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Polycystic Nephroblastoma
Vol. 98, Nov. Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1968 hy The Williams & Wilkins Co.
POLYCYSTIC NEPHROBLASTOMA M. L. CHRIST From the Otto Saphir Department of Pathology, Michael Reese Hospital ancl ]J;Ieclical Center, Chicago, Illinois
Nephroblastomas (Wilms tumors) are classified by Willis as embryonic tumors which arise from and consist of primitive renal tissue. 1 They occur almost exclusively in infants and young children and a number of congenital cases have been reported in fetuses and stillborn infants. 2 - 5 Nephroblastomas account for the second largest group of malignant tumors of childhood (being second to neuroblastomas) and are considered to be highly malignant and fatal unless treated early. However, the tumors are notorious for their silent growth, usually attaining a large size before becoming manifest as palpable or visible abdominal masses. This paper is a report of an unusually welldifferentiated nephroblastoma which was diffusely cystic, grossly resembling a multilocular cyst of the kidney. vVhile pseudocysts resulting from liquefaction necrosis are frequent in vVihns tumors and true epithelial-lined cysts are occasionally seen, one which is diffusely polycystic appears to be distinctly unusual. The literature is reviewed and the possible relationship between nephroblastoma and rn.ultilocular cyst is discussed. CASE REPORT
A 10-month-old white girl was admitted to :\Iichael Reese Hospital on November 11, 1965, 2 weeks after the discovery of an abdominal mass by her mother. A firm, irregular tumor filled the right side of the abdomen and extended slightly across the midline. The re1nainder of the physical Accepted for publication December 13, 1966. 1 Willis, R. A.: The Borderland of Embryology and Pathology. London: Butterworths, 1958. 2 Nicholson, G. W.: Embryonic tumour of kidney in foetus. J. Path. Bact., 34: 711, 1931. 3 Wells, H. G.: Occurrence and significance of congenital malignant neoplasms. Arch. Path., 30: 535, 1940. 4 Hou, L. T. and Holman, R. L.: Bilateral nephroblastomatosis in a premature infant. J. Path. Bact., 82: 249, 1961. 5 Pasternack, A. and Hj elt, L.: Developmental anomaly of metanephros and observations on congenital nephroblastoma. Ann. Paediat. Fenn.,
8: 208, 1962.
examination, chest x-ray and routine laboratory tests revealed no abnormalities. Excretory urography disclosed a 13 cm. mass compressing and displacing the upper calyces of the right kidney. The clinical diagnosis of Wilms tumor was made and actinomycin-D and radiation therapy were given preoperatively with apparent decrease in the size of the mass. On November 19 a right transperitoneal nephrectomy vvas performed. The mass was encapsulated and confined to the kidney. There was no evidence of local spread or metastasis and the contralateral kidney appeared normal. Convalescence was complicated by severe diarrhea, but this subsided; the patient was discharged from the hospital December 1. Radiation therapy was resumed; a total dose of 3,lOOr was give in 41 days (700r preoperatively, 2,400r postoperatively). The child is being followed in the clinic and, 1 year post-nephrectomy, had no evidence of recurrent or metastatic tumor. PATHOLOGY
The kidney weighed 400 gm. and its upper and middle portion was occupied by a multinoclular mass (12 cm.. in diameter). The renal vessels and segment of ureter were unremarkable. Section revealed an encapsulated, multilocular cystic tumor composed of 4 nodules separated and surrounded by dense fibrous tissue (fig. 1, A.). The larger nodules appeared to be more cystic than the smaller ones. The cysts ranged from pinpoint to 1.5 cm. in diameter, had smooth inner surfaces and contained clear colorless fluid. Some of the larger cysts communicated with adjacent ones but there was no demonstrable communication with the pelvis. The more solid areas had a homogeneous yellow-tan color and, on closer inspection, a honeycomb appearance was apparent, due to the presence of multiple tiny cysts (fig. 1, B). The remaining renal parenchyma showed no abnorm.alities other than compression by the mass. :Microscopically, a uniform picture of epitheliallined cysts separated by a variable amount of 570
POLYCYSTIC NEPHEOBLASTOMA
FrG. A, hemisectecl kidney containing encapsulated, nodular, multilocnlar cystic tnmor. tissue is compressed bui not infiltrated. B, higher magnification shows minute cysts in more solid. appcmring; a,reas,
:Fm 2. Epithelial-lined cysts and cellular stroma containing irregular branching tubules. H&E X200
572
CHRIST
FIG. 3. Higher magnification of figure 2 shows undifferentiated round or spindle-shaped stromal cells and tubules. H&E X500.
