High-Grade Glioma: Understanding Aggressive Brain and Spinal Tumors
Updated: 3 days ago
Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026
Quick Answer
A high-grade glioma is a fast-growing mass of cells that forms in the brain or spinal cord when glial cells grow out of control, classified as Grade 3 or Grade 4 [1]. Its cells invade between healthy cells, often making complete surgical removal difficult [1]. It is the second most common type of malignant brain tumor in children [1].
What the research says
Outcomes in children are still poor, and the group of tumors is diverse. A review of pediatric hemispheric high-grade glioma reports that these tumors affect about 0.85 children per 100,000 each year and that 5-year survival is below 20%. Large genomic studies show they are a heterogeneous group of tumors rather than one disease, which has opened the door to subtype-specific treatments, such as targeted drugs for tumors with NTRK fusions (Coleman et al., Cancer and Metastasis Reviews, 2020 [2]).
Children's tumors are not the same as adult tumors. An expert perspective explains that pediatric high-grade gliomas differ biologically from those in adults. Using treatment strategies developed purely from adult glioblastoma data has led to repeated trials and ineffective treatments with limited improvement in outcomes for children (Jones et al., Neuro-Oncology, 2017 [3]).
Surgery and radiation remain the foundation, and newer approaches are still being tested. A review notes that treatments beyond surgical removal and radiation are not yet established as standard of care. It describes four subgroups (histone 3-mutant, IDH-mutant, histone 3/IDH-wildtype, and radiation-induced) and new approaches such as convection-enhanced delivery of chemotherapy and immunotherapy (Chatwin et al., The FEBS Journal, 2021 [4]).
Key Takeaways
Category | Clinical Details |
Classification | WHO Grade 3 and Grade 4 (malignant) [1]. |
Main Locations | The supratentorial compartment (cerebrum, thalamus, hypothalamus) and the brainstem (DIPG) [1]. |
Common Symptoms | Headaches (often worst in the morning), nausea, vomiting, seizures, and coordination problems [1]. |
Diagnosis Tools | Contrast-enhanced MRI, CT scans, and stereotactic biopsy [1]. |
Treatment Pillars | Surgery, focal radiation, chemotherapy, targeted therapy, and palliative care [1]. |
Pediatric Context | The second most common malignant brain tumor in children [1]. |
The Nature of High-Grade Gliomas
High-grade gliomas are an aggressive form of cancer of the central nervous system. They develop from glial cells, which support the neurons in the brain and spinal cord [1]. When these cells grow out of control, they form a mass that can quickly invade healthy brain tissue. Healthy cells and cancer cells become bound together, so the boundary between them is hard to see and surgery can be difficult without damaging healthy tissue [1].
Grading and Classification
The World Health Organization (WHO) grades gliomas as low grade (Grades 1 and 2) or high grade (Grades 3 and 4) [1]. High-grade gliomas grow faster than low-grade gliomas [1].
Grade 3 gliomas: High grade, with faster growth than low-grade tumors.
Grade 4 gliomas: The most aggressive grade.
In adults, gliomas may start as low grade and later progress to high grade [1]. In children, high-grade gliomas usually start as high grade [1], while low-grade gliomas in children are treatable and rarely progress.
Where They Form
Supratentorial compartment: The part of the brain that includes the cerebrum, the thalamus, and the hypothalamus [1].
Brainstem: Often in the part called the pons. These tumors are called diffuse intrinsic pontine gliomas (DIPG) [1]. Tumors in the brainstem often cannot be removed safely with surgery [1].
Recognizing Signs and Symptoms
Symptoms come from the pressure and swelling caused by the growing tumor. They vary with the child's age, how quickly the tumor grows, and which part of the brain or spinal cord is affected.
Common Clinical Presentations
Headaches and nausea: Headache is the most common symptom, especially with nausea or vomiting [1]. Headaches may feel most intense in the morning and can be severe enough to wake a child from sleep [1].
Neurological problems: Trouble with vision, hearing, or speech, and difficulty with muscle coordination or balance (ataxia) [1].
Behavior and energy changes: Confusion, memory loss, sleepiness, and lack of energy, and seizures can also occur [1].
In infants: Unusual fussiness or irritability, changes in eating habits, a growing head, and soft spots that visibly bulge [1].
Causes and Risk Factors
Researchers are not sure what causes high-grade gliomas [1]. In adults, previous radiation therapy may raise the risk [1], and the same may be true for children, but more research is needed. Most children with high-grade gliomas have no family history of them [1].
Genetic Predispositions
Certain rare inherited genetic syndromes may raise the risk in children [1]:
Neurofibromatosis type 1 (NF1): A genetic condition that can cause tumors to grow along nerves.
