Pictorial Essay. Primary Lymphoma of the Central Nervous System: Typical and Atypical CT and MR Imaging Appearances

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1 Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved Primary Lymphoma of the entral Nervous System: Typical and typical T and MR Imaging ppearances P rimary central nervous system (NS) 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 NS is now encountered frequently, in both immunocompetent and immunocompromised patients. HIV infection and IDS are the leading risk factors [1]. y definition, diagnosis of primary NS lymphoma in a patient with HIV is an independent criterion for IDS. ongenital causes of immunodeficiency (e.g., Wiskott-ldrich syndrome, Ig 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 NS. Recent epidemiologic data show an increased incidence of primary NS lymphoma in low-risk immunocompetent patients as well [1, 2]. This pictorial essay illustrates various imaging appearances of primary NS lymphoma and should aid in its early recognition. Namik Erdag 1,2, Rajeev M. horade 1, Ronald. lberico 1,3, Naveed Yousuf 1,4, Mahesh R. Patel 1,5 Received July 13, 2000; accepted after revision October 19, Presented in part at the annual meeting of the merican Roentgen Ray Society, San Francisco,. pril May Department of Radiology, eth Israel Deaconess Medical enter, Harvard Medical School, 330 rookline ve., oston, M Pictorial Essay linical spects Primary NS 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. fter 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 NS lymphoma vary depending on the location of the masses and the immune status of the patient. Primary NS 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 NS 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]. ecause 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 NS lymphoma almost always reveals intermediate- to high-grade extranodal non-hodgkin s lymphoma of -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 NS lymphoma from systemic lymphoma; the latter typically invades dural and leptomeningeal coverings of the brain. high-attenuation lesion on T and a periventricular T2 low-signal-intensity mass with ependymal seeding on MR imaging favor the diagnosis of primary lymphoma [3]. T, MR imaging, and 201 Tl scintigraphy remain the mainstay in diagnostic imaging workup of primary NS lymphoma [3, 4]. Imaging Features Typical ppearance in Immunocompetent Patients In patients with normal immunity, lymphoma classically presents as a solitary ho- 2 Present address: Department of Radiology, righam and Women s Hospital, 75 Francis St., oston, M ddress correspondence to N. Erdag. 3 Present address: Department of Radiology, Roswell Park ancer Institute, Elm and arlton Sts., uffalo, NY Present address: loomington Radiology, S.., 200 S. Towanda ve., Normal, IL Present address: Valley Radiology, 3031 Tisch Way, Ste. 01, Plaza South, San Jose, JR 2001;176: X/01/ merican Roentgen Ray Society JR:176, May

2 Erdag et al. Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved Fig year-old woman with left-sided weakness. Note typical appearance of hemispheric primary central nervous system lymphoma in immunocompetent adult., xial unenhanced T scan shows typical hyperdense mass (arrows) in right parietal lobe surrounded by low-density zone, consistent with vasogenic edema., xial contrast-enhanced T scan shows homogeneous enhancement (arrows) of lesion near midline., xial T2-weighted MR image shows heterogeneous mass (black arrows) of predominantly low signal intensity. Note central linear T2 hyperintensity (arrowhead ), likely representing necrosis. lso note surrounding vasogenic edema (white arrows). D, xial gadolinium-enhanced T1-weighted MR image shows marked contrast enhancement of lesion (arrows). Note mass effect on adjacent right lateral ventricle. D mogeneously enhancing mass [5 7] (Fig. 1). Unenhanced T typically shows a high-density (70%) lesion in a central hemispheric location, which often reaches or crosses the midline (Fig. 2). 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 IDS (Fig. 3). Internal calcification is unusual in NS 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. 1). lassic findings of a space-occupying 1320 JR:176, May 2001

3 T and MR Imaging of entral Nervous System Lymphoma Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved Fig 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., xial unenhanced T scan shows lobulated mass (arrows) of high attenuation extending across splenium of corpus callosum., xial proton density weighted MR image reveals mass (arrows) isointense to gray matter in same location as in. ilateral parietooccipital generalized edema caused by lesion is typical for transcallosal tumors. Note white matter edema in frontal lobes resulting from chemotherapy., xial gadolinium-enhanced T1-weighted MR image shows marked homogeneous enhancement (arrows) of callosal tumor with extension to left occipital lobe. lesion, including mass effect and surrounding vasogenic edema, are seen on imaging studies [3]. fter the infusion of paramagnetic contrast material, intense homogeneous enhancement (74%) of a solitary mass is the hallmark of primary NS lymphoma in immunocompetent patients (Fig. 1D). Typical ppearance 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). ontrast enhancement is variable, commonly of an inhomogeneous or bizarre pattern. Solitary ringlike enhancement is more likely seen in this group [8] (Fig. 5). 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. 7). However, meningeal enhancement is surprisingly not frequent. typical NS Lymphomas lthough lymphomas are usually hyperdense, they may also show isodensity or JR:176, May