appeared as an elaborate system of irregular branching channels lined by peg-shaped cuboidal cells with small, uniform, dark nuclei and scant cytoplasm (fig. 2). The epithelium of these tubules showed continuity with that of the cysts and a few blunt papillary structures projected into the lumens (fig. 5). The second type of tubule was less conspicuous and most easily seen in PASstained sections because of the presence of a thin basement membrane. These tubules were almost always seen in cross-section without apparent branching and were lined by cuboidal cells with abundant clear cytoplasm. and round vesicular nuclei. Eosinophilic hyaline material was present in some of the lumens (fig. 6). There were a few minute areas of necrosis, edema and inflammation, but mitotic figures, cellular atypia and capsular invasion were absent. There were no unusual changes in the surrounding kidney tissue. DISCUSSION
The two basic histologic features of nephroblastoma: 1) undifferentiated mesenchymal stroma and 2) primitive tubulo-glomerular structures, were present throughout this lesion, making that diagnosis unavoidable. The unusual features were the striking degree of differentiation and the presence of multiple true cysts. Two possibilities were considered: 1) that the unusual features were the result of preoperative therapy and 2) that the lesion represented the co-incidental association of a nephroblastoma and a multilocular cyst of the kidney.
FIG. 4. Papillary H&E X500.
glomerulus-like
structure.
stroma was characteristic of sections from all areas of the tumor (fig. 2). The cysts were lined by a single layer of uniform flattened or cuboidal cells and the lumens contained eosinophilic droplets and desquamated cells. The intercystic stroma varied in cellularity, being composed of well-differentiated collagen and smooth muscle fibers in some areas and of small, dark, round or spindle cells in others (fig. 3). Within the stroma were numerous tubules and a few well-formed glomerular structures, some of which contained capillaries (fig. 4). Two distinct types of tubules could be recognized. The more prominent type
., •!'t
IL
FIG. 5. Continuity between epithelium of cyst, and that of branching tubules. H&E X500.
POL YCYS'rIC NEPHROBLASTOMA
The possibility that the original appearance of the tumor was altered preoperative therapy, with destruction of the undifferentiated tissue and preservation of the differentiated areas, appears unlikely in view of the short duration of therapy and the absence of radiation changes either in the tumor or in the adjacent normal kidney tissue. As a, matter of fact, the latter suggests that this tumor is less radiosensitive than the more common, less well-differentiated 1Vilms tumor. The cysts were lined by epithelium and, therefore, cannot be attributed to necrosis as a result of therapy. Because of the gross appearance of the lesion, the possibility that it represented a co-incidental association of a 1Vilms tumor and a multilocular cyst was considered. However, the diffuse distribution of the nephroblastornatous areas and the continuity between the epithelium of the cysts and that of the neoplastic tubules speak against this possibility and indicate that the cysts are an integral part of the tumor, representing dilated tubules rather than a co-incidental concurrence. It was concluded that the lesion is a well-differentiated polcystic nephroblastoma, either benign or of low-grade malignancy. Contrary to the widely held concept that histologic pattern has no bearing on the prognosis of Wilms tumors, Hardwick and Stowens have recently shown a significant correlation between these 2 factors. 6 The general failure to recognize this is probably due to the limited number of well-differentiated Wilms tumors available to any one investigator. Wnile exhibiting a brnad range of differentiation when classified according to the extent to which the appearance of adult renal tissue is approached, most nephroblastomas fall into an intermediate group, the differentiated and undifferentiated tumors being uncommon. In this regard, it is interesting that in 1894 Birch-Hirschfeld postulated the possible existence of a pure embryonic adenoma at one extreme of the broad spectrum of differentiation exhibited by embryonic tun10rs of the kidney and a pure sarcoma at the other. 7 Some have explained the variability of differentiation seen in nephroblastomas by the theory that they arise at different stages of development of the embryonic kidney, the most undifferentiated tumors arising from mesenchymal preHardwick, D. F. and Stowens, D.: Wilms tumors. J, Urol., 85: 903, 19Gl. 7 Thomasson, B. and Ravitch, NL M.: Wilms tumor. Urol. Survey, 11: 83, 1961. 6
FIG. 6. Unbranched tubules lined bv cells with clear cytoplasm and ronnd vesiciilar nuclei. Periodic acid-Schiff, X 500.
