Ann Thorac Surg 1997;64:1822-1824
© 1997 The Society of Thoracic Surgeons
Case Report
Posttransplantation Lymphoproliferative Disorder in Cardiac Transplant Allografts
Alan J. Ying, BA,
P. David Myerowitz, MD,
William L. Marsh, Jr, MD
Department of Pathology and Division of Thoracic and Cardiovascular Surgery, The Ohio State University Medical Center, Columbus, Ohio
Accepted for publication July 18, 1997.
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Abstract
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Posttransplantation lymphoproliferative disorder occurs in 1.5% to 13% of heart transplant recipients and rarely involves the allograft. We report a case of posttransplantation lymphoproliferative disorder restricted to the mitral valve in a heart transplant recipient. Thirteen cases of cardiac allograft involvement by posttransplantation lymphoproliferative disorder are reported in the literature. None are restricted to the allograft. Five specify sites of cardiac involvement. Valvular masses without infection necessitate evaluation for posttransplantation lymphoproliferative disorder involvement of the cardiac allograft valve.
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Introduction
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Posttransplantation lymphoproliferative disorders (PTLDs) occur in 1.5% to 13% of heart transplant recipients and are the third leading cause of death in these patients [1–5]. Involvement of the cardiac allograft by PTLD is extremely rare [3]. We report a primary cardiac PTLD restricted to the mitral valve in a heart transplant patient.
A 49-year-old man underwent orthotopic heart transplantation in June 1988 for ischemic cardiomyopathy. He was maintained on standard doses of prednisone, azathioprine, and cyclosporine, and required no additional immunosuppression. Echocardiography at 12 months after transplantation revealed a lobular mass associated with the mitral valve. With no symptoms of infection and negative blood cultures, the patient was managed conservatively and observed. At 18 months after transplantation, the patient underwent operation to remove the growing mass and to replace the mitral valve. The postoperative course was uneventful. The patient manifested no symptoms of recurrence; therefore, his immunosuppressive therapy was not modified. At 25 months after transplantation the patient died of massive peritoneal candidiasis. Extensive gross and histologic postmortem examination found no evidence of residual lymphoproliferative disorder.
The lobular mass consisted of multiple 0.2 to 0.8-cm polypoid nodules involving the chordae tendineae of the anterior leaflet of the mitral valve (Fig 1A
). The polypoid nodules consisted primarily of fibrin with a peripheral population of large B cells (CD20+ by L26 and B1) showing oval to irregular nuclei, cleared chromatin, nucleoli, and mitoses; occasional plasmacytoid features were noted (Fig 1B). Clonality could not be definitively evaluated (although of prognostic utility, determination of monoclonality is not necessary for diagnosis of PTLD). The large lymphoid cells demonstrated Epstein-Barr virus (EBV) latent membrane protein by immunohistochemistry, and were positive for EBV encoded RNA by in situ hybridization. The patient's EBV serostatus was monitored beginning after the operation and suggested primary infection in the peritransplantation period. The donor's EBV serostatus was unknown. This PTLD was classified as a large cell lymphoma of B-cell type with plasmacytoid features [6].
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Fig 1. . (A) Gross photograph of anterior leaflet of mitral valve showing polypoid nodules attached to the chordae tendineae. (B) Photomicrograph of large B-cell lymphoid proliferation enmeshed in a fibrin network. Hematoxylin and eosin; x 400 before 28% reduction.)
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Comment
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Subsequent to the identification of PTLD in the 1970s, its association with primary EBV infection and immunosuppression has been discussed extensively [2, 6], with a comprehensive overview recently published by Nalesnik and Starzl [7]. Disseminated disease occurs in 23% to 86% of patients with PTLD, most often involving the brain, lung, or bowel [2, 4]. Cardiac involvement is not uncommon, with an incidence of 4% to 5% in all PTLDs (Penn I; personal communication based on data in Cincinnati Transplant Tumor Registry, 10/96). Allograft involvement occurs in up to 23% of all PTLDs [4, 8, 9], with an apparent affinity of PTLD for the allograft in cases of isolated organ involvement, possibly due to continued antigenic stimulation [6]. Rates of allograft involvement by PTLD vary widely depending on types of transplant, and are reported to be as high as 60% to 80% in heart-lung transplants (nearly always involving only the lung [2]), 17% to 33% in renal transplants, and 8.6% to 33% in liver transplants [2, 4, 6]. Although few studies have examined PTLD recurrence, it is of interest that no recurrence was identified in this case.
