Differential Diagnosis of CNS Tumors

Multiple Sclerosis. Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. Imaging typically reveals multiple lesions in a characteristic pattern, such as “Dawson’s fingers” (periventricular lesions oriented perpendicular to the long axis of the lateral ventricle on fluid attenuated inversion recovery [FLAIR] sequences). These plaques have very little mass effect. Active lesions are usually enhancing, representing the breakdown of the blood-brain barrier. Tumefactive MS is a special subtype that affects patients in the second or third decade. Imaging reveals large (>2 cm) tumor-like masses that demonstrate incomplete ring enhancement with the incomplete area abutting the cortical gray matter or basal ganglia. These lesions can be associated with mass effect and vasogenic edema. Unlike hypercellular brain tumors, these lesions tend to have a relatively low cerebral blood volume on perfusion imaging and an increased apparent diffusion coefficient (ADC) on diffusion sequences. Furthermore, magnetic resonance spectroscopy can help distinguish demyelinating lesions from neoplasm. Appreciation of the clinical history in conjunction with ancillary testing, such as cerebrospinal (CSF) studies or evoked potentials, may aid in the differentiation of demyelinating disease from CNS tumors.

Sarcoidosis. Sarcoidosis is a multisystem granulomatous disease that can affect the central nervous system. About 5% of known sarcoidosis patients will manifest with neurosarcoidosis, although de novo presentation is also possible. It initially develops in the leptomeninges, allowing entry of the inflammatory process into the brain parenchyma, where granulomatous masses can develop. There is a predilection for cranial nerves, hypothalamus, and the pituitary gland, but any part of the central nervous system can be affected. On imaging, neurosarcoidosis can present with meningeal or pachymeningeal enhancement in association with nonenhancing periventricular white matter lesions. With cranial nerve involvement, enhancement along the nerves can be seen, although the extracranial portion is affected more often. Less common are enhancing granulomatous nodules in the parenchyma and dural mass lesions. With the relatively high frequency of leptomeningeal involvement, neurosarcoidosis can be mistaken for carcinomatous meningitis. Again, clinical history, systemic imaging, and CSF studies must be considered in distinguishing the two.

Radiation Effects. Since the establishment of chemoradiation as the standard of care for glioblastoma, there has been an increasing awareness of a phenomenon termed “pseudoprogression,” in which post-treatment imaging reveals the presence of enhancing lesions secondary to radiation injury, resulting in increased capillary permeability and breakdown of the blood-brain barrier. Eventually, these lesion decrease in size or stabilize without the need for further treatment. Evidence suggests that these treatment-related effects occur more frequently with the use of temozolomide and significantly correlate with O6-methylguanine– DNA-methyltransferase (MGMT) promoter methylation status. Clinically and radiographically, pseudoprogression can appear and behave identically to true tumor progression. Adjunct studies, such as dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging and positron emission tomography (PET) scans, may be useful. Pseudoprogression typically exhibits low cerebral blood volume and is “cold” on PET imaging, whereas tumor progression will have elevated cerebral blood volume and be metabolically active. Occasionally, biopsy of the lesion may be necessary to establish the correct diagnosis and appropriate management.

Cerebral Abscess. Intracranial abscesses can appear very similar to cystic or necrotic brain tumors. Both appear as ring-enhancing lesions with associated mass effect, causing associated neurologic deficits. Fever is not always present and is only found in less than half of patients. Other parameters diagnostic for infection, such as leukocytosis, elevated erythrocyte sedimentation rate (ESR), and positive blood cultures, are not reliably present in patients affected by cerebral abscess. Studies such as lumbar puncture are less useful because findings are often nonspecific and cultures are rarely positive. Proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging have both been reported to be helpful in distinguishing abscesses from nonpyogenic lesions, with abscesses displaying a specific metabolite profile on MRS and hyperintense signal on diffusion imaging.

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