0022-5347/79/1224-0539$02.00/0 Vol. 122, October Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Case Reports CYSTIC NEPHROMA: AN ULTRASTRUCTURAL AND BIOCHEMICAL STUDY ARTHUR B. ABT,* LAURENCE M. DEMERS
AND
STEPHEN J. SHOCHAT
From the Departments of Pathology and Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania
ABSTRACT
A case of a multilocular renal cyst (cystic nephroma) in an 18-month-old girl is presented. The light and electron microscopy studies failed to demonstrate nephroblastomatous elements. Analysis of cystic fluid constituents showed levels resembling serum. Measurable levels of prostaglandins E and F also were found. The possible relationship of a cystic nephroma to a nephroblastoma is discussed. Cystic nephromas are uncommon lesions that have been reported variously under many names, including benign multilocular cystic nephroma and multilocular cyst of the kidney. 1- 3 The latter term appears to be the most frequently used. A recent report by Gallo and Penchansky summarized the reported cases and the varied nomenclature. 4 About half of all cystic nephromas have been reported in children. Their clinical presentation is similar to that of a nephroblast na (Wilms tumor). Whether these lesions are a benign cystic form of nephroblastoma or a variant of renal dysplasia has yet to be determined. Herein we report a case of a cystic nephroma and discuss the ultrastructural aspects of this entity as well as the chemical content of the cystic fluid. CASE REPORT
An 18-month-old white girl was referred to us for evaluation of a mass in the right flank. An excretory urogram demonstrated an avascular mass in the upper pole of the right kidney. The right renal pelvis and caliceal system were distorted by the mass. A chest x-ray revealed a bullous lesion in the right upper lobe. Laboratory data included a normal hemoglobin and hematocrit. Urinalysis showed 2+ proteinuria. A vanillyl mandelic acid screening spot test was negative. A right nephrectomy was done. Examination of the left kidney and liver was normal. A simple cyst in the upper lobe of the right lung was excised 1 year later. There was no other evidence of disease at the time of this second operation or during the subsequent year. MATERIALS AND METHODS
Tissue for light microscopy was stained with hematoxylin and eosin, Masson trichrome and phosphotungstic acid hematoxylin. Material for electron microscopy was fixed in 4 per cent glutaraldehyde after 24 hours in buffered formaldehyde. The tissue was then processed according to standard procedures. Cystic fluid for chemical analysis was aspirated from the cyst immediately after excision. The fluid was kept frozen until chemical analysis was performed using the Technicon SMA 12/
60 chemical analyzer. Fluid prostaglandin measurements were performed by radioimmunoassay. 5 PATHOLOGIC FINDINGS
The excised kidney weighed 260 gm. and measured 12 X 9 x 7 cm. The mass was cystic with a densely adherent white fibrous capsule. The kidney could not be dissected free from the cystic mass. On cut section multiple thin-walled irregular cysts of varying size that contained clear, pale yellow fluid were noted (fig. 1). The cysts were lined by cells ranging from flattened cuboidal to columnar epithelium (fig. 2). Some of the columnar cells appeared to be vacuolated. The tissue between the cysts contained spindle cells with scattered lymphocytes and plasma cells. No immature cellular elements were present. Smooth muscle was identified within the capsule of the mass and in large blood vessels in the cystic nephroma. Adjacent renal tissue exhibited a compression artifact. The capsule between the cystic mass and adjacent renal parenchyma was composed of dense fibrous tissue. It contained occasional normal-appearing tubular structures and glomeruli. No glomeruli were seen within the cystic tumor. The ultrastructural studies demonstrated cysts lined by cells that were adherent to and interdigitated with a thick underlying basement membrane (fig. 3, A). Junctional complexes were observed frequently (fig. 3, B). A few microvilli were present on the luminal aspect of the cells. The cytoplasm contained a moderate amount of rough endoplasmic reticulum and round to oval-shaped mitochondria. Occasional intracytoplasmic vacuoles were present. The interstitial tissues demonstrated cells with spindle-shaped nuclei (fibroblasts) and adjacent collagen fibers. Cells exhibiting rhabdomyoblastic differentiation were not observed. The cystic fluid was examined for a number of chemical constituents, including levels ofprostaglandins E and F. Results of these findings with comparable normal serum values are shown in the table. DISCUSSION
The criteria for establishing a diagnosis of cystic nephroma
Accepted for publication January 5, 1979. 1 • Requests for reprints: Division of Anatomic Pathology, The Milton were defined in 1956 by Boggs and Kimmelstiel. These criteria S. Hershey Medical Center, The Pennsylvania State University, Her- have not changed and include the following: 1) the lesion must shey, Pennsylvania 17033. be multilocular, 2) the cysts must, for the most part, be lined 539
540
ABT, DEMERS AND SHOCHAT
FIG. 1. Multilocular cyst is sharply demarcated from renal tissue seen in lower left corner.