Li-Fraumeni syndrome: A rare disorder that greatly raises the risk of several types of cancer.
Turcot syndrome: A condition linked to colorectal polyps and primary brain tumors.
Diagnostic Evaluation
Your child's provider will review their symptoms and medical history, and use imaging and tissue testing to confirm a glioma and its grade.
Imaging
Contrast-enhanced MRI: The most detailed option. A safe dye injected into the arm makes tumors show up more clearly [1].
CT scan: Gives additional information about the structure of the brain and spinal cord.
Biopsy and Molecular Testing
A stereotactic biopsy pinpoints the tumor's exact location and removes a small tissue sample [1]. A pathologist examines the cells to confirm the tumor and look for features that may guide treatment, such as changes that new targeted drugs are designed to treat. If possible, the surgeon may remove the whole tumor instead of taking a sample. A biopsy is not always possible, especially in sensitive areas such as the brainstem, and then diagnosis relies on imaging [1].
Management and Therapeutic Strategies
Treatment aims to remove the tumor where possible, slow its growth, and ease symptoms. Many specialists may be involved, such as a neurosurgeon, a neuro-oncologist, a radiation oncologist, an endocrinologist, a nurse practitioner, and a social worker [1].
Core Treatment Pillars
Surgery: The primary treatment for tumors that can be removed safely [1]. The surgeon removes as much of the tumor as possible without damaging healthy tissue.
Radiation therapy: Focal radiation is standard for children ages 3 and older [1]. A machine directs high-dose X-rays at the tumor while sparing nearby healthy tissue. It is usually avoided in younger children to allow the brain to develop [1].
Chemotherapy: Given to slow tumor growth when radiation is avoided in younger children [1]. Its use is debated, because drugs such as temozolomide that work on some adult gliomas are not as effective in children [1].
Targeted therapy and clinical trials: When tumors come back, treatments aimed at abnormal molecules in the tumor may be available, sometimes through clinical trials [1] and sometimes outside them if the drugs are on the market [1].
Radiation spares healthy tissue as much as possible, but some is still affected, so it can affect brain function, cause developmental problems, and disrupt hormone production [1]. Talk to your child's care team about the benefits and risks.
Prognosis and Palliative Care
Whether a high-grade glioma can be cured depends on the child's age, the genetic changes in the tumor cells, and how much of the tumor can be removed [1]. These tumors usually return after treatment, and the five-year survival rate for high-grade gliomas in children is below 20% [1] [2]. They vary widely, though, and where the tumor forms and the characteristics of its cells shape each child's outlook.
Palliative care professionals can advise on decisions that put the child's quality of life first [1] and suggest ways to relieve symptoms and help the child cope with the diagnosis.
Conclusion
A high-grade glioma diagnosis is hard, and these tumors grow quickly and often return. Talk with your child's healthcare team about all treatment options, including clinical trials, use available supports such as palliative care, and lean on family, friends, and care-team resources through the process.
Frequently Asked Questions
What is a high-grade glioma?
A fast-growing cancer of the brain or spinal cord that forms when glial cells grow out of control.
What grades are considered high grade?
The WHO classifies Grade 3 and Grade 4 gliomas as high grade [1].
Are high-grade gliomas common in children?
They are the second most common malignant brain tumor in children, making up about 10% to 20% of childhood central nervous system tumors [1].
Can high-grade gliomas be cured?
It depends on the child's age, the gene changes in the tumor cells, and how much of the tumor can be removed [1]. These tumors often return, and treatment aims to slow growth and ease symptoms.
What is the most common symptom?
Headache, especially with nausea or vomiting, and often most intense in the morning [1].
What are glial cells?
Cells that support and protect neurons in the nervous system [1].
What is DIPG?
Diffuse intrinsic pontine glioma, a type of high-grade glioma in the pons of the brainstem [1].
Who can get high-grade gliomas?
Infants, children, adolescents, and adults can, but tumors in infants and young children differ from those in adolescents and adults [1].
Is an MRI better than a CT scan for diagnosis?
An MRI, especially a contrast-enhanced MRI, gives a more detailed image than a CT scan [1].
What is a stereotactic biopsy?
A procedure that pinpoints a tumor's exact location and removes a small tissue sample for testing.
Why is surgery difficult for these tumors?
The cancer cells invade between healthy cells and become bound to them [1], so the tumor is hard to separate from healthy tissue.
What is the primary treatment?
Surgery, when the tumor can be removed safely [1].
Is radiation used for infants?
Radiation is usually avoided in children under 3 to allow the brain to develop [1].
What is chemotherapy's role?
It is used to slow tumor growth, especially in younger children when radiation is avoided, though it is not as effective in children as some drugs are in adult gliomas [1].
What is palliative care?
Care focused on symptom relief and quality of life during treatment.