cursors of the nephrotome, the most mature tu-· mors originating in the rn.etanephros. 8 • 9 The possibility that nephroblastomas, like neuroblastomas, may undergo spontaneous maturation with rare transformation into a benign lesion has not been documented but is suggested the greater degree of maturation seen in tumors of older children and adult patients' and by the single ease report of what was considered to be benign nephroblastoma in an adult patient.1° The presence of both branched and unbranched tubules, as seen in the present case, has been described in well-differentiated tumors and cited as evidence that they arise from the metanephros, with participation of both the nephrogenic blasten1a and the ureteral bud of the wolf-fiau duct. 2 • 11 The branched tubules are a:;sumccl to be collecting tubules originating from the wolffian duct, whereas the unbranched tubule:; are thought to be part of the nephron whicb ari:;e,, from_ the nephrogenic blastema. Niost descriptions of nephroblastomas 111.ention the presence of occasional epithelial-lined cyst,. but there are few reports of tumors with cliffusE' 8 Geschickter, C. F. and Widenhorn, H.: Xepbrogenic tumors. Amer. J. 22: 620, HJ:34 9 Dean, A. L., Jr. and Pack, T.: Embryonal adenosarcoma of the kidney . .J. A. J\I. A., 98: 10,
1932.
10 .Jenckel, A.: Beitrag znr Kenntniss clPr so-· genannten embryonalen Dri\sengeschwiHste der Niere. Dentsche Ztschr. f. Chir., 60: 500, HJOl. 11 wicCurdy, G. A.: Renal neoplasms in child-· hood . .J. Path. Bact., 39: 623, 1934.
574
CHRIST
Differential features of polycystic kidneys Multicystic Kidney (Cystic Dysplasia)
True Polycystic Kidney of Infancy
Multilocular Cyst of Kidney
Unilateral; occasionally bilateral
Bilateral
Unilateral
Involves entire kidney with distortion; rarely segmental
Involves entire kidney with retention of renal shape
Segmental with normal umnvolved renal tissue
Cysts vary in size and do not communicate with pelvis
Cysts small and uniform and communicate with pelvis
Cysts vary in size, are loculated, and do not communicate with pelvis
Stroma abundant, containing dysplastic tubules, cartilage, and occasional primitive nephrons
Stroma sparse, containing normal functioning nephrons
Stroma composed of fibrous tissue containing occasional primitive nephrons
Associated with ureteral and other anomalies
Associated with cysts in other organs
No associated congenital anomalies
Not familial
Familial
Not familial
cyst formation and even fewer reports of vVilms tumors associated with polycystic kidney. Masson attributed the presence of many cysts in a welldifferentiated nephroblastoma which he described as resembling a polycystic kidney, at least in part, to secretion by the relatively mature tubules. 12 A nephroblastmna with many large cysts is illustrated and described by Lucke and Schlumberger. 13 Of the reports of vVilms tumors in association with polycystic kidney, those of Campbell, 14 Feeney15 and Potter16 are unclear as to the type of polycystic kidney involved. The case of Vellios was a unilateral multicystic kidney containing a small island of undifferentiated nephroblastomatous tissue. 17 Similar foci are infrequently seen in otherwise normal kidneys; whether they eventually regress or develop into clinically apparent Wilms tumors is not known. 12 Masson, P.: The role of the neural crests in the embryonal adenosarcomas of the kidney. Amer. J. Cancer, 33: 1, 1938. 13 Lucke, B. and Schlumberger, H. G.: Tumors of the kidney, renal pelvis and ureter. In: Atlas of Tumor Pathology. Washington: Armed Forces Institute of Pathology, 1957, sect. 8, fasc. 30. 14 Campbell, M. F.: Bilateral embryonal adenomyosarcoma of the kidney (Wilms tumor). J. Urol., 59: 567, 1948. 15 Feeney, M. J., :Mullenix, R. B., Prentiss, R. J. and Whisenand, J. M.: Clinical experiences with Wilms' tumors. J. Urol., 74: 301, 1955. 16 Potter, E. L.: Pathology of the Fetus and Infant. Chicago: Year Book Publishers, Inc., 1961. 17 Vellios, F. and Garrett, R. A.: Congenital unilateral multicystic disease of the kidney. A clinical and anatomic study of seven cases. Amer. J. Clin. Path., 35: 244, 1961.
There are two and possibly 3 reports of lesions similar to that described in this paper; that is, they had the gross appearance of benign multilocular cysts but contained microscopic elements of nephroblastoma, apparently diffusely distributed. In 1956, Boggs and Kimmelstiel described a multilocular cyst in which histologic elements characteristic of "\Vilms tmnor were found. 18 In a review of previously reported cases which fulfilled their criteria for the diagnosis of multilocular cyst, they were able to find one, that of Frazier, in which mention was made of primitive connective tissue and tubules in the septa. 19 They concluded that probably all multilocular cysts of the kidney are neoplasms rather than a form of congenital polycystic kidney and that, unless studied extensively, the neoplastic areas would be easily overlooked. Because of the benign histologic appearance of the lesion and in order to avoid the malignant connotation of the term Wilms tumor, they reported the case as a benign multilocular cystic nephroma. The tumor occurred in a 5-month-old boy who received no therapy other than nephrectomy. In 1960 Uson and associates reported another case of multilocular cyst with microscopic features of Wilms tumor. 20 The diagnosis was made 18 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. 19 Frazier, T. H.: Multilocular cysts of the kidney. J. Urol., 65: 351, 1951. 20 Uson, A. C., del Rosario, C. and Melicow, M.
