Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991), pp. 376-378
CASE R E P O R T
Ampullary Tumor Caused by Metastatic Renal Cell Carcinoma R.P. VENU, MD, P. ROLNY, MD, PhD, J.E. GEENEN, MD, W.J. HOGAN, MD, R.A. KOMOROWSKI, MD, and R. FERSTENBERG, MD KEY WORDS: ampullary neoplasm; endoscopic diagnosis.
The ampullary region is an unusual site of metastatic malignancy (1). Among the tumors involving the ampulla of Vater, only one case of metastatic renal cell carcinoma has been described in detail to date (2). In this paper we describe a second case of renal cell carcinoma that metastasized to the papilla.
CASE REPORT A 64-year-old male was hospitalized with a one-week history of malaise, fatigue, and shortness of breath. The patient underwent a left nephrectomy for renal cell carcinoma 11 years previously. There was no evidence of metastases at the time of nephrectomy. One year prior to admission a lobect0my had been performed for a metastatic lesion in the left lung. On admission, the patient was pale and severely anemic; the hemoglobin was 5.0 g/liter, hematocrit 17%, and MCV 68 ~m2. Stool was positive for occult blood. Coagulation studies and liver function tests were normal. An upper gastrointestinal series revealed an ampullary mass with a central ulcer (Figure 1). At endoscopic examination (Olympus 1T20, lateral-viewing endoscope), the papilla appeared enlarged. It was covered with normal mucosa and an irregularly shaped ulcer was noted on its summit (Figure 2). Fresh blood was seen at the base of the ulcer. Using a standard forceps, multiple biopsies were obtained from the ampullary lesion, and histology revealed a metastatic renal cell carcinoma (Figure 3). The patient was treated with Megace (megestrol acetate) (BristolMyers Institutional Products, A Bristol-Myers Company, 2400 W. Lloyd Expressway, Evansville, Indiana 477210001), for tumor regression. He did well for two years and then developed recurrent bleeding. Surgical consultation was therefore obtained and the tumor was resected. Postoperatively the patient succumbed to massive pulmonarY embolism. Manuscript received June 13, 1990; revised manuscript received September 24, 1990; accepted October 1, 1990. From the Digestive Disease Center, St. Luke's Hospital, Racine, Wisconsin; and Departments of Pathology and Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin. Address for reprint requests: Dr. R.P. Venu, Gastroenterology Consultants, Inc., 1333 College Ave., Racine, Wisconsin 53403.
376
DISCUSSION Symptoms associated with ampullary tumors are usually the result of obstruction of the bile duct and/or pancreatic duct, which leads to jaundice, acute pancreatitis, or malabsorption. Less commonly, ulceration of the tumor may produce occult and/or overt gastrointestinal bleeding (3). Our patient's clinical picture was characterized by severe anemia due to chronic blood loss and in the case previously reported malabsorption was the presenting symptom (2). Thus, both patients with ampullary tumors due to metastatic renal cell carcinoma displayed symptoms which, although uncommon, are recognized features of ampullary neoplasms. Gastrointestinal bleeding in patients with renal cell carcinoma is usually the result of involvement of the small intestine by direct invasion or metastatic spread of the tumor (4). Our case illustrates that gastrointestinal bleeding may also be caused by metastatic spread of the neoplasm to the ampulla of Vater. Barium studies of the stomach and small bowel, which are often utilized to evaluate chronic upper gastrointestinal bleeding, might easily overlook an ampullary tumor (5). In addition, the laboratory and/or clinical signs of biliary tract obstruction that normally alert clinicians to the possibility of ampullary disease may occasionally be absent, as in our case and in the case previously reported (6). Awareness of ampullary pathology as a possible source of bleeding is, therefore, very important, and endoscopic evaluation using a lateral-viewing scope is essential. Clinical evidence for metastases in our patient occurred 10 and 11 years following the initial diagnosis. Such a long interval between initial diagnosis of renal cell carcinoma and the appearance of metastatic disease has been observed previously Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991)
0163-2116/91/0309-037656.50/09 1991PlenumPublishingCorporation
METASTATIC RENAL CELL CARCINOMA
Fig. 2. Endoscopic picture of the papilla showing enlarged papilla with ulceration.
