Primary cardiac lymphoma (PCL) is a very rare lymphoma that primarily affects the heart and/or pericardium and causes cardiac symptoms due to myocardial infiltration. Early clinical diagnosis is challenging due to the lack of specificity in early clinical symptoms and ancillary testing, and the survival of PCL patients is restricted to a few months if not treated early and effectively. It is therefore critical to investigate the clinical aspects of PCL patients and develop more effective auxiliary diagnostics. This research presents one case of PCL and compares our findings to those described in the literature. To characterize the clinicopathological characteristics, management, and outcome of PCL patients at home and abroad, data from 121 affected individuals were analyzed retrospectively.

A 73-year-old female patient was admitted to the hospital on November 6, 2020, reporting chest tightness after physical activity, which had persisted for over a month. The patient had a four-year history of thrombocytosis, which was managed with oral hydroxyurea. Upon examination, her vital signs were as follows: temperature 36.1°C, heart rate 110 beats/min, respiratory rate 12 breaths/min, blood pressure 94/60 mmHg, peripheral capillary oxygen saturation (SpO₂) 98%. The patient was conscious and exhibited steady breathing and responsiveness, and had an Eastern Collaborative Oncology Group performance status of 1. The physical examination showed no significant abnormalities, except for coarse breath sounds detected in both lungs.

Initial laboratory tests indicated leukocyte levels at 11.90×10⁹/L, hemoglobin at 135.0 g/L, neutrophils at 7.78×10⁹/L, platelets at 265×10⁹/L, and a monocyte percentage of 18.4%. C-reactive protein was measured at 18.3 mg/L, lactate dehydrogenase at 360.0 U/L, while liver and kidney function tests, coagulation parameters, and electrolyte levels remained within normal ranges. Cardiac color ultrasound revealed enlargement of both the right atrium and ventricle, with the right ventricular end-diastolic transverse diameter measuring 42 mm. A hyperechoic mass, approximately 56 mm × 53 mm, was identified in the right atrium, indicating a possible mucinous tumor. This mass partially shifted toward the right ventricular side through the tricuspid valve during diastole. This movement resulted in accelerated blood flow at the tricuspid opening. Additionally, a small amount of pericardial effusion was observed ( Figure 4A ). A follow-up ultrasound on November 11, 2020, demonstrated an increase in the size of the hypoechoic mass in the right atrium, which now measured approximately 75 mm × 50 mm ( Figure 4B ). This mass, attached to the atrial septum, exhibited increased mobility and intermittently obstructed the tricuspid valve orifice during cardiac cycles. The patient’s family, considering their financial situation, did not proceed with PET-CT for tumor staging assessment.

The patient underwent resection of a cardiac tumor under general anesthesia on November 16. Intraoperative findings revealed multiple cauliflower-shaped masses in the right atrium, varying in size, with the largest measuring approximately 8 cm × 4.5 cm, extending to the tricuspid valve and interatrial septum. A palliative resection of the tumor was performed. Postoperative pathology identified the masses as diffuse large B-cell lymphoma (non-germinal center origin), confirmed through immunohistochemical profiling: CD3 (-), CD20 (+), CD21 (-), Ki67-MIB1 (70%), CD30 (few +), Bcl-2 (+), CK (-), CD10 (-), Bcl-6 (+), MUM-1 (+), c-myc (50%), P53 (few +), Pax-5 (+), Cyclin D1 (-), CD5 (-), and negative EBER in situ hybridization ( Figure 5 ).

The final diagnosis was cardiac diffuse large B-cell lymphoma (non-germinal center origin), according to the 2015 World Health Organization (WHO) Classification of Cardiac and Pericardial Tumors (1). Considering the patient’s age, the hematology department recommended low-dose chemotherapy. However, her family, taking into account the patient’s age and their own financial situation, decided to refuse chemotherapy. The postoperative cardiac ultrasound revealed findings consistent with changes typically observed in right and left atrial occupying lesions. A hypoechoic mass, measuring approximately 40 mm × 28 mm, was present in the right atrium, extending from the base to the upper part of the interatrial septum, with a protrusion into the left atrium measuring approximately 22 mm × 16 mm ( Figure 4C ). After recovery, the patient was discharged on November 20, 2020. Unfortunately, she passed away on April 20, 2021, without seeking further medical consultations during this period.

