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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 1  |  Page : 139-143
Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss

1 Department of Medicine, Section of Nephrology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
2 Department of Medicine, Section of Nephrology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia; Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt
3 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

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Date of Web Publication15-Jan-2016


The incidence of renal cell carcinomas (RCCs) in renal transplant recipients is reported as 1.1-1.5% in the native kidneys and 0.22-0.25% in the renal allograft. There are no data to support routine surveillance for tumors in transplant recipients. Most reported cases of RCCs occurring in renal allografts were incidental findings in asymptomatic patients. Herein, we report the second case of lone chromophobe RCC (ChRCC) of the renal allograft presenting with weight loss. Loss of weight is a presenting symptom in one-third of ChRCCs occurring in the native kidneys in the general population. Based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical nephrectomy. We suggest that RCCs should be considered in the differential diagnosis of a transplant recipient presenting with weight loss even in the absence of localizing symptoms or signs.

How to cite this article:
Althaf MM, Al-Sunaid MS, Abdelsalam MS, Alkorbi LA, Al-Hussain TO, Dababo MA, Haq N. Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss. Saudi J Kidney Dis Transpl 2016;27:139-43

How to cite this URL:
Althaf MM, Al-Sunaid MS, Abdelsalam MS, Alkorbi LA, Al-Hussain TO, Dababo MA, Haq N. Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Dec 4];27:139-43. Available from: https://www.sjkdt.org/text.asp?2016/27/1/139/174165

   Introduction Top

For patients with end-stage renal disease (ESRD) of any cause, the best option for renal replacement therapy in terms of long-term survival and quality of life is transplantation. [1],[2] Living donor renal transplants have the longest half-life of around 12 years. [3] Patient death with a functioning graft continues to be a major problem. [4],[5] While there are many causes of graft failure, rejection due to alloimmunity and glomerular disease are more common. [6] Renal transplant recipients have a higher incidence of malignancy for any organ system as compared with the general population, with cutaneous and hematological malignancies having the highest incidence as a result of the use of immunosuppressive medication. [7],[8] The risk of developing renal cell carcinoma (RCC) in the native kidneys of transplant recipients is 15-times higher than in the normal population. [7] In four major studies, where retrospective analysis was conducted among their renal trans-plant recipients, the incidence of RCC was 1.1-1.5% and 0.22-0.25% in native kidney and renal allograft, respectively. In all these studies, the diagnosis of RCC in the allograft was an incidental finding on routine imaging performed for other reasons and the patients were clinically asymptomatic. [9],[10],[11],[12] In three other case reports of RCC in the renal allograft, the patients were asymptomatic and the tumor was detected on imaging carried out for other reasons. [13],[14],[15] We are presenting a patient who lost her graft as a result of post-transplant lone chromophobe RCC (ChRCC) as the only histological subtype in the renal allograft who presented with a poor appetite and significant weight loss. To the best of our knowledge, this is the second case of RCC in a renal allograft with the histological diagnosis of pure ChRCC without any other cell type. Our patient presented with weight loss as the predominant symptom. The first reported case of a ChRCC in the literature was by Greco et al, [16] which was detected as an incidental finding in a 13.5-year-old boy 5 years after receiving a living-related renal transplant.

   Case Report Top

A 20-year-old female with ESRD of unknown etiology had undergone a living related kidney transplantation five years ago. The donor was her older brother who was 24 years old at the time of donation. The donor was healthy and renal workup was unremarkable. The patient was on hemodialysis for a few months and then switched to peritoneal dialysis before transplantation. The early post-transplant period was complicated with delayed graft function and biopsy performed at that time revealed mild acute tubular necrosis with no evidence of acute rejection. She required a few sessions of hemodialysis and received a total of 12 doses of intravenous thymoglobulin (total dose of 900 mg) to avoid possible rejection and delay the start of calcineurin inhibitor. For prophylaxis against cytomegalovirus infection, she received valgancyclovir 450 mg once daily. Her renal function improved and she was off hemodialysis by Day 7 post-transplant. Protocol biopsy performed two months after the transplant revealed moderate interstitial fibrosis with tubular atrophy and no evidence of acute rejection. Serum creatinine at that time was 75μmol/L. She was maintained on tacrolimus 3 mg twice daily, mycofenolate mofetil 750 mg twice daily and prednisone 5 mg daily. Two months after the transplant, she developed newonset diabetes and was treated with metformin as well as dietary and lifestyle modification. Unfortunately, her glycemic control had been erratic and over time she re-quired incremental doses of mixtard insulin 70/30 reaching up to 55 units in the morning and 25 units in the evening, together with a total metformin dose of 1500 mg. Despite this regime, her HbA1c was ranging between 9.0 and 13.0. Her post-transplant period was unremarkable except for an episode of urosepsis with Klebsiella pneumoniae three years after transplantation, treated with 14 days of intravenous meropenem. An ultrasound of the graft at that time was unremarkable.

