A case of diffuse large B-cell lymphoma with cardiac tumor presenting tachycardia-bradycardia syndrome associated with atrial fibrillation

Abstract

We report a rare case of diffuse large B-cell lymphoma (DLBCL) presenting with both nasal and cardiac tumors. The patient was a 77-year-old man who initially visited a local clinic with a two-month history of right-sided nasal discharge and nasal obstruction. A tumor lesion was identified in the nasal cavity, and he was subsequently referred to our hospital. Blood tests revealed leukocytosis, and computed tomography demonstrated a right nasal tumor, multiple lymphadenopathies, and an irregular mass in the right atrium. A biopsy of the nasal lesion confirmed the diagnosis of DLBCL. Transthoracic echocardiography revealed a relatively immobile cardiac mass, approximately 50 mm in diameter, located in the right atrium, which was suspected to represent cardiac infiltration of lymphoma. Chemotherapy with polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone was initiated. During the clinical course, the patient exhibited tachycardic atrial fibrillation and sinus pauses lasting up to approximately six seconds, suggesting tachycardia–bradycardia syndrome. With ongoing chemotherapy, the cardiac tumor showed a marked reduction in size over time. To date, the patient has been successfully managed without pacemaker implantation. This case suggests that careful management, including close monitoring, is crucial for arrhythmias associated with cardiac involvement of malignant lymphoma.

Learning objective

We encountered a rare case of malignant lymphoma with a cardiac tumor complicated by tachycardia–bradycardia syndrome and atrial fibrillation. Tumor reduction was achieved through chemotherapy, and careful observation allowed management without pacemaker implantation. This case highlights the need for cautious and individualized clinical judgment in the management of arrhythmias associated with cardiac lymphoma.

Introduction

Cardiac tumors associated with malignant lymphoma are a rare condition and are considered poor prognostic factors [1]. Although tumor location and clinical severity vary, early and appropriate diagnosis followed by chemotherapy intervention is desirable. Here, we report a rare case of diffuse large B-cell lymphoma (DLBCL) with a cardiac tumor presenting tachycardia-bradycardia syndrome (TBS) associated with atrial fibrillation (AF), discussing the diagnostic challenges and therapeutic considerations in such cases.

Case report

The patient was a 77-year-old man who presented to a local otolaryngology clinic with a two-month history of right-sided nasal discharge and nasal obstruction. A tumorous lesion in the nasal cavity was detected, and he was referred to our hospital's department of otolaryngology for further evaluation. Blood tests performed at the outpatient clinic showed elevated values: white blood cell count 25,900/μL, lactate dehydrogenase 971 U/L, soluble interleukin-2 receptor 1790 U/mL, and C-reactive protein 14.9 mg/dL. Subsequent computed tomography (CT) imaging demonstrated a right nasal cavity tumor, multiple enlarged lymph nodes (including mediastinal, right nasal, left palatine tonsillar, and right upper internal jugular nodes), and an irregular mass in the right atrium (Fig. 1a, b). A biopsy of the nasal cavity lesion was performed under suspicion of malignant lymphoma, and pathological examination revealed CD20+, CD79a+, CD3−, CD5− DLBCL (Fig. 1c). At initial presentation, a 12‑lead electrocardiogram demonstrated sinus rhythm, with flattened P waves in leads II, III, and aVF (Fig. 2a). Transthoracic echocardiography identified a relatively immobile mass measuring approximately 50 mm in the right atrium. Left ventricular ejection fraction (LVEF) was 66%, with no left ventricular dysfunction (Fig. 1d).

Fig. 1.

(a) Paranasal sinus CT image at the outpatient visit. (b) Chest CT images (left: axial view, right: coronal view) at the outpatient visit. (c) Pathological images of a nasal tumor biopsy (upper left: HE staining, upper right: CD20 immunostaining, lower left: CD59a immunostaining, lower right: CD3 immunostaining) (d) Transthoracic echocardiographic image at the outpatient visit (right: 3D echocardiographic image). All white arrows indicate the tumor.

CT, computed tomography; HE, hematoxylin and eosin.

Fig. 2.

(a) 12‑lead ECG at the outpatient visit. (b) 12‑lead ECG on admission. (c) Telemetry ECG image during hospitalization (at the occurrence of sinus pause). (d) Limb‑lead ECG (left: after 1 cycle of chemotherapy, right: after 3 cycles of chemotherapy).

ECG, electrocardiography.

The disease was classified as stage IV-A according to the Ann Arbor staging system, and chemotherapy with polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (PV-R-CHP regimen) was initiated. During the initial hospitalization, tachycardic AF was observed (Fig. 2b), and treatment with edoxaban 60 mg and a bisoprolol 2 mg transdermal patch was initiated. However, the patient subsequently developed asymptomatic sinus pauses of approximately six seconds (Fig. 2c), leading to a diagnosis of TBS. The bisoprolol patch was discontinued, but intermittent sinus pauses of approximately four seconds continued to occur. Pacemaker implantation was considered in the event of symptomatic episodes such as syncope. However, it was deemed technically challenging because the intracardiac mass occupied most of the right atrium. As the patient remained asymptomatic, a conservative approach with careful monitoring was chosen. After the first cycle of chemotherapy, the cardiac mass had reduced to approximately 25 mm, and after the third cycle, to under 10 mm—indicating a marked reduction in size (Fig. 3). During the course of treatment, the P waves in leads I, III, and aVF returned to a clearly positive deflection (Fig. 2d). No significant electrolyte abnormalities were observed before or after treatment, with serum potassium levels remaining within the range of 4.2–5.2 mmol/L. The frequency of TBS episodes also decreased. To date, the patient has completed six cycles of chemotherapy without experiencing syncope or cardiac events, and he continues to be followed closely with careful observation.

