Glioblastoma multiforme

DiseasesDB = 29448
MeshID = D005909

Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs occur in only 2-3 cases per 100,000 people in Europe and North America.
The standard WHO-2007 name for this brain tumor is “Glioblastoma” [Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues PThe 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathol (2007) 114:97-109. [ PMID 17618441]
(See also [ WHO Classification > 2007 WHO Classification] .)
In [ WHO Classification] are the previous WHO classifications.
On is the 2007 WHO Classification (with explicative notes) at ("Classification of the Tumors of the Central Nervous System").
The companion article is ("Grading of the Tumors of the Central Nervous System").
] .

Treatment can involve chemotherapy, radiotherapy, and surgery, all of which are acknowledged as palliative measures, meaning that they do not provide a cure. Even with complete surgical resection of the tumor, combined with the best available treatment, the survival rate for GBM remains very low. However, many advances in microsurgery techniques, radiotherapy and chemotherapy are slowly increasing the survival time of patients diagnosed with glioblastoma.


Although common symptoms of the disease include seizure, nausea and vomiting, headache, and hemiparesis, the single most prevalent symptom is a progressive memory, personality, or neurological deficit due to temporal and frontal lobe involvement. The kind of symptoms produced depends highly on the location of the tumor, more so than on its pathological properties. The tumor can start producing symptoms quickly, but occasionally is asymptomatic until it reaches an enormous size.


When viewed with MRI, glioblastomas often appear as ring-enhancing lesions. The appearance is not specific, however, as other lesions such as abscess, metastasis, tumefactive multiple sclerosis and other entities may have a similar appearance. [cite journal |author=Smirniotopoulos JG, Murphy FM, Rushing EJ, Rees JH, Schroeder JW.Patterns of contrast enhancement in the brain and meninges.Radiographics. 2007 Mar-Apr;27(2):525-51. Review.PMID: 17374867] Definitive diagnosis of a suspected GBM on CT or MRI requires a stereotactic biopsy or a craniotomy with tumor resection. Because the tumor grade is based upon the most malignant portion of the tumor, biopsy or subtotal tumor resection can result in undergrading of the lesion.


GBM is more common in males, although the reason for this is not clear. [cite journal |author=Ohgaki H, Kleihues P|title=Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas |journal=J Neuropathol Exp Neurol |volume=64 |pages=479–89 |year=2005 |pmid=15977639] Most glioblastoma tumors appear to be sporadic, without any genetic predisposition. No links have been found between glioblastoma and smoking, [cite journal |author=Zheng, T, Cantor KP, Zhang Y, "et al" |title=Risk of brain glioma not associated with cigarette smoking or use of other tobacco products in Iowa |journal=Cancer Epidemiol Biomarkers Prev |volume=10 |pages=413–4 |year=2001 |pmid=11319186] diet, [cite journal |author=Huncharek M, Kupelnick B, Wheeler L |title=Dietary cured meat and the risk of adult glioma: a meta-analysis of nine observational studies |journal=J Environ Pathol Toxicol Oncol |volume=22 |pages=129–37 |year=2003 |pmid=14533876 |doi=10.1615/JEnvPathToxOncol.v22.i2.60] cellular phones [cite journal |author=Inskip PD, Tarone RE, Hatch EE, "et al" |title=Cellular-telephone use and brain tumors |journal=N Engl J Med |volume=344 |pages=79–86 |year=2001 |pmid=11150357 |doi=10.1056/NEJM200101113440201] electromagnetic fields. [cite journal |author=Savitz DA, Checkoway H, Loomis DP |title=Magnetic field exposure and neurodegenerative disease mortality among electric utility workers |journal=Epidemiology |volume=9 |pages=398–404 |year=1998 |pmid=9647903 |doi=10.1097/00001648-199807000-00009] Until recently, there was no evidence of a viral cause [cite journal |author=Vilchez RA, Kozinetz CA, Arrington AS, "et al" |title=Simian virus 40 in human cancers |journal=Am J Med |volume=114 |pages=675–84 |year=2003 |pmid=12798456 |doi=10.1016/S0002-9343(03)00087-1] , but new evidence may suggest that there is. [ [ "Target acquired"] , "The Economist", May 29th, 2008] There also appears to be a small link between ionizing radiation and glioblastoma. [cite journal |author=Cavenee L |title=High-grade gliomas with chromosome 1p loss |journal=J Neurosurg |volume=92 |pages=1080–1 |year=2000 |pmid=10839286]


