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Acquired Renal Cystic Disease and Renal Cell Carcinoma in an Allograft Kidney
0022-5347/95/1532-0395$03.00/0
THEJOURNAL OF UROLOGY Copyright 0 1995 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol 153, 395-396, February 1995 Printed i n V.S.A.
ACQUIRED RENAL CYSTIC DISEASE AND RENAL CELL CARCINOMA I N AN ALLOGRAFT KIDNEY J. CHANDLER WILLIAMS, PAUL A. MERGUERIAN, ALAN R. SCHNED AND PATRICIA M. MORRISON From the Section of Urology, Department
of
Surgery and Departments of Pathology and Internal Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
ABSTRACT
Acquired renal cystic disease has been reported in the kidneys of patients with end stage renal disease who have been untreated, treated with dialysis or undergone renal transplantation. The incidence of renal tumor development in patients with acquired renal cystic disease is greater t h a n 5% in those undergoing chronic hemodialysis. Recently, cases of renal cell carcinoma occurring with acquired renal cystic disease of the native kidneys of transplant recipients have been reported. Transplant patients have an increased incidence of malignancy when compared to t h e general population. Including our case, 19 cases of de novo renal neoplasms developing in renal allografts have been reported. To t h e best of our knowledge we report the longest interval to presentation of a de novo renal tumor in a n allograft kidney (228 months) and the first case of renal cell carcinoma associated with acquired renal cystic disease in an allograft kidney. KEYWORDS:carcinoma, renal cell; kidney transplantation; kidney; kidney neoplasms; immunosuppression
Transplant patients have an increased incidence of malignancy compared to the general population.' The natural history of cancers developing in renal transplant patients often is more aggressive than that in the general population,' which is thought t o be a complication of immunosuppressive therapy used in organ tran~plantation.~ Transplantation of tumor within the donated organ has also been documented.435The development of de novo renal cell carcinoma in a renal allograft has been reported infrequently.6 We report a case of a small renal cell carcinoma developing in a renal allograft with acquired renal cystic disease 19 years (228 months) after transplantation. CASE REPORT
A 54-year-old white man underwent cadaveric renal transplantation in February 1974 for treatment of renal failure secondary to autosomal dominant polycystic kidney disease. The graft failed 17 years after transplantation due to chronic rejection and hemodialysis was begun. During the 2 years after the institution of hemodialysis, the patient had multiple episodes of pyelonephritis. Abdomino-pelvic computerized tomography (CT) during these episodes demonstrated heterogeneous fluid collections within the cysts of the native kidneys. These findings were consistent with infected cysts Accepted for publication May 27, 1994.
and they resolved with antibiotic therapy. The development of multiple cysts within the allograft kidney was apparent on serial CT during an 11-month interval (fig. 1). Total nephrectomy (bilateral native and allograft kidneys) was performed for chronic pyelonephritis 19 years after transplantation. Gross specimens consisted of the 27 X 15 x 12.5 cm. right kidney, the 29.5 X 14.5 X 9.0 cm. left kidney and the 11.5 X 7.5 X 4.0 cm. allograft. Histopathological examination of the allograft kidney demonstrated cystic changes and a clear cell pattern renal cell carcinoma approximately 1 cm. in diameter within 1 cyst (fig. 2). The native kidneys were polycystic with evidence of chronic inflammation but free of malignancy. Convalescence was complicated by disseminated intravascular coagulation, necessitating a prolonged hospital stay. The patient remains on hemodialysis with no evidence of local recurrence or metastatic disease. DISCUSSION
The Cincinnati Transplant Tumor Registry recorded 6,123 types of cancer in 5,753 organ transplant recipients, of whom 5,130 were kidney recipient^.^ Penn and the Cincinnati Transplant Tumor Registry documented the increased incidence of cancer in allograft recipients.' Malignancy accounts for approximately 2.3% of deaths in patients who receive kidney t r a n ~ p l a n t sRenal .~ cell carcinoma comprises 2.3% of
FIG. 1. Serial CT of pelvis shows development of acquired renal cystic disease of allograft during 11 months. A, allograft without visible cyst (arrow).B, allograR with cortical cyst (arrow). C, allograft with cortical cyst ( m o w ) . 395
396
ACQUIRED RENAL CYSTIC DISEASE AND RENAL CELL CARCINOMA IN ALLOGRAFT KIDNEY of renal cell carcinoma development than the general popu-
1ati0n.I~ There have been 6 reported cases of renal cell carcinoma occurring with acquired renal cystic disease of the native kidneys of transplant recipients.12. ’‘,l6 These reports suggest that patients with acquired renal cystic disease before or after transplantation continue to be at risk for renal cell carcinoma. A reasonable conclusion is that acquired renal cystic disease in a renal allograft would also be a risk factor for a renal cell carcinoma b u t this possibility has not been reported previously. We report the nineteenth case of renal cell carcinoma i n an allograft kidney. To our knowledge our report represents the longest interval to presentation of a de novo renal tumor in a n allograft (228months) a n d the first case of renal cell carcinoma associated with acquired renal cystic disease i n an allograft kidney. FIG. 2. Photomicrograph of allograft cyst shown in figure 1, B. Cyst contains renal cell carcinoma with clear cell pattern involvement (arrow). H & E, reduced from X20.
