Diffuse Large B-Cell Lymphoma with Cardiac Metastasis: A Case Report

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for about one-third of newly diagnosed lymphoma cases globally [1]. DLBCL can arise as a primary tumor in virtually any anatomical site, with the gastrointestinal tract being the most frequent extranodal involvement location [2]. Most patients present with a rapidly growing tumor mass involving 1 or more lymph and extranodal nodes. Approximately 40% of patients present with extranodal lesions. The World Health Organization’s latest classification of lymphoid tumors identifies over 15 subtypes of DLBCL that are associated with site and viral or genetic abnormalities [3].

The R-CHOP regimen (rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone) administered in 21-day cycles is the current first-line therapeutic standard for DLBCL. Despite the complex molecular heterogeneity and different biological subtypes of DLBCL, R-CHOP has been the criterion standard for the treatment of DLBCL for over 15 years, with a complete response rate of approximately 80% [4]. Relevant studies indicate that anthracyclines are a crucial component for efficacy in the treatment of DLBCL [5]. For DLBCL patients treated with R-CHOP, 10-year progression-free survival (PFS) was 36.5% and 10-year overall survival (OS) was 43.5% [4]. Recent advances demonstrate that polatuzumab vedotin-based Pola-R-CHP (replacing vincristine with the antibody-drug conjugate) shows superior PFS compared to R-CHOP while having comparable safety profiles. The global POLARIX trial confirmed consistent efficacy and safety outcomes for Pola-R-CHP across Asian and Western populations [6]. These new regimens may become first-line treatment options in the future, especially in specific subtypes or refractory cases. Nevertheless, R-CHOP remains the most extensively validated and widely used first-line therapeutic regimen in current clinical practice, supported by robust long-term efficacy data and extensive clinical experience across diverse patient populations.

The incidence of cardiac metastasis in malignant tumors is about 1.8% [7]. Cardiac metastasis can occur with any malignant tumor [8]. The most common tumors with cardiac metastasis are pleural mesothelioma, malignant melanoma, lung adenocarcinoma, and undifferentiated carcinomas [9]. Most metastatic cardiac tumors cause no apparent symptoms and are often detected postmortem [10]. DLBCL is the most common histopathological subtype of secondary cardiac lymphoma [11], and the risk of sudden death in patients with secondary cardiac lymphoma is high. Therefore, early detection of cardiac metastasis and timely therapeutic intervention are important for improving patient prognosis.

Case Report

A 63-year-old woman was admitted to the hospital on 1 June 2024 with a 15-day history of progressive abdominal distension and epigastric pain, which had acutely exacerbated over the preceding 5 days. She reported complete cessation of flatus and bowel movements for 48 hours prior to admission. The concomitant symptoms included poor appetite, acid reflux, general fatigue, subjective chills, and mild facial edema. She reported inadequate symptomatic relief despite self-administered analgesic use (specific agent and dosage unknown).

Her physical examination revealed alert mental status, mild facial edema, regular heart rhythm, and diminished heart sounds. The examination results after her admission to the Emergency Department were as follow:

The electrocardiogram (ECG) showed sinus rhythm, normal electrical axis, prolonged QTc, and non-specific ST-T change. Abdominal ultrasound and abdominal standing film indicated no apparent abnormality. A chest computed tomography (CT) scan indicated multiple pulmonary nodules, calcification foci, and possible tuberculosis. The right atrium was enlarged. Cardiac biomarkers showed brain natriuretic peptide precursor (NT-proBNP) was 2052.00 pg/ml (Table 1, severely elevated), and hypersensitive troponin-1 was 0.0540 ng/ml (mildly elevated). Inflammatory markers showed IL-6 (interleukin-6) was 132.67 pg/ml (mildly elevated), procalcitonin was 0.390 ng/ml (mildly elevated), white blood cell count was 12.5×109/L (mildly elevated), and the C-reactive protein level was 192.30 mg/L (severely elevated). Her erythrocyte sedimentation rate was 73 mm/h (moderately elevated). An autoimmune workup revealed positive ANA (1: 100 by IIF); therefore, she was admitted to the Infectious Diseases Department with provisional diagnoses of infectious lesions combined with acute heart failure. She received symptomatic treatment, including anti-infection treatment and pain relief, while completing further relevant examinations. She had long-term use of oral painkillers due to abdominal pain, and digestive ulcers and intestinal obstruction could not be excluded. Contrast-enhanced abdominal CT, gastroscopy, and cardiac color ultrasound were further performed to evaluate her condition.

