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Benign Retroperitoneal Fibrosis and Renal Cell Carcinoma
0022-5347 /93/l496-1535$0'.].00/0 June 1993
TH2 ,JOURNAL OF UROLOGY
Copyright
in U.S.A.
1993 by AMERICAN UROLOGICAL ASSOC!AT!ON, INC.
BENIGN RETROPERITONEAL FIBROSIS AND RENAL CELL CARCINOMA JOHN CONNOLLY, DAVID EISNER, STANFORD GOLDMAN, RAY STUTZMAN MITCHELL STEINER
AND
From the James Buchanan Brady Urological Institute, The Johns Hopkins Hospital and Department of Radiology, Francis Scott Key Medical Center, Baltimore, Maryland
ABSTRACT
We report benign retroperitoneal fibrosis associated with renal cell carcinoma in a 56-year-old woman. Based on the preoperative evaluation and initial surgical exploration, the retroperitoneal mass was assumed to be metastatic renal cell carcinoma and chemotherapy rather than surgical resection was offered to the patient. A second opinion was sought and repeat exploration revealed a resectable renal cell carcinoma and retroperitoneal tissue that was pathologically benign idiopathic retroperitoneal fibrosis. This report emphasizes that a patient with an otherwise resectable primary tumor must undergo multiple, deep biopsies of retroperitoneal masses before making a presumptive diagnosis of malignant retroperitoneal fibrosis secondary to metastatic cancer. KEY WORDS:
retroperitoneal fibrosis; carcinoma, renal cell
Malignant retroperitoneal fibrosis has been associated with many different types of tumor and usually it is due to fibrosis surrounding periureteral metastases. We describe a case of benign fibrosis of the retroperitoneum associated with renal cell carcinoma. The benign nature of the fibrosis was not initially appreciated. This report emphasizes the importance of retroperitoneal exploration and biopsy in all cases when a retroperitoneal fibrotic process is found in association with an otherwise resectable neoplasm.
CASE REPORT
A previously healthy 56-year-old Hispanic woman presented elsewhere with a 2-day history of anuria, low back pain, nausea and vomiting. Examination revealed no palpable abdominal masses and moderately tender costovertebral angles. The serum blood urea nitrogen was 25 mg.% and serum creatinine was 5.3 mg.% (normal 0.4 to 1.5). Abdominal computerized tomography (CT) showed a mass in the lower pole of the right kidney contained within Gerota's fascia (fig. 1, A). The renal vein and inferior vena cava did not contain thrombus. Both kidneys were moderately hydronephrotic secondary to a large retroperitoneal soft tissue mass that surrounded the aorta and ureters (fig. 1, B). Following placement of bilateral ureteral stents (fig. 2) the bilateral hydronephrosis improved, and serum blood urea nitrogen and creatinine returned to normal. Simultaneous open biopsies of the right renal lesion and the retroperitoneal mass revealed, respectively, well differentiated renal cell carcinoma and retroperitoneal fibrosis, It was believed that the retroperitoneal tissue represented metastatic tumor despite the negative biopsy of the retroperitoneum and chemotherapy was planned. Before evaluation for possible metastatic chemotherapy protocol, the patient presented to our clinic for a second opinion. She had severe low back pain and anuria. Investigation revealed blockage of both ureteral stents and a nephrostomy tube was placed into the left kidney. The serum creatinine level decreased from 5.0 to 1.2 mg.% in 2 weeks. After review of the previous x-rays and pathology report we elected to reexplore the retroperitoneum. Through a modified thoracoabdominal incision, a midline incision extending into the right flank, the retroperitoneum and right kidney were exposed. The renal lesion appeared confined to the kidney. Biopsies of the retroperitoneal soft tissue revealed fibrotic tissue without malignant Accepted for publication December 11, 1992.
