Unusual spontaneous improvement in Asian variant of intravascular large B-cell lymphoma

doi:10.4236/ojim.2012.21004

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Open Journal of Internal Medicine, 2012, 2, 15-18 OJIM

http://dx.doi.org/10.4236/ojim.2012.21004 Published Online March 2012 (http://www.SciRP.org/journal/ojim/)

Unusual spontaneous improvement in Asian variant of

intravascular large B-cell lymphoma

Takashi Ninomiya1,2*, Toru Nakamura2, Nobuharu Fujii1, Akio Hiraki1, Shigeki Umemura2,

Hiromichi Yamane2, Atsuko Shirakawa3, Haruhito Kamei2

1Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan

2Department of Medicine, Sumitomo-Besshi Hospital, Niihama, Japan

3Department of Pathology, Sumitomo-Besshi Hospital, Niihama, Japan

Email: *[email protected]

Received 23 January 2012; revised 15 February 2012; accepted 29 February 2012

ABSTRACT

The clinical course of the Asian variant of intravas-

cular large B-cell lymphoma (AIVL) is generally very

aggressive. We describe a case of AIVL demonstrat-

ing an unusual clinical course, with spontaneous im-

provement. An 81-year-old man with high-grade fe-

ver and thrombocytopenia was admitted to our hos-

pital. Although we could not confirm the origin of his

symptoms, they disappeared completely without in-

tervention within 2 weeks. Three months later, how-

ever, thrombocytopenia reappeared and progressed.

Finally, he was readmitted due to a subdural hemor-

rhage with high fever and he finally died of rapidly

progressive multiple organ failure. Autopsy findings

revealed the presence of B-cell lymphoma cells in mi-

croscopic vessels of many organs as well as hemo-

phagocytosis in the bone marrow. He was diagnosed

with AIVL with an unusual indolent clinical course

with spontaneous improvement.

Keywords: Lymphoma; Intravascular Large B-Cell

Lymphoma; Spontaneous Improvement;

Hemophagocytosis

1. INTRODUCTION

Intravascular large B-cell lymphoma (IVLBCL) is a rare

subtype of extranodal diffuse large B-cell lymphoma

(DLBCL). Most Japanese cases of IVLBCL with hemo-

phagocytic syndrome have been categorized as the

“Asian variant” of IVLBCL (AIVL) [1]. The typical cli-

nical course of AIVL is very progressive and spontane-

ous improvement is extremely rare. Here, we report an

unusual indolent clinical course of AIVL demonstrating

spontaneous improvement and mimicking low-grade

lymphoma.

2. CASE REPORT

An 81-year-old man was admitted to our hospital owing

to high fever > 39˚C in August 2006. Physical examina-

tion revealed hepatosplenomegaly with no other abnor-

mal findings, such as lymph node swelling or skin rash.

Laboratory data showed pancytopenia (white blood cell

count (WBC), 2870/μL; hemoglobin (Hgb), 10.7 g/dL;

platelet count (Plt), 21,000/μL), and elevation of serum

lactate dehydrogenase (LDH, 779 IU/L), C-reactive pro-

tein (CRP, 5.0 mg/dL), and soluble interleukin-2 receptor

(sIL-2 receptor, 10,800 U/mL). The results of other se-

rological tests were within normal ranges, including liver

enzyme and ferritin test. We performed chest and ab-

dominal computed tomography (CT) (Figure 1) or mag-

netic resonance imaging of the brain; however, no evi-

dence was found for any abnormality except hepa-

tosplenomegaly. At that point, we suspected hemo-

phagocytic syndrome, due to viral infection or malignant

lymphoma, but neither malignant cells nor hemophago-

cytosis were detected after two individual aspirations and

biopsies of the bone marrow, respectively. Additionally,

Figure 1. Abdominal computed tomography (CT) at initial ad-

mission showing hepatomegaly and splenomegaly.

*Corresponding author.

OPEN ACCESS

T. Ninomiya et al. / Open Journal of Internal Medicine 2 (2012) 15-18

no abnormality was observed following gallium scinti-

graphy. Fluorodeoxyglucose-positron emission tomo-

graphy (FDG-PET) examination was not available in our

hospital. The quantitative polymerase chain reaction

(PCR) result of Epstein-Barr virus DNA in his serum was

negative (<2 × 102 copies/mL). We thought that IVLBCL

was still a possibility and considered performing a liver

biopsy. However, his fever had suddenly normalized and

his LDH and platelet levels had become normal without

therapy on day 14 after admission. Thus, we excluded

the possibility of IVLBCL and did not perform a liver

biopsy; we suspected that he had suffered from a viral

infection. Finally, he was discharged in October 2006

and was followed as an outpatient.

His fever with thrombocytopenia and elevation of

LDH levels gradually reappeared in December 2006. In

February 2007, he was readmitted to our hospital owing

to a consciousness disorder. On admission, he was diag-

nosed with acute subdural hematoma by head CT (Fig-

ure 2). His hematoma was treated conservatively and

progression was not observed; unfortunately, however,

his consciousness disorder did not improve. Eight days

after readmission, a high fever, >39˚C, appeared. He had

pleural effusions and ascites as well as hepatospleno-

megaly, without lymphadenopathy (Figure 3). A blood

examination revealed that his LDH and sIL-2 receptor

levels were substantially elevated (LDH, 1,186 IU/L;

sIL-2 receptor, 35,500 U/mL) and hyperuricemia was

also present. His hepatic and renal injuries progressed

rapidly, and he died of multiple organ failure in March

2007 (Figure 4).

