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Congenital cystic mesoblastic nephroma
MEDICAL I N T E L L I G E N C E
C O N G E N I T A L CYSTIC MESOBLASTIC NEPHROMA
J.
DOROTltYJ. GANICK, M.D.,* ENID F. GILBERT, M.D.,'[" BRUCE BECKWITll, M.D.,:]: AND NANCY KIVlAT, M.D.w
A case of cystic mesoblastic nephroma occurring in a five month old infant is presented. This unusual case provides additional information regarding the spectrum of differentiation of both solid and cystic kidney tumors in the developing embryo. Our concept of the morphogenesis of congen#al renal neoplasms is presented, tlum Pathol 12:1039-1043, 1981. Congenital mesoblastic n e p h r o m a is a benign mesenchymal t u m o r o f the kidney occurring most frequently in the infant d u r i n g the first three months of life. It was first described as a separate t u m o r distinct from Wilms' t u m o r by Bolande et al? in 1967. Microscopically this t n m o r is c o m p o s e d o f whorls o f fibrous tissue and smooth muscle, resembling a uterine fibroid or infantile fibromatosis. T h e t u m o r has no distinct capsule and may penetrate into the
Accepted for publication January 23, 1981. * Assistant Professor, Department of Pediatrics, University of Wisconsin Center for Health Sciences, Madison, Wis. 53792. Present address: Marshall University Medical School, Huntington, W. Va. 25701. [ Professor, Department of Pediatrics, University of Wisconsin Clinical Science Center, Madison, Wis. 53792. :~ Professor, The Children's Orthopedic Hospital and Medical Center, Department of Pathology, Seattle, Wash. wAssistant Professor, The Children's Orthopedic ttospital and Medical Center, Department of Pathology, Seattle, Wash.
s u r r o n n d i n g renal fat a n d adjacent tissue. ~'z In contrast to Wilms' tumor, this t u m o r does not metastasize or u n d e r g o malignant transformation3 However, there have been reports of local recurrence of the t u m o r in wlfich there was initially incomplete surgical resection. 3-5 T h e treatment for this t u m o r is surgical resection. Deaths resuhing from the therapy of this t u m o r with radiotherapy or chemotherapy have been reported in several reviews3 "6a We wish to report a case o f congenital mesoblastic nephroma, which was unttsual in that the t u m o r was predominantly cystic. Although cystic disease of the kidney and multilocnlar cysts have been reported in association with Wilms' tttmor, s-x~ to o u r knowledge a cystic mesoblastic n e p h r o m a has not been described. This type 9f congenital mesoblastlc n e p h r o m a must be distingnished~from other cystic conditions of the kidney that can present in the newborn period. REPORT OF A CASE T h e patient was a 4.4 kg. prodnct o f a ternt pregnancy born to a gravida 1, para 0 woman after an uncomplicated pregnancy, labor, and delivery. Tile infant had a normal neonatal period. At almost five months of age she was seen by her pediatrician because o f an upper respiratory tract infection. On physical examination a large n o n t e n d e r abdominal mass occupying the left side of the abdomen was palpated. She was admitted to a local hospital where a computed tomographic scan revealed a large left renal mass with a water density centrally and with t h i n n e d cortical margins. These findings were consistent with either congenital hydronephrosis or a multicystic kidney. T h e right kidney and liver were interpreted as being normal. Cystoscopy and retrograde pyelography showed an intrarenal mass in the left kidney that displaced the cortex a n d suggested the presence of a Wilms tumor.
Figure I. Gross appearance of kidney, showing replacement by cysts of varying sizes sepaltated by broad trabectdae of dense firm tissue.
