| Abstract|| |
We reviewed the incidence and types of de novo malignancies which developed in 792 renal transplant recipients who received their grafts between 1979 and 1996 and followed up for an average period of 5.6 years. There were 56 malignant tumors detected in 54 patients, representing an overall incidence of 6.8%. These tumors occurred in a relatively young group of patients whose average age was 33.4 years at the time of transplantation and 40 years at the time of diagnosis of malignancy. The average latency period between transplantation and malignant disease was 7.4 years for solid tumors and 16 months for Kaposi's sarcoma. Tumors included 39 Kaposi's sarcomas, four malignant lymphomas, three hepatomas, two bladder cancers, one renal cell carcinoma of the allograft, two colorectal cancers, two thyroid cancers, one adenocarcinoma of unknown primary, one nasopharyngeal carcinoma and one leiomyosarcoma of the uterus. Kaposi's sarcoma was the most common malignancy and comprised 70% of all tumors in this study. It is imperative for renal transplant recipients to have diligent follow-up at regular intervals for early detection of cancer.
Keywords: Renal transplantation, Malignancy, Immunosuppression, Saudi Arabia.
|How to cite this article:|
Shaaban AA. Incidence and Types of Malignant Tumors in Renal Transplant Recipients: A Single Center Experience. Saudi J Kidney Dis Transpl 1998;9:116-22
|How to cite this URL:|
Shaaban AA. Incidence and Types of Malignant Tumors in Renal Transplant Recipients: A Single Center Experience. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2020 Feb 29];9:116-22. Available from: http://www.sjkdt.org/text.asp?1998/9/2/116/39282
| Introduction|| |
Renal allograft recipients have a well documented increased incidence of malignant neoplasia, particularly cancers of the skin and lips, malignant lymphomas and Kaposi's sarcoma ,,,,, . Conversely, malignancies commonly encountered in the general population, such as carcinoma of the breast, prostate, lung and colon are not seen more frequently in transplant recipients , .
Immunosuppression is known to favor the development of various types of tumors ,,, . The other possible risk factors in the development of post transplant malignancies include chronic antigenic stimulation, activation of oncogenic viruses, carcinogenic action of immuno-suppressive agents, uremia and genetic susceptibility.
Renal transplant surgery had started in Riyadh Armed Forces Hospital (RAFH) and developed in Saudi Arabia since 1979. The patient and graft survival in our institution is as good as the international results , .
The purpose of this retrospective follow up study was to evaluate the incidence and frequency of different types of malignancies which occurred after renal transplantation.
| Patients and Methods|| |
From March 1979 to December 1996, 792 renal transplant patients presented for periodic follow up in Riyadh Armed Forces Hospital: 453 patients were males and 339 females. Grafts were given from living donors in 471 patients and from cadavers in 321. Of these, 5% had more than one transplant [Table - 1].
The immunosuppressive regimens were modified over the time period of the study. The early protocols included azathioprine and prednisolone. Since 1982, cyclosporin A has been utilized in combination with prednisolone and/or azathioprine. Only two patients received FK506. Cyclosporin A was administered orally with an initial dose of 12 mg/kg body weight to reach a blood concentration of 600-800 ng/ml (measured by RIA Abbott in whole blood), for the initial 6 months, and a level of 400-600 ng/ml thereafter. Azathioprine was given at 2 mg/kg body weight and based on the leucocyte and lymphocyte count. Prednisolone was reduced from 250 mg intraoperatively to 60 mg/day for 2 days then to 30 mg/day and gradually tapered to a final maintenance dose of 7.5-10 rag/day. Patients with immunological rejection received 3-4 doses of methyl prednisolone 500 mg each, intravenously.
In this retrospective study, patient records were reviewed and data were collected on cancer patients in terms of sex, age, post-transplant period, types of denovo tumors, treatment and outcome.
| Results|| |
The 792 patients were followed for an average period of 5.6 years after renal transplantation (range 3 months to 17 years). The average age at transplant was 33.4 years (range 11-60 years).
Incidence of Malignancy:
There were 56 tumors in 54 patients (6.8% of those included in the study).
Age and Sex of Patients with Malignancy:
Post transplant malignant tumors developed in 37 males and 17 females. The average age of patients at the time of diagnosis of their malignant tumors was 40 years (range 20-65 years).
