Shinshu Med J, 65⑴：51～56, 2017

An Unusual Case of Multicentric Castleman’s Disease,
Complicated by Pleural Effusion
Shuhei Nozawa, Masanori Yasuo＊, Hiroshi Yamamoto, Mineyuki Hama
Kazunari Tateishi, Atsuhito Ushiki and Masayuki Hanaoka
First Department of Internal Medicine, Shinshu University School of Medicine

A 72-year-old female with systemic lymphadenopathy was diagnosed with multicentric Castleman’s disease(MCD), following a needle biopsy of her axillary lymph node. She experienced recurrent fever and a rash, andwas then transferred to our respiratory department. She had fever and dyspnea with consolidation and pleural
effusion on computed tomography (CT). Lung lesions are common but pleural effusion is an unusual symptom inCastleman’s disease. We administered antibacterial agents but her condition worsened. Symptoms rapidly im­
proved following administration of systemic corticosteroid, and the consolidation and pleural effusion also disap­
peared. We suggest that pleural effusion in Castleman’s disease should be considered as a differential diagnosis
for pleural effusion that is unresponsive to antibacterial treatment. Shinshu Med J 65 : 51―56, 2017
(Received for publication March 24, 2016 ; accepted in revised form October 24, 2016)
Key words : multicentric Castleman’s disease, pleural effusion, corticosteroid treatment
hyaline vascular type (HV type), which comprises

Ⅰ Introduction

90 ％ of cases, or as the plasma cell type (PC type),

Castlemanʼs disease was first described by B. Cas­or a third variant, which is a mix of HV and PC.

tleman in 19561）. This disease is a polyclonal lymph­

The HV pathologic variant is characterized by theoproliferative disorder, characterized by a tumor-​

growth of vascular endothelial cells and angioneo­

forming lymphadenopathy. The cause of the disease

genesis ; the PC variant is typified by infiltration ofis unknown, but an infectious etiology, including

plasma cells between lymphatic follicles4）. The PC

infections by hepatitis B virus (HBV), Epstein-Barr

type is generally associated with multiple lymphade­virus (EBV), human herpesvirus 8 (HHV8), or humannopathy and generalized symptoms. Many MCD cas­2）

immunodeficiency virus (HIV) , have all been sug­

es with pulmonary lesions were reported. In generalgested. Causal roles for abnormal immune responses,

the clinical features of MCD are mediastinal lymph­

including immunopathy, and aberrant cytokine pro­adenopathy, hyperplasia of bronchovascular and in­duction, have also been proposed. Clinically, cases in­terlobular septa, and cyst5）; however, pleural effu­

volving a single lymphadenopathy are defined assion is unusual.

unicentric Castleman’s disease (UCD), while those

Here we describe a case of a 72-year-old female

with multiple lymphadenopathy are defined as mul­diagnosed with MCD with pleural effusion that was3）

ticentric Castleman’s disease (MCD) . Patients withdifficult to distinguish from effusion associated with

MCD generally present with fever and multiorganpneumonia who was successfully treated with corti­

disease. Pathologically, MCD is classified as either acosteroids.

＊

Corresponding author : Masanori Yasuo
First Department of Internal Medicine, Shinshu University
School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan
E-mail : yasumasa@shinshu-u.ac.jp

No. 1, 2017

Ⅱ

Case Report

A 72-year-old Japanese woman with multiple
lymphadenopathy had been diagnosed with the PC
variant of MCD following biopsy of her axillary lymph
51

Nozawa・Yasuo・Yamamoto et al.

A

B

Fig. 1 Photomicrograph of a biopsy specimen obtained from an axillary lymph node
Scattered, variously sized, lymph node follicles (A), with plasma cell (PC) infiltration (B).
This phenotype denotes the PC variant. Hematoxylin & Eosin staining,(A) original magnification×40 ; (B) original magnification×100.

A

B

Fig. 2 Chest radiography on admission, and after corticosteroid administration
A right pleural effusion was observed (A), which was barely evident after 14 days (B).

node one year earlier at her local hospital (Fig. 1).

neutrophilia, and elevated serum IgG and IL-6 lev­Six months after the diagnosis, she developed recur­

els. A chest drainage tube was inserted into her

rent fever, and a rash but received conservative

right thoracic cavity to drain the effusion and ame­treatment (antipyretic analgesic) at that time.

liorate dyspnea. Yellow turbid fluid was drained.

