Glioblastoma Multiforme

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Contents 1 More Specific Terms 2 Epidemiology 3 Pathology 4 Microscopic-pathology 5 Genetics 6 Laboratory 7 Radiology 8 Complications 9 Management 10 More General Terms 11 Internet Database 12 References

More Specific Terms

• giant cell glioblastoma
• gliosarcoma

Epidemiology

• ~12 -5% of intracranial neoplasms
• ~50-60% of astrocytic tumors
• any age, peak between 45 and 70

Pathology

• may occur as primary glioblastoma or progression from diffuse or anaplastic astrocytoma
• most often occur in subcortical white matter of cerebral hemispheres
• infiltrative, poorly delineated
• may cross corpus callosum into other hemisphere ('butterfly glioma'), similar rapid spread seen in other white matter tracts - internal capsule, fornix, anterior commisure
• extension and infiltration along perivascular spaces seen
• metastasis:

• tends not to invade subarachnoid space & rarely
• metastasizes through CSF
• metastases outside the CNS are rare

Microscopic-pathology

• increased cellularity
• nuclear atypia
• mitoses
• endothelial proliferation
• necrosis

• The presence of 3 of the above criteria (excluding #1) is sufficient for diagnosis of GBM; presence of necrosis is not necessary.

Genetics

• chromosome 9p loss in 50% of anaplastic astrocytomas & GBMs primarily affecting CDKN2A gene
• chromosome 13q loss in 1/3 - 1/2 of high grade astrocytomas RB gene inactivated in 20% of anaplastic astrocytomas, 35% GBMs
• chromosome 12q13-14 amplification in 15% malignant gliomas including gene for CDK4
• allelic loss on chromosome 19q in up to 40% of anaplastic astrocytomas and GBMs
• chromosome 10 loss in 60-95% of GBMs PTEN mutations in ~10% of GBMs DMBT1 gene
• EGFR gene amplification in ~40% of primary GBMs less commonly amplified genes: N-myc, gli, c-myc, myb, K-ras, PDGF receptor alpha, MDM2
• homozygous deletion in chromosome 6q21 results in expression of a GOPC- ROS1 chimeric protein with constitutive receptor tyrosine kinase activity
• chromosomal translocation t(10;19)(q26;q13.3) involving ZNF320 with BRWD2/ WDR11
• diminished or absent expression of PHF3, JARID1B, THEM4, RIG
• expression of STAT3 & c-ebpb portend poor prognosis
• other implicated genes: MMP24, MMP25

• Two subtypes based on clinical characteristics:

• primary GBM associated with

• ink4A loss
• EGFR gene amplification in ~40% of primary GBMs (rare in secondary GBMs)
• PTEN loss >30% (rare in secondary GBM)
• MDM2 amplification

• secondary GBM associated with

• initially

• p53 loss
• PDGF/ PDGFR overexpression

• progressing with

• RB loss
• CDK4 amplification

Laboratory

• biopsy (tissue needed for diagnosis)

• stereotactic needle biopsy
• open biopsy

• autoantibodies: PHF20

Radiology

• magnetic resonance imaging ( MRI)
• computed tomography ( CT)
• in general, higher grade astrocytic tumors show contrast enhancement

Complications

• 
  
• disease interaction(s) of cancer with Alzheimer's disease

Management

• surgery:

• debulking if patient will not suffer neurologic deficit
• not clear that debulking of tumor enhances survival

• radiation

• 5000-6500 cGy
• prolongs survival
• administered in multiple fractions to an area around the tumor
• radiation necrosis may produce clinical picture indistinguishable from recurrent high-grade tumor

• chemotherapy ( BCNU) combined with radiation

• treatment of choice

• temozolomide ( Temodar) at 1st relapse
• prognosis

• 1-2 months without surgery
• 4 months with surgery alone
• 6-9 months with surgery plus radiation
• 10-12 months with surgery plus radiation plus chemotherapy
• 80% recur after surgical resection plus whole brain irradiation
• radiation plus brachytherapy may give best results (18 months)

• attenuated HSV-1 in clinical trials (Univ of Alabama)

More General Terms

• malignant neoplasm (cancer)
• astrocytoma (astrocytic neoplasm)

Internet Database

OMIM: 137800

References

1. OMIM 137800
2. Mark Felmus, M.D., Ph.D., Dept. of Medicine, UCSF Fresno
3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
4. Levin et al, Neoplasms of the central nervous system, in: Cancer: Principles & Practice of Oncology, DeVita et al, eds, Lippincott, Williams & Wilkins, Philadelphia, 2001, pg 2100
5. WHO Classification Tumours of the Nervous System. Kleihues & Cavenee eds. IARC Press 2000
6. National Guideline Clearinghouse Glioblastoma. Alberta Health Services, Cancer Care ngc-guideline: [1]

glioblastoma multiforme (GBM) or astrocytoma grade IV