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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 1  |  Page : 271-275
De novo chromophobe renal cell carcinoma in the graft three decades after renal transplantation in a patient with a history of three renal transplants

Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

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Date of Submission16-Jan-2019
Date of Acceptance03-Mar-2019
Date of Web Publication3-Mar-2020


De novo renal allograft tumors were reported sporadically. Most of them were small, low-grade, and papillary renal cell carcinoma (RCC) type. A 46-year-old male presented with hematuria three decades after the first transplant. The patient had a history of three renal transplants. A tumor (12 cm × 13 cm) was diagnosed in the nonfunctioning first transplanted kidney. Radical nephrectomy of the graft harboring the tumor with preservation of the adjacent functioning graft was done and identified to be chromophobe RCC. After two-year follow-up, the patients had a perfect graft function with no evidence of oncological failure. We suggest that allograft tumor be considered in patient evaluation for hematuria. Regular follow-up imaging of transplanted kidney is mandatory even after graft failure for early detection of graft tumors.

How to cite this article:
Zahran MH, Soltan MA, Kamal AI, Abdelrahim M, Fakhreldin I, Osman Y, Ali-El-Dein B. De novo chromophobe renal cell carcinoma in the graft three decades after renal transplantation in a patient with a history of three renal transplants. Saudi J Kidney Dis Transpl 2020;31:271-5

How to cite this URL:
Zahran MH, Soltan MA, Kamal AI, Abdelrahim M, Fakhreldin I, Osman Y, Ali-El-Dein B. De novo chromophobe renal cell carcinoma in the graft three decades after renal transplantation in a patient with a history of three renal transplants. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2022 May 20];31:271-5. Available from: https://www.sjkdt.org/text.asp?2020/31/1/271/279952

   Introduction Top

Renal transplant patients are very delicate population due to immunosuppression (IS) therapy, which raises the incidence of infection and malignancy. Young recipients have 15-30-fold greater risk of developing malignancy in comparison to age-matched popu- lation.[1] Renal cell carcinoma (RCC) is the most common form of genitourinary malignancy in these patients with a reported incidence of 0.3%-3.9%, whereas renal graft RCC is 10 times less than those of native kidneys.[2]

Till now, the characteristics of graft renal tumors are not well elucidated. This is because of the limited number of the reported cases in literature. Graft RCC may be transmitted from the donor or de novo arising from the recipient.[3] The time limit between transmitted and de novo RCC is unclear. While two years or less between transplantation and diagnosis of graft tumor was considered a cutoff value for transmitted malignancy,[4] a diagnosed case of transmitted graft RCC was confirmed after 21 years.[5]

Unlike normal population, papillary RCC is the predominant form. It is reported in 50% of cases after renal transplant.[3] In two cases only, renal allograft chromophobe RCC was reported.[6],[7] Herein, we report on the 3rd case of chromophobe RCC diagnosed in non-functioning graft 30 years after transplantation in patients who received three transplanted kidneys.

   Case Report Top

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Twenty-nine years ago, an 18-year-old male attended to our hospital with end-stage renal disease (ESRD). His medical history was significant for hypertension (HTN) and persistent hematuria over the preceding 10 years. No renal biopsies were done prior to presentation. The patient received his first renal allograft from his father on April 1989. The grafted kidney was placed in the right lumbar region. The renal vessels were anastomosed to common iliac vessels. The postoperative course was smooth apart from an early mild acute cellular rejection, which was reversed by pulse steroid. The patient was maintained on steroid, cyclosporine, and azathioprine, as a maintenance IS. Two years later, he presented again with graft impairment. Graft biopsy revealed mild degree of chronic tubulo-interstitial fibrosis with no evidence of rejection. The patient’s serum creatinine continued to creep, reaching ESRD on 1995, and the patient resumed chronic hemodialysis.