0046-8177181ll 100/1039 $01.00 O W. B. Saunders Company
] 039
H U M A N P A T H O L O G Y - - V O L U M E 12, NUMBER 11 November 1981
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MEDICAL I N T E L L I G E N C E
Figure 2 (facing page, above). Low power view of tumor, showing a cyst on either side of a broad band of spindle cells. (Hematoxylin and eosin stain, x40.) Figure 3 (facing page, below) High power view of cellular component of the tumor, showing haphazard array of spindle cells between cystic spaces. The strmna contains foci of small tubular structures resembling metanephric blastenm. (Henmtoxylinand eosin stain. • 100.) Figure 4. Electron micrograph showing spindle shaped cells. The nuclei are oval; mitochondria and organnels are sparse. Microfilaments (arrows) are present. Intercellular collagen is abundant. (Epon embedded. Uranyl acetate and lead citrate stain. •
T h e patient was transferred to the University o f Wisconsin Hospitals. At surgery a t u m o r 12 cm. in diameter involving the kidney was found. T h e t u m o r appeared well encapsulated and did not invade vascular or s u r r o u n d i n g structures. It was easily mobilized from its attachement to the u n d e r l y i n g psoas muscle. T h e r e was no gross t u m o r involvement of the renal pedicle or periaortic nodes. T h e patient had a benign postoperative course. No adjuvant therapy was given. She was alive and well without evidence of t u m o r recurrence 24 months following surgery. P A T H O L O G I C A L DESCRIPTION T h e resected kidney weighed 460 grams and measured 11 by 8 by 8 cm. (Fig. 1). T h e capsule was smooth and somewhat bosselated. On section the kidney parenchyma was found to be markedly attenuated, forming a thin rim a r o u n d a markedly cystic lesion, which compressed most of the specimen. T h e cysts measured up to 2.5 cm. in diameter, had smooth surfaces, and were flied with a clear, straw colored fluid. T h e cysts were separated by broad bands o f homogeneous grayish white, fibrous appearing septa. A small a m o u n t of perirenal adipose tissue was attached to the capsular surface. T h e calyceal system was stretcited at the bilum. T h e renal vessels and proximal ureter were not remarkable, and several periaortic nodes were small, discrete, and grossly normal.
Sections o f the t u m o r showed a rather sharp line of demarcation between t u m o r and compressed nondysplastic renal parenchyma. T h e lesion was composed o f broad bands of spindle shaped cells forming trabeculae between variably sized cysts lined by somewhat flattened epithelial cells (Fig. 2). In addition to the compact spindle cells, within the trabeculae there were areas of loose myxoid cells, occasional tubular structures resembling tubules, and small foci of immature hyaline cartilage (Fig. 3). Trichrome staining demonstrated both smooth muscle and immature fibroblastic ceils. Mitoses were p r o m i n e n t in some microscopic fields. T h e capsule was intact, and there was no evidence of invasion of perinephric adipose tissue or of the renal artery or vein. T h e lympb nodes were unrenmrkable. A diagnosis of cystic mesoblastic n e p h r o m a was made.
Electron Microscopy Portions o f the tissue were fixed in 2.5 p e r cent glutaraldehyde, postfixed in osmium tetroxide, and embedded in Epon. Ultrathin sections were examined in a Hitachi HS9 electron microscope. Ttle cells forming t h e septa between tile cystic spaces were spindle shaped cells (Fig. 4). T h e nualei were oval witb frequent foldings of the nuclear membranes. Heterochromatin formed a thin m a r g i n b e n e a t h the n u c l e a r membrane. T h e cytoplasm contained sparse mitochondria and
1041
H U M A N P A T H O L O G Y - - V O L U M E 12, NUMBER 11 November 1981 Oreteric
bud
Interaction
Metanephric blastema Stroma and epithelium (central (peripheral location) location)
Full differentiation
tv
Pelvic calyces Collecting tubules
Metanephros (adult kidney)
J Epithelial predominance
Ugeter
Stromal Persistent metanephric predominance blastema (cystic or solid) Full differentiation MesobIastic nephroma
Cystic
Solid
[ Neoplastic transformation Witms' tumor /
Figure 5. Schema of renal morphogenesis.