Glioblastomas multiforme are characterized by the presence of small areas of necrotizing tissue that is surrounded by anaplastic cells (pseudopalisading necrosis). This characteristic, as well as the presence of hyperplastic blood vessels, differentiates the tumor from Grade 3 astrocytomas, which do not have these features. Although glioblastoma multiforme can be formed from lower-grade astrocytomas, post-mortem autopsies have revealed that most glioblastomas multiforme are not caused by previous lesions in the brain.

Unlike oligodendrogliomas, glioblastomas multiforme can form in either the gray matter or the white matter of the brain; but most GBM arises from the deep white matter and quickly infiltrate the brain, often becoming very large before producing symptoms. The tumor may extend to the meningeal or ventricular wall, leading to the high protein content of cerebrospinal fluid (CSF) (> 100 mg/dL), as well as an occasional pleocytosis of 10 to 100 cells, mostly lymphocytes. Malignant cells carried in the CSF may spread to the spinal cord or cause meningeal gliomatosis. However, metastasis of GBM beyond the central nervous system is extremely rare. About 50% of GBM occupy more than one lobe of a hemisphere or are bilateral. Tumors of this type usually arise from the cerebrum and may exhibit the classic infiltrate across the corpus callosum, producing a butterfly (bilateral) glioma.

The tumor may take on a variety of appearances, depending on the amount of hemorrhage, necrosis, or its age. A CT scan will usually show a nonhomogeneous mass with a hypointense center and a variable ring of enhancement surrounded by edema. Part of a lateral ventricle is usually deformed, and both lateral and third ventricles may be displaced.


It is very difficult to treat glioblastoma due to several complicating factors:cite journal
author = Lawson HC, Sampath P, Bohan E, "et al"
title = Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience
journal = Journal of Neuro-Oncology
volume = 83
issue = 1
year = 2007
pages = 61–70
pmid = 17171441
doi = 10.1007/s11060-006-9303-1
* The tumor cells are very resistant to chemotherapy and other conventional therapies
* The brain is susceptible to damage due to therapy
* The brain has a very limited capacity to repair itself
* Many drugs cannot cross the blood brain barrier to act on the tumor

Treatment of primary brain tumors and brain metastases consists of both symptomaticand palliative therapies.

ymptomatic therapy

Supportive treatment focuses on relieving symptoms and improving the patient’sneurologic function. The primary supportive agents are anticonvulsants and

*Historically, around ninety percent of patients with glioblastoma underwent anticonvulsant treatment, although is has been estimated that only approximately 40% of patients required this treatment. Recently, it has not been recommended that neurosurgeons administer anticonvulsants prophylactically, and should wait until a seizure occurs before prescribing this medication [cite journal |author=Stevens GHJ |title=Antiepileptic therapy in patients with central nervous system malignancies |journal=Current Neurology and Neuroscience Reports |volume=6 |pages=311–318 |year=2006 |pmid=16822352 | doi=10.1007/s11910-006-0024-9] . Those receiving phenytoin concurrent with radiation may have serious skin reactions such as erythema multiforme and Stevens-Johnson syndrome.

*Corticosteroids, usually dexamethasone given 4 to 10 mg every 4 to 6 h, can reduce peritumoral edema (through rearrangement of the blood-brain barrier), diminishing mass effect and lowering intracranial pressure, with a decrease in headache or drowsiness.

Palliative therapy

Palliative treatment usually is conducted to improve quality of life and to achieve a longer survival time. It includes surgery, radiation therapy, and chemotherapy. A maximally feasible resection with maximal tumor-free margins ("debulking") is usually performed along with external beam radiation and chemotherapy.


Surgery is the first stage of treatment of glioblastoma. An average GBM tumor contains 1011 cells, which is on average reduced to 109 cells after surgery.It is used to take a section for diagnosis, to remove some of the symptoms of a large mass pressing against the brain, to remove disease before secondary resistance to radiotherapy and chemotherapy, and to prolong survival.