REFERENCES
1. Penn, I.: Post-transplant kidney cancers and skin cancers (in-
all malignancies in the general population but it is more common in allograft recipients, in whom it constitutes 4.8% of all malignancies.6 Renal tumors may develop de novo in recipient allograft or native kidneys and may also be transplanted from the donor to the recipient?.‘ Of 202 renal tumors in allograft recipients 177 developed in the native kidney, 7 were of unknown origin and 18 developed in t h e allograft itself. The longest interval from transplantation to tumor presentation previously reported in an allograft is 156 months a n d the mean interval after transplantation to tumor development is 42 months6 Our patient presented 228 months aRer renal transplantation, which t o our knowledge is the longest interval reported to date. Since both native kidneys were available for pathological examination and were free of tumor, we believe that the tumor arose de novo in the allograft itself. Despite its small size, this tumor deserves the designation adenocarcinoma due to its low but real potential for malignant behavior: the fact that its histological appearance is virtually indistinguishable from larger lesions that are clearly malignant and the realization that size is an arbitrary criterion for defining an a d e n ~ m a .lo ~ CT . clearlv documented the evolution of multiple cysts developing wiihin the renal allograft after the patient was started on hemodialysis. An interesting hypothesis is that acquired renal cystic disease developed in the allograft kidney and the development of the renal cell carcinoma within the cyst was secondary to a carcinogenic toxin associated with uremia. Acquired renal cystic disease has been reported i n the kidneys of patients undergoing chronic hemodialysis, in patients with uremia who have not been treated with hemodialysis, i n the native kidneys of renal transplant recipients and i n renal allografts associated with chronic rejection.” The definitive etiology of acquired renal cystic disease is unknown. Possible etiological factors include toxins associated with uremia, renal tubular obstruction, ischemia a n d alterations in the basement membrane.12 Of hemodialysis patients 47% will have acquired renal cystic disease in less t h a n 3 years.13 The incidence of renal tumor development in patients with acquired renal cystic disease is 5.8 to 19% i n those undergoing chronic hemodialysis,” which is 7-fold higher than in the general population. In contrast to patients with acquired renal cystic disease, those with autosomal dominant polycystic kidney disease do not have a higher rate
cluding Kaposi’s sarcoma). In: De-Novo Cancers in Organ Transplantation Patients. New York: Springer-Verlag,pp. 4653, 1991. 2. Barrett, W. L., First, M. R., Aron, B. S. and Penn, I.: Clinical
course of malignancies in renal transplant recipients. Cancer, 7 2 2186,1993. 3. Penn, I.: Tumors after renal and cardiac transplantation. Hematol. Oncol. Clin. N. Amer., ?: 431, 1993. 4. Penn, I.: Donor transmitted disease: cancer. Transplant. Proc., 2 3 2629,1991. 5. Lawrence, S. K, Van Buren, D. H., MacDonell, R. C. and
Delbeke, D.: Carcinoma in a transplanted kidney detected with MAG3 scintigraphy. J . Nucl. Med., 34: 2185, 1993. 6. Feldman, J. D. and Jacobs, S. C.: Late development of renal carcinoma in allograft kidney. J . Urol., 148: 395, 1992. 7. Dlugosz, B. A., Bretan, P. N., Jr., Novick, A. C., Steinmuller, D. R., Streem, S. B., Badwar, K. and Woodard, R. M.: Causes of death in kidney transplant recipients: 1970 to present. Transplant. Proc., part 2, 21: 2168, 1989. 8. Hellsten, S., Berge, T. and Wehlin, L.: Unrecognized renal cell carcinoma. Clinical and pathological aspects. Scand. J. Urol. Nephrol., 15: 273, 1981. 9. Bennington, J. L. and Beckwith, J . B.: Histologic structure of the nephron. In: Atlas of Tumor Pathology: Tumors of the Kidney, Renal Pelvis, and Ureter. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 12, p. 12, 1975. 10. Bannayan, G. A. and Lamm, D. L.: Renal cell tumors. Path. Ann., part 2, 15: 271, 1980. 