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Published online before print August 11, 2005, 10.1148/radiol.2371041087
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(Radiology 2005;237:265-273.)
© RSNA, 2005

Neuroradiology

Lymphomatoid Granulomatosis: Abnormalities of the Brain at MR Imaging1

Athos D. Patsalides, MD, Gokce Atac, MD, Upendra Hedge, MD, John Janik, MD, Nicole Grant, RN, Elaine S. Jaffe, MD, Andrew Dwyer, MD, Nicholas J. Patronas, MD and Wyndham H. Wilson, MD, PhD

1 From the Department of Diagnostic Radiology, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bldg 10, Room 1C660, 9000 Rockville Pike, Bethesda, MD 20892-1182 (A.D.P., G.A., A.D., N.J.P.); Georgetown University Hospital, Washington, DC (A.D.P.); and Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md (U.H., J.J., N.G., E.S.J., W.H.W.). From the 2001 RSNA Annual Meeting. Received June 21, 2004; revision requested August 27; revision received November 21; accepted December 30. Address correspondence to A.D.P. (e-mail: apatsalides{at}cc.nih.gov).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To retrospectively evaluate the magnetic resonance (MR) imaging features of lymphomatoid granulomatosis in the brain.

MATERIALS AND METHODS: The study, including retrospective analysis of data, was approved by the institutional review board of the National Cancer Institute and complied with Health Insurance Portability and Accountability Act. All patients gave written informed consent. Thirty-one patients with pathologically confirmed lymphomatoid granulomatosis were enrolled in a natural history and treatment study at the National Institutes of Health. Twenty-five patients (median age, 50 years; range, 18–62 years; 18 men, seven women) were evaluated with MR imaging of the brain at study entry for the presence of brain lesions and enhancing characteristics. Patients with abnormal findings were reexamined at intervals ranging from 2 to 19 months, as medically indicated. Cytologic analysis and flow cytometry of cerebrospinal fluid (CSF) were performed. Statistical analysis was performed to compare neurologic and CSF findings in patients with brain MR imaging abnormalities and in patients without abnormalities. The sensitivity of brain MR imaging was compared with that of CSF studies.

RESULTS: Thirteen (52%) of 25 patients evaluated with MR imaging had a variety of brain abnormalities. Multiple focal intraparenchymal lesions, which exhibited T2 prolongation and commonly punctate or linear enhancement, were the most frequent abnormalities, and they were encountered in seven patients. The second most common finding was involvement of leptomeninges and cranial nerves, which manifested as abnormal enhancement on MR images obtained after contrast agent administration. This abnormality was seen in six patients. Involvement of dura mater was noted in another. Four patients had brain masses. Two had abnormal engorgement and intense enhancement of the choroid plexus. Most lesions resolved after treatment, but seven resulted in lacunar infarctions. Abnormal B cells were detected in the CSF with either cytologic techniques or flow cytometry in five patients.

CONCLUSION: Lymphomatoid granulomatosis has a high rate of central nervous system involvement and a variable spectrum of lesions at MR imaging. Findings in this study suggest that MR imaging is more sensitive than CSF cytologic analysis or flow cytometry for detection of central nervous system involvement from lymphomatoid granulomatosis.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Lymphomatoid granulomatosis, described by Liebow et al (1), is a rare Epstein-Barr virus (EBV)–associated B-cell lymphoproliferative disorder that shares similarities with posttransplantation lymphoproliferative disorders (2–5). Pathologically, lymphomatoid granulomatosis is characterized by an angiocentric and angiodestructive polymorphous lymphoid infiltrate composed predominantly of lymphocytes admixed with plasma cells, immunoblasts, and histiocytes (6). Well-formed granulomas usually are absent. The classic infiltrate contains scattered EBV-positive atypical B cells within a predominantly T-cell background. Vascular changes are frequent, with lymphocytic infiltration of the vascular wall and variable necrosis. Grades of the disease are assigned with a scale of 1–3, on the basis of the numbers of the atypical EBV-positive B cells and the amount of necrosis. The male-female ratio is 2:1. Patients of all ages may be affected, but the disease is most commonly encountered in adults between the 4th and the 6th decades of life (1,2). On rare occasions, children also can be affected (7). Just as posttransplantation lymphoproliferative disorder is associated with the development of lymphomatoid granulomatosis so too is immunodeficiency, and evidence of subtle immune deficits has been found in otherwise immunocompetent individuals with the disease (3,8,9). B-cell activation by EBV is the underlying pathogenetic cause of lymphomatoid granulomatosis, and it provokes T-cell infiltration in affected tissues with perivascular distribution (9). Patients with lymphomatoid granulomatosis may eventually develop lymphoma of the large B-cell type, with an incidence ranging from 10% to 60% (5,10,11).

The lungs are virtually always affected in lymphomatoid granulomatosis and are the initial site of manifestation in more than 90% of cases (5). Radiographically, the pulmonary disease is characterized by multiple nodules that range in from a few millimeters to several centimeters and have occasional cavities. Lymphadenopathy is rare and, when present, suggests the presence of an aggressive lymphoma. The skin is the second most common organ of lymphomatoid granulomatosis involvement, which manifests with cutaneous and dermal nodules, maculopapular rashes, macular erythema, and even ulcers (12).

