Indian Journal of Pathology and Microbiology

: 2022  |  Volume : 65  |  Issue : 5  |  Page : 2--4

The Evolving World Health Organization (WHO) classification of tumors of the central nervous system (CNS): Challenges and opportunities

Chitra Sarkar1, Megha Uppin2, Anita Mahadevan3,  
1 Department of Pathology, AIIMS, New Delhi, India
2 Department of Pathology, NIMS, Hyderabad, Telangana, India
3 Department of Neuropathology, NIMHANS, Bangalore, Karnataka, India

Correspondence Address:
Chitra Sarkar
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi

How to cite this article:
Sarkar C, Uppin M, Mahadevan A. The Evolving World Health Organization (WHO) classification of tumors of the central nervous system (CNS): Challenges and opportunities.Indian J Pathol Microbiol 2022;65:2-4

How to cite this URL:
Sarkar C, Uppin M, Mahadevan A. The Evolving World Health Organization (WHO) classification of tumors of the central nervous system (CNS): Challenges and opportunities. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Jul 5 ];65:2-4
Available from:

Full Text

“Every challenge contains within it the seeds of opportunity and growth”

~Roy P. Bennett

Cancer classification has been traditionally based on histopathological features. However, new technologies are now transforming the field of pathology and our understanding of cancer, especially at the molecular level has now reached a point wherein this information must be included in the diagnosis. Thus in 2016, for the first time, a paradigm shift in the World Health Organization (WHO) classification of central nervous system (CNS) tumors was introduced (updated 4th edition) wherein the concept of 'integrated diagnosis' was initiated by incorporating molecular parameters along with histopathological features.[1] The subsequent 5th edition (WHO CNS5) released in late 2021 added further important changes relating to taxonomy, nomenclature and grading of CNS tumors as well as introduced several newly recognized tumor types and subtypes.[2] Many of these changes have increased the reliance on molecular alterations and importantly in some tumors like gliomas, molecular subgrouping and grading has now been shown to be superior to histopathological grading for risk stratification.

The reviews in this section of the special issue of IJPM cover all the relevant changes in WHO CNS5 in a concise manner and hence will provide very useful reference material for both students and faculty of Pathology. They are written by experts in the field, many of whom are contributors to one or more chapters in the WHO CNS5 classification (Dr. Tariq Tihan, Dr. Takashi Komori, Dr. Felice Giangaspero, Dr. Mehar Chand Sharma, Dr. Vani Santosh, Dr. Kirti Gupta, and Dr. Chitra Sarkar). An important feature of these reviews is the inclusion of flowchart(s) demonstrating simple and practical algorithms for the approach to diagnosis of these tumors, which are expected to help guide pathologists in their routine reporting.

This new WHO CNS5 classification has been welcomed by the neuro-oncology community as it is expected to help in more accurate diagnosis and prognostication of CNS tumors, better prediction of treatment response, risk stratification, improvement in management, design of more specific targeted therapies, and analysis of clinical trials.[3],[4] However, as the saying goes 'Every coin has two sides' and WHO CNS5 is no exception to this as it raises few challenges, queries, and fears as well as provides new opportunities, which are discussed below.

The major challenge relating to WHO CNS5 is the practical applicability of the classification especially in low- and middle-income countries (LMICs) like India, where there is restricted availability of molecular testing facilities owing to the high cost, high turnaround time, lack of technological infrastructure facilities as well as trained manpower (both trained pathologists and technical staff). It is becoming more and more difficult over time to keep pace with the rapidly increasing number of molecular biomarkers and equally complex laboratory testing platforms. Further the relevance and real added value of several of the molecular markers in clinical management is not very clear at the current stage.

Hence, the two most frequently asked questions (FAQs) are: (i) what are the minimum number of mandatory molecular tests that should be included for optimal classification/diagnosis of any particular group of CNS tumors? (ii) what are the acceptable techniques/methods/platforms for each of the individual molecular genetic assays? However, WHO CNS5 does not address both these issues, and justifiably so because there cannot be a 'one size fits all' answer to these questions owing to the immense diversity among and within countries with relation to the resources available.

Thus, how should LMICs react to these challenges? There are two options – either they continue to fret over the lack of facilities or they take these challenges positively and turn them into opportunities to grow. Following are three suggested approaches that LMICs may adopt to facilitate this challenge into an opportunity and India has taken a major lead in the first two:

