Primary Lymphoma of the Central Nervous System: Typical and Atypical CT and MR Imaging Appearances
Primary central nervous system (CNS) lymphoma refers to isolated involvement of the craniospinal axis in the absence of primary tumor elsewhere in the body. Once considered a rare occurrence, primary lymphomatous disease of the CNS is now encountered frequently, in both immunocompetent and immunocompromised patients. HIV infection and AIDS are the leading risk factors [1]. By definition, diagnosis of primary CNS lymphoma in a patient with HIV is an independent criterion for AIDS. Congenital causes of immunodeficiency (e.g., Wiskott-Aldrich syndrome, IgA deficiency, and X-linked lymphoproliferative syndrome) and acquired causes, including an immunosuppressive regimen after organ transplantation, are also associated with greater risk for primary lymphoma of the CNS. Recent epidemiologic data show an increased incidence of primary CNS lymphoma in low-risk immunocompetent patients as well [1, 2]. This pictorial essay illustrates various imaging appearances of primary CNS lymphoma and should aid in its early recognition.
Clinical Aspects
Primary CNS lymphoma may arise from different parts of the brain, with deep hemispheric periventricular white matter being the most common; corpus callosum, cerebellum, orbits, and cranial nerves may also harbor the tumor. After the diagnosis is made, an examination is done that includes MR imaging of the craniospinal tract; cerebrospinal fluid and bone marrow examinations; and screening for primary tumor in the eye, chest, and abdomen [1]. The presenting symptoms in primary CNS lymphoma vary depending on the location of the masses and the immune status of the patient. Primary CNS lymphoma in immunocompetent patients tends to present with a large solitary hemispheric mass. HIV-positive patients often present with an acute change in mental status and an encephalopathy-like picture, likely related to combined effects from other concomitant infections and the side effects of antiretroviral drugs. The traditional method of administering 2 weeks of empiric antitoxoplasmosis treatment to distinguish between primary CNS lymphoma and toxoplasmosis, the most common cause of solitary or multiple brain masses in an HIV patient, is not warranted in patients with negative serology findings for Toxoplasma organisms [2]. Because of the rapid course of primary lymphoma, a delay in whole brain irradiation and chemotherapy markedly decreases the effectiveness of the treatment and survival. Therefore, early diagnosis is critical.
Histology of the primary CNS lymphoma almost always reveals intermediate- to high-grade extranodal non-Hodgkin's lymphoma of B-cell origin [1, 2]. Systemic lymphoma, on the other hand, may also present with neurologic symptoms in one third of patients sometime during the course of the disease [2]. Imaging studies are often helpful to distinguish primary CNS lymphoma from systemic lymphoma; the latter typically invades dural and leptomeningeal coverings of the brain. A high-attenuation lesion on CT and a periventricular T2 low-signal-intensity mass with ependymal seeding on MR imaging favor the diagnosis of primary lymphoma [3]. CT, MR imaging, and 201Tl scintigraphy remain the mainstay in diagnostic imaging workup of primary CNS lymphoma [3, 4].
Imaging Features
Typical Appearance in Immunocompetent Patients
In patients with normal immunity, lymphoma classically presents as a solitary homogeneously enhancing mass [5,6,7] (Fig. 1A,1B,1C,1D). Unenhanced CT typically shows a high-density (70%) lesion in a central hemispheric location, which often reaches or crosses the midline (Fig. 2A,2B,2C). Highly packed abnormal cells are thought to be responsible for the increased attenuation. Hemorrhage within the tumor is rarely seen, although it is more common in lymphoma associated with AIDS (Fig. 3). Internal calcification is unusual in CNS lymphomas unless the patient has undergone prior chemotherapy or radiation treatment. In most patients, MR imaging reveals intermediate- to low-signal-intensity tumor on T1-weighted images and either isointense or hypointense signal relative to the gray matter on T2-weighted images (Fig. 1C). Classic findings of a space-occupying lesion, including mass effect and surrounding vasogenic edema, are seen on imaging studies [3]. After the infusion of paramagnetic contrast material, intense homogeneous enhancement (74%) of a solitary mass is the hallmark of primary CNS lymphoma in immunocompetent patients (Fig. 1D).








Typical Appearance in HIV Patients
In more than half (55%) the patients, a cerebral mass is detected in a supratentorial parenchymal location with frequent involvement of the corpus callosum, basal ganglia, and other deep cerebral nuclei (Fig. 4). Contrast enhancement is variable, commonly of an inhomogeneous or bizarre pattern. Solitary ringlike enhancement is more likely seen in this group [8] (Fig. 5A,5B). When necrosis develops in the tumor (64%), the periphery still maintains an isointense signal and the center becomes hyperintense. Multiple lesions may be seen in as many as 50% of patients (Fig. 6). Extension along the Virchow-Robin spaces is a well-known feature of primary lymphoma. Periventricular lesions frequently invade the ventricular surface, causing ependymal seeding (38%) (Fig. 7A,7B,7C,7D). However, meningeal enhancement is surprisingly not frequent.








Atypical CNS Lymphomas
Although lymphomas are usually hyperdense, they may also show isodensity or even hypodensity on CT. In the setting of a periventricular low-density lesion, lymphoma may easily be misdiagnosed as chronic small vessel ischemia or encephalomalacia (Fig. 7A). Diffusely infiltrative lymphomas may not exhibit parenchymal enhancement at all (Fig. 8A,8B,8C). In addition, unenhancing periventricular lymphomas may respect deep anatomic boundaries. We have observed a primary CNS lymphoma of the left temporal lobe with significant vasogenic edema sparing the basal ganglia, a feature previously described in herpes encephalitis and, more recently, in progressive multifocal leukoencephalopathy [9]. The tumor sometimes may show mild hyperintensity on T1-weighted images. Dense cellularity and high nucleus-to-cytoplasm ratio of the tumor accounts for the isointense or slightly hypointense signal seen on T2-weighted sequences. Hemorrhage in the tumor also results in low signal intensity on gradient-echo images because of magnetic susceptibility [3, 5] (Fig. 9).




Atypical Locations
A rare primary lymphoma of the pineal gland appears similar to a primary neoplasm of pineal origin (Fig. 10A,10B,10C). Cranial nerves, brainstem, cavernous sinus, or tuber cinereum may have lymphomatous involvement (Figs. 11,12A,12B,13A,13B). In general, primary CNS lymphoma in unusual locations is more common in patients with AIDS.








Conclusion
In contrast to the large high-attenuation mass in a hemispheric or central location that is seen in immunocompetent patients, primary CNS lymphoma in HIV patients may present as a single lesion or as multiple lesions in deep portions of the brain. A necrotic core within the tumor and peculiar enhancement in an unusual location are also more likely because of HIV-associated lymphoma. Subependymal enhancement should be actively sought on imaging studies as a potential clue to lymphomatous involvement. Presence of a T2-hypointense component resulting from increased cellularity should also be noted. These imaging features may allow earlier detection of primary CNS lymphoma and facilitate optimal treatment.
Footnotes
Presented in part at the annual meeting of the American Roentgen Ray Society, San Francisco, CA. April-May 1998.
Address correspondence to N. Erdag.
References
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Submitted: July 13, 2000
Accepted: October 19, 2000
First published: November 23, 2012
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