FIG. 3. A, cells lining cyst show cytoplasmic interdigitations with thick basement membrane. Few microvilli are present on luminal aspect of cells. Reduced from X13,000. B, portions of 2 adjacent cells show junctional complexes. Cytoplasm contains scattered bundles of filaments and free ribosomes. Intracellular vacuoles and intercellular spaces are noted. Reduced from X48,000.
Cystic Fluid
FIG. 2. Parts of several epithelial-lined cysts are noted. Within interstitium plasma cells and lymphocytes are admixed with fibroblasts. H & E, reduced from X325. by epithelium, 3) the cysts must not communicate with the pelvis, 4) the residual renal tissue should be essentially normal except for pressure atrophy and 5) fully developed, mature nephra or portions of such should not be present within the septa of the cystic lesion. While these criteria adequately describe cystic nephroma a small number of cases also exhibit solid areas or wide septa with features of nephroblastoma. 4 ' 6- 8 The identification of such foci requires multiple sections of the intercystic trabeculae. Gallo and Penchansky found striated rhabdomyoblasts in 2 of their 4 cases. 4 One of the cases described by Boggs and Kimmelstiel 1 and another reported by Gibson2 contained primitive connective tissue elements without striated rhabdomyoblasts. In our case immature mesenchymal elements were not observed either by light or electron microscopy. The possible relationship of cystic nephroma to either renal dysplasia or nephroblastoma has been considered previously.1· 4 • 6- 8 The sharp demarcation from adjacent normal renal parenchyma, lack of associated pelvic or ureteral abnor-
Sodium Potassium Calcium Phosphorus Urea nitrogen Uric acid Creatinine Lactic dehydrogenase Aspartate transaminase Prostaglandin E Prostaglandin F
130.0 mEq./1. 4.3 mEq./1. 6.1 mg./dl. 0.4 mg./dl. 10.0 mg./dl. 3.9 mg./dl. 0.4 mg./dl. 60.0µ./I. 22.0 µ./1. 35.8 pg./ml. 7.4 pg./ml.
Normal Serum 136.0 to 142 mEq./1. 3.5 to 4.8 mEq./1. 8.5 to 10.5 mg.fell. 2.5 to 4.5 mg./di. 10.0 to 20 mg./dl. 2.5 to 8 mg./dl. 0. 7 to 1.4 mg./di. 80.0 to 220 µ./1. 8.0 to 40 µ./1. 25.0 to 150 pg./ml. (plasma) 25.0 to 200 pg./ml. (plasma)
malities and absence of intralesional cartilage and embryonal ducts all militate against a diagnosis of renal dysplasia. The failure of the cysts in cystic nephroma to communicate with the renal pelvis has been well demonstrated. 1· 2 All but 1 of the previous cases with primitive mesenchymal elements were reported in children. The 64-year-old woman described by Gibson exhibited structures suggestive of metanephric blastema. It is interesting to speculate that the lack of undifferentiated elements in most adult cystic nephromas may · be owing to subsequent maturation of the undifferentiated metanephric blastema. While 50 per cent of cystic nephromas are found in the adult population it is presently unknown if
541
CYSTIC NEPHROMA
these lesions were present since childhood or if they developed later. As judged by the chemical content of the cystic fluid in our case the fluid is strikingly similar to serum. This had been mentioned previously by Kissane 9 as well as Powell and associates, 10 who performed limited studies on cystic fluid. Significant prostaglandin synthesis in renal cell carcinomas 11 and in benign conditions such as Bartter's syndrome 12 has been noted. In the latter disease excessive renal prostaglandin E synthesis is believed to be causative of the hyperrenin state. Little information is available on renal cystic fluid prostaglandins. In our patient measurable levels of prostaglandins were identified within the cystic nephroma but the significance of these levels is unknown. However, it is clear that the levels observed in this fluid were not markedly elevated. The relationship of prostaglandins to nephroblastoma, although unknown, is currently under investigation. Neither pulmonary cysts nor other congenital abnormalities were described in the cases reported previously. While this may be an incidental pulmonary finding a chest x-ray should be obtained in subsequent cases of cystic nephroma. We agree with those authors who suggest that a cystic nephroma is a benign neoplasm rather than a form of dysplasia.1· 4 • G-B While this tumor may be the benign counterpart of a nephroblastoma additional cases with blastomatous elements and prolonged clinical followup should be reported to confirm the relationship. Mr. Dallas Fisher and Mr. Suriyonta Trapukdi assisted in the photography.
