ADENOCARCINOMA ON RENAL ALLOGRAFT AS A COMPLICATION AT 5 YEARS

Abstract

We report a new case of renal carcinoma in allograft kidney, 5 years after transplantation, which presented as a suspect allograft abscess in a complex history of recurrent urinary infection. Only surgical management with peroperative histological evaluation permitted us to confirm the diagnosis of malignancy.

The increased incidence of malignancy in organ transplant recipients is currently well documented. Primary carcinomas of the kidney account for 4.6% of cancers in renal transplant recipients compared with 3% in the general population ⁽¹⁾. The majority of these cases develop in the native kidneys in cases of acquired renal cystic disease in end stage renal failure ⁽²⁾. The risk of renal carcinoma in allograft kidney is inadvertently introduced via the transplant organ and from de novo tumor development enhanced by immunosuppression ⁽³⁾.

CASE REPORT

The recipient was a 26-year-old woman with spina bifida and high grade bilateral vesicorenal reflux in the neurological bladder, who gradually lost renal function over a 10-year period. To prevent upper tract damage, a clam enterocystoplasty with bilateral ureteral reimplantation was performed. However, the patient progressed to end stage renal disease and, after a brief period on hemodialysis, received a cadaveric renal transplant. The donor was a 30-year-old man who died of a cerebral hemorrhage. Maintenance immunosuppression therapy comprised prednisone 10 mg daily and azathioprine 25 mg every day. A number of urinary infections after renal transplant, particularly pyelonephritis, was reported and easily explained by the patient's previous medical history. A severe reflux was observed in the transplanted kidney on retrograde cystography. Anticholinergic medication with clean intermittent catheterization was proposed to decrease bladder pressure. The patient remained asymptomatic for 6 months until she presented with fever and soreness in the area above the renal allograft. During this episode, a significant alteration of white blood cell count and creatinine level was confirmed from laboratory data.

Ultrasonic evaluation confirmed an enlarged allograft with a large lesion, localized at the mediorenal region, measuring 7.5×6.8 cm. Despite broad spectrum antibiotics, a heterogenous tumor was confirmed few days later by computerized tomography (Fig. 1). The differential diagnosis of infection process and allograft abscess was lymphoma, chronic rejection, or renal cell carcinoma. A surgical approach was decided and a large excision of this lesion with peroperative histological analysis was performed. Microscopic examination revealed renal cell carcinoma associated with multiple areas of necrosis and hemorrhage and because of the size and the localization of the tumor, an en bloc radical transplant nephrectomy was carried out (Fig. 2). There was no capsular penetration or renal vein or lymph node involvement. DNA analysis of the tumor was clearly different from the recipient DNA. At 2 years follow-up, there is currently no evidence of disease at the last routine computerized tomography scan.

Figure 1: CT scan of renal allograft with voluminous suspected tumoral lesion.

Figure 2: Macroscopic illustration of the mediorenal tumor after transplant nephrectomy. We observed a cystic center of the tumor with multiple areas of necrosis and hemorrhage with surrounding renal carcinoma cells.

DISCUSSION

A recent review of the Cincinnati Transplant Tumor Registry has well documented the increased incidence of cancer in allograft recipients. Of the 256 posttransplant de novo kidney tumors, 222 arose in native kidneys and 24 developed in the allograft itself ⁽¹⁾. It has been well established that immuno-suppression itself can facilitate subclinical tumor growth. Chronic antigenic stimulation, from the allograft or from repeated infections, may induce lymphocytic proliferation and lead to the development of lymphoproliferative disorders such as loss of suppressor T cell function. Another complication that must be reported is the transfer of malignancy grafting cancerous organs in recipients ⁽⁴⁾. According to Penn ⁽⁵⁾, the risk of transmitting such malignant lesions was recently computed as 43 to 47%. No apparent tumor at the time of harvesting are usually transplanted, neverless small tumors or disseminated tumor cells lodging within the kidney are not visible despite the conventional battery of tests that are given in the donnor work-up ⁽⁶⁾.

Generally, renal cell carcinomas in transplant kidneys are less aggressive than those in the native kidneys ⁽⁷⁾. This fact was confirmed in our observation of a low grade Führman tumor. Currently, there are more than 20 tumors known to have arisen from a renal allograft and the majority of these have been treated by transplant nephrectomy ⁽¹⁾. To our knowledge, only four cases of partial nephrectomy in a transplant kidney for malignancy have been reported ^{(8, 9)}. Tumor excision was proposed to be small (2 to 3 cm) low-grade lesions and facilitated by preoperative selective embolization of a segmental artery. In our patient, the transplant lesion with the history of recurrent urinary infection initially suggested an allograft abscess or infection process. Due to noncontributive computerized tomography scan evaluation and the size of the tumor, we decided to propose surgery with large excision and peroperative histological examination rather than a percutaneously biopsy of this lesion. As the diagnosis was a renal cell carcinoma with a potential risk of local recurrence, we performed a transplant nephrectomy with the resection of the main renal vessels at their anastomotic origins rather than in the hilum. The DNA analysis confirmed that the tumor in fact originated from the allograft tissue ⁽¹⁰⁾. Immunosuppression was discontinued except for prednisone with currently no disease recurrence. A minimum of a 2-year waiting period was recommended before attempting a new transplantation.

In conclusion, ultrasound examination combined with baseline biopsy of grafts before transplantation is easy to perform and should be considered in the future to avoid donor-associated malignancies. Moreover, the recipient should undergo close follow-up with serial CT of the allograft to detect renal cell carcinoma at an early stage, which could be suggested by atypical infectious symptoms.