The central nervous system (CNS) is involved in as many as one-third of patients, and peripheral nerve involvement has been reported in 7% of patients (3,5,13). Most CNS abnormalities have been described in pathologic specimens and histologic studies. Antemortem diagnosis of these lesions by using imaging techniques has been difficult. Although investigators in a number of case reports have described variable imaging features, a diagnostic pattern has not emerged from these studies (11,14–20). Some of these reports include data from outdated imaging methods (8,20–23). Thus, the purpose of our study was to retrospectively evaluate the magnetic resonance (MR) imaging features of lymphomatoid granulomatosis in the brain.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Patients
The study, including retrospective analysis of data, was approved by the institutional review board of the National Cancer Institute, and all patients gave written informed consent. Our study was compliant with the Health Insurance Portability and Accountability Act. Between 1991 and 2004, 31 patients were enrolled in a natural history and treatment study of interferon alfa and/or dose-adjusted chemotherapy with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, also known as EPOCH, at the National Cancer Institute (13,24). Briefly, patients with grade 1 or 2 lymphomatoid granulomatosis initially received interferon alfa at a starting dose of 7.5 million units three times per week. The dose was progressively increased in increments of 5 million units every 1–2 weeks until the disease began to resolve or unacceptable toxic reactions prevented further escalation in the dose. In general, patients with grade 3 lymphomatoid granulomatosis received this dose-adjusted chemotherapy, although, in some cases, such patients initially received interferon alfa. Furthermore, patients who did not respond to interferon alfa were treated with the dose-adjusted chemotherapy. Dose-adjusted chemotherapy was administered as previously described (24). This dose-adjusted chemotherapy is an infusion-based regimen and is administered as follows: Over days 1–4, the following drugs were administered as a 96-hour continuous infusion: etoposide, 200 mg/m2; doxorubicin, 40 mg/m2; and vincristine sulfate, 1.6 mg/m2. On days 1–5, prednisone, 60 mg/m2, was administered by mouth twice daily. On day 5, cyclophosphamide, 750 mg/m2, was administered intravenously. On day 1 of each cycle, several of the patients who entered the study at a later time also received rituximab, 375 mg/m2, intravenously (25). Beginning on day 6, all patients received filgrastim, 5 µg/kg, and administration of this medication was continued until recovery of the absolute neutrophil nadir was achieved at greater than 5000 cells per cubic millimeter (5 x 109/L). Treatment was repeated every 3 weeks for six to eight cycles, depending on the response. The doses of etoposide, doxorubicin, and cyclophosphamide were adjusted by 20% for each cycle to achieve an absolute neutrophil nadir of less than 500 cells per cubic millimeter, as previously described (24).

The patients' ages at the time of entry into the study ranged from 17 to 67 years, with a median age of 44 years, and 68% of the patients were male and 32% were female. A pathologic diagnosis of lymphomatoid granulomatosis, according to the World Health Organization classification of tumors of hematopoietic and lymphoid tissues (6), was confirmed by one of the authors (E.S.J.) in all patients at the National Cancer Institute. At the time of enrollment, the distribution of highest histologic grade was grade 1 or 2 in 17 patients and grade 3 in 14 patients; in two of these latter patients, the tumor was transformed into an EBV-positive diffuse large B-cell lymphoma.

All patients underwent an initial evaluation with a physical examination, blood tests, and whole-body computed tomography (CT), which were performed by several authors (U.H., J.J., N.G., G.A., W.H.W.). The CNS was evaluated by using a lumbar puncture for analysis of the cerebrospinal fluid (CSF), with cytologic analysis, flow cytometry, and white blood cell count. Brain imaging was performed in all 31 patients for grading of the disease at study entry. Of these, six underwent CT and 25 underwent MR imaging. CT was performed in these six patients because MR imaging was not available at the time. The CT studies were negative for intracranial abnormalities in all patients. The 25 patients in whom MR imaging studies were performed constitute the subjects of our study. The median age of these patients was 50 years (range, 18–62 years), and 18 (72%) were men and seven (28%) were women.

MR Imaging
All MR images were obtained with a 1.5-T magnet (Signa; GE Medical Systems, Milwaukee, Wis). T1-weighted (repetition time msec/echo time msec, 400–600/8–12) and T2-weighted (2500–3000/90–120) images were acquired in each patient who underwent imaging. In addition, fluid-attenuated inversion-recovery sequences were performed (repetition time msec/echo time msec/inversion time msec, 10 000/137/2200). T1-weighted MR imaging was repeated after intravenous administration of 0.1 mmol/kg of contrast material (Magnevist; Berlex Laboratories, Wayne, NJ). Follow-up MR imaging was performed in all patients with brain abnormalities. MR imaging was repeated at least every 2 months until stability was reached or resolution of the abnormalities was observed, and then it was repeated every 6–12 months thereafter. The interval between the time the first and the last images were obtained ranged from 2 to 19 months (median, 15 months). Two to 12 images per patient (median, seven images) were obtained by using the same basic imaging parameters.

Image Interpretation
All MR images were evaluated retrospectively by two neuroradiologists (N.J.P. and A.D.P., with 20 and 3 years ofexperience with MR imaging, respectively). Results were determined with consensus of the two readers. All serial images obtained in each patient were reviewed at the same time. This analysis included identification and characterization of meningeal and cranial nerve enhancement and focal parenchymal lesions at presentation, and change in enhancement and lesions over time on subsequent images; these findings were tabulated, and the frequency of each was calculated. The number, size, location, signal intensity, and enhancement characteristics of parenchymal lesions were recorded. The size of each lesion was measured with electronic calipers at a picture archiving and communication system viewing station. All lesions that were counted per patient exhibited abnormally increased signal intensity, as compared with that of the adjacent normal brain parenchyma, on the fluid-attenuated inversion-recovery and T2-weighted MR images. Each lesion that exhibited increased signal intensity on the postcontrast T1-weighted MR images, compared with that on the precontrast T1-weighted MR images, was considered enhancing. No grading system of abnormal signal intensity or enhancement was used. In the evaluation of the choroid plexus, abnormal engorgement of this structure was considered in those patients in whom there was a dramatic asymmetry compared with the contralateral site or when the choroid plexus occupied a substantial portion of the ventricle or the CSF space. Decreased signal intensity with the T2-weighted techniques was used to identify products of hemoglobin degradation.