REFERENCES
1. Boggs, L. K. and Kimmelstiel, P.: Benign multilocular cystic nephroma: report of two cases of so-called multilocular cyst of the kidney. J. Urol., 76: 530, 1956. 2. Gibson, T. E.: Multilocular cyst of the kidney: case report. J. Urol., 87: 297, 1962. 3. Uson, A. C. and Melicow, M. M.: Multilocular cysts of kidney with intrapelvic herniation of a "daughter" cyst: report of 4 cases. J. Urol., 89: 341, 1963. 4. Gallo, G. E. and Penchansky, L.: Cystic nephroma. Cancer, 39: 1322, 1977. 5. Demers, L. M. and Gabbe, S. G.: Placental prostaglandin levels in pre-eclampsia. Amer. J. Obst. Gynec., 126: 137, 1976. 6. Uson, A. C., Del Rosario, C. and Melicow, M. M.: Wilms tumor in association with cystic renal disease: report of two cases. J. Urol., 83: 262, 1960. 7. Brown, J. M.: Cystic partially differentiated nephroblastoma. J. Path., 115: 175, 1975. 8. Datnow, B. and Daniel, W. W., Jr.: Polycystic nephroblastoma. J.A.M.A., 236: 2528, 1976. 9. Kissane, J. M.: Congenital malformations. In: Pathology of the Kidney, 2nd ed. Edited by R. H. Heptinstall. Boston: Little Brown & Co., vol. 1, pp. 69-119, 1974. 10. Powell, T., Shackman, R. and Johnson, H. D.: Multilocular cysts of the kidney. Brit. J. Urol., 23: 142, 1951. 11. Brereton, H. D., Halushka, P. V., Alexander, R. W., Mason, D. M., Keiser, H. R. and DeVita, V. T., Jr.: lndomethacin-responsive hypercalcemia in a patient with renal-cell adenocarcinoma. New Engl. J. Med., 291: 83, 1974. 12. Fichman, M. P., Telfer, N., Zia, P., Speckart, P., Golub, M. and Rude, R.: Role of prostaglandins in the pathogenesis of Bartter's syndrome. Amer. J. Med., 60: 785, 1976.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Case Reports CYSTIC NEPHROMA: AN ULTRASTRUCTURAL AND BIOCHEMICAL STUDY ARTHUR B. ABT,* LAURENCE M. DEMERS
AND
STEPHEN J. SHOCHAT
From the Departments of Pathology and Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania
ABSTRACT
A case of a multilocular renal cyst (cystic nephroma) in an 18-month-old girl is presented. The light and electron microscopy studies failed to demonstrate nephroblastomatous elements. Analysis of cystic fluid constituents showed levels resembling serum. Measurable levels of prostaglandins E and F also were found. The possible relationship of a cystic nephroma to a nephroblastoma is discussed. Cystic nephromas are uncommon lesions that have been reported variously under many names, including benign multilocular cystic nephroma and multilocular cyst of the kidney. 1- 3 The latter term appears to be the most frequently used. A recent report by Gallo and Penchansky summarized the reported cases and the varied nomenclature. 4 About half of all cystic nephromas have been reported in children. Their clinical presentation is similar to that of a nephroblast na (Wilms tumor). Whether these lesions are a benign cystic form of nephroblastoma or a variant of renal dysplasia has yet to be determined. Herein we report a case of a cystic nephroma and discuss the ultrastructural aspects of this entity as well as the chemical content of the cystic fluid. CASE REPORT
An 18-month-old white girl was referred to us for evaluation of a mass in the right flank. An excretory urogram demonstrated an avascular mass in the upper pole of the right kidney. The right renal pelvis and caliceal system were distorted by the mass. A chest x-ray revealed a bullous lesion in the right upper lobe. Laboratory data included a normal hemoglobin and hematocrit. Urinalysis showed 2+ proteinuria. A vanillyl mandelic acid screening spot test was negative. A right nephrectomy was done. Examination of the left kidney and liver was normal. A simple cyst in the upper lobe of the right lung was excised 1 year later. There was no other evidence of disease at the time of this second operation or during the subsequent year. MATERIALS AND METHODS
Tissue for light microscopy was stained with hematoxylin and eosin, Masson trichrome and phosphotungstic acid hematoxylin. Material for electron microscopy was fixed in 4 per cent glutaraldehyde after 24 hours in buffered formaldehyde. The tissue was then processed according to standard procedures. Cystic fluid for chemical analysis was aspirated from the cyst immediately after excision. The fluid was kept frozen until chemical analysis was performed using the Technicon SMA 12/
60 chemical analyzer. Fluid prostaglandin measurements were performed by radioimmunoassay. 5 PATHOLOGIC FINDINGS