Time between Transplantation and Appearance of Malignancy:
The average latency period between transplantation and diagnosis of malignant tumors was 7.4 years (range 3-189 months) for solid tumors and 16 months (3 to 89 months) for Kaposi's sarcoma.
Types of Malignant Neoplasms:
All tumors were de novo malignancies. Thirty-nine patients had Kaposi's sarcomas (4.9% of all patients, 70% of all tumors) which were the most common. Of these, one female patient had associated non-Hodgkin's lymphoma and one male patient had papillary carcinoma of the thyroid. The characteristics of 17 patients who developed tumors other than Kaposi's sarcoma are summarized in [Table - 2]. Four patients had non-Hodgkin's lymphoma (7% of all tumors) with no evidence of previous Epstein Barr virus (EBV) infection and all tumors were large cell lymphomas.
Three patients had hepatocellular carcinoma, two patients were hepatitis B virus positive and one patient was hepatitis C virus positive. Two patients had bladder carcinoma; one was multifocal transitional cell carcinoma associated with bilharziasis after 13 years of transplantation, and the other was in situ squamous cell carcinoma associated with bilharziasis and condyloma acuminatum after 18 months of transplantation. One patient developed undifferentiated renal cell carcinoma 28 months after transplantation. The other malignancies were two colorectal cancers, two papillary cancers of the thyroid, one adenocarcinoma of unknown origin, one nasopharyngeal carcinoma and one leiomyosarcoma of the uterus.
| Discussion|| |
The risk of development of malignant neoplasms in renal transplant recipients is approximately 100 times greater than in the general population  . Data from several large renal transplant programs show an overall incidence of cancer ranging from 4 to 18%, with an average of 6% , . Most of the malignancies are de novo neoplasms, while a very small number of tumors are transplanted accidentally from a cadaver or a living donor  .
In this study, the incidence of malignant tumors in 792 renal allograft recipients who have been followed for an average period of 5.6 years, was 6.8% which is in agreement with the literature , . The tumors occurred in a relatively young group of patients whose average age was 33.4 years at the time of transplantation and 40 years at the time of diagnosis of their malignant tumors. Sixty eight percent of patients were males and 32% females. The average interval between transplantation and development of malignancy was 7.4 years for solid tumors and 16 months for Kaposi's sarcoma.
Our study demonstrates high incidence of Kaposi's sarcoma (KS) in renal transplant recipients versus a negligible incidence in the general Saudi population  . This figure is close to the 6% incidence quoted by Penn  . However, the frequency of malignancies other than KS in this report is low: a finding that seems to be peculiar to our patients. This discrepancy might be explained by genetic and/or environmental factors. Kaposi's sarcoma is the most common malignancy in renal transplant recipients in Saudi Arabia ,,,, . It comprised 70% of all tumors in this study. There is a high incidence of KS in transplant patients who are Arab, Black, Jewish or of Mediterranean ancestry  . The tumor is a multicentric vascular neoplasm of mesenchymal pluripotent cell origin and presents in two forms: nonvisceral KS (60%) confined to the skin or oropharynglolaryngeal mucosa and visceral disease (40%) involving mainly the gastrointestinal tract, lungs and lymph nodes , . Diagnosis and staging of KS depend on biopsy of the accessible lesions, CT scans of abdomen and chest in addition to upper and lower gastrointestinal endoscopy  . The mainstay of treatment of post transplant KS is reduction or discontinuation of immunosuppressive therapy  . Other modalities include rediotheraphy, recombinant interferon alpha and chemotheraphy. The outcome of patients with nonvisceral JS in much better than those with visceral disease. Children with JS seemed to be particularly prone to pulmonary disease without skin involvement and the prognosis was generally poor  . Comprehensive reports were previously published on patients with KS from our hospital ,,, .
The incidence of malignant lymphomas in this study is low(7%) compared with the 23% incidence reported by Penn  . All of our four patients had non-Hodgkin's lymphoma with no evidence of previous Epstein Barr virus (EBV) infection and all tumors were large cell lymphomas. Post transplant lymphomas differ from their counterparts in the general population in several aspects  . Most tumors are non-Hodgkin's lymphomas. There is a higher incidence of extranodal involvement especially the central nervous system. Another remarkable feature is the frequency of eithermicroscopic or macroscopic allograft involvement which occurs in 23% of patients. Histologically, the infiltrate may be mistaken for rejection. Because there is an ill-defined zone between inflammatory and neoplastic growth of lymphocytes, some pathologists prefer to use the term: post transplant lymphoprolifrative disorder (PTLD)  .
