Shinshu M ed J, 59 ⑶ :177〜183, 2011

Successful Treatment of Cardiac Diﬀuse Large B‑cell Lymphoma:
A Report of Two Cases
Setsuo KUMAZAKI , Atsushi IZAWA ＊, Masatoshi MINAMISAWA , Fumihiro ISHIDA
Kenji SANO , Takeshi UEHARA , Hiroki KASAI , Takeshi TOMITA
Yusuke MIYASHITA , Jun KOYAMA and Uichi IKEDA
1） Department of Medicine, Cardiovascular Medicine, Shinshu University School of Medicine
2） Department of Medicine, Hematology, Shinshu University School of Medicine
3） Department of Pathology, Shinshu University School of Medicine

Cardiac lymphoma is a rare neoplasm of the heart,deﬁned as an extranodal lymphoma exclusively locatedin the heart and/or pericardium.M ultiple imaging modalities may help to diagnose cardiac tumors;however,pathological diagnosis is diﬃcult because of the limited approaches for obtaining tissue samples.This report
describes two cases of prompt histological diagnosis of cardiac lymphoma as diﬀuse large B‑cell type and theirsuccessful treatment with chemotherapy. Immunohistochemical analyses revealed one case as CD5‑positive
and the other as CD5‑negative lymphoma.This report highlights the necessityof histological diagnosis and theimportance of clinicopathological characterization of cardiac lymphoma.Shinshu Med J 59 : 177 ―183, 2011
(Received for publication January 7, 2011;accepted in revised form February 16, 2011)
Key words:malignant lymphoma, cardiac tumor, chemotherapy, pathology

Introduction
Cardiac lymphoma is described as a lymphomawith 6 courses of standard chemotherapy. The
importance of prompt pathological diagnosis andimmunophenotyping is highlighted in this report.

involving only the heart and/or the pericardium,orCase Reports

with the main bulk of the tumor localized intrapericardially. It is a very rare disease in immuno-Case 1

competent patients,estimated to account for 1‑2%

A 58‑year‑old man presented with a history ofof primary cardiac tumors and for 0.5% of non‑low‑grade fever, general fatigue, and palpitation

Hodgkin lymphoma cases; cardiac metastases ofsince 2 months before admission. Transthoracic

malignant lymphoma are more common with an

echocardiography indicated the presence of anincidence of 9 ‑24% . Here, the authors report twoabnormal mass at the posterior wall of the leftcases of cardiac lymphoma with representative

ventricle and atrium, and the patient was referred

images of the tumor. Tissue biopsy specimens

to our hospital. On admission, the patientʼs bodyrevealed both cases as diﬀuse large B‑celltemperature was 36.8 ℃, and blood pressure waslymphoma (DLBCL), and immunohistochemical

132/88 mmHg. Physical examinations were normal

analyses for CD5 expression demonstrated that caseand no swelling of the superﬁcial lymph nodes was

1 was CD5‑positive,whereas case 2 was CD5‑nega-observed. Standard laboratory examinations dis-tive. The two patients were successfully treatedclosed no abnormalities other than elevations inbrain natriuretic peptide (147.6 pg/mL), C‑reactive

Corresponding author:Atsushi Izawa
Department of M edicine, Cardiovascular M edicine,protein (6.79 mg/dL),and soluble interleukin‑2 rece-

Shinshu University School of M edicine, 3‑1‑1 Asahi,ptor (sIL‑2R,1,498 U/mL)levels.The patient tested

M atsumoto‑city, Nagano‑prefecture 390‑8621, Japan

negative for human immunodeﬁciency virus infec-No. 3, 2011177

Kumazaki.Izawa.Minamisawa et al.

