eMedicine Specialties > Neurology > Neuro-oncology

Glioblastoma Multiforme

Author: ABM Salah Uddin, MD, Consulting Staff, Department of Internal Medicine, St Vincent's Hospital
Coauthor(s): Tambi Jarmi, MD, Resident Physician, Department of Internal Medicine, Carraway Methodist Medical Center
Contributor Information and Disclosures

Updated: Sep 8, 2009

Introduction

Background

Glioblastoma multiforme (GBM) is the most common and most aggressive of the primary brain tumors. The current World Health Organization (WHO) classification of primary brain tumors lists GBM as a grade IV astrocytoma. Astrocytoma is one of 3 distinct types of gliomas in the brain, although mixed cell types occur as well. GBMs are highly malignant, infiltrate the brain extensively, and at times may become enormous before turning symptomatic.

Pathophysiology

GBM is an anaplastic, highly cellular tumor with poorly differentiated, round, or pleomorphic cells, occasional multinucleated cells, nuclear atypia, and anaplasia. Under the modified WHO classification, GBM differs from anaplastic astrocytomas (AA) by the presence of necrosis under the microscope. Variants of the tumor include gliosarcoma, multifocal GBM, or gliomatosis cerebri (in which the entire brain may be infiltrated with tumor cells). These variants, however, do not alter the prognosis of the tumor. Multifocal metastasis of GBM is extremely rare but is increasing, including spinal drop metastasis, as patients live longer.1

Frequency

United States

Among primary brain tumors, malignant astrocytomas are the most common in all age groups. (However, among all brain tumors, metastases are the most common.) GBMs are the most common primary brain tumors in adults, accounting for 12-15% of intracranial tumors and 50-60% of primary brain tumors. Several authors have reported a true increase in the incidence of brain tumors, especially among the elderly, and many have attributed the observed changes to developments in diagnostic imaging or changes in the classification system.2

International

International incidence of GBM is similar to that of the United States.

Mortality/Morbidity

Morbidity is from the tumor location, progression, and pressure effects. The overall prognosis for GBM has changed little in the past 2 decades, despite major improvements in neuroimaging, neurosurgery, radiation treatment techniques, adjuvant chemotherapy, and supportive care. Few patients with GBM survive longer than 3 years and only a handful survive 5 years. Previously reported long-term survivors of GBM may be patients diagnosed with GBM who actually harbor low-grade glioma, pleomorphic xanthoastrocytoma, ganglioglioma, or other lesions. Occasional patients with a single necrotic, demyelinating plaque of multiple sclerosis also may be misdiagnosed with GBM, especially if only CT scans are obtained.

Race

High-grade astrocytomas (HGAs) are slightly more common in whites than in blacks, Latinos, and Asians.

Sex

GBM is slightly more common in men than in women; the male-to-female ratio is 3:2.

Age

While GBM occurs in all age groups, its incidence is increasing in elderly patients. A true increase in incidence of primary brain tumors exists, which cannot be explained by the aging population, better imaging techniques, or earlier detection at surgery.

Clinical

History

Glioblastoma multiforme (GBM), like other brain tumors, produces symptoms by a combination of focal neurologic deficits from compression and infiltration of the surrounding brain, vascular compromise, and raised intracranial pressure. Presenting features include the following:

  • Headaches (30-50%)
    • Headaches are nonspecific and indistinguishable from tension headache.
    • As the tumor enlarges, it may have features of increased intracranial pressure.
  • Seizures (30-60%): Depending on the tumor location, seizures may be simple partial, complex partial, or generalized.
  • Focal neurologic deficits (40-60%): As some patients with GBM survive longer, an increasing number of patients experience cognitive problems, neurologic deficits resulting from radiation necrosis, communicating hydrocephalus, and occasionally cranial neuropathies and polyradiculopathies from leptomeningeal spread.
  • Mental status changes (20-40%): With the advent of MRI, GBMs are increasingly diagnosed at an earlier stage and with subtle personality changes.