11. Ishikawa, I., Shikura, N., Kitada, H., Yuri, T., Shinoda, A. and Nakazawa, T.: Severity of acquired renal cysts in native kidneys and renal allograft with long-standing poor function. h e r . J. Kidney Dis., 1 4 18, 1989. 12. Levine, L. A. and Gburek, B. M.: Acquired cystic disease and renal adenocarcinoma following renal transplantation. J. Urol., 151: 129, 1994. 13. Ishikawa, I., Saito, Y., Shikura, N., Kitada, H., Shinoda, A. and Suzuki, S.: Ten-year prospective study on the development of renal cell carcinoma in dialysis patients. Amer. J. Kidney Dis., 1 6 452, 1990. 14. Glassberg,K. I.: Renal dysplasia and cystic disease of the kidney. In: Campbell’s Urology, 6th ed. Edited by P. C. Walsh, A. B. Retik, T. A. Stamey and E.D. Vaughan, Jr. Philadelphia: W. B. Saunders Co., vol. 2, chapt. 35, p. 1443, 1992. 15. Almirall, J., Ricart, M. J., Campistol, J. M., Vilardell, J., Openheimer, F. and Andreu, J.: Renal cell carcinoma and acquired cystic kidney disease after renal transplantation. Transplant. Int., 3: 49, 1990. 16. Garcia de la Oliva, T. and Gonzalez Molina, M.: Metastatic malignant tumor in native kidney with acquired cystic disease after renal transplantation. Eur. J. Rad., 11: 154, 1990.
THEJOURNAL OF UROLOGY Copyright 0 1995 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol 153, 395-396, February 1995 Printed i n V.S.A.
ACQUIRED RENAL CYSTIC DISEASE AND RENAL CELL CARCINOMA I N AN ALLOGRAFT KIDNEY J. CHANDLER WILLIAMS, PAUL A. MERGUERIAN, ALAN R. SCHNED AND PATRICIA M. MORRISON From the Section of Urology, Department
of
Surgery and Departments of Pathology and Internal Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
ABSTRACT
Acquired renal cystic disease has been reported in the kidneys of patients with end stage renal disease who have been untreated, treated with dialysis or undergone renal transplantation. The incidence of renal tumor development in patients with acquired renal cystic disease is greater t h a n 5% in those undergoing chronic hemodialysis. Recently, cases of renal cell carcinoma occurring with acquired renal cystic disease of the native kidneys of transplant recipients have been reported. Transplant patients have an increased incidence of malignancy when compared to t h e general population. Including our case, 19 cases of de novo renal neoplasms developing in renal allografts have been reported. To t h e best of our knowledge we report the longest interval to presentation of a de novo renal tumor in a n allograft kidney (228 months) and the first case of renal cell carcinoma associated with acquired renal cystic disease in an allograft kidney. KEYWORDS:carcinoma, renal cell; kidney transplantation; kidney; kidney neoplasms; immunosuppression
Transplant patients have an increased incidence of malignancy compared to the general population.' The natural history of cancers developing in renal transplant patients often is more aggressive than that in the general population,' which is thought t o be a complication of immunosuppressive therapy used in organ tran~plantation.~ Transplantation of tumor within the donated organ has also been documented.435The development of de novo renal cell carcinoma in a renal allograft has been reported infrequently.6 We report a case of a small renal cell carcinoma developing in a renal allograft with acquired renal cystic disease 19 years (228 months) after transplantation. CASE REPORT
A 54-year-old white man underwent cadaveric renal transplantation in February 1974 for treatment of renal failure secondary to autosomal dominant polycystic kidney disease. The graft failed 17 years after transplantation due to chronic rejection and hemodialysis was begun. During the 2 years after the institution of hemodialysis, the patient had multiple episodes of pyelonephritis. Abdomino-pelvic computerized tomography (CT) during these episodes demonstrated heterogeneous fluid collections within the cysts of the native kidneys. These findings were consistent with infected cysts Accepted for publication May 27, 1994.