Statistical Analysis
The {chi}2 test for independence was used to compare the frequency of abnormal clinical neurologic findings and the frequency of abnormal CSF findings in patients with and patients without abnormal MR imaging findings. The frequency of MR imaging results and that of CSF results were compared by using the McNemar test for paired-sample nominal scale data. Results with P values of .05 or less were considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Patient Characteristics
The frequency of abnormal CNS findings at MR imaging in the patients who underwent imaging in this series of patients with lymphomatoid granulomatosis was 13 (52%) of 25. The Table summarizes the clinical characteristics and the MR imaging findings of the patients with findings that were positive for the disease. The clinical characteristics of these 13 patients were similar to those of the entire cohort of 31 patients in the study; the median age was 43 years (range, 17–60 years), and nine (69%) patients were male and four (31%) were female. Notably, 46% of the patients with CNS findings had grade 3 lymphomatoid granulomatosis, compared with 47% of the entire cohort, and this finding suggests that there is no association between the grade of the disease and the spread of disease to the CNS. Most patients (10 [77%] of 13) with evidence of CNS disease at MR imaging also had neurologic signs or symptoms of cranial nerve involvement, such as hearing loss, diplopia or dysarthria, and/or other symptoms, such as hemiparesis, ataxia, or atonic bladder. None of the 12 patients with normal brain MR imaging results had neurologic findings. This difference in frequency of neurologic findings between the patients with positive MR imaging findings and those with negative MR imaging findings was statistically significant, with P < .001 ({chi}2 test). Furthermore, of the 13 patients with abnormal MR imaging findings, only five (38%) had atypical cells consistent with lymphomatoid granulomatosis (Table). In contrast, none of the 12 patients with normal MR imaging findings had evidence of lymphomatoid granulomatosis that was detectable in the CSF. This difference was statistically significant, with P < .02 ({chi}2 test). The sensitivity of MR imaging for detection of CNS disease was significantly greater than was the sensitivity of CSF analysis, with P < .02 (McNemar test).


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  		Clinical and MR Imaging Findings

 
MR Imaging Findings at Study Entry
The MR imaging findings were abnormal in all 10 patients with clinical CNS findings, as well as in three asymptomatic patients. The most common finding for brain involvement was the presence of focal intraparenchymal lesions. These lesions were observed in seven patients and were characterized by multiple foci of abnormally increased signal intensity on the fluid-attenuated inversion-recovery and T2-weighted MR images. They were located in at least one of the following structures: cerebral and cerebellar white matter, basal ganglia, midbrain, brainstem, and corpus callosum. Most were small and were a few millimeters in diameter; in some instances, they were confluent and formed larger areas of T2 prolongation. The number of lesions ranged from four to too numerous to count. In six patients, multiple abnormal punctate or linear foci of enhancement were also demonstrated in the center of most but not all intraparenchymal lesions on the postcontrast images. The enhancing abnormalities appeared to reside along the medullary vessels (Fig 1).



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  		Figure 1a. Patient 6. Typical pattern of angiocentric involvement with lymphomatoid granulomatosis in 53-year-old man. (a) Sagittal and (b) transverse postcontrast T1-weighted MR images (400/9) of the brainstem and (c) transverse postcontrast T1-weighted images (400/9) of the cerebral hemispheres show multiple punctate enhancing foci (arrows) in the corpus callosum, midbrain, pons, medulla, and proximal cervical cord. Edema also was present around these lesions; some are noted with arrows in (d) transverse T2-weighted MR image (2500/100). (e, f) Transverse postcontrast T1-weighted MR images (400/9) obtained after treatment show complete resolution of the enhancing lesions in the (e) brainstem and the (f) cerebral hemispheres.

 


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  		Figure 1b. Patient 6. Typical pattern of angiocentric involvement with lymphomatoid granulomatosis in 53-year-old man. (a) Sagittal and (b) transverse postcontrast T1-weighted MR images (400/9) of the brainstem and (c) transverse postcontrast T1-weighted images (400/9) of the cerebral hemispheres show multiple punctate enhancing foci (arrows) in the corpus callosum, midbrain, pons, medulla, and proximal cervical cord. Edema also was present around these lesions; some are noted with arrows in (d) transverse T2-weighted MR image (2500/100). (e, f) Transverse postcontrast T1-weighted MR images (400/9) obtained after treatment show complete resolution of the enhancing lesions in the (e) brainstem and the (f) cerebral hemispheres.

 


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  		Figure 1c. Patient 6. Typical pattern of angiocentric involvement with lymphomatoid granulomatosis in 53-year-old man. (a) Sagittal and (b) transverse postcontrast T1-weighted MR images (400/9) of the brainstem and (c) transverse postcontrast T1-weighted images (400/9) of the cerebral hemispheres show multiple punctate enhancing foci (arrows) in the corpus callosum, midbrain, pons, medulla, and proximal cervical cord. Edema also was present around these lesions; some are noted with arrows in (d) transverse T2-weighted MR image (2500/100). (e, f) Transverse postcontrast T1-weighted MR images (400/9) obtained after treatment show complete resolution of the enhancing lesions in the (e) brainstem and the (f) cerebral hemispheres.

 


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  		Figure 1d. Patient 6. Typical pattern of angiocentric involvement with lymphomatoid granulomatosis in 53-year-old man. (a) Sagittal and (b) transverse postcontrast T1-weighted MR images (400/9) of the brainstem and (c) transverse postcontrast T1-weighted images (400/9) of the cerebral hemispheres show multiple punctate enhancing foci (arrows) in the corpus callosum, midbrain, pons, medulla, and proximal cervical cord. Edema also was present around these lesions; some are noted with arrows in (d) transverse T2-weighted MR image (2500/100). (e, f) Transverse postcontrast T1-weighted MR images (400/9) obtained after treatment show complete resolution of the enhancing lesions in the (e) brainstem and the (f) cerebral hemispheres.

 


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  		Figure 1e. Patient 6. Typical pattern of angiocentric involvement with lymphomatoid granulomatosis in 53-year-old man. (a) Sagittal and (b) transverse postcontrast T1-weighted MR images (400/9) of the brainstem and (c) transverse postcontrast T1-weighted images (400/9) of the cerebral hemispheres show multiple punctate enhancing foci (arrows) in the corpus callosum, midbrain, pons, medulla, and proximal cervical cord. Edema also was present around these lesions; some are noted with arrows in (d) transverse T2-weighted MR image (2500/100). (e, f) Transverse postcontrast T1-weighted MR images (400/9) obtained after treatment show complete resolution of the enhancing lesions in the (e) brainstem and the (f) cerebral hemispheres.