4 Erdag et al. Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved 3 Fig 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. xial unenhanced T scan shows large necrotic mass in left frontal lobe with posterior hemorrhagic component (arrow). Fig 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. Fig year-old man with HIV who presented with disorientation and confusion. Note HIV-associated primary brain lymphoma mimicking toxoplasmosis. erebral toxoplasmosis may show identical appearance, except that toxoplasmosis usually will not have hypointense center on T2-weighted images., xial T2-weighted MR image shows nodular well-defined right frontal subcortical lesion (arrows) with central hypointense core (arrowhead )., xial gadolinium-enhanced T1-weighted MR image shows solitary ringlike enhancement of mass and peripheral low-signalintensity halo (arrows). 4 even hypodensity on T. In the setting of a periventricular low-density lesion, lymphoma may easily be misdiagnosed as chronic small vessel ischemia or encephalomalacia (Fig. 7). Diffusely infiltrative lymphomas may not exhibit parenchymal enhancement at all (Fig. 8). In addition, unenhancing periventricular lymphomas may respect deep anatomic boundaries. We have 1322 JR:176, May 2001

5 T and MR Imaging of entral Nervous System Lymphoma Fig year-old man with HIV who presented with acute change in mental status. oronal gadolinium-enhanced T1-weighted MR image shows two enhancing parietal masses (straight and curved arrows) associated with vasogenic edema (arrowheads). Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved Fig 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 T, initially thought to be a lacunar infarct., xial contrast-enhanced T scan shows barely discernible ill-defined area (arrow ) of low attenuation in right globus pallidus., xial proton density weighted MR image obtained 3 months after shows hyperintense lesion (arrows) with irregular borders at same location., oronal gadolinium-enhanced T1- weighted MR image obtained at same time as again reveals interval growth and enhancement of pallidal mass (arrows). Subtle enhancement (arrowhead ) is also seen in ependymal surface. iopsy revealed primary lymphoma. D, oronal gadolinium-enhanced MR image obtained 3 months after shows multiple large ependymal seeding lesions (arrows) and enlargement of ventricular system. D JR:176, May

6 Erdag et al. Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved Fig year-old man with HIV who presented with acute onset of confusion. xial 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. Fig 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., xial T2-weighted MR image shows ill-defined T2 hyperintensity (arrows) surrounding left internal capsule and adjacent left temporal lobe., xial gadolinium-enhanced MR image reveals barely discernible parenchymal enhancement in corresponding region., xial contrast-enhanced T 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). observed a primary NS 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) JR:176, May 2001

7 T and MR Imaging of entral Nervous System Lymphoma Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved typical Locations rare primary lymphoma of the pineal gland appears similar to a primary neoplasm of pineal origin (Fig. 10). ranial nerves, brainstem, cavernous sinus, or tuber cinereum may have lymphomatous involvement (Figs ). In general, primary NS lymphoma in unusual locations is more common in patients with IDS. onclusion Fig year-old woman with normal immune status who presented with intermittent headache., xial 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., xial gadolinium-enhanced T1-weighted MR image shows homogeneous enhancement (arrows) of lesion., 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. Fig year-old man with IDS who presented with ataxia and weakness in extremities. Note pontine involvement by lymphoma. xial gadolinium-enhanced T1-weighted MR image shows solid homogeneous parenchymal enhancement (arrow ) in left side of pons. In contrast to the large high-attenuation mass in a hemispheric or central location that is seen in immunocompetent patients, primary NS lymphoma in HIV patients may present as a single lesion or as multiple lesions in deep portions of the brain. 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. JR:176, May

8 Erdag et al. Downloaded from by on 02/11/18 from IP address opyright RRS. For personal use only; all rights reserved These imaging features may allow earlier detection of primary NS lymphoma and facilitate optimal treatment. References Fig year-old immunocompromised woman who presented with headache. Note unusual hypothalamic location of primary lymphoma. Hypothalamic glioma should be considered in differential diagnosis., oronal gadolinium-enhanced T1-weighted MR image shows solitary mass (arrows) in hypothalamus at region of tuber cinereum, causing splaying of postchiasmatic optic nerves., Sagittal gadolinium-enhanced T1-weighted MR image shows markedly enhancing midline mass (arrows). Upper aspect of pituitary stalk also appears to be involved. Fig year-old man with IDS 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., oronal 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., oronal gadolinium-enhanced T1-weighted MR image posterior to shows marked enhancement and thickening of adjacent dura (arrowhead ) and right trigeminal nerve (double arrows). Left trigeminal nerve (single arrow ) is normal. 1. Maher E, Fine H. Primary NS lymphoma. Semin Oncol 1999;26: Dengelis LM, Yahalom J. Primary central nervous system lymphoma. In: DeVita VT Jr, Hellman S, Rosenberg S, eds. ancer: principles and practice of oncology. Philadelphia: Lippincott-Raven, 1997: Ruiz, Post MJD, undschu, Ganz WI, Georgiou M. Primary central nervous system lymphoma in patients with IDS. Neuroimaging lin N m 1997;7: Koeller KK, Smirniotopoulos JG, Jones RV. Primary central nervous system lymphoma: radiologic-pathologic correlation. RadioGraphics 1997;17: Johnson, Fram EK, Johnson P, Jacobowitz R. The variable MR appearance of primary lymphoma of the central nervous system: comparison with histopathologic features. JNR 1997;18: Lanfermann H, Heindel W, Schaper J, et al. T and MR imaging in primary cerebral non-hodgkin s lymphoma. cta Radiol 1997;38: Roman-Goldstein SM, Goldman DL, Howieson J, elkin R, Neuwelt E. MR of primary NS lymphoma in immunologically normal patients. JNR 1992;13: Dina TS. Primary central nervous system lymphoma versus toxoplasmosis in IDS. Radiology 1991;179: aldemeyer KS, Edwards MK, Smith RR, Moran. Viral and postviral demyelination central nervous system infection. Neuroimaging lin N m 1993;3: JR:176, May 2001

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