Secondary Cardiac Lymphoma Presenting as Effusive–Constrictive Pericarditis

Abstract

Background

Diffuse large B-cell lymphoma (DLBCL) may present as effusive constrictive pericarditis.

Case Summary

A 40-year-old woman with relapsed high-grade DLBCL presented with worsening dyspnea and acute decompensated heart failure. Two weeks prior, she underwent a pericardial window with preserved left ventricular ejection fraction of 50%. On admission, transthoracic echocardiography revealed nodular pericardial thickening consistent with metastatic disease and a new reduction in left ventricular ejection fraction to 39%. Doppler imaging revealed expiratory diastolic hepatic vein flow reversal, ventricular interdependence with septal bounce, and annulus reversus with a medial mitral annular e’ velocity preserved at 9 cm/s and a reduced lateral e’ velocity of 6 cm/s. These findings were diagnostic of effusive-constrictive pericarditis following recent pericardial drainage.

Discussion

This case highlights secondary cardiac lymphoma as a rare cause of effusive-constrictive pericarditis and underscores the diagnostic importance of echocardiography.

Take-Home Message

DLBCL-related pericardial involvement carries a poor prognosis with limited therapeutic options.

Graphical Abstract

History of Present Illness

A 40-year-old woman with recently relapsed diffuse large B-cell lymphoma (DLBCL) presented to the emergency department at an outside hospital with worsening dyspnea and chest pain. On presentation, she was tachycardic and hypotensive. Computed tomography angiography (CTA) of the chest revealed a large pericardial effusion. Transthoracic echocardiography (TTE) demonstrated a moderate-to-large circumferential pericardial effusion with a mildly reduced left ventricular ejection fraction of 50%. Given her borderline hypotension, tachycardia, and clinical signs of tamponade, she underwent emergent pericardial window. Pericardial fluid cytology was positive for DLBCL, activated B-cell/nongerminal center phenotype (CD20 positive, CD30 negative). Pericardial biopsy revealed atypical lymphoid infiltrates consistent with DLBCL (Figure 1). Repeat TTE 3 days after the pericardial window showed resolution of the pericardial effusion. The pericardial drain was removed, and the patient was discharged with plans for outpatient oncology follow-up.

Figure 1.

Histological Evidence of DLBCL for Pericardium Biopsy

Histopathologic evaluation of the pericardial biopsy demonstrating involvement of diffuse large B-cell lymphoma (DLBCL). (A) Hematoxylin and eosin stain showing sheets of large atypical lymphoid cells with prominent nucleoli. (B) Ki-67 immunohistochemical stain highlighting a high proliferative index (present in 60% of the neoplastic B cell), supporting the diagnosis of DLBCL involving the pericardium.

One week later, she was readmitted for persistent shortness of breath and chest pain. Her CTA chest was negative for pulmonary embolism but showed increased nodularity of the pericardium and a possible mass in the right atrium. TTE showed a preserved left ventricular ejection fraction of 60% and a small pericardial effusion without clinical tamponade. C-reactive protein was 6.0. Her symptoms were attributed to progressive malignancy given the stability of the pericardial effusion. She was discharged once more with plans for close oncology follow-up. She presented 3 days later for worsening shortness of breath, leg swelling, and abdominal bloating. Her brain natriuretic peptide was 573. Electrocardiogram showed sinus tachycardia at 115 bpm. TTE showed an unchanged small pericardial effusion. CTA chest showed no pulmonary embolism and redemonstrated previous findings without significant change. CT abdomen and pelvis showed moderate-volume ascites. Her lactate dehydrogenase was 515, which raised concern for high tumor burden. She was started on Decadron but unfortunately left against medical advise without completing further workup. She presented to our facility 3 days later with worsening dyspnea and bilateral leg swelling.

Previous Medical History

The patient had a history of stage IIIB intrathoracic nodal primary DLBCL with maxillary sinus involvement, diagnosed 1 year prior. She completed 6 cycles of R-CHOP chemotherapy. Posttreatment positron emission tomography-computed tomography demonstrated complete metabolic response with no evidence of residual disease.

Differential Diagnosis

Differential diagnoses for the etiology of her pericarditis included, but were not limited to, viral syndrome, prior radiation exposure, postoperative myocardial injury from her recent pericardial window, malignant infiltration of the pericardium, uremic pericarditis, and autoimmune disease (ie, lupus).

Investigation

On her third, most recent admission, she was persistently hypotensive and tachycardic. Labs were significant for brain natriuretic peptide of 5,523, C-reactive protein 54.5, and lactate dehydrogenase 657. Chest radiograph showed small bilateral pleural effusions with enlarged cardiac silhouette. Electrocardiogram demonstrated sinus tachycardia with low-voltage QRS in the precordial and limb leads. TTE showed small circumferential pericardial effusion with nodular pericardial masses, no evidence of cardiac tamponade, and newly reduced ejection fraction of 39% (Video 1). Notably, there was a small left ventricular chamber size, moderate generalized hypokinesis, and moderate-severely reduced right ventricular systolic function. Echocardiogram was remarkable for interventricular septal bounce, consistent with ventricular interdependence (Video 2). Doppler evaluation demonstrated diastolic hepatic vein flow reversal, accentuated during expiration (Figure 2). Concurrently, the inferior vena cava was dilated to 2.2 cm. The medial mitral annular e’ velocity was 9 cm/s, and the lateral mitral annular velocity was 6 cm/s (Figure 3), consistent with annulus reversus. The TTE findings suggested constrictive pathology, concerning for effusive–constrictive pericarditis in the setting of recent pericardial window and malignancy.

