**4.3. The 2016 World Health Organization classification of tumors of the central nervous system**

According to the 2016 World Health Organization classification of tumors of the central nervous system [13], the diffuse gliomas include the WHO grade II and grade III astrocytic tumors, the grade II and III oligodendrogliomas, the grade IV glioblastomas, as well as the related diffuse gliomas of childhood. Then, all diffusely infiltrating gliomas (whether astrocytic or oligodendroglial) are grouped together: based not only on their growth pattern and behaviors but also more pointedly on the shared genetic driver mutations in the *IDH1* and *IDH2* genes. This approach leaves those astrocytomas that have a more circumscribed growth pattern, lack IDH gene family alterations, and frequently have *BRAF* alterations (pilocytic astrocytoma, pleomorphic xanthoastrocytoma) or *TSC1*/*TSC2* mutations (subependymal giant cell astrocytoma) distinct from the diffuse gliomas.

The WHO grade II diffuse astrocytomas and WHO grade III anaplastic astrocytomas are now each divided into IDH-mutant, IDH-wildtype, and NOS categories. It is recommended that WHO grading is retained for both IDH-mutant and IDH-wildtype astrocytomas, although the prognosis of the IDH-mutant cases appears more favorable in both grades.

Glioblastomas are divided into: (1) glioblastoma, IDH-wildtype (about 90% of cases), which corresponds most frequently with the clinically defined primary or de novo glioblastoma and predominates in patients over 55 years of age [14]; (2) glioblastoma, IDH-mutant (about 10% of cases), which corresponds closely to so-called secondary glioblastoma with a history of prior lower grade diffuse glioma and preferentially arises in younger patients [14];and (3) glioblastoma, NOS, a diagnosis that is reserved for those tumors for which full IDH evaluation cannot be performed.
