Glioblastoma

Glioblastoma is a highly malignant primary tumor of the central nervous system arising from astrocytic-lineage cells. In the current WHO classification, adult glioblastoma is generally an IDH-wildtype diffuse astrocytic tumor with grade 4 behavior; necrosis or microvascular proliferation supports the diagnosis, while certain molecular findings can establish it even when those microscopic features are absent.¹ Common defining alterations include TERT promoter mutation, EGFR amplification, or combined chromosome 7 gain and chromosome 10 loss.² The tumor infiltrates brain beyond the visible mass, making complete surgical removal biologically difficult. Its cells can migrate along white-matter tracts and blood vessels, while regions of hypoxia promote treatment resistance and new-vessel formation.

Symptoms depend mainly on the tumor’s location, size, growth rate, and associated swelling. Seizures, progressive headaches, weakness, speech or visual changes, personality change, and cognitive difficulties are common presenting patterns, although no single symptom identifies the disease. Magnetic resonance imaging with contrast usually shows an irregularly enhancing mass surrounded by edema, but imaging alone cannot establish the exact tumor type. Diagnosis requires tissue obtained through biopsy or resection, followed by histopathology and molecular testing. Testing commonly includes IDH1 and IDH2 status, ATRX, TP53, TERT promoter, EGFR, chromosome 7/10 changes, and MGMT promoter methylation. MGMT methylation is primarily a prognostic and treatment-response biomarker for temozolomide, not a substitute for tissue diagnosis.³

Initial treatment usually combines maximal safe surgical resection, radiotherapy, and the chemotherapy drug temozolomide. Surgery reduces tumor burden and supplies diagnostic tissue, but microscopic infiltrating cells remain; radiotherapy therefore targets the operative region and surrounding high-risk tissue. The landmark Stupp trial found longer survival when concurrent and adjuvant temozolomide was added to radiotherapy than with radiotherapy alone, with a median overall survival of about 15 months in the study population.⁴ Treatment is adjusted for age, functional status, molecular findings, tumor location, and patient preferences. Tumor-treating fields may be considered in selected newly diagnosed patients, while recurrent disease may be managed with further surgery, reirradiation, systemic therapy, clinical trials, or supportive care.

Glioblastoma often appears more extensive biologically than it does on a scan because infiltrating cells can lie outside the enhancing margin. A postoperative or post-radiation MRI may also show pseudoprogression: treatment-related inflammation and disrupted blood-brain barrier can mimic tumor growth, particularly soon after chemoradiation. Conversely, nonenhancing tumor may remain clinically important and is difficult to measure reliably. Glioblastomas are molecularly heterogeneous, so different regions of one tumor may contain distinct subclones and respond differently to therapy. Recurrence is usually local or near the original site, but multifocal and multicentric presentations occur. The tumor’s blood-brain barrier abnormalities are uneven, which helps explain why drug delivery is inconsistent. These features have made clinical trials, tissue sampling strategies, imaging interpretation, and quality-of-life care central parts of management.⁵

IDH-wildtype

Lacking a pathogenic mutation in IDH1 or IDH2; the molecular category associated with most adult glioblastomas.

MGMT promoter methylation

An epigenetic change associated with reduced MGMT DNA-repair expression and greater likelihood of benefit from temozolomide.

Pseudoprogression

Treatment-related imaging change that resembles tumor enlargement but does not necessarily represent viable tumor growth.

Maximal safe resection

Removal of as much visible tumor as possible while preserving essential neurological function.