History

The clinical history of patients with glioblastoma (GBM) is usually short, spanning less than 3 months in 68% of patients and < 6 months in 84% of patients.^[4]Note the following:

The most common presenting symptoms of GBM are seizure and cognitive disorder. ^[5]
Other common presenting symptoms include slowly progressive focal neurologic deficits, such as motor weakness, sensory loss, memory loss, language deficits, and visual impairments. ^[6]
Alternatively, patients may present with generalized symptoms of increased intracranial pressure (ICP), including headaches, nausea and vomiting, and personality changes. ^[6]
A minority of patients present with stroke-like symptoms and signs following intratumoral/intracranial hemorrhage. ^[2]
In general, the three histologic subtypes—giant cell glioblastoma, gliosarcoma, and eplthelioid glioblastoma—present similarly. ^[2]

Physical Examination

Neurologic symptoms and signs affecting patients with glioblastomas can be either general or focal and reflect the location of the tumor. General symptoms include headaches, nausea and vomiting, personality changes, and slowing of cognitive function. Note the following:

Changes in personality, mood, mental capacity, and concentration can be early indicators or may be the only abnormalities observed.
Common focal neurologic signs and symptoms include hemiparesis, sensory loss, visual loss, and aphasia.
Headaches can vary in intensity and quality but tend to be exacerbated by lying supine and are thus usually more severe upon first awakening or in the early morning; they may be induced by asking the patient to cough or perform the Valsalva maneuver. ^[6]
Headache along with a new neurologic deficit (particularly cognitive impairment or focal weakness) significantly increases the likelihood of an underlying brain tumor. ^[156]

Differential Diagnoses

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Media Gallery

Axial CT scan without intravenous contrast reveals a large right temporal intra-axial mass (glioblastoma). Extensive surrounding edema is present, as demonstrated by the peritumoral hypodensity, and a moderate right-to-left midline shift can be noted. All of the radiologic studies in this article are of the same patient.
A T1-weighted axial MRI without intravenous contrast demonstrates a hemorrhagic multicentric glioblastoma in the right temporal lobe. Effacement of the ventricular system is present on the right, along with mild impingement of the right medial temporal lobe on the midbrain.
A T1-weighted axial MRI with intravenous contrast shows heterogeneous enhancement of the lesion within the right temporal lobe. The hypointensity circumscribed within the enhancement is suggestive of necrosis. This radiologic appearance is typical of a multicentric glioblastoma.
A T1-weighted coronal MRI with intravenous contrast demonstrates a glioblastoma within the medial temporal lobe and the stereotypical pattern of contrast enhancement.
A T1-weighted sagittal MRI with intravenous contrast demonstrates a glioblastoma.
On T2-weighted axial MRI, the tumor (glioblastoma) and surrounding white matter within the right temporal lobe show increased signal intensity compared with a healthy brain, suggesting extensive tumorigenic edema.
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.
Histopathologic slide demonstrating classic glioblastoma (GBM).
Magnetic resonance (MR) spectroscopy signal representative of glioblastoma (GBM) demonstrating a high peak ratio of choline (CHO) to creatine (CR), a decreased N-acetylaspartate (NAA) peak, and an increased lactate (LAC) peak.
Hematoxylin and eosin stain of a biopsy specimen of a glioblastoma shows prominent microvascular proliferation (formation of a mulitlayered "glomeruloid tuft"). Courtesy of Wikimedia Commons [author Jensflorian, https://commons.wikimedia.org/wiki/File:Glioblastoma_endothelial_proliferations.jpg].
Necrosis is another histopathologic hallmark of glioblastoma. As seen here, necrotic areas often create serpentine patterns, and tumor cells form pseudopalisades around the periphery of these necrotic areas. Courtesy of Wikimedia Commons [author Jensflorian, https://commons.wikimedia.org/wiki/File:GBM_pseudopalisading_necrosis.jpg].
Coronal section of a glioblastoma in the left temporal lobe with typical coloration: thickened tan cortex overlying a large central region of yellowish necrosis stippled with red and brown lesions from new and old hemorrhage. Courtesy of Wikimedia Commons [author Sbrandner, https://commons.wikimedia.org/wiki/File:Glioblastoma_macro.jpg].
Histology section of a giant cell glioblastoma. Several bizarre, multinucleated giant cells are visible against a background of smaller tumor cells. Courtesy of Wikimedia Commons (author Jensflorian, https://commons.wikimedia.org/wiki/File:Giant_cell_glioblastoma_HE_X200.jpg].
Histology section of a gliosarcoma with Van Gieson’s stain highlighting connective tissue. The classic alternating pattern of gliomatous (pink) and sarcomatous (yellow-brown) tissue is evident. Courtesy of Wikimedia Commons [author Marvin 101, https://commons.wikimedia.org/wiki/File:Gliosarcoma_Histopathology_200x_EVG.jpg].
This glioblastoma is composed of large epithelioid cells that are immunoreactive for glial fibrillary acidic protein (GFAP) (hematoxylin and eosin, 40× original magnification). Courtesy of Roger E McLendon, MD.
This typical untreated glioblastoma, here with the classic "butterfly" configuration, is a necrotic hemorrhagic mass. Courtesy of Wikimedia Commons [author Rodney D McComb, MD and The Armed Forces Institute of Pathology, https://commons.wikimedia.org/wiki/File:Glioblastoma_multiforme.jpg].

