eMedicine Specialties > Oncology > Carcinomas of the Central and Peripheral Nervous System

Glioblastoma Multiforme: Differential Diagnoses & Workup

Author: Jeffrey N Bruce, MD, Edgar M Housepian Professor of Neurological Surgery Research, Professor of Neurological Surgery, Director of Brain Tumor Tissue Bank, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University College of Physicians and Surgeons
Coauthor(s): Benjamin Kennedy,, Columbia University College of Physicians and Surgeons
Contributor Information and Disclosures

Updated: Nov 5, 2009

Differential Diagnoses

Other Problems to Be Considered

Anaplastic astrocytoma
Cavernous malformation
Cerebral abscess
CNS lymphoma
Encephalitis
Intracranial hemorrhage
Metastasis
Oligodendroglioma
Radiation necrosis
Toxoplasmosis

Workup

Laboratory Studies

  • Currently, no specific laboratory studies are helpful in making a diagnosis of glioblastoma.
  • Response to adjuvant therapy may be predicted based on the tumor's genetics.

Imaging Studies

  • Imaging studies of the brain are essential to make the diagnosis of glioblastoma multiforme (GBM).
  • On CT scans, glioblastomas usually appear as irregularly shaped hypodense lesions with a peripheral ringlike zone of contrast enhancement and a penumbra of cerebral edema (see Image 2).
A T1-weighted axial MRI without intravenous contr...

A T1-weighted axial MRI without intravenous contrast. This image demonstrates a hemorrhagic multicentric tumor (glioblastoma multiforme [GBM]) in the right temporal lobe. Effacement of the ventricular system is present on the right, and mild impingement of the right medial temporal lobe can be observed on the midbrain.

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A T1-weighted axial MRI without intravenous contr...

A T1-weighted axial MRI without intravenous contrast. This image demonstrates a hemorrhagic multicentric tumor (glioblastoma multiforme [GBM]) in the right temporal lobe. Effacement of the ventricular system is present on the right, and mild impingement of the right medial temporal lobe can be observed on the midbrain.


  • MRI with and without contrast is the study of choice. These lesions typically have an enhancing ring observed on T1-weighted images (see Images 3-6) and a broad surrounding zone of edema apparent on T2-weighted images (see Images 7-8). The central hypodense core represents necrosis, the contrast-enhancing ring is composed of highly dense neoplastic cells with abnormal vessels permeable to contrast agents, and the peripheral zone of nonenhancing low attenuation is vasogenic edema containing varying numbers of invasive tumor cells. Several pathological studies have clearly shown that the area of enhancement does not represent the outer tumor border because infiltrating glioma cells can be identified easily within, and occasionally beyond, a 2-cm margin.30
A T1-weighted axial MRI with intravenous contrast...

A T1-weighted axial MRI with intravenous contrast. Heterogenous enhancement of the lesion is present within the right temporal lobe. The hypointensity circumscribed within the enhancement is suggestive of necrosis. This radiologic appearance is typical of a multicentric glioblastoma multiforme (GBM).

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A T1-weighted axial MRI with intravenous contrast...

A T1-weighted axial MRI with intravenous contrast. Heterogenous enhancement of the lesion is present within the right temporal lobe. The hypointensity circumscribed within the enhancement is suggestive of necrosis. This radiologic appearance is typical of a multicentric glioblastoma multiforme (GBM).


A T1-weighted coronal MRI with intravenous contra...

A T1-weighted coronal MRI with intravenous contrast. This image demonstrates the lesion (glioblastoma multiforme [GBM]) within the medial temporal lobe and the stereotypical pattern of contrast enhancement.

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A T1-weighted coronal MRI with intravenous contra...

A T1-weighted coronal MRI with intravenous contrast. This image demonstrates the lesion (glioblastoma multiforme [GBM]) within the medial temporal lobe and the stereotypical pattern of contrast enhancement.


A T1-weighted sagittal MRI with intravenous contr...

A T1-weighted sagittal MRI with intravenous contrast in a patient with glioblastoma multiforme (GBM).

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A T1-weighted sagittal MRI with intravenous contr...

A T1-weighted sagittal MRI with intravenous contrast in a patient with glioblastoma multiforme (GBM).


A T2-weighted axial MRI. The tumor (glioblastoma ...

A T2-weighted axial MRI. The tumor (glioblastoma multiforme [GBM]) and surrounding white matter within the right temporal lobe show increased signal intensity compared to a healthy brain, suggesting extensive tumorigenic edema.

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A T2-weighted axial MRI. The tumor (glioblastoma ...

A T2-weighted axial MRI. The tumor (glioblastoma multiforme [GBM]) and surrounding white matter within the right temporal lobe show increased signal intensity compared to a healthy brain, suggesting extensive tumorigenic edema.


A fluid-attenuated inversion recovery (FLAIR) axi...

A fluid-attenuated inversion recovery (FLAIR) axial MRI. This image is similar to the T2-weighted image and demonstrates extensive edema in a patient with glioblastoma multiforme (GBM).

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A fluid-attenuated inversion recovery (FLAIR) axi...

A fluid-attenuated inversion recovery (FLAIR) axial MRI. This image is similar to the T2-weighted image and demonstrates extensive edema in a patient with glioblastoma multiforme (GBM).


Histopathologic slide demonstrating a glioblastom...

Histopathologic slide demonstrating a glioblastoma multiforme (GBM).