The greater the extent of tumor removal, the longer the survival time. Removal of 98% or more of the tumor has been associated with a significantly longer median survival time than if less than 98% of the tumor is removed. [cite journal |author=Lacroix M, Abi-Said D, Fourney DR, "et al" |title=A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival |journal=J Neurosurg |volume=95 |issue=2 |pages=190–8 |year=2001 |pmid=11780887 ] The chances of near-complete initial removal of the tumor can be greatly increased if the surgery is guided by a fluorescent dye known as 5-aminolevulinic acid. [cite journal |author=Stummer W, Pichimeier U, Meinel T, "et al" |title=Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial |journal=The Lancet Oncology |volume=7 |issue=5 |pages=392–401 |year=2006 | pmid=16648043 | doi=10.1016/S1470-2045(06)70665-9]


On average, radiotherapy after surgery can reduce the tumor size to 107 cells. Whole brain radiotherapy does not improve survival when compared to the more precise and targeted three-dimensional conformal radiotherapy. [cite journal |author=Showalter T, Andrel J, Andrews D, "et al" |title=Multifocal Glioblastoma Multiforme: Prognostic Factors and Patterns of Progression |journal=International Journal of Radiation OncologyBiologyPhysics, |volume=69 |issue=3 |pages=820–824 |year=2007 | pmid=17499453 | doi=10.1016/j.ijrobp.2007.03.045 ] A total radiation dose of 60-65 Gy has been found to be optimal for treatment. [cite journal
author = Fulton DS, Urtasun RC, Scott-Brown, I, "et al"
title = Increasing radiation dose intensity using hyperfractionation in patients with malignant glioma. Final report of a prospective phase I-II dose response study
journal = Journal of Neuro-Oncolog
volume = 14
issue = 1
pages = 63–72
year = 1992
pmid = 1335044

Boron neutron capture therapy has been tested as an alternative treatment for glioblastoma multiforme but is not in common use.


The standard of care for glioblastoma includes chemotherapy during and after radiotherapy. On average, chemotherapy after surgery and radiotherapy can initially reduce the tumor size to 106 cells. The use of temozolomide both during radiotherapy and for six months post radiotherapy results in a significant increase in median survival with minimal additional toxicity. [cite journal |author=Stupp R, Mason WP, van den Bent MJ, "et al" |title=Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma |journal=NEJM |volume=352 |issue=10 |pages=987–996 |year=2005 | pmid=15758009 |doi=10.1056/NEJMoa043330 ] This treatment regime is now standard for most cases of glioblastoma where the patient is not enrolled in a clinical trial. [cite journal |author=Mason WP, Mirimanoff RO, Stupp R, "et al" |title=Radiotherapy with Concurrent and Adjuvant Temozolomide: A New Standard of Care for Glioblastoma Multiforme |journal=Progress in Neurotherapeutics and Neuropsychopharmacology |volume=1 |pages=37–52 |year=2006 | doi = 10.1017/S1748232105000054 ] [cite web |url= |title=Temozolomide Plus Radiation Helps Brain Cancer - National Cancer Institute |accessdate=2007-09-15 |format= |work=]


Long-term disease-free survival is unlikely but possible, and the tumor will often reappear, usually within 2 cm of the original site, and 10% may develop new lesions at distant sites. More extensive surgery and intense local treatment after recurrence has been associated with improved survival. [cite journal
author=Nieder C, Adama M, Mollsa M and Grosu AL
title=Therapeutic options for recurrent high-grade glioma in adult patients: Recent advances
journal=Critical Reviews in Oncology/Hematology
issue = 3
pages = 181–193
] .


The median survival time from the time of diagnosis without any treatment is 3 months. Increasing age (> 60 years of age) carries a worse prognostic risk. Death is usually due to cerebral edema or increased intracranial pressure. One in twenty of glioblastoma patients survive for more than three years, and approximately one in 5,000 glioblastoma patients survive for decadescite journal
author=Krex D, Klink B, Hartmann C, "et al"
title=Long-term survival with glioblastoma multiforme
journal = Brain
volume= 130
issue = 10
pages = 2596–2606
] .