In May 2012 (5 years post-transplant), the patient complained of worsening appetite and weight loss. Records revealed that she lost 12.4 kg between April 2011 (52.3 kg) and May 2012 (39.9 kg). Her weight loss had been steady and represented a loss of 26.3% of her body weight. Serum creatinine was unchanged from her baseline of 110 μmol/L. Physical examination was unremarkable and there was no evidence of graft tenderness. She was admitted for work up of unexplained weight loss. The differential diagnosis included malignancy, poor glycemic control, endocrine dysfunction or chronic infection. Routine laboratory investigations were unremarkable. Further work-up included computed tomography (CT) of the chest, abdomen and pelvis in search for an occult malignancy. The CT scan revealed a heterogeneous mass with contrast enhancement arising in the upper half of the transplanted kidney measuring 2.5 cm × 3.0 cm × 2.5 cm [Figure 1]a. The R.E.N.A.L nephrometry score [17] was calculated to be 9×. Based on the TNM classification, [18] it was scored as Stage I, T1aNxM0. Ultrasound imaging of the graft is shown in [Figure 1]b. Ultrasound-guided fine needle aspiration of the mass was performed and microscopic examination revealed loosely cohesive clusters of tumor cells that have koilocytoid appearance with abundant cytoplasm and occasional binucleation [Figure 2]a. Immunohistochemical stain for cytokeratin 7 (SP52, Ventana) was performed on cell block and showed diffuse strong cytoplasmic staining. The diagnosis was ChRCC. The patient was counseled that the best treatment would be radical graft nephrectomy due to her moderatecomplexity nephrometry score. She agreed and the procedure was performed without any complications. Hemodialysis was initiated via a right internal jugular tunneled catheter. Macroscopically, the excised kidney showed a well-circumscribed firm mass measuring 3.5 cm × 3 cm × 2.5 cm and located in the renal pelvis. The cut-surface was tan-brown with foci of hemorrhage. Microscopically, the tumor was composed of solid sheets and variable nests consisting of cells with pale and eosinophilic cytoplasm with frothy appearance and perinuclear halo. Prominent cell membranes, binucleation and raisinoid nuclei were identified [Figure 2]b. Thus, the diagnosis of ChRCC was confirmed.
Figure 1: (a) Computed tomography showing a mass (arrow) arising from the transplanted kidney in the right iliac fossa and (b) ultrasound of the renal allograft.

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Figure 2: (a) Fine needle aspiration cytology and (b) histopathology.

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   Discussion Top

ChRCCs of the native kidney in the general population often remains clinically silent. The classical triad of hematuria, pain and flank mass is present in only a small percentage of patients, and often indicates advanced disease. Other signs and symptoms include hypochromic anemia secondary to hematuria or hemolysis (29-88%), pyrexia (20%) and cachexia, fatigue and weight loss (33%). [19] Our case is unique as it is most probably the second case of pure ChRCC arising in a renal allograft presenting with weight loss. As previously mentioned, the reported incidence of RCC in renal allografts is around 0.22-0.25%. [9],[10],[11],[12] Surveillance for tumors in renal allograft remains controversial, with no data to support early or more frequent screening. [20] It is important to note that in the reported cases of RCC occurring in the renal allograft, diagnosis was either made on routine screening in asymptomatic recipients or by serendipity in patients presenting with a different clinical picture. Histological subtypes of RCC arising in allografts documented in the literature include clear cell carcinoma, papillary cell carcinoma (chromophillic and eosinophilic cytoplasm) and sarcomatoid RCC. [10],[11],[12] ChRCC occurring in a renal allograft was reported in one case occurring in an allograft in association with clear cell carcinoma. This also was as an incidental finding on routine imaging, and that patient was asymptomatic. [9] The first case of lone ChRCC was reported in a 13.5-year-old boy five years after receiving a living-related renal transplant. That tumor was found by serendipity during the evaluation of fever and inguinal lymphadenopathy. [16] It is also interesting to note that the incidence of RCC in patients with a cardiac transplant is similar to the general population, suggesting that development of RCC is unaffected by immunosuppression. [21] We had a second look at the pre-transplant imaging performed for her donor and there was no evidence to support that the tumor may have been pre-existing. The donor was called again after the recipient was diagnosed with RCC to be screened and the work-up was negative.

