Feb. 21, 2024
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The most recent edition of the World Health Organization Classification of Tumours of the Central Nervous System (WHO CNS-5), in conjunction with a presentation of histological and immunohistochemical tumor characteristics, features substantial advances in the role of molecular diagnostics in the classification of CNS tumors (25; 19). Updated diagnostic criteria, including the most commonly altered gene and molecular profiles of adult- and pediatric-type diffuse gliomas, are discussed in this article.
• Glioblastoma is now defined as an infiltrating (diffuse) astrocytic glioma with no mutations in IDH1/2 genes nor histone H3 genes, histologically characterized by microvascular proliferation, necrosis, or molecular features, including TERT promoter mutation, EGFR gene amplification, and +7/-10 chromosome.
• IDH-mutant astrocytomas are graded 2-4. IDH-mutant WHO grade 4 was previously referred to as IDH-mutant glioblastoma.
• Homozygous deletion of CDKN2A/B is a molecular signature of WHO grade 4 in IDH-mutant astrocytomas.
• Diffuse hemispheric glioma H3 G34-mutant and diffuse midline glioma H3 K27-altered are distinct gliomas corresponding to WHO grade 4.
• In children and young adults, subtypes of IDH‐wildtype or H3‐wildtype diffuse gliomas have distinct clinical features in the setting of a BRAF V600E mutation, FGFR1 alteration, other MAPK pathway alteration, or an MYB or MYBL1 rearrangement.
• Glioblastoma is no longer used in the setting of a pediatric-type neoplasm.
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