Partial differentiation Cystic partially differentiated nephroblastoma
Disappearance of stromal components /
Complete disappearance of recognizable elements renal
Multilocular cyst "#-
o r g a n e l l e s , a n d rottgh e n d o p l a s m i c r e t i c u l u m f o r m e d anastomotic cisternae. Many cells contained microfilaments. Myofilaments or dense bodies along the microfilaments were also seen. Basement m e m b r a n e s were not present. Intercellular spaces contained collagen. T h e s e cells had features o f myofibroblasts. DISCUSSION Congenital mesoblastic n e p h r o m a is a benign kidney t u m o r found almostly exclusively in the neonatal period. Tile usual clinical presentation is a large abdominal mass in an asymptomatic infant. Polyhydramnios has been r e p o r t e d with increased frequency in mothers who have given birth to i n f a n t s f o u n d to have a c o n g e n i t a l m e s o b l a s t i c nep h r o m a ? t T h e t u m o r is curable if complete surgical resection is possible. No o t h e r therapy is indicated for this benign t u m o r . T h e t h e r a p y for an incompletely resected t u m o r is not known. Attempts at repeat surgical resection as well as c h e m o t h e r a p y and radiation t h e r a p y have been tried. 2-G O u r patient presented a little later in infancy and had a unique pathologic picture o f multiple cysts interspersed in large sheets o f homogeneous spindle cells characteristic o f congenital mesoblastic n e p h r o m a . T h e few tubules found within the tulnor anti small areas o f blastemal cells were consistent with tile development o f this stromal t u m o r in the embryonic kidney. T h e r e were no primitive tubules o r glomeruloid structures, ruling out a diagnosis o f partially d i f f e r e n t i a t e d Wihns' t u m o r . P r e v i o u s u h r a s t r u c t u r a l studies have shown tile major c o m p o n e n t o f the t u m o r to be cells o f the myofibroblastic t y p e ? z A cystic mesoblastic n e p h r o m a may therefore be ano t h e r ~ntity in the spectrum o f renal neoplasms o f childhood. One may consider congenital mesoblastic n e p h r o m a as a benign variant o f Wilms' tumor. 2 This concept is supp o r t e d by the usual presence o f primitive a p p e a r i n g tubules within the lesions and especially by the studies o f Crocker
1042
and Vernier, ~ who showed that culture o f mesoblastic nephroma tissue with fetal mouse brain resulted in induction o f primitive renal blastema in the t u m o r tissue. This suggested the primitive n e p h r o g e n i c potential o f this tumor, t h o u g h contamination o f the lesion by admixed nephric elements could not be completely excluded. T h e spectrum o f Wilms' t u m o r may then encompass forms from the solid blastemal pattern classically seen in Wilms' t u m o r to an entirely cystic, differentiated Wilms' t u m o r referred to in tile literature as a muhilocular cyst o f the kidney. T h e cystic form o f Wilms' t u m o r can be associated with classic histologic features o f Wilms' t u m o r as described by Datnow and Daniel a in which a few cysts are found within the tumor, o r with a m o r e h o m o g e n e o u s cystic form in which the septa are composed o f solid primitive renal blastema as described by Christ, ~~ Uson et al., s and Young e t a ] . t4 F u r t h e r along the spectrum are tumors almost entirely composed o f cysts with a few p r i m i t i v e a n d d i f f e r e n t i a t e d tubules a n d g l o m e r u l o i d structures dispersed in the septa. This pathologic picture was r e p o r t e d in thffee cases by Joshi et al? s These a u t h o r s reviewed the literature and classified o t h e r cases r e p o r t e d as multilocular cysts o f the kidney that exhibited some primitive and differentiated renal elements in the septa. T h e y classified this pathologic picture as "cystic partially differentiated nephroblastoma." This