cells. The patient underwent radical right nephrectomy and ureterolysis of the left ureter. In addition, the ureter was lateralized and wrapped in omentum. Permanent pathological evaluation showed a well differentiated renal cell carcinoma (stage 1) confined to the kidney. The retroperitoneal biopsies were consistent with retroperitoneal fibrosis with no evidence of malignant cells. Convalescence was uneventful and 1 year postoperatively the patient was healthy with normal renal function and no evidence on CT of either metastatic tumor or increasing retroperitoneal tissue. DISCUSSION
Retroperitoneal fibrosis is an uncommon disease that can cause either unilateral or bilateral ureteral obstruction. I Although most cases are idiopathic, other entities that are associated with retroperitoneal fibrosis include malignancy, drugs (methysergide), retroperitoneal hematoma, surgery, radiation therapy and urine extravasation. 2 In 8% of the cases the fibrosis is associated with a malignant process. Tumors cause retroperitoneal fibrosis in 1 of 3 ways: primary retroperitoneal tumor, periureteral metastases or serotonin production associated with a carcinoid tumor. 3 • 4 The primary tumors that are most com·· monly associated with retroperitoneal fibrosis include lymphomas and retroperitoneal sarcomas. Periureteral metastases usually occur from tumors of the breast, stomach, pancreas, prostate and cervix. Retroperitoneal 1S associated with urothelial tumors or renal parenchymal tumors. 5 - 8 In common with Forsythe et al, 9 we also found capsule-confined renal cell carcinoma of the right kidney associated with benign fibrosis of the retroperitoneum causing bilateral ureteral obstruction. The only definitive method to distinguish between the different groups of retroperitoneal fibrosis is multiple, deep biopsies. A careful drug history, clinical examination and radiological studies are important. Excretory urography is abnormal in many patients, with the classical triad of upper ureteral hydronephrosis, medial deviation of the ureters and extrinsic ureter al compression being often, but not invariably, present.Io Retrograde pyelography is useful to assess the extent and severity of the disease and the patency of the ureters. However, neither study can distinguish between benign and malignant processes except on the rare occasion when tumor invading the ureter is apparent. Ease in passing a retrograde ureteral catheter is suggestive of a benign etiology. The ureteral obstruction asso-
1536
CONNOLLY AND ASSOCIATES
FIG. 1. A, large renal cell carcinoma projecting anteriorly from right kidney (arrow). B; retroperitoneal soft tissue mass on CT was found histologically to represent retroperitoneal fibrosis without evidence of malignant cells. Retroperitoneal fibrosis (arrowheads) surrounds aorta and inferior vena cava.
FIG. 2. Film of kidneys, ureters and bladder after stents were passed bilaterally to relieve obstruction caused by retroperitoneal fibrosis shows medial deviation of ureters caused by fibrotic process.
plan. Macroscopically, it is difficult to distinguish between benign and malignant fibrosis of the retroperitoneum, the usual finding in both being a grayish-white firm plaque of tissue. The typical microscopic appearance is dense collagenous tissue with chronic inflammatory cells, notably lymphocytes, plasma cells, eosinophils and polymorphonuclear leukocytes. 3 In fibrosis due to malignancy there are nests of tumor cells within this collagen meshwork. 