The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

Abstract

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion

“…The standard of care treatment for newly diagnosed GB relies on maximal surgical resection, followed by irradiation and concomitant chemotherapy with the alkylating agent temozolomide (TMZ) [ 1 ]. Most recently, the sixth version of the international standard for the WHO Classification of Tumors of the Central Nervous System (CNS) [ 2 ] and European Association of Neuro-Oncology (EANO) suggestions [ 3 ], stated that the classification of GB is not only based on histology but also on the expression of several molecular markers and is now defined as a diffuse astrocytic glioma with no mutations in IDH genes nor histone H3 genes mutations. Grade IV astrocytoma is genetically distinct from a much more common IDH-wild type GB, although its histological appearance is similar.…”

Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus

“…This in vitro study also showed that metformin would affect the survival of normal stem cells less while administered to glioblastoma cancer cells of Warburg-like phenotypes [73]. Therefore, it is reasonable to expect that the effect of metformin on the prevention of MBT might not be the same to all tumors classified under the category of glioblastoma by the World Health Organization [74]. We were not able to answer questions related to such different bioenergetic phenotypes and more in-depth investigation should be tailored to the bioenergetic phenotypes of the tumor cells in future observational studies or interventional clinical trials.…”

“…However, we did not have histopathological data of MBT for disease confirmation and could only use the ICD-9-CM code as a diagnostic tool. The ICD-9-CM code of 191 for MBT diagnosis does not provide detailed information on the histopathology of MBT as classified by the World Health Organization [74].…”

Proton Therapy and Gliomas: A Systematic Review

“…Pilocytic astrocytoma (WHO Grade I) and astrocytoma (WHO Grade II) correspond to low-grade gliomas and high-grade gliomas, comprising anaplastic astrocytoma (WHO Grade III) and glioblastoma multiforme (WHO Grade IV), have the worst prognosis [2]. Advances in molecular genetics have allowed for the identification of additional prognostic and/or predictive mutations and epigenetic changes, such as isocitrate dehydrogenase (IDH) mutation, chromosome 1p/19q codeletion, and methyl-guanine methyl transferase (MGMT) gene promotor hypermethylation [1], used to refine the classification [3][4][5].…”