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Case Report

An Unusual Cause of New-onset Atrial Flutter:


Primary Cardiac Lymphoma
Don Hayes, Jr.,

MD,

Darla K. Liles,

MD,

and Vincent L. Sorrell,

Abstract: Primary cardiac lymphoma is a rare disease with a high


mortality rate due to the advanced stage of myocardial involvement
at presentation. The diagnosis is extremely difficult to make because
of the rarity of the disease, variability of clinical manifestations,
limited noninvasive diagnostic techniques available, and difficulties
and/or delays in the use of invasive measures. The incidence of the
disease is increasing, especially among immunocompromised patients,
with those suffering from acquired immunodeficiency syndrome accounting for the greatest increase. We report the case of an immunocompetent 76-year-old black woman who presented with near-syncopal
episodes. Transthoracic echocardiogram revealed a right atrial mass.
Surgical resection was performed, and a diagnosis of large B-cell nonHodgkins lymphoma was made. Primary cardiac lymphoma should be
considered in any patient with a cardiac mass. Prompt diagnosis and
treatment of primary cardiac lymphoma is imperative for survival.
Key Words: atrial flutter, B cell, cardiac neoplasm, echocardiography, lymphoma, primary cardiac lymphoma, transesophageal

alignant neoplasms rarely occur in the heart,1 8 and


primary tumors of pericardial and myocardial origin
are even more uncommon.1,7 In autopsy series, the incidence
of primary cardiac tumors varies between 0.0017% and
0.28%.6 Among 533 cases of primary tumors or cysts of the
heart and pericardium reviewed by the Armed Forces Institute of Pathology, 60% were benign tumors, 17% were cysts,
and 23% were malignant tumors.6 Tumors metastatic to the
heart and pericardium are 20 to 30 times more common than
primary lesions, because 10 to 20% of patients with known
malignancy have secondary involvement at autopsy.9,10
Primary cardiac lymphoma (PCL) is defined as nonHodgkins lymphoma (NHL) involving only the heart and/or

From the Sections of General Internal Medicine, Hematology/Oncology, and


Cardiology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC.
Reprint requests to Vincent L. Sorrell, MD, FACC, FACP, FASE, Department
of Medicine, University of Arizona College of Medicine, Arizona Health
Sciences Center, 6th Floor, Room 6334, Box 210201, 1501 N. Campbell
Avenue, Tucson, AZ 85724-5035. Email: vsorrell@email.arizona.edu
Accepted May 6, 2002.
Copyright 2003 by The Southern Medical Association
0038-4348/03/9608-0799

Southern Medical Journal Volume 96, Number 8, August 2003

MD

the pericardium, as described by McAllister and Fenoglio.6 Few


cases of PCL meeting this criterion have been reported.1125
Cardiac involvement with disseminated NHL has been reported
in approximately 20% of autopsy patients;4,5,23,26 however, PCL
is a rare malignancy and is seldom recognized before death.17,27
Early and accurate diagnosis is of the highest importance
in initiating appropriate therapy to prolong survival. Diagnosis of cardiac tumors has been facilitated by the use of modern imaging, but histologic diagnosis is required, and access
to the tumor is often difficult.

Case Report
An immunocompetent, 76-year-old black woman
presented to the emergency department of a tertiary care
facility with a 1-week history of intermittent dizziness,
lightheadedness, and diaphoresis. She denied any other
associated symptoms of shortness of breath, chest pain,
orthopnea, paroxysmal nocturnal dyspnea, palpitations,
or pedal edema. Her only other medical problem was
glaucoma. Upon admission, the only significant finding
at physical examination was an irregular heartbeat, with
a heart rate of 100 beats/min. An electrocardiogram (ECG)
was performed, which confirmed atrial flutter with variable
atrioventricular (AV) block with left-axis deviation. The
initial laboratory workup was unremarkable, showing
(continued next page)

Key Points
Primary cardiac lymphoma remains difficult to diagnose, and patient prognosis is poor.
The incidence of the disease is increasing, with immunocompromised patients and patients with acquired immunodeficiency syndrome accounting for most of the
increase.
Primary cardiac lymphoma should be considered in any
patient who has a cardiac mass and/or refractory pericardial effusion of undetermined cause, with the highest
suspicion raised in patients with a history of immunosuppression or acquired immunodeficiency syndrome.