entity and some o f the cases in the literature u n d e r the name multilocular cyst o f the kidney (case 1 described by Boggs, TM case 2 o f Frazier, 17 cases 2 and 3 o f Baldauf, Is and tile case described by FowlerJ 9) may be partially differentiated forms o f Wihns' t u m o r as suggested b~,Joshi et a l ) 3 F u r t h e r m o r e , if differentiation progresses, an entirely cystic t u m o r may result with dense collagenous septa containing no renal structures, as seen in case 1 o f Frazier 17and case 14 o f Baldauf? s T h e s e tumors would be classified as true mu[tilocular cysts. It has been pointed out by Potter 2~ in her discussion o f congenital mesoblastic n e p h r o m a that early in d e v e l o p m e n t the embryonic kidney, especially adjacent to the developing
MEDICAL I N T E L L I G E N C E ureteric bud, manifests relatively more stromagenic than epithelial differentiation. Potter suggested that exuberant stromagenic activity may explain the typical appearance o f cystic mesoblastic nephroma, since the congenital nature o f this lesion indicates an origin early in metanephrogenesis. Later in development nephronic tubular and glomerular differentiation predominates over stromagenic activity. This concept has led two of us (NK and JBB) to postulate that there may be a pathogenetic spectrnm of Wilms' tumors and related lesions, ranging from early arising lesions corresponding to the first divisions o f the ureteric bud a n d their associated stromagenic regions, to tumors with prominent tubuloglomerular differentiation corresponding to later stages in cortical formation. T h e former lesions wotdd be expected to occnpy a more central portion within tlm renal lobule, whereas those at the other end o f the spectrum would be expected to arise peripherally in the renal tubule. T h e former end o f the spectrum of"centrally" arising renal tumors o f infants would include cystic mesoblastic nephroma, some multilocular cysts, and perhaps certain variants o f mixed Wilms' tumors in which stromal differentiation predominates. T h e other extreme would best be illustrated by ttte various forms o f nephroblastomatosis described by Bore and McAdams. 2t Between these two extremes there is room for a wide variety o f intermediate patterns. Tim concept described concurrently unifies cystic mesoblastic n e p h r o m a , Wilms' tumor, and nephroblastomatosis. According to this scitema, cystic" mesoblastic nephroma would represent the relatively "central" portion o f the pathogenetic spectrum and nephroblastomatosis the "'peripheral" end. Since Wilms' tumor, as described, may be cystic to a variable degree as well as variably differentiated, it is possible that cystic specimens may exist at any point along the spectrum just postulated. T h e cystic mesoblastic n e p h r o m a reported in this article may serve to link mesoblastic n e p h r o m a conceptually with some multilocular cysts in which stromagenic differentiation o f cyst walls is the predominant element. According to this scheme, snch muItilocular cysts would be relatively "central" in origin. Wilms' tumors o f classic mixed types might, when higldy differentiated, result in relatively more "peripheral" variants o f the multilocular cyst. This general hypothesis of"central" and "peripherar' pathogenetic variants o f Wilms' tumors and related entities is currently u n d e r active study at the Pathology Center o f the National Wilms' T u m o r Study. A schema o f o u r concept o f the spectrum o f renal morphogenesis is summarized in Figure 5.
References
