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Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours

Abstract

A new edition of the WHO classification of tumours of the CNS was published in 2021. Although the previous edition of this classification was published just 5 years earlier, in 2016, rapid advances in our understanding of the molecular underpinnings of CNS tumours, including the diversity of clinically relevant molecular types and subtypes, necessitated a new classification system. Compared with the 2016 scheme, the new classification incorporates even more molecular alterations into the diagnosis of many tumours and reorganizes gliomas into adult-type diffuse gliomas, paediatric-type diffuse low-grade and high-grade gliomas, circumscribed astrocytic gliomas, and ependymal tumours. A number of new entities are incorporated into the 2021 classification, especially tumours that preferentially or exclusively arise in the paediatric population. Such a substantial revision of the WHO scheme will have major implications for the diagnosis and treatment of patients with CNS tumours. In this Perspective, we summarize the main changes in the classification of diffuse and circumscribed gliomas, ependymomas, embryonal tumours and meningiomas, and discuss how each change will influence post-surgical treatment, clinical trial enrolment and cooperative studies. Although the 2021 WHO classification of CNS tumours is a major conceptual advance, its implementation on a routine clinical basis presents some challenges that will require innovative solutions.

Key points

  • The new 2021 WHO classification of CNS tumours has further integrated molecular data into the typing, subtyping and grading of major tumour groups.

  • Such integration especially affects the classification of adult-type and paediatric-type diffuse gliomas, circumscribed astrocytic gliomas, ependymomas, embryonal tumours and (to a lesser extent) meningiomas.

  • The strengths of this revised scheme include more accurate conceptualization of CNS tumour types, improved diagnostic accuracy and more reliable prognostic subgroups.

  • Challenges include greater need for faster, more widespread molecular testing, more issues with third party payor reimbursement, and greater difficulty in finding and enrolling patients who are eligible for specific clinical trials.

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Fig. 1: Methylation patterns of CNS tumours.
Fig. 2: Decision tree for the evaluation of adult-type diffuse gliomas.
Fig. 3: Therapy for glioblastoma, IDH-wildtype, WHO grade 4.
Fig. 4: Therapy for IDH-mutant glioma.

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Acknowledgements

The authors thank N. Wadhwani for providing the paediatric neuropathology materials used to generate the representative photomicrographs included in the supplementary information of this manuscript. The authors thank L. Jennings, L. Santana dos Santos and P. Jamshidi for the copy number plots in Supplementary Fig. 2. C.H. was supported by grants R01NS102669, R01NS117104, R01NS118039, the Northwestern University P50CA221747 SPORE in Brain Tumour Research, and the Lou and Jean Malnati Brain Tumour Institute at Northwestern.

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C.H., R.J.P. and P.Y.W. researched data for the article, made a substantial contribution to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. T.B. researched data for the article, wrote the article, and reviewed and edited the manuscript before submission.

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Correspondence to Craig Horbinski.

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Nature Reviews Neurology thanks Jan Buckner, who co-reviewed with Ugur Sener; Pieter Wesseling; Christine Marosi; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

WHO grade

World Health Organization tumour grading system; the higher the grade, the greater the tumour malignancy.

Anaplastic

Old term referring to CNS WHO grade 3 tumours.

Chromosome 1p/19q codeletion

Unbalanced translocation leading to a hybrid 1p/19q chromosome that is subsequently lost; one of the hallmark molecular alterations in oligodendrogliomas.

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Horbinski, C., Berger, T., Packer, R.J. et al. Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours. Nat Rev Neurol (2022). https://doi.org/10.1038/s41582-022-00679-w

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