Clinical impact of revisions to the WHO classification of diffuse gliomas and associated future problems

Abstract

The publication of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 WHO CNS) represented a major change in the classification of brain tumors. It is essential to determine the IDH and 1p/19q statuses of diffuse gliomas to ensure that the final diagnosis is accurate. The integrated diagnostic method outlined in the 2016 WHO CNS has enabled more precise prediction of the prognoses of diffuse gliomas. However, there are further two points that need to be addressed when planning future clinical trials. The first is the problems with the WHO grading system for diffuse gliomas. The second is that examinations for IDH mutations and 1p/19q co-deletion are not sufficient on their own to accurately predict the prognosis of diffuse glioma patients. Risk of an IDH-mut diffuse glioma should be evaluated based on a combination of clinical factors (age and the resection rate), molecular factors (the presence/absence of CDKN2A deletion), and histological factors (morphology and the mitotic index). Glioblastoma (GBM) have also been classified according to their IDH status; however, the frequency of IDH gene mutations is only 5-10% in GBM. Other molecular markers such as MGMT methylation, pTERT mutations and EGFR amplification could be more important to predict clinical outcome. Therefore, the next revision of the classification of diffuse gliomas will propose a detailed classification based on additional markers. In the near future, treatments for diffuse gliomas will be chosen according to the molecular profile of each tumor.

Keywords: 1p/19q co-deletion; 2016 WHO CNS; Diffuse glioma; IDH mutation.