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Year : 2019  |  Volume : 2  |  Issue : 4  |  Page : 165-166

The 2016 revision of the World Health Organization classification of tumors of the central nervous system: Evidence-based and morphologically flawed

Department of General and Clinical Pathology, Forensic Medicine and Deontology, Faculty of Medicine, Medical University - Varna “Prof. Dr. Paraskev Stoyanov”, Varna, Bulgaria., Bulgaria

Date of Submission07-Dec-2019
Date of Acceptance19-Dec-2019
Date of Web Publication23-Jan-2020

Correspondence Address:
Dr. George S Stoyanov
Hr. Smirnenski 1 Blvd, Varna 900
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/glioma.glioma_24_19

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How to cite this article:
Stoyanov GS. The 2016 revision of the World Health Organization classification of tumors of the central nervous system: Evidence-based and morphologically flawed. Glioma 2019;2:165-6

How to cite this URL:
Stoyanov GS. The 2016 revision of the World Health Organization classification of tumors of the central nervous system: Evidence-based and morphologically flawed. Glioma [serial online] 2019 [cited 2022 Nov 27];2:165-6. Available from: http://www.jglioma.com/text.asp?2019/2/4/165/276697

The 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) was one of the first to introduce genetic subtyping in the histological groups of these tumors.[1] However, since its introduction and based on the lack of histological criteria in the article summary of the classification, which is often cited as the classification itself, nonpathologists have become extremely ignorant of the difficulties in identifying these rare and diverse tumor entries.[2]

The few histological features mentioned in the article have great suggestions to clinicians and neuroscientists that the classification is based solely on the presence or absence of genetic mutations [Figure 1]. This has largely left pathologists and their pivotal role in the dark. While extensive morphological features are placed in the full text of the revised 2016 edition WHO classification of CNS tumors, the bluebook is often read only by pathologists, and only they are acquainted with the place of morphological evaluation in the diagnostic process. Without morphology, the identification of CNS tumors would be an impossible task; however, it rarely, if at all, is mentioned.
Figure 1: Diagnostic process for central nervous system tumors. The article summary focuses solely on the additions to the edited classification, whilst gross, morphological, and immunohistochemical depictions are noted only in the World Health Organization (WHO) bluebook

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This has had several side effects, mainly clinicians not understanding the full diversity of CNS tumors and their ability to mimic both other primary tumors and metastatic entries. Furthermore, the presence of some mutations in only one histological group has also made clinicians underestimate the role of the pathologist in the diagnostic process. As per the classification, the pathologist should only evaluate the presence of mutations. Second, many epidemiological studies have focused solely on primary entries as metastatic ones are not included in the classification and as such are omitted from the study as well as other nontumor lesions, also requiring a differential diagnosis histologically with tumors such as demyelinating pseudotumors and echinococcosis.

Third, this has led to a genetic frenzy in trying to identify new molecular features in studies that have only a hand full of tumors, without assessing the overall patient condition, concomitant diseases and the presence of any secondary and tertiary factors, such as percentage of cells with the mutation, type of cell, etc.

Furthermore, multiple journals have denied publications of research focused on some tumors, such as glioblastoma multiforme, if the tumors included were not otherwise specified, which sadly is the case with a multitude of healthcare centers as the WHO defined mutations cannot be evaluated due to cost purposes.

This has led to further, nonofficial editions to the WHO classification in the form of short articles elaborating on new findings to try and decrease the presence of not elsewhere classified category of CNS tumors and elaborate on the extent of the WHO defined mutations. One such classification is the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy–Not Official WHO (cIMACT-NOW), further elaborating on the WHO diagnostic criteria, often defining that the diagnosis is histology-based, as a single mutation cannot define the WHO grade of morphological group and that the WHO defined classes correlate to patient prognosis only in some instances.[3],[4],[5] Worthy of note is that the cIMPACT-NOW members are also on the WHO board and have taken part in the 2016 classification.

The intent of these members to further clarify and improve their own classification is worthy of noting and identifies their own understanding of the misinterpretation of multiple scientists across many disciplines on the defined criteria and the diagnostic process.[3]

Therefore, from a peer and reviewers' point of view, it is important for all authors to have included an interpretation of this evolving nomenclature into their manuscripts as to follow their statements over time and their overall understanding of the topic. Furthermore, it is the role of specialized journals to subject manuscripts to extensive peer reviews and not to allow manuscripts with an improper interpretation of the diagnostic criteria of the WHO and cIMPACT-NOW guidelines to overpraise the findings, while downplaying histopathology.[3]

With the next edition of the WHO classification of CNS tumors, being planned for late 2020, which is an extremely short active period for the current classification (the current 2016 classification represents an edited fourth classification from 2007, with the latest unrelated classification being the third one from 2000).[2] This showcases both a paradigm shift for the new evidence aggregated in the field and intent for evidence-based mutational status to be included and possible expansion and better integration of histology and genetics, which in the current edited form of the classification is difficult to balance and understand for some in the field.

As the first to officially include genetic markers, the revised 2016 WHO classification of CNS tumors has had a difficult task of balancing the histopathological diagnosis with the genetic grouping of CNS tumors, evident by the revisions by the committee themselves and the extremely short shelf life of the classification when compared to previous entries.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO Classification of Tumours of the Central Nervous System: WHO Classification of Tumours. Revised 4th edition., Vol. 1. Lyon: International Agency for Research on Cancer; 2016.  Back to cited text no. 1
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 2
Louis DN, Ellison DW, Brat DJ, Aldape K, Capper D, Hawkins C, et al. cIMPACT-NOW: A practical summary of diagnostic points from Round 1 updates. Brain Pathol 2019;29:469-72.  Back to cited text no. 3
Louis DN, Wesseling P, Paulus W, Giannini C, Batchelor TT, Cairncross JG, et al. cIMPACT-NOW update 1: Not Otherwise Specified (NOS) and Not Elsewhere Classified (NEC). Acta Neuropathol 2018;135:481-4.  Back to cited text no. 4
Louis DN, Giannini C, Capper D, Paulus W, Figarella-Branger D, Lopes MB, et al. cIMPACT-NOW update 2: Diagnostic clarifications for diffuse midline glioma, H3 K27M-mutant and diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant. Acta Neuropathol 2018;135:639-42.  Back to cited text no. 5


  [Figure 1]

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