POLYCYS'l'IC NEPHROBLASTOMA
in a \l-month-old girl who wa~ given postoperative radiation and was well at the age of 6 years. The lesion was interpreted as the re,mlt of two different developmental errors present in the same kiclrwy at the same time. i\Iultilocular cyst of the kidney is a rare lesion which has been described as a distinct pathologic to be distinguished from other types of kidney, 21 - 24 but which is considered by some a scg1nental form of multicyfitic kiduey. 25 The differentiating features are pres0nted in the table. _.l,.rey suggested that multilocular cysts be regarded as cystic hamartonms ;2 6 others considered them to be cystadenonms. Campbell stated that thc~
A1.: Wilms tumor in association with cystic renal disease: Report of two cases . .J. Urol., 83: 262,
possibly benign, po\cystic Progrcs,ivc dilatation of cliffcrcntiat(·cl tubule, may result in pressure and filirosi,, of septa, so that the c,lemcnts lwcumt' more sparse and difficult to find u11lcss man: section;; arc examined. That \Vilm, tumor and kiclm,y arc rehll'd developn1entally ha;; been .Nic-holson28 and recent reports of increased inc;iclertc.c congenital anomalie;; with 1Vilms turnurn lm,,·e raised the question of a common or rdatecl e1 iology .29 - 31 It is suggested that the '>reU-differentiated polycystic form of nephroblastoma repn> sents an intermediate or borderline lesion with con1bined features of nephrobla,stoma ancl cystic kidney. SUMJVL\.RY
A well-differentiated nephroblastorna with Uw
gross appearance of a rnultilocular cyst of the kidney, occurring in a 10-month·old girl, is described. The few previously reported c:ases of similar lesions :1re reviewed and the pos;;ihle relationship between nephroblastomas and cystic kidneys is discussed. It 1s suggested that Wilms tumors and congenital lesions of tlw kidntoy may be related and lhaithe tmnor reported herein may represe11t, borderline lesion with features of both.
1960.
Spence, H M., Baird, S.S. and Ware, E.W., Cystic disorders of the kidney--Classification, diagnosis, treatment. J ..A. M.A., 163: 1466, 1957. 22 Powell, T., Shackman, R. and Johnson, H. D.: Multilocular cysts of the kidney. Brit ..J. Urol., 21
Jr.:
23: 142. 1951. 2" Spence, H. M .. Congenital unilateral multicystic kidney: An entity to be distinguished from polycystic kidney disease and other cystic disorders. J. Urol., 74: 693, 1955. 24 Da.inko, E. A., Darnmers, Y.1. R. and Economou, S. U.: Multilocular cysts of the kidney in children: Report of a case and revie,v of the literature. J. Pecliat., 63: 24\J, 1963. "Osathanonclh, ,-. and Potter, E. L.: Pathogenesis of polycystic kidneys. 2 clue to in-· hibition of arnpullary activity. Path., 77:
19G4.
Arey, .J. B.: Cystic lesions of the kidney in infants and children. J. Pediat., 54: 429, 1959. z, Campbell, JVL F. l;rology. Philadelphia: W. B. Saunders Co., 196:3.
ADDENDUM
Since the submission of this paper, referern:e to au almost identical renal tumor was fcmnd. Thi.,; was a "well differentiated and nign) vVilms' tumor" presented Landi.ng at the 1958 Cancer Seminar m Dem·er Seminar, 2: llO, 28 Nicholson, G. VV.: Studies on tumour fornrn-tion. Guy's Hosp. Rep., 73: :37, 102:3, 29 ,Jagasia, K. H. and Thurman, W. C .. Cou-· genital anomalies of the kidney in associat,ion with Wilms' tumor. Pediatrics, 35: 338, 19G5. 30 Miller, R. W.: Relation between e,rncer micl congenital· defects in man. New .Engl. ,r :Vied., 275: 87, 1966. 31 DiPaolo,. J. A. and Kotin, P.: Teratogenesi;;-oncogenesis: A study of possible relationships. Arch. Path., 81: 3, 1966.
