Is high-grade glioma the same as glioblastoma?

Not exactly. Glioblastoma is a specific type of Grade 4 glioma defined by being IDH wild-type. Other high-grade gliomas include Grade 3 IDH-mutant astrocytoma, Grade 3 oligodendroglioma, and Grade 4 IDH-mutant astrocytoma. They are related diseases but are classified and treated differently, and outcomes vary significantly between them.

How is a high-grade glioma treated?

Standard treatment combines maximal safe surgical resection, radiation therapy, and chemotherapy. The specific chemotherapy regimen and the treatment sequence depend on the tumor’s molecular features, particularly IDH mutation status and 1p/19q codeletion status.

Can a high-grade glioma progress to a higher grade?

Yes. Grade 3 gliomas, particularly IDH-mutant astrocytomas, can progress over time to Grade 4 tumors. This is one of the reasons that ongoing monitoring with imaging is standard after initial treatment and that treatment plans are often adjusted over time based on how the disease evolves.

Should I get a second opinion?

Yes, particularly to confirm the molecular classification and to identify any clinical trial options. High-grade glioma treatment has changed significantly with the 2021 WHO classification, and ensuring that your diagnosis reflects the current standard matters. A specialist evaluation can confirm the diagnosis, review the molecular profile, and clarify the full range of treatment options.

High-Grade Glioma

Specialized surgical and multidisciplinary treatment for Grade 3 and Grade 4 brain tumors, guided by modern molecular diagnosis.

Overview

What Is a High-Grade Glioma?

High-grade glioma is a type of brain cancer that grows from the supportive cells of the brain. It includes Grade 3 and Grade 4 tumors under the World Health Organization grading system, with higher grades meaning the tumor grows more quickly and behaves more aggressively. About 4 out of every 100,000 adults are diagnosed with a high-grade glioma each year in the United States.

Common symptoms include new seizures, persistent or worsening headaches, weakness or numbness on one side of the body, and changes in speech, vision, memory, or behavior. Symptoms depend on where in the brain the tumor is growing.

Treatment usually starts with surgery to remove as much of the tumor as possible, followed by radiation and chemotherapy chosen based on the tumor’s specific features. Dr. Sherman has experience treating high-grade gliomas at Rutgers Cancer Institute in New Brunswick, NJ.

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The information on this page is general educational information and is not medical advice. It does not create a doctor-patient relationship or reflect a treatment recommendation for any individual. Treatment decisions require an individual evaluation by a qualified physician.

High-grade glioma symptoms usually develop gradually, over weeks to a few months, and depend on where in the brain the tumor is growing. Some patients first experience a single event like a seizure; others notice subtle changes that build up over time.

Here’s what makes symptoms worth investigating.

New seizures. A first seizure in an adult is one of the most common presenting symptoms of a Grade 3 glioma. Any first seizure warrants prompt brain imaging, even if the patient recovers completely afterward.

Persistent or worsening headaches. Headaches that are new, gradually worsening, worse in the morning, or come with nausea or vomiting warrant evaluation. Occasional headaches are common and almost never a brain tumor, but a new pattern over weeks is worth imaging.

Weakness or numbness on one side of the body. New focal neurologic symptoms affecting one specific side or one specific function point to a specific area of the brain and deserve prompt evaluation.

Changes in speech, vision, or memory. New difficulty finding words, changes in vision that don’t resolve, or new problems with short-term memory are all worth reporting to a doctor.

Personality, mood, or behavior changes. Subtle changes noticed more by family than by the patient can be an early sign of a tumor in the frontal lobes and often warrant imaging if they persist over weeks.

Difficulty with balance or coordination. New problems walking, unsteadiness, or coordination changes can be caused by tumors affecting specific brain regions and warrant evaluation.

A single neurologic event that doesn’t fully resolve. Sometimes the first sign of a high-grade glioma is a transient event, a brief episode of weakness, confusion, speech trouble, or vision change, that the patient initially attributes to stress or fatigue. Any episode that doesn’t fully return to normal is worth reporting.

When to treat it as an emergency. Sudden severe symptoms, loss of consciousness, sudden inability to speak, or a seizure that doesn’t stop should be treated as an emergency. Go to the nearest emergency room rather than waiting for an appointment.

For everything else, new neurologic symptoms warrant evaluation within days to a couple of weeks. High-grade gliomas grow more quickly than lower-grade tumors, so the pace of workup is typically faster than for a slower-growing lesion.

Imaging

MRI of the brain with and without contrast is the standard imaging study for any suspected brain tumor. On MRI, high-grade gliomas typically appear as masses that take up contrast, often with irregular borders, areas of swelling in the surrounding brain tissue, and sometimes areas of cell death in the center of the tumor. Experienced neuroradiologists can often identify features that suggest a high-grade glioma on imaging, but the imaging alone cannot definitively distinguish between a Grade 3 tumor, a Grade 4 glioblastoma, or certain other conditions that can look similar.

Additional imaging, such as MR spectroscopy or perfusion imaging, is sometimes used to gather more information about a suspected high-grade glioma before a biopsy or surgery. These techniques can suggest the tumor’s aggressiveness and help with surgical planning, but they do not replace tissue diagnosis.

Tissue Diagnosis and Molecular Profiling

Definitive diagnosis of a high-grade glioma requires tissue, obtained either through a stereotactic biopsy or, more commonly, during surgical removal of the tumor. A neuropathologist examines the tissue under a microscope to determine the tumor’s grade and specific type.

For high-grade gliomas, the microscopic examination is only the beginning. Modern diagnosis requires molecular profiling, which analyzes the tumor’s DNA to identify specific features that determine both the exact classification and the treatment approach. The most important markers for Grade 3 gliomas include:

IDH mutation status. The presence or absence of a mutation in the IDH1 or IDH2 gene is the single most important molecular finding. IDH-mutant Grade 3 tumors are a distinct disease with a more favorable prognosis than IDH wild-type tumors, and they are treated somewhat differently.