and they resolved with antibiotic therapy. The development of multiple cysts within the allograft kidney was apparent on serial CT during an 11-month interval (fig. 1). Total nephrectomy (bilateral native and allograft kidneys) was performed for chronic pyelonephritis 19 years after transplantation. Gross specimens consisted of the 27 X 15 x 12.5 cm. right kidney, the 29.5 X 14.5 X 9.0 cm. left kidney and the 11.5 X 7.5 X 4.0 cm. allograft. Histopathological examination of the allograft kidney demonstrated cystic changes and a clear cell pattern renal cell carcinoma approximately 1 cm. in diameter within 1 cyst (fig. 2). The native kidneys were polycystic with evidence of chronic inflammation but free of malignancy. Convalescence was complicated by disseminated intravascular coagulation, necessitating a prolonged hospital stay. The patient remains on hemodialysis with no evidence of local recurrence or metastatic disease. DISCUSSION
The Cincinnati Transplant Tumor Registry recorded 6,123 types of cancer in 5,753 organ transplant recipients, of whom 5,130 were kidney recipient^.^ Penn and the Cincinnati Transplant Tumor Registry documented the increased incidence of cancer in allograft recipients.' Malignancy accounts for approximately 2.3% of deaths in patients who receive kidney t r a n ~ p l a n t sRenal .~ cell carcinoma comprises 2.3% of
FIG. 1. Serial CT of pelvis shows development of acquired renal cystic disease of allograft during 11 months. A, allograft without visible cyst (arrow).B, allograR with cortical cyst (arrow). C, allograft with cortical cyst ( m o w ) . 395
396
ACQUIRED RENAL CYSTIC DISEASE AND RENAL CELL CARCINOMA IN ALLOGRAFT KIDNEY of renal cell carcinoma development than the general popu-
1ati0n.I~ There have been 6 reported cases of renal cell carcinoma occurring with acquired renal cystic disease of the native kidneys of transplant recipients.12. ’‘,l6 These reports suggest that patients with acquired renal cystic disease before or after transplantation continue to be at risk for renal cell carcinoma. A reasonable conclusion is that acquired renal cystic disease in a renal allograft would also be a risk factor for a renal cell carcinoma b u t this possibility has not been reported previously. We report the nineteenth case of renal cell carcinoma i n an allograft kidney. To our knowledge our report represents the longest interval to presentation of a de novo renal tumor in a n allograft (228months) a n d the first case of renal cell carcinoma associated with acquired renal cystic disease i n an allograft kidney. FIG. 2. Photomicrograph of allograft cyst shown in figure 1, B. Cyst contains renal cell carcinoma with clear cell pattern involvement (arrow). H & E, reduced from X20.