THE JOURNAL OF UROLOGY
Copyright © 1968 hy The Williams & Wilkins Co.
POLYCYSTIC NEPHROBLASTOMA M. L. CHRIST From the Otto Saphir Department of Pathology, Michael Reese Hospital ancl ]J;Ieclical Center, Chicago, Illinois
Nephroblastomas (Wilms tumors) are classified by Willis as embryonic tumors which arise from and consist of primitive renal tissue. 1 They occur almost exclusively in infants and young children and a number of congenital cases have been reported in fetuses and stillborn infants. 2 - 5 Nephroblastomas account for the second largest group of malignant tumors of childhood (being second to neuroblastomas) and are considered to be highly malignant and fatal unless treated early. However, the tumors are notorious for their silent growth, usually attaining a large size before becoming manifest as palpable or visible abdominal masses. This paper is a report of an unusually welldifferentiated nephroblastoma which was diffusely cystic, grossly resembling a multilocular cyst of the kidney. vVhile pseudocysts resulting from liquefaction necrosis are frequent in vVihns tumors and true epithelial-lined cysts are occasionally seen, one which is diffusely polycystic appears to be distinctly unusual. The literature is reviewed and the possible relationship between nephroblastoma and rn.ultilocular cyst is discussed. CASE REPORT
A 10-month-old white girl was admitted to :\Iichael Reese Hospital on November 11, 1965, 2 weeks after the discovery of an abdominal mass by her mother. A firm, irregular tumor filled the right side of the abdomen and extended slightly across the midline. The re1nainder of the physical Accepted for publication December 13, 1966. 1 Willis, R. A.: The Borderland of Embryology and Pathology. London: Butterworths, 1958. 2 Nicholson, G. W.: Embryonic tumour of kidney in foetus. J. Path. Bact., 34: 711, 1931. 3 Wells, H. G.: Occurrence and significance of congenital malignant neoplasms. Arch. Path., 30: 535, 1940. 4 Hou, L. T. and Holman, R. L.: Bilateral nephroblastomatosis in a premature infant. J. Path. Bact., 82: 249, 1961. 5 Pasternack, A. and Hj elt, L.: Developmental anomaly of metanephros and observations on congenital nephroblastoma. Ann. Paediat. Fenn.,
8: 208, 1962.
examination, chest x-ray and routine laboratory tests revealed no abnormalities. Excretory urography disclosed a 13 cm. mass compressing and displacing the upper calyces of the right kidney. The clinical diagnosis of Wilms tumor was made and actinomycin-D and radiation therapy were given preoperatively with apparent decrease in the size of the mass. On November 19 a right transperitoneal nephrectomy vvas performed. The mass was encapsulated and confined to the kidney. There was no evidence of local spread or metastasis and the contralateral kidney appeared normal. Convalescence was complicated by severe diarrhea, but this subsided; the patient was discharged from the hospital December 1. Radiation therapy was resumed; a total dose of 3,lOOr was give in 41 days (700r preoperatively, 2,400r postoperatively). The child is being followed in the clinic and, 1 year post-nephrectomy, had no evidence of recurrent or metastatic tumor. PATHOLOGY
The kidney weighed 400 gm. and its upper and middle portion was occupied by a multinoclular mass (12 cm.. in diameter). The renal vessels and segment of ureter were unremarkable. Section revealed an encapsulated, multilocular cystic tumor composed of 4 nodules separated and surrounded by dense fibrous tissue (fig. 1, A.). The larger nodules appeared to be more cystic than the smaller ones. The cysts ranged from pinpoint to 1.5 cm. in diameter, had smooth inner surfaces and contained clear colorless fluid. Some of the larger cysts communicated with adjacent ones but there was no demonstrable communication with the pelvis. The more solid areas had a homogeneous yellow-tan color and, on closer inspection, a honeycomb appearance was apparent, due to the presence of multiple tiny cysts (fig. 1, B). The remaining renal parenchyma showed no abnorm.alities other than compression by the mass. :Microscopically, a uniform picture of epitheliallined cysts separated by a variable amount of 570
POLYCYSTIC NEPHEOBLASTOMA
FrG. A, hemisectecl kidney containing encapsulated, nodular, multilocnlar cystic tnmor. tissue is compressed bui not infiltrated. B, higher magnification shows minute cysts in more solid. appcmring; a,reas,
:Fm 2. Epithelial-lined cysts and cellular stroma containing irregular branching tubules. H&E X200
572
CHRIST
FIG. 3. Higher magnification of figure 2 shows undifferentiated round or spindle-shaped stromal cells and tubules. H&E X500.
