High-Grade Gliomas
High-grade gliomas are aggressive and infiltrative primary brain tumors arising from neoplastic glial cells. They represent the largest proportion of malignant primary CNS neoplasms. Classification follows the World Health Organization (WHO) criteria; high-grade tumors are primarily grade III and grade IV, with glioblastoma (WHO grade IV) being the most common diagnosis.
Clinical presentation depends on tumor location and may include headache, seizures, changes in personality or behavior, and focal neurologic deficits (e.g., weakness, speech disturbance, or visual changes). Treatment is always individualized, but the foundation of care typically includes: surgery (for tissue diagnosis/decompression and the safest possible cytoreduction), radiation therapy (fractionated radiotherapy, FRT), and chemotherapy (most often temozolomide—TMZ).
What are high-grade gliomas?
These are malignant, infiltrative primary brain tumors that extend into surrounding tissue and do not have a true capsule.
Gliomas arise from glial cells (astrocytic, oligodendroglial, or mixed lineages) and account for a substantial share of CNS tumors. Under the WHO classification, high-grade gliomas are primarily grade III (anaplastic gliomas) and grade IV (glioblastoma). In clinical practice, many patients are diagnosed upfront with WHO grade IV disease.
How common are they, and who is typically affected?
High-grade gliomas are the most common malignant primary brain tumors in adults.
The incidence of gliomas overall is estimated at > 5 per 100,000 per year. There is a slight male predominance, and diagnosis occurs most often in the 6th–7th decade of life. Most cases are sporadic.
Less commonly, there is a familial predisposition (a small minority of cases) or association with rare inherited syndromes (e.g., neurofibromatosis type 1/2, Li-Fraumeni syndrome). Prior therapeutic ionizing radiation is a recognized risk factor in selected contexts, whereas an association with everyday electromagnetic exposure (e.g., mobile phones) has not been established in a way that changes clinical practice.
What causes the symptoms (tumor, edema, pressure), and what are the most common presentations?
Symptoms result from the tumor itself, surrounding edema, and involvement of functionally eloquent brain regions.
Common presentations include:
- Headache: typically progressive in frequency and/or intensity; may be worse in the morning and accompanied by nausea.
- Seizures: may be the first manifestation—often focal, sometimes secondarily generalized.
- Personality/behavioral changes or cognitive slowing, depending on the region involved.
- Focal neurologic deficits: weakness (hemiparesis), language impairment, visual field deficits, and more.
In high-grade gliomas, peritumoral edema can be substantial and may significantly amplify symptoms. Corticosteroids may provide temporary relief in selected patients, but they do not replace definitive treatment.
How do they appear on MRI, and which sequences help (FLAIR, DWI, MRS)?
MRI is the cornerstone investigation. Imaging can resemble metastasis, lymphoma, or even abscess—so interpretation must be comprehensive.
On MRI, malignant gliomas often appear as irregular, poorly marginated lesions with contrast enhancement (gadolinium-enhancing components). Enhancement may be solid, heterogeneous, or ring-enhancing around central necrosis. In WHO grade III tumors, limited or absent enhancement does not exclude high-grade biology.
FLAIR/T2
Extensive T2/FLAIR hyperintensity is common and may reflect a mixture of edema and infiltrative tumor, which can complicate distinction from other entities such as metastases in certain scenarios.
DWI
In cystic or ring-enhancing lesions, DWI helps the differential diagnosis: abscesses tend to show marked diffusion restriction, whereas glioblastomas typically do not demonstrate the same pattern.
MRS (MR Spectroscopy)
MRS can support grading: an elevated choline/NAA ratio suggests increased cellular turnover, while increased lactate may point to necrosis and hypoxia—features commonly associated with high-grade tumors.
Why is biopsy/tissue sampling needed, and what does pathology show?
Even with excellent imaging, definitive diagnosis and modern classification require histology plus molecular characterization.
Pathology defines tumor type and WHO grade and is central to both prognosis and treatment planning. In anaplastic gliomas (grade III), pathologists see increased mitotic activity and cellular atypia. In glioblastoma (grade IV), hallmark features include microvascular proliferation and necrosis, often with a “pseudopalisading” arrangement of tumor cells around necrotic foci.
What is the role of surgery, and what does “maximal safe resection” mean?
Surgery is a pivotal step: it provides tissue for diagnosis, reduces tumor burden, and often improves symptoms—while prioritizing preservation of neurologic function.
Primary goals of surgery include:
- Histologic and molecular diagnosis (tumor type, grade, and markers).
- Decompression (reducing mass effect and edema) to improve symptoms and quality of life.
- Cytoreduction, which in many series is associated with improved outcomes when achieved safely.
Maximal safe resection means aiming for the greatest possible removal of tumor without compromising critical functions (speech, movement, vision, etc.). The operative plan depends on tumor location, degree of infiltration, proximity to eloquent areas, and the patient’s clinical condition.
Even when a “complete” resection is not achievable, aggressive yet safe debulking can be clinically meaningful.
Radiation therapy (FRT): why is it needed, and how is it planned?