Do these tumors often return?
Yes. High-grade gliomas often return after treatment [1].
What are targeted therapies?
Medicines aimed at specific abnormal molecules in cancer cells.
Are clinical trials an option?
Yes. Targeted therapies for tumors that come back may be available through clinical trials [1].
Can genetic syndromes increase risk?
Yes. Rare syndromes such as NF1, Li-Fraumeni syndrome, and Turcot syndrome can raise the risk in children [1].
Is there a known environmental cause?
Previous radiation therapy may raise the risk in adults [1]. The same may be true in children, but more research is needed.
What is the supratentorial compartment?
The part of the brain that includes the cerebrum, the thalamus, and the hypothalamus [1].
Can brainstem tumors be removed?
They often cannot be removed safely because of their sensitive location [1].
What is ataxia?
Difficulty with muscle coordination or balance [1].
Can high-grade gliomas cause seizures?
Yes. Seizures are a recognized symptom [1].
How do infants show symptoms?
They may be unusually fussy or irritable, eat differently, have a growing head, or have soft spots that visibly bulge [1].
What is a neuro-oncologist?
A specialist who treats brain and spinal cord cancers.
What is focal radiation?
Radiation therapy aimed at a specific area, in this case the tumor, while sparing nearby healthy tissue.
What is temozolomide?
A chemotherapy drug that works well on some adult gliomas but is not as effective in children [1].
What is a pathologist?
A lab specialist who examines cells to diagnose disease.
Can vision be affected?
Yes. Problems with vision are a common symptom.
What does malignant mean?
The tumor is cancerous and can invade surrounding tissue.
What is the central nervous system?
The brain and spinal cord.
Can memory loss occur?
Yes. Confusion and memory loss are possible symptoms [1].
Why are headaches often worst in the morning?
Morning headaches are typical of pressure from a growing tumor and can be intense enough to wake a child from sleep.
What is Turcot syndrome?
A rare inherited condition linked to colorectal polyps and primary brain tumors.
Is focal radiation standard?
Yes, for children ages 3 and older [1].
Can these tumors spread to other organs?
They spread rapidly within the central nervous system [1], and spread outside of it is rare.
What is an endocrinologist's role?
They may be part of the care team to help manage hormone issues related to the tumor or its treatment.
Are high-grade gliomas in infants different?
Yes. High-grade gliomas in infants and young children are different from those in adolescents and adults [1], so treatments differ.
What is a molecular mutation?
A change in the genetic code that can drive cancer growth.
Can hearing be affected?
Yes. Problems with hearing are possible symptoms [1].
What is the pons?
A part of the brainstem where DIPG tumors form.
Is surgery always the first step?
It is when the tumor is in a place where it can be reached safely.
What percentage of childhood CNS tumors are high-grade gliomas?
About 10% to 20% [1].
Can high-grade gliomas cause sleepiness?
Yes. Sleepiness and lack of energy are possible symptoms [1].
What is contrast-enhanced imaging?
Imaging that uses a safe dye to make abnormal areas show up more clearly.
Is there a family history in most cases?
No. Most children with high-grade gliomas do not have a family history of them [1].
Can targeted therapy be given outside clinical trials?
Yes, if the drugs are on the market or earlier testing has shown they work against the type of glioma [1].
What is the WHO?
The World Health Organization, which sets the standards for grading tumors.
How quickly do Grade 4 tumors grow?
High-grade gliomas grow faster than low-grade ones, and Grade 4 is the most aggressive grade.
Related Reading
Cancer Staging and Grading: What They Are, Why They Matter, Tests and Results explains how doctors stage and grade cancer and why the results guide treatment.
References
Cleveland Clinic. High-Grade Glioma: Symptoms, What It Is & Prognosis. Cleveland Clinic. Last updated October 5, 2022. https://my.clevelandclinic.org/health/diseases/24259-high-grade-glioma
Coleman C, Stoller S, Grotzer M, et al. Pediatric hemispheric high-grade glioma: targeting the future. Cancer and Metastasis Reviews. 2020;39(1):245-260. PMID 31989507. https://doi.org/10.1007/s10555-020-09850-5
Jones C, Karajannis MA, Jones DTW, et al. Pediatric high-grade glioma: biologically and clinically in need of new thinking. Neuro-Oncology. 2017;19(2):153-161. PMID 27282398. https://doi.org/10.1093/neuonc/now101
Chatwin HV, Cruz Cruz J, Green AL. Pediatric high-grade glioma: moving toward subtype-specific multimodal therapy. The FEBS Journal. 2021;288(21):6127-6141. PMID 33523591. https://doi.org/10.1111/febs.15739
Disclaimer
The information provided in this article is for educational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of any health condition.
Comments