An unusual cause of new-onset atrial flutter: primary cardiac lymphoma.

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 non-Hodgkin's 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

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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 immunodeficieney 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.

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 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 x 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) continued the presence of a right atrial mass noted to be predominantly in the right atrial cavity that measured 5 x 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 x 1.5 cm; the smaller one at the base of the left atrial appendage measured 0.5 x 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.

[FIGURE 1 OMITTED]

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 projecting 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.

[FIGURE 2 OMITTED]

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 x 4.8 x 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 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.

Malignant 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 non-Hodgkin's lymphoma (NHL) involving only the heart and/or the pericardium, as described by McAllister and Fenoglio. (6) Few cases of PCL meeting this criterion have been reported. (11-25) 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.

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 extranodal (1) 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 present: pericardial effilsion 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 cases (3) 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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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: [e-mail]

Accepted May 6, 2002.