Two years later, he received his second allograft from his brother in the Kingdom of Saudi Arabia. This kidney was placed in the left iliac region. The second transplantation was uneventful on early stages, but unfortunately, the graft function deteriorated slowly because of chronic rejection in spite of being maintained on steroid, tacrolimus, and myco- phenolic acid protocol. He reached ESRD again on 2002.

In the following year, he received his third renal allograft from an unrelated donor in Pakistan. The graft was placed in the right iliac fossa caudal to the first transplanted kidney. The patient was maintained on steroid, cyclos- porine, and mycophenolic acid. He suffered two attacks of cellular rejection in the 1st year, which were totally reversed by high-dose steroid treatment and then enjoyed a perfect graft function.

In January 2017, he attended complaining of recurrent attacks of hematuria. He has diabetes mellitus, HTN, and hypothyroidism. Ultra- sonography revealed pyelonephritis in both native kidneys and the graft on the left iliac region. On the right iliac region, there was a solid mass related to the upper pole of a normal kidney graft. His serum creatinine was 1.5 mg/dL. The results of all other laboratory tests were normal. Non-contrast computed tomography was done, which revealed that the failed 1st graft is a seat of heterogeneous soft- tissue mass which measured 12 × 13 cm with calcific foci inside the mass [Figure 1]a. Magnetic resonance imaging demonstrated that the failed graft is a seat of heterogeneous soft-tissue mass (12 × 13 cm) with abnormal signal intensity. The mass is in close relation to the upper pole of the functioning graft [Figure 1]b.
Figure 1: The renal graft tumor; (a) non-contrast spiral computed tomography of the abdomen and pelvis, (b) magnetic resonance imaging of the abdomen and pelvis.

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The patient was prepared for graft tumor nephrectomy. In supine position and under general anesthesia, he was explored via right para-rectal incision at the site of the previous scar. The tumor was approached extraperito- neally. The first transplanted kidney was a seat of large tumor arising and replacing the upper and middle zones of the kidney. The graft was dissected from the caudal functioning graft and from the surrounding tissue. Selective ligation and division of the artery, vein, and ureter was done. The mass was sent for histo- pathological examination. The wound was closed in layers leaving one drain.

On examination of the specimen, the tumor was composed of large polygonal cells arranged in alveolar pattern. The cells had distinct cell border and abundant pale eosinophilic granular cytoplasm. The nuclei were rounded to ovoid with irregular nuclear membrane and peri- nuclear halo. The tumor exhibited focal areas of hemorrhage and necrosis [Figure 2]a. The renal vein was patent. The ureter showed mild mucosal inflammatory changes. The immuno- histochemical profile was positive for cyto- keratin 7 [Figure 2]b, epithelial membrane antigen, and CD117 [Figure 2]c, while it was negative for CD10 and racemose. The diagnosis of chromophobe RCC was settled, Stage III (pT3a) [Figure 3].
Figure 2: The intraoperative finding of the graft tumor; (a) the functioning graft, (b) the nonfunctioning graft harboring the tumor, and (c) the graft tumor.

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Figure 3: Histopathological illustration of the tumor specimen using H and E (a and b), CK-7 (c), and CD-117 (d).

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The postoperative course was uneventful, and the patient was discharged safely with perfect graft function (serum creatinine was 1.5 mg/ dL). We modified the IS and maintained him on steroid, cyclosporine, and m-TOR inhibitor (rapamycin), with close follow-up keeping a high index of suspicious toward the development of rejection at any time. After two years of follow-up, the patient is living with normal graft function with no evidence of tumor recurrence or distant metastasis.

   Discussion Top

Paradoxically to the dogma of increased incidence of renal tumors in transplant patients, de novo renal graft tumors were reported sporadically with an incidence of 0.2%-0.7%.[3] Among 3000 live-donor renal transplants, this is the first case of a diagnosed renal graft tumor (0.03%). The exact etiology of the lower incidence of graft tumor is unknown. This may be attributed to the high selection criteria for all live donors. Genetic analysis can identify the origin of the tumor, however, this may be of clinical significance in deceased transplant in order to follow up closely other recipients of the same donor.