Figure 2.

Hepatic Vein Reversal During Diastole and Expiration

(Left) Hepatic vein reversal coinciding with diastole and expiration. (Right) A dilated inferior vena cava of 2.2 cm.

Figure 3.

Mitral Annular Tissue Doppler in Constrictive Pericarditis

Tissue doppler imaging shows preserved septal e′ (9 cm/s) with reduced lateral e′ (6 cm/s), consistent with annulus reversus and supportive of constrictive physiology.

Management

She was started on intravenous dexamethasone and intravenous lasix and experienced significant improvement in fatigue and dyspnea. Given the aggressive nature of her malignancy, urgent salvage chemotherapy with rituximab, ifosfamide, carboplatin, and etoposide (RICE) followed by definitive treatment with chimeric antigen receptor T-cell therapy was recommended. Medical oncology estimated this antineoplastic therapy would offer a 20% to 30% chance of cure or long-term survival. Inpatient chemotherapy was arranged; however, the patient was apprehensive to proceed with additional chemotherapy due to intolerable side effects with prior chemotherapy, including nausea, vomiting, and pain. The patient was urged to proceed with therapy but declined, stating that she would prefer conservative management of her cardiac comorbidities and to go home to be with her family. The patient was informed that without anticancer treatment, survival may be limited to days to weeks given the aggressive nature of her lymphoma. The patient voiced understanding of her condition and prognosis and stated that her primary goal was to limit suffering in the end of her life and to go home to be with her children. Cardiac magnetic resonance imaging was ordered but subsequently deferred due to the patient's preference to avoid additional workup as she elected to enroll in hospice care.

Outcome and Follow-Up

Ultimately, the patient maintained decision-making capacity and declined further cancer-directed therapies despite our recommendations. She enrolled in hospice and went home with her family. Eleven days later, she presented once more to the emergency department with acute renal and liver failure and severe lactic acidosis. Given the gravity of her prognosis, she chose to focus on comfort measures and died in the hospital 12 hours later.

Discussion

We present a case of effusive constrictive pericarditis resulting from secondary cardiac involvement by DLBCL. DLBCL with cardiac involvement is rare but often fatal. It may occur as either primary or secondary disease, with secondary cardiac involvement being more common, as observed in our case.¹ Secondary cardiac involvement has been reported in up to 20% of cases of malignant lymphomas evaluated at autopsy.¹ Secondary cardiac lymphoma typically manifests as pericardial effusion, not constriction. Other infiltrative diseases, such as sarcoidosis and asbestosis, are well known to cause constrictive physiology. Constrictive pericarditis from direct malignant involvement is a relatively uncommon etiology of constriction. In a large case series, direct malignant infiltration was estimated to account for <10% of constrictive pericarditis cases.²

The incidence of constrictive pericarditis caused by secondary cardiac lymphoma is extremely rare and not well described in the literature. In fact, a specific incidence rate of constrictive pericarditis from secondary cardiac lymphoma has not been defined in the available literature, which consists of autopsy series, case series, and case reports. Of the available case reports, secondary cardiac lymphoma is described as manifesting acutely with pericardial effusion and tamponade physiology, not constrictive pericarditis.2, 3, 4, 5 Constrictive pericarditis from pericardial infiltrates may be underreported because patients typically improve with chemotherapy or succumb to their disease before workup of constrictive pericarditis can begin.

Effusive constrictive pericarditis is defined as persistent constrictive physiology after drainage of a pericardial effusion, characterized by persistently elevated filling pressures, most notably right atrial pressure, despite pericardiocentesis.⁴ This typically arises from inflammation, thickening, and fibrosis of the visceral pericardium.^6,7 In our case, however, constrictive physiology was driven by lymphoma infiltration of the pericardium, resulting in persistent restriction of cardiac filling even after pericardial fluid removal. In our case, the patient had a recent pericardial window, which preceded the effusive nature of her constrictive pericarditis. In addition, several echocardiographic features were demonstrated such as ventricular interdependence, expiratory diastolic hepatic vein reversal, dilated inferior vena cava, and annulus reversus with lateral annular e’ velocity lower than the medial annular e’ velocity.

Given the rarity of cardiac involvement in DLBCL, no standard of care has been established. Our hematology team recommended RICE therapy followed by chimeric antigen receptor T-cell therapy; however, the patient declined further anticancer therapy due to previous intolerance of chemotherapy toxic effects and preference for comfort care. Future studies should aim to determine management options for DLBCL with cardiac involvement.

Conclusions

This case highlights the importance of recognizing effusive-constrictive pericarditis as a rare manifestation of secondary cardiac lymphoma and underscores the diagnostic value of comprehensive echocardiographic assessment in patients with malignancy-associated pericardial disease.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Take-Home Messages

• •Effusive–constrictive pericarditis is a rare but important manifestation of secondary cardiac involvement in diffuse large B-cell lymphoma and should be suspected in patients with malignancy who develop persistent constrictive physiology despite pericardial drainage.
• •Key echocardiographic findings include ventricular interdependence, annulus reversus, and expiratory diastolic hepatic vein flow reversal.

Appendix

Video 1

Pericardial Nodules With Pericardial Effusion

Small circumferential pericardial effusion with pericardial notching and nodular hyperenhancement consistent with malignant pericardial involvement.

Video 2

Septal Bounce Demonstrated on M-Mode

Interventricular interdependence via abnormal septal motion with M-mode on transthoracic echocardiography.