□ CASE REPORT □

Diffuse Cerebral Vasoconstriction in a Intravascular
Lymphoma Patient with a High Serum MPO-ANCA Level
Atsuhiko Sugiyama 1,2, Makoto Kobayashi 1, Ayaka Daizo 3, Miyako Suzuki 3,
Hirotoshi Kawashima 3, Shin-ichiro Kagami 3, Hiroaki Tanaka 4, Yoshio Suzuki 5,
Takashi Matsunaga 1 and Satoshi Kuwabara 2

Abstract
An 87-year-old woman presented with a 3-month history of fever, edema of the lower legs, and gait disturbance. A laboratory examination revealed high serum levels of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA). Although microscopic polyangiitis was initially suspected and treated, the
patient subsequently developed transient hemiparesis and disturbed consciousness. Brain magnetic resonance
imaging/angiography revealed infarct-like lesions, pachymeningeal involvement, and diffuse cerebral vasoconstriction. A random skin biopsy confirmed the histological diagnosis of intravascular lymphoma. Diffuse cerebral vasoconstriction and a high serum MPO-ANCA level have rarely been reported in patients with intravascular lymphoma. Endothelial damage due to immune-mediated mechanisms, tumor derived factors, or the direct interaction of lymphoma cells with endothelial cells may commonly predispose patients to both cerebral
vasoconstriction and the development of ANCAs.
Key words: intravascular lymphoma, vasoconstriction, magnetic resonance angiography, myeloperoxidasespecific antineutrophil cytoplasmic antibody

(Intern Med 56: 1715-1718, 2017)
(DOI: 10.2169/internalmedicine.56.8051)

with diffuse cerebral vasoconstriction on MRA and a high
serum myeloperoxidase-specific antineutrophil cytoplasmic
antibody (MPO-ANCA) level.

Introduction
Intravascular lymphoma (IVL) is a rare type of extranodal
lymphoma with an aggressive clinical course. It is characterized by a propensity for the proliferation of lymphoma cells
within the lumina of small vessels with a predilection for
the central nervous system and skin (1). Regarding the central nervous system involvement, several characteristic findings of brain magnetic resonance imaging (MRI) have been
reported, including infarct-like lesions, dural/meningeal enhancement, mass-like lesions, and nonspecific white matter
lesions (2-4). Because the angiotropic growth of this neoplasm mainly affects the small vessels, the magnetic resonance angiography (MRA) findings are usually normal (5).
We herein report the case of an IVL patient who presented

Case Report
An 87-year-old woman who had developed fever and
edema of the lower legs, which had persisted for three
months, was admitted to our hospital. Other than being
medicated for hypertension and hyperlipidemia for seven
years, she had previously been well. Before this episode, she
had been able to walk over short distances using a Zimmerframe; however, she was bedridden at the time of admission.
A physical examination revealed that her body temperature
was 36.0℃ and her blood pressure was 118/76 mmHg. She
had bilateral pitting edema of the lower legs. There were no

１

Department of Neurology, Asahi General Hospital, Japan, ２ Department of Neurology, Graduate School of Medicine, Chiba University, Japan,
Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Japan, ４ Department of Hematology, Asahi General Hospital,
Japan and ５ Department of Clinical Pathology, Asahi General Hospital, Japan
Received for publication July 25, 2016; Accepted for publication October 28, 2016
Correspondence to Dr. Atsuhiko Sugiyama, chinneosyo0624@yahoo.co.jp

３

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DOI: 10.2169/internalmedicine.56.8051

Figure 1. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA).
On admission, brain MRI (A) and MRA (B) were normal. On day 39, diffusion weighted imaging
(DWI) showed a high intensity area in the left temporal lobe (white arrow) (C), and MRA revealed the
bilateral diffuse narrowing of the M2 portion of the middle cerebral arteries (white arrowheads) (D).
On day 49, DWI showed high-intensity areas in the left frontal lobe and bilateral parietal lobes (E),
and MRA revealed the diffuse narrowing of the bilateral middle cerebral arteries, the anterior cerebral arteries, and the posterior cerebral arteries (white arrowheads) (F). After two cycle of R-CHOP
therapy, the high intensity lesions on DWI had partially disappeared (G), and MRA showed the alleviation of the narrowing observed in the cerebral arteries (H).

signs of superficial lymphadenopathy or cutaneous eruptions. A laboratory examination revealed the following findings: serum MPO-ANCA, 150 U/mL (reference range:
<3.50); serum soluble IL-2 receptor, 1,570 U/mL (reference
range: 145-519); serum CRP, 7.41 mg/dL (reference range:
<0.15); and erythrocyte sedimentation rate, 113 mm/h (refer-

ence range: <20). A urinalysis revealed microscopic hematuria and proteinuria. Brain MRI and MRA revealed no abnormalities (Fig. 1A, B). A nerve conduction study revealed
decreased action potentials in the bilateral tibial nerve and
the right median nerve but failed to detect action potentials
in the bilateral peroneal nerve, suggesting multiple