Most of the reported graft’s tumors were small in size and of low-grade. Histologically, papillary type was the predominant type followed by clear cell RCC.[3] Chromophobe RCC was reported previously in two cases after five years of live donor renal trans- plant.[6],[7] This is the third reported case of renal allograft chromophobe RCC. Unlike the previous two cases, the tumor had a delayed onset (after 334 months), larger in size, and developed in a nonfunctioning graft. In the three cases, the donors were genetically related. There was no evidence of hereditary RCC in the previous cases. In our case, the donor denied any history of malignancy after the onset of donation with negative screening for other common malignancies.

Unlike the incidental diagnosis graft RCC, this case and the two previously reported chro- mophobe RCCs were symptomatic. In the first case, the tumor was diagnosed during the evaluation of fever and inguinal lymphadeno- pathy.[7] Weight loss and loss of appetite were the presenting symptoms in the second case.[6]

Herein, hematuria was the presenting symptom, and the patient has no other lower urinary tract symptoms.

Despite the reported favorable prognosis of chromophobe RCC and the small size of the lesion (2.1 cm and 2.5 cm × 3 cm, respectively), transplantectomy was the treatment of choice in the previously reported cases. Two explanations were postulated. First, the patient’s young age and data deficiency regarding the prognosis and biological behavior of this tumor in the context of long-term immuno- suppression.[7] Second, the moderate complex nephrometry score (RENAL nephrometry scoring 9×) with high risk of postoperative surgical complications.[6] Here, the tumor was very large and originated from a non-functioning graft, so transplantectomy was performed aiming to preserve the caudal functioning graft.

The relation between IS and development of de novo graft RCC is not confirmed yet. Modulation of the IS regimen after diagnosis of malignancies in renal transplant population is not well established. However, the use of mammalian target of rapamycin (mTOR) inhibitors seems to be the most interested targeted therapy in this situation because of its anti- neoplastic properties. IS was maintained in most of the cases after partial nephrectomy or minimally invasive procedure. Reduction of the dose or shift to mTOR inhibitors was the main reported modification.[3],[8]. No reported rejection episode or deterioration of the graft function was reported in the last year.

De novo renal allograft RCC should be considered in patient evaluation for hematuria. It can develop at any time throughout patients’ life, so annual abdominal ultrasound scan is recommended for early detection of renal mass even in nonfunctioning graft.

Conflict of interest: None declared.

   References Top

Webster AC, Craig JC, Simpson JM, Jones MP, Chapman JR. Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: A cohort study of 15,183 recipients. Am J Transplant 2007;7:2140-51.  Back to cited text no. 1
Viart L, Surga N, Collon S, Jaureguy M, Elalouf V, Tillou X. The high rate of de novo graft carcinomas in renal transplant recipients. Am J Nephrol 2013;37:91-6.  Back to cited text no. 2
Tillou X, Doerfler A, Collon S, et al. De novo kidney graft tumors: Results from a multicentric retrospective national study. Am J Transplant 2012;12:3308-15.  Back to cited text no. 3
Penn I. Primary kidney tumors before and after renal transplantation. Transplantation 1995;59: 480-5.  Back to cited text no. 4
Park KI, Inoue H, Kim CJ, Tomoyoshi T. Nephron sparing surgery for de novo renal cell carcinoma in an allograft kidney: A case report. Int J Urol 1997;4:611-4.  Back to cited text no. 5
Althaf MM, Al-Sunaid MS, Abdelsalam MS, et al. 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.  Back to cited text no. 6
[PUBMED]  [Full text]  
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. 7
Barama A, St-Louis G, Nicolet V, Hadjeres R, Daloze P. Renal cell carcinoma in kidney allo- grafts: A case series from a single center. Am J Transplant 2005;5:3015-8.  Back to cited text no. 8

Correspondence Address:
Mohamed H Zahran
Urology and Nephrology Center, Mansoura University, Mansoura
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.279952

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