Response to letter to the editor by Moudgil-Joshi and Kaliaperumal

We are pleased that our summary of the major changes in the 2021 WHO Classification of Tumors of the Central Nervous System¹ has generated commentary from Drs. Moudgil-Joshi and Kaliaperumal. In response, we make the following comments regarding the classification and diagnostic approaches, with the understanding that the letter to the editor was in response to a general review article rather than the actual classification, which is yet to be published.

1. The editors of the WHO Classification of Tumours, published as the WHO Blue Books and online, are well aware of the importance of making their recommendations relevant around the world, including in countries that have fewer medical resources. All editors are reminded of this frequently during the preparation of the books. Although the 2021 CNS volume has not yet been published, when it is, readers will find that there are options for diagnosis in patients for whom it is not possible to do further tests. For example, as touched upon in the review article, liberal endorsement of terms such as NOS (not otherwise specified) and NEC (not elsewhere classified) enables widespread use of the terminology, including in low-income situations in any country, or in settings in which further tests will not alter management.

2. The major change in incorporating molecular parameters into the classification of CNS tumors came with the preceding 2016 CNS Blue Book. For the 2016 volume, two surveys informed the editors by demonstrating that techniques such as immunohistochemistry and simpler molecular assays were more widely available than anticipated.^2,3 For 2021, although formal surveys were not redone, there was an assumption that similar access to technologies was available in centers with neurosurgery units.

3. There is often a tension between two ends of a spectrum: making a classification too technology-dependent vs hobbling a classification by not taking advantage of the information generated by new technologies. We are therefore eager to emphasize the distinction between (1) using advanced molecular technologies and the resulting biological knowledge to develop a classification vs (2) necessitating the use of advanced methodologies for diagnosis. The 2021 CNS Blue Book has certainly done the former, but it has not endorsed the latter except in very rare situations. Indeed, in most cases, one can use new methods to define an entity, but utilize readily available surrogates for diagnosis. As mentioned by Drs. Moudgil-Joshi and Kaliaperumal, the 2016 CNS Blue Book was followed by intelligent and creative adaptations of the classification by pathologists in a variety of countries.^4,5 We trust that a similar set of activities will follow the publication of the 2021 CNS Blue Book.

In summary, the 2021 Blue Book is intended to help patients with CNS tumors “around the world,” even if its practical implementation will vary in different places (countries, states, institutions) depending on available resources.