Primary Cardiac Lymphoma in an Immunocompetent 71-Year-Old Man

Abstract

Isolated cardiac lymphomas are very rare, especially in immunocompetent patients. As a consequence, little is known about the best therapeutic management and about patients' outcomes in these cases. Diffuse large B-cell lymphoma is the most frequent subtype; anthracycline-based chemotherapy has been the most successful treatment. We describe the case of a primary cardiac lymphoma in an immunocompetent 71-year-old man. As of December 2015, the patient had been in clinical remission for 2 years. The most relevant literature on primary cardiac lymphoma is reported and discussed.

To date, epidemiologic data indicate that the prevalence of primary cardiac tumors (PCTs) in the general population is between 0.001% and 0.3%.¹ According to most studies, approximately 10% of PCTs are malignant.^1–7 Cardiac involvement can occur in up to 20% of patients with lymphomas, whereas primary cardiac lymphoma (PCL) is rare and accounts for 1.3% of all PCTs.⁸ In 1978, McAllister and Fenoglio⁹ defined PCL as an extranodal lymphoma involving only the heart, pericardium, or both. Later, Cairns and colleagues¹⁰ proposed to extend the definition of PCL to tumors that present small secondary lesions nearby. Currently, the clinically accepted definition of PCL is “a lymphoma presenting as cardiac disease, especially if the bulk of the tumor is intrapericardial.”¹¹

A close association exists between PCLs and immunodepression, because most reported PCL cases are in patients who are taking immunosuppressive drugs or are infected with human immunodeficiency virus (HIV). Here we describe a case of PCL occurring in an immunocompetent patient who was otherwise in good health.

Case Report

A 71-year-old man came to our attention when he presented with a 2-month history of fatigue and intense exertion-induced dyspnea. Arterial hypertension, for which he was on drug therapy, was the patient's only known medical condition. Physical examination of the patient was unremarkable. Electrocardiography (ECG) showed a complete atrioventricular block with idioventricular rhythm (45 beats/min). He was transferred to our clinical cardiology ward for further investigation and eventual pacemaker implantation.

The patient's blood count was abnormal. In particular, lymphocytes were fewer than normal (700/mm³, 9.3% of total leukocytes). Despite that, the patient was considered to be fairly immunocompetent, and his subsequent test for HIV was negative.

Transthoracic (TTE) and transesophageal (TEE) echocardiography—routine before pacemaker implantation—revealed severe pericardial effusion (3 cm posterior, 5–6 cm anterior), with right atrial collapse in diastole; yet the patient's left ventricular (LV) systolic function was normal. Some round, nodular, and variable-in-dimension echogenic masses were present in the atrioventricular sulcus and in the free wall of the right ventricle (RV). The RV had mild systolic dysfunction. The inferior vena cava appeared dilated (2.6 cm), but collapsed normally during inspiration.

We drained 230 mL of pericardial fluid. The results of cytology showed a cellular population compatible with a lymphoproliferative process. Total-body computed tomography (Fig. 1) and cardiac magnetic resonance imaging (Fig. 2) confirmed the presence of a mass in the atrioventricular sulcus of the RV, surrounding the right coronary artery and infiltrating the posterior interventricular sulcus, the left coronary sulcus, the epicardial adipose tissue, the RV inferior wall, and the LV basal posterior wall. This mass was 3 cm thick and 6 cm long from base to apex; it displayed late enhancement after gadolinium-based contrast administration, compatible with tumor. Some nodules were visible in the visceral pericardium, and the pericardial effusion was still present.

Fig. 1.

Computed tomographic scan of the thorax shows a mass in the cardiac atrioventricular sulcus (black arrow) and pericardial drainage (white arrow). Image artifacts are the consequence of pericardial drainage.

Fig. 2.

Cine magnetic resonance image (right 2-chamber long-axis view) shows a mass in the atrioventricular sulcus surrounding the right coronary artery (arrow). Pericardial effusion is also evident. Image artifacts are caused by pericardial drainage. Because of the patient's precarious clinical condition, breath-hold during image acquisition was not easily obtainable. Therefore, a low-matrix acquisition protocol was adopted, which resulted in greater acquisition speed but lower resolution.