15 The amount of malignant tissue present may be relatively small compared to the size of the fibrotic plaque and, consequently, it is important to perform multiple, deep biopsies to confirm the presence or absence of tumor. To our knowledge we report the second case of benign retroperitoneal fibrosis associated with renal cell carcinoma. The initial diagnosis was a renal tumor with metastatic adenopathy. However, biopsies of the retroperitoneum demonstrated fibrotic tissue and the retroperitoneal fibrosis associated with a clearly resectable renal cell carcinoma was completely benign. The fibrotic tissue excised was not caused by direct extension of tumor or by periureteral metastases. More likely, this was coincidental idiopathic fibrosis. Although speculative, one wonders whether the retroperitoneal fibrosis was secondary to some substance elaborated by the renal cell carcinoma. In the presence of an otherwise resectable primary neoplasm it should not be assumed that retroperitoneal soft tissue on CT represents either tumor extension or metastatic adenopathy. Rather, the retroperitoneal fibrosis associated with renal cell carcinoma should be considered benign unless the deep biopsies of this tissue prove otherwise. REFERENCES
ciated with retroperitoneal fibrosis is usually not a result of extrinsic compression but rather the fibrotic process causes the ureter to have ineffective peristalsis. Lymphangiography is most often normal or nonspecific. 11 CT is also nonspecific and fails to demonstrate the fibrotic plaques in up to 33 % of the cases. 12 Magnetic resonance imaging has recently been shown to be the most useful nonoperative study for differentiating benign fibrosis from that associated with malignancy. Tumor associated fibrosis tends to be heterogeneous on magnetic resonance imaging with high signal intensity on T2-weighted images. 13 Fibrosis of a benign nature is homogeneous with a low signal intensity on T2 studies. 67 Gallium radioisotope imaging is not helpful in differentiating benign from malignant retroperitoneal fibrosis but it may be useful in identifying suitable sites for biopsy by delineating the areas of maximum inflammatory activity. 14 Deep biopsy of any retroperitoneal process is needed to confirm a diagnosis of retroperitoneal fibrosis, as clearly illustrated by our case in which an erroneous diagnosis of metastatic cancer was initially made leading to an inappropriate treatment
1. Albarran, J. J.: Retention renale par petriureterite, liberation et externe de l'uretere. Ass. France Urol., 9: 511, 1905. 2. Koep, L. and Zuidema, G. D.: The clinical significance of retroperitoneal fibrosis. Surgery, 81: 250, 1977. 3. Lepor, H. and Walsh, P. C.: Idiopathic retroperitoneal fibrosis. J. Urol., 122: 1, 1979. 4. Morin, L. J. and ZuernP,r, R. T.: Retroperitoneal fibrosis and carcinoid tumor. J.A.M.A., 216: 1647, 1971. 5. Reiner, I., Yachia, D., Nissim, F. and Fishelowitz, Y.: Retroperitoneal fibrosis in association with urothelial tumor. J. Urol., 132: 115, 1984. 6. Alexander, S., Kyung, K., Pinck, B. D. and Brendler, H.: Metastatic ureteral tumors. J. Urol., 110: 288, 1973. 7. Chordia, M. L., Ockuly, E. A., Ockuly, J. J. and Ockuly, E. F.: Ureteral and vesical metastases from parenchymal renal cell carcinoma: case report and review of the literature. J. Urol., 102: 298, 1969. 8. Young, I. S.: Ureteral implant from renal adenocarcinoma: report of a case and review of the literature. J. Urol., 98: 661, 1967. 9. Forsythe, J. L., Robinson, M. C. and Neal, D. E.: Renal carcinoma with adjacent retroperitoneal fibrosis. Brit. J. Urol., 64: 651, 1989. 10. Witten, D. M.: Retroperitoneal fibrosis. In: Clinical Urography.
BENIGN RETROPERITONEAL FIBROSIS AND RENAL CELL CARCINOMA Edited by H. M. Pollack. Philadelphia: W.B. Saunders Co., vol. 3,chapt.95,pp. 2470-2471, 1990. 11. Clouse, M. E., Fraley, E. E. and Litwin, S. B.: Lymphangiographic criteria for diagnosis of retroperitoneal fibrosis. Radiology, 83: 1, 1964. 12. Brun, B., Laursen, K., S0rensen, I. N., Lorentzen, J. E. and Kristensen, J. K.: CT in retroperitoneal fibrosis. AJR, 137: 535, 1981.
1537
13. Arrive, L., Hricak, H., Tavares, N. J. and Miller, T. R.: Malignant versus nonmalignant retroperitoneal fibrosis: differentiation with MR imaging. Radiology, 172: 139, 1989. 14. Jacobson, A. F.: Gallium-67 imaging in retroperitoneal fibrosis: significance of a negative result. J. Nucl. Med., 32: 521, 1990. 15. Thomas, M. H. and Chisholm, G. D.: Retroperitoneal fibrosis associated with malignant disease. Brit. J. Cancer, 28: 453, 1973.
