Neurologic Manifestations of Glioblastoma Multiforme Workup

  • Author: ABM Salah Uddin, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA   more...
 
Updated: Apr 19, 2010
 

Laboratory Studies

Routine laboratory workup results often are negative, but excluding a metabolic or infective process is important in an otherwise healthy patient who presents with new-onset seizures or mental status changes for the first time.

Next

Imaging Studies

  • The preferred workup is diagnostic neuroimaging studies; MRI with and without contrast is the most sensitive and specific study.
    • These tumors characteristically have low-signal intensity on T1-weighted images and high-signal intensity on T2-weighted images.
    • With contrast, the tumors usually enhance. The enhanced T1-weighted images typically have a central hypodensity surrounded by a thick enhancing rim of tumor.T1-weighted axial gadolinium-enhanced MRI demonstrT1-weighted axial gadolinium-enhanced MRI demonstrates an enhancing tumor of the right frontal lobe. Image courtesy of George Jallo, MD. T2-weighted image demonstrates notable edema and mT2-weighted image demonstrates notable edema and midline shift. This finding is consistent with a high grade or malignant tumor. Image courtesy of George Jallo, MD.
  • CT scan can be ordered with or without contrast when MRI is contraindicated or unavailable.
    • On CT scan, GBMs have a variable, inhomogeneous hypodense or isodense appearance with surrounding edema.
    • GBMs tend to infiltrate along the white matter tracts and frequently involve and cross the corpus callosum.
    • Approximately 4-10% of GBMs and 30-50% of AAs do not enhance, while a significant percentage of low-grade gliomas do not enhance.
Previous
Next

Other Tests

  • Functional neuroimaging such as positron emission tomography (PET scan), single-photon emission computed tomography (SPECT), or MR spectroscopy may help differentiate the tumor from other benign mass lesions, brain abscess, or toxoplasmosis. However, the definitive diagnosis is confirmed by stereotactic or open brain biopsy.Magnetic resonance spectroscopy is representative Magnetic resonance spectroscopy is representative of a glioblastoma multiforme.
  • Functional imaging is commonly used to differentiate between treatment-related radiation necrosis and tumor recurrence.
  • Functional imaging is also used in defining the margins of the tumor for surgical resection and planning for the radiation fields.
  • Additionally, functional imaging may be helpful in determining the most abnormal region of the tumor to improve the diagnostic accuracy in case a small biopsy sample is taken.
Previous
Next

Histologic Findings

High-grade astrocytomas (HGAs) are extremely heterogenous tumors characterized by varying degrees of increased cellularity, pleomorphism, mitoses, endothelial proliferation, and necrosis.

Histopathologic slide demonstrating a glioblastomaHistopathologic slide demonstrating a glioblastoma multiforme.
Previous
Next

Staging

Many different grading systems exist for gliomas. The current WHO classification of gliomas is based on the presence or absence of 4 histologic criteria: (1) nuclear atypia, (2) mitoses, (3) endothelial proliferation, and (4) necrosis. Grade I tumors have none of the criteria, grade II have at least 1, grade III have at least 2, and grade IV (GBM) have at least 3 or 4 criteria present. Prominent microvascular proliferation and/or necrosis must be one of the criteria for GBM.

Previous
Proceed to Treatment & Management
 
 
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.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

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

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: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Stephen A Berman, MD, PhD, MBA  Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

References

  1. Seiz M, Nolte I, Pechlivanis I, Freyschlag CF, Schmieder K, Vajkoczy P, et al. Far-distant metastases along the CSF pathway of glioblastoma multiforme during continuous low-dose chemotherapy with temozolomide and celecoxib. Neurosurg Rev. Mar 2010;Epub.

  2. Tuettenberg J, Grobholz R, Seiz M, Brockmann MA, Lohr F, Wenz F, et al. Recurrence pattern in glioblastoma multiforme patients treated with anti-angiogenic chemotherapy. J Cancer Res Clin Oncol. Sep 2009;135(9):1239-44. [Medline].

  3. Buhl R, Barth H, Hugo HH, Hutzelmann A, Mehdorn HM. Spinal drop metastases in recurrent glioblastoma multiforme. Acta Neurochir (Wein). 1998;140(10):1001-5.

  4. Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. Nov 15 2004;101(10):2293-9. [Medline].

  5. Hardell L, Carlberg M, Söderqvist F, Mild KH, Morgan LL. Long-term use of cellular phones and brain tumours: increased risk associated with use for > or =10 years. Occup Environ Med. Sep 2007;64(9):626-32. [Medline].

  6. Pichlmeier U, Bink A, Schackert G, Stummer W. ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioninganalysis of ALA study patients. Neuro-Oncol. Oct 2008;(6):1025-34.

  7. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. May 2009;10(5):459-66. [Medline].

  8. Hatanaka H. Analysis of clinical results of long surviving brain tumor patients who underwent Boron-neutron-capture therapy with mercapto undeca hydrocarborate. Acapulco Mexico: Abs; X international congress of Neurosurgery; 1993, pp199.

  9. Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol. Apr 2003;5(2):79-88. [Medline].

  10. Darakchiev BJ, Albright RE, Breneman JC, Warnick RE. Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme. J Neurosurg. Feb 2008;108(2):236-42. [Medline].

  11. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. Mar 10 2005;352(10):997-1003. [Medline].

