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Gliomas and glioblastoma multiforme

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Brain tumours article more useful, or one of our other health articles.

See also the separate Brain Tumours in Children and Brain Tumours in Adults articles.

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What are gliomas?

Gliomas are tumours arising from glial cells and may occur in the spinal cord or the brain, the latter being more common. Gliomas are the most common type of brain tumour and (anatomically) they can be either supratentorial or infratentorial.

There are three common types of gliomas, which are classified based on the phenotypic cell characteristics: astrocytomas, ependymomas and oligodendrogliomas.

These are further classified to low-grade, atypical, and high-grade tumours based on cell morphology, mitotic activities, and molecular markers.

  • Astrocytomas1 : originate from astrocytes and can be encapsulated, preserving clear borders between normal and tumour cells, or infiltrative, indicating advanced grade. Low grades are common in children, while high grades are common in young adults and older patients.

  • Oligodendrogliomas2 : originate from oligodendrocyte cells. These are less infiltrating than astrocytomas and are common in adults.

  • Ependymomas3 : originate from ependymal cells which are found lining the ventricular cavities and the central canal of the spinal cord. These are common in paediatric patients.


Until 2016 gliomas were graded according to their likely rate of growth (grade 1 is the slowest growing and grade 4 is the fastest growing). Grades 1 and 2 were considered low-grade gliomas, well differentiated and usually associated with a better outcome. Grade 3 and 4 gliomas were considered high-grade gliomas, were undifferentiated or anaplastic and with a worse prognosis.

To provide more targeted therapy and better prognostic forecasting, the 2016 WHO classification moves from the former principle of diagnosis based solely on microscopy and integrates phenotypic and genotypic parameters4 . Lower-grade gliomas and infiltrating gliomas are classified separately and according to chromosomal or histone mutations - eg, chromosome 1p/19q loss, isocitrate dehydrogenase (IDH ) mutation and telomerase reverse transcriptase (TERT) mutations. Additionally gliomas are classified in grade I to IV based on the degree of proliferation indicated by the mitotic index and the presence or absence of necrosis.

2016 WHO grades of gliomas5

1. Diffuse astrocytic and oligodendroglial tumors:

  • Diffuse astrocytoma, IDH-mutant (Grade II).

  • Anaplastic astrocytoma, IDH- mutant (Grade III).

  • Glioblastoma, IDH wild-type (Grade IV).

  • Glioblastoma, IDH wild-type (Grade IV).

  • Oligodendroglioma, IDH-mutant, and 1p/19q-co-deleted (Grade II).

Anaplastic oligodendroglioma, IDH-mutant, and 1p/19q-co-deleted (Grade II).2.

Other astrocytic tumours:

  • Pilocytic astrocytoma (Grade I).

  • Subependymal giant cell astrocytoma (Grade I).

  • Pleomorphic xanthoastrocytoma (Grade II).

  • Anaplastic pleomorphic xanthoastrocytoma (III).

3. Ependymal tumours:

  • Subependymoma (Grade I).

  • Myxopapillary ependymoma (Grade I).

  • Ependymoma (Grade II).

  • Ependymoma, RELA fusion-positive ( Grade II or III).

  • Anaplastic ependymoma (Grade III).

4. Other gliomas:

  • Angiocentric glioma (Grade I).

  • Chordoid glioma of the third ventricle (Grade II).

Glioma epidemiology6

  • The annual incidence of malignant glioma is 3-5/100,000.

  • There is a slight predominance in males.

  • Malignant glioma may develop at all ages, but the peak incidence is between 50-60 years.

  • Exposure to ionising irradiation has been associated with increased risk of development of glioma.

  • Certain hereditary syndromes carry an increased risk for glioma, including neurofibromatosis type 1.

  • GBM is the most common glioma to occur in adults, being diagnosed at an average age of 55 years.

  • Low-grade astrocytomas tend to be seen in younger adults aged 20-30 and anaplastic astrocytomas and oligodendrogliomas typically present in the mid-forties.

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Glioma symptoms (presentation)7

Brain tumours present as a space-occupying lesion with symptoms, depending on the size, location and degree of infiltration of the tumour. The following are some features that might be seen:

  • Headache - typically worse on waking.

  • Nausea and vomiting.

  • Seizures - especially low-grade astrocytomas.

  • Visual disturbance.

  • Speech and language problems.

  • Changes in cognitive and/or functional ability.

  • Acute intracranial haemorrhage, which may rarely occur in association with GBM.


  • Involves brain imaging - eg, CT scan and/or MRI scan with or without contrast. GBM typically has ring enhancement.

  • Tissue specimens for pathology are usually required (if they are possible to obtain), as there is a large variety of tumours that may occur.

