Glioblastoma is the most common and aggressive form of glioma, a classification that describes brain tumors originating from the supportive glial cells of the central nervous system. Glioblastoma is definitively a type of glioma. Understanding the relationship between these terms requires examining their cellular origins, pathology, and grading systems.
Understanding Gliomas
Gliomas are tumors that arise from neuroglia, or glial cells, which provide support, protection, and insulation for the brain’s neurons. They are broadly classified based on the specific glial cell type from which they originate. The three primary cell types are astrocytes, oligodendrocytes, and ependymal cells.
Tumors are often named after their cell of origin (e.g., astrocytomas and oligodendrogliomas). Gliomas represent a diverse group, ranging from slow-growing to highly malignant types, with behavior determined by their cellular makeup and molecular characteristics.
Glioblastoma Defined
Glioblastoma (GBM) is a specific type of glioma and the most malignant primary brain tumor in adults. It is characterized by extremely rapid growth and a highly invasive nature, with cells quickly dispersing throughout the brain tissue. Glioblastoma is always designated as a World Health Organization (WHO) Grade 4 tumor, reflecting its aggressive biological behavior.
The tumor’s pathology is marked by three distinct microscopic features: significant cellular proliferation, microvascular proliferation, and widespread necrosis. Microvascular proliferation is the formation of abnormal new blood vessels the tumor uses to sustain its rapid growth. Necrosis involves large areas of dead tissue, often surrounded by tumor cells that line up in a pattern called pseudopalisading.
Classification and Grading Systems
Gliomas are categorized using the World Health Organization (WHO) grading system, which assigns a grade from 1 to 4 to indicate aggressiveness. Grade 1 tumors are typically slow-growing, while Grade 4 tumors, including glioblastoma, are the most aggressive and malignant. Grading traditionally relied on histological features, such as cellular atypia, mitotic activity, necrosis, or microvascular proliferation.
Modern classification integrates molecular diagnostics alongside the tumor’s appearance. Genetic alterations, particularly the status of the Isocitrate Dehydrogenase (IDH) gene, are fundamental to defining glioma subtypes and determining their grade. The 2021 WHO classification defines glioblastoma as an IDH-wildtype tumor, meaning it lacks the IDH gene mutation.
Tumors that are histologically similar to glioblastoma but possess the IDH mutation are now classified as Astrocytoma, IDH-mutant, Grade 4. This distinction is significant because the IDH mutation is associated with a better prognosis. Furthermore, the presence of specific molecular markers, such as a TERT promoter mutation or EGFR gene amplification, can automatically classify a tumor as Glioblastoma, IDH-wildtype, Grade 4, even without classic histological signs.
Management Approaches
Treatment for glioblastoma is typically a multi-modal approach designed to limit tumor progression. The first step involves maximal safe surgical resection, where the neurosurgeon removes as much visible tumor as possible without causing significant neurological damage. Since glioblastomas are highly infiltrative, complete removal is rarely possible, leaving microscopic tumor cells behind.
Following surgery, the standard treatment protocol, often called the Stupp protocol, involves combined radiation therapy and chemotherapy. This includes concurrent daily radiation therapy with the oral chemotherapy drug Temozolomide, followed by a period of adjuvant Temozolomide cycles.
Some patients are also candidates for Tumor Treating Fields (TTFields), which involve wearing a cap that delivers low-intensity electrical fields to the brain. These fields interfere with tumor cell division. Despite these aggressive strategies, the highly malignant nature of glioblastoma means the overall prognosis remains poor, with median survival measured in months.