 


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  		Figure 1f. Patient 6. Typical pattern of angiocentric involvement with lymphomatoid granulomatosis in 53-year-old man. (a) Sagittal and (b) transverse postcontrast T1-weighted MR images (400/9) of the brainstem and (c) transverse postcontrast T1-weighted images (400/9) of the cerebral hemispheres show multiple punctate enhancing foci (arrows) in the corpus callosum, midbrain, pons, medulla, and proximal cervical cord. Edema also was present around these lesions; some are noted with arrows in (d) transverse T2-weighted MR image (2500/100). (e, f) Transverse postcontrast T1-weighted MR images (400/9) obtained after treatment show complete resolution of the enhancing lesions in the (e) brainstem and the (f) cerebral hemispheres.

 
The second most common pattern of involvement was observed in six patients and consisted of leptomeningeal and/or cranial nerve enhancement (Figs 2, 3). The seventh and the eighth cranial nerves were affected bilaterally in three patients (patients 1, 3, and 5), and in one of these patients, there was also enhancement of the fifth cranial nerve (patient 5). Involvement of both ninth cranial nerves was seen in another patient (patient 13). The abnormal enhancement was associated with cranial nerve palsy of the affected nerves in all four patients. Images from one of these four patients with cranial nerve involvement (patient 5) displayed leptomeningeal enhancement in the prepontine, the cerebellopontine, and the perimesencephalic cisterns. In two additional patients (patients 7 and 9), leptomeningeal enhancement was present around the brainstem, without involvement of the cranial nerves. There were no clinical symptoms attributed to these meningeal abnormalities. It should be noted that all five patients with CSF findings that were positive for lymphomatoid granulomatosis had involvement of the leptomeninges, the cranial nerves, or both (Table).



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  		Figure 2a. Patient 5. Leptomeningeal involvement with lymphomatoid granulomatosis in 37-year-old man. Transverse (a, b) precontrast and (c, d) postcontrast T1-weighted MR images (400/9) show abnormal enhancement in the leptomeninges (arrows) of the suprasellar region. Slight dilatation of the temporal horns is also present. (e) Transverse postcontrast T1-weighted MR image (400/9) of the posterior fossa shows enhancement and increased thickness of the leptomeninges in the cerebellomedullary cisterns bilaterally and choroid plexus involvement in the foramen of Luschka (arrows) on the left. (f) Transverse fluid-attenuated inversion-recovery MR image (10 000/137) of the posterior fossa after intravenous contrast material administration demonstrates abnormally increased signal intensity in the left internal auditory canal (short arrow), which is indicative of leptomeningeal inflammation, and also involves the seventh and eighth cranial nerves. There is edema (long arrow) in the left cerebellar peduncle and adjacent pons.

 


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  		Figure 2b. Patient 5. Leptomeningeal involvement with lymphomatoid granulomatosis in 37-year-old man. Transverse (a, b) precontrast and (c, d) postcontrast T1-weighted MR images (400/9) show abnormal enhancement in the leptomeninges (arrows) of the suprasellar region. Slight dilatation of the temporal horns is also present. (e) Transverse postcontrast T1-weighted MR image (400/9) of the posterior fossa shows enhancement and increased thickness of the leptomeninges in the cerebellomedullary cisterns bilaterally and choroid plexus involvement in the foramen of Luschka (arrows) on the left. (f) Transverse fluid-attenuated inversion-recovery MR image (10 000/137) of the posterior fossa after intravenous contrast material administration demonstrates abnormally increased signal intensity in the left internal auditory canal (short arrow), which is indicative of leptomeningeal inflammation, and also involves the seventh and eighth cranial nerves. There is edema (long arrow) in the left cerebellar peduncle and adjacent pons.

 


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  		Figure 2c. Patient 5. Leptomeningeal involvement with lymphomatoid granulomatosis in 37-year-old man. Transverse (a, b) precontrast and (c, d) postcontrast T1-weighted MR images (400/9) show abnormal enhancement in the leptomeninges (arrows) of the suprasellar region. Slight dilatation of the temporal horns is also present. (e) Transverse postcontrast T1-weighted MR image (400/9) of the posterior fossa shows enhancement and increased thickness of the leptomeninges in the cerebellomedullary cisterns bilaterally and choroid plexus involvement in the foramen of Luschka (arrows) on the left. (f) Transverse fluid-attenuated inversion-recovery MR image (10 000/137) of the posterior fossa after intravenous contrast material administration demonstrates abnormally increased signal intensity in the left internal auditory canal (short arrow), which is indicative of leptomeningeal inflammation, and also involves the seventh and eighth cranial nerves. There is edema (long arrow) in the left cerebellar peduncle and adjacent pons.

 


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  		Figure 2d. Patient 5. Leptomeningeal involvement with lymphomatoid granulomatosis in 37-year-old man. Transverse (a, b) precontrast and (c, d) postcontrast T1-weighted MR images (400/9) show abnormal enhancement in the leptomeninges (arrows) of the suprasellar region. Slight dilatation of the temporal horns is also present. (e) Transverse postcontrast T1-weighted MR image (400/9) of the posterior fossa shows enhancement and increased thickness of the leptomeninges in the cerebellomedullary cisterns bilaterally and choroid plexus involvement in the foramen of Luschka (arrows) on the left. (f) Transverse fluid-attenuated inversion-recovery MR image (10 000/137) of the posterior fossa after intravenous contrast material administration demonstrates abnormally increased signal intensity in the left internal auditory canal (short arrow), which is indicative of leptomeningeal inflammation, and also involves the seventh and eighth cranial nerves. There is edema (long arrow) in the left cerebellar peduncle and adjacent pons.

