomeninges without apparent intraparenchymal masses (Klüver-Barrera staining). (b) Showing the mixture of small, round oligodendroglia-like cells and irregularly oriented neuronal cells. (c) Occasionally tumor tissue shows mucin-rich microcystic background. (d) Neuronal cells as well as the neoplastic stroma show positive synaptophysin immunoreactivity. (e, f) Axial FLAIR MRIs show a irregular cortical lesion in the right medial temporal lobe. (g) Multiple nodular or patchy lesions in the subcortical white matter are evident in Klüver-Barrera staining. (h) Dysplastic cells having an abundant amphiphilic to eosinophilic cytoplasm with peripheral Nissl substance showed focal clustering. (i). Tumor cells are strongly positive for α-internexin on the cell membranes. (j) The dysplastic neurons were intensely stained by HuC/Hu.