AJR 2001; 176:1319-1326
© American Roentgen Ray Society
Primary Lymphoma of the Central Nervous System
Typical and Atypical CT and MR Imaging Appearances
Namik Erdag1,2,
Rajeev M. Bhorade1,
Ronald A. Alberico1,3,
Naveed Yousuf1,4 and
Mahesh R. Patel1,5
1
Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical
School, 330 Brookline Ave., Boston, MA 02115.
2
Present address: Department of Radiology, Brigham and Women's Hospital, 75
Francis St., Boston, MA 02115.
3
Present address: Department of Radiology, Roswell Park Cancer Institute, Elm
and Carlton Sts., Buffalo, NY 14263.
4
Present address: Bloomington Radiology, S.C., 200 S. Towanda Ave., Normal, IL
61761.
5
Present address: Valley Radiology, 3031 Tisch Way, Ste. 01, Plaza South, San
Jose, CA 95128.
Received July 13, 2000;
accepted after revision October 19, 2000.
Presented in part at the annual meeting of the American Roentgen Ray
Society, San Francisco, CA. April-May 1998.
Address correspondence to N. Erdag.
Introduction
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).
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Fig. 1A. —64-year-old woman with left-sided weakness. Note typical
appearance of hemispheric primary central nervous system lymphoma in
immunocompetent adult. Axial unenhanced CT scan shows typical hyperdense mass
(arrows) in right parietal lobe surrounded by low-density zone,
consistent with vasogenic edema.
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Fig. 1B. —64-year-old woman with left-sided weakness. Note typical
appearance of hemispheric primary central nervous system lymphoma in
immunocompetent adult. Axial contrast-enhanced CT scan shows homogeneous
enhancement (arrows) of lesion near midline.
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Fig. 1C. —64-year-old woman with left-sided weakness. Note typical
appearance of hemispheric primary central nervous system lymphoma in
immunocompetent adult. Axial T2-weighted MR image shows heterogeneous mass
(black arrows) of predominantly low signal intensity. Note central
linear T2 hyperintensity (arrowhead), likely representing necrosis.
Also note surrounding vasogenic edema (white arrows).
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Fig. 1D. —64-year-old woman with left-sided weakness. Note typical
appearance of hemispheric primary central nervous system lymphoma in
immunocompetent adult. Axial gadolinium-enhanced T1-weighted MR image shows
marked contrast enhancement of lesion (arrows). Note mass effect on
adjacent right lateral ventricle.
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Fig. 2A. —67-year-old immunocompetent woman who presented with
confusion and change in mental status. Note primary lymphoma that crosses
midline through corpus callosum. High-grade gliomas and radiation necrosis may
have similar appearance. Axial unenhanced CT scan shows lobulated mass
(arrows) of high attenuation extending across splenium of corpus
callosum.
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Fig. 2B. —67-year-old immunocompetent woman who presented with
confusion and change in mental status. Note primary lymphoma that crosses
midline through corpus callosum. High-grade gliomas and radiation necrosis may
have similar appearance. Axial proton density-weighted MR image reveals mass
(arrows) isointense to gray matter in same location as in A.
Bilateral parietooccipital generalized edema caused by lesion is typical for
transcallosal tumors. Note white matter edema in frontal lobes resulting from
chemotherapy.
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Fig. 2C. —67-year-old immunocompetent woman who presented with
confusion and change in mental status. Note primary lymphoma that crosses
midline through corpus callosum. High-grade gliomas and radiation necrosis may
have similar appearance. Axial gadolinium-enhanced T1-weighted MR image shows
marked homogeneous enhancement (arrows) of callosal tumor with
extension to left occipital lobe.
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Fig. 3. —69-year-old immunocompetent man with acute onset of headache.
Other primary or secondary hemorrhagic and necrotic brain neoplasms may appear
similar to this primary central nervous system lymphoma associated with
spontaneous bleeding. Axial unenhanced CT scan shows large necrotic mass in
left frontal lobe with posterior hemorrhagic component (arrow).
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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.
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Fig. 4. —43-year-old woman with HIV who presented with seizure.
Sagittal gadolinium-enhanced T1-weighted MR image shows irregularly enhancing
mass (arrows) in rostrum and genu of corpus callosum. Primary
lymphoma frequently invades corpus callosum and periventricular cerebral
parenchyma.
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Fig. 5A. —38-year-old man with HIV who presented with disorientation
and confusion. Note HIV-associated primary brain lymphoma mimicking
toxoplasmosis. Cerebral toxoplasmosis may show identical appearance, except
that toxoplasmosis usually will not have hypointense center on T2-weighted
images. Axial T2-weighted MR image shows nodular well-defined right frontal
subcortical lesion (arrows) with central hypointense core
(arrowhead).
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Fig. 5B. —38-year-old man with HIV who presented with disorientation
and confusion. Note HIV-associated primary brain lymphoma mimicking
toxoplasmosis. Cerebral toxoplasmosis may show identical appearance, except
that toxoplasmosis usually will not have hypointense center on T2-weighted
images. Axial gadolinium-enhanced T1-weighted MR image shows solitary ringlike
enhancement of mass and peripheral low-signal-intensity halo
(arrows).
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Fig. 6. —39-year-old man with HIV who presented with acute change in
mental status. Coronal gadolinium-enhanced T1-weighted MR image shows two
enhancing parietal masses (straight and curved arrows)
associated with vasogenic edema (arrowheads).
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Fig. 7A. —35-year-old man with HIV who presented with lower extremity
weakness. Note atypical lymphoma in immunocompromised patient presented as
nonenhancing low-density lesion in right basal ganglia on CT, initially
thought to be a lacunar infarct. Axial contrast-enhanced CT scan shows barely
discernible ill-defined area (arrow) of low attenuation in right
globus pallidus.