 


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  		Figure 2e. Patient 5. Leptomeningeal involvement with lymphomatoid granulomatosis in 37-year-old man. Transverse (a, b) precontrast and (c, d) postcontrast T1-weighted MR images (400/9) show abnormal enhancement in the leptomeninges (arrows) of the suprasellar region. Slight dilatation of the temporal horns is also present. (e) Transverse postcontrast T1-weighted MR image (400/9) of the posterior fossa shows enhancement and increased thickness of the leptomeninges in the cerebellomedullary cisterns bilaterally and choroid plexus involvement in the foramen of Luschka (arrows) on the left. (f) Transverse fluid-attenuated inversion-recovery MR image (10 000/137) of the posterior fossa after intravenous contrast material administration demonstrates abnormally increased signal intensity in the left internal auditory canal (short arrow), which is indicative of leptomeningeal inflammation, and also involves the seventh and eighth cranial nerves. There is edema (long arrow) in the left cerebellar peduncle and adjacent pons.

 


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  		Figure 2f. Patient 5. Leptomeningeal involvement with lymphomatoid granulomatosis in 37-year-old man. Transverse (a, b) precontrast and (c, d) postcontrast T1-weighted MR images (400/9) show abnormal enhancement in the leptomeninges (arrows) of the suprasellar region. Slight dilatation of the temporal horns is also present. (e) Transverse postcontrast T1-weighted MR image (400/9) of the posterior fossa shows enhancement and increased thickness of the leptomeninges in the cerebellomedullary cisterns bilaterally and choroid plexus involvement in the foramen of Luschka (arrows) on the left. (f) Transverse fluid-attenuated inversion-recovery MR image (10 000/137) of the posterior fossa after intravenous contrast material administration demonstrates abnormally increased signal intensity in the left internal auditory canal (short arrow), which is indicative of leptomeningeal inflammation, and also involves the seventh and eighth cranial nerves. There is edema (long arrow) in the left cerebellar peduncle and adjacent pons.

 


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  		Figure 3a. Patient 3. Cranial nerve involvement in 24-year-old man. (a) Transverse postcontrast T1-weighted MR image (400/9) of the internal auditory canals (composite image from two consecutive transverse images) before treatment shows abnormal enhancing seventh and eighth cranial nerves bilaterally (arrows). (b) Transverse postcontrast T1-weighted MR image (400/9) of the internal auditory canals after treatment shows resolution of the abnormal enhancement of the seventh and eighth cranial nerves (arrows).

 


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  		Figure 3b. Patient 3. Cranial nerve involvement in 24-year-old man. (a) Transverse postcontrast T1-weighted MR image (400/9) of the internal auditory canals (composite image from two consecutive transverse images) before treatment shows abnormal enhancing seventh and eighth cranial nerves bilaterally (arrows). (b) Transverse postcontrast T1-weighted MR image (400/9) of the internal auditory canals after treatment shows resolution of the abnormal enhancement of the seventh and eighth cranial nerves (arrows).

 
Other types of abnormalities distinct from the two major patterns were also found in seven patients. Specifically, four patients (patients 3 and 11–13) demonstrated a total of five intracranial masses. In one of these patients, the mass was originally localized to the medial aspect of the right frontal lobe, but, with time, it enlarged, crossed the interhemispheric fissure, and involved the left frontal lobe as well. In the second patient, two masses were found, one in the right basal ganglia (Fig 4) and the other in the left frontal lobe. In the third patient, one mass was seen in the right basal ganglia, and one, in the right cerebellar hemisphere. The fourth patient had a mass in the suprasellar area that infiltrated the pituitary stalk. With the exception of the mass in the pituitary stalk that exhibited homogeneous enhancement, all other masses initially manifested with heterogeneous enhancement surrounded by edema in the adjacent brain parenchyma. With time, these lesions evolved and showed a ringlike enhancement in the periphery and a nonenhancing center. Two more patients had enlargement and intense enhancement of the choroid plexus in the lateral ventricles, and these findings were bilateral in one (patient 7) and unilateral in the other (patient 5) (Fig 5). Patient 5 also had unilateral choroid plexus involvement in the foramen of Luschka (Fig 2e). In both patients, abnormal leptomeningeal enhancement was found around the brainstem (patients 5 and 7); one (patient 5) also had cranial nerve enhancement. The seventh patient had thickening and prominent enhancement of the dura mater, without an associated leptomeningeal component.



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  		Figure 4a. Patient 11. Intraparenchymal mass in lymphomatoid granulomatosis in 17-year-old female patient. Transverse (a) postcontrast T1-weighted (400/9) and (b) fluid-attenuated inversion-recovery (10 000/137) MR images of the brain before treatment show a large heterogeneously enhancing mass in the right basal ganglia (arrow in a), surrounded by a relatively small zone of edema (arrow in b). Transverse (c) postcontrast T1-weighted (400/9) and (d) fluid-attenuated inversion-recovery (10 000/137) MR images after treatment show resolution of the granulomatous mass (arrow in c). An area of gliosis, possibly with a cavitation, is noted at the site of the mass (arrow in d).

 


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  		Figure 4b. Patient 11. Intraparenchymal mass in lymphomatoid granulomatosis in 17-year-old female patient. Transverse (a) postcontrast T1-weighted (400/9) and (b) fluid-attenuated inversion-recovery (10 000/137) MR images of the brain before treatment show a large heterogeneously enhancing mass in the right basal ganglia (arrow in a), surrounded by a relatively small zone of edema (arrow in b). Transverse (c) postcontrast T1-weighted (400/9) and (d) fluid-attenuated inversion-recovery (10 000/137) MR images after treatment show resolution of the granulomatous mass (arrow in c). An area of gliosis, possibly with a cavitation, is noted at the site of the mass (arrow in d).