The increased incidence of post transplant hepatomas was described with a substantial number of patients having previous hepatitis B virus infection and occasionally hepatitis c virus infection ,, . The etiologic relationship between hepatitis virus infection, liver cirrhosis and hepatocellular carcinoma has been widely observed. In this study, two hepatitis B and one hepatitis C antigen-positivepatients had developed hepatoceflular carcinoma.
In this report, two cases of low stage bladder cancer developed in bilharzial patients 18 and 156 months after renal transplantation. The interplay of immunosuppression and urinary bilharziasis might be responsible for the carcinogenesis. Previously reported cases of condyloma acuminata and associated urothelial malignancy may result from involvement by human papilloma virus which was not detected in our patient  . Carcinoma of the bilharzial bladder was reported to be advanced and muscle invasive at the time of diagnosis  conversely, the early diagnosis of both bladder cancers in this report might be attributed to the regular follow up of renal transplant recipients and endoscopic assessment once lower urinary symptoms had appeared.
Development of bladder carcinoma in renal transplant recipients poses special diagnostic and therapeutic problems. It may be necessary to visualize the native upper urinary tract by retrograde ureteropyelography to exclude other foci of urothelial cancer  . Also, if compromised allograft function precludes excretory urography, retrograde or antegrade ureteropyelographic studies may be necessary. The mainstay of treatment of superficial bladder cancer remains transurethral resection and diligent follow up cystoscopy. Adjuvant intravesical therapy was indicated in multifocal recurrences of transitional cell carcinoma. Presently, Bacillus Calmette-Gurein (BCG) is the most effective agent known for the prevention of recurrence and progression of this disease  . However, intravesical BCG should be avoided in immunosuppressed patients as it may amplify the consequences of systemic infection and its local efficacy may be decreased  . Also, thiotepa may increase the toxic effects of immuno-suppressive agents on the hematopoietic cells. On the other hand, interferon is useful id the treatment of transitional cell carcinoma by direct inhibition of tumor cell growth and enhancement of the tumoricidal capacity of host defense cells  . We used this agent in the treatment of transitional cell carcinoma because of its efficacy, negligible systemic absorption and minimal toxicity.
Several reports in the literature have suggested that the prevalence of renal cell carcinoma is greater in hemodialysis patients and in the native kidneys of renal transplant recipients than in the general population , . Predisposing factors include analgesic nephropathy and acquired cystic disease. Contrary to these reports, we treated a case of renal cell carcinoma of the transplanted kidney harvested from a patient with brain tumor four years after transplantation. This tumor may have developed de novo after transplantation or it was present, although not clinically evident, in the kidney at the time of harvesting from the donor. It should be emphasized that the potential donors with brain tumors should be avoided if they have been surgically treated or when these cancers are expected to be metastases from an occult primary neoplasm  .
Cancers that develop in renal transplant recipients frequently demonstrate a more aggressive biologic behavior than do similar tumors in patients who have not undergone transplantation  .
Other reports on post transplant malignancy have been published from different countries ,,,, . It is generally accepted that malignancy is a long-term complication of immuno-suppression per se, independent of the agents used.
| Conclusions|| |
From this study, we conclude that Saudi kidney transplant recipients have a higher incidence of malignant tumor development than the general population and that the most frequent type is Kaposi's sarcoma. It is necessary for patients to have diligent follow up at regular intervals for the development of signs of cancer. Furthermore, efforts should be directed to define effective immuno-suppressive protocols that are associated with a lower incidence of malignancy.
| Acknowledgements|| |
The author is grateful to Dr. Abdullah A. Al-Khader and all colleagues in the Department of Nephrology, Riyadh Armed Forces Hospital, for their valuable help in data collection and contribution on editing the manuscript.
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Atallah A Shaaban
Department of Urology, Armed Forces Hospital, P.O. Box 7897, Riyadh 11159
[Table - 1], [Table - 2]