1. Bolande, R. P., Brough, A.J., and lzant, R.J.: Congenital mesoblastic nephroma of infancy. Pediatrics, 40:272, 1967. 2. Bolande, R.P.: Congenital mesoblastic nephroma of infancy. Persp. Peal. PathoI_, 1:227, 1973. 3. Joshi, V. V., Kay, S., Milsten, R., Koont2, W. W., and McWilliams, N.: Congenital mesoblastic nephroma of infancy. Am. J. Clin. Path., 60:811, 1973. 4. Fu, Y., and Kay 5.: Congenital mesoblastic nephroma and its recurrence. Arch. PathoL, 96:66, 1973. 5. Walker, D., and Richard G. A.: Fetal hamartoma of the kidney: recurrence and death of patient. J. Urol., 110:359, 1973. 6. Richmond, ll_, and Dougall, A.J.: Neonatal renal tumors. J. Ped. Surg., 5:413, 1979. 7. Bogdan, R., Taylor, D. E. hi., and Mostofi. F. K.: Leiomyomatus hamartoma of the kidney. Cancer, 31:462, 1973. 8. Uson, A. C., Del Rosario, C., and Melicow, M. M.: Wilms' tumor association ~'ith cystic rena! disease: report of two cases. J. Urot., 83:262, 1960. 9. Datnow, B., and Daniel, W. W., Jr.: Polyc}stic nephroblastoum. J.A.M.A., 236:2528, 1976. 10. Christ, M. L.: Polycystic nephroblastoma. J. Urol., 98:570, 1968. 11. Blank, E., Nerhout, R. C., and Burr)', R.A.: Congenital mesoblastic nephroma and polyhydramnios. J.A.M.A., 240:1504, 1978. 12. Shen, S. C., and Yunis, E. J.: A stud)" of the cellularity and uhrastructure of congenital mesoblastic nephroma. Cancer, 45:306, 1980. 13. Crocker, J. F. S., and Vernier, R. L.: Congenital nephroma of infancy. Induction of renal structures by organ culture. J. Pediatr., 80:69, 1972. 14. Young, G., L'llereux, P., and Dehner, L. P.: Cystic nephroma (so-called polycystic Wilms' tumor) of childhood. A CT-pathologic study. Am. j. Ped. Hem. Oncol., 1:i79, 1979. 15. Joshi, V. V., Banerjee, A. K., Yadav, K., and Pathak., I. C.: Cystic partially differentiated nephroblastoma. Cancer, 40:789, 1977. 16. Boggs, L. K., and Kimmelstiel, P.: Benign muhilocular cystic nephroma: report of t~'o cases of so-called multilocular cyst of the kidney. J. Urol., 76:530, 1956. 17. Frazier, T. tl_: Multilocular cysts of the kidney. J. Urol., 65:351, 1951. 18. Baldauf, M. D., and Schulz, D. M.: Multilocular cyst of the kidney. Am. J. Clin. Path., 65:93, 1976. 19. Fowler, M.: Differentiated nephroblastoma: solid cystic or mixed. J. Path., 215, 1971. 20. Potter, E. L.: Wilms' tumor: nephroblastoma. In Normal and Abnormal Development of the Kidney. Chicago, Year Book Medical Publishers, Inc., 1972, p. 262. 21. Bore, K. E., and McAdams, A.J.: The nephroblastomatosls complex and its relationship to Wilms" tumor: a clinical pathologic treatise. Persp. Ped_ Pathol., 3:185, 1976.
Department of Pediatrics Marshall University Huntington, W_ Va. 25701 (Dr. Ganick)
1043
C O N G E N I T A L CYSTIC MESOBLASTIC NEPHROMA
J.
DOROTltYJ. GANICK, M.D.,* ENID F. GILBERT, M.D.,'[" BRUCE BECKWITll, M.D.,:]: AND NANCY KIVlAT, M.D.w
A case of cystic mesoblastic nephroma occurring in a five month old infant is presented. This unusual case provides additional information regarding the spectrum of differentiation of both solid and cystic kidney tumors in the developing embryo. Our concept of the morphogenesis of congen#al renal neoplasms is presented, tlum Pathol 12:1039-1043, 1981. Congenital mesoblastic n e p h r o m a is a benign mesenchymal t u m o r o f the kidney occurring most frequently in the infant d u r i n g the first three months of life. It was first described as a separate t u m o r distinct from Wilms' t u m o r by Bolande et al? in 1967. Microscopically this t n m o r is c o m p o s e d o f whorls o f fibrous tissue and smooth muscle, resembling a uterine fibroid or infantile fibromatosis. T h e t u m o r has no distinct capsule and may penetrate into the
Accepted for publication January 23, 1981. * Assistant Professor, Department of Pediatrics, University of Wisconsin Center for Health Sciences, Madison, Wis. 53792. Present address: Marshall University Medical School, Huntington, W. Va. 25701. [ Professor, Department of Pediatrics, University of Wisconsin Clinical Science Center, Madison, Wis. 53792. :~ Professor, The Children's Orthopedic Hospital and Medical Center, Department of Pathology, Seattle, Wash. wAssistant Professor, The Children's Orthopedic ttospital and Medical Center, Department of Pathology, Seattle, Wash.