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Author

Jeffrey N Bruce, MD Edgar M Housepian Professor of Neurological Surgery Research, Vice-Chairman and Professor of Neurological Surgery, Director of Columbia Brain Tumor Center, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University Vagelos College of Physicians and Surgeons

Jeffrey N Bruce, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, American Society of Clinical Oncology, Congress of Neurological Surgeons, New York Academy of Sciences, North American Skull Base Society, Pituitary Society, Society for Neuro-Oncology, Society of Neurological Surgeons

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Theracle, Inc. <br/>Received grant/research funds from NIH for other.

Coauthor(s)

Cole M Chokran, AB MD/MS Candidate, Columbia University Vagelos College of Physicians and Surgeons

Disclosure: Nothing to disclose.

William M Savage, BA MD Candidate, Columbia University Vagelos College of Physicians and Surgeons

Disclosure: Nothing to disclose.

Nina Teresa Yoh, MD Resident Physician, Department of Neurological Surgery, Columbia University Irving Medical Center, New York-Presbyterian Hospital

Nina Teresa Yoh, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Gold Humanism Honor Society, Neurocritical Care Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Herbert H Engelhard, III, MD, PhD, FACS, FAANS Affiliated Professor of Bioengineering, University of Illinois at Chicago

Herbert H Engelhard, III, MD, PhD, FACS, FAANS is a member of the following medical societies: American Association for Cancer Research, American Association of Neurological Surgeons, American College of Surgeons, American Medical Association, Congress of Neurological Surgeons, Illinois State Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

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 Association for Physician Leadership, European Society for Medical Oncology, Association of Clinical Research Professionals, American Federation for Clinical Research, Eastern Cooperative Oncology Group, Society for Immunotherapy of Cancer, American Medical Informatics Association, American College of Physicians, American Federation for Medical Research, American Medical Association, American Society of Hematology, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Benjamin C Kennedy, MD Assistant Professor of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania; Director of Epilepsy and Functional Neurosurgery, The Children’s Hospital of Philadelphia

Disclosure: Nothing to disclose.

Acknowledgements

We would like to acknowledge previous contributions to this chapter from Katharine Cronk, MD,PhD; Richard C Anderson, MD; Chris E Mandigo, MD; Andrew T Parsa MD, PhD; Patrick B Senatus, MD, PhD; and Allen Waziri, MD.

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