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Histopathologic slide demonstrating a glioblastom...

Histopathologic slide demonstrating a glioblastoma multiforme (GBM).


  • Positron emission tomography (PET) scans and magnetic resonance (MR) spectroscopy can be helpful to identify glioblastomas in difficult cases, such as those associated with radiation necrosis or hemorrhage. On PET scans, increased regional glucose metabolism closely correlates with cellularity and reduced survival. MR spectroscopy demonstrates an increase in the choline-to-creatine peak ratio, an increased lactate peak, and decreased N- acetylaspartate (NAA) peak in areas with glioblastomas.
  • Cerebral angiograms are not necessary for the diagnosis or clinical management of glioblastomas.
Magnetic resonance (MR) spectroscopy is represent...

Magnetic resonance (MR) spectroscopy is representative of a glioblastoma multiforme (GBM).

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Magnetic resonance (MR) spectroscopy is represent...

Magnetic resonance (MR) spectroscopy is representative of a glioblastoma multiforme (GBM).


Other Tests

  • Electroencephalography (EEG) performed on a patient with glioblastoma multiforme may show generalized diffuse slowing and/or epileptogenic spikes over the area of the tumor. However, findings specific for glioblastoma cannot be observed on EEG.

Procedures

  • Lumbar puncture is generally contraindicated in the setting of a brain tumor because of the possibility of transtentorial herniation with increased intracranial pressure. However, if ruling out lymphoma, it may be necessary.
  • CSF studies do not aid significantly in the specific diagnosis of glioblastoma multiforme.

Histologic Findings

As its name suggests, the histopathology of glioblastoma multiforme is extremely variable. Glioblastoma multiformes are composed of poorly differentiated, often pleomorphic astrocytic cells with marked nuclear atypia and brisk mitotic activity. Necrosis is an essential diagnostic feature, and prominent microvascular proliferation is common. Macroscopically, glioblastomas are poorly delineated, with peripheral grayish tumor cells, central yellowish necrosis from myelin breakdown, and multiple areas of old and recent hemorrhages. Most glioblastomas of the cerebral hemispheres are clearly intraparenchymal with an epicenter in the white matter, but some extend superficially and contact the leptomeninges and dura.31,32,33,34,35,36,37

Despite the short duration of symptoms, these tumors are often surprisingly large at the time of presentation, occupying much of a cerebral lobe. Undoubtedly, glial fibrillary acidic protein (GFAP) remains the most valuable marker for neoplastic astrocytes. Although immunostaining is variable and tends to decrease with progressive dedifferentiation, many cells remain immunopositive for GFAP even in the most aggressive glioblastomas. Vimentin and fibronectin expression are common but less specific.38

The regional heterogeneity of glioblastomas is remarkable and makes histopathological diagnosis a serious challenge when it is based solely on stereotactic needle biopsies. Tumor heterogeneity is also likely to play a significant role in explaining the meager success of all treatment modalities, including radiation, chemotherapy, and immunotherapy.

Histopathologic slide demonstrating a glioblastom...

Histopathologic slide demonstrating a glioblastoma multiforme (GBM).

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Histopathologic slide demonstrating a glioblastom...

Histopathologic slide demonstrating a glioblastoma multiforme (GBM).


Staging

Completely staging most glioblastomas is neither practical nor possible because these tumors do not have clearly defined margins. Rather, they exhibit well-known tendencies to invade locally and spread along compact white matter pathways, such as the corpus callosum, internal capsule, optic radiation, anterior commissure, fornix, and subependymal regions. Such spread may create the appearance of multiple glioblastomas or multicentric gliomas on imaging studies.

Careful histological analyses have indicated that only 2-7% of glioblastomas are truly multiple independent tumors rather than distant spread from a primary site. Despite its rapid infiltrative growth, the glioblastoma tends not to invade the subarachnoid space and, consequently, rarely metastasizes via cerebrospinal fluid (CSF). Hematogenous spread to extraneural tissues is very rare in patients who have not had previous surgical intervention, and penetration of the dura, venous sinuses, and bone is exceptional.39,40,41,42,43,44

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, brain cancer, brain malignancy, glioblastoma, WHO grade IV glioma, Kernohan grade IV astrocytoma, St. Anne/Mayo astrocytoma grade 4, p53, EGFR, MDM2, PDGF, PTEN, brain tumors, primary brain tumors, glial tumors, lower-grade astrocytomas, anaplastic astrocytomas, primary GBMs, secondary GBMs, astrocytic brain tumors, butterfly glioma, intracranial neoplasms, progressive neurologic deficit, motor weakness, seizures, supratentorial brain tumors, neurofibromatosis

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Contributor Information and Disclosures

Author

Jeffrey N Bruce, MD, Edgar M Housepian Professor of Neurological Surgery Research, Professor of Neurological Surgery, Director of Brain Tumor Tissue Bank, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University College of Physicians and Surgeons
Jeffrey N Bruce, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Neurological Surgeons, Congress of Neurological Surgeons, New York Academy of Sciences, North American Skull Base Society, Society for Neuro-Oncology, and Southwest Oncology Group
Disclosure: NIH Grant/research funds Other

Coauthor(s)

Benjamin Kennedy,, Columbia University College of Physicians and Surgeons
Disclosure: Nothing to disclose.

Medical Editor

Robert C Shepard, MD, FACP, Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International
Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy
Disclosure: Nothing to disclose.

Pharmacy Editor

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

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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