Malignant lymphoma with diffuse cardiac involvement and pulmonary stenosis

Abstract

Lymphoma is one of the most common tumors with the risk of cardiac metastasis. The pattern of cardiac involvement is usually as focal masses. As early diagnosis of lymphoma plays a crucial role in its response to treatment and patient survival longevity, we report a rare case of cardiac lymphoma with diffuse cardiac involvement and acquired pulmonary stenosis. The patient was referred to our center for further evaluation because of dyspnea and systolic ejection murmur. In pericardial biopsy, T cell lymphoblastic lymphoma was reported. After a full course of chemotherapy and one-year follow up, symptoms had improved and echocardiography was normal except for small pericardial effusion.

<Learning objective: Early diagnosis of lymphoma plays a crucial role in its response to treatment and introducing atypical presentation form could be helpful for early diagnosis.>

Introduction

The three most common cardiac metastases are lung carcinoma, esophageal carcinoma, and lymphoma [1]. Pericardium, including epicardium, was the most common location of cardiac involvement, followed by myocardium and endocardium [2].

The incidence of cardiac involvement by lymphoma – as identified by autopsy – varies widely, ranging from 8.7% to 20% [3]. Cardiac lymphoma could be associated with evidence of pericardial effusion, intrathoracic masses, unexplained dysrhythmia, or valve involvement [1]. Early diagnosis of lymphoma might result in achievement of better treatment response and patient^’s longer term of survival. We encountered a rare case of cardiac lymphoma, presented with pulmonary stenosis, who was followed up for one year after chemotherapy.

Case report

An 18-year-old white male patient was referred to our center. He had exertional dyspnea and heart murmur. Physical examination revealed a grade 3/6 systolic ejection murmur, best heard at upper left sternal border. There were low QRS voltages in electrocardiography. Transthoracic echocardiography was done, showing large pericardial effusion without tamponade physiology. Global left ventricular systolic function was normal. Right ventricle (RV) and right atrium were mildly enlarged in size and RV systolic function was mildly reduced. There was diffuse myocardial involvement with increased biventricular and biatrial wall thickness and unusual heterogenous granular echocardiographic texture. Thickening of the pericardium was also noted (Fig. 1A,B and Movie 1).

Fig. 1.

2D transthoracic echocardiography in parasternal long-axis view shows diffuse thickening of the myocardium in all chambers with unusual heterogenous granular texture. Note the increased thickness of the pericardium (A). Large pericardial effusion (yellow arrow) with increased thickness (red arrow). 2D echocardiography in short-axis view (B) shows narrowing in subpulmonic region (yellow arrow) and thickening of pulmonic valve leaflets (white arrow) and pericardial involvement (red arrow). Continuous wave Doppler gradients of pulmonary valve (C) was shown, before the treatment. Color Doppler study (D) reveals systolic turbulent flow passing this region (yellow arrow).

Increased thickness in sub pulmonary region and pulmonary valve with restricted motion of leaflets was also noted, resulting in significant systolic turbulent flow passing this region, with overall peak pressure gradient of about 50 mmHg (Fig. 1B,C,D and Movie 2A,B).

Despite the diffuse myocardial and pericardial involvement and thickening, there was no echocardiographic evidence of restrictive or constrictive physiology (E velocity/A velocity = 1.4 in mitral inflow, Em velocity in mitral annulus = 8 cm/s, E/Em = 10).

Computed tomography scan was done, which confirmed the findings in the echocardiography study. There was no evidence of involvement of other organs. Cardiac infiltrative disease was suspected. Pericardial thickening was apparent in echocardiography, and there was large pericardial effusion, and the patient had shortness of breath. Such large amounts of effusion was defined to be problematic and persuaded us to do pericardial drainage and biopsy, for patient relief of symptoms and also as a diagnostic strategy (to get tissue biopsy). It should be mentioned that the symptoms were improved obviously after the drainage.

In pericardial pathology assessment, diffuse proliferation of atypical lymphoid cells with irregular nuclear borders and fine chromatin and high mitotic activity were defined. These findings were consistent with the diagnosis of T cell lymphoblastic lymphoma. In immunohistochemical staining, the tumoral cells were positive for CD3, TDT, CD99, CD5, and were negative for CD20, CD15, CD10 (Fig. 2).

Fig. 2.