TH2 ,JOURNAL OF UROLOGY
Copyright
in U.S.A.
1993 by AMERICAN UROLOGICAL ASSOC!AT!ON, INC.
BENIGN RETROPERITONEAL FIBROSIS AND RENAL CELL CARCINOMA JOHN CONNOLLY, DAVID EISNER, STANFORD GOLDMAN, RAY STUTZMAN MITCHELL STEINER
AND
From the James Buchanan Brady Urological Institute, The Johns Hopkins Hospital and Department of Radiology, Francis Scott Key Medical Center, Baltimore, Maryland
ABSTRACT
We report benign retroperitoneal fibrosis associated with renal cell carcinoma in a 56-year-old woman. Based on the preoperative evaluation and initial surgical exploration, the retroperitoneal mass was assumed to be metastatic renal cell carcinoma and chemotherapy rather than surgical resection was offered to the patient. A second opinion was sought and repeat exploration revealed a resectable renal cell carcinoma and retroperitoneal tissue that was pathologically benign idiopathic retroperitoneal fibrosis. This report emphasizes that a patient with an otherwise resectable primary tumor must undergo multiple, deep biopsies of retroperitoneal masses before making a presumptive diagnosis of malignant retroperitoneal fibrosis secondary to metastatic cancer. KEY WORDS:
retroperitoneal fibrosis; carcinoma, renal cell
Malignant retroperitoneal fibrosis has been associated with many different types of tumor and usually it is due to fibrosis surrounding periureteral metastases. We describe a case of benign fibrosis of the retroperitoneum associated with renal cell carcinoma. The benign nature of the fibrosis was not initially appreciated. This report emphasizes the importance of retroperitoneal exploration and biopsy in all cases when a retroperitoneal fibrotic process is found in association with an otherwise resectable neoplasm.
CASE REPORT
A previously healthy 56-year-old Hispanic woman presented elsewhere with a 2-day history of anuria, low back pain, nausea and vomiting. Examination revealed no palpable abdominal masses and moderately tender costovertebral angles. The serum blood urea nitrogen was 25 mg.% and serum creatinine was 5.3 mg.% (normal 0.4 to 1.5). Abdominal computerized tomography (CT) showed a mass in the lower pole of the right kidney contained within Gerota's fascia (fig. 1, A). The renal vein and inferior vena cava did not contain thrombus. Both kidneys were moderately hydronephrotic secondary to a large retroperitoneal soft tissue mass that surrounded the aorta and ureters (fig. 1, B). Following placement of bilateral ureteral stents (fig. 2) the bilateral hydronephrosis improved, and serum blood urea nitrogen and creatinine returned to normal. Simultaneous open biopsies of the right renal lesion and the retroperitoneal mass revealed, respectively, well differentiated renal cell carcinoma and retroperitoneal fibrosis, It was believed that the retroperitoneal tissue represented metastatic tumor despite the negative biopsy of the retroperitoneum and chemotherapy was planned. Before evaluation for possible metastatic chemotherapy protocol, the patient presented to our clinic for a second opinion. She had severe low back pain and anuria. Investigation revealed blockage of both ureteral stents and a nephrostomy tube was placed into the left kidney. The serum creatinine level decreased from 5.0 to 1.2 mg.% in 2 weeks. After review of the previous x-rays and pathology report we elected to reexplore the retroperitoneum. Through a modified thoracoabdominal incision, a midline incision extending into the right flank, the retroperitoneum and right kidney were exposed. The renal lesion appeared confined to the kidney. Biopsies of the retroperitoneal soft tissue revealed fibrotic tissue without malignant Accepted for publication December 11, 1992.
