doi:10.1111/j.1750-3639.2009.00304.

x
COM MARCH 2009 CASE 2 b pa _ 3 0 4 541..544

A 69-YEAR-OLD MAN WITH LEFT HEMISPHERIC

NECROTIZING MASS LESION bpa_304 541..544

Frauke Otto MD , Eva Neuen-Jacob MD , Gabriele Arendt MD1, Olaf Stüve MD PhD1,3 and
1 2

Hans-Peter Hartung MD1

1
Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany
2
Department of Neuropathology, Heinrich-Heine University, Düsseldorf, Germany
3
Department of Neurology, University of Texas Southwestern Medical Center at Dallas VA, Dallas, TX , U.S.A.

cranial CT scan showed no abnormalities (Figure 1). His total leu-

CLINICAL HISTORY kocyte count in the PB was 4100/ml, and his lymphocyte count
A 69-year-old patient with a four-year history of CIDP was admit- 600/ml. Plasma exchange and oral corticosteroids temporarily
ted for evaluation of further treatment options at a tertiary Univer- improved his sensorimotor symptoms and signs.
sity hospital. Diagnostic criteria for CIDP established by the AAN Following plasma exchange the patient developed diarrhoea, and
were fulfilled (1). Six months prior to this admission, the patient his cognitive impairment continued to worsen. A brain MR scan
had suffered from a granulocytic meningitis while he was treated showed bilateral periventricular edema with multiple gadolinium-
with azathioprine and prednisolone. At that time, evaluation of his enhancing T1 lesions in the periventricular parenchyma (Figure 2).
cerebrospinal fluid (CSF) revealed a pleocytosis of 1240 white CSF analysis revealed increased albumin and IgG in the absence of
blood cells (WBC)/ml. Immunosuppressive therapy was immedi- WBC. Candida albicans was detected in stool specimens. Despite
ately suspended. The causative pathogen could not be identified, intravenous antibiotic, antiviral and antifungal therapy as well as
but the patient partially recovered after empiric antibiotic treatment administration of intravenous immunoglobulins (IVIG), the patient
with ceftriaxon and ampicillin. Residual neurological deficits further deteriorated clinically with right-sided hemiparesis and a
included persisting mild cognitive impairment. At that time, a Broca dysphasia. Polymerase chain reaction (PCR) of the CSF
cranial computer tomography (CT) and a magnetic resonance for Epstein-Barr virus (EBV) was positive, while no DNA copy
imaging (MRI) scan of the brain were normal. numbers of Candida, Aspergillus, toxoplasma, and other neurotro-
After 2 months of progressively worsening CIDP, treatment with pic viruses, including VZV, HSV, CMV, HIV were detected. Despite
mycophenolate mofetil was commenced but had to be stopped supportive intensive care treatment the patient died within 4 weeks.
within 3 weeks because of gastrointestinal side effects. Azathio-
prine medication was re-instituted, and the total leukocyte count in
the peripheral blood (PB) was in the range of 3600–4700/ml. The
MICROSCOPIC EXAMINATION AND
patient was re-admitted because of acute-onset confusion, cogni-
NEUROPATHOLOGIC FINDINGS
tive decline, and increasing weakness. On physical examination, A stereotactic brain biopsy of affected white matter parenchyma
the patient displayed significant attention deficits, disorientation in revealed non-specific necrosis without evidence of malignant
time, dysarthrophonia, a mild flaccid tetraparesis, areflexia of the or inflammatory cellular infiltrates. Three tiny specimens with a
lower limbs, gait disturbance, distal symmetric hypo- and dysesthe- total size of 0,5 ¥ 0.5 ¥ 0.5 mm were submitted for examination
sia, right-sided hemiataxia and bradydysdiadochokinesia. A (Figure 3 left side, H&E; -right side, expression of CD68).

Figure 1. Figure 2.

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Correspondence

Figure 3.

An autopsy was performed and gross examination of the positive pleomorphic polynuclear Reed-Sternberg like cells
brain demonstrated a necrotizing mass lesion in the left cerebral (Figure 5A and 5B). There was a high mitotic and proliferative
hemisphere approaching the ependyma and infiltrating the activity (Figure 5C). In addition, perifocal edema with marked
corpus callosum mimicking a glioblastoma (Figure 4). glial fibrillary acid protein (GFAP)-positive reactive astrocytic
Microscopic examination disclosed angiocentric pleomorphic gliosis was noted. The EBV antigen EBNA2 was detected
infiltrates of lymphocytes, histiocytes, large CD20-positive cells immunohistochemically in the majority of CD20-positive cells
resembling lymphoblasts, centroblasts, and scattered CD30- (Figure 5D).

Figure 4.

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© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
 Correspondence

B C D

Figure 5.

Brain Pathology 19 (2009) 541–544 543

© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Correspondence

This case of CNS lymphoma in a patient with CIDP emphasizes

DIAGNOSIS the need for vigilantly monitoring of patients with immune-
EBV-associated diffuse large B cell lymphoma and additional mediated neurological disorders undergoing immunosuppressive
microglial nodule encephalitis of the brainstem with associated therapies. Cognitive deficits, psychiatric aberrations and focal
severe hypoxic injury of neurons. signs should prompt a careful diagnostic work-up for infectious
complications and CNS malignancy.
DISCUSSION
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ABSTRACT
bowel disease, rheumatoid arthritis and transplant recipients We report the first case of primary non-Hodgkin lymphoma of the
treated with this mercaptopurine (5, 9). Azathioprine treatment can central nervous system in a 69-year-old patient with chronic inflam-
result in leukopenia and lymphopenia, which may impair an effec- matory demyelinating polyneuropathy (CIDP) on long-term immu-
tive immune surveillance, and could allow the emergence of neo- nosuppression. CIDP was diagnosed 4 years earlier and treated with
plastic growth (3). plasma exchange, corticosteroids, azathioprine and mycophenolate
Four patients suffering from neurological autoimmune disease mofetil. The patient developed an organic brain syndrome and
(all myasthenia gravis) treated with azathioprine that developed cerebral MRI revealed multiple enhancing T1 lesions in the periven-
primary CNS non-Hodgkin lymphoma have been reported (4, 6), tricular parenchyma. A stereotactic biopsy was not diagnostic, but
and one patient with Crohn’s disease (5). It appears reasonable to Epstein-Barr virus (EBV) was detected in the cerebrospinal fluid.
assume that impaired immunosurveillance iatrogenically induced After a fulminant course of an illness resembling an encephalitis the
by azathioprine treatment was causative. patient died. Postmortem analysis confirmed the diagnosis of EBV-
We consider short-term (3 weeks) exposure to mycophenolate associated diffuse large B cell lymphoma. This case illustrates
mofetil not contributory. Recently, non-Hodgkin lymphoma of the the risks of life-threatening infections associated with continuous
brain diagnosed by stereotactic biopsy was reported in an elderly immunosuppression, and emphasizes the need for an extensive
patient who had been treated with mycophenolate mofetil 2 g/day diagnostic work-up in patients who present with signs and symp-
for 37 months (10). toms of an unexpected encephalopathy.

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