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Adult Urology

enal Cell Carcinoma in Renal Transplantatients

uiz Estevan Ianhez, Marcos Lucon, William Carlos Nahas, Emil Sabbaga,uiz Balthazar Saldanha, Antonio Marmo Lucon, and Miguel Srougi

BJECTIVES To report our experience with renal cell carcinoma in patients with end-stage renal failurereceiving dialysis at two institutions that perform a large number of transplantations. Renal cellcarcinoma is more frequent in patients with end-stage renal failure treated with dialysis and inrenal transplant patients than in the population at large.

ETHODS We reviewed the case histories of 1375 consecutive patients who had transplanted kidneysfunctioning for more than 1 year.

ESULTS Eleven renal tumors were found in 10 patients (1.37%); 10 of the tumors (90%) were in thenative kidney (9 unilateral and 1 bilateral) and 1 (10%) was in the transplanted kidney. Thetumors in the native kidneys were discovered incidentally. Three were in organs removed fortreatment of arterial hypertension and the other seven were found by ultrasonography. Thetumor in the transplanted kidney was found after nephrectomy for the treatment of hematuria.The tumor types were clear cell in six, papillary in four, and chromophobe in one. Of the 9patients who were treated with radical nephrectomy, 7 were alive with no evidence of the diseaseand 2 had died of other causes, also with no evidence of the disease. One patient who alreadyhad metastases at the diagnosis did not undergo surgery and died 4 months later.

ONCLUSIONS The native kidneys of renal transplant patients should be examined by ultrasonography annuallybecause they are at greater risk of renal cell carcinoma. Radical nephrectomy cures those casesin which the tumors are clinically localized and 6 cm or less in size. UROLOGY 69: 462–464,

2007. © 2007 Elsevier Inc.

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he immunosuppression necessary for the preser-vation of renal function achieved in patients whohave received renal transplants leads to an inci-

ence of prostate cancer twice that of the population atarge and to an incidence of bladder cancer and testicularancer that is three times greater and an incidence ofenal cancer that is 15 times greater.1 These latter tumorsan appear in the transplanted kidney but are morerequent in the native one, especially in those who de-elop acquired cystic disease.2 The objective of this studyas to describe the incidence, diagnosis, treatment, his-

ologic type, and outcome of cases with transplantedidneys and renal tumors.

ATERIAL AND METHODS

he case histories of 1375 consecutive patients who had hadenal transplants functioning for more than 1 year from twonstitutions (1125 at Hospital das Clinicas of the Medicalchool of the University of São Paulo and 250 at the Hospital

rom the Department of Urology, São Paulo University Medical School, São Paulo, Sãoaulo, BrazilReprint requests: Marcos Lucon, M.D., Department of Urology, São Paulo Uni-

ersity Medical School, Avenida Enéas de Carvalho Aguiar, 255, São Paulo, São Paulo

t5403-000, Brazil. E-mail: mlucon@uol.com.brSubmitted: June 17, 2006; accepted (with revisions): November 16, 2006

62 © 2007 Elsevier Inc.All Rights Reserved

lemão Oswaldo Cruz) were reviewed. In all patients, routineltrasound scans were obtained every 2 years or as deemedecessary during follow-up because of loss of renal function,rinary infection, or hematuria.

ESULTSleven renal tumors were found in 10 patients (1.37%).f the 11 tumors, 10 (90%) were in the native kidney (9

nilateral and 1 bilateral) and 1 (10%) was in a trans-lanted kidney that had been donated by the patient’sother and had ceased to function after 156 months.his patient had a second transplanted kidney that was

unctioning normally. The diagnosis of renal cell tumorpapilliferous type, grade II) had been made after ne-hrectomy to treat severe hematuria arising in this sameidney. The mean patient age was 47 years (range 25 to5), 8 patients were men and 2 were women, and theean period of dialysis was 25.4 months (range 0 to 40).he mean time from end-stage renal failure and theiagnosis and treatment of the renal tumor was 101onths (range 43 to 267).The 10 tumors in the native kidneys were incidental

ndings: 3 of them in 2 patients whose organs wereemoved by bilateral nephrectomy to treat arterial hyper-

ension and the other 7 by ultrasonography. Six of the

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atter were treated with radical nephrectomy; one ofhese patients did not undergo surgery because he pre-ented with metastases at diagnosis (case 6). The tumorn the nonfunctioning kidney was found after nephrec-omy for the treatment of hematuria.

The tumor size, histologic type, Fuhrman grade, andutcomes are given in Table 1. Seven patients were stilllive with no evidence of the disease, two had died ofther causes (one of myocardial infarction and one ofquamous cell carcinoma), and one had died 4 monthsfter diagnosis of lung and cerebral metastases withoutndergoing surgery (case 6). This was the only patientho presented with Stage IV disease, a 10-cm tumor, andetastases. All the tumors in the native kidneys were

ssociated with acquired cystic disease.

