Glioblastoma Multiforme

Excerpt

Glioblastoma multiforme (GBM) comprises glioma's most malignant and pervasive subtype. GBM is the most common primary brain tumor in adults, accounting for 45.2% of primary malignant brain and central nervous system (CNS) tumors. Magnetic resonance imaging (MRI) shows poorly circumscribed marginal enhancement. Central hypointensity in T1 due to necrosis and peripheral hyperintensities in T2/FLAIR sequences due to edema are salient MRI features. MR spectroscopy has a choline peak. The definitive diagnosis is made through a histopathological examination that reveals poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmark features of GBM. GBM also shows glial fibrillary acidic protein (GFAP), vimentin, and S100 positivity with varying Ki-67 indices. Testing is also recommended for the presence or absence of GFAP, IDH mutation V status, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.

GBM remains an incurable disease with a median survival of only 15 months. Only 5.5% of patients survive 5 years post-diagnosis. GBM has been classified into isocitrate dehydrogenase (IDH) wild-type and mutant variants. IDH variants bear the cytosine-phosphate-guanine (CpG) island methylation phenotype (G-CIMP).

IDH wild types, arising de novo, constitute almost 90% of all GBM. They are usually observed among cohorts older than age 55 years. Histologically, they comprise the giant cell, gliosarcoma, and epithelioid cell subtypes. They are associated with mutations in the epidermal growth factor receptor (EFGR), telomerase reverse transcriptase gene (TERT), or O-methylguanine DNA methyltransferase (MGMT). IDH-mutants arise from precursor diffuse or anaplastic astrocytoma. They are associated with ATRX and TP53 mutations and typically affect younger patients. They comparatively have longer median survival rates.