s u r r o n n d i n g renal fat a n d adjacent tissue. ~'z In contrast to Wilms' tumor, this t u m o r does not metastasize or u n d e r g o malignant transformation3 However, there have been reports of local recurrence of the t u m o r in wlfich there was initially incomplete surgical resection. 3-5 T h e treatment for this t u m o r is surgical resection. Deaths resuhing from the therapy of this t u m o r with radiotherapy or chemotherapy have been reported in several reviews3 "6a We wish to report a case o f congenital mesoblastic nephroma, which was unttsual in that the t u m o r was predominantly cystic. Although cystic disease of the kidney and multilocnlar cysts have been reported in association with Wilms' tttmor, s-x~ to o u r knowledge a cystic mesoblastic n e p h r o m a has not been described. This type 9f congenital mesoblastlc n e p h r o m a must be distingnished~from other cystic conditions of the kidney that can present in the newborn period. REPORT OF A CASE T h e patient was a 4.4 kg. prodnct o f a ternt pregnancy born to a gravida 1, para 0 woman after an uncomplicated pregnancy, labor, and delivery. Tile infant had a normal neonatal period. At almost five months of age she was seen by her pediatrician because o f an upper respiratory tract infection. On physical examination a large n o n t e n d e r abdominal mass occupying the left side of the abdomen was palpated. She was admitted to a local hospital where a computed tomographic scan revealed a large left renal mass with a water density centrally and with t h i n n e d cortical margins. These findings were consistent with either congenital hydronephrosis or a multicystic kidney. T h e right kidney and liver were interpreted as being normal. Cystoscopy and retrograde pyelography showed an intrarenal mass in the left kidney that displaced the cortex a n d suggested the presence of a Wilms tumor.
Figure I. Gross appearance of kidney, showing replacement by cysts of varying sizes sepaltated by broad trabectdae of dense firm tissue.
0046-8177181ll 100/1039 $01.00 O W. B. Saunders Company
] 039
H U M A N P A T H O L O G Y - - V O L U M E 12, NUMBER 11 November 1981
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MEDICAL I N T E L L I G E N C E
Figure 2 (facing page, above). Low power view of tumor, showing a cyst on either side of a broad band of spindle cells. (Hematoxylin and eosin stain, x40.) Figure 3 (facing page, below) High power view of cellular component of the tumor, showing haphazard array of spindle cells between cystic spaces. The strmna contains foci of small tubular structures resembling metanephric blastenm. (Henmtoxylinand eosin stain. • 100.) Figure 4. Electron micrograph showing spindle shaped cells. The nuclei are oval; mitochondria and organnels are sparse. Microfilaments (arrows) are present. Intercellular collagen is abundant. (Epon embedded. Uranyl acetate and lead citrate stain. •
T h e patient was transferred to the University o f Wisconsin Hospitals. At surgery a t u m o r 12 cm. in diameter involving the kidney was found. T h e t u m o r appeared well encapsulated and did not invade vascular or s u r r o u n d i n g structures. It was easily mobilized from its attachement to the u n d e r l y i n g psoas muscle. T h e r e was no gross t u m o r involvement of the renal pedicle or periaortic nodes. T h e patient had a benign postoperative course. No adjuvant therapy was given. She was alive and well without evidence of t u m o r recurrence 24 months following surgery. P A T H O L O G I C A L DESCRIPTION T h e resected kidney weighed 460 grams and measured 11 by 8 by 8 cm. (Fig. 1). T h e capsule was smooth and somewhat bosselated. On section the kidney parenchyma was found to be markedly attenuated, forming a thin rim a r o u n d a markedly cystic lesion, which compressed most of the specimen. T h e cysts measured up to 2.5 cm. in diameter, had smooth surfaces, and were flied with a clear, straw colored fluid. T h e cysts were separated by broad bands o f homogeneous grayish white, fibrous appearing septa. A small a m o u n t of perirenal adipose tissue was attached to the capsular surface. T h e calyceal system was stretcited at the bilum. T h e renal vessels and proximal ureter were not remarkable, and several periaortic nodes were small, discrete, and grossly normal.
Sections o f the t u m o r showed a rather sharp line of demarcation between t u m o r and compressed nondysplastic renal parenchyma. T h e lesion was composed o f broad bands of spindle shaped cells forming trabeculae between variably sized cysts lined by somewhat flattened epithelial cells (Fig. 2). In addition to the compact spindle cells, within the trabeculae there were areas of loose myxoid cells, occasional tubular structures resembling tubules, and small foci of immature hyaline cartilage (Fig. 3). Trichrome staining demonstrated both smooth muscle and immature fibroblastic ceils. Mitoses were p r o m i n e n t in some microscopic fields. T h e capsule was intact, and there was no evidence of invasion of perinephric adipose tissue or of the renal artery or vein. T h e lympb nodes were unrenmrkable. A diagnosis of cystic mesoblastic n e p h r o m a was made.