Autopsy findings showed that lymphoma cells were

present in microscopic vessels and sinusoids of his lung,

myocardium, thyroid glands, adrenal glands, liver, kid-

neys, prostatic glands, pancreas, spleen, and gastrointes

Figure 2. Head CT at readmission showing right subdural

bleeding.

Figure 3. Chest and abdominal CT at 8 days after readmission

showing pleural effusion, ascites, and hepatosplenomegaly.

tinal tract (Figure 5). Additionally, hemophagocytosis

was evident in the bone marrow. Immunohistochemical

studies indicated that the phenotypes of the lymphoma

cells were positive for bcl2, CD20, and CD79a, but

negative for CD10, CD56, and CD5. Finally, he was di-

agnosed with AIVL.

3. DISCUSSION

IVLBCL is a rare subtype of extranodal DLBCL charac-

terized by massive proliferation of large tumor cells

T. Ninomiya et al. / Open Journal of Internal Medicine 2 (2012) 15-18

Figure 4. Clinical course and fluctuation of platelet and serum lactate dehydrogenase levels.

Figure 5. Pathological lung specimen: malignant lymphoma cells fill a small vessel (hematoxylin and eosin staining; magnification,

×400). Malignant lymphoma cells (immunochemical staining for CD20).

within the lumina of small-to-medium-sized vessels [2].

Highly variable symptoms, due to tumor occlusion of

microvessels in various organs, have been reported. Mu-

rase et al. reported that most Japanese cases were associ-

ated with hemophagocytic syndrome and these cases

were recognized as AIVL. They proposed diagnostic

criteria for AIVL [1,3,4] and reported a higher incidence

of hepatosplenomegaly, bone marrow invasion, and th-

rombocytopenia in AIVL. Conversely, neurological and

dermatological signs that were specific to IVLBCL in

Western countries were not common in a study of 96

Japanese IVLBCL patients [1].

In our case, B-cell lymphoma cells were evident only

in microscopic vessels and sinusoids and hemophagocy-

tosis was observed in the bone marrow. Although hepa-

tosplenomegaly was observed, lymphadenopathy was not

apparent throughout the clinical course. Because cyto-

penia of erythrocytes and platelets was evident, he was

OPEN ACCESS

T. Ninomiya et al. / Open Journal of Internal Medicine 2 (2012) 15-18

diagnosed with AIVL on the basis of Murase’s criteria

for AIVL [2-4]. Although we could not obtain histopa-

thological confirmation of malignant lymphoma or he-

mophagocytosis on the first admission, his symptoms

were suspected to be caused by AIVL.

The clinical course of AIVL is typically very aggres-

sive. However, a few reports have demonstrated an indo-

lent type of IVLBCL. Ishiko et al. reported that a 59-

year-old woman with ataxia and gait disturbance after a

3-year history of serum LDH elevation was finally diag-

nosed with IVLBCL by brain biopsy [5]. They suggested

that there are certain IVLBCL patients with brain in-

volvement who present with relatively slow progression,

similar to a low-grade lymphoma [5]. Nakao et al. re-

ported that a 62-year-old woman with slowly developing

paraplegia and a 7-month history of recto-urinary dys-

function was diagnosed with IVLBCL by autopsy [6]. In

that case, lymphoma cells were only identified in the

bone marrow and blood vessels of the cauda equina. Ad-

ditionally, Sekine et al. reported that a 71-year-old man

with respiratory failure after developing intermittent fe-

ver and a high serum LDH for 7 months was diagnosed

with IVLBCL by lung biopsy [7]. In that case, lym-

phoma cells were identified in the cauda equina and lung.

From these different lines of evidence, we suggest that

IVLBCL may have a slow progressive clinical course

when lymphoma cells are present in limited organs. Al-

though we could not show the limited lymphoma cell

involvement in a specific organ, our case might be one of

indolent AIVL similar to these previous reported cases.

In two of three previous cases, a diagnosis of IVLBCL

was established in living patients who were treated using

CHOP (cyclophosphamide, doxorubicin, vincristine, pred-

nisone) with rituximab and showed complete remission.

In the other case and in our case, the diagnosis was es-

tablished at autopsy. IVLBCL is difficult to diagnose

because patients generally show little or no tumor mass

formation and more than half of patients are diagnosed

postmortem. Recently, some reports have suggested that

a random skin biopsy may be efficacious for the early

diagnosis of IVLBCL. Asada et al. reported that early

diagnosis of IVLBCL was possible by random skin bi-

opsy and the early institution of rituximab-based chemo-

therapy induced a favorable response [8]. In our case, a

liver biopsy or random skin biopsy should have been

performed even after the high fever and thrombocyto-

penia disappeared.

In conclusion, we present a case of AIVL with an un-

usual clinical course and spontaneous improvement. We

suggest that an indolent clinical course or spontaneous

improvement does not exclude AIVL, although most

AIVL cases are aggressive and progressive. Importantly,

AIVL should be treated immediately with intensive ex-

amination for diagnosis, even though the clinical course

is apparently indolent.

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