A Rare Case of Atrial Septal Mass Secondary to Lymphoma: Case Report and Review of Literature

Abstract

The antemortem diagnosis of secondary cardiac involvement by lymphoma remains suboptimal. Prognosis is worse with delayed diagnosis as the tumor burden increases with the multicompartment participation. Chemotherapy may improve survival, but there is a risk of mortality due to treatment-related complications, such as myocardial rupture and fatal arrhythmias. Modified chemotherapy regimens may prevent such complications, but the data are limited. We report the case of a 72-year-old woman diagnosed with diffuse large B-cell lymphoma with cardiac involvement, where early diagnosis prevented cardiac complications from the disease and its treatment as well. The aim of this case report is to highlight the fact that cardiac involvement in lymphoma is frequent and can be easily missed, leading to complications. Treatment requires an individualized approach.

Background

Primary cardiac lymphoma (PCL), an extranodal manifestation of non-Hodgkin lymphoma, is exceptionally rare, accounting for less than 0.5% of all extranodal lymphomas. ¹ On the contrary, secondary cardiac involvement in disseminated lymphoma is relatively common but frequently goes undetected before death. Autopsy studies have reported secondary involvement by lymphoma to be approximately 9% to 24%.^2,3

Case Presentation

A 72-year-old woman with a history of gastritis was evaluated by her primary care physician for complaints of mild diffuse abdominal pain, poor appetite, night sweats, and unintentional weight loss for the last 3 months. There was a suspicion of underlying malignancy, and a computed tomography (CT) scan of the abdomen and pelvis was obtained. Compared with an ultrasound abdomen study done a year ago, the CT scan now shows new para-aortic lymphadenopathy, large bilateral adrenal mass, and infiltrating soft tissue involving the right kidney with subcapsular involvement. It was followed up with a positron emission tomography (PET)/CT, which showed hypermetabolic bilateral adrenal, para-aortic, and mediastinal lymphadenopathy, increased uptake in the uterine cervix, right renal hilum, pericardium, and left atrium. It appeared that the cardiac involvement was not an effect of contiguous involvement from the mediastinal mass but rather a metastatic site.

The patient presented to our facility 2 weeks later with a complaint of worsening dyspnea on exertion. She denied any infectious symptoms. She did not have any other cardiac symptoms such as chest pain, palpitation, pedal edema, orthopnea, and syncope. On presentation, she was hemodynamically stable and saturating well on room air. Laboratory work shows mild normocytic anemia (hemoglobin 9.5 g/dL), normal electrolytes, and elevated lactate dehydrogenase of 322 U/L (range: 313-618 U/L). The electrocardiography revealed normal sinus rhythm with normal intervals, no ischemic changes. The CT angiography did not reveal any pulmonary emboli, but moderate pericardial effusion was noted. Transthoracic followed by a transesophageal echocardiogram was done, which revealed moderate pericardial effusion without evidence of pericardial tamponade, large multilobed soft tissue mass involving the interatrial septum (Figures 1 and 2). It had a major extension into the left and right atrium without evidence of interference with valvular or cardiac functions. The patient underwent abdominal lymph node biopsy, which was consistent with diffuse large B-cell lymphoma (DLBCL) of germinal center origin. Fluorescence in situ hybridization showed c-MYC- and BCL2-negative and BCL6-positive rearrangement. The patient was started on R-CHOP regimen at the standard dose for 6 cycles total. Repeat pan CT done at 2 and 6 months shows progressive resolution in previously noted masses, including the atrial mass.

Figure 1.

TEE mid-esophageal view demonstrating multilobed mass involving atrial septum. [zero degree]

Figure 2.

TEE mid-esophageal view demonstrating multilobed mass involving atrial septum.