Physical

Physical findings depend on the location, size, and rate of growth of the tumor, as with any other CNS tumor. Tumors in less critical areas (eg, anterior frontal or temporal lobe) may present with subtle personality changes and memory problems. Similarly, motor weakness and sensory hemineglect are the hallmarks of tumors arising in the frontal or parietal lobes and thalamic regions. Sensory neglect is more prominent in right hemispheric lesions.

  • Seizures are a common presentation of small tumors in the frontoparietal regions (simple motor or sensory partial seizure) and temporal lobe (simple or complex partial seizure).
  • Occipital lobe tumors may present with visual field defects. Although these tumors are less frequent than tumors originating at other sites, patients generally are unaware of the slow onset of a cortically based hemianopsia.
  • Brainstem GBMs are rare in adults. However, they may present with bilateral crossed neurological deficits (eg, weakness on one side with contralateral cranial nerve palsy). Alternatively, they may present with rapidly progressive headache or altered consciousness.

Causes

The etiology of GBM is unknown. However, at least 2 genetic pathways have been delineated in its development: de novo (primary) glioblastomas and secondary glioblastomas. De novo glioblastomas are most common. De novo GBM develops in older patients and demonstrates a high rate of epidermal growth factor receptor (EGFR) overexpression, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutations, and p16INK4A deletions. In contrast, secondary GBM develops in younger patients and develops from a malignant transformation of a previously diagnosed low-grade tumor. TP53 and retinoblastoma gene (RB) mutations are more common in the development of secondary glioblastomas.

Several genetic disorders are associated with increased incidence of gliomas (eg, tuberous sclerosis, neurofibromatosis type 1 and type 2, Turcot syndrome, Li-Fraumeni syndrome). An association exists between ionizing radiation and astrocytomas. Children who receive low-dose intracranial radiation have a 2.6-fold increase in prevalence of astrocytomas, and prophylactic whole-brain radiation therapy in patients with acute lymphocytic leukemia increased the incidence of astrocytomas 22-fold.

Other suspected risk factors, such as electromagnetic radiation and cellular telephone use, are yet to be substantiated by large epidemiologic studies. However, researchers reviewed 16 published studies that looked at cell phone use and the risk of brain cancers and concluded that using cell phones for more than 10 years gives a consistent pattern of increased risk of at least 2 types of brain cancer such as acoustic neuroma and gliomas. The risk is significantly higher for the ipsilateral exposure (tumor on the same side of the brain as cell phone exposure).3

More on Glioblastoma Multiforme

Overview: Glioblastoma Multiforme
Differential Diagnoses & Workup: Glioblastoma Multiforme
Treatment & Medication: Glioblastoma Multiforme
Follow-up: Glioblastoma Multiforme
Multimedia: Glioblastoma Multiforme
References
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Further Reading

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Keywords

glioblastoma multiforme, GBM, malignant glioma, grade IV astrocytoma, grade IV glioma, high-grade astrocytoma, HGA, high-grade glioma, primary brain tumor, gliosarcoma, multifocal GBM, gliomatosis cerebri, intracranial tumor, MMAC1 mutations, CDKN2A deletions, MDM2 amplifications, tuberous sclerosis, neurofibromatosis type 1, neurofibromatosis type 2, Turcot syndrome, Li-Fraumeni syndrome, brain tumors, malignant astrocytoma, de novo glioblastomas, secondary glioblastomas, primary glioblastoma

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Contributor Information and Disclosures

Author

ABM Salah Uddin, MD, Consulting Staff, Department of Internal Medicine, St Vincent's Hospital
ABM Salah Uddin, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Tambi Jarmi, MD, Resident Physician, Department of Internal Medicine, Carraway Methodist Medical Center
Tambi Jarmi, MD is a member of the following medical societies: American College of Physicians and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Amy A Pruitt, MD, Associate Professor of Neurology, University of Pennsylvania; Attending Neurologist, Hospital of the University of Pennsylvania
Amy A Pruitt, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jorge Kattah, MD, Head, Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria
Jorge Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and New York Academy of Sciences
Disclosure: Biogen Honoraria Consulting; Bayer Corporation Honoraria Consulting

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center
Stephen A Berman, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

 
 
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