This case aligns with several characteristics of PCL described in the existing literature, including its demographic predilections, tumor size, common sites of involvement, and histological subtypes. The patient’s presenting symptoms of chest discomfort and exertional dyspnea are consistent with the commonly reported symptoms of PCL, such as chest pain and dyspnea. Moreover, the brief interval between surgical intervention and the patient’s demise highlights the highly aggressive nature, rapid progression, and high mortality rate associated with PCL. This also underscores the limitations of palliative surgical resection as a standalone treatment strategy. However, this case exhibits unique clinical features that may be influenced by individual factors and disparities in access to medical resources. Notably, the patient had a four-year history of primary thrombocythemia and was undergoing treatment with hydroxyurea, an unusual finding among PCL patients. Additionally, the patient demonstrated an exceptionally rapid tumor growth rate, as evidenced by a marked increase in tumor volume between the initial echocardiogram and subsequent follow-up examinations. This suggests a more aggressive disease course than what is typically observed in PCL cases. These distinct features warrant further investigation to better understand their implications for disease progression and management.

PCL is an exceedingly rare malignancy, predominantly presenting as cardiac and/or pericardial tumor tissue or as myocardial infiltration of lymphomas, which results in cardiac symptoms. Representing only 1% of primary cardiac malignancies and 0.5% of all extranodal lymphomas (121). This article summarizes the clinical presentation, ancillary investigations, diagnosis, treatment and prognosis from a decade of case reports and describes a particular PCL patient.

As the second most prevalent primary cardiac malignancy, PCL has a dire prognosis without treatment, often limited to just a few months. Therefore, prompt and accurate diagnosis and treatment are crucial. However, the non-specific clinical manifestations and auxiliary examinations present challenges for early diagnosis. Clinically, the approach to pathological biopsy should evolve from non-invasive to invasive methods to achieve efficient and cost-effective diagnosis.

The incidence of B symptoms in patients with PCL is notably low. Instead, the condition commonly presents with symptoms such as shortness of breath, chest tightness, and lower limb edema. These may occasionally be accompanied by additional symptoms, including loss of appetite, anxiety, and chest pain, further contributing to the clinical complexity of PCL. Besides, it can cause a variety of arrhythmias, with atrial fibrillation, atrial flutter, and third-degree atrioventricular block being the most common. Lesions are predominantly located in the cardiac and pericardial regions, with the right atrium being the most commonly involved site. This finding aligns with our study, where 86.1% of cases involved the right atrium. Notably, 8 patients (6.6%) presented to the hospital with syncope, which was associated with a poor prognosis. Among these, 2 patients experienced disease progression, and 3 succumbed to the condition within 4 months. These findings underscore the importance of considering this disease in the differential diagnosis when evaluating comatose patients. Clinicians are advised to maintain a high index of suspicion to ensure timely identification and management. Overall, the symptoms of PCL are subtle at first, becoming more pronounced as the lymphoma progresses, often leading to late-stage diagnoses.

The need for new diagnostic methods is paramount, even as the accuracy of existing imaging examinations improves. Commonly utilized clinical auxiliary examinations include electrocardiography (ECG), transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), cardiac computed tomography (CT), cardiac magnetic resonance (CMR) and FDG-PET. Echocardiography, as an adjunctive test for the initial diagnosis of cardiac tumors, is able to dynamically observe the location, size, morphology, mobility of cardiac tumors and their relationship with the surrounding tissues, to find the presence of hypoechoic masses and to detect associated pericardial effusions. TTE is not as sensitive as TEE in identifying cardiac tumors, and a retrospective study by Ceresoli (2) et al. demonstrated that TTE detected a cardiac tumors, whereas TEE provides better visualization of cardiac structures, especially those away from the chest wall (63). Therefore, we prefer TEE for the initial diagnosis of cardiac tumors. The use of CT and CMR imaging in the diagnosis of PCL has been increasing steadily in recent years. Asadian (122) et al. have highlighted that these imaging modalities, with their ability to employ various parameter settings and provide excellent soft tissue contrast, are valuable tools for characterizing PCL. They allow for detailed assessment of tumor characteristics, differentiation between benign and malignant lesions, and evaluation with or without contrast enhancement. This capability is particularly beneficial in distinguishing PCL from cardiac thrombus, thereby aiding in the differential diagnosis. Furthermore, PET-CT offers a non-invasive approach to assess the metabolic activity of tumors using fluorodeoxyglucose (FDG). Studies have demonstrated that PCL exhibits higher standardized uptake values (SUVs) and larger metabolic tumor volumes on PET imaging compared to primary cardiac sarcoma (PCS) (123). Additionally, PET-CT provides a clearer delineation of tumor invasion, facilitating safer biopsy procedures and guiding subsequent surgical interventions.