  12. Iwamoto FM, Fine HA. Bevacizumab for malignant gliomas. Arch Neurol. Mar 2010;67(3):285-8. [Medline].

  13. Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, et al. Phase II Trial of Continuous Dose-Intense Temozolomide in Recurrent Malignant Glioma: RESCUE Study. J Clin Oncol. Mar 22 2010;[Medline].

  14. Rosati A, Tomassini A, Pollo B, Ambrosi C, Schwarz A, Padovani A. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. Jul 2009;93(3):395-400. [Medline].

  15. Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain. Oct 2007;130:2596-606. [Medline].

  16. Luther N, Cheung NK, Souliopoulos EP, Karempelas I, Bassiri D, Edgar MA, et al. Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38. Mol Cancer Ther. Apr 2010;9(4):1039-46. [Medline].

  17. Wang LF, Fokas E, Juricko J, You A, Rose F, Pagenstecher A, et al. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC Cancer. Mar 25 2008;8:79. [Medline].

  18. Liang Y, Bollen AW, Aldape KD, Gupta N. Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006;6:97. [Medline].

  19. Grossman SA, Ye X, Chamberlain M, Mikkelsen T, Batchelor T, Desideri S, et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol. Sep 1 2009;27(25):4155-61. [Medline].

  20. Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. Apr 15 2010;16(8):2443-9. [Medline].

  21. Bruner JM. Neuropathology of malignant gliomas. Semin Oncol. Apr 1994;21(2):126-38. [Medline].

  22. Burger PC, Vogel FS, Green SB, Strike TA. Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer. Sep 1 1985;56(5):1106-11. [Medline].

  23. Byrne TN. Imaging of gliomas. Semin Oncol. Apr 1994;21(2):162-71. [Medline].

  24. Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol. Mar 2010;67(3):279-83. [Medline].

  25. Colombo F, Barzon L, Franchin E, et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results. Cancer Gene Ther. Oct 2005;12(10):835-48. [Medline].

  26. Eagan RT, Scott M. Evaluation of prognostic factors in chemotherapy of recurrent brain tumors. J Clin Oncol. Jan 1983;1(1):38-44. [Medline].

  27. Gilbert MR, Loghin M. The Treatment of Malignant Gliomas. Curr Treat Options Neurol. Jul 2005;7(4):293-303. [Medline].

  28. Green SB, Byar DP, Walker MD, et al. Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep. Feb 1983;67(2):121-32. [Medline].

  29. Kaye AH, Laws ER Jr. Brain Tumors: An Encyclopedic Approach. New York, NY: Churchill Livingtone; 1995:449-77.

  30. Kleihus P, Cavenee WK. Pathology and Genetics: Tumors of the Nervous System. Lyon, France: IARC Press; 2000:56-64.

  31. Lakka SS, Rajan M, Gondi C, et al. Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene. Nov 14 2002;21(52):8011-9. [Medline].

  32. Leibel SA, Scott CB, Pajak TF. The management of malignant gliomas with radiation therapy: Therapeutic results and research strategies. Semin Radiat Oncol. 1991;1:32-49.

  33. Loeffler JS, Alexander E, Wen PY, et al. Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. J Natl Cancer Inst. Dec 19 1990;82(24):1918-21. [Medline].

  34. Lu KV, Jong KA, Kim GY, et al. Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. J Biol Chem. Jul 22 2005;280(29):26953-64. [Medline].

  35. Macdonald DR. Adjuvant chemotherapy for brain tumor. Semin Radiat Oncol. 1991;1:54-61.

  36. Pallasch CP, Struss AK, Munnia A, et al. Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival. Int J Cancer. Nov 10 2005;117(3):456-9. [Medline].

  37. Rich JN, Hans C, Jones B, et al. Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res. May 15 2005;65(10):4051-8. [Medline]. [Full Text].

  38. Schold SC, Burger PC, Minna JD, et al. Primary Tumors of the Brain and Spinal Cord. Boston, Mass: Butterworth-Heinemann; 1997:41-59.

  39. Sipos EP, Brem H. New delivery systems for brain tumor therapy. Neurol Clin. Nov 1995;13(4):813-25. [Medline].

  40. Stupp R, Mason WP. Concomitant and adjuvant temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Conclusive results of randomized phase III trial by the EORTC brain and RT Groups and NCIC clinical trials group. American Society of Clinical Oncology. 2004;23:1.

  41. Valk PE, Budinger TF, Levin VA, et al. PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome. J Neurosurg. Dec 1988;69(6):830-8. [Medline].

  42. Vile R, Russell SJ. Gene transfer technologies for the gene therapy of cancer. Gene Ther. Mar 1994;1(2):88-98. [Medline].

  43. Wallner KE, Galicich JH, Krol G, et al. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys. Jun 1989;16(6):1405-9. [Medline].

  44. Wen PY, Fine HA, Black PM, et al. High-grade astrocytomas. Neurol Clin. Nov 1995;13(4):875-900. [Medline].

  45. Westermark B, Nister M. Molecular genetics of human glioma. Curr Opin Oncol. May 1995;7(3):220-5. [Medline].

 
Previous
Next
 
T1-weighted axial gadolinium-enhanced MRI demonstrates an enhancing tumor of the right frontal lobe. Image courtesy of George Jallo, MD.
T2-weighted image demonstrates notable edema and midline shift. This finding is consistent with a high grade or malignant tumor. Image courtesy of George Jallo, MD.
Histopathologic slide demonstrating a glioblastoma multiforme.
Magnetic resonance spectroscopy is representative of a glioblastoma multiforme.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.