Fig.1 Images of transesophageal echocardiogram (A) and enhanced CT scan (B) showing bulky, immobile, broad‑based mass involving posterior wall of the left myocardium (Case 1). The surface protruded partly into the left
atrium.

tion. The cardiothoracic ratio was 52% with nodoxorubicin, vincristine, and prednisone combined

abnormalities on the chest radiograph. Electrocar-with rituximab (R ‑CHOP), and successfully

diography showed normal sinus rhythm at 99 bpm.

achieved complete remission for 20 months after theTransesophageal echocardiography demonstratedend of 6 courses of the chemotherapy.

an abnormal mass echo involving the posterior wall

Case 2of the left ventricle and atrium (Fig. 1A). The sur-A 63‑year‑old man presented with a 2‑monthface of the tumor partially protruded and evolved

history of low‑grade non‑speciﬁc fever with eleva-

into the left atrium.

tion of serum C‑reactive protein levels.The patient

A CT scan revealed heterogeneous enhancement

developed dyspnea on eﬀort and had pretibialof the tumor (Fig. 1B), and cardiac M R showededema with weight gain of 10 kg over 2 months;heheterogeneous intensity (Fig. 2A). An enhanced

was referred to our hospital with an echocardiogra-uptake of gallium‑67 citrate was observed at thephic diagnosis of a space‑occupying lesion in thecardiac lesion with no other signiﬁcant uptake (Fig.

right atrium. On physical examination, blood pres-3A). Left ventricular endomyocardial biopsy failed

sure was 96/69 mmHg and the jugular vein wasto obtain tissue samples;surgical open biopsy wasmarkedly dilated.Chest auscultation revealed bilat-

therefore performed to conﬁrm the pathologicaleral coarse crackles, while the heart murmur wasdiagnosis. Histopathological and immunohisto-

not signiﬁcant.Enlargement of the liver and marked

chemical analyses revealed DLBCL (Fig. 3B, left)

pitting edema suggested right‑sided heart failure.

with positive staining for CD20 and M UM1, but

Laboratory examinations revealed elevations in

negative for CD3, CD10, and CD5 (Fig. 3B, right).

lactate dehydrogenase (526 IU/L), ferritin (758 ng/The patient was treated with cyclophosphamide,mL), brain natriuretic peptide (513.5 pg/mL), C‑

178

Shinshu M ed J Vol. 59

Successful treatment of cardiac diﬀuse large B‑cell lymphoma :A report of two cases

Fig.2 Cardiac MR images of case 1 before(A)and after (B)a course of R‑CHOP chemotherapy showing a signiﬁcantreduction in tumor size.

reactive protein (6.54 mg/dL), and sIL‑2R (6,999 U/and BCL6.

mL) levels. The patient developed hepatorenal

The patient was treated with R‑CHOP chemo-insuﬃciency;none of the ﬁndings suggested humantherapy, and after 3 courses, the tumor had de-immunodeﬁciency virus infection. Chest radiogra-

creased in size,right heart failure had disappeared,

physhowed an increased cardiothoracic ratio (57%)

and the level of sIL‑2R had decreased to 612 U/mL.

with bilateral lung congestion.Electrocardiography

A residual tumor was observed predominantly

showed sinus tachycardia at 105 bpm with rightin the pericardial fat, indicating the origin ofbundle‑branch block. Transesophageal echocardio-

the tumor (Fig. 4C). At present, the patient hasgraphy conﬁrmed a large solid tumor in the rightremained in complete remission for 10 months withcardiac cavity, which almost completely occupied

no symptoms after the end of 6 courses of thethe right atrium and hampered the blood ﬂow acrosschemotherapy.

the tricuspid valve (Fig.4A).CT scan (Fig.4B)and
MR images disclosed the bulk of the cardiac tumor