Because malignant gliomas are infiltrative, radiotherapy is designed to treat beyond the visible margins on MRI.
After surgery, the typical standard is fractionated radiotherapy (FRT) with modern conformal planning. Common regimens include approximately 33 fractions × 1.8 Gy (total ~59.4 Gy), depending on protocol and clinical context.
Target volumes usually include the enhancing lesion and relevant FLAIR abnormality with an appropriate margin, because recurrence most often occurs locally, near the original tumor bed.
Chemotherapy (TMZ/PCV): when is it used, and what should I expect?
In glioblastoma, temozolomide (TMZ) administered with FRT (concurrently and then adjuvantly) remains a cornerstone of therapy when tolerated.
Temozolomide (TMZ) is an alkylating agent used in combination with radiotherapy. In practice, many patients receive TMZ during the ~6-week course of radiation, followed by monthly cycles as adjuvant therapy, with duration individualized based on response and tolerability.
In selected WHO grade III tumors—depending on histology and molecular features—radiotherapy and/or chemotherapy (TMZ or PCV) may be discussed as initial strategies, sometimes with the intent of reserving additional options for recurrence—always through individualized oncologic decision-making.
Treatment tolerability, blood counts, and supportive medications are monitored closely by the oncology team.
Molecular markers (MGMT, IDH, 1p/19q, EGFR): why do they matter?
Molecular profiling informs prognosis, likely treatment response, and—more and more—eligibility for targeted strategies and clinical trials.
- MGMT promoter methylation: is associated with better response to TMZ (greater chemotherapy sensitivity).
- IDH1/2 mutations: are more common in certain grade III tumors and secondary grade IV gliomas and are generally linked to a more favorable course.
- 1p/19q codeletion: is characteristic of many oligodendroglial tumors and correlates with better prognosis and chemosensitivity (PCV/TMZ).
- EGFR amplification/EGFRvIII: occurs in a subset of glioblastomas and is associated with more aggressive tumor biology.
Recurrence: what does it mean, and what options exist (reoperation, BVZ, re-irradiation)?
Unfortunately, recurrence is common. Second-line options are selected based on functional status (KPS), lesion location, and prior therapies.
Recurrence may be local (at or near the original site) or more diffuse. Options may include:
- Reoperation in selected patients (age, clinical status, accessibility, distance from eloquent cortex).
- Re-irradiation with carefully chosen protocols, balancing potential benefit with the risk of radiation necrosis.
- Bevacizumab (BVZ) — anti-VEGF therapy: may reduce enhancement/edema and provide symptomatic benefit in selected settings.
- Alternative regimens and clinical trials, when available and appropriate.
A key challenge at recurrence is distinguishing true tumor progression from treatment-related change (e.g., radiation necrosis or pseudoprogression). This often requires expert neuroradiology review and longitudinal assessment.
Prognosis & quality of life: what influences the course?
Clinical course is shaped by tumor biology, extent of safe resection, baseline functional status, and response to adjuvant therapies.
Key prognostic factors include:
- Functional status (KPS) and neurologic deficits at presentation.
- Extent of safe resection (when feasible).
- Molecular markers (MGMT, IDH, 1p/19q, etc.).
- Tolerance of radiotherapy/chemotherapy and treatment-related complications.
The goal is not only “the numbers.” We aim for a plan that preserves neurologic function, controls symptoms, and supports the most stable quality of daily life possible—while maintaining access to therapies that offer benefit.
FAQs & when should you seek a second opinion?
If the tumor does not enhance strongly on MRI, does that mean it is not high-grade?
Not necessarily. Some WHO grade III gliomas can show limited—or no—contrast enhancement. The overall picture (FLAIR, clinical course, evolution over time), and especially histopathology (histology plus molecular profiling), are decisive.
Why can’t the surgeon “remove the entire tumor” in every case?
Because these are infiltrative tumors that often extend into normal brain and may be adjacent to eloquent functional networks. The priority is maximal safe resection—not a resection that would cause a permanent, severe neurologic deficit.
Will I need anti-seizure medication if I have never had a seizure?
Not always. The decision is individualized (tumor location, history, surgery, neurologic status). If a seizure occurs, management typically becomes more proactive.
When is this considered an emergency?
- New or persistent seizure or a cluster of seizures.
- Rapid worsening of speech, strength, or vision.
- Severe headache with nausea/vomiting, drowsiness, or confusion.
At Neuroknife, our approach is structured: expert neurosurgical evaluation, detailed MRI analysis, planning for maximal safe resection when indicated, and close collaboration with neuro-oncology and radiation oncology to deliver an integrated treatment plan.
When should you seek a specialized evaluation for a high-grade glioma?
If you experience a new seizure, progressive headache, behavioral change, or a focal neurologic deficit, timely evaluation matters. In high-grade gliomas, time is clinically important—both for symptom relief and for optimal treatment planning.
With appropriately selected therapy (surgery when indicated, FRT, TMZ, and personalization based on molecular markers), we aim for better disease control and a more stable quality of life.
Schedule an appointment or request a second opinion© Neuroknife — Original medical content by our physicians, provided exclusively for patient education and informational purposes.