Fig. 1. Upper gastrointestinal tract showing papillary mass with barium-filled ulcer crater (arrow).
(7). Unusual sites of such metastases are a characteristic feature of renal cell carcinoma. The overall 10-year survival rate of renal cell carcinoma after nephrectomy is about 18-27% (8). Similar to malignant melanoma, spontaneous tumor regression has been reported in renal cell carcinoma. Rarely, regression of metastatic tumor might occur following removal of the primary tumor. These observations have generated great interest in the immune mechanism and its impact on tumor biology. Additionally, biologic response modifiers such as bacillus Calmette-Guerin (BCG), interleukin-2 (IL-2), and interferon have been tried in the therapy of metastatic renal cell carcinoma (9). However, the evidence for the role of an immune mechanism in tumor biology is minimal. Regression of renal tumors has been noted among experimental animals using hormone treatment such as progestational agents and androgens, Early trials with progestins in RCC have shown a favorable response, while more recent studies have yielded a rather Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991)
poor result (10). It seems that there was at least a transient improvement in our patient with hormone therapy. However, one might argue for surgical treatment at the initial diagnosis of ampuUary metastasis since most solitary metastasis respond favorably to an operative approach. More recently, laser therapy, for coagulation and tumor ablation, has been utilized in ampullary tumors, although data to support its role in controlling bleeding is lacking. The endoscopic appearance of the ampullary tumor in our patient was that of an enlarged papilla with central ulceration suggestive of malignancY, whereas in the previously reported case (2) the enlarged papilla was covered with normal-appearing mucosa and was suggestive of an impacted stone. Therefore, endoscopic features of ampullary tumors are unreliable and tissue diagnosis is mandatory to establish the diagnosis. Conventional endoscopic examination using an end-viewing instrument can often miss tumors arising from the papilla. Hence a lateral-viewing endoscope should always be used for endoscopic inspection and biopsy of ampullary tumors. SUMMARY
In this paper we report the case of a renal cell carcinoma (RCC) metastatic to the ampullary region. The patient presented with severe anemia due 377
VENU ET AL
Fig. 3. Section of ampulla showing collections of clear cells (arrows) beneath the epithelium in the lamina propria. Tumor cells have small, central, hyperchromatic nuclei, and abundant, clear cytoplasm. Hematoxylin and eosin, •
to blood loss from the ampullary tumor 11 years after nephrectomy for the primary renal cancer. The diagnosis was established by means of endoscopy and biopsy. REFERENCES 1. Venu RP, Geenen JE: Diagnosis and treatment of diseases of the papilla. Clin Gastroenterol 15:439-457, 1986 2. McKenna JI, Kozarek RA: Metastatic hypernephroma of the ampulla of Vater: an unusual cause of malabsorption diagnosed at endoscopic sphincterotomy. Am J Gastroenterol 84:81-83, 1989 3. Sivak MV: Clinical and endoscopic aspects of tumors of the ampulla of Vater. Endoscopy 20:211-217, 1988
378
4. Graham AP: Malignancy of the kidney, survey of 195 cases. J Urol 58:10, 1947 5. Nakao NL, Siegel JH, Stenger RJ, Geb AM: Tumors of the ampulla of Vater: early diagnosis by intraampullary biopsy during endoscopic cannulation. Gastroenterology 83:459, 1982 6. Robertson JFT, Imrie CW: Acute pancreatitis associated with carcinoma of the ampulla of Vater. Br J Surg 74:395397, 1987 7. Strijk SP: Pancreatic metastasis of renal cell carcinoma: Report of two cases. Gastrointest Radiol 14:123-126, 1989 8. Stenzl A, de Kernion JB: Pathology, biology and clinical staging of renal cell carcinoma. Semin Oncol 16:3-11, 1989 9. Harris DT: Hormonal therapy and chemotherapy of renal cell carcinoma. Semin Oncol 10:422-440, 1983 10. Buzaid AC, Todd MB: Therapeutic options in renal cell carcinoma. Semin Oncol 16(1):12-19, 1989
Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991)
CASE R E P O R T
Ampullary Tumor Caused by Metastatic Renal Cell Carcinoma R.P. VENU, MD, P. ROLNY, MD, PhD, J.E. GEENEN, MD, W.J. HOGAN, MD, R.A. KOMOROWSKI, MD, and R. FERSTENBERG, MD KEY WORDS: ampullary neoplasm; endoscopic diagnosis.