Discussion

to have heterogeneous enhancement. An enhanced

The most common histological type of cardiac

uptake of gallium‑67 citrate was observed in thelymphoma, accounting for over 90% of cases, isarea consistent with the cardiac tumor (Fig.5A).InDLBCL . Rare diagnoses include T‑cell lym-addition, increased uptake in the left supra-phoma ,Burkittʼs lymphoma ,anaplastic large‑cellclavicular lymph node was noted ;this provided thelymphoma , and primary eﬀusion lymphoma ofopportunity to obtain tissue samples. Histopath-

the pericardium. Cardiac lymphoma is locatedological examination of the left supraclavicularpredominantly in the right atrium and right ventri-

lymph node conﬁrmed the diagnosis as DLBCL (Fig.

cle and less often in the left atrium and left ventri-5B);tumor cells were positive for CD20 (Fig. 5C),

cle. Thus, the presentation of cardiac lymphoma at

CD5 (Fig. 5D), and MUM 1 but negative for CD10

the left posterior wall as shown in case 1 is remark-No. 3, 2011179

Kumazaki.Izawa.Minamisawa et al.

ＡＢ

Fig.3 Gallium‑67 scintigram (A) showing an enhanced uptake in the left posterior segment of the heart, which isconsistent with the tumor mass.Surgical tissue biopsy specimens (B)showing diﬀuse large lymphoma cells (left)
with negative immunostaining for CD5 (right). Scale bars, 50μm.

ably rare, whereas the extension onto the pericar-

rituximab to the CHOP regimen (R ‑CHOP)

dial surfaces is typical. A rare case of malignant

increases the complete‑response rate and prolongs

lymphoma arising in a large left atrial myxoma has

event‑free and overall survival in 60‑# to 80‑year‑

also been reported .

old patients with DLBCL . At two years after

Common symptoms of cardiac lymphoma include

chemotherapy,70 percent of patients treated with R‑

chest pain, low‑grade fever, shortness of breath,

CHOP were alive as compared with 57 percent ofpalpitations, and syncope. Clinical presentations

those treated with CHOP alone ; therefore, R‑

may depend on the location of the tumor and vary

CHOP is currently the ﬁrst‑line chemotherapy for

as follows:congestive heart failure (mostly right‑

DLBCL, especially accompanied with CD20 expres-sided as shown in case 2),pericardial and/or pleuralsion .Since the tissue samples were CD20‑positive,

eﬀusion, conduction disturbances, and arrhyth-the patients in this report were treated with R‑

mia . It has been established that the addition ofCHOP chemotherapy based on the standard regi-180

Shinshu M ed J Vol. 59

Successful treatment of cardiac diﬀuse large B‑cell lymphoma :A report of two cases

Fig.4 Images of case 2 before (A and B)
and after (C) chemotherapy. Transesophageal echocardiogram (A)showing the right atrium almost obliterated by a large intracavitary
mass (arrows).A cardiac CT scan (B,upper) and a M R image (B, lower)
showing a large tumor mass (arrows)
with heterogeneous enhancement andbilateral pleural eﬀusion. Involvement of the right atrium, the rightventricle, and the tricuspid valve wassigniﬁcantly reduced after 3 coursesof R‑CHOP chemotherapy (C).

men for focal DLBCL (stage Ⅰ and Ⅱ). Radiation

except in the case of primary eﬀusion lymphoma oftherapy protocols for cardiac lymphoma have not

the pericardium

been established because of the risk of unexpected

is essential for successful treatment ;therefore,anlocal tissue injuries.The ﬁrst course treatment wasopen surgical biopsy is sometimes necessary as

administered carefully,because the patients were at

performed in case 1 in this report.

. Prompt histological diagnosis

risk of death secondary to tissue necrosis causing

The importance of CD5 expression has been high-pulmonary tumor embolisms or cardiac rupture .

lighted in the World Health Organization

The diagnosis of cardiac lymphoma is often

classiﬁcation of tumors of lymphoid tissues (2008)

diﬃcult, owing to its rarity, nonspeciﬁc clinicaland in the National Comprehensive Cancer Net-

presentation,and the limited opportunities for non‑work practice guidelines for non ‑Hodgkinʼsinvasive tumor biopsy. In addition, identiﬁcation oflymphomas .Clinically,CD5‑positive DLBCL had alymphoma cells from pericardial ﬂuid is rare,poor prognosis and higher staging grades with aNo. 3, 2011

181

Kumazaki.Izawa.Minamisawa et al.