appeared as an elaborate system of irregular branching channels lined by peg-shaped cuboidal cells with small, uniform, dark nuclei and scant cytoplasm (fig. 2). The epithelium of these tubules showed continuity with that of the cysts and a few blunt papillary structures projected into the lumens (fig. 5). The second type of tubule was less conspicuous and most easily seen in PASstained sections because of the presence of a thin basement membrane. These tubules were almost always seen in cross-section without apparent branching and were lined by cuboidal cells with abundant clear cytoplasm. and round vesicular nuclei. Eosinophilic hyaline material was present in some of the lumens (fig. 6). There were a few minute areas of necrosis, edema and inflammation, but mitotic figures, cellular atypia and capsular invasion were absent. There were no unusual changes in the surrounding kidney tissue. DISCUSSION
The two basic histologic features of nephroblastoma: 1) undifferentiated mesenchymal stroma and 2) primitive tubulo-glomerular structures, were present throughout this lesion, making that diagnosis unavoidable. The unusual features were the striking degree of differentiation and the presence of multiple true cysts. Two possibilities were considered: 1) that the unusual features were the result of preoperative therapy and 2) that the lesion represented the co-incidental association of a nephroblastoma and a multilocular cyst of the kidney.
FIG. 4. Papillary H&E X500.
glomerulus-like
structure.
stroma was characteristic of sections from all areas of the tumor (fig. 2). The cysts were lined by a single layer of uniform flattened or cuboidal cells and the lumens contained eosinophilic droplets and desquamated cells. The intercystic stroma varied in cellularity, being composed of well-differentiated collagen and smooth muscle fibers in some areas and of small, dark, round or spindle cells in others (fig. 3). Within the stroma were numerous tubules and a few well-formed glomerular structures, some of which contained capillaries (fig. 4). Two distinct types of tubules could be recognized. The more prominent type
., •!'t
IL
FIG. 5. Continuity between epithelium of cyst, and that of branching tubules. H&E X500.
POL YCYS'rIC NEPHROBLASTOMA
The possibility that the original appearance of the tumor was altered preoperative therapy, with destruction of the undifferentiated tissue and preservation of the differentiated areas, appears unlikely in view of the short duration of therapy and the absence of radiation changes either in the tumor or in the adjacent normal kidney tissue. As a, matter of fact, the latter suggests that this tumor is less radiosensitive than the more common, less well-differentiated 1Vilms tumor. The cysts were lined by epithelium and, therefore, cannot be attributed to necrosis as a result of therapy. Because of the gross appearance of the lesion, the possibility that it represented a co-incidental association of a 1Vilms tumor and a multilocular cyst was considered. However, the diffuse distribution of the nephroblastornatous areas and the continuity between the epithelium of the cysts and that of the neoplastic tubules speak against this possibility and indicate that the cysts are an integral part of the tumor, representing dilated tubules rather than a co-incidental concurrence. It was concluded that the lesion is a well-differentiated polcystic nephroblastoma, either benign or of low-grade malignancy. Contrary to the widely held concept that histologic pattern has no bearing on the prognosis of Wilms tumors, Hardwick and Stowens have recently shown a significant correlation between these 2 factors. 6 The general failure to recognize this is probably due to the limited number of well-differentiated Wilms tumors available to any one investigator. Wnile exhibiting a brnad range of differentiation when classified according to the extent to which the appearance of adult renal tissue is approached, most nephroblastomas fall into an intermediate group, the differentiated and undifferentiated tumors being uncommon. In this regard, it is interesting that in 1894 Birch-Hirschfeld postulated the possible existence of a pure embryonic adenoma at one extreme of the broad spectrum of differentiation exhibited by embryonic tun10rs of the kidney and a pure sarcoma at the other. 7 Some have explained the variability of differentiation seen in nephroblastomas by the theory that they arise at different stages of development of the embryonic kidney, the most undifferentiated tumors arising from mesenchymal preHardwick, D. F. and Stowens, D.: Wilms tumors. J, Urol., 85: 903, 19Gl. 7 Thomasson, B. and Ravitch, NL M.: Wilms tumor. Urol. Survey, 11: 83, 1961. 6
FIG. 6. Unbranched tubules lined bv cells with clear cytoplasm and ronnd vesiciilar nuclei. Periodic acid-Schiff, X 500.