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3

) and an increased protein level (62 mg/dL). Brain MRI on
day 49 described multiple hyperintense lesions on T2weighted imaging with diffusion restriction in the right cerebellum and both hemispheres (Fig. 1E). Focal hypertrophy
and contrast enhancement in the pachymeninges of the right
side convex was observed on T1-weighted images with contrast (not shown). MRA revealed the diffuse narrowing of
the bilateral anterior cerebral arteries, the MCAs, and the
posterior cerebral arteries (Fig. 1F). We performed random
skin biopsies from the lower abdomen to investigate the
cause of the infarct-like lesions and pachymeningeal involvement. The biopsy specimens showed intravascular large
B cell lymphoma (Fig. 2).
Treatment with reduced-dose R-CHOP therapy (rituximab
375 mg/m2, doxorubicin 30 mg/body, cyclophosphamide 500
mg/body, vincristine 0.8 mg/body, and prednisolone 50 mg/
day) was immediately initiated. After two cycles of RCHOP brain MRI and MRA revealed the alleviation of
vasoconstriction (Fig. 1G, H). After three cycles of RCHOP, she was transferred to another hospital.

Discussion

Figure 2. Skin biopsy. A histological specimen with Hematoxylin and Eosin staining, showing tumor cells in the lumen of
the capillaries in subcutaneous fat (arrow) (A: low magnification, B: high magnification). The tumor cells in the capillaries
were positively stained with a CD20 B-cell marker (C).

mononeuropathy. Microscopic polyangiitis (MPA) was suspected based on these findings, and treatment with prednisone (45 mg/day) and rituximab (375 mg/m2/week) was initiated to prevent the further progression of MPA.
After the initiation of therapy, the inflammation subsided,
and by day 32, the serum MPO-ANCA titer had decreased
from 150 to 19.5 U/mL. However, she developed transient
hemiparesis of the right side on day 30. At that time, brain
MRI revealed a small high-intensity lesion on diffusionweighted imaging (DWI) in the white matter of the left temporal lobe. MRA showed the bilateral narrowing of the distal middle cerebral arteries (MCA) (Fig. 1C, D). Thereafter,
she gradually presented fluctuating disturbed consciousness.
Her cerebrospinal fluid had a normal leukocyte count (0/mm

The MRA findings observed in our case were reversible,
and were too diffuse and symmetric to have been caused by
the direct invasion of lymphoma cells. We assume that the
MRA findings in our case represented vasoconstriction,
which occurred in the course of IVL. To the best of our
knowledge, no cases of IVL with diffuse cerebral vasoconstriction have been reported; however, a case of IVL with
diffuse pulmonary vasoconstriction has been described (6).
This previous report assumed that the diffuse pulmonary
vasoconstriction was caused by vasoactive mediators that
were mainly released by activated platelets. Unfortunately,
the previous report provided no clear evidence of the elevation of vasoactive mediators, and other mechanisms, including the direct interaction of lymphoma cells with endothelial
cells might have caused the vasoconstriction. In IVL patients, endothelial injury might be caused by tumor-derived
factors or by direct the interaction of lymphoma cells with
endothelial cells. This endothelial damage leads to platelet
activation and the formation of microthrombi (7), which can
cause vasoconstriction. Drug-induced vasoconstriction is another possible cause of changes to the cerebral arteries.
However, we considered this to be unlikely. The narrowing
of the cerebral arteries was presumed to have started between the day of admission and day 30, and an improvement in the narrowing of the cerebral arteries was observed
despite all of the drugs that were initiated during this period
being continued.
The inflammatory reaction, the high serum MPO-ANCA
titers, and multiple mononeuropathy at the initial evaluation
of this case misled us into diagnosing the patient with MPA.
Previous reports have indicated that several drugs can induce
ANCA-associated vasculitis (8); however, these drugs were
not prescribed to our case on admission. Cases of “false

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positive ANCA” have been reported in patients with several
diseases such as HIV, tuberculosis, atrial myxomas/clot, and
non-Hodgkin’s lymphoma (9). In addition to the present
case, there is only one other reported case of IVL in a patient with a high serum MPO-ANCA level (10). Under these
conditions, vascular damage, due to immune-mediated
mechanisms or to secondary to embolic damage appeared to
predispose the patient to the development of ANCA antibodies (9).
In conclusion, diffuse cerebral vasoconstriction and a high
serum MPO-ANCA level were observed in a patient with
IVL. Endothelial damage caused by immune-mediated
mechanisms, tumor-derived factors, or the direct interaction
of lymphoma cells with endothelial cells may predispose a
patient to both cerebral vasoconstriction and the development of ANCA antibodies.
The authors state that they have no Conflict of Interest (COI).

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