Glioblastoma multiforme (GBM)

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Glioblastoma multiforme (GBM)
MRI showing GBM
Tumor Class	Astrocytoma
Cell of origin	Glial precursor
WHO Grade	IV
Survival	10-12 Months
Treatment	Surgery,Radiation,Chemotherapy
Histologic Features Gross variable appearance may have evidence of old and recent hemorrhage, necrosis and areas of firm tissue. Micro pleomorphic cells, mitotic figures, endothelial proliferation, necrosis
Radiographic Features
MRI	usually a peripherally enhancing mass with a necrotic center
CT	non contrast appears hypodense, with contrast appears ring enhancing

Glioblastoma is the most common primary brain tumor. There are approximately 20,000 new cases annually of primary malignant brain tumors in the United States per year and 12,900 of these are glioblastoma. Despite aggressive treatments including surgical resection, radiation and chemotherapy, median survival is approximately 12 months. The median survival has not yielded significantly in the last 25 years.

Definition

GBM is an astrocytic neoplasm, typically affecting adults, biologically characterized by cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular necrosis and necrosis. These lesions may arise de novo (primary), or following malignant degeneration of a lower-grade astrocytic lesion (secondary). GBM corresponds to WHO Grade IV astrocytoma.

Epidemiology

GBM is the most common primary brain tumor, accounting for 12-15% of all intracranial neoplasms and about 50-60% of all astrocytic tumors. The peak incidence is in young adults between age 45 and 70, with a mean age of occurrence at 53 years. There is a male predominance (1.5:1).

Localization

GBM occurs most often in the subcortical white matter of the cerebral hemispheres. Tumor infiltration into the adjacent cortex, basal ganglia or contralateral hemisphere is common.

Clinical presentation

Patients may present with seizure or with signs and symptoms attributable to mass effect or brain invasion.

Imaging

On MRI, GBMs are ring-enhancing. Associated brain edema and mass effect are characteristic.

Gross specimen depicting a glioblastoma in the insula of the right hemisphere.

Macroscopy

GBMs are poorly delineated lesions. Much of the tumor mass may be made up of necrotic tissue, with a surrounding rim of hypercellular tissue that may allow the surgeon to find a pseudo-plane between tumor and normal brain.

Histopathology

GBM is characterized by poorly differentiated, often pleomorphic, neoplastic astrocytes with marked nuclear atypia and high mitotic activity. The presence of vascular (endothelial) proliferation and necrosis are necessary for diagnosis.

Molecular genetics

See Molecular Genetics of Gliomagenesis.

Therapy

The standard of care for GBM involves gross total resection of the enhancing disease if feasible, followed by concurrent chemotherapy with temozolomide and radiotherapy (usually 60Gy in 6 weeks). This is typically followed by a higher dose of temozolomide.

Prognosis

Median survival time following surgical intervention is 10-14 months. Median survival without surgical intervention is significantly shorter (4 months). Young age (<40) and gross total resection (of enhancing disease) are considered predictive of longer survival.

Notes

1. CBTRUS, (2005), Statistical report: Primary Brain Tumors in the United States, 1998-2002. Published by theCentral Brain Tumor Registry of the United States.