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Hayes, Liles, and Sorrell Atrial Flutter in Primary Cardiac Lymphoma

(Case Report continued from previous page)

negative levels of cardiac enzymes. Two-view chest x-ray


films showed cardiomegaly with slightly prominent pulmonary vessels in the upper lobe, suggesting mild pulmonary venous hypertension, as well as a mild right basilar
atelectasis and a small right pleural effusion.
Transthoracic echocardiography (TTE) was performed
as part of the evaluation for atrial flutter and revealed a
large, mobile mass in the right atrium, measuring 4 4.5
cm and extending into the tricuspid valve and the right
ventricle. There was normal left ventricular systolic function, with hyperdynamic contractility and an estimated ejection fraction of more than 70%. Transesophageal echocardiography (TEE) confirmed the presence of a right atrial
mass noted to be predominantly in the right atrial cavity that
measured 5 3 cm. It was highly mobile and appeared to
enter through the coronary sinus, which was markedly dilated
and nearly completely obstructed. The mass prolapsed within
the right atrial cavity across the tricuspid valve (Fig. 1) and
partially impaired both the tricuspid valve and the right ventricular filling. There were two additional masses noted on
TEE: the larger one within the right atrial appendage measured 2.2 1.5 cm; the smaller one at the base of the left
atrial appendage measured 0.5 0.6 cm. A mural thrombus
was identified in the left atrial cavity as well. The pulmonary
artery was normal, without significant mass or enlargement.
The superior vena cava, pulmonary vein, and inferior vena
cava appeared uninvolved by this mass. Concentric left ventricular hypertrophy was seen, and left ventricular systolic
function was well preserved, with an estimated ejection fraction of 70%. There was trivial valvular regurgitation throughout, with mild tricuspid-valve obstruction seen on color flow
Doppler imaging.
Computed tomography (CT) of the chest (Fig. 2) with
oral and intravenous contrast suggested that the cardiac
mass was enveloping much of the left atrium and project-

ing into the right atrium and right ventricle, as well as


extending along the superior aspect of the left ventricle. No
other potential tumors were identified. CT of the abdomen
and pelvis with oral and intravenous contrast showed negative for disease, and the CT of the head without contrast
revealed only changes of chronic microvascular ischemia
in the periventricular white matter. The patient underwent
cardiac catheterization; no significant coronary artery disease was found, but there was a mild increase in left ventricular end-diastolic pressures, with evidence of a vascularized right atrial mass.
The patient was offered surgical removal of the mass
and debulking of the tumor in hopes of preventing syncope
or even sudden death related to tricuspid-valve obstruction.
She underwent a median sternotomy without complication.
Five tissue specimens were obtained during the surgical
procedure and were sent for pathologic evaluation; specimens included the right atrial mass, a pericardial lymph
node, a right atrial-wall clot, a left atrial-wall clot, and a
sample of the pericardium. The margins of resection were
positive for tumor, suggesting that at least microscopic
disease was left behind. The gross specimen of the right
atrial mass measured 4.8 4.8 2.8 cm and weighed
24 g. It was soft, nodular, red to pink-tan, and irregularly
shaped. Examination of frozen section showed that the
specimen from the right atrium was composed of large,
dyshesive cells with variable quantities of pale cytoplasm
and areas of necrosis. There were scattered, multinucleated
cells with generally round nuclei, many of which had prominent nucleoli and frequent mitotic figures. A preliminary
diagnosis of poorly differentiated malignancy was made,
with the pathologist favoring a diagnosis of large B-cell
lymphoma. Definitive diagnosis was made by immunohistochemical techniques and flow cytometry. The neoplastic
(continued next page)

Fig. 1 Two-dimensional transesophageal echocardiogram in a modified 4-chamber view showing the right atrial mass in (A) systole
and (B) diastole. LA, left atrium; RA, right atrium.