cursors of the nephrotome, the most mature tu-· mors originating in the rn.etanephros. 8 • 9 The possibility that nephroblastomas, like neuroblastomas, may undergo spontaneous maturation with rare transformation into a benign lesion has not been documented but is suggested the greater degree of maturation seen in tumors of older children and adult patients' and by the single ease report of what was considered to be benign nephroblastoma in an adult patient.1° The presence of both branched and unbranched tubules, as seen in the present case, has been described in well-differentiated tumors and cited as evidence that they arise from the metanephros, with participation of both the nephrogenic blasten1a and the ureteral bud of the wolf-fiau duct. 2 • 11 The branched tubules are a:;sumccl to be collecting tubules originating from the wolffian duct, whereas the unbranched tubule:; are thought to be part of the nephron whicb ari:;e,, from_ the nephrogenic blastema. Niost descriptions of nephroblastomas 111.ention the presence of occasional epithelial-lined cyst,. but there are few reports of tumors with cliffusE' 8 Geschickter, C. F. and Widenhorn, H.: Xepbrogenic tumors. Amer. J. 22: 620, HJ:34 9 Dean, A. L., Jr. and Pack, T.: Embryonal adenosarcoma of the kidney . .J. A. J\I. A., 98: 10,
1932.
10 .Jenckel, A.: Beitrag znr Kenntniss clPr so-· genannten embryonalen Dri\sengeschwiHste der Niere. Dentsche Ztschr. f. Chir., 60: 500, HJOl. 11 wicCurdy, G. A.: Renal neoplasms in child-· hood . .J. Path. Bact., 39: 623, 1934.
574
CHRIST
Differential features of polycystic kidneys Multicystic Kidney (Cystic Dysplasia)
True Polycystic Kidney of Infancy
Multilocular Cyst of Kidney
Unilateral; occasionally bilateral
Bilateral
Unilateral
Involves entire kidney with distortion; rarely segmental
Involves entire kidney with retention of renal shape
Segmental with normal umnvolved renal tissue
Cysts vary in size and do not communicate with pelvis
Cysts small and uniform and communicate with pelvis
Cysts vary in size, are loculated, and do not communicate with pelvis
Stroma abundant, containing dysplastic tubules, cartilage, and occasional primitive nephrons
Stroma sparse, containing normal functioning nephrons
Stroma composed of fibrous tissue containing occasional primitive nephrons
Associated with ureteral and other anomalies
Associated with cysts in other organs
No associated congenital anomalies
Not familial
Familial
Not familial
cyst formation and even fewer reports of vVilms tumors associated with polycystic kidney. Masson attributed the presence of many cysts in a welldifferentiated nephroblastoma which he described as resembling a polycystic kidney, at least in part, to secretion by the relatively mature tubules. 12 A nephroblastmna with many large cysts is illustrated and described by Lucke and Schlumberger. 13 Of the reports of vVilms tumors in association with polycystic kidney, those of Campbell, 14 Feeney15 and Potter16 are unclear as to the type of polycystic kidney involved. The case of Vellios was a unilateral multicystic kidney containing a small island of undifferentiated nephroblastomatous tissue. 17 Similar foci are infrequently seen in otherwise normal kidneys; whether they eventually regress or develop into clinically apparent Wilms tumors is not known. 12 Masson, P.: The role of the neural crests in the embryonal adenosarcomas of the kidney. Amer. J. Cancer, 33: 1, 1938. 13 Lucke, B. and Schlumberger, H. G.: Tumors of the kidney, renal pelvis and ureter. In: Atlas of Tumor Pathology. Washington: Armed Forces Institute of Pathology, 1957, sect. 8, fasc. 30. 14 Campbell, M. F.: Bilateral embryonal adenomyosarcoma of the kidney (Wilms tumor). J. Urol., 59: 567, 1948. 15 Feeney, M. J., :Mullenix, R. B., Prentiss, R. J. and Whisenand, J. M.: Clinical experiences with Wilms' tumors. J. Urol., 74: 301, 1955. 16 Potter, E. L.: Pathology of the Fetus and Infant. Chicago: Year Book Publishers, Inc., 1961. 17 Vellios, F. and Garrett, R. A.: Congenital unilateral multicystic disease of the kidney. A clinical and anatomic study of seven cases. Amer. J. Clin. Path., 35: 244, 1961.
There are two and possibly 3 reports of lesions similar to that described in this paper; that is, they had the gross appearance of benign multilocular cysts but contained microscopic elements of nephroblastoma, apparently diffusely distributed. In 1956, Boggs and Kimmelstiel described a multilocular cyst in which histologic elements characteristic of "\Vilms tmnor were found. 18 In a review of previously reported cases which fulfilled their criteria for the diagnosis of multilocular cyst, they were able to find one, that of Frazier, in which mention was made of primitive connective tissue and tubules in the septa. 19 They concluded that probably all multilocular cysts of the kidney are neoplasms rather than a form of congenital polycystic kidney and that, unless studied extensively, the neoplastic areas would be easily overlooked. Because of the benign histologic appearance of the lesion and in order to avoid the malignant connotation of the term Wilms tumor, they reported the case as a benign multilocular cystic nephroma. The tumor occurred in a 5-month-old boy who received no therapy other than nephrectomy. In 1960 Uson and associates reported another case of multilocular cyst with microscopic features of Wilms tumor. 20 The diagnosis was made 18 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. 19 Frazier, T. H.: Multilocular cysts of the kidney. J. Urol., 65: 351, 1951. 20 Uson, A. C., del Rosario, C. and Melicow, M.