Ao = aorta; RA = right atrium; RV = right ventricle

We successfully implanted a bicameral pacemaker. Under radioscopic and TEE guidance, 5 samples of RV myocardium were collected for biopsy. Histologic examination yielded a diagnosis of B-cell non-Hodgkin lymphoma-like cellular infiltrate (large and intermediate-to-large dimensions), compatible with diffuse large B-cell lymphoma (DLBCL). The immunophenotype was CD20⁺, CD10⁺, bcl-6^+/−, CD3m⁻, cyclin D1⁻, CD56⁻, CD34⁻, TdT⁻. Bone marrow histology produced evidence of minimal lymphoma localization, together with mild reduction of other cellular lineages; ¹⁸fluorodeoxyglucose positron emission tomography showed a significant tracer uptake, in correspondence with the cardiac lesion. Our patient's Karnofsky performance status was 80. According to the Ann Arbor staging of non-Hodgkin lymphomas, he presented with stage IV-B DLBCL.

We therefore treated our patient in accordance with the R-CHOP 21 plan, making use of liposomal doxorubicin. R-CHOP 21 provides 6 cycles of drug administration, with 3-week intervals between cycles. It consists of rituximab (375 mg/m² on day 1), cyclophosphamide (750 mg/m² on day 1), liposomal doxorubicin (50 mg/m² on day 1), vincristine (2 mg on day 1), and oral prednisone (75 mg, days 1–5). After the 3rd cycle, TTE documented a significant reduction of LV ejection fraction to 0.40. Our patient's serum troponin T determinations had always been negative. The R-CHOP^* plan was therefore converted to R-CEOP^**; that is, liposomal doxorubicin was replaced by etoposide (100 mg/m² on day 1). Thereafter, his LV ejection fraction increased to 0.53.

After the last of 6 expected cycles of chemotherapy, repeated staging showed evidence of complete clinical remission, which was maintained after 2 years of monitoring.

Discussion

The present report describes a rare case of PCL in an immunocompetent patient who was successfully treated with anthracycline-based chemotherapy. Despite the fact that it is impossible to exclude the possibility of lymphoma localization in other sites, our separate staging of images in other locations did not reveal any other detectable disease in our patient. Although PCL is not characterized by specific cardiologic signs or symptoms, the combination of ECG abnormalities, prominent involvement of the right side of the heart by heterologous tissue, and systemic symptoms (such as fatigue) hint that cardiac lymphoma should be considered in the differential diagnosis. Various imaging techniques—together with histologic analysis of the myocardium and eventually of other tissues—are necessary to confirm the diagnosis. Anthracycline-based chemotherapy is the first-line treatment for DLBCLs. Primary cardiac lymphoma presents no exception to this approach: indeed our patient's good outcome at his 2-year follow-up provides reasonable confirmation. No pathognomonic clinical signs set apart PCL. The patient can present with heart failure, pericardial effusion, chest pain, cardiac tamponade, pleural effusion, arrhythmia, superior vena cava syndrome, myocardial infarction, pulmonary embolism, or dyspnea, depending on the location and the extent of the tumor.¹²

In immunocompetent patients, primary cardiac lymphomas (of which DLBCL is the principal subtype) have rarely been reported. Our report thus confirms information already present in the literature. To our knowledge, only 23 cases of PCL in immunocompetent patients have been reported to date (Table I).^13–30 According to these reports, no patient presented with noncardiac lymphomatous localization, but, as in our patient, it was impossible to absolutely exclude noncardiac involvement in the absence of autopsic investigation, which was performed in only 2 patients^17,20 and revealed no extracardiac metastasis.

TABLE I.

Reports of Primary Cardiac Lymphomas in Immunocompetent Patients

Nine of these patients were treated with surgical excision followed by chemotherapy, and 5 of them survived at least 6 months after treatment. No evidence exists concerning the necessity of surgery as an adjunct to chemotherapy in PCL; moreover, in those 9 cases surgery was the final diagnostic step, along with excision as treatment. Therefore, it is not possible to conclude that ablative surgery leads to better results than chemotherapy alone, which is the gold-standard treatment in lymphomas at other sites.

Patients who died of lymphoma were diagnosed with a clinically advanced disease, which underscores the importance of early diagnosis. In fact, cardiologists are frequently slow to suspect such an uncommon neoplasm, especially in immunocompetent patients in whom PCL is extremely rare. The main aim of this report is to alert cardiologists to the possibility of such a diagnosis.