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2003 Southern Medical Association

Case Report

(Case Report continued from previous page)

cells were reactive with antibodies directed against leukocyte common antigen and had spotty reactivity with
L26 (CD20), which is a B-cell marker. Flow cytometry
revealed characteristics of large B-cell lymphoma of follicular center cell origin. The final diagnosis of the four
other specimens were a pericardial fibrotic lymph node,
a right atrial-wall fibrin clot, a left atrial-wall fibrin clot
that had a layer of malignant cells focally on the periphery similar to those in the right atrial mass, and pericardial fibrous and adipose tissue without malignancy.
Postoperatively, the patient required inotropic support for 4 days. She had intermittent episodes of AV
dissociation with first degree AV block. She was atrially
paced initially, with removal of the pacing wires on the
eighth postoperative day. She remained in sinus rhythm
from that point on until she was discharged 3 days later.
Radionuclide angiography was performed as part of the
baseline protocol in preparation for chemotherapy and revealed normal biventricular systolic function with a left
ventricular ejection fraction of 66%. A long-term, indwelling, right upper central line was placed for chemotherapy
infusion. She was treated with the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy regimen and tolerated it well initially. Soon after completing her second cycle of CHOP, however, she developed
neutropenic fevers. Despite receiving appropriate supportive care, she died 10 weeks after surgery due to sepsis
related to severe immunosuppression from chemotherapy.

Discussion
PCL has been identified predominantly as a B-cell lymphoma of diffuse large cell type,1 and it seems to have a
propensity to involve the right chambers of the heart.3 PCL is
extremely rare in immunocompetent patients, accounting for
1.3% of all cardiac tumors and 0.5% of all extranodal1 lymphomas.28 The incidence of the disease is increasing, primarily in immunocompromised patients, and patients with acquired immunodeficiency syndrome (AIDS) are most at
risk.3,28 It has a high mortality rate due to the advanced stage
of myocardial involvement at initial presentation.
Clinical presentation is variable, with a wide array of
symptoms that could be cardiac or noncardiac, leading to
difficulty in recognizing cardiac lymphoma.11,29 35 The initial workup should include chest x-ray, TTE, and CT. A
review of 48 published cases of PCL between 1980 and 1996
revealed that chest x-ray, TTE, and CT are standard procedures in the workup of this disease, but TEE and magnetic
resonance imaging had greater than 90% sensitivity and could
provide more information that would allow for early confirmation of suspected PCL.3 Pericardiocentesis can provide a
diagnostic cytology specimen if pericardial effusion is
Southern Medical Journal Volume 96, Number 8, August 2003

Fig. 2 Computed tomography of the chest suggesting that the


cardiac mass envelops the left atrium and projects into the right
atrium and the right ventricle.

present; pericardial effusion cytology is a diagnostic in 67%


of the cases.3 Less invasive procedures to obtain cardiac tissue for cytologic examination are available, including mediastinoscopy, endomyocardial transvenous biopsy, thoracoscopic pericardial window, and TEE-guided biopsy, but all of
these are associated with high false-negative rates.3 Thoracotomy with open biopsy was a diagnostic in all cases3 and
may be indicated to avoid treatment delay or if complications
arise. Once the diagnosis is made and confirmed with immunohistochemical studies, early systemic chemotherapy is imperative for any chance of cure.

Conclusions
PCL remains difficult to diagnosis, and the prognosis is
poor. Because of the rarity of the disease itself, the variability
of the clinical manifestations, the limited noninvasive diagnostic techniques available, and the difficulties and/or delays
in the use of invasive measures, the diagnosis of PCL is
extremely difficult to make. Fewer than 100 cases have been
reported in immunocompetent patients. The incidence of the
disease is increasing, with immunocompromised and AIDS
patients accounting for the highest number of increased reports. PCL should be considered in any patient who has a
cardiac mass and/or refractory pericardial effusion of undetermined etiology, with the highest suspicion in patients with
a history of immunosuppression or AIDS.

Acknowledgment
We thank the members of the Cardiothoracic Surgery
Division of the Brody School of Medicine for their assistance
and for the expert care that they provided in the management
of this patient.

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Hayes, Liles, and Sorrell Atrial Flutter in Primary Cardiac Lymphoma

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