cells. The patient underwent radical right nephrectomy and ureterolysis of the left ureter. In addition, the ureter was lateralized and wrapped in omentum. Permanent pathological evaluation showed a well differentiated renal cell carcinoma (stage 1) confined to the kidney. The retroperitoneal biopsies were consistent with retroperitoneal fibrosis with no evidence of malignant cells. Convalescence was uneventful and 1 year postoperatively the patient was healthy with normal renal function and no evidence on CT of either metastatic tumor or increasing retroperitoneal tissue. DISCUSSION
Retroperitoneal fibrosis is an uncommon disease that can cause either unilateral or bilateral ureteral obstruction. I Although most cases are idiopathic, other entities that are associated with retroperitoneal fibrosis include malignancy, drugs (methysergide), retroperitoneal hematoma, surgery, radiation therapy and urine extravasation. 2 In 8% of the cases the fibrosis is associated with a malignant process. Tumors cause retroperitoneal fibrosis in 1 of 3 ways: primary retroperitoneal tumor, periureteral metastases or serotonin production associated with a carcinoid tumor. 3 • 4 The primary tumors that are most com·· monly associated with retroperitoneal fibrosis include lymphomas and retroperitoneal sarcomas. Periureteral metastases usually occur from tumors of the breast, stomach, pancreas, prostate and cervix. Retroperitoneal 1S associated with urothelial tumors or renal parenchymal tumors. 5 - 8 In common with Forsythe et al, 9 we also found capsule-confined renal cell carcinoma of the right kidney associated with benign fibrosis of the retroperitoneum causing bilateral ureteral obstruction. The only definitive method to distinguish between the different groups of retroperitoneal fibrosis is multiple, deep biopsies. A careful drug history, clinical examination and radiological studies are important. Excretory urography is abnormal in many patients, with the classical triad of upper ureteral hydronephrosis, medial deviation of the ureters and extrinsic ureter al compression being often, but not invariably, present.Io Retrograde pyelography is useful to assess the extent and severity of the disease and the patency of the ureters. However, neither study can distinguish between benign and malignant processes except on the rare occasion when tumor invading the ureter is apparent. Ease in passing a retrograde ureteral catheter is suggestive of a benign etiology. The ureteral obstruction asso-
1536
CONNOLLY AND ASSOCIATES
FIG. 1. A, large renal cell carcinoma projecting anteriorly from right kidney (arrow). B; retroperitoneal soft tissue mass on CT was found histologically to represent retroperitoneal fibrosis without evidence of malignant cells. Retroperitoneal fibrosis (arrowheads) surrounds aorta and inferior vena cava.
FIG. 2. Film of kidneys, ureters and bladder after stents were passed bilaterally to relieve obstruction caused by retroperitoneal fibrosis shows medial deviation of ureters caused by fibrotic process.
plan. Macroscopically, it is difficult to distinguish between benign and malignant fibrosis of the retroperitoneum, the usual finding in both being a grayish-white firm plaque of tissue. The typical microscopic appearance is dense collagenous tissue with chronic inflammatory cells, notably lymphocytes, plasma cells, eosinophils and polymorphonuclear leukocytes. 3 In fibrosis due to malignancy there are nests of tumor cells within this collagen meshwork. 