Develop country/region specific evidence-based guidelines by balancing between the availability of resources, cost, expertise, and turnaround time versus the clinical benefit in the management so that it does not become an unnecessary burden to the patient without real clinical value. Mandatory and optional tests could preferably be indicated by carefully weighing the options between the use of surrogate molecular markers which can be easily done by immunohistochemistry versus sophisticated molecular platforms. Such guidelines have been published based on the 2016 WHO classification of CNS tumors by the Indian Society of Neuro-Oncology (for gliomas and medulloblastomas)[5],[6] and by the Japanese Society of Brain Tumor Pathology (for gliomas).[7] The first guideline as per the WHO CNS5 classification for diagnosis of diffuse gliomas has been recently published by the College of American pathologists andit is hoped that more such guidelines will follow soon.[8]Develop few referral molecular diagnostic labs in selected tertiary care hospitals of every resource limited country/region with all the technological infrastructure and manpower facilities to provide molecular tests at subsidized costs (funded by hospital management/government/funding agencies, etc.). In India, the Department of Health Research-Indian Council of Medical Research has taken up such an initiative called DIAMONDS (DHR-ICMR Advanced Molecular Oncology Diagnostic Services) in 12 major hospitals distributed all over India and another 4 are expected to be added soon. In the first phase, molecular diagnosis is being provided for lung and breast carcinomas and we hope that these services will possibly get extended to CNS tumors in the near future.Redefine Pathology training at a national level. The major training programmes in Pathology continue to be morphology based in most centers and hence need to be redefined to keep pace with the advances in this field. We need to train our next generation of pathologists in molecular pathology to take up this challenging new role.[9] We also need to train our technical staff to handle the complex lab platforms and new technologies.

The next challenge regarding the WHOCNS5 classification is the overarching fear of the replacement of traditional histomorphology by molecular pathology. Where does one strike the balance and preserve the traditional pathologist's knowledge, experience and his/her diagnostic acumen based on the 'trained eye' for observations under the microscope in the face of rapidly advancing molecular technologies? It must be emphasized here that this fear is unfounded because both 2016 and 2021 WHO classifications stress on the concept of 'integrated diagnosis' wherein histopathology still has a central role. The addition of genotype to the phenotype adds objectivity and provides greater reliability as well as translational value (prognostic and predictive) to the diagnosis. Further, WHO endorses the liberal use of the term NOS (not otherwise specified) in settings where further molecular tests cannot be done, reinforcing that only histomorphology based reports can still be given out. It must also be noted that in the WHO CNS5 classification there are a little more than 100 tumor types. However, diagnostically relevant molecular signatures prevailing over histopathology are used only for some of these types such as diffuse gliomas and embryonal tumors, while for most of the other tumors such as meningiomas, microscopy continues to play a pivotal role.

Thus the “molecular revolution” should not be taken as a threat to undermine the value of traditional histomorphology. Instead, this should be taken as an opportunity for traditional pathologists to accept their changing role, expand their horizon beyond morphology and embrace the power of molecular diagnostics. In the era of 'precision oncology' and 'personalised medicine,' molecular pathology has provided pathologists with a unique opportunity to gain a pivotal role in the translation of biomarker discovery into clinical application and in the therapeutic decision-making process. Let us utilize this opportunity to build the Pathology of the 21st century, namely “Morpho-Molecular Pathology”.[10] In the words of the great Indian philosopher Swami Vivekananda, 'Let us not lower our goals to the level of our abilities. Instead let us raise our abilities to the level of our goals.'

To conclude, we wish to convey our sincere thanks to the editorial board of IJPM and the executive committee of IAPM for giving us this opportunity to edit this special issue on Neuropathology. We sincerely appreciate the efforts, time, as well as valuable contributions and suggestions by the authors and reviewers. Last but not the least, we gratefully acknowledge the unstinting support and guidance of the editor-in-chief – Dr. Ranjan Agrawal. We do hope that this special issue on Neuropathology will benefit all students and faculty of Pathology.


1Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. World Health Organization Classification of Tumors of the Central Nervous System. (Revised 4th ed). Lyon: International Agency for Research on Cancer; 2016.
2Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of tumors of the central nervous system: A summary. Neuro Oncol 2021;23:1231-51.
3Gritsch S, Batchelor TT, Gonzalez Castro LN. Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system. Cancer 2022;128:47-58.
4Wen PY, Packer RJ. The 2021 WHO Classification of Tumors of the Central Nervous System: Clinical implications. Neuro Oncol 2021;23:1215-7.
5Santosh V, Sravya P, Gupta T, Muzumdar D, Chacko G, Suri V, et al. ISNO consensus guidelines for practical adaptation of the WHO 2016 classification of adult diffuse gliomas. Neurol India 2019;67:173-82.
6Gupta T, Sarkar C, Rajshekhar V, Chatterjee S, Shirsat N, Muzumdar D, et al. Indian Society of Neuro-Oncology consensus guidelines for the contemporary management of medulloblastoma. Neurol India 2017;65:315-32.
7Sonoda Y, Yokoo H, Tanaka S, Kinoshita M, Nakada M, Nishihara H, et al. Practical procedures for the integrated diagnosis of astrocytic and oligodendroglial tumors. Brain Tumor Pathol 2019;36:56–62.
8Brat DJ, Aldape K, Bridge JA, Canoll P, Colman H, Hameed MR, et al. Molecular biomarker testing for the diagnosis of diffuse gliomas. Arch Pathol Lab Med 2022. doi: 10.5858/arpa. 2021-0295-CP.
9Moore DA, Young CA, Morris HT, Oien KA, Lee JL, Jones JL, et al. Time for change: A new training programme for morpho-molecular pathologists? J Clin Pathol 2018;71:285-90.
10Masood S. The changing role of pathologists from morphologists to molecular pathologists in the era of precision medicine. Breast J 2020;26:27-34.