Development of malignancy after solid-organ transplant is a well-known long-term complication of immunosuppressive therapy. Thus far, there are no specific oncologic recommendations regarding management of de novo tumors in transplanted kidneys. Here, we present the case of a 63-year-old male patient who developed a de novo renal cell carcinoma 6 years after the transplant procedure. The patient underwent nephron-sparing surgery with transperitoneal enucleation of the tumor. We discuss the decision-making process and the operative challenges that we faced. We conclude that this technique should be considered as a therapeutic strategy for selected patients so that transplant nephrectomy can be avoided.
Key words : Cancer, De novo, Immunosuppression, mTOR, Sirolimus
Development of malignancy after solid-organ transplant is a well-known long-term complication of immunosuppressive therapy.1,2 Until recently, data available regarding tumors developing in renal allografts were limited.3 Penn reported that all kidney cancers represented 4.6% of cancers observed in transplant patients, 10% of which occurred in kidney grafts.4 Tillou and associates reported that the incidence of de novo kidney allograft renal cell carcinomas (RCC) in a large retrospective cohort was 0.19%. The diagnosis is usually incidental during ultrasonography or computed tomography scan of the graft for various indications.5 Thus far, there are no specific oncologic recommendations regarding management of de novo tumors in transplanted kidneys. Tillou and associates recently reported the results of nephron-sparing surgery on transplant kidney tumors from the largest described cohort of patients in France.6
Our patient, a 63-year-old male, was diagnosed with end-stage renal failure due to lupus nephritis at the age of 51 years. He received a 1:1:0 mismatched kidney from a deceased from brain death donor at the age of 57 years. Maintenance immunosuppression consisted of tacrolimus at 1 mg twice a day, azathioprine at 125 mg twice a day, and a low dose of prednisolone at 5 mg once a day, which he had already been taking preoperatively.
Six years after the transplant procedure, the patient was investigated for nonspecific gastrointestinal symptoms. An abdominal ultrasonography scan detected a lesion in the kidney allograft that was biopsied and histologically confirmed to be RCC. He then had computed tomography and magnetic resonance scans that confirmed a 4.3 × 4-cm tumor located in the central part of the kidney (Figure 1) and ruled out distal metastases.
A multidisciplinary team discussion decided that partial nephrectomy would not be an option because of the tumor’s central location and size. Two further options were considered: (1) a transplant nephrectomy followed by renal replacement therapy, with potential retransplant in the future, and (2) an isolated excision of the tumor. The rationale to support the latter was based on the tumor appearing to be well encapsulated and because there was good allograft function. The great difficulty in obtaining vascular access for this particular patient was also taken into consideration. However, the team felt that a graft-sparing approach could be beneficial to the patient and, with the patient’s consent, a decision was made to proceed with excision of the tumor.
The transplanted kidney was approached transperitoneally through a lower midline incision. The graft was completely mobilized, and vascular control of the graft artery and vein was achieved separately. Once vascular control was achieved, tumor excision was performed in a bloodless field. The tumor had a well-defined capsule and was in effect enucleated outside the capsule through a plane of cleavage, a nonstandard procedure (Figures 2 and 3). The patient made an uneventful recovery and was discharged 6 days postoperatively. The same immunosuppression regimen was continued postoperatively. His creatinine levels 4 months postoperatively had returned to preoperative baseline levels, and the patient was clinically well.
Macroscopic examination of the specimen showed the tumor to measure 5.2 × 4.4 × 3.5 cm. The tumor appeared grossly to extend to within less than 1 mm of the deep (renal) margin. Histology showed a type 2 papillary RCC, Fuhrman grade 3, with probable microvascular invasion. There was no necrosis and no sarcomatoid change. Excision was marginal (< 1 mm). The patient, who received the paired kidney from the same donor, was well at the time of writing of this report (4 months postresection) with excellent graft function.
Although the first case of an allograft RCC was described in 1976,7 there are currently no guidelines on the management of de novo graft tumors in renal transplant patients. A basic principle is preservation of the kidney function, if possible. Size and location of the tumor, graft function, and patient’s general condition are the factors that influence the treatment modality of choice.
Treatment options described in the literature include a watchful waiting approach with periodic follow-up with ultrasonography, open and laparoscopic graft nephrectomy, open and laparoscopic partial nephrectomy, radiofrequency ablation, percutaneous cryoablation, and robotic-assisted laparoscopic partial nephrectomy.5,8,9
Graft nephrectomy is generally the preferred approach for good oncologic prognosis, although it returns the patient to hemodialysis. Poorer survival outcomes for hemodialysis versus prognosis with RCC and improved experience with partial nephrectomies have led to a shift toward partial nephrectomy as the preferred option for certain cases. Partial nephrectomy is generally considered for single, peripheral, small (usually smaller than 4 cm) lesions.8,10
Mundel and associates described a case similar to ours that was managed with enucleation of a 2-cm tumor from an allograft kidney. This was a relatively small tumor, and the authors did not comment on whether the approach was trans- or extraperitoneal.11
Our patient underwent a tumor enucleation that may not be entirely curative, based on the histology report suggesting the possibility of vascular invasion and marginal excision. It is hoped that conversion to sirolimus could prevent a relapse. Recent literature suggests that modification of the immunosuppression therapy, with reduction or suspension of calcineurin inhibitors and introduction of mammalian target of rapamycin inhibitor-based agents, is associated with a reduction in the incidence of posttransplant malignancy12,13 and a decrease in the potential for recurrence and progression of the tumor after surgical treatment of RCC in transplant patients.5
Temsirolimus and everolimus have demonstrated survival benefits for advanced RCC in the general population and metastatic RCC originating in the native kidneys of transplant patients, but there is no evidence of its effects on allograft RCC.14,15 Not needing to modify the dose for age or renal function makes everolimus ideal for cases of malignancy in the kidney graft where there may be a need to continue with immunosuppression treatment.16 Although a promising therapeutic intervention, there is no consensus on this strategy and further research is necessary to address the conversion to mammalian target of rapamycin inhibitor therapy in allograft RCC before any recommendations can be made.8
In conclusion, this is a case report of transperitoneal enucleation of a central de novo RCC in an allograft kidney. This technique, to the best of our knowledge, has not been previously reported for a large, central tumor, and we believe it represents an interesting and challenging therapeutic maneuver, from both a decision-making perspective and an operative point of view. However, it should be considered as a therapeutic strategy for selected patients so that transplant nephrectomy can be avoided.
Volume : 16
Issue : 5
Pages : 614 - 616
DOI : 10.6002/ect.2016.0037
From the 1Department of Renal and Pancreas Transplantation and the
of Histopathology, Manchester Royal Infirmary, Manchester, United Kingdom; the
3Department of Nephrology, Salford Royal NHS Foundation Trust, Salford, United
Kingdom; and the 4Institute of Human Development, University of Manchester,
Manchester, United Kingdom
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Ioannis Sarantitis, Department of Renal and Pancreas Transplantation, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK
Phone: +44 77 5215 4053
Figure 1. Magnetic Resonance Scan of the Abdomen Showing Size and Location of the Renal Cell Carcinoma
Figure 2. Tumor Being Enucleated in an Avascular Field After Vascular Control of the Allograft Vessels
Figure 3. The Allograft With the Dead Space That the Tumor Occupied Before Approximation and Closure