Glial Tumors: Diffuse Gliomas

Glial Tumors

• Diffuse gliomas are a group of glial neoplasms that grow in an infiltrative manner, spreading along white matter tracts, perivascular spaces, subpial regions, and surrounding neurons.
• Diffuse gliomas are classified into different categories based on morphologic and genetic features, leading to more biologically uniform diagnoses.

IDH-Mutant and IDH-Wildtype Gliomas

• IDH-mutant diffuse astrocytomas and oligodendrogliomas have more in common with each other than with other entities previously categorized based on lineage assumptions.
• Mutations in the IDH gene are found in 10% of glioblastoma patients and 80% of lower-grade (WHO grade II-III) gliomas, regardless of astrocytic or oligodendroglial lineage.
• Additional mutations such as ATRX and TP53 drive the precursor cell towards astrocytoma morphology, while 1p19q codeletion with mutations of TERT, CIC, and FUBP1 provoke oligodendroglioma phenotype.

Primary Glioblastoma

• Primary (de novo) glioblastoma in older adults is IDH-wildtype by definition, often with associated TERT mutations, cytogenetic alterations, and epidermal growth factor receptor (EGFR) gene amplifications.
• These tumors vary in epidemiologic features, morphologic attributes, growth patterns, genetic profiles, and clinical behavior.

Pediatric and Anatomic Variants

• Pediatric low-grade gliomas often have FGFR1 or MYB alterations.
• H3 K27M-mutant diffuse midline gliomas, BRAF V600-mutant epithelioid glioblastomas, and H3 G34R/V-mutant high-grade hemispheric gliomas are examples of genetically distinct subtypes within different anatomic locations.

Diffusely Infiltrating Astrocytomas

• Diffusely infiltrating astrocytomas are the largest group, with a tendency to biologic progression that reflects a stepwise accumulation of defined genetic abnormalities.
• IDH1 mutations represent the earliest and most common genetic alterations in WHO grade II-III diffuse astrocytomas and secondary glioblastomas.
• The fibrillary type is the most frequently encountered and is considered the de facto subtype when discussing diffuse astrocytomas in general.

Learn about the clinical, pathological, and genetic diversity of diffuse gliomas, a type of glial neoplasm that grows in an infiltrative manner.