The ampullary region is an unusual site of metastatic malignancy (1). Among the tumors involving the ampulla of Vater, only one case of metastatic renal cell carcinoma has been described in detail to date (2). In this paper we describe a second case of renal cell carcinoma that metastasized to the papilla.
CASE REPORT A 64-year-old male was hospitalized with a one-week history of malaise, fatigue, and shortness of breath. The patient underwent a left nephrectomy for renal cell carcinoma 11 years previously. There was no evidence of metastases at the time of nephrectomy. One year prior to admission a lobect0my had been performed for a metastatic lesion in the left lung. On admission, the patient was pale and severely anemic; the hemoglobin was 5.0 g/liter, hematocrit 17%, and MCV 68 ~m2. Stool was positive for occult blood. Coagulation studies and liver function tests were normal. An upper gastrointestinal series revealed an ampullary mass with a central ulcer (Figure 1). At endoscopic examination (Olympus 1T20, lateral-viewing endoscope), the papilla appeared enlarged. It was covered with normal mucosa and an irregularly shaped ulcer was noted on its summit (Figure 2). Fresh blood was seen at the base of the ulcer. Using a standard forceps, multiple biopsies were obtained from the ampullary lesion, and histology revealed a metastatic renal cell carcinoma (Figure 3). The patient was treated with Megace (megestrol acetate) (BristolMyers Institutional Products, A Bristol-Myers Company, 2400 W. Lloyd Expressway, Evansville, Indiana 477210001), for tumor regression. He did well for two years and then developed recurrent bleeding. Surgical consultation was therefore obtained and the tumor was resected. Postoperatively the patient succumbed to massive pulmonarY embolism. Manuscript received June 13, 1990; revised manuscript received September 24, 1990; accepted October 1, 1990. From the Digestive Disease Center, St. Luke's Hospital, Racine, Wisconsin; and Departments of Pathology and Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin. Address for reprint requests: Dr. R.P. Venu, Gastroenterology Consultants, Inc., 1333 College Ave., Racine, Wisconsin 53403.
376
DISCUSSION Symptoms associated with ampullary tumors are usually the result of obstruction of the bile duct and/or pancreatic duct, which leads to jaundice, acute pancreatitis, or malabsorption. Less commonly, ulceration of the tumor may produce occult and/or overt gastrointestinal bleeding (3). Our patient's clinical picture was characterized by severe anemia due to chronic blood loss and in the case previously reported malabsorption was the presenting symptom (2). Thus, both patients with ampullary tumors due to metastatic renal cell carcinoma displayed symptoms which, although uncommon, are recognized features of ampullary neoplasms. Gastrointestinal bleeding in patients with renal cell carcinoma is usually the result of involvement of the small intestine by direct invasion or metastatic spread of the tumor (4). Our case illustrates that gastrointestinal bleeding may also be caused by metastatic spread of the neoplasm to the ampulla of Vater. Barium studies of the stomach and small bowel, which are often utilized to evaluate chronic upper gastrointestinal bleeding, might easily overlook an ampullary tumor (5). In addition, the laboratory and/or clinical signs of biliary tract obstruction that normally alert clinicians to the possibility of ampullary disease may occasionally be absent, as in our case and in the case previously reported (6). Awareness of ampullary pathology as a possible source of bleeding is, therefore, very important, and endoscopic evaluation using a lateral-viewing scope is essential. Clinical evidence for metastases in our patient occurred 10 and 11 years following the initial diagnosis. Such a long interval between initial diagnosis of renal cell carcinoma and the appearance of metastatic disease has been observed previously Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991)
0163-2116/91/0309-037656.50/09 1991PlenumPublishingCorporation
METASTATIC RENAL CELL CARCINOMA
Fig. 2. Endoscopic picture of the papilla showing enlarged papilla with ulceration.