The ultrasound demonstrated an intramyocardial mass in the right atrium with moderate-intensity perfusion; the effective volume of the right chamber had decreased with the increase of the right-chamber volume. The right atrial obstruction was demonstrated by widening of the inferior vena cava. The right-heart radiography suggested positive grade I, considering the intracardiac shunt (Figure 1). The gastroscopy examination indicated chronic atrophic gastritis C1. Contrast-enhanced abdominal CT demonstrated space-occupying lesions with abnormal enhancement in the bilateral adnexal area (ovarian serous cystadenocarcinoma was considered), and multiple enlarged lymph and large retroperitoneal vessels were (suggesting metastasis). Cardiac enhanced CT indicated right atrial enlargement right atrial enlargement with an intramyocardial mass lesion in the right atrium, which suggested a metastatic tumor (Figure 2). For the space-occupying lesions of the right atrium, further specialized treatment was proposed by the Cardiology Department. Following case discussion in the Department, systemic metastasis of ovarian malignant tumor was considered, which was shown to be invading the heart. Currently, there are no relevant surgical pointers, and systemic chemotherapy is recommended as a treatment option for this condition.

The patient was transferred to the Department of Oncology on 11 June 2024. Following transfer, the ECG showed sinus bradycardia, long Q-T interphase/long Q-Tc interphase, and low and inverted T waves (I, aVL, V2–V6). Pelvic puncture biopsy was performed on June 11, 2024, revealing DLBCL (non-GCB). The immunohistochemical results were: CK7 (−), Ck20 (−), Pax-8 (−), CK8-18 (−), CD45 (+), CKP (−), Syn (−), CgA (−), CD56 (−), MPO (−), CD68 (−), CD117 (−), CD99 (−), CD34 (+), TdT (−), CD79a(+), CD20 (+), CD3 (−), CD5 (−), CD10 (−), BCL-2 (+ 80%), BCL (+)-6, MUM1 (+), C-Myc (+ 40%), cyclin D1 (−), and Ki7 (+ 70%) (Figure 3). The fluorescence in situ hybridization (FISH) test results indicated lack of fracture in BCL2, BCL6, and Myc (negative). Based on the above results, she was diagnosed with non-Hodgkin’s lymphoma (B-cell type, stage 4); lymphoma invading the retroperitoneum, lymph nodes, heart, and ovaries; heart failure; lung infection; and abnormal liver function.

In accordance with guidelines, the R-CHOP regimen was administered on June 21, 2024, coupled with symptomatic supportive treatment and continuous monitoring of cardiac adverse reactions. The levels of the marker NT-proBNP were estimated to be 1894.00 pg/ml (Table 1). ECG showed long Q-T interval/long Q-Tc interval, and low T wave, which was inverted (I, aVL, V2–V6). During the course of the disease, her heart rate was extremely slow (~47 beats/min) and the ECG indicated cardiac escape (Figure 4). There was concern for potential life-threatening risks including that tumor embolization from right atrial mass leading to pulmonary embolism and subsequent cardiopulmonary arrest, or atrial tumor rupture causing cardiac rupture. After obtaining informed consent from her family, the regimen was adjusted to rituximab 0.6 g, cyclophosphamide 1.2 g, pirarubicin 60 mg, and etoposide 0.1 g (R-CEOD). The follow-up echocardiography after completion of this chemotherapy indicated right atrial obstruction, pulmonary embolism, and other imminent life-threatening conditions. The patient had significant clinical improvement following targeted supportive care, with stabilization of vital signs and resolution of acute symptoms. She was re-admitted on 8 July 2024 for continuation of R-CEOD chemotherapy. After this treatment, she developed persistent bradycardia at rest. To avoid further deterioration of cardiac function, cardiotoxic drugs were withdrawn from the next treatment cycle. Therefore, R-CEOD treatment was administered on 3 August 2024 (rituximab 600 mg; cyclophosphamide 1.2 g; etoposide 100 mg). The levels of NT-proBNP were significantly decreased and were close to the normal reference values, and the ECG indicated no abnormality. Contrast-enhanced CT indicated that the bilateral adnexal area, the right pericardium and right atrium lesions, the pericardiac phrenic angle, and the retroperitoneal lymph nodes were smaller than shown by CT on June 5, 2024 (Figure 2). Echocardiography demonstrated the cardiac mass has decreased in size compared to previous imaging (Figure 1). According to the RECIST 1.1 criteria, the sum of target lesion diameters decreased ≥30%, meeting the criteria for partial remission (PR).