Electron Microscopy Portions o f the tissue were fixed in 2.5 p e r cent glutaraldehyde, postfixed in osmium tetroxide, and embedded in Epon. Ultrathin sections were examined in a Hitachi HS9 electron microscope. Ttle cells forming t h e septa between tile cystic spaces were spindle shaped cells (Fig. 4). T h e nualei were oval witb frequent foldings of the nuclear membranes. Heterochromatin formed a thin m a r g i n b e n e a t h the n u c l e a r membrane. T h e cytoplasm contained sparse mitochondria and
1041
H U M A N P A T H O L O G Y - - V O L U M E 12, NUMBER 11 November 1981 Oreteric
bud
Interaction
Metanephric blastema Stroma and epithelium (central (peripheral location) location)
Full differentiation
tv
Pelvic calyces Collecting tubules
Metanephros (adult kidney)
J Epithelial predominance
Ugeter
Stromal Persistent metanephric predominance blastema (cystic or solid) Full differentiation MesobIastic nephroma
Cystic
Solid
[ Neoplastic transformation Witms' tumor /
Figure 5. Schema of renal morphogenesis.
Partial differentiation Cystic partially differentiated nephroblastoma
Disappearance of stromal components /
Complete disappearance of recognizable elements renal
Multilocular cyst "#-
o r g a n e l l e s , a n d rottgh e n d o p l a s m i c r e t i c u l u m f o r m e d anastomotic cisternae. Many cells contained microfilaments. Myofilaments or dense bodies along the microfilaments were also seen. Basement m e m b r a n e s were not present. Intercellular spaces contained collagen. T h e s e cells had features o f myofibroblasts. DISCUSSION Congenital mesoblastic n e p h r o m a is a benign kidney t u m o r found almostly exclusively in the neonatal period. Tile usual clinical presentation is a large abdominal mass in an asymptomatic infant. Polyhydramnios has been r e p o r t e d with increased frequency in mothers who have given birth to i n f a n t s f o u n d to have a c o n g e n i t a l m e s o b l a s t i c nep h r o m a ? t T h e t u m o r is curable if complete surgical resection is possible. No o t h e r therapy is indicated for this benign t u m o r . T h e t h e r a p y for an incompletely resected t u m o r is not known. Attempts at repeat surgical resection as well as c h e m o t h e r a p y and radiation t h e r a p y have been tried. 2-G O u r patient presented a little later in infancy and had a unique pathologic picture o f multiple cysts interspersed in large sheets o f homogeneous spindle cells characteristic o f congenital mesoblastic n e p h r o m a . T h e few tubules found within the tulnor anti small areas o f blastemal cells were consistent with tile development o f this stromal t u m o r in the embryonic kidney. T h e r e were no primitive tubules o r glomeruloid structures, ruling out a diagnosis o f partially d i f f e r e n t i a t e d Wihns' t u m o r . P r e v i o u s u h r a s t r u c t u r a l studies have shown tile major c o m p o n e n t o f the t u m o r to be cells o f the myofibroblastic t y p e ? z A cystic mesoblastic n e p h r o m a may therefore be ano t h e r ~ntity in the spectrum o f renal neoplasms o f childhood. One may consider congenital mesoblastic n e p h r o m a as a benign variant o f Wilms' tumor. 2 This concept is supp o r t e d by the usual presence o f primitive a p p e a r i n g tubules within the lesions and especially by the studies o f Crocker
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and Vernier, ~ who showed that culture o f mesoblastic nephroma tissue with fetal mouse brain resulted in induction o f primitive renal blastema in the t u m o r tissue. This suggested the primitive n e p h r o g e n i c potential o f this tumor, t h o u g h contamination o f the lesion by admixed nephric elements could not be completely excluded. T h e spectrum o f Wilms' t u m o r may then encompass forms from the solid blastemal pattern classically seen in Wilms' t u m o r to an entirely cystic, differentiated Wilms' t u m o r referred to in tile literature as a muhilocular cyst o f the kidney. T h e cystic form o f Wilms' t u m o r can be associated with classic histologic features o f Wilms' t u m o r as described by Datnow and Daniel a in which a few cysts are found within the tumor, o r with a m o r e