Fig. 1. Upper gastrointestinal tract showing papillary mass with barium-filled ulcer crater (arrow).
(7). Unusual sites of such metastases are a characteristic feature of renal cell carcinoma. The overall 10-year survival rate of renal cell carcinoma after nephrectomy is about 18-27% (8). Similar to malignant melanoma, spontaneous tumor regression has been reported in renal cell carcinoma. Rarely, regression of metastatic tumor might occur following removal of the primary tumor. These observations have generated great interest in the immune mechanism and its impact on tumor biology. Additionally, biologic response modifiers such as bacillus Calmette-Guerin (BCG), interleukin-2 (IL-2), and interferon have been tried in the therapy of metastatic renal cell carcinoma (9). However, the evidence for the role of an immune mechanism in tumor biology is minimal. Regression of renal tumors has been noted among experimental animals using hormone treatment such as progestational agents and androgens, Early trials with progestins in RCC have shown a favorable response, while more recent studies have yielded a rather Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991)
poor result (10). It seems that there was at least a transient improvement in our patient with hormone therapy. However, one might argue for surgical treatment at the initial diagnosis of ampuUary metastasis since most solitary metastasis respond favorably to an operative approach. More recently, laser therapy, for coagulation and tumor ablation, has been utilized in ampullary tumors, although data to support its role in controlling bleeding is lacking. The endoscopic appearance of the ampullary tumor in our patient was that of an enlarged papilla with central ulceration suggestive of malignancY, whereas in the previously reported case (2) the enlarged papilla was covered with normal-appearing mucosa and was suggestive of an impacted stone. Therefore, endoscopic features of ampullary tumors are unreliable and tissue diagnosis is mandatory to establish the diagnosis. Conventional endoscopic examination using an end-viewing instrument can often miss tumors arising from the papilla. Hence a lateral-viewing endoscope should always be used for endoscopic inspection and biopsy of ampullary tumors. SUMMARY
In this paper we report the case of a renal cell carcinoma (RCC) metastatic to the ampullary region. The patient presented with severe anemia due 377
VENU ET AL
Fig. 3. Section of ampulla showing collections of clear cells (arrows) beneath the epithelium in the lamina propria. Tumor cells have small, central, hyperchromatic nuclei, and abundant, clear cytoplasm. Hematoxylin and eosin, •
to blood loss from the ampullary tumor 11 years after nephrectomy for the primary renal cancer. The diagnosis was established by means of endoscopy and biopsy. REFERENCES 1. Venu RP, Geenen JE: Diagnosis and treatment of diseases of the papilla. Clin Gastroenterol 15:439-457, 1986 2. McKenna JI, Kozarek RA: Metastatic hypernephroma of the ampulla of Vater: an unusual cause of malabsorption diagnosed at endoscopic sphincterotomy. Am J Gastroenterol 84:81-83, 1989 3. Sivak MV: Clinical and endoscopic aspects of tumors of the ampulla of Vater. Endoscopy 20:211-217, 1988
378
4. Graham AP: Malignancy of the kidney, survey of 195 cases. J Urol 58:10, 1947 5. Nakao NL, Siegel JH, Stenger RJ, Geb AM: Tumors of the ampulla of Vater: early diagnosis by intraampullary biopsy during endoscopic cannulation. Gastroenterology 83:459, 1982 6. Robertson JFT, Imrie CW: Acute pancreatitis associated with carcinoma of the ampulla of Vater. Br J Surg 74:395397, 1987 7. Strijk SP: Pancreatic metastasis of renal cell carcinoma: Report of two cases. Gastrointest Radiol 14:123-126, 1989 8. Stenzl A, de Kernion JB: Pathology, biology and clinical staging of renal cell carcinoma. Semin Oncol 16:3-11, 1989 9. Harris DT: Hormonal therapy and chemotherapy of renal cell carcinoma. Semin Oncol 10:422-440, 1983 10. Buzaid AC, Todd MB: Therapeutic options in renal cell carcinoma. Semin Oncol 16(1):12-19, 1989
Digestive Diseases and Sciences, Vol. 36, No. 3 (March 1991)