1p/19q codeletion. The loss of specific portions of chromosomes 1 and 19 defines oligodendroglioma, which responds especially well to a combination of radiation and chemotherapy and carries a more favorable long-term outlook.

MGMT methylation status. A gene that affects how well the tumor responds to chemotherapy.

ATRX status and other markers. Additional markers that help confirm the specific tumor type and guide treatment.

Comprehensive molecular profiling is now central to high-grade glioma classification and informs how treatment options are weighed. At NCI-designated cancer centers, including Rutgers Cancer Institute, the only NCI-designated comprehensive cancer center in New Jersey, molecular testing is part of the routine diagnostic process.

High-grade glioma is almost always treated with a combination of surgery, radiation, and chemotherapy. The specific plan depends on the tumor’s molecular profile, location, size, and the patient’s overall health.

Surgery: The Foundation

Surgery is almost always the first step. The goal is maximal safe resection, which means removing as much of the visible tumor as possible without damaging the parts of the brain that control speech, movement, memory, and other essential functions. Evidence consistently shows that more complete surgical removal is associated with better long-term outcomes, and for high-grade gliomas, supramaximal resection (removing tumor tissue slightly beyond what’s visible on imaging) may offer additional benefit in some cases. Surgery also provides the tissue needed for molecular profiling, which shapes every decision that follows.

Several specialized surgical techniques are available depending on the tumor’s location and characteristics. Awake craniotomy, where the patient is awake for parts of the procedure, allows brain function to be mapped in real time and is used for tumors in or near areas controlling speech or motor function. Fluorescence-guided surgery uses a fluorescent marker that makes high-grade glioma tissue visible under specialized light, helping distinguish tumor from healthy brain and improving the extent of safe removal.

Radiation Therapy

After surgery, most patients with high-grade glioma receive radiation therapy to the area where the tumor was, typically delivered in small daily doses over several weeks. Radiation targets residual tumor cells that cannot be seen or removed during surgery. The specific radiation plan depends on the tumor’s location, molecular features, and the extent of surgical removal.

Chemotherapy

Chemotherapy is a standard part of treatment for most high-grade gliomas. The specific regimen depends on the molecular features of the tumor. For IDH-mutant Grade 3 astrocytomas, chemotherapy with an oral drug is typically given along with or after radiation. For oligodendrogliomas with 1p/19q codeletion, a different chemotherapy combination has been shown to be particularly effective and is often used. The treatment sequence, including when chemotherapy starts and how long it continues, is tailored to the specific tumor type.

Clinical Trials

Clinical trials are an active area in high-grade glioma care, testing new treatment combinations, targeted therapies matched to specific molecular markers, and newer approaches including immunotherapies. For patients with IDH-mutant tumors in particular, several trials are evaluating drugs that target the IDH mutation directly. Whether a trial is appropriate depends on the tumor’s specific molecular profile, the patient’s overall health, and what’s currently enrolling.

LITT for Deep or Recurrent Disease

For high-grade gliomas located deep in the brain where traditional surgery carries significant risk, or for tumors that recur after initial treatment, Laser Interstitial Thermal Therapy offers a minimally invasive option that uses targeted heat to destroy tumor tissue.

How the Plan Gets Made

High-grade glioma treatment is built on coordination. Decisions typically involve neurosurgery, radiation oncology, medical oncology, and neuropathology, and the plan is usually made by weighing all of the factors together: the tumor’s molecular profile, its location, how much was removed at surgery, and the patient’s overall condition and priorities. For patients with IDH-mutant or oligodendroglial tumors, long-term planning matters just as much as the initial treatment, because these are diseases that can be managed over years.

Treatments commonly used for this conditionBrain Tumor Surgery, Awake Craniotomy, Fluorescence-Guided Surgery, Laser Interstitial Thermal Therapy (LITT), and Clinical Trial Enrollment.

Technology

Using XR Technology To Advance Medical Care

Dr. Sherman integrates VR and AR visualization into surgical planning and patient education, giving patients a clearer picture of their diagnosis and the approach to treatment.

Common Questions About High-Grade Gliomas

Glioma grade describes how aggressive the tumor appears under the microscope and how it tends to behave. Low-grade gliomas (Grade 2) generally grow more slowly and are less aggressive. High-grade gliomas (Grade 3 and Grade 4) grow more quickly and require more intensive treatment. Grade 3 and Grade 4 tumors are also classified by their molecular features, which are often as important as the grade itself.

Prognosis varies widely based on molecular features, age, overall health, and extent of surgical removal. Published outcomes for IDH-mutant Grade 3 tumors are generally substantially better than for IDH wild-type tumors (which under current classification are often reclassified as glioblastoma). Outcomes are most favorable in published series for oligodendrogliomas with 1p/19q codeletion. Individual prognosis depends on a tumor’s full profile and on factors that can only be assessed by a treating physician.

Under the 2021 WHO classification, molecular markers like IDH status and 1p/19q codeletion don’t just refine the diagnosis, they determine it. Two tumors that look the same under a microscope can be entirely different diseases depending on their molecular profile, and they respond to treatment differently. Modern high-grade glioma treatment is built around these distinctions, which is why full molecular profiling at an experienced center makes a meaningful difference.

Next Step

Newly Diagnosed or Seeking a Second Opinion?

Dr. Sherman is accepting new patients at Rutgers Cancer Institute in New Brunswick, New Jersey. Whether you’ve just been diagnosed or you’re looking for another perspective on a treatment plan, a consultation is the first step toward understanding your options.

Schedule a Consultation 732-235-6333