She visited the hematology department in our hos­

Bacterial culture of the pleural effusion was negative

pital, and continued the conservative treatment andand the feature was exudative with neutrophils pre­follow-up of laboratory examinations. After a five-dominating (the neutrophil rate was 96% and lym­

month follow-up in the hematology department, she

phocyte was 3 ％ : Table 2). Pneumonia with pleurisy

was transferred to our respiratory department due

was therefore suspected and meropenem 1.5 g/day

to fever and dyspnea with radiographic abnormali­

was administered as treatment.

ties. The pleural effusion was observed by chest

On day 5 of the antibacterial therapy, her dyspnea

X-ray (Fig. 2A), and CT scan also revealed right-sid­

worsened and wheezing developed. Levels of C-re­ed dominant pleural effusion with consolidation (Fig.

active protein and white blood cells were elevated

3A,B). Laboratory examinations (Table. 1) revealedwith no eosinophilia. Re-examination of her pleural52

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Vol. 65MCD with pleural effusion

A

B

C

D

Fig. 3 Chest CT scan on admission and after corticosteroid administration
Mediastinal lymphadenopathies (A), and a right predomint pleural effusion (B), were apparent on admission.
After 10 days the pleural effusion had diminished (C), and after 5 months the effusion was almost gone (D).
Table 1

Laboratory data on admission

Peripheral blood
WBC
24.13
103/μ
Neu
94.0
％
Lym
4.1
％
Mo
1.3
％
Eo
0
％
Ba
0
％
RBC
385
104/μ
Hb
10.3
g/dl
Ht
33.8
％
MCV
90.1
fl
Plt
37.8
104/μ
Biochemistry
TP
8.1
mg/dl
Alb
2.2
mg/dl
AST
48
IU/l
ALT
39
IU/l
LDH
154
IU/l
ALP
422
IU/l
γGTP
62
IU/l
T-Bil
0.57
IU/l
BUN
28
IU/l
CRE
0.97
mg/dl

Na
K
Cl
Ca
CRP
IL-6
HIV
HBsAg
HCV
PCT
BNP
IgA
IgM
IgG
IgE

137
4.3
96
7.2
29.4
321
0.2
0.2
0.5
0.70
24.7
488
88
3021
234

mEq/l
mEq/l
mEq/l
mg/dl
mg/dl
pg/ml
C.O.I
C.O.I
ng/ml
ng/ml
pg/ml
mg/ml
mg/ml
mg/ml
IU/ml

(≦4)
(≦0.9)(≦0.6)(≦0.9)(0.00-0.5)(0.1-20.0)(110-410)(35-220)(870-1700)(≦173)

Arterial blood gas (O2 2 l/min)
pH
PaO2
PaCO2
HCO3

7.451
61.8
38.2
26.2

torr
torr
torr

WBC, white blood cells ; Neu, neutrophils ; Lym, lymphocytes ; Mo, mononucleosis ; Eo, eosinophils ;Ba, basophils ; RBC, red blood cells ; Hb, hemoglobin ; Ht, hematocrit ; MCV, mean cell volume ; Plt, platelets ;TP, total protein ; Alb, albumin ; AST, aspartate aminotransferase ; ALT, alanine aminotransferase ;LDH, lactate dehydrogenase ; ALP, alkaline phosphatase ; γGTP, γ-glutamyl transpeptidase ;T-Bil, total bilirubin ; BUN, blood urea nitrogen ; CRE, creatinine ; Na, sodium ; K, potassium ; Cl, chlorine ;Ca, calcium ; CRP, C-reactive protein ; IL-6, interleukin-6 ; HIV, human immunodeficiency virus ;HBsAg, hepatitis B virus surface antigen ; HCV, hepatitis C virus ; PCT, procalcitonin ; BNP, brain natriuretic
peptide ; Ig, Immunoglobulin ;PaO2, arterial oxygen pressure ; PaCO2, arterial carbon dioxide pressure ; HCO3, bicarbonate ion.
No. 1, 201753

Nozawa・Yasuo・Yamamoto et al.
Table 2

Data of pleural effusion

On admission
TP
6.3
g/dl
Alb
2.0
g/dl
LDH
467
IU/l
GLU
119
mg/dl
pH
8.0
Total cell count 13333
/μl
MONO
533
/μl
SEG
12800
/μl
Bacterial culture : negative

Day 5 after admission
TP
4.4
g/dl
Alb
1.3
g/dl
LDH
121
IU/l
GLU
125
mg/dl
pH
8.5
Total cell count 1128
/μl
MONO
677
/μl
SEG
451
/μl
Bacterial culture : negative

TP, total protein ; Alb, albumin ; LDH, lactate dehydrogenase ; Glu, glucose ;MONO mononucleosis ; SEG, segmented neutrophils.
MEPM

mPSL(mg/day)