Survival of more than three years has been associated with younger age at diagnosis, a good initial KPS, and MGMT methylation . A DNA test can be conducted on glioblastomas to determine whether or not the promoter of the MGMT gene is methylated. Patients with a methylated MGMT promoter have been associated with significantly greater long-term survival than patients with an unmethylated MGMT promoter [cite journal
author = Martinez R, Schackert G, Yaya-Tur R, "et al"
title = Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of glioblastoma multiforme
journal = Journal of Neuro-Oncology
volume= 83
issue = 1
pages = 91–93
] . This DNA characteristic is intrinsic to the patient and currently cannot be altered externally.

Long-term survival has also been associated with those patients who receive surgery, radiotherapy, and temozolomide chemotherapy. However, much remains unknown about why some patients survive longer with glioblastoma.

UCLA Neuro-Oncology publishes [ real-time survival data] for patients with this diagnosis. They are the only institution in the United States that shows how their patients are performing. They also show a listing of chemotherapy agents used to treat GBM tumors.

According to a 2003 study, glioblastoma multiforme prognosis can be divided into three subgroups dependent on Karnofsky Performance Score (KPS), the age of the patient, and treatment: [cite journal |author=Shawl, EG, Seiferheld, W, Scott, C, "et al" |title=Re-examining the radiation therapy oncology group (RTOG) recursive partitioning analysis (RPA) for glioblastoma multiforme (GBM) patients |journal=International Journal of Radiation Oncology*Biology*Physics |volume=57 |issue=2 |pages=S135–S136 |year=2003 |pmid=15758009 |doi=10.1016/S0360-3016(03)00843-5]


External links

* [ Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke)]
* [ Glioblastoma Images] MedPix Medical Image Database
* [ Astrocytoma Radiologic-Pathologic Correlation] AFIP Lectures
* [ Cancer Management: Brain Tumors]
* [ Treatment Options for Glioblastoma and other Glios]
* [ North America Brain Tumor Coalition]
* [ Samantha Dickson Brain Tumour Trust] UK

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Look at other dictionaries:

  • glioblastoma multiforme — Tumor maligno de crecimiento rápido, pulposo o quístico, del cerebro o, en ocasiones, de la médula espinal. La lesión se disemina mediante proyecciones en forma de seudópodos. Diccionario Mosby Medicina, Enfermería y Ciencias de la Salud,… …   Diccionario médico

  • Glioblastoma multiforme — Klassifikation nach ICD 10 C71 Bösartige Neubildung des Gehirns C71.0 Zerebrum, ausgenommen Hirnlappen und Ventrikel C71.1 …   Deutsch Wikipedia

  • glioblastoma multiforme — GBM. A fast growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma multiforme usually occurs in adults and affects …   English dictionary of cancer terms

  • glioblastoma multiforme — Eng. Glioblastoma multiforme Tumor cerebral maligno con gran tendencia infiltrativa y rápido crecimiento. Aunque su localización más frecuente es la hemisférica puede asentar o afectar de forma secundaria al quiasma óptico, nervio óptico u órbita …   Diccionario de oftalmología

  • glioblastoma multiforme — A glioma consisting chiefly of undifferentiated anaplastic cells of astrocytic origin that show marked nuclear pleomorphism, necrosis, and vascular endothelial proliferation; frequently, tumor …   Medical dictionary

  • glioblastoma multiforme — noun see glioblastoma …   New Collegiate Dictionary

  • glioblastoma multiforme — noun The most common and most aggressive type of primary brain tumor …   Wiktionary

  • multiforme — see ERYTHEMA MULTIFORME, GLIOBLASTOMA MULTIFORME …   Medical dictionary

  • glioblastoma — A fast growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more… …   English dictionary of cancer terms

  • glioblastoma — noun (plural mas; also glioblastomata) Etymology: New Latin, from glia glia + blast + oma Date: circa 1923 a malignant rapidly growing astrocytoma of the central nervous system and usually of a cerebral hemisphere called also glioblastoma… …   New Collegiate Dictionary

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