The National Institute for Health and Care Excellence (NICE) recommends that as well as histopathological assessment, include molecular markers such as8 :

  • IDH1 and IDH2 mutations.

  • ATRX mutations to identify IDH mutant astrocytomas and glioblastomas.

  • 1p/19q co-deletion to identify oligodendrogliomas.

  • histone H3.3 K27M mutations in midline gliomas.

  • BRAF fusion and gene mutation to identify pilocytic astrocytoma.

In addition NICE recommends that all high-grade glioma specimens be tested for MGMT promoter methylation to inform prognosis and guide treatment and that IDH-wildtype glioma specimens be tested for TERT promoter mutations to inform prognosis.

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Glioma treatment and management

Treatment of glioma involves surgery and may involve additional treatments according to classification7 :

  • Grade I: these gliomas are surgically curable.

  • Grade II: a safe gross total resection and radiographic follow-up are acceptable current practices.

  • Grade III: a safe gross total resection, concomitant chemoradiation, and radiographic follow-up for recurrence are an acceptable treatment.

  • Grade IV (glioblastoma): a safe gross total resection, concomitant chemoradiation, and radiographic follow-up for recurrence are an acceptable treatment.

After surgery of low-grade gliomas, NICE recommends offering radiotherapy followed by up to six cycles of PCV chemotherapy (procarbazine, CCNU [lomustine] and vincristine) for people who have a 1p/19q co-deleted, IDH-mutated low-grade glioma (oligodendroglioma or astrocytoma) and are aged around 40 or over, or have residual tumour on postoperative MRI8 .

Treatment protocols for Grade III and IV vary according to prognostic features. Temozolomide is recommended by NICE as an option for treating malignant glioma that has recurred or progressed after standard therapy - if the person has a Karnofsky performance status score greater than or equal to 70 and a life expectancy of 12 weeks or more9 .

Other treatments: high-grade glioma patients are prone to seizures, malignant oedema, and complication related immobility. Therefore, these patients need antiepileptic medications, deep venous thrombosis (DVT) prophylaxis, and steroids - before, during and after the course of treatments - to avoid cerebral oedema.


Complications include:

  • Cerebral oedema and raised intracranial pressure.

  • Seizures.

  • Thromboembolic events (tumour-induced hypercoagulable state as well as a consequence of neurological deficits, immobilisation and steroid treatment).

Glioma prognosis10

The prognosis of gliomas depends on several factors including: the age of the patient. comorbidities, grade and location of the tumour, presence of hydrocephalus, response to adjuvant therapy and the extent of surgical resection required/achievable.

  • Gliomas are associated with a poor prognosis, especially high-grade tumours in older patients. Survival rates of approximately 30% at one year and 14% at two years have been reported.

  • Patients with high-grade gliomas have a better prognosis if they are younger, have a better performance status, have a Grade 3 tumour or if complete resection is achieved11 .

  • The median survival of patients with anaplastic astrocytoma is two to three years, and that of patients with GBM approximately one year11 .

  • Low-grade astrocytomas can rarely recur and therefore long-term follow-up is required.

Further reading and references

  1. Kapoor M, Gupta V; Astrocytoma
  2. Tork CA, Atkinson C; Oligodendroglioma
  3. Zamora EA, Alkherayf F; Ependymoma
  4. Louis DN, Perry A, Reifenberger G, et al; The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016 Jun;131(6):803-20. doi: 10.1007/s00401-016-1545-1. Epub 2016 May 9.
  5. Chen R, Smith-Cohn M, Cohen AL, et al; Glioma Subclassifications and Their Clinical Significance. Neurotherapeutics. 2017 Apr;14(2):284-297. doi: 10.1007/s13311-017-0519-x.
  6. High-grade gliomas: ESMO Clinical Practice Guidelines for diagnosis treatment and follow up; European Society of Medical Oncology (2014)
  7. Mesfin FB, Al-Dhahir MA; Gliomas
  8. Brain tumours (primary) and brain metastases in adults; NICE Guideline (July 2018, updated Jan 2021)
  9. Guidance on the use of temozolomide for the treatment of recurrent malignant glioma (brain cancer); NICE Technology Appraisal Guidance, April 2001 - last updated March 2016
  10. Sharma A, Graber JJ; Overview of prognostic factors in adult gliomas. Ann Palliat Med. 2021 Jan;10(1):863-874. doi: 10.21037/apm-20-640. Epub 2020 Aug 7.
  11. Glioma (newly diagnosed and high grade) - carmustine implants and temozolomide; NICE Technology Appraisal Guidance, June 2007

Article history

The information on this page is written and peer reviewed by qualified clinicians.

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