Our review of the literature found only 13 cases of cardiac allograft involvement by PTLDs [5, 8–14] (Table 1). Five reports specified areas within the heart involved by the lesion, including the myocardium, epicardium, and right coronary artery [8–11, 14]. Twelve of the 13 cases reported multiorgan involvement, and none reported PTLD restricted to the heart. Furthermore, the isolation of this lesion to the chordae tendineae of the anterior MV leaflet is a very unusual presentation of PTLD, and was not reported even in a literature review of cases of non–transplant-related cardiac lymphomas [15].
In conclusion, although infectious causes are more likely in the transplant patient population, PTLD involvement of heart valves should be considered when a patient shows no signs or symptoms of infection in the presence of a valvular mass detected by echocardiography or catheterization [14]. Delay of appropriate treatment due to misdiagnosis may allow progression of the PTLD [1, 5, 6]. Late-presenting PTLD (>1 year) in heart transplant recipients may be less responsive to treatment than early-presenting lesions (<1 year) [1], resulting in long-term mortality rates of between 70% and 92% [1, 2, 5].
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Acknowledgments
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We thank Drs Margaret E. Billingham, Israel Penn, and Thomas E. Starzl for their feedback on the manuscript.
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Footnotes
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Address reprint requests to Dr Myerowitz, The Ohio State University Medical Center, 410 W 10th Ave, N825 Doan Hall, Columbus, OH 43210 (e-mail: myerowitz.1{at}osu.edu).
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References
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- Armitage JM, Kormos RL, Stuart RS, et al. Posttransplantation lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant 1991;10:877–86.[Medline]
- Cohen J. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine 1991;70:137–60.[Medline]
- Harris KM, Schwartz ML, Slasky BS, Nalesnik M, Makowka L. Posttransplantation cyclosporine-induced lymphoproliferative disorders: clinical and radiologic manifestations. Radiology 1987;162:697–700.[Abstract/Free Full Text]
- Penn I. Tumors after renal and cardiac transplantation. Hematol Oncol Clin North Am 1993;7:431–45.[Medline]
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- Nalesnik MA, Jaffe R, Starzl TE, et al. The pathology of post-transplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. Am J Pathol 1988;133:173–92.[Abstract]
- Nalesnik MA, Starzl TE. Epstein-Barr virus, infectious mononucleosis, and posttransplant lymphoproliferative disorders. Transplant Sci 1994;4:61–79.[Medline]
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- Abu-Farsakh H, Cagle PT, Buffone GJ, Bruner JM, Weilbaecher D, Greenberg SD. Heart allograft involvement with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder. Arch Pathol Lab Med 1992;116:93–5.[Medline]
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- Gambacorta M, Bonacina E, Falini B, Sabattini E, Pileri S. Malignant lymphoma in the recipient of a heart transplant from a donor with malignant lymphoma: lymphoma transplantation or de novo disease? Transplantation 1990;51:920–2.
- Hanasono MM, Kamel OW, Chang PP, Rizeq MN, Billingham ME, van de Rijn M. Detection of Epstein-Barr virus in cardiac biopsies of heart transplant patients with lymphoproliferative disorders. Transplantation 1995;60:471–3.[Medline]
- Sibley RK, Olivari MT, Bolman RM, Ring WS. Endomyocardial biopsy in the cardiac allograft recipient: a review of 570 biopsies. Ann Surg 1986;203:177–87.[Medline]
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Abstract
Introduction