POLYCYS'l'IC NEPHROBLASTOMA
in a \l-month-old girl who wa~ given postoperative radiation and was well at the age of 6 years. The lesion was interpreted as the re,mlt of two different developmental errors present in the same kiclrwy at the same time. i\Iultilocular cyst of the kidney is a rare lesion which has been described as a distinct pathologic to be distinguished from other types of kidney, 21 - 24 but which is considered by some a scg1nental form of multicyfitic kiduey. 25 The differentiating features are pres0nted in the table. _.l,.rey suggested that multilocular cysts be regarded as cystic hamartonms ;2 6 others considered them to be cystadenonms. Campbell stated that thc~
A1.: Wilms tumor in association with cystic renal disease: Report of two cases . .J. Urol., 83: 262,
possibly benign, po\cystic Progrcs,ivc dilatation of cliffcrcntiat(·cl tubule, may result in pressure and filirosi,, of septa, so that the c,lemcnts lwcumt' more sparse and difficult to find u11lcss man: section;; arc examined. That \Vilm, tumor and kiclm,y arc rehll'd developn1entally ha;; been .Nic-holson28 and recent reports of increased inc;iclertc.c congenital anomalie;; with 1Vilms turnurn lm,,·e raised the question of a common or rdatecl e1 iology .29 - 31 It is suggested that the '>reU-differentiated polycystic form of nephroblastoma repn> sents an intermediate or borderline lesion with con1bined features of nephrobla,stoma ancl cystic kidney. SUMJVL\.RY
A well-differentiated nephroblastorna with Uw
gross appearance of a rnultilocular cyst of the kidney, occurring in a 10-month·old girl, is described. The few previously reported c:ases of similar lesions :1re reviewed and the pos;;ihle relationship between nephroblastomas and cystic kidneys is discussed. It 1s suggested that Wilms tumors and congenital lesions of tlw kidntoy may be related and lhaithe tmnor reported herein may represe11t, borderline lesion with features of both.
1960.
Spence, H M., Baird, S.S. and Ware, E.W., Cystic disorders of the kidney--Classification, diagnosis, treatment. J ..A. M.A., 163: 1466, 1957. 22 Powell, T., Shackman, R. and Johnson, H. D.: Multilocular cysts of the kidney. Brit ..J. Urol., 21
Jr.:
23: 142. 1951. 2" Spence, H. M .. Congenital unilateral multicystic kidney: An entity to be distinguished from polycystic kidney disease and other cystic disorders. J. Urol., 74: 693, 1955. 24 Da.inko, E. A., Darnmers, Y.1. R. and Economou, S. U.: Multilocular cysts of the kidney in children: Report of a case and revie,v of the literature. J. Pecliat., 63: 24\J, 1963. "Osathanonclh, ,-. and Potter, E. L.: Pathogenesis of polycystic kidneys. 2 clue to in-· hibition of arnpullary activity. Path., 77:
19G4.
Arey, .J. B.: Cystic lesions of the kidney in infants and children. J. Pediat., 54: 429, 1959. z, Campbell, JVL F. l;rology. Philadelphia: W. B. Saunders Co., 196:3.
ADDENDUM
Since the submission of this paper, referern:e to au almost identical renal tumor was fcmnd. Thi.,; was a "well differentiated and nign) vVilms' tumor" presented Landi.ng at the 1958 Cancer Seminar m Dem·er Seminar, 2: llO, 28 Nicholson, G. VV.: Studies on tumour fornrn-tion. Guy's Hosp. Rep., 73: :37, 102:3, 29 ,Jagasia, K. H. and Thurman, W. C .. Cou-· genital anomalies of the kidney in associat,ion with Wilms' tumor. Pediatrics, 35: 338, 19G5. 30 Miller, R. W.: Relation between e,rncer micl congenital· defects in man. New .Engl. ,r :Vied., 275: 87, 1966. 31 DiPaolo,. J. A. and Kotin, P.: Teratogenesi;;-oncogenesis: A study of possible relationships. Arch. Path., 81: 3, 1966.