1 Departments of Nephrology, 2 Medical Oncology, 3 Surgery and Transplantation, and 4 Pathology, Baskent University Faculty of Medicine, Ankara, Turkey
Keywords: Kaposi's sarcoma; non-Hodgkin's lymphoma; renal transplantation
Introduction
Although renal transplantation is the preferred treatment for patients with end-stage renal disease transplant recipients are at substantially higher risk of developing several types of malignancies due to their immunosuppressive treatment. Non-Hodgkin's lymphoma (NHL) and Kaposi's sarcoma (KS) are the most common tumours found in patients following solid organ transplantation, but these usually occur as separate entities. Solid organ transplantation is associated with a greater than 40-fold increase in the incidence of NHL, and a 400-fold increase in the incidence of KS. NHL and KS represent 16% and 4% of all post-transplantation tumours, respectively [1].
While the increased incidence of these malignancies as sequelae to renal transplantation has been well documented, the literature cites only two cases of simultaneous NHL and KS following solid organ transplantation [2,3]. We could find no data concerning the development of lymphoma in recipients who had received organs from the same donor. Here we present the cases of two patients who received a kidney from the same donor; one who developed NHL and KS simultaneously, and another who developed cutaneous T cell NHL.
Case reports
Case 1
A 52-year-old man was diagnosed with end-stage renal disease secondary to autosomal dominant polycystic kidney disease (ADPKD). In January 1997, after 3 years of haemodialysis, the patient underwent cadaveric kidney transplantation. Immunosupressive treatment of cyclosporin A (CsA) (3 mg/kg/day), azathioprine (1.5 mg/kg/day), and prednisone (10 mg/day) was maintained during the post-transplantation period. Fourteen months post-surgery, the patient developed hyperaemic skin lesions on his chest. Physical examination revealed purple lesions on the oral mucosa and right axillary lymphadenopathy. Pathological evaluation of a mucosal biopsy specimen revealed spindle cells with moderate atypia forming slits containing red blood cells. The lymph node and skin biopsy specimens contained diffuse lymphoid tumour cells with large nuclei, prominent nucleoli, and were CD20-positive with frequent mitoses. The lesions of the oral mucosa were diagnosed as KS, and lymph node and skin biopsies indicated the presence of B cell NHL. Computed tomography of the chest and abdomen revealed only inguinal lymphadenopathy. There was no infiltration of NHL on examination of the patient's bone marrow biopsy. We tested for the presence of human herpesvirus type 8 (HHV8) DNA using the polymerase chain reaction, and the result was negative.
We started combination systemic chemotherapy of cyclophosphamide, adriamycine and vincristine, discontinued the azathioprine treatment, and reduced the dose of CsA to 1.5 mg/kg/day. Twenty-six months after transplantation, the patient had normal graft function and both malignancies had been in complete remission for 8 months after beginning the chemotherapy.
Case 2
In January 1997, a 46-year-old woman underwent renal transplantation, receiving the second kidney from the cadaveric donor that was involved in case 1. The aetiology of end-stage renal failure in this patient was ADPKD, and she had undergone 2 years of haemodialysis by the time of her surgery. The patient was treated with a similar immunosuppressive regimen to that used to treat case 1 and she experienced no complications in the immediate post-transplantation period. However, at 13 months post-surgery, the patient developed purple subcutaneous nodules on her hip and abdomen. Biopsies of the nodules were taken and histological study confirmed the presence of dermal atypical lymphocyte infiltration, several immunoblastic cells, frequent mitotic activity, and angiotrophism. Atypical lymphocytes were stained with T cell marker (UCHL-1) and CD30 antibodies. A diagnosis of T cell NHL was made based on these findings, and radiotherapy treatment was initiated at the lesion sites. Azathioprine was discontinued and the dose of CsA was decreased to 1.5 mg/kg/day. While the patient's renal function remained normal, her cutaneous lesions recurred 2 months after the radiotherapy had been discontinued. Radiotherapy was recommenced and the dose of CsA was again reduced, this time to 1 mg/kg/day. She had normal graft function and was in complete remission at 13 months after radiotherapy.
The incidence of NHL and KS is markedly higher in patients who have undergone renal transplantation than in the general population. It has been shown that the risk of developing malignancy increases with longer graft survival time [4]. Penn [4] reported that when CsA was given, the average time for the appearance of NHL was 15 months, while that for KS was 20 months. Our male patient presented with both NHL and KS at 14 months following renal transplantation and our female patient presented with NHL at 13 months post-transplantation.
The development of NHL and KS in immunosuppressed patients is thought to have an infectious origin. At present, the aetiologic factors behind the high incidence of lymphoproliferative disorders in transplant recipients are not well understood. These conditions are predominantly B cell neoplasia, and in many cases EpsteinBarr virus (EBV) antigens have also been detected in the tumour cells. Thus, it has been hypothesized that these lymphomas arise as a result of antigenic stimulation by viral antigens, in conjunction with impaired immunologic surveillance due to T cell suppression by CsA [5]. This agent is also known to induce cutaneous, benign T lymphocyte infiltrates and pseudolymphomas [6]. It is likely that CsA causes an imbalance in T cell regulatory systems, which ultimately results in an expanded T-cell subpopulation. HHV8 DNA has been found in the transplantation-related form of KS, and in a rare variant of lymphoma [7]. As mentioned above HHV8 DNA was not found in case 1.
Based on an extensive literature search, our male patient with KS and B cell NHL and our female patient with cutaneous T-cell NHL exhibit rare findings [2,3,11]. Two cases of simultaneous KS and NHL have been reported in Saudi Arabia, where KS is the most common tumour found in renal transplant recipients [2,3].
The therapeutic approach to NHL and KS in solid organ transplant recipients involves the reduction or cessation of immunosuppression in hopes of achieving regression of the tumour [4]. In our patients, we discontinued all azathioprine therapy and decreased the CsA doses. In case 1, we also used combination chemotherapy of cyclophosphamide, adriamycine and vincristine, and achieved complete remission. In our second case, the desired response was achieved with radiotherapy, but cutaneous lesion recurrence 2 months later dictated that radiotherapy be resumed and the CsA dosage be further reduced.
There is currently no data in the literature on the development of lymphoma in multiple recipient organs from one donor. Solid organ transplantation is associated with the transfer of biologically active lymphocytes. These transplanted lymphocytes can undergo malignant transformation, as evidenced by lymphomas that have arisen after allogenic bone marrow transplantation [8]. The possibility that the numerous types of lymphoma that arise in solid organ allografts are of donor cell origin has not been investigated in depth. However, intragraft lymphomas have been reported in transplanted kidneys and hearts [9]. In addition, Spiro reported one case with lymphoma of donor origin occurring in the porta hepatis of a transplanted liver, whereas lymphoma was not seen in two renal recipients with grafts from same donor [10].
The significance of our two cases, and the conclusions that can be drawn from them are several.
Notes
Correspondence and offprint requests to: Mehmet Haberal, MD, FACS, Departmet of General Surgery and Transplantation Unit, Rector of Baskent University, Baskent University Hospital, Fevzi Çakmak Bulvar 10. Sokak No:45, Bahçelievler, Ankara 06490, Turkey.
References