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Fig. 7B. —35-year-old man with HIV who presented with lower extremity
weakness. Note atypical lymphoma in immunocompromised patient presented as
nonenhancing low-density lesion in right basal ganglia on CT, initially
thought to be a lacunar infarct. Axial proton density-weighted MR image
obtained 3 months after A shows hyperintense lesion (arrows)
with irregular borders at same location.
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Fig. 7C. —35-year-old man with HIV who presented with lower extremity
weakness. Note atypical lymphoma in immunocompromised patient presented as
nonenhancing low-density lesion in right basal ganglia on CT, initially
thought to be a lacunar infarct. Coronal gadolinium-enhanced T1-weighted MR
image obtained at same time as B again reveals interval growth and
enhancement of pallidal mass (arrows). Subtle enhancement
(arrowhead) is also seen in ependymal surface. Biopsy revealed
primary lymphoma.
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Fig. 7D. —35-year-old man with HIV who presented with lower extremity
weakness. Note atypical lymphoma in immunocompromised patient presented as
nonenhancing low-density lesion in right basal ganglia on CT, initially
thought to be a lacunar infarct. Coronal gadolinium-enhanced MR image obtained
3 months after B shows multiple large ependymal seeding lesions
(arrows) and enlargement of ventricular system.
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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).
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Fig. 8A. —90-year-old woman with normal immune status who presented
with right-sided weakness and difficulty finding words. High-grade glioma may
appear similar to this diffusely infiltrative pattern of primary brain
lymphoma. Axial T2-weighted MR image shows ill-defined T2 hyperintensity
(arrows) surrounding left internal capsule and adjacent left temporal
lobe.
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Fig. 8B. —90-year-old woman with normal immune status who presented
with right-sided weakness and difficulty finding words. High-grade glioma may
appear similar to this diffusely infiltrative pattern of primary brain
lymphoma. Axial gadolinium-enhanced MR image reveals barely discernible
parenchymal enhancement in corresponding region.
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Fig. 8C. —90-year-old woman with normal immune status who presented
with right-sided weakness and difficulty finding words. High-grade glioma may
appear similar to this diffusely infiltrative pattern of primary brain
lymphoma. Axial contrast-enhanced CT scan obtained 4 months later shows marked
expansion of left basal ganglia and thalamus caused by infiltrating neoplasm,
with loss of normal anatomic boundaries (arrows).
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Fig. 9. —36-year-old man with HIV who presented with acute onset of
confusion. Axial gradient-echo MR image shows large heterogeneous mass
(straight arrows) in left basal ganglia and region of
susceptibility-induced signal loss (curved arrow), representing a
hemorrhagic focus. Physiologic calcification in left globus pallidus indicated
by arrowhead is displaced posteromedially.
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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.
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Fig. 10A. —71-year-old woman with normal immune status who presented
with intermittent headache. Axial T2-weighted MR image shows
well-circumscribed mass (arrows), isointense to gray matter, in
pineal region. Note associated enlargement of lateral and third ventricles
from obstruction of cerebrospinal fluid flow at cerebral aqueduct.
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Fig. 10B. —71-year-old woman with normal immune status who presented
with intermittent headache. Axial gadolinium-enhanced T1-weighted MR image
shows homogeneous enhancement (arrows) of lesion.
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Fig. 10C. —71-year-old woman with normal immune status who presented
with intermittent headache. Sagittal gadolinium-enhanced T1-weighted MR image
shows enhancing pineal mass (arrows) that was found to be primary
lymphoma at pathology after surgical resection. Primary and secondary pineal
gland tumors and exophytic thalamic gliomas may yield similar findings.
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Fig. 11. —43-year-old man with AIDS who presented with ataxia and
weakness in extremities. Note pontine involvement by lymphoma. Axial
gadolinium-enhanced T1-weighted MR image shows solid homogeneous parenchymal
enhancement (arrow) in left side of pons.
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Fig. 12A. —42-year-old immunocompromised woman who presented with
headache. Note unusual hypothalamic location of primary lymphoma. Hypothalamic
glioma should be considered in differential diagnosis. Coronal
gadolinium-enhanced T1-weighted MR image shows solitary mass (arrows)
in hypothalamus at region of tuber cinereum, causing splaying of
postchiasmatic optic nerves.
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Fig. 12B. —42-year-old immunocompromised woman who presented with
headache. Note unusual hypothalamic location of primary lymphoma. Hypothalamic
glioma should be considered in differential diagnosis. Sagittal
gadolinium-enhanced T1-weighted MR image shows markedly enhancing midline mass
(arrows). Upper aspect of pituitary stalk also appears to be
involved.
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Fig. 13A. —25-year-old man with AIDS who presented with headache and
blurred vision. Note primary lymphoma involving cavernous sinus, pituitary
gland, and cranial nerve. Invasive pituitary adenoma and cavernous sinus
meningioma may look similar. Coronal gadolinium-enhanced T1-weighted MR image
shows pituitary mass (arrowheads) and asymmetric thickening of right
cavernous sinus (arrow). Flow voids in both internal carotid arteries
appear to be preserved.
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Fig. 13B. —25-year-old man with AIDS who presented with headache and
blurred vision. Note primary lymphoma involving cavernous sinus, pituitary
gland, and cranial nerve. Invasive pituitary adenoma and cavernous sinus
meningioma may look similar. Coronal gadolinium-enhanced T1-weighted MR image
posterior to A shows marked enhancement and thickening of adjacent dura
(arrowhead) and right trigeminal nerve (double arrows). Left
trigeminal nerve (single arrow) is normal.
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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.
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Introduction
Clinical Aspects