The excised kidney weighed 260 gm. and measured 12 X 9 x 7 cm. The mass was cystic with a densely adherent white fibrous capsule. The kidney could not be dissected free from the cystic mass. On cut section multiple thin-walled irregular cysts of varying size that contained clear, pale yellow fluid were noted (fig. 1). The cysts were lined by cells ranging from flattened cuboidal to columnar epithelium (fig. 2). Some of the columnar cells appeared to be vacuolated. The tissue between the cysts contained spindle cells with scattered lymphocytes and plasma cells. No immature cellular elements were present. Smooth muscle was identified within the capsule of the mass and in large blood vessels in the cystic nephroma. Adjacent renal tissue exhibited a compression artifact. The capsule between the cystic mass and adjacent renal parenchyma was composed of dense fibrous tissue. It contained occasional normal-appearing tubular structures and glomeruli. No glomeruli were seen within the cystic tumor. The ultrastructural studies demonstrated cysts lined by cells that were adherent to and interdigitated with a thick underlying basement membrane (fig. 3, A). Junctional complexes were observed frequently (fig. 3, B). A few microvilli were present on the luminal aspect of the cells. The cytoplasm contained a moderate amount of rough endoplasmic reticulum and round to oval-shaped mitochondria. Occasional intracytoplasmic vacuoles were present. The interstitial tissues demonstrated cells with spindle-shaped nuclei (fibroblasts) and adjacent collagen fibers. Cells exhibiting rhabdomyoblastic differentiation were not observed. The cystic fluid was examined for a number of chemical constituents, including levels ofprostaglandins E and F. Results of these findings with comparable normal serum values are shown in the table. DISCUSSION
The criteria for establishing a diagnosis of cystic nephroma
Accepted for publication January 5, 1979. 1 • Requests for reprints: Division of Anatomic Pathology, The Milton were defined in 1956 by Boggs and Kimmelstiel. These criteria S. Hershey Medical Center, The Pennsylvania State University, Her- have not changed and include the following: 1) the lesion must shey, Pennsylvania 17033. be multilocular, 2) the cysts must, for the most part, be lined 539
540
ABT, DEMERS AND SHOCHAT
FIG. 1. Multilocular cyst is sharply demarcated from renal tissue seen in lower left corner.
FIG. 3. A, cells lining cyst show cytoplasmic interdigitations with thick basement membrane. Few microvilli are present on luminal aspect of cells. Reduced from X13,000. B, portions of 2 adjacent cells show junctional complexes. Cytoplasm contains scattered bundles of filaments and free ribosomes. Intracellular vacuoles and intercellular spaces are noted. Reduced from X48,000.
Cystic Fluid
FIG. 2. Parts of several epithelial-lined cysts are noted. Within interstitium plasma cells and lymphocytes are admixed with fibroblasts. H & E, reduced from X325. by epithelium, 3) the cysts must not communicate with the pelvis, 4) the residual renal tissue should be essentially normal except for pressure atrophy and 5) fully developed, mature nephra or portions of such should not be present within the septa of the cystic lesion. While these criteria adequately describe cystic nephroma a small number of cases also exhibit solid areas or wide septa with features of nephroblastoma. 4 ' 6- 8 The identification of such foci requires multiple sections of the intercystic trabeculae. Gallo and Penchansky found striated rhabdomyoblasts in 2 of their 4 cases. 4 One of the cases described by Boggs and Kimmelstiel 1 and another reported by Gibson2 contained primitive connective tissue elements without striated rhabdomyoblasts. In our case immature mesenchymal elements were not observed either by light or electron microscopy. The possible relationship of cystic nephroma to either renal dysplasia or nephroblastoma has been considered previously.1· 4 • 6- 8 The sharp demarcation from adjacent normal renal parenchyma, lack of associated pelvic or ureteral abnor-
Sodium Potassium Calcium Phosphorus Urea nitrogen Uric acid Creatinine Lactic dehydrogenase Aspartate transaminase Prostaglandin E Prostaglandin F
130.0 mEq./1. 4.3 mEq./1. 6.1 mg./dl. 0.4 mg./dl. 10.0 mg./dl. 3.9 mg./dl. 0.4 mg./dl. 60.0µ./I. 22.0 µ./1. 35.8 pg./ml. 7.4 pg./ml.