ＡＢ

Ｃ

Ｄ

Fig.5 Gallium‑67 scintigram of case 2 (A) demonstrating enhanced uptakes in the right‑sided heart and the supraclavicular lymph node. Tissue sections of the supraclavicular lymph node showing diﬀuse large lymphoma cells(B)with positive immunostaining for CD20 (C)and also positive for CD5 (D). Scale bars, 50μm.

greater number of extranodal sites .In addition,apositive cardiac DLBCL with the tumor chromo-

recent report has demonstrated that the eﬀect of R‑

some showing t (8; 14)(q24; q32) and c‑myc re-

CHOP chemotherapy on CD5‑negative DLBCL isarrangement . Exploring the importance of CD5

signiﬁcant, but this is not true for the CD5‑positiveexpression and/or cytogenetic analyses are essen-group, i.e., 2 year overall survival was signiﬁcantly

tial for a new clinicopathological characterization

poorer in CD5‑positive patients as compared withof cardiac lymphoma.

that of CD5‑negative patients (45% versus 91%) .
Although R‑CHOP chemotherapy proved eﬀectiveConclusion

in both the CD5‑positive and CD5‑negative patients

The present cases are didactic for the following

in this report, further investigation is required topoints:(1)a prompt histological diagnosis is essen-

evaluate the impact of CD5 expression on the treat-tial for successful treatment ; therefore, surgicalment eﬀectiveness and the prognosis of patients

open biopsy is valuable and is sometimes necessarywith primary cardiac DLBCL. M ore importantly,

to obtain the tissue samples;and (2)the diagnostic

the eﬀect of rituximab combined with chemother-

and/or prognostic value of the presence or absence

apy is still controversial in patients with CD5‑posi-of CD5 expression needs to be elucidated in detail.

tive DLBCL.

The prognosis of primary cardiac lymphoma has

Acknowledgement

not been fully established and may also depend on

The authors wish to thank Dr. Mayumi Ueno,

the proﬁling of gene expression. In fact, poor prog-

Department of Hematology, Nagano Red Cross

nosis have been reported for patients with CD5‑Hospital, for her invaluable advice.

182

Shinshu M ed J Vol. 59

Successful treatment of cardiac diﬀuse large B‑cell lymphoma :A report of two cases