The treatment options for PCL include surgical resection, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation, etc. Chemotherapy plays a central role in the treatment of PCL, especially the R-CHOP regimen, which has been widely utilized since 2010. This regimen has notably enhanced the progression-free survival of patients with non-Hodgkin’s B-cell lymphoma (the most common type of PCL). In our study, 44.6% of patients underwent tumor removal surgery, while 76.0% opted for chemotherapy, and only 32.2% combined these approaches. An analysis conducted by Yin et al. (124) using the SEER database revealed that surgical intervention did not improve survival outcomes in patients with PCL, with chemotherapy identified as the sole effective treatment modality (65, 125, 126). However, our study demonstrated that patients who underwent combined surgical resection and chemotherapy exhibited superior survival outcomes compared to those who received surgery or chemotherapy alone. Moreover, for hemodynamically unstable patients, surgical intervention remains a critical and urgent treatment to stabilize their condition (127). Emerging therapeutic options, such as autologous hematopoietic stem cell transplantation (auto-HSCT), allogeneic hematopoietic stem cell transplantation (allo-HSCT), and molecularly targeted therapeutic agents, are showing promise in improving survival rates and prognosis for PCL patients. In parallel, supportive care plays a vital role in the comprehensive management of PCL. This includes symptomatic treatment, nutritional support, palliative care, and psychological counseling. For instance, while the Fontan procedure does not directly treat PCL, it enhances cardiac function, improves the patient’s quality of life, and increases the likelihood of long-term survival, thereby facilitating opportunities for subsequent follow-up treatments.

The prognosis for PCL is generally unfavorable. According to statistics from the SEER database, which included 184 cases of PCL, the 1-year, 3-year, and 5-year survival rates were 59%, 41%, and 34% (128), respectively. More than half of the patients had an overall survival (OS) of less than 3 years, or even shorter. Although there is no uniform conclusion on the treatment of PCL at home and abroad, the R-CHOP regimen is still the most important treatment for PCL because of its remarkable efficacy in B-cell lymphoma. In the case presented, a large, mobile PCL mass that obstructed the tricuspid valve and extended into the left atrium was surgically removed. However, the absence of postoperative chemotherapy led to a poor prognosis, and the patient unfortunately passed away within two months after being discharged from the hospital. This underscores the significance of chemotherapy in the treatment process.

In conclusion, it is crucial to consider cardiac lymphoma as a differential diagnosis when patients present with unexplained cardiac abnormalities, such as heart failure, atrial fibrillation, pericardial effusion, or superior vena cava syndrome, particularly if cardiac ultrasound identifies an intracardiac mass accompanied by unexplained fever. Advancements in imaging modalities, including cardiac CT, CMR, and PET-CT, play a pivotal role in characterizing the mass, assessing its benign or malignant nature, and determining the disease stage. These tools not only guide subsequent biopsy and potential surgical intervention but also enable dynamic adjustments to diagnostic and therapeutic strategies, thereby minimizing the risk of misdiagnosis or delayed diagnosis. Once a diagnosis of cardiac lymphoma is confirmed, individualized clinical judgment is essential to evaluate the need for surgical tumor resection to alleviate cardiac dysfunction. This approach, combined with chemotherapy, can significantly enhance treatment efficacy and improve patient outcomes.