Follow-up of a pair of renal transplant recipients from a donor with a malignant lymphoma

Richard E. Power1, Molly P. Eng1, Elaine W. Kay2, David P. Hickey1 and Dilly M. Little1,

1 Department of Transplantation Surgery and 2 Department of Pathology, Beaumont Hospital, Dublin, Ireland

Keywords: graft nephrectomy; malignant lymphoma; renal transplant



   Introduction
 Top
 Introduction
 Case report
 Discussion
 References
 
Transmission of cancer from donor organs is a well recognized phenomenon. Despite the exclusion of patients with a malignancy and extensive screening of potential cadaveric donors, sporadic cases of donor-transmitted malignancy continue to be reported. The consensus amongst most clinicians upon diagnosing an occult malignancy in a donor would be to withdraw immunosuppression and explant the graft. We report the outcome of two cadaveric renal transplant recipients when it transpired on subsequent autopsy that the donor had an occult malignant lymphoma.



   Case report
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 Introduction
 Case report
 Discussion
 References
 
A bilateral donor nephrectomy was performed on a 34-year-old Caucasian male. No other organs were retrieved. The cause of death was secondary to a head injury sustained in a motorcycle accident. There were no other injuries; he had a normal urinary output and a serum creatinine of 86 mmol/l. There was no significant past medical history. The donor received no inotropic support.

Within 24 h both kidneys were transplanted. Recipient 1 was a 51-year-old female. She was dialysis dependent (continuous ambulatory peritoneal dialysis; CAPD) secondary to adult polycystic kidney disease and on the transplant waiting list for 6 weeks. She had a panel reactive antibody (PRA) of 0% and received a 1:1:1 mismatched graft. The left kidney was implanted onto the right external iliac vessels. The cold ischaemic time was 14 h and the warm ischaemic time was 28 min.

The second recipient was a 47-year-old male who again was dialysis dependent (CAPD) secondary to chronic glomerulonephritis. He was on the transplant waiting list for 10 weeks. He had a PRA of 0% and received a 1:0:1 mismatched graft. The contralateral right kidney was implanted onto the right external iliac vessels. The cold ischaemic time was 17 h and the warm ischaemic time was 35 min.

Post-transplant immunosuppression consisted of cyclosporine, azathioprine and prednisolone. Cyclosporine dosage is altered to maintain whole blood levels within the range of 250–350 ng/dl (Incstar®) initially and 200–300 ng/dl by 6 months. Azathioprine and prednisolone were tapered to maintenance doses of 25 and 7.5 mg daily, respectively. Both patients received anti-pneumocystis (PCP) treatment using trimethoprimsulphamethoxazole. Both grafts functioned immediately with reduction in serum creatinine on day 1. On the third day post-transplant, an autopsy result carried out on the donor indicated an occult malignant lymphoma found in a lymph node, measuring 1x1.5 cm, sampled from the duodenal-jejunal flexure. The autopsy was performed, as this was a coroner's case. The appearances were of a small, centrocytic cell, B-cell lymphoma, BCL-2 positive. It was described as a low-grade lymphoma but extra-nodal spread occurs in 30% of cases (Figures 1 and 2).



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Fig. 1.  Histological section from the retrieved lymph node from the duodenal-jejunal flexure. This section shows a malignant lymphoma, follicular and diffuse pattern, centrocytic, B-cell type. There is extracapsular extension of the malignant lymphoid cells (H & E, magnificationx100). This figure can be viewed in colour as supplementary material at NDT Online.

 


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Fig. 2.  Immunohistochemical staining show the atypical cells to be of B-cell phenotype and to be BCL-2 positive (H & E, magnificationx40). This figure can be viewed in colour as supplementary material at NDT Online.

 
Both recipients were informed of these findings and the lack of sound medical evidence to base an outcome upon. Ultrasonography of both grafts revealed no suspicious lesions. Recipient 1 decided to opt for a graft nephrectomy 16 days post-transplant having attained a creatinine of 122 mmol/l. She commenced on haemodialysis and 19 months later she was re-transplanted and has good graft function to date. Recipient 2 having had a normal transplant renal biopsy, decided not to have his functioning graft removed and was discharged home on day 14 post-transplant with a serum creatinine of 176 mmol/l. He is currently very well with a serum creatinine of 167 mmol/l and is 5 years 2 months post-transplant. His immunosuppression was maintained in accordance with our department's protocol, i.e. not reduced. He is seen and examined 3 monthly in outpatients with routine bloods and a renal ultrasound.