REFERENCES
1. Penn, I.: Post-transplant kidney cancers and skin cancers (in-
all malignancies in the general population but it is more common in allograft recipients, in whom it constitutes 4.8% of all malignancies.6 Renal tumors may develop de novo in recipient allograft or native kidneys and may also be transplanted from the donor to the recipient?.‘ Of 202 renal tumors in allograft recipients 177 developed in the native kidney, 7 were of unknown origin and 18 developed in t h e allograft itself. The longest interval from transplantation to tumor presentation previously reported in an allograft is 156 months a n d the mean interval after transplantation to tumor development is 42 months6 Our patient presented 228 months aRer renal transplantation, which t o our knowledge is the longest interval reported to date. Since both native kidneys were available for pathological examination and were free of tumor, we believe that the tumor arose de novo in the allograft itself. Despite its small size, this tumor deserves the designation adenocarcinoma due to its low but real potential for malignant behavior: the fact that its histological appearance is virtually indistinguishable from larger lesions that are clearly malignant and the realization that size is an arbitrary criterion for defining an a d e n ~ m a .lo ~ CT . clearlv documented the evolution of multiple cysts developing wiihin the renal allograft after the patient was started on hemodialysis. An interesting hypothesis is that acquired renal cystic disease developed in the allograft kidney and the development of the renal cell carcinoma within the cyst was secondary to a carcinogenic toxin associated with uremia. Acquired renal cystic disease has been reported i n the kidneys of patients undergoing chronic hemodialysis, in patients with uremia who have not been treated with hemodialysis, i n the native kidneys of renal transplant recipients and i n renal allografts associated with chronic rejection.” The definitive etiology of acquired renal cystic disease is unknown. Possible etiological factors include toxins associated with uremia, renal tubular obstruction, ischemia a n d alterations in the basement membrane.12 Of hemodialysis patients 47% will have acquired renal cystic disease in less t h a n 3 years.13 The incidence of renal tumor development in patients with acquired renal cystic disease is 5.8 to 19% i n those undergoing chronic hemodialysis,” which is 7-fold higher than in the general population. In contrast to patients with acquired renal cystic disease, those with autosomal dominant polycystic kidney disease do not have a higher rate
cluding Kaposi’s sarcoma). In: De-Novo Cancers in Organ Transplantation Patients. New York: Springer-Verlag,pp. 4653, 1991. 2. Barrett, W. L., First, M. R., Aron, B. S. and Penn, I.: Clinical
course of malignancies in renal transplant recipients. Cancer, 7 2 2186,1993. 3. Penn, I.: Tumors after renal and cardiac transplantation. Hematol. Oncol. Clin. N. Amer., ?: 431, 1993. 4. Penn, I.: Donor transmitted disease: cancer. Transplant. Proc., 2 3 2629,1991. 5. Lawrence, S. K, Van Buren, D. H., MacDonell, R. C. and
Delbeke, D.: Carcinoma in a transplanted kidney detected with MAG3 scintigraphy. J . Nucl. Med., 34: 2185, 1993. 6. Feldman, J. D. and Jacobs, S. C.: Late development of renal carcinoma in allograft kidney. J . Urol., 148: 395, 1992. 7. Dlugosz, B. A., Bretan, P. N., Jr., Novick, A. C., Steinmuller, D. R., Streem, S. B., Badwar, K. and Woodard, R. M.: Causes of death in kidney transplant recipients: 1970 to present. Transplant. Proc., part 2, 21: 2168, 1989. 8. Hellsten, S., Berge, T. and Wehlin, L.: Unrecognized renal cell carcinoma. Clinical and pathological aspects. Scand. J. Urol. Nephrol., 15: 273, 1981. 9. Bennington, J. L. and Beckwith, J . B.: Histologic structure of the nephron. In: Atlas of Tumor Pathology: Tumors of the Kidney, Renal Pelvis, and Ureter. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 12, p. 12, 1975. 10. Bannayan, G. A. and Lamm, D. L.: Renal cell tumors. Path. Ann., part 2, 15: 271, 1980. 11. Ishikawa, I., Shikura, N., Kitada, H., Yuri, T., Shinoda, A. and Nakazawa, T.: Severity of acquired renal cysts in native kidneys and renal allograft with long-standing poor function. h e r . J. Kidney Dis., 1 4 18, 1989. 12. Levine, L. A. and Gburek, B. M.: Acquired cystic disease and renal adenocarcinoma following renal transplantation. J. Urol., 151: 129, 1994. 13. Ishikawa, I., Saito, Y., Shikura, N., Kitada, H., Shinoda, A. and Suzuki, S.: Ten-year prospective study on the development of renal cell carcinoma in dialysis patients. Amer. J. Kidney Dis., 1 6 452, 1990. 14. Glassberg,K. I.: Renal dysplasia and cystic disease of the kidney. In: Campbell’s Urology, 6th ed. Edited by P. C. Walsh, A. B. Retik, T. A. Stamey and E.D. Vaughan, Jr. Philadelphia: W. B. Saunders Co., vol. 2, chapt. 35, p. 1443, 1992. 15. Almirall, J., Ricart, M. J., Campistol, J. M., Vilardell, J., Openheimer, F. and Andreu, J.: Renal cell carcinoma and acquired cystic kidney disease after renal transplantation. Transplant. Int., 3: 49, 1990. 16. Garcia de la Oliva, T. and Gonzalez Molina, M.: Metastatic malignant tumor in native kidney with acquired cystic disease after renal transplantation. Eur. J. Rad., 11: 154, 1990.