Neurosurgery

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Glioblastoma Multiforme:
Disseminated Glioma

by Sean Snodgress, MD, neuroradiologist

 

Glioblastoma multiforme (GBM ) is the most aggressive primary brain tumor in humans, and accounts for approximately 20 percent of all intracranial tumors and approximately 50 to 60 percent of the 17,000 primary brain tumors diagnosed each year in the United States.

 

GBM tumors are of astrocytic origin, and result from de-differentiation of lower-grade astrocytomas or, more commonly, arise de novo. GBM has a peak incidence between the ages of 45 and 70, but can occur at any age. Prognosis is very poor, with an average life expectancy on diagnosis of between 9 and 12 months.

 

Sean Snodgress, MD

 


See Case Study below >


GBM tends to be a rapidly enlarging tumor that outgrows its blood supply despite extensive neovascularity. These characteristics result in a typical imaging appearance. The tumors demonstrate irregular peripheral enhancement, with central nonenhancement correlating with tumor necrosis. GBM typically does not demonstrate areas of restricted diffusion, but in uncommon cases may show small areas of peripheral restriction diffusion correlating with sites of high tumor cellularity.

 

The lesions are usually surrounded by T1 hypointensity and T2 hyperintensity. This signal abnormality represents one of the more intriguing and challenging aspects of brain tumor imaging, as it often represents a combination of vasogenic edema and tumor infiltration, and differentiation between the two is often very difficult with imaging. This creates an obvious challenge in planning for tumor resection.

 

The majority of GBM cases are unifocal masses, but may rarely—in approximately 2 percent of cases, though some case series report an up to 10 or even 15 percent incidence— present with multiple, seemingly discontiguous sites of tumor involvement. These diffusely distributed tumors have been classified as either multifocal or multicentric.

 

GBM Pathophysiology

The most commonly accepted theory on multifocal GBM is that the tumor originates at a single site, and spreads via typical pathways: along white matter tracts, via CSF dissemination, or via local metastases. Others have theorized that multifocal glioma is the result of neoplastic transformation of a large area of brain parenchyma, with various rates of tumor proliferation within the larger field giving rise to apparently separate lesions. This second theory is of particular interest in consideration of gliomatosis cerebri: gliomatous involvement of large portions of the brain (even entire hemispheres) with low-grade glioma. It is easy to conceive of de-differentiation of multiple foci within this larger area of involvement resulting in apparent multifocality. Regardless of mechanism, the apparently uninvolved areas between lesions may correlate with areas of T2 hyperintensity on MR imaging, but may also have no imaging correlate, with imaging occult involvement of apparent “skip areas” only evident histologically.

 

In contrast to multifocal gliomas, multicentric gliomas are tumors of differing genetic origin, arising either synchronously or metachronously. Multicentric tumors are characterized by an absence of either macroscopic or microscopic connections, and while they may develop de novo, have also been reported as secondary tumors developing in radiation fields following therapy for other primary brain tumors.

 

Differential Diagnostic Imaging Considerations

Cases of multifocal or multicentric GBM such as our index case present a unique diagnostic challenge to the neuroradiologist. Multiple intracranial masses are typically due to metastatic disease in the adult population, although the location (gray-white junction in metastases vs. more central white matter in GBM), shape (metastatic lesions tend to be round to oval, whereas gliomas are often more irregular), and enhancement pattern (metastases tend to enhance homogeneously, and gliomas irregularly) often allow differentiation of the two entities.

 

However, multifocal GBM may be more difficult to differentiate from a tumefactive demyelinating process (tumefactive multiple sclerosis or acute disseminated encephalomyelitis). Lymphoma may also manifest with multiple sites of involvement, and in cases where the typical imaging features of lymphoma—periventricular and basal ganglia involvement, extension along ependymal surfaces, restricted diffusion due to high cellularity—are absent, may be very difficult to differentiate from multifocal GBM. Multifocal abscesses also may be difficult to differentiate based on imaging features alone. Cerebrospinal fluid analysis is often very helpful in distinguishing among these entities. Ultimately, however, surgical biopsy is often necessary to establish a definitive diagnosis.

 

To meet the specialists at Santa Barbara Neuroscience Institute at Cottage Health System, visit www.sbni.org. To refer a patient, please contact the transfer center at 1-888-MY-CAL-NEURO.

 

  

Case Study: Glioblastoma Multiforme

 

A 49-year-old male presented to the emergency department with a two-week history of left leg weakness and progressive facial numbness. He underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain, which demonstrated several discrete enhancing lesions, the most prominent of which are evident in the accompanying image series.

 

The dominant lesion demonstrated rim enhancement and was located in the right pons. The second lesion also demonstrated irregular rim enhancement and was located within the high right cerebral peduncle and extended to involve the thalamus. The third lesion was a small, more homogeneously enhancing lesion in the posterior right subinsular white matter. Also noted (not shown) was a small enhancing lesion in the posterior superior right temporal lobe and an area of T2 signal hyperintensity and expansion, involving both cortex and adjacent white matter along the anterior right temporal pole.

 

Initial differential diagnosis was wide and included multifocal primary neoplasm, metastatic disease and a multifocal demyelinating process. Diagnostic computed tomography of the chest, abdomen and pelvis demonstrated no evidence of a primary neoplasm. As demyelinating disease remained a differential possibility, the patient underwent steroid therapy, with follow-up MRI in approximately two weeks demonstrating progressive lesion enlargement (evident in Figure 2A and Figure 2B).

 

Biopsy of the peduncular/thalamic lesion was performed and demonstrated findings compatible with high-grade glioma.

 

Figure 1A & Figure 1B

Axial T1 weighted images demonstrate enhancing lesions within the right pons and right cerebral peduncle.

 

Figure 2A & Figure 2B

Axial contrast enhanced T1 weighted images demonstrate lesions in the right pons, right cerebral peduncle, and posterior right subinsular white matter.

 

Figure 3A & Figure 3B

Follow-up images obtained approximately two weeks later following steroid therapy demonstrate slight increase in size of the lesions, which now demonstrate irregular thick rim enhancement.

 

 

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