   Discussion
 Top
 Introduction
 Case report
 Discussion
 References
 
It has been estimated that the risk of transferral of malignancy with a transplanted kidney ranges from 32 to 43% if the donor is known to harbour a tumour [1]. Accordingly, each donor must be carefully screened pre-operatively for possible neoplasms, careful examination of all organs at the time of harvesting with biopsy of any suspicious lesions and routine donor kidney biopsy if possible. McCanty et al. [2] go as far as advocating ultrasonography of all donor kidneys. Donors who have malignancies should not be used with the following exceptions: low-grade skin neoplasms, such as basal cell carcinomas; carcinoma in situ of the uterine cervix; or primary brain tumours, which rarely spread outside the central nervous system [3].

A difficult decision arises when a donor has a past history of cancer treatment in the remote past. Most surgeons would accept a 5-year and, certainly a 10-year, disease-free survival as evidence of a ‘cure’. However, it is well recognized that late metastases do occur and it is possible that these may be present as micrometastases at the time of organ retrieval and thus may be transplanted into a recipient. However, one must also consider the critical shortage of cadaver organs in some countries and the surgeon must weigh the small, but real risk of transplanting cancer with organs from such a donor against the hazard of discarding many potentially usable organs [3].

When a kidney has been transplanted from a cadaver donor in whom a subsequent autopsy shows a previously unsuspected cancer the consensus would be to promptly remove the allograft and if cancer becomes evident at a later stage the allograft should be removed and immunosuppression discontinued [4]. Our case illustrates such a situation where a recipient made an informed decision to retain their allograft having been informed of the donor autopsy findings (malignant B-cell lymphoma) and the potential risk for transferral of a malignancy.

Malignant lymphoma is a frequent complication of organ transplantation. It is postulated that such neoplasms arise as a result of uncontrolled proliferation of Epstein–Barr virus (EBV)-infected B lymphocytes in an immunosuppressed host [5]. Several authors would agree that malignant transformation of donor lymphocytes can occur in solid organ recipients in the absence of EBV genetic material [5,6]. Herzig et al. [7] propose that treatment of a malignant lymphoma of donor origin could consist of reduction of immunosuppression before graft removal to facilitate a host-versus-tumour response.

To the best of our knowledge this is the first reported case whereby a recipient of an organ from a donor with a malignant B-cell lymphoma has no evidence of malignancy 5 years post-transplantation. Registry data would suggest that there is a 43% chance that the allograft contains neoplastic cells [2] but the recipient opted not to have a graft nephrectomy. We have not performed routine graft biopsies in this recipient as a negative biopsy would not exclude systemic seeding of neoplastic cells and furthermore, allograft biopsies are not without associated morbidity. In conclusion, we do not recommend that a recipient keep their allograft in all circumstances, but the recipient should be informed of the medical uncertainty surrounding these cases and their decision fully respected.



   Notes
 
Correspondence and offprint requests to: Miss Dilly Little, Consultant in Urology and Transplantation, Beaumont Hospital, Dublin 9, Ireland. Email: richiep{at}eircom.net Back



   References
 Top
 Introduction
 Case report
 Discussion
 References
 

  1. Penn I. Transmission of cancer with donor organs. Transplant Proc1988; 20: 739–740[ISI][Medline]
  2. McCanty TC, Jonsson J, Khawand N, Ali A, Edson M, Light J. Transferral of a malignancy with a transplanted kidney. Transplantation1989; 48: 877–879[ISI][Medline]
  3. Penn I. Transmission of cancer from organ donors. Ann Transplant1997; 2: 7–12[Medline]
  4. Penn I. Malignancy in transplanted organs. Transplant Int1993; 6: 1–3[ISI][Medline]
  5. Hjelle B, Evans-Holm M, Yen TS, Garovoy M, Guis M, Edman JC. A poorly differentiated lymphoma of donor origin in a renal allograft recipient. Transplantation1989; 47: 945–948[ISI][Medline]
  6. Meduri G, Fromentin L, Vieillefond A, Fries D. Donor-related non-Hodgkin's lymphoma in a renal allograft recipient. Transplant Proc1991; 23: 2649[ISI][Medline]
  7. Herzig KA, Falk MC, Jonsson JR et al. Novel surveillance and cure of a donor-transmitted lymphoma in a renal allograft recipient. Transplantation2000; 70: 149–152[ISI][Medline]
Received for publication: 4. 4.02
Accepted in revised form: 4. 7.02





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