The Integrated Histopathologic and Molecular Approach to Adult-type Diffuse Astrocytomas: Status of the Art,Based on the 2021 WHO Classification of Central Nervous System Tumors

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) improved our understanding of the brain neoplasm biology. In more details, differences between diffuse gliomas that primarily occur in adults and those that primarily occur in children have been identified by the terms “adult-type” and “pediatric-type” diffuse gliomas. More importantly, both diagnostic and grading criteria for adult-type diffuse astrocytomas have been modified, by adopting novel molecular markers: diffuse astrocytomas, IDH-mutant have been grouped into a single entity and graded as CNS WHO grades 2, 3, or 4, with the assignment of Grade 4 in the presence of CDKN2A/B homozygous deletion, regardless of the histology 1]. Additionally, at least one of the following genetic alterations has been considered as sufficient to confer to astrocytomas, IDH wild type, a CNS WHO grade 4: i) TERT promoter mutation, ii) EGFR gene amplification, iii) combined gain of whole chromosome 7 and loss of whole chromosome 10 +7/?10]. However, histology remains the solid basis to support these new complementary molecular data, and an integrated diagnosis is highly recommended.