120

40

30

40

40

35

35

P

30

30

25

25

20

20

15

15

10

10

5

5

0

0

(103/μL)
On admission(thoracentesis①) Day 5 after admission(thoracentesis②)(mg/dl)Day 14 after admission

Fig. 4 Treatment progress in this patient
Antibiotics were not effective. In contrast, corticosteroid therapy was effective for the patient’s disease.

effusion revealed predominant lymphocytes (the neu­

subsequently discharged from hospital with no

trophil rate was 39 ％ and lymphocyte was 60 ％) andsymptoms after a total of 29 days of corticosteroid

bacterial culture was negative (Table 2). Non-bacterial

treatment. The serum IL-6 levels subsequently fell

pleural effusion was confirmed twice in bacterial cul­

to 2.10 pg/ml, after another six months of corticoste­ture, therefore, corticosteroid therapy was adminis­roid treatment.

trated with methylprednisolone 120 mg/day on theassumption that the effusion was associated with

Ⅲ

Discussion

MCD. A few days after corticosteroid administration,

We here report a case of MCD with pleural effu­

her dyspnea, wheezing, and inflammatory bloodsion and its successful treatment using corticoste­

markers were dramatically improved and the pleu­

roid. Generally, the clinical manifestations of MCD

ral effusion was diminished.

are fever, multiple lymphadenopathy, anemia, hepa­

Thereafter, the corticosteroid treatment was ta­

tosplenomegaly, polyclonal hypergammaglobulinae­

pered to a dose of 30 mg/day prednisolone. The clin­

mia, and other organ pathology, but pleural effusion

ical course is illustrated in Fig. 4. The patient wasis unusual. Polyneuropathy, organomegaly, endocr­

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Vol. 65MCD with pleural effusion

inopathy, monoclonal gammopathy, and skin changes

cases will ultimately relapse as the disease progress­(POEMS) syndrome, similar to MCD, usually causees14）. In the current case, corticosteroid therapy has,

6）

pleural effusion , but this case failed to meet the cri­thus far, proven to be effective. However, the advanced

teria of a diagnosis of POEMS. To our knowledge,

age and frailty of our patient requires us to provide

there were two case reports that described MCD

a strict follow-up schedule as intervention will havewith pleural effusion. The differential cell counts into be tolerable if required.

these pleural effusions showed predominant lym­7）

It is thought that the symptoms of MCD are caused

8）

phocytes (the lymphocyte rate was 96 ％ and 70 ％by excessive IL-6 production15）-17）, which provokes

respectively). In our patient, the pleural effusion was

multiple physiologic effects. This hypothesis agrees

bilateral with predominance on the right side of thewith data showing that patients with MCD frequent­

chest (Fig. 3A-C), with the characteristic of neutro­

ly demonstrate increased serum IL-6 levels. Kawa­

phils being predominant. No previous case reports

bata et al.18） reported that serum IL-6 was elevated,

describing MCD with pleural effusion having consoli­

on average, to 21.9 pg/ml (normal value≦4.0 pg/ml),

dation are available. The improvement of consolida­

which correlated significantly with CRP levels in 21

tion was not as marked as that of pleural effusion.

cases of MCD. Similarly, the serum IL-6 level in the

From these facts, we suggest that the first neu­

current case rose to 321 pg/ml, then declined to 2.10

trophil-dominant pleural effusion was influenced

pg/ml after corticosteroid treatment. Tocilizumabby bacterial pneumonia and the second, lympho­(approved in April 2005 in Japan) is an antibody di­cyte-dominant effusion after antibacterial therapy

rected against the IL-6 receptor ; its blockade of thatwas influenced by MCD. Although we did not detect

receptor has proven to be an effective therapeutic

bacteria in the first pleural effusion, it might be thestrategy for MCD patients. Nishimoto et al.19） report­

reason for the cell fraction change in the effusion be­

ed that 28 cases of MCD improved rapidly with thefore and after the antibacterial agent (the neutrophil

administration of tocilizumab, which was well toler­

and lymphocyte rates were 96 ％ and 3 ％, to 39 ％ated. We would suggest that tocilizumab might beand 60 ％, respectively). The IL-6 levels in the pleu­

considered as a second-line therapy for the recur­ral effusion of an MCD patient are markedly higher

rence of MCD for the present case.

9）10）than serum levels

although, unfortunately in thisⅣ Conclusioncase, we did not measure the IL-6 in the effusion.
The standard therapy for MCD has not yet been

Castleman’s disease with pleural effusion is unusu­

established, but several successfully treated cases

al but it should be considered. It is important to dis­have been reported in which corticosteroids, immu­

tinguish it from other diseases and select the appro­

nosuppressive therapy, rituximab, and chemothera­

priate therapy.

11）
-13）

py were administered. However, most of these
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