Normal Serum 136.0 to 142 mEq./1. 3.5 to 4.8 mEq./1. 8.5 to 10.5 mg.fell. 2.5 to 4.5 mg./di. 10.0 to 20 mg./dl. 2.5 to 8 mg./dl. 0. 7 to 1.4 mg./di. 80.0 to 220 µ./1. 8.0 to 40 µ./1. 25.0 to 150 pg./ml. (plasma) 25.0 to 200 pg./ml. (plasma)
malities and absence of intralesional cartilage and embryonal ducts all militate against a diagnosis of renal dysplasia. The failure of the cysts in cystic nephroma to communicate with the renal pelvis has been well demonstrated. 1· 2 All but 1 of the previous cases with primitive mesenchymal elements were reported in children. The 64-year-old woman described by Gibson exhibited structures suggestive of metanephric blastema. It is interesting to speculate that the lack of undifferentiated elements in most adult cystic nephromas may · be owing to subsequent maturation of the undifferentiated metanephric blastema. While 50 per cent of cystic nephromas are found in the adult population it is presently unknown if
541
CYSTIC NEPHROMA
these lesions were present since childhood or if they developed later. As judged by the chemical content of the cystic fluid in our case the fluid is strikingly similar to serum. This had been mentioned previously by Kissane 9 as well as Powell and associates, 10 who performed limited studies on cystic fluid. Significant prostaglandin synthesis in renal cell carcinomas 11 and in benign conditions such as Bartter's syndrome 12 has been noted. In the latter disease excessive renal prostaglandin E synthesis is believed to be causative of the hyperrenin state. Little information is available on renal cystic fluid prostaglandins. In our patient measurable levels of prostaglandins were identified within the cystic nephroma but the significance of these levels is unknown. However, it is clear that the levels observed in this fluid were not markedly elevated. The relationship of prostaglandins to nephroblastoma, although unknown, is currently under investigation. Neither pulmonary cysts nor other congenital abnormalities were described in the cases reported previously. While this may be an incidental pulmonary finding a chest x-ray should be obtained in subsequent cases of cystic nephroma. We agree with those authors who suggest that a cystic nephroma is a benign neoplasm rather than a form of dysplasia.1· 4 • G-B While this tumor may be the benign counterpart of a nephroblastoma additional cases with blastomatous elements and prolonged clinical followup should be reported to confirm the relationship. Mr. Dallas Fisher and Mr. Suriyonta Trapukdi assisted in the photography.
REFERENCES
1. Boggs, L. K. and Kimmelstiel, P.: Benign multilocular cystic nephroma: report of two cases of so-called multilocular cyst of the kidney. J. Urol., 76: 530, 1956. 2. Gibson, T. E.: Multilocular cyst of the kidney: case report. J. Urol., 87: 297, 1962. 3. Uson, A. C. and Melicow, M. M.: Multilocular cysts of kidney with intrapelvic herniation of a "daughter" cyst: report of 4 cases. J. Urol., 89: 341, 1963. 4. Gallo, G. E. and Penchansky, L.: Cystic nephroma. Cancer, 39: 1322, 1977. 5. Demers, L. M. and Gabbe, S. G.: Placental prostaglandin levels in pre-eclampsia. Amer. J. Obst. Gynec., 126: 137, 1976. 6. Uson, A. C., Del Rosario, C. and Melicow, M. M.: Wilms tumor in association with cystic renal disease: report of two cases. J. Urol., 83: 262, 1960. 7. Brown, J. M.: Cystic partially differentiated nephroblastoma. J. Path., 115: 175, 1975. 8. Datnow, B. and Daniel, W. W., Jr.: Polycystic nephroblastoma. J.A.M.A., 236: 2528, 1976. 9. Kissane, J. M.: Congenital malformations. In: Pathology of the Kidney, 2nd ed. Edited by R. H. Heptinstall. Boston: Little Brown & Co., vol. 1, pp. 69-119, 1974. 10. Powell, T., Shackman, R. and Johnson, H. D.: Multilocular cysts of the kidney. Brit. J. Urol., 23: 142, 1951. 11. Brereton, H. D., Halushka, P. V., Alexander, R. W., Mason, D. M., Keiser, H. R. and DeVita, V. T., Jr.: lndomethacin-responsive hypercalcemia in a patient with renal-cell adenocarcinoma. New Engl. J. Med., 291: 83, 1974. 12. Fichman, M. P., Telfer, N., Zia, P., Speckart, P., Golub, M. and Rude, R.: Role of prostaglandins in the pathogenesis of Bartter's syndrome. Amer. J. Med., 60: 785, 1976.