Case Discussion

Cardiac involvement in secondary lymphoma can manifest with nonspecific symptoms or even asymptomatic at times. Symptoms from cardiac metastases depend on various factors such as tumor location, size, growth rate, degree of invasion, and friability. Cardiac involvement is frequently a late-stage manifestation of disseminated lymphoma. Cardiac involvement may occur due to contiguous spread from a mediastinal mass, leading predominantly to pericardial disease, obliteration of the pericardial space, and compression and invasion of the heart. ⁴ Presentation mechanisms include obstruction of blood flow or valve function by a cardiac mass, invasion of the conduction pathways resulting in arrhythmias, invasion of the pericardium leading to pericardial effusion or tamponade, tumor embolization, and constitutional symptoms. The retrograde lymphatic spread leads to epicardial and adventitial involvement. Common symptoms include chest pain, palpitation, arrhythmia, and superior vena cava syndrome. Embolic phenomenon and hemodynamic instability have been reported as well.^5,6

Diagnosis requires an individualized multimodal approach. Transthoracic echocardiography is the first-line diagnostic tool, but transesophageal echocardiography offers higher sensitivity in detecting lymphomatous involvement (97% vs 75.9%, respectively). ⁷ The PET/CT is superior to each modality alone and simultaneously provides anatomical and functional imaging. However, the PET/CT may have limited application in evaluating diseases with low FDG uptake, such as primary cutaneous anaplastic large T-cell lymphoma and extranodal marginal zone lymphoma. ⁸ Cardiac magnetic resonance imaging has advantage in terms of superior tissue characterization and is highly sensitive in detecting tumor infiltration. Tissue biopsy is crucial for establishing a diagnosis. In patients with secondary cardiac involvement, tissue biopsy can be obtained from the most accessible lymph node. If PCL is suspected, examining cytological samples from pleural or pericardial fluid can detect monoclonal lymphocytes. Invasive diagnostic procedures, such as cardiac catheterization with echocardiography-guided transvenous biopsy, may be considered in certain cases. ⁹

Currently, there are no standardized treatment guidelines for cardiac lymphoma. Most anecdotal data suggest that cardiac lymphoma (primary or secondary) should be considered a systemic disease and should be treated systemically. ¹⁰ In general, chemotherapy is the primary treatment approach for managing cardiac involvement from various origins and should be tailored based on the individual’s condition and comorbidities. The extent of cardiac involvement may predispose to treatment-related complications such as tumor lysis, septal and ventricular rupture from rapid tumor destruction, severe heart failure, and ventricular fibrillation and require close monitoring and multiple adjustments to treatment plans. ¹¹

The DLBCL is often extremely sensitive to the R-CHOP regimen. ¹² Various modified regimens have been described in the literature to reduce the risk of complications, but there is no consensus. Al-Mehisen et al ¹² described a case of PCL with right atrial mass, which was treated with 50% dose-reduced CHOP. Dawson et al ¹³ managed a case involving a lymphomatous mass in the right atrioventricular region by administering cyclophosphamide and Adriamycin at a reduced dosage of 50%, aiming to minimize the risk of sudden death associated with rapid tumor regression. Shah and Shemisa ¹¹ pretreated their patient with DLBCL-related atrial mass causing severe tricuspid stenosis with rituximab and prednisone for 10 days, followed by low-dose R-CHOP that was eventually escalated to the full-dose R-CHOP regimen. Other possible regimens such as DA-EPOCH (a R-CHOP-based regimen with dose-adjusted etoposide), R-COMP (R-CHOP with nonpegylated liposomal doxorubicin replacing doxorubicin), and R-CEOP (doxorubicin replaced with etoposide in R-CHOP) used for low cardiac toxicities have an advantage over the R-CHOP regimen. ¹⁴ Radiotherapy is effective against cardiac lymphoma but is usually reserved for cases resistant to chemotherapy, due to potential cardiovascular side effects. ¹⁵

Conclusion

The DLBCL with cardiac involvement carries a grim prognosis, with a survival rate of only 10% over 9 to 12 months if left untreated. ¹⁶ The diagnosis is often delayed, which leads to more complications from the disease itself and treatment as well. Our case highlights the importance of early diagnosis and management to improve survival outcomes. In our case, the patient has a very aggressive lymphoma with diffuse involvement throughout the body, including cardiac. As the tumor was detected early in the course of the disease while it was small and before extensive myocardial infiltration occurred, it allowed us to treat the patient with a full dose of chemotherapy, which led to a better outcome. Clinicians should maintain a high level of suspicion to diagnose such asymptomatic cases. Extensive research is warranted to formulate treatment protocols for cardiac lymphoma to prevent complications from the chemotherapy regimen.