Primary Cardiac Lymphoma in a Heart Transplant Recipient

Primary Cardiac Lymphoma in a Heart Transplant Recipient D. Nart, S. Nalbantgil, T. Yagdi, F. Yılmaz, M. Hekimgil, G. Yüce, and A. Hamulu ABSTRACT Posttransplantation lymphoproliferative disease (PTLD) is one of the most serious complications of chronic immunosuppression in transplant recipients. Involvement of the cardiac allograft or development of lymphoma in the heart is extremely rare. We report a primary cardiac lymphoma that developed about 14 months after the operation in a cardiac recipient. The patient presented with vague abdominal complaints. Multiorgan failure developed within a short period of time, and the patient died. The diagnosis of “diffuse large cell lymphoma of B cell type” was made on postmortem examination. P OSTTRANSPLANTATION lymphoproliferative diseases (PTLDs) are the most serious and frequently fatal complications of chronic immunosuppression in transplant recipients. The incidence ranges from 2% to 6% in heart transplants.1– 4 It is the third leading cause of death in these patients.2–5 More than 50% of patients with PTLD present with extranodal masses.6 The disease occurs frequently in the gastrointestinal tract, lungs, skin, liver, central nervous system, but involvement of the cardiac allograft or development of lymphoma in the heart is extremely rare.7 We report a primary cardiac lymphoma that developed as a PTLD in a cardiac recipient. CASE REPORT A 50-year-old man underwent orthotopic heart transplantation for ischemic cardiomyopathy. The operation and postoperative course were uncomplicated. He was discharged 15 days after surgery on an immunosuppressive regimen of prednisone, azathioprine, and cyclosporine (CyA). He had no acute rejection episode requiring antilymphocytic antibody. Although the patient’s clinical and laboratory status had been stable, CMV reactivation was observed at 12 months after transplantation. Gancyclovir was administered. Fourteen months after transplantation, the patient presented with fatigue and vague abdominal pain. His liver function tests were mildly elevated, but other chemistry determinations were within the normal range. Abdominal ultrasonography revealed hepatic congestion. Histopathological examination of the liver biopsy was also consistent with congestion. Echocardiography revealed global hypokinesia. Congestion was believed to be the consequence of cardiac failure due to rejection. Cardiac biopsy was performed. There was a mixed CD3 (⫹) T lymphocyte and CD20 (⫹) B lymphocyte infiltration in the subepicardial fat tissue, but there was no rejection. However, occasional large lymphoid cells appeared in the myocardium. Possible sources of infection were extensively sought, but all cultures were negative. A mass that was located between the right ventricle and the sternum was detected by computed tomography of the chest. The patient’s overall clinical picture and hemodynamic status worsened gradually. The patient died of multiorgan failure before the diagnostic workup of this lesion could be performed. On postmortem examination, a mass lesion, 5 cm in its greatest dimension, was seen within the pericardial cavity. This subepicardial mass was located on the anterior wall of the right ventricle and atrium bridging the atrioventricular groove. It also invaded the inferior vena cava at the diaphragmatic level. The cut surface revealed a nodular, gray-white appearence with hemorrhagic and necrotic areas (Fig 1). Microscopic examination showed an infiltrate of small lymphocytes plasma cells and transformed lymphocytes with scattered large, bizarre lymphoid cells containing vesicular nuclei and nucleoli. Mitosis and necrosis were abundant. Immunohistochemically, tumor cells were CD45and CD20-positive and CD3, CD15, CD30, cytokeratin and bcl-2 negative. In situ hybridization showed staining with a probe for Epstein-Barr virus-encoded RNA (EBER) (Fig From the Department of Pathology (D.N., F.Y., M.H., G.Y.), Department of Cardiology (S.N.), and Department of Cardiovascular Surgery (T.Y., A.H.), Ege University Medical Faculty, Bornova, Turkey. Address reprint requests to Sanem Nalbantgil, MD, Ege University Medical Faculty, Department of Cardiology, Bornova, Izmir 35100, Turkey. E-mail: sanamn@hotmail.com 0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.01.034 © 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 1362 Transplantation Proceedings, 37, 1362–1364 (2005) CARDIAC LYMPHOMA IN HEART TRANSPLANT Fig 1. Macroscopic appearance of the cardiac lymphoma. 2). Based on these pathological findings, the diagnosis was “diffuse large cell lymphoma of B cell type.” DISCUSSION Two pathogenetic factors are important in PTLD: immunosuppressive therapy3,4 and Epstein-Barr virus (EBV) infection.7,8 The degree of immunosuppression is a major determinant of the development of a lymphoproliferative disorder. The incidence appears to be highest among heart recipients9 in whom a greater degree of immunosuppres- 1363 sion is required because of the most serious consequences of transplant rejection. Transplant patients at increased risk for PTLD are those receiving both CyA and azathioprine, or polyclonal (antilymphocyte serum) or monoclonal (OKT3) antilymphocyte antibodies.3,4,10 The incidence of PTLD is highest in the first year, which could be due to intense immunosuppression.1 The pathogenesis of PTLD in most cases, appears to be related to B-cell proliferation induced by infection with EBV, in the setting of chronic immunosuppression.11,12 Although EBV has been linked to PTLD in the majority of cases, EBV is not found in 10% to 20% of patients.13 There seems to be an increase in the proportion of EBV-negative PTLD; the EBV-negative PTLD appears to have a delayed-onset compared with EBV-positive disease.14 The PTLDs range from indolent polyclonal hyperplasia to aggressive monoclonal lymphomas.15–17 The rates of allograft involvement by PTLD vary widely depending on the types of transplant. They have been reported to be as high as 60% to 80% of heart–lung transplants,18 17% to 33% in renal transplants and 8.6% to 33% in liver transplants.6,18 Affinity of PTLD for the allograft in cases of isolated organ involvement suggests that a local immune reaction against the graft may play a role in promoting malignant transformation. Reported cases of cardiac allograft involvement by PTLD had multiorgan involvement.19 –23 Cardiac involvement showed an incidence of 4% to 5% among all PTLDs.24 However, isolated heart involvement is rare. Ying et al19 reported a case of lymphoma that was confined to a cardiac allograft valve. Confirming the presence of cardiac lymphoma is often difficult, and the diagnosis is often estab- Fig 2. Microscopic examination showed an infiltrate of small lymphocytes plasma cells and transformed lymphocytes with scattered large, bizarre lymphoid cells with vesicular nuclei and nucleoli. 1364 lished on postmortem examination.23 Empirical antibiotherapy without any positive cultures and pulse steroids without any definitive sign of rejection failed to prevent the clinical deterioration in this patient. A mass lesion detected by CT was difficult to reach for biopsy without a resternotomy. However, this was the only positive finding that could have led to a definitive diagnosis premortem. Our case is a rare example of PTLD confined to the heart. In heart transplant recipients, the whole body, including the transplanted organ, must be aggressively searched for PTLD, especially if a downhill clinical course cannot be explained by either rejection or infection. REFERENCES 1. 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