15 The amount of malignant tissue present may be relatively small compared to the size of the fibrotic plaque and, consequently, it is important to perform multiple, deep biopsies to confirm the presence or absence of tumor. To our knowledge we report the second case of benign retroperitoneal fibrosis associated with renal cell carcinoma. The initial diagnosis was a renal tumor with metastatic adenopathy. However, biopsies of the retroperitoneum demonstrated fibrotic tissue and the retroperitoneal fibrosis associated with a clearly resectable renal cell carcinoma was completely benign. The fibrotic tissue excised was not caused by direct extension of tumor or by periureteral metastases. More likely, this was coincidental idiopathic fibrosis. Although speculative, one wonders whether the retroperitoneal fibrosis was secondary to some substance elaborated by the renal cell carcinoma. In the presence of an otherwise resectable primary neoplasm it should not be assumed that retroperitoneal soft tissue on CT represents either tumor extension or metastatic adenopathy. Rather, the retroperitoneal fibrosis associated with renal cell carcinoma should be considered benign unless the deep biopsies of this tissue prove otherwise. REFERENCES
ciated with retroperitoneal fibrosis is usually not a result of extrinsic compression but rather the fibrotic process causes the ureter to have ineffective peristalsis. Lymphangiography is most often normal or nonspecific. 11 CT is also nonspecific and fails to demonstrate the fibrotic plaques in up to 33 % of the cases. 12 Magnetic resonance imaging has recently been shown to be the most useful nonoperative study for differentiating benign fibrosis from that associated with malignancy. Tumor associated fibrosis tends to be heterogeneous on magnetic resonance imaging with high signal intensity on T2-weighted images. 13 Fibrosis of a benign nature is homogeneous with a low signal intensity on T2 studies. 67 Gallium radioisotope imaging is not helpful in differentiating benign from malignant retroperitoneal fibrosis but it may be useful in identifying suitable sites for biopsy by delineating the areas of maximum inflammatory activity. 14 Deep biopsy of any retroperitoneal process is needed to confirm a diagnosis of retroperitoneal fibrosis, as clearly illustrated by our case in which an erroneous diagnosis of metastatic cancer was initially made leading to an inappropriate treatment
1. Albarran, J. J.: Retention renale par petriureterite, liberation et externe de l'uretere. Ass. France Urol., 9: 511, 1905. 2. Koep, L. and Zuidema, G. D.: The clinical significance of retroperitoneal fibrosis. Surgery, 81: 250, 1977. 3. Lepor, H. and Walsh, P. C.: Idiopathic retroperitoneal fibrosis. J. Urol., 122: 1, 1979. 4. Morin, L. J. and ZuernP,r, R. T.: Retroperitoneal fibrosis and carcinoid tumor. J.A.M.A., 216: 1647, 1971. 5. Reiner, I., Yachia, D., Nissim, F. and Fishelowitz, Y.: Retroperitoneal fibrosis in association with urothelial tumor. J. Urol., 132: 115, 1984. 6. Alexander, S., Kyung, K., Pinck, B. D. and Brendler, H.: Metastatic ureteral tumors. J. Urol., 110: 288, 1973. 7. Chordia, M. L., Ockuly, E. A., Ockuly, J. J. and Ockuly, E. F.: Ureteral and vesical metastases from parenchymal renal cell carcinoma: case report and review of the literature. J. Urol., 102: 298, 1969. 8. Young, I. S.: Ureteral implant from renal adenocarcinoma: report of a case and review of the literature. J. Urol., 98: 661, 1967. 9. Forsythe, J. L., Robinson, M. C. and Neal, D. E.: Renal carcinoma with adjacent retroperitoneal fibrosis. Brit. J. Urol., 64: 651, 1989. 10. Witten, D. M.: Retroperitoneal fibrosis. In: Clinical Urography.
BENIGN RETROPERITONEAL FIBROSIS AND RENAL CELL CARCINOMA Edited by H. M. Pollack. Philadelphia: W.B. Saunders Co., vol. 3,chapt.95,pp. 2470-2471, 1990. 11. Clouse, M. E., Fraley, E. E. and Litwin, S. B.: Lymphangiographic criteria for diagnosis of retroperitoneal fibrosis. Radiology, 83: 1, 1964. 12. Brun, B., Laursen, K., S0rensen, I. N., Lorentzen, J. E. and Kristensen, J. K.: CT in retroperitoneal fibrosis. AJR, 137: 535, 1981.
1537
13. Arrive, L., Hricak, H., Tavares, N. J. and Miller, T. R.: Malignant versus nonmalignant retroperitoneal fibrosis: differentiation with MR imaging. Radiology, 172: 139, 1989. 14. Jacobson, A. F.: Gallium-67 imaging in retroperitoneal fibrosis: significance of a negative result. J. Nucl. Med., 32: 521, 1990. 15. Thomas, M. H. and Chisholm, G. D.: Retroperitoneal fibrosis associated with malignant disease. Brit. J. Cancer, 28: 453, 1973.