Urothelial carcinoma of donor origin in a kidney transplant patient

Abstract

BackgroundMalignancy after transplantation is an uncommon multifactorial occurrence. Immunosuppression to prevent graft rejection is described as a major risk factor in malignancy development in the post-transplant state. Donor-derived malignancy is a rare reported complication. Herein, we review our patient history and discuss diagnostic strategies and the implications of immunosuppression for donor-derived malignancy.Case presentationThis is a 69-year-old man with post-renal-transplant urothelial carcinoma determined to be of donor origin. His course was complicated by BK virus at six years post-transplant; urothelial carcinoma was identified nine years post-transplant. Cystectomy was performed, but because of immunosuppression and underlying chronic kidney disease, the patient was considered ineligible for adjuvant chemotherapy. Two years after resection, screening MRI demonstrated retroperitoneal lymphadenopathy and a right upper pole mass in the transplanted kidney. Urine cytology confirmed the presence of malignant cells; FISH showed 2-8 copies of the X chromosome and no Y chromosome consistent with female origin of the malignant cells. CT-guided renal mass and paraaortic lymph node biopsies demonstrated that about 50 % of cells had an XY complement, while the remainder showed a XX genotype by chromosomal SNP microarray analysis. Immunosuppression was discontinued and the donor kidney removed. X/Y FISH of the urothelial carcinoma identified in the explanted kidney confirmed that the malignant cells were of female donor origin. Follow-up at 3, 6 and 12 months after discontinuation of immunosuppression and surgery demonstrated normalization of the lymphadenopathy and absence of new lesions.ConclusionsImmunosuppression is a major risk factor for development of malignancy in transplant recipients. Donor-derived malignancy can arise and current molecular studies allow an accurate diagnosis. Withdrawal of immunosuppression and surgical resection of the transplant kidney proved an effective treatment in our case.

Urothelial Carcinoma of the Graft Kidney With Molecular Analyses: A Rare Case Report

“…Following renal transplant, kidney cancer almost exclusively occurs in native kidneys with papillary RCC as the most common type 9 . However, donor-derived malignancies are rarely reported 6,7 . Our case is a rare donor-derived UC in the graft kidney with a few very interesting facts.…”

“…These patients also have a 3-fold increased risk of developing urothelial carcinoma (UC) in the native bladder, which is associated with BK polyomavirus. However, donor-derived UC is rarely reported 6,7 . We herein report a high grade papillary urothelial carcinoma of the graft kidney, involving the graft ureter and native urinary bladder, invading one left obturator lymph node, and sparing the two native kidneys and ureters.…”

Metastatic Urothelial Carcinoma from Transplanted Kidney with Complete Response to an Immune Checkpoint Inhibitor

“…We present a case of post-renal-allotransplantation donor-derived, disseminated UTUC that achieved complete response with transplant nephrectomy, retroperitoneal lymphadenectomy, immunosuppression cessation, and immunotherapy. There have been several cases described in the literature where withdrawal of immunosuppression has been sufficient for treatment of squamous cell carcinomas, undifferentiated epithelioid tumor, and donor-derived urothelial carcinoma in renal transplant patients [ 11 – 14 ]. To our knowledge, this is the first reported case where a patient who developed donor-derived urothelial carcinoma achieved complete response on immune checkpoint inhibitor therapy and is now considering a repeat renal transplant.…”

“…Features reported in 36 published allograft upper tract urothelial carcinoma (UTUC) cases include long latency (mean 10 years) from transplant to disease presentation, immunosuppression and BK infection as risk factors, and highly aggressive tumor biology [ 10 ]. Ortega et al described a case of donor-derived UTUC discovered nine years postrenal transplant and complicated by BK viremia six years posttransplant successfully managed with transplant nephrectomy and immunosuppression withdrawal [ 11 ].…”

Urologic malignancies in kidney transplantation

“…UC is rarely found in the transplanted kidney, and the allograft can often be preserved during treatment. However, there are case reports of allograft malignancies requiring either local resection and reconstruction or nephroureterectomy and lymphadnectomy . One of the largest series detailing treatment of bladder cancer after kidney transplantation followed standard therapy despite immunosuppression: intravesical BCG [live attenuated bacteria and works through immunomodulation and therefore has 2 implications in the transplant population: (i) may be less effective in someone receiving immunosuppression and (ii) immunosuppressed patients may be at higher risk for BCG complication including sepsis] for noninvasive tumors and radical cystoprostatectomy with lymphadenectomy and urinary diversion for invasive tumors .…”