References
1) M iguel CE, Bestetti RB :Primary cardiac lymphoma. Int J Cardiol (Epub ahead of print)20102) Giunta R,Cravero RG,Granata G,Sellitto A,Romano C,De Fanis U,Foccillo G,De Capite C,Santini M ,RossielloL, Rossiello R, Lucivero G :Primary cardiac T‑cell lymphoma. Ann Hematol 83:450‑454, 20043) Peng CF,Tauras J,Tong T,Taub C :A rare case of Burkittʼs lymphoma presenting as a mediastinal and cardiac
mass. Clin Cardiol 32:E88, 20094) Punnoose LR, Roh JD, Hu S, Udell JA, Wagle N, Kirshenbaum JM, Lacasce AS : Cardiac presentation ofanaplastic large‑cell lymphoma. J Clin Oncol 28:e314‑316, 20105) Dimitrova KR, Hoﬀman DM, Geller CM , Thiagarjah P, M aster J, Berger M , Tranbaugh RF :Malignant B‑celllymphoma arising in a large, left atrial myxoma. Ann Thorac Surg 89 :626‑629, 2010
6) White RW, Hirst NA, Edward S, Nair UR : Plasmacytoid lymphoma within a left atrial myxoma : a rare
coincidental dual pathology. Interact Cardiovasc Thorac Surg 10:140‑141, 2010
7) Patel J,M elly L,Sheppard M N :Primary cardiac lymphoma :B‑and T‑cell cases at a specialist UK centre.AnnOncol 21:1041‑1045, 20108) Coiﬃer B,Lepage E,Briere J,Herbrecht R,Tilly H,Bouabdallah R,Morel P,Van Den Neste E,Salls G,GaulardP,Reyes F,Lederlin P,Gisselbrecht C :CHOP chemotherapy plus rituximab compared with CHOP alone in elderly
patients with diﬀuse large‑B‑cell lymphoma. N Engl J M ed 346:235‑242, 2002
9) Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Byrd JC, Czuczman M S, Fayad L, Forero A, Glenn M J,Gockerman JP,Gordon LI,Harris NL,Hoppe RT,Horwitz SM,Kaminski M S,Kim YH,Lacasce AS,M ughal TI,
Nademanee A, Porcu P, Press O, Prosnitz L, Reddy N, Smith M R, Sokol L, Swinnen L, Vose JM , Wierda WG,Yahalom J,Yunus F :NCCN Clinical Practice Guidelines in Oncology:non‑Hodgkinʼs lymphomas.J Natl Compr
Canc Netw 8:288‑334, 2010
10) Fujisawa S,Tanioka F,Matsuoka T,Ozawa T :CD5＋ diﬀuse large B‑cell lymphoma with c‑myc/IgH rearrangement presenting as primary eﬀusion lymphoma. Int J Hematol 81:315‑318, 2005
11) Chen YB, Rahemtullah A, Hochberg E :Primary eﬀusion lymphoma. Oncologist 12:569 ‑576, 2007
12) Yamaguchi M,Seto M,Okamoto M ,Ichinohasama R,Nakamura N,Yoshino T,Suzumiya J,Murase T,M iura I,Akasaka T, Tamaru J,Suzuki R,Kagami Y,Hirano M ,M orishima Y,Ueda R,Shiku H,Nakamura S :De novo
CD5＋ diﬀuse large B‑cell lymphoma :a clinicopathologic study of 109 patients. Blood 99 :815‑821, 200213) Ennishi D, Takeuchi K, Yokoyama M , Asai H, M ishima Y, Terui Y, Takahashi S, Komatsu H, Ikeda K,Yamaguchi M, Suzuki R, Tanimoto M , Hatake K : CD5 expression is potentially predictive of poor outcome
among biomarkers in patients with diﬀuse large B‑cell lymphoma receiving rituximab plus CHOP therapy. AnnOncol 19 :1921‑1926, 200814) Hyo R,Tomita N,Takeuchi K,Aoshima T,Fujita A,Kuwabara H,Hashimoto C,Takemura S,Taguchi J,SakaiR,Fujita H,Fujisawa S,Ogawa K,M otomura S,Suzuki R,Ishigatsubo Y :The therapeutic eﬀect of rituximab on
CD5‑positive and CD5‑negative diﬀuse large B‑cell lymphoma. Hematol Oncol 28:27‑32, 201015) M iyazaki K,Yamaguchi M,Suzuki R,Kobayashi Y,Maeshima AM,Niitsu N,Ennishi D,Tamaru JI,Ishizawa K,Kashimura M,Kagami Y,Sunami K,Yamane H,Nishikori M ,Kosugi H,Yujiri T,Hyo R,Katayama N,Kinoshita
T, Nakamura S :CD5‑positive diﬀuse large B‑cell lymphoma :a retrospective study in 337 patients treated bychemotherapy with or without rituximab. Ann Oncol (Epub ahead of print)201116) Takai K,Sanada M,Hirose Y,Shibuya H :Diﬀuse large B‑cell lymphoma mainly involving the heart and showingt (8;14)(q24;q32)with c‑myc rearrangement. Rinsho Ketsueki 38:757‑762, 1997

（2011. 1. 7 received ;2011. 2.16 accepted）

No. 3, 2011183