Fig. 3.

Serial changes in cardiac tumor size on transthoracic echocardiography. (a) Before chemotherapy. (b) After 1 cycle of chemotherapy. (c) After 3 cycles of chemotherapy. All white arrows indicate the tumor.

Discussion

We herein report a case of DLBCL presenting with TBS associated with AF, which we consider clinically noteworthy for three reasons. First, TBS is relatively rare as a complication of cardiac lymphoma. Second, the sinoatrial node dysfunction was reversible and showed improvement in parallel with the reduction of the right atrial mass following chemotherapy. Third, despite frequent sinus pauses, the patient remained asymptomatic and was ultimately managed without permanent pacemaker implantation. These findings highlight the importance of individualized arrhythmia management in patients with cardiac tumors.

Cardiac metastasis, either by tumor formation or infiltration, occurs in approximately 2.3% to 18.3% of malignant tumor cases and is more common than primary malignant cardiac tumors. Among these cardiac metastases, malignant lymphoma accounts for a notable proportion, second only to lung cancers [2]. Nevertheless, cardiac lymphoma itself remains extremely rare, representing only about 0.03% of all lymphoma cases [3]. DLBCL is the most common subtype of aggressive non-Hodgkin lymphoma (NHL), accounting for 30% to 40% of all NHL cases [4]. Although cardiac involvement is an uncommon complication of DLBCL, when present, it typically affects the right atrium, right ventricle, pericardium, or major cardiac vessels. DLBCL tends to spread hematogenously or through the lymphatic system, resulting in direct myocardial invasion or cardiac tumor formation, which is associated with a poor prognosis [2], [5].

Pathological examination of a nasal tumor in this patient revealed DLBCL. The right atrial mass was therefore considered cardiac infiltration by DLBCL. Cardiac lymphoma can lead to heart failure, pericardial effusion, and arrhythmias [6]. However, in this case, neither heart failure nor pericardial effusion was observed. The patient exhibited TBS associated with AF. After termination of AF, a maximum sinus pause of approximately 6 seconds was noted, raising concern for sinoatrial node dysfunction. CT images revealed that the tumor occupied the anterior and superior portions of the right atrium, extending to the superior vena cava–right atrial junction and the crista terminalis, suggesting possible involvement of the region encompassing the sinoatrial node. Although direct infiltration could not be confirmed, mechanical compression or local inflammation may have contributed to AF and sinus pauses. The recovery of P-wave morphology after tumor reduction supports this mechanism. Electrolyte disturbances from tumor lysis syndrome were unlikely contributors, as serum potassium, uric acid, phosphate, and calcium remained stable throughout the course of treatment. While preexisting sinoatrial node dysfunction could not be entirely excluded, the close temporal correlation between tumor reduction and arrhythmia improvement strongly suggests a tumor-related cause.

Despite frequent sinus pauses, the patient remained asymptomatic, and current guidelines did not recommend pacemaker implantation [7]. Nevertheless, careful monitoring was required due to the potential risk of syncope. It has been reported that chemotherapy improved arrhythmias associated with cardiac lymphoma, allowing for the avoidance of pacemaker implantation, and similar therapeutic effects were expected in this patient [8]. In this case, the patient could have become a candidate for permanent pacemaker implantation if symptoms had been observed. In the presence of a cardiac tumor, a leadless VVI pacemaker may represent an effective option if pacemaker implantation becomes necessary.

Chemotherapy is the mainstay for malignant lymphoma but can be cardiotoxic, especially in patients with reduced LVEF. In this case, preserved LVEF allowed safe administration of anthracyclines. The patient received PV-R-CHP, in which vincristine is replaced by polatuzumab vedotin, a regimen showing favorable outcomes for high-risk, newly diagnosed DLBCL [9]. This case involved a high-risk DLBCL patient with an International Prognostic Index score of 4. Prompt initiation of PV-R-CHP therapy resulted in gradual reduction of the right atrial tumor, confirming cardiac infiltration and emphasizing the importance of timely diagnosis and treatment [10]. Fortunately, six months after the initiation of treatment, the patient has not experienced syncope or any serious cardiac events. The frequency of TBS has decreased, allowing management without pacemaker implantation under careful follow-up. This case demonstrates the value of careful and individualized clinical judgment in managing tumor-related arrhythmias.

Patient permission/consent statement

Informed consent was obtained from the patient.

Funding sources

The authors declare that there are no funding sources.

Declaration of competing interest

The authors declare that there is no conflict of interest.

Abbreviations and acronyms

AF

atrial fibrillation

CRP

C-reactive protein

CT

Computed tomography

DLBCL

diffuse large B-cell lymphoma

ECG

electrocardiogram

IL-2

Interleukin-2

LDH

Lactate Dehydrogenase

LVEF

left ventricular ejection fraction

NHL

non-Hodgkin lymphoma

PV-R-CHP

polatuzumab vedotin + rituximab + cyclophosphamide + doxorubicin + prednisone

TBS

tachycardia–bradycardia syndrome

WBC

white blood cell count