OMMENTn patients with transplanted kidneys, the tumors of therinary tract are the second most frequent, immediatelyfter those of the skin.3 The organs most affected are therostate, kidneys, bladder, and testes. The 15 timesreater frequency of renal tumors in patients with renalransplantation than in the population in general is notue solely to immunosuppression. Kidney cancer haseen found in 1.8% to 4.2% of routine nephrectomies,efore transplantation.4,5 Acquired renal cystic disease isidely prevalent in dialysis patients, and its incidence

ncreases with the duration of treatment. In this series,nd in others,2,6 tumors in native kidneys have beenssociated with the presence of acquired cystic renalisease, but this correlation has not always been foundie, the absence of acquired cystic renal disease does notreclude the propensity to develop a renal tumor).7 Longeriods of dialysis are not needed for tumors to appear,uch as was the case for Patient 8 of our series and forthers7 whose tumors were diagnosed before dialysis be-an. The period could be as short as 8 months,8 although

Table 1. Pathologic data of tumors and outcome of trans-planted patients

Pt.No.

HistologicClassification

Size(cm) Grade Outcome

1 Papillary 6 III Alive at 124 mo2 Clear cell 3.5 I Dead of MI at 24 mo3 Chromophobic 3.5 I Dead of penile tumor

at 33 mo4 Clear cell 3 I Alive at 92 mo5 Clear cell 3.5 I Alive at 192 mo6 Clear cell 10 IV Dead at 4 mo*7† Papillary 3 III Alive at 4 mo

2 I8 Clear cell 2 II Alive at 24 mo9 Clear cell 3 III Alive at 4 mo

10‡ Papillary 2 I Alive at 14 mo

MI � myocardiac infarction.* Not treated (no surgery).† Bilateral.‡ Transplanted kidney.

he series with long follow-up periods (average 102

ROLOGY 69 (3), 2007

onths) found an incidence of 3.9%,7 greater than thatf the series with shorter follow-up periods (average 48onths) in which the incidence was 1.6%.2

In most cases in our series and in other series, theiagnosis has been made by ultrasonography. However, inur series, routine ultrasonography every 2 years did noteveal tumors that were later found in kidneys removedor the treatment of arterial hypertension nor in theonfunctioning transplanted kidney removed because ofematuria. This is why all the patients undergoing dial-sis or who have received renal transplants should un-ergo abdominal ultrasonography at least annually. Therevalence of the histologic types of renal cell tumors inur cases, as in others,6 was the same as that whichccurred in nontransplanted patients; most were thelear cell type followed by the papillary type and thehromophobic type. Other investigators have not hadhese results.2,7,9 Radical nephrectomy cured all of ouratients with Stage I renal tumors, as already described.7

atients with tumors that are larger often progress toeath,8 as happened to one of our patients.

Tumors of the transplanted kidneys are 10 times lessrequent than those of the native kidneys.10 The diagno-is is made by ultrasonography, and if the tumor is small,t can be removed by partial nephrectomy to preserveenal function.11,12 The histologic type can be clear cellr papillary. In our case, ultrasonography did not revealhe tumor, instead hematuria was the symptom that ledo the diagnosis.

ONCLUSIONSenal transplant patients should be examined by ultra-

onography of the native kidneys annually because theyre at greater risk of renal cell carcinoma. Radical ne-hrectomy cures those cases in which the tumors arelinically localized and 6 cm or less in size.

eferences

1. Kasiske B, Snyder JJ, and Gilbertson DT: Cancer after kidneytransplantation in the United States. Am J Transplant 4: 905–913,2004.

2. Heinz-Peer G, Schoder M, Rand T, et al: Prevalence of acquiredcystic kidney disease and tumors in native kidney of renaltransplant patients: a prospective study. Radiology 195: 667–671, 1995.

3. U.S. Renal Data System: USDRDS 2003 Annual Data Report:Atlas of End Stage Renal Disease in the United States. Bethesda,National Institute of Health, National Institute of Diabetes andDigestive and Kidney Diseases, 2003.

4. Denton MD, Magec CC, and Ovuworie C: Prevalence of renal cellcarcinoma in patients with ECRD pre transplantation: a pathologicanalysis. Kidney Int 61: 2201–2209, 2002.

5. Fischeredeer M, and Janch KW: Prevalence of cancer history priorto renal transplantation. Transpl Internet 18: 779–784, 2005.

6. Hughson MD, Schmidt L, Zbar B, et al: Renal cell carcinoma ofend-stage renal disease: a histopathologic and molecular genetic

study. J Am Soc Nephrol 7: 2461–2464, 1996.

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7. Douvlet JD, Peraldi MN, Gattegno B, et al: Renal cell carcinoma ofnative kidneys: prospective study of 129 renal transplant patients.J Urol 158: 42–44, 1997.

8. Kliem V, Kolditz M, Behrend M, et al: Risk of renal cell carcinomaafter kidney transplantation. Clin Transpl 11: 255–258, 1997.

9. Muruve NA, and Schoskes DA: Genitourinary malignancies insolid organ transplant recipients. Transplantation 80: 709–716,

2005.

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0. Penn I: Occurrence of cancer in immunosuppressed organ trans-plant recipients. Clin Transpl 12: 147–158, 1998.

1. Burama A, St-Louis G, Nicolet V, et al: Renal carcinoma in kidneyallografts: a case series from a single center. Am J Transpl 5:3015–3018, 2005.

2. Moudouni SM, Tligui M, Doublet JP, et al: Nephron-sparing sur-gery for de novo renal cell carcinoma in allograft kidneys. Trans-

plantation 80: 865–867, 2005.

UROLOGY 69 (3), 2007