Histologic finding showing diffuse proliferation of atypical lymphoid cells (hematoxylin and eosin ×400) (A). Immunohistochemical staining of tumoral cells was positive for CD3 (B) and negative for CD20 (C). (Immunohistochemical staining, B and C ×400).

The patient was scheduled to receive ICE chemotherapy (ifosfamide, carboplatin, etoposide phosphate) plus granulocyte colony-stimulating factor in the medical oncology department. After six courses of chemotherapy and one-year follow up, the patient was completely asymptomatic. Cardiac auscultation was normal. Repeated echocardiography was done and revealed significant reduction of myocardial thickness with normal pulmonary and sub pulmonary valve anatomy and Doppler gradient. A small amount of pericardial effusion remained (Fig. 3A,B,C and Movie 3). Left ventricular diastolic function assessment showed E velocity = A velocity, Em velocity = 5 cm/sec, E/Em = 12 compatible with grade I diastolic dysfunction (Fig. 3D). According to laboratory data and imaging modalities, we thought the patient was in remission phase but echocardiographic follow up according to small pericardial effusion was recommended.

Fig. 3.

In 2D echocardiography in long- (A) and short-axis (B) views after chemotherapy, no evidence of malignant deposits is seen. There is only small size pericardial effusion posterior to the left ventricle. Continuous wave doppler gradients of pulmonary valve (C) was shown, after the treatment. (D) Doppler study of mitral inflow as an assessment of diastolic function of left ventricle.

Discussion

Increased left ventricular wall thickness and mass can be seen in different cardiovascular diseases including hypertrophic cardiomyopathy, hypertensive heart disease, or infiltrative cardiomyopathies. In our case, increased left ventricular wall thickness with atrial and valvular involvement, raised the suspicion of cardiac tumor involvement. Cardiac lymphoma was considered as a differential diagnosis. Chen et al. showed that when more than one chamber is involved, lymphoma should be suspected [4].

A malignant lymphoma usually involves the heart as focal masses and diffuse pattern as in this case are uncommon [5]. In a few papers, right atrium was listed as the most common site for cardiac involvement [5], [6] but the reason is unknown and it might be due to lymph drainage path through thoracic duct into superior vena cava and subsequently into right atrium [6]. Sometimes tumor spreads from myocardium to the adjacent region, encasing aorta, coronary arteries, and pulmonary artery causing a compression effect on these structures [7]. In our case according to diffuse cardiac and pericardial involvement, contiguous spread of tumor from the nearby mediastinal lymph nodes to the pericardium and then the heart is the most probable way for the cardiac involvement.

Left ventricular failure and cardiac arrhythmia could be another presenting symptom [4]. Lymphoma can involve cardiac valves, a few cases with valve involvement were reported, appearing as regurgitation or stenosis [6]. Rapid destruction of tumor cells and myocardial rupture have been reported, during the course of chemotherapy as a possible complication, but we did not have similar experiences in our center [7].

Acquired pulmonary stenosis is a rare entity. In the setting of lymphoma, pulmonary stenosis, could have two reasons; extrinsic compression of pulmonary artery by a mediastinal mass [8] and intrinsic one in which there is direct tumor involvement of sub pulmonary or pulmonary valve. In this case, abnormal cardiac murmur was an early finding, resulting in early diagnosis. To the best of our knowledge diffuse cardiac involvement with intrinsic pulmonary stenosis is a rare entity, and only one case has been previously reported by Janeczek et al. [9]. Acquired pulmonary stenosis following lymphoma is hard to be included as a differential diagnosis of a heart murmur and clinicians need to be aware of variable lymphoma presentation signs and cardiac involvement for early diagnosis and better patient outcome.

Conclusion

Cardiac lymphoma may present with variable figures and atypical signs and should be regarded as a differential diagnosis for acquired pulmonary stenosis and the cardiologist needs to be aware of such a rare presentation to accelerate the referral process for early diagnosis and treatment.

Conflict of interest

The authors declare that there is no conflict of interest.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. This consent form including his/her/their images and other clinical information to be reported in the journal.

Financial support and sponsorship

None.

Author contributions

Dr Alimi and Dr Poorzand contributed in concept/design and data interpretation and Dr Jafarian in final revision of the article.

Appendix A. Supplementary data

The following are Supplementary data to this article: