0022~5347 /90 /l 434-0797$02.00 /0 THE ,JOURNAL OF UROLOGY Copyright (C) 1990 hy AMERICAN UROLOGICAL ASSOCIATION, lNC.
RENAL CELL CARCINOMA IN A RENAL CYST: A CASE REPORT AND REVIEW OF THE LITERATURE BORJE LJUNGBERG, GORAN HOLMBERG, JAN-GUNNAR SJODIN, SVEN-OLA HIETALA AND ROGER STENLING From the Departments of Urology, Andrology, Radiology and Pathology, University of Umea, Umea, Sweden
ABSTRACT
We report a case of renal cell carcinoma within a simple renal cyst in the lower pole of the right kidney. Excretory urography showed a mass and ultrasonography revealed multiple renal cysts with a solid component arising from the wall in 1. This finding also was visualized by computerized tomography. Analysis of the cystic fluid showed a high cholesterol level but negative cytological results. At operation a 7 mm. tumor arose from the wall of the cyst. Histopathological examination showed grade 3 renal cell carcinoma with an aneuploid deoxyribonucleic acid content. (J. Ural., 143: 797-799, 1990) The incidence of a simple renal cyst and renal cell carcinoma coexisting in the same kidney is approximately 2 to 3 % but a tumor arising within a renal cyst is rare. 1 Emmett and associates presented only 10 cases with cysts and tumors among a total of 1,007 patients who underwent exploration. 2 In that study no case was found of a tumor in the wall of a renal cyst. However, others have described this entity. 3 - 8 We describe a case of renal cell carcinoma within a renal cyst. The diagnostic evaluation was complemented by analysis of tumor deoxyribonucleic acid (DNA) content and biochemistry of the cystic fluid. CASE REPORT
A 71-year-old man was hospitalized in January 1988 because of macroscopic hematuria. He had undergone an operation 7 years previously for rectal carcinoma. There was no sign of recurrence. Excretory urography revealed a renal mass in the lower pole of the right kidney. Ultrasonography showed 2 renal cysts in the right kidney with a solid component in the most caudal and largest cyst (fig. 1). Computerized tomography (CT) confirmed the existence of a solid mass, less than 1 cm. in diameter, emerging into a renal cyst with otherwise low attenuation (10 Hounsfield units). Selective renal angiography showed hypovascular renal masses and bilateral parenchymal scarring, apparently due to pyelonephritis. No tumor vessels were visualized. The patient had decreased renal function bilaterally, with a total glomerular filtration rate of 38 ml. per minute per 1.73 m. 2 (ethylenediaminetetraacetic acid). Of the total renal function 65% was localized to the right kidney. Surgical approach. Due to renal dysfunction a conservative operation was planned. The right kidney was explored and the renal cyst with the solid component was identified in the lower third. The cystic fluid was aspirated and the roof the cyst was excised. Inside the cyst a mass protruded into the cavity as shown by ultrasound and CT. This expansive 6 to 7 mm. tumor was excised. Just beneath this mass, in the excised tissue, another small palpable tumor was found. Additional normal renal parenchyma was excised under the apparent renal tumors for evaluation of radicality. Histopathological examination. The tumors were divided: half of each tumor was taken for histopathological examination and half was used for DNA analysis. Both tumors were histopathologically grade 3 renal cell carcinoma according to the grading system of Skinner and associates (fig. 2). 9 The tumors were sharply demarcated from the surrounding tissue. The adjacent kidney tissue beneath the tumors was free of neoplastic cells. Accepted for publication November 17, 1989.
DNA analysis. Flow cytometry of the fresh tissue samples was performed as described previously with a FACscan* unit. 10 The tumor tissues were aneuploid with a DNA index of 1. 7 and 1.8 (fig. 3), respectively. The adjacent kidney tissue had a diploid DNA content. Cyst fluid analysis. The aspirated cystic fluid was straw colored and slightly cloudy. Cytological examination revealed no tumor cells. Fat analysis showed a cholesterol content of 2.9 mmol./1. and a triglyceride concentration of 0.26 mmol./1. Electrophoresis revealed a serum-like protein content with an albumin level of 46 gm./1. The cystic fluid was analyzed for the tumor marker CA-50, a monoclonal antibody. A value of 225 units per ml. was found. The patient had a normal serum level (less than 17 units per ml.). In the cystic fluid of 5 patients with simple renal cysts the CA-50 level ranged from 7.8 to 8.4 units per ml. (unpublished data). Followup. The patient was followed with CT scans of the abdomen and pulmonary x-ray at 6, 12 and 18 months postoperatively with no evidence of local recurrence or metastases. DISCUSSION
Renal cell carcinoma within a cyst rarely is encountered. Only a few previous cases have been reported with this combination of renal cell carcinoma and renal cyst. 3 ~ 8 A strict evaluation of every renal mass is mandatory so as not to overlook
FIG. 1. Ultrasonography shows tumor within renal cyst * Becton Dickinson, United States.
797
798
LJUNGBERG AND ASSOCIATES
this type of tumor, especially when the tumor is small and the patient has multiple cysts. The investigation in our patient was prompted because of hematuria. It may be questioned whether the hematuria was produced by the small renal cell carcinoma or by other causes. In patients with simple renal cysts a 4% frequency of hematuria is described with no other causes found. 11 Our case further illustrates the importance of adequate examination of patients with hematuria. When radiological evaluation with ultrasound and CT do not fulfill all of the criteria for a simple renal cyst further examination is necessary. Percutaneous puncture with analysis of the cystic fluid and also selective renal angiography have been suggested as complementary methods. 12-14 The tumor in our patient was not visualized by angiography. Cytological exami-
nation has been reported to have a low sensitivity in cases of cystic tumor, 13 which was confirmed in our case by the negative cytological findings. However, the cystic fluid had a high content of cholesterol. This finding supports previous studies suggesting that analysis of the lipid content in cyst fluid is a reliable method of tumor detection. 13• 14 Interestingly, the tumor marker CA-50 had a high level in the cyst fluid in our patient. In patients with simple renal cysts normal levels were found. To our knowledge there has been no previous report of this tumor marker in a renal cyst with or without coexistence of a renal cell carcinoma. Serum levels of CA-50 were elevated in 5 of 19 patients with renal cell carcinoma. 15 Whether this marker might be useful in the evaluation of cystic renal masses needs further study. The solid component in the wall of the simple renal cyst had a diameter of less than 1 cm. Lesions with a diameter of less than 3 cm. have been classified previously as adenomas. However, despite the small size, the tumor in our patient was grade 3 renal cell carcinoma with an aneuploid DNA content. It has been reported that small renal cortical tumors may be aneuploid and that renal cell carcinomas of less than 3 cm. may metastasize.16' 17 We showed previously that aneuploid tumors generally do not respect the surrounding tissues and for these tumors enucleation or near excision might not be radical. 10 In our patient the aneuploid tumor seems to have been excised radically, since the adjacent kidney tissue showed no malignant cells and had a diploid DNA content. The surgical approach with local excision used in our patient is somewhat controversial. The malignant nature of the mass was not known preoperatively and since the patient had impaired renal function a conservative operation was planned. If the definite diagnosis in our patient had been known preoperatively a pole resection would have been planned, which has been reported to be sufficient in cases with a single kidney or impaired renal function. 18·19 Our case represents a rare renal cell carcinoma diagnosed within a renal cyst. The difficulties in preoperative diagnosis are illustrated by the limitation of cytological analysis of cyst fluid. When the radiological criteria of a simple renal cyst are not fulfilled exploration with histopathological examination is recommended.
FIG. 2. Specimen through renal cell carcinoma (T) protruding into cyst. Arrow shows demarcation to surrounding normal renal parenchyma (N). C, lumen of cyst. Reduced from Xl30.
1. Lang, E. K.: Coexistence of cyst and tumor in the same kidney. Radiology, 101: 7, 1971. 2. Emmett, J. L., Levine, S. R. and Woolner, L.B.: Coexistence of renal cyst and tumour: incidence in 1007 cases. Brit. J. Urol., 35: 403, 1963. 3. Silverman, J. F. and Kilhenny, C.: Tumor in the wall of a simple renal cyst. Report of a case. Radiology, 93: 95, 1969. 4. Weitzner, S.: Clear cell carcinoma of the free wall of a simple renal cyst. J. Urol., 106: 515, 1971. 5. Srimannarayana, A., Kelly, D. G. and Duff, F. A.: Renal cell carcinoma in the free wall of a simple renal cyst. Brit. J. Urol., 47: 152, 1975. 6. Sufrin, G., Etra, W., Gaeta, J. and Merrin, C. E.: Hypernephroma arising in wall of simple renal cyst. Urology, 6: 507, 1975. 7. Khorsand, D.: Carcinoma within solitary renal cysts. J. Urol., 93: 440, 1965. 8. Bruun, E. and Nielsen, K.: Solitary cyst and clear cell adenocarcinoma of the kidney: report of 2 cases and review of the literature. J. Urol., 136: 449, 1986. 9. Skinner, D. G., Colvin, R. B., Vermillion, C. D., Pfister, R. C. and Leadbetter, W. F.: Diagnosis and management of renal cell carcinoma: a clinical and pathologic study of 309 cases. Cancer, 28: 1165, 1971. 10. Ljungberg, B., Stenling, R. and Roos, G.: Tumor spread and DNA content in human renal cell carcinoma. Cancer Res., 48: 3165, 1988. 11. Steg, A.: Renal cysts in adults. III. Clinical aspect and diagnostic approach, based on the analysis of 1,342 cases. Eur. Urol., 2: 209, 1976.
REFERENCES
800
r-i r-i (1)
v
0
(1
1 E10 DNA
200
content
Fm. 3. DNA histogram with DNA index of 1.8 in 1 part of renal cell carcinoma.
RElsJAL CELL CARCLNOJvtA Il,~ RENitL CYST 120 Holmberg, Go, Hietaia, So-Oo and Ljungberg, R: A comparison of
radiologic methods in the diagnosis of renal mass lesionso Scando Jo UroL NephroL, 22: 185, 198R 130 Kleist, ff, Jonsson, 00, Lundstam, So, Naucler, Jo, Nilson, Ao K and Pettersson, So: Quantitative lipid analysis in the differential diagnosis of cystic renal lesionso Brito Jo UroL, 54: 441, 19820 140 Lang, K K: Roentgenographic assessment of asymptomatic renal lesionso An analysis of the confidence level of diagnosis established by sequential roentgenographic investigationo Radiology, 109: 257, 1973o 150 Holmgren, Jo, Lindholm, L, Persson, R, Lagergard, To, Nilsson, 00, Svennerholm, Lo, Rudenstam, Co-Mo, Unsgaard, R,
160 170
180 190
799
Yngvason, Fo, Pettersson, So and Killander, Ao Fo: Detection by monoclonal antibody of carbohydrate antigen CA 50 in serum of patients with carcinomao Brito Medo Jo, 288: 1479, 19840 Bennington, Jo L: Renal adenomao World Jo UroL, 5: 66, 19870 Curry, No So, Schabel, So L and Betsill, WO L, Jro: Small renal neoplasms: diagnostic imaging, pathologic features, and clinical courseo Radiology, 158: 113, 19860 Novick, Ao Co, Zincke, ff, Neves, R Jo and Topley, H. Mo: Surgical enucleation for renal cell carcinomao Jo UroL, 135: 235, 19860 Topley, Mo, Novick, k Co and Montie, Jo K: Long-term results following partial nephrectomy for localized renal adenocarcinomao Jo UroL, 131: 1050, 19840
RENAL CELL CARCINOMA IN A RENAL CYST: A CASE REPORT AND REVIEW OF THE LITERATURE BORJE LJUNGBERG, GORAN HOLMBERG, JAN-GUNNAR SJODIN, SVEN-OLA HIETALA AND ROGER STENLING From the Departments of Urology, Andrology, Radiology and Pathology, University of Umea, Umea, Sweden
ABSTRACT
We report a case of renal cell carcinoma within a simple renal cyst in the lower pole of the right kidney. Excretory urography showed a mass and ultrasonography revealed multiple renal cysts with a solid component arising from the wall in 1. This finding also was visualized by computerized tomography. Analysis of the cystic fluid showed a high cholesterol level but negative cytological results. At operation a 7 mm. tumor arose from the wall of the cyst. Histopathological examination showed grade 3 renal cell carcinoma with an aneuploid deoxyribonucleic acid content. (J. Ural., 143: 797-799, 1990) The incidence of a simple renal cyst and renal cell carcinoma coexisting in the same kidney is approximately 2 to 3 % but a tumor arising within a renal cyst is rare. 1 Emmett and associates presented only 10 cases with cysts and tumors among a total of 1,007 patients who underwent exploration. 2 In that study no case was found of a tumor in the wall of a renal cyst. However, others have described this entity. 3 - 8 We describe a case of renal cell carcinoma within a renal cyst. The diagnostic evaluation was complemented by analysis of tumor deoxyribonucleic acid (DNA) content and biochemistry of the cystic fluid. CASE REPORT
A 71-year-old man was hospitalized in January 1988 because of macroscopic hematuria. He had undergone an operation 7 years previously for rectal carcinoma. There was no sign of recurrence. Excretory urography revealed a renal mass in the lower pole of the right kidney. Ultrasonography showed 2 renal cysts in the right kidney with a solid component in the most caudal and largest cyst (fig. 1). Computerized tomography (CT) confirmed the existence of a solid mass, less than 1 cm. in diameter, emerging into a renal cyst with otherwise low attenuation (10 Hounsfield units). Selective renal angiography showed hypovascular renal masses and bilateral parenchymal scarring, apparently due to pyelonephritis. No tumor vessels were visualized. The patient had decreased renal function bilaterally, with a total glomerular filtration rate of 38 ml. per minute per 1.73 m. 2 (ethylenediaminetetraacetic acid). Of the total renal function 65% was localized to the right kidney. Surgical approach. Due to renal dysfunction a conservative operation was planned. The right kidney was explored and the renal cyst with the solid component was identified in the lower third. The cystic fluid was aspirated and the roof the cyst was excised. Inside the cyst a mass protruded into the cavity as shown by ultrasound and CT. This expansive 6 to 7 mm. tumor was excised. Just beneath this mass, in the excised tissue, another small palpable tumor was found. Additional normal renal parenchyma was excised under the apparent renal tumors for evaluation of radicality. Histopathological examination. The tumors were divided: half of each tumor was taken for histopathological examination and half was used for DNA analysis. Both tumors were histopathologically grade 3 renal cell carcinoma according to the grading system of Skinner and associates (fig. 2). 9 The tumors were sharply demarcated from the surrounding tissue. The adjacent kidney tissue beneath the tumors was free of neoplastic cells. Accepted for publication November 17, 1989.
DNA analysis. Flow cytometry of the fresh tissue samples was performed as described previously with a FACscan* unit. 10 The tumor tissues were aneuploid with a DNA index of 1. 7 and 1.8 (fig. 3), respectively. The adjacent kidney tissue had a diploid DNA content. Cyst fluid analysis. The aspirated cystic fluid was straw colored and slightly cloudy. Cytological examination revealed no tumor cells. Fat analysis showed a cholesterol content of 2.9 mmol./1. and a triglyceride concentration of 0.26 mmol./1. Electrophoresis revealed a serum-like protein content with an albumin level of 46 gm./1. The cystic fluid was analyzed for the tumor marker CA-50, a monoclonal antibody. A value of 225 units per ml. was found. The patient had a normal serum level (less than 17 units per ml.). In the cystic fluid of 5 patients with simple renal cysts the CA-50 level ranged from 7.8 to 8.4 units per ml. (unpublished data). Followup. The patient was followed with CT scans of the abdomen and pulmonary x-ray at 6, 12 and 18 months postoperatively with no evidence of local recurrence or metastases. DISCUSSION
Renal cell carcinoma within a cyst rarely is encountered. Only a few previous cases have been reported with this combination of renal cell carcinoma and renal cyst. 3 ~ 8 A strict evaluation of every renal mass is mandatory so as not to overlook
FIG. 1. Ultrasonography shows tumor within renal cyst * Becton Dickinson, United States.
797
798
LJUNGBERG AND ASSOCIATES
this type of tumor, especially when the tumor is small and the patient has multiple cysts. The investigation in our patient was prompted because of hematuria. It may be questioned whether the hematuria was produced by the small renal cell carcinoma or by other causes. In patients with simple renal cysts a 4% frequency of hematuria is described with no other causes found. 11 Our case further illustrates the importance of adequate examination of patients with hematuria. When radiological evaluation with ultrasound and CT do not fulfill all of the criteria for a simple renal cyst further examination is necessary. Percutaneous puncture with analysis of the cystic fluid and also selective renal angiography have been suggested as complementary methods. 12-14 The tumor in our patient was not visualized by angiography. Cytological exami-
nation has been reported to have a low sensitivity in cases of cystic tumor, 13 which was confirmed in our case by the negative cytological findings. However, the cystic fluid had a high content of cholesterol. This finding supports previous studies suggesting that analysis of the lipid content in cyst fluid is a reliable method of tumor detection. 13• 14 Interestingly, the tumor marker CA-50 had a high level in the cyst fluid in our patient. In patients with simple renal cysts normal levels were found. To our knowledge there has been no previous report of this tumor marker in a renal cyst with or without coexistence of a renal cell carcinoma. Serum levels of CA-50 were elevated in 5 of 19 patients with renal cell carcinoma. 15 Whether this marker might be useful in the evaluation of cystic renal masses needs further study. The solid component in the wall of the simple renal cyst had a diameter of less than 1 cm. Lesions with a diameter of less than 3 cm. have been classified previously as adenomas. However, despite the small size, the tumor in our patient was grade 3 renal cell carcinoma with an aneuploid DNA content. It has been reported that small renal cortical tumors may be aneuploid and that renal cell carcinomas of less than 3 cm. may metastasize.16' 17 We showed previously that aneuploid tumors generally do not respect the surrounding tissues and for these tumors enucleation or near excision might not be radical. 10 In our patient the aneuploid tumor seems to have been excised radically, since the adjacent kidney tissue showed no malignant cells and had a diploid DNA content. The surgical approach with local excision used in our patient is somewhat controversial. The malignant nature of the mass was not known preoperatively and since the patient had impaired renal function a conservative operation was planned. If the definite diagnosis in our patient had been known preoperatively a pole resection would have been planned, which has been reported to be sufficient in cases with a single kidney or impaired renal function. 18·19 Our case represents a rare renal cell carcinoma diagnosed within a renal cyst. The difficulties in preoperative diagnosis are illustrated by the limitation of cytological analysis of cyst fluid. When the radiological criteria of a simple renal cyst are not fulfilled exploration with histopathological examination is recommended.
FIG. 2. Specimen through renal cell carcinoma (T) protruding into cyst. Arrow shows demarcation to surrounding normal renal parenchyma (N). C, lumen of cyst. Reduced from Xl30.
