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.
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.
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