 


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  		Figure 4c. Patient 11. Intraparenchymal mass in lymphomatoid granulomatosis in 17-year-old female patient. Transverse (a) postcontrast T1-weighted (400/9) and (b) fluid-attenuated inversion-recovery (10 000/137) MR images of the brain before treatment show a large heterogeneously enhancing mass in the right basal ganglia (arrow in a), surrounded by a relatively small zone of edema (arrow in b). Transverse (c) postcontrast T1-weighted (400/9) and (d) fluid-attenuated inversion-recovery (10 000/137) MR images after treatment show resolution of the granulomatous mass (arrow in c). An area of gliosis, possibly with a cavitation, is noted at the site of the mass (arrow in d).

 


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  		Figure 4d. Patient 11. Intraparenchymal mass in lymphomatoid granulomatosis in 17-year-old female patient. Transverse (a) postcontrast T1-weighted (400/9) and (b) fluid-attenuated inversion-recovery (10 000/137) MR images of the brain before treatment show a large heterogeneously enhancing mass in the right basal ganglia (arrow in a), surrounded by a relatively small zone of edema (arrow in b). Transverse (c) postcontrast T1-weighted (400/9) and (d) fluid-attenuated inversion-recovery (10 000/137) MR images after treatment show resolution of the granulomatous mass (arrow in c). An area of gliosis, possibly with a cavitation, is noted at the site of the mass (arrow in d).

 


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  		Figure 5a. Patient 5. Choroid plexus involvement with lymphomatoid granulomatosis in 37-year-old man. (a) Transverse postcontrast T1-weighted (400/9) MR image of the brain before treatment shows abnormally increased volume of the right choroid plexus in the body of the lateral ventricle, associated with intense and homogeneous enhancement (arrow). (b) Transverse postcontrast T1-weighted (400/9) MR image of the brain after treatment shows near complete resolution of the abnormality in the right choroid plexus.

 


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  		Figure 5b. Patient 5. Choroid plexus involvement with lymphomatoid granulomatosis in 37-year-old man. (a) Transverse postcontrast T1-weighted (400/9) MR image of the brain before treatment shows abnormally increased volume of the right choroid plexus in the body of the lateral ventricle, associated with intense and homogeneous enhancement (arrow). (b) Transverse postcontrast T1-weighted (400/9) MR image of the brain after treatment shows near complete resolution of the abnormality in the right choroid plexus.

 
Follow-up MR Imaging Findings
On follow-up MR images obtained during and after treatment, there was complete resolution of all but seven punctate brain lesions that exhibited T2 prolongation and abnormal enhancement. These seven lesions, which were seen in three patients (patient 5, 37-year-old man; patient 6, 53-year-old man; patient 8, 32-year-old man), progressed to lacunar infarctions that resulted in the formation of small cavities after completion of treatment. Five infarctions were located in the basal ganglia, and two, in the pons. The enhancement of the cranial nerves and the leptomeninges in all patients with follow-up studies also disappeared. The mass lesions observed in patients 3 and 11–13 gradually decreased in size. With the exception of the mass in the pituitary stalk, which resolved completely, a small nonenhancing glial scar was seen in the remaining four masses on the last MR image. Small irregular areas of decreased signal intensity on the T2-weighted MR images were observed within the glial scar, and these areas were believed to represent products of hemoglobin degradation. The enlarged choroid plexus returned to normal at posttreatment MR imaging.

Conditions in most patients with neurologic manifestations of disease improved, with complete resolution in four (40%) of 10 and partial improvement in five (50%). Of this symptomatic group, three patients died from systemic manifestations of disease. The time to clinical improvement or resolution of symptoms varied. Improvements were seen as early as the 1st week of interferon treatment, and, in most patients, maximal improvement of symptoms was observed within 6 months. Although MR imaging was not performed as often as were history taking and physical examination, it is safe to say that the resolution of the imaging findings lagged behind the clinical improvement.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
In our study, we present the spectrum of MR imaging findings that can be encountered in patients with CNS involvement from lymphomatoid granulomatosis. Several aspects of the present study distinguish it from those of prior reports. First, to our knowledge, the results are based on the largest group of patients examined; all were comprehensively evaluated at a single institution that employed modern imaging and staging techniques. Second, the accuracy of the diagnosis of lymphomatoid granulomatosis in a series of patients was a major issue in prior studies in which the pathologic criteria for lymphomatoid granulomatosis were inexact and the B-cell lineage of the disease or the importance of in situ localization of EBV were not recognized (3,4). Indeed, researchers in prior studies included some patients in their series of patients who would not be considered to have lymphomatoid granulomatosis according to current pathologic standards, such as patients with extranodal nasal natural killer/T-cell lymphomas (formerly known as angiocentric T-cell lymphomas), and, hence, the inclusion of these patients confounded the accuracy of the data in the older studies (10,26,27). Nevertheless, our findings do corroborate some findings in the series of patients reported in earlier articles but are inconsistent with others, as noted later.

In the present study, multiple focal lesions that involve the white matter, the deep gray matter, or the brainstem represent the most common abnormalities encountered in seven of 13 patients. The high signal intensity of these lesions on the T2-weighted MR images is a nonspecific finding commonly observed in a large variety of pathologic processes of the brain. Punctate and/or linear enhancement in these lesions appears to be a characteristic finding of lymphomatoid granulomatosis in the brain. Our findings corroborate the findings recently reported by Tateishi et al (28), who found punctate and linear enhancement within focal lesions that exhibited T2 prolongation in all four of their patients. This type of enhancement corresponds to the known perivascular and vascular wall infiltration by pleomorphic and lymphoid cells, an infiltration that was previously shown in biopsy specimens of the brain (19,20,23,28). A range of severity of the angiocentric cellular infiltration may be assumed on the basis of the fact that some of these lesions manifested with only T2 prolongation, whereas others, in addition, demonstrated enhancement on the postcontrast image. Variation of severity of angiocentric infiltration is further demonstrated by the fact that seven lesions resulted in lacunar infarction in spite of the overall response to treatment of most brain abnormalities. Such an outcome suggests the presence of even more severe vascular wall infiltration, which leads to occlusion of the lumen of the vessel.