To the best of our knowledge, we report the second case of lone ChRCC in a renal allograft where the patient presented with worsening appetite and steady significant weight loss over the period of one year. While others [15] have reported success with nephron-sparing treatment using percutaneous ultrasoundguided radiofrequency ablation, in our patient based on the R.E.N.A.L nephrometry score of the tumor of 9×, our patient was categorized as having a moderate-complexity nephrometry score. If partial nephrectomy was attempted, it carries a higher risk of surgical complications such as post-operative bleeding and/or urinary fistula. Low-complexity nephrometry score (between 4 and 6) tumors are ideal for partial nephrectomy with minimal complications. After a multidisciplinary meeting with renal transplant surgery, renal pathology and oncology, based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical allograft nephrectomy. The patient and her family were counseled and they consented to radical allograft nephrectomy. Currently, no standard of treatment has been established and most of the evidence is from small retrospective series or anecdotal cases. [22] However, establishing the diagnosis at an early stage leads to favorable patient survival. [23] We suggest that RCCs occurring in a renal allograft should be considered in the differential diagnosis of a recipient presenting with weight loss even in the absence of localizing signs along with the other common conditions.

Conflict of Interest: None declared.

   References Top

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Kontodimopoulos N, Niakas D. An estimate of lifelong costs and QALYs in renal replacement therapy based on patients' life expectancy. Health Policy 2008;86:85-96.  Back to cited text no. 2
Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: A critical reappraisal. Am J Transplant 2011;11:450-62.  Back to cited text no. 3
Cosio FG, Hickson LJ, Griffin MD, Stegall MD, Kudva Y. Patient survival and cardiovascular risk after kidney transplantation: The challenge of diabetes. Am J Transplant 2008;8:593-9.  Back to cited text no. 4
Gill JS, Rose C, Pereira BJ, Tonelli M. The importance of transitions between dialysis and transplantation in the care of end-stage renal disease patients. Kidney Int 2007;71:442-7.  Back to cited text no. 5
El-Zoghby ZM, Stegall MD, Lager DJ, et al. Identifying specific causes of kidney allograft loss. Am J Transplant 2009;9:527-35.  Back to cited text no. 6
Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905-13.  Back to cited text no. 7
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Ploussard G, Chambade D, Meria P, et al. Biopsy-confirmed de novo renal cell carcinoma (RCC) in renal grafts: A single-centre management experience in a 2396 recipient cohort. BJU Int 2012;109:195-9.  Back to cited text no. 9
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Chakera A, Leslie T, Roberts I, O'Callaghan CA, Cranston D. A lucky fall? Case report. Transplant Proc 2010;42:3883-6.  Back to cited text no. 13
Gerth HU, Pohlen M, Thoennissen NH, et al. Two papillary renal cell carcinomas of different origin following renal transplantation (Case report). Oncol Lett 2012;4:80-2.  Back to cited text no. 14
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Greco AJ, Baluarte JH, Meyers KE, et al. Chromophobe renal cell carcinoma in a pediatric living-related kidney transplant recipient. Am J Kidney Dis 2005;45:e105-8.  Back to cited text no. 16
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Linehan WM, RB, Yang J. Cancer of the Kidney. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology, 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.  Back to cited text no. 19
EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.3. Cancer risk after renal transplantation. Solid organ cancers: Prevention and treatment. Nephrol Dial Transplant 2002;17 Suppl 4:32, 34-6.  Back to cited text no. 20
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Vera-Badillo FE, Conde E, Duran I. Chromophobe renal cell carcinoma: a review of an uncommon entity. Int J Urol 2012;19: 894-900.  Back to cited text no. 22
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Correspondence Address:
Naveed Haq
Department of Medicine, Section of Nephrology, MBC #46, King Faisal Specialist Hospital and Research Center, P. O. Box 3354, Riyadh 11211, Kingdom of Saudi Arabia

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.174165

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