1. Lang, E. K.: Coexistence of cyst and tumor in the same kidney. Radiology, 101: 7, 1971. 2. Emmett, J. L., Levine, S. R. and Woolner, L.B.: Coexistence of renal cyst and tumour: incidence in 1007 cases. Brit. J. Urol., 35: 403, 1963. 3. Silverman, J. F. and Kilhenny, C.: Tumor in the wall of a simple renal cyst. Report of a case. Radiology, 93: 95, 1969. 4. Weitzner, S.: Clear cell carcinoma of the free wall of a simple renal cyst. J. Urol., 106: 515, 1971. 5. Srimannarayana, A., Kelly, D. G. and Duff, F. A.: Renal cell carcinoma in the free wall of a simple renal cyst. Brit. J. Urol., 47: 152, 1975. 6. Sufrin, G., Etra, W., Gaeta, J. and Merrin, C. E.: Hypernephroma arising in wall of simple renal cyst. Urology, 6: 507, 1975. 7. Khorsand, D.: Carcinoma within solitary renal cysts. J. Urol., 93: 440, 1965. 8. Bruun, E. and Nielsen, K.: Solitary cyst and clear cell adenocarcinoma of the kidney: report of 2 cases and review of the literature. J. Urol., 136: 449, 1986. 9. Skinner, D. G., Colvin, R. B., Vermillion, C. D., Pfister, R. C. and Leadbetter, W. F.: Diagnosis and management of renal cell carcinoma: a clinical and pathologic study of 309 cases. Cancer, 28: 1165, 1971. 10. Ljungberg, B., Stenling, R. and Roos, G.: Tumor spread and DNA content in human renal cell carcinoma. Cancer Res., 48: 3165, 1988. 11. Steg, A.: Renal cysts in adults. III. Clinical aspect and diagnostic approach, based on the analysis of 1,342 cases. Eur. Urol., 2: 209, 1976.
REFERENCES
800
r-i r-i (1)
v
0
(1
1 E10 DNA
200
content
Fm. 3. DNA histogram with DNA index of 1.8 in 1 part of renal cell carcinoma.
RElsJAL CELL CARCLNOJvtA Il,~ RENitL CYST 120 Holmberg, Go, Hietaia, So-Oo and Ljungberg, R: A comparison of
radiologic methods in the diagnosis of renal mass lesionso Scando Jo UroL NephroL, 22: 185, 198R 130 Kleist, ff, Jonsson, 00, Lundstam, So, Naucler, Jo, Nilson, Ao K and Pettersson, So: Quantitative lipid analysis in the differential diagnosis of cystic renal lesionso Brito Jo UroL, 54: 441, 19820 140 Lang, K K: Roentgenographic assessment of asymptomatic renal lesionso An analysis of the confidence level of diagnosis established by sequential roentgenographic investigationo Radiology, 109: 257, 1973o 150 Holmgren, Jo, Lindholm, L, Persson, R, Lagergard, To, Nilsson, 00, Svennerholm, Lo, Rudenstam, Co-Mo, Unsgaard, R,
160 170
180 190
799
Yngvason, Fo, Pettersson, So and Killander, Ao Fo: Detection by monoclonal antibody of carbohydrate antigen CA 50 in serum of patients with carcinomao Brito Medo Jo, 288: 1479, 19840 Bennington, Jo L: Renal adenomao World Jo UroL, 5: 66, 19870 Curry, No So, Schabel, So L and Betsill, WO L, Jro: Small renal neoplasms: diagnostic imaging, pathologic features, and clinical courseo Radiology, 158: 113, 19860 Novick, Ao Co, Zincke, ff, Neves, R Jo and Topley, H. Mo: Surgical enucleation for renal cell carcinomao Jo UroL, 135: 235, 19860 Topley, Mo, Novick, k Co and Montie, Jo K: Long-term results following partial nephrectomy for localized renal adenocarcinomao Jo UroL, 131: 1050, 19840