Leptomeningeal involvement with lymphomatoid granulomatosis has been shown at histologic examinations and in autopsy data. Such findings, however, have been reported by using imaging only once (29), as far as we know. In our study, we have shown abnormal enhancement of the leptomeninges and cranial nerves in six of 13 patients with abnormal MR imaging findings. Since the enhancement of the cranial nerves was confined to the subarachnoid segment of these nerves, it is likely that their involvement represents, at least in part, leptomeningeal infiltration. In previous publications, cranial nerve palsy has been reported as one of the clinical features of CNS involvement in patients with lymphomatoid granulomatosis (5,13). Our findings confirm such involvement and provide an anatomic explanation for the symptoms.

Dural enhancement without the leptomeningeal component was demonstrated in one patient in our series. Similar findings have been reported previously in three patients; in two of these patients, cavernous sinus involvement was present, and in the other, there was histologic evidence of angiocentric lymphomatoid infiltrates of the dura mater. Our patient with dural enhancement had CSF cytologic findings that were positive for lymphomatoid granulomatosis. It should be noted, however, that dural enhancement is a nonspecific finding and can be encountered in a large variety of pathologic processes. Therefore, this finding by itself has no diagnostic value.

Brain masses commonly have been reported by previous authors in patients with lymphomatoid granulomatosis. As reported in the literature (8,14,16,20,28), eight (57%) of 14 patients with CNS involvement had brain masses, and this frequency is substantially higher than that observed in the present series of patients. The relatively high incidence of brain masses in the other series of patients may reflect the inadequacy of older treatment approaches, as compared with those in the present study, and the natural progression of the disease. Indeed, most of the reports are old, and the lesions were discovered either by using outdated technologies or at autopsy. It is also likely that some of these lesions may represent lymphomas that are not associated with lymphomatoid granulomatosis, since they responded favorably to chemotherapy. Although lymphomatoid granulomatosis can evolve into an EBV-positive diffuse large B-cell lymphoma (grade 3B lymphomatoid granulomatosis), this evolution is not a common event in the CNS and suggests that some of the older cases may not represent lymphomatoid granulomatosis. In our series, only four (31%) of 13 patients developed mass lesions. A brain biopsy from one patient showed both grade 1 and grade 3B lymphomatoid granulomatosis, and both are EBV-positive diffuse large B-cell lymphomas. Although no brain biopsy was obtained in the second case, a biopsy of a pulmonary lesion showed grade 2 lymphomatoid granulomatosis; cytologic analysis of the CSF showed large B cells, and the presence of these cells is consistent with an aggressive B-cell lymphoma. Thus, two of four patients in our series of those with brain masses had evidence of a high-grade lymphomatoid granulomatosis process.

The involvement of the choroid plexus that was found in two of our patients has not been previously reported, as far as we know. Enlargement and increased enhancement of the choroid plexus can occur in a variety of infiltrative, inflammatory, or neoplastic processes, but with an appropriate clinical setting, involvement with lymphomatoid granulomatosis also should be considered. We have found no imaging features that distinguish lymphomatoid granulomatosis from other similar lesions of the choroid plexus. The response to treatment is the only diagnostic clue to the pathologic process behind this finding.

No hemorrhagic brain lesions were encountered in 11 of the patients in this series. Yet, other investigators (19) have reported such an intracranial complication, but the exact cause of bleeding remains unknown. In one of the older reports, a cerebral aneurysm was found, whereas in another patient, irregularities in the wall of the cerebral arteries were demonstrated by using cerebral angiography. Since none of our patients underwent cerebral angiography, we are not in a position to assess the frequency of such complications.

Previously, cortical cerebral ischemic infarctions have been reported (15,21) in two patients. Considering the anatomic location of the lesions in this disease, it is not surprising that such a complication can take place. The lacunar infarctions that were encountered in seven of the lesions in this series of patients probably share a common pathologic process with the infarctions in those two patients.

A potential limitation of this study is the absence of histologic documentation of the brain abnormalities. With the exception of one patient, whose primary diagnosis of lymphomatoid granulomatosis was determined at biopsy of the brain, however, a histologic diagnosis of lymphomatoid granulomatosis was determined with tissue from another site in all other patients. Because of the difficulty of determining a diagnosis of lymphomatoid granulomatosis at stereotactic biopsy and the clinically consistent manifestation in the CNS, we believe that performance of a biopsy of the brain is not medically indicated in such patients. Indeed, the high radiologic and clinical response of the CNS lesions to treatment was also consistent with a diagnosis of CNS lymphomatoid granulomatosis. Because of the rarity of lymphomatoid granulomatosis and relatively small number of patients in this series of patients, it is important to recognize that the frequency and type of CNS lesions we have described may not prove to be representative of this entity.

Our findings indicate that the sensitivity of CSF analysis for the diagnosis of lymphomatoid granulomatosis in the brain is relatively low. This result, however, is consistent with the known biologic features of lymphomatoid granulomatosis; in the latter, the EBV-positive B cells, compared with the reactive T cells, are rare (3,6).

In conclusion, focal intraparenchymal lesions presumably caused by angiocentric infiltrations, as well as meningeal and cranial nerve abnormalities, are the most common patterns of involvement seen at MR imaging. Such lesions, if treated appropriately in the course of the disease, can resolve completely, with improvement of the neurologic function. Because of the high frequency of CNS involvement with lymphomatoid granulomatosis and the higher sensitivity of MR imaging compared with CSF examination, MR imaging of the CNS should be performed in all patients with lymphomatoid granulomatosis.