Discussion

R-CHOP is the preferred first-line treatment for most patients with DLBCL, and has been shown to improve patient outcomes. Although most patients are in an advanced stage at diagnosis, more than 60% can be cured with the R-CHOP regimen [12]. Anthracyclines are a crucial component for efficacy in the treatment of DLBCL [5]. The relative dose strength of anthracyclines is considered an independent predictor of response and survival [13,14]. For patients with DLBCL with contraindications to anthracyclines, replacement with gemcitabine or etoposide can produce satisfactory results, whereas trials on anthracycline alternatives and cardioprotectants have not yet provided evidence for their safety or efficacy [15,16]. Therefore, since anthracyclines are a key component of DLBCL treatment efficacy, patients with DLBCL should receive anthracycline-containing regimens whenever possible. However, if the patient has a heart disease, the choice of this cardiotoxic drug should be carefully considered according to the situation.

Our patient presented with non-specific symptoms of abdominal discomfort, lack of chest or respiratory discomfort, abnormal increase of NT-proBNP, prolonged Q-T interval on electrocardiogram, positive anti-nuclear antibodies, and significantly elevated white blood cell counts and C-reactive protein levels. Therefore, she was initially misdiagnosed as having tuberculosis combined with acute heart failure. Further evaluation with echocardiography, cardiac angiography, and contrast-enhanced abdominal CT revealed space-occupying lesions in the right atrium and ovary. However, the risk of cardiac puncture biopsy was high. Therefore, ovarian biopsy, immunohistochemical analysis, and FISH detection were performed, and non-Hodgkin’s lymphoma B-cell type was confirmed following comprehensive examination of the results. The diagnosis of DLBCL depends on a pathological biopsy of the tumor tissue [17]. PET-CT with optimal sensitivity and specificity has been the main imaging method for staging invasive lymphoma since 2007 [18,19]. Our patient was diagnosed with advanced lymphoma, and due to financial reasons, a PET-CT examination was not performed. The patient had complications with multiple distant metastasis and could not be prepared for surgery; therefore, systemic chemotherapy was used as the main treatment method. Her condition was generally good at the beginning; however, during the first cycle of treatment with R-CHOP and monitoring of adverse drug reactions, it was found that her heart rate was very slow. Considering the cardiotoxic adverse effects of doxorubicin, we could not rule out arrhythmia caused by the instability of heart metastases during chemotherapy. The risk of heart rupture and pulmonary embolism is very high in such patients [20]. Pirarubicin causes less cardiac toxicity than doxorubicin and is safer to use. Subsequently, the chemotherapeutic regimen was changed to the R-CEOD regimen. After the second cycle of treatment, the patient developed persistent bradycardia at rest. To avoid further deterioration of cardiac function, the anthracycline chemotherapy was stopped at the third cycle of treatment. After 3 cycles of treatment, the levels of NT-proBNP were significantly decreased and close to the normal reference values, and the electrocardiogram indicated no abnormality. Most importantly, the lesion was significantly reduced, and the overall efficacy was evaluated as partial remission. The diagnosis and treatment of this case of lymphoma complicated with cardiac metastasis may be useful as a reference for related research.

Conclusions

DLBCL complicated with right atrial metastasis is a rare clinical condition, which often indicates poor prognosis. The treatment plan is mainly systemic chemotherapy, aiming at improving the quality of life and prolonging survival. Timely diagnosis and early treatment are critical for good outcomes. Treatment should be individualized, and the most effective treatment is anthracycline-containing chemotherapy combined with radiotherapy [21]. However, prior to chemotherapy with anthracyclines, all patients should be evaluated for comorbidities with echocardiography, electrocardiography, and examination of the levels of BNP, and adverse reactions should be closely monitored for during chemotherapy.