   FOOTNOTES
 

Abbreviations: CNS = central nervous system • CSF = cerebrospinal fluid • EBV = Epstein-Barr virus

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, A.D.P., N.J.P., W.H.W.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, A.D.P., G.A., U.H., J.J., E.S.J., W.H.W.; clinical studies, A.D.P., G.A., U.H., J.J., N.G., E.S.J., N.J.P., W.H.W.; statistical analysis, A.D.P., A.D.; and manuscript editing, A.D.P., A.D., N.J.P., W.H.W.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Liebow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972;3:457–558.[Medline]
  2. Jaffe ES, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 1997;30:233–248.[Medline]
  3. Wilson WH, Kingma DW, Raffeld M, Wittes RE, Jaffe ES. Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. Blood 1996;87:4531–4537.[Abstract/Free Full Text]
  4. Myers JL, Kurtin PJ, Katzenstein AL, et al. Lymphomatoid granulomatosis: evidence of immunophenotypic diversity and relationship to Epstein-Barr virus infection. Am J Surg Pathol 1995;19:1300–1312.[Medline]
  5. Katzenstein AL, Carrington CB, Liebow AA. Lymphomatoid granulomatosis: a clinicopathologic study of 152 cases. Cancer 1979;43:360–373.[CrossRef][Medline]
  6. Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: a progress report. Am J Clin Pathol 1999; 111(1 suppl 1):S8–S12.[Medline]
  7. Paspala AB, Sundaram C, Purohit AK, Immaneni D. Exclusive CNS involvement by lymphomatoid granulomatosis in a 12-year-old boy: a case report. Surg Neurol 1999;51:258–260.[CrossRef][Medline]
  8. Demetrick DJ, Hamilton MG, Curry B, Tranmer BI. Epstein-Barr virus-associated primary B-cell lymphoproliferative disorder of the cerebellum in an immune competent man. Cancer 1992;70:519–528.[CrossRef][Medline]
  9. Haque AK, Myers JL, Hudnall SD, et al. Pulmonary lymphomatoid granulomatosis in acquired immunodeficiency syndrome: lesions with Epstein-Barr virus infection. Mod Pathol 1998;11:347–356.[Medline]
  10. Fauci AS, Haynes BF, Costa J, Katz P, Wolff SM. Lymphomatoid granulomatosis: prospective clinical and therapeutic experience over 10 years. N Engl J Med 1982;306:68–74.[Abstract]
  11. Hamilton MG, Demetrick DJ, Tranmer BI, Curry B. Isolated cerebellar lymphomatoid granulomatosis progressing to malignant lymphoma: case report. J Neurosurg 1994;80:314–320.[Medline]
  12. Beaty MW, Toro J, Sorbara L, et al. Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features. Am J Surg Pathol 2001;25:1111–1120.[CrossRef][Medline]
  13. Wilson WH, Gutierrez M, Raffeld M, Raggio RN, Jaffe ES. Lymphomatoid granulomatosis: phase II study of dose-adjusted interferon-{alpha} or EPOCH chemotherapy [abstr]. Blood 1999; 94(suppl 1, pt 1):599a.
  14. Ng P, Dwyer R, Hughes A, Despas P. Lymphomatoid granulomatosis: case report and review of the literature. Australas Radiol 1997;41:57–62.[Medline]
  15. Capone PM, Mechtler LL, Bates VE, Kanna A, Kinkel PR. Multiple giant intracranial aneurysms associated with lymphomatoid granulomatosis: a magnetic resonance imaging and angiographic study. J Neuroimaging 1994;4:109–111.[Medline]
  16. George JC, Caldemeyer KS, Smith RR, Czaja JT. CNS lymphomatoid granulomatosis in AIDS: CT and MR appearances. AJR Am J Roentgenol 1993;161:381–383.[Free Full Text]
  17. Bushunow PW, Casas V, Duggan DB. Lyphomatoid granulomatosis causing central diabetes insipidus: case report and review of the literature. Cancer Invest 1996;14:112–119.[Medline]
  18. Kerslake R, Rowe D, Worthington BS. CT and MR imaging of CNS lymphomatoid granulomatosis. Neuroradiology 1991;33:269–271.[CrossRef][Medline]
  19. Kapila A, Gupta KL, Garcia JH. CT and MR of lymphomatoid granulomatosis of the CNS: report of four cases and review of the literature. AJNR Am J Neuroradiol 1988;9:1139–1143.[Abstract]
  20. Podlas HB, Gritzman MC, Thomaides S, Roos H. CT of CNS lesions in lymphomatoid granulomatosis: case report. AJNR Am J Neuroradiol 1988;9:592–594.[Medline]
  21. Sackett JF, ZuRhein GM, Bhimani SM. Lymphomatoid granulomatosis involving the central nervous system: radiologic-pathologic correlation. AJR Am J Roentgenol 1979;132:823–826.[Medline]
  22. Simon RH, Adeles M, Farber NJ, Grunnet M, Brennan TG Jr. Lymphomatoid granulomatosis with multiple intracranial lesions: care report. J Neurosurg 1981;55:293–298.[Medline]
  23. Whelan HT, Moore P. Central nervous system lymphomatoid granulomatosis. Pediatr Neurosci 1987;13:113–117.[Medline]
  24. Wilson WH, Grossbard ML, Pittaluga S, et al. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood 2002;99:2685–2693.[Abstract/Free Full Text]
  25. Wilson WH. Chemotherapy sensitization by rituximab: experimental and clinical evidence. Semin Oncol 2000;27:30–36.
  26. Brazis PW, Menke DM, McLeish WM, et al. Angiocentric T-cell lymphoma presenting with multiple cranial nerve palsies and retrobulbar optic neuropathy. J Neuroophthalmol 1995;15:152–157.[Medline]
  27. Kleinschmidt-DeMasters BK, Filley CM, Bitter MA. Central nervous system angiocentric, angiodestructive T-cell lymphoma (lymphomatoid granulomatosis). Surg Neurol 1992;37:130–137.[CrossRef][Medline]
  28. Tateishi U, Terae S, Ogata A, et al. MR imaging of the brain in lymphomatoid granulomatosis. AJNR Am J Neuroradiol 2001;22:1283–1290.[Abstract/Free Full Text]
  29. Bhagavatula K, Scott TF. Magnetic resonance appearance of cerebral lymphomatoid granulomatosis. J Neuroimaging 1997;7:120–121.[Medline]



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