h o m o g e n e o u s cystic form in which the septa are composed o f solid primitive renal blastema as described by Christ, ~~ Uson et al., s and Young e t a ] . t4 F u r t h e r along the spectrum are tumors almost entirely composed o f cysts with a few p r i m i t i v e a n d d i f f e r e n t i a t e d tubules a n d g l o m e r u l o i d structures dispersed in the septa. This pathologic picture was r e p o r t e d in thffee cases by Joshi et al? s These a u t h o r s reviewed the literature and classified o t h e r cases r e p o r t e d as multilocular cysts o f the kidney that exhibited some primitive and differentiated renal elements in the septa. T h e y classified this pathologic picture as "cystic partially differentiated nephroblastoma." This entity and some o f the cases in the literature u n d e r the name multilocular cyst o f the kidney (case 1 described by Boggs, TM case 2 o f Frazier, 17 cases 2 and 3 o f Baldauf, Is and tile case described by FowlerJ 9) may be partially differentiated forms o f Wihns' t u m o r as suggested b~,Joshi et a l ) 3 F u r t h e r m o r e , if differentiation progresses, an entirely cystic t u m o r may result with dense collagenous septa containing no renal structures, as seen in case 1 o f Frazier 17and case 14 o f Baldauf? s T h e s e tumors would be classified as true mu[tilocular cysts. It has been pointed out by Potter 2~ in her discussion o f congenital mesoblastic n e p h r o m a that early in d e v e l o p m e n t the embryonic kidney, especially adjacent to the developing
MEDICAL I N T E L L I G E N C E ureteric bud, manifests relatively more stromagenic than epithelial differentiation. Potter suggested that exuberant stromagenic activity may explain the typical appearance o f cystic mesoblastic nephroma, since the congenital nature o f this lesion indicates an origin early in metanephrogenesis. Later in development nephronic tubular and glomerular differentiation predominates over stromagenic activity. This concept has led two of us (NK and JBB) to postulate that there may be a pathogenetic spectrnm of Wilms' tumors and related lesions, ranging from early arising lesions corresponding to the first divisions o f the ureteric bud a n d their associated stromagenic regions, to tumors with prominent tubuloglomerular differentiation corresponding to later stages in cortical formation. T h e former lesions wotdd be expected to occnpy a more central portion within tlm renal lobule, whereas those at the other end o f the spectrum would be expected to arise peripherally in the renal tubule. T h e former end o f the spectrum of"centrally" arising renal tumors o f infants would include cystic mesoblastic nephroma, some multilocular cysts, and perhaps certain variants o f mixed Wilms' tumors in which stromal differentiation predominates. T h e other extreme would best be illustrated by ttte various forms o f nephroblastomatosis described by Bore and McAdams. 2t Between these two extremes there is room for a wide variety o f intermediate patterns. Tim concept described concurrently unifies cystic mesoblastic n e p h r o m a , Wilms' tumor, and nephroblastomatosis. According to this scitema, cystic" mesoblastic nephroma would represent the relatively "central" portion o f the pathogenetic spectrum and nephroblastomatosis the "'peripheral" end. Since Wilms' tumor, as described, may be cystic to a variable degree as well as variably differentiated, it is possible that cystic specimens may exist at any point along the spectrum just postulated. T h e cystic mesoblastic n e p h r o m a reported in this article may serve to link mesoblastic n e p h r o m a conceptually with some multilocular cysts in which stromagenic differentiation o f cyst walls is the predominant element. According to this scheme, snch muItilocular cysts would be relatively "central" in origin. Wilms' tumors o f classic mixed types might, when higldy differentiated, result in relatively more "peripheral" variants o f the multilocular cyst. This general hypothesis of"central" and "peripherar' pathogenetic variants o f Wilms' tumors and related entities is currently u n d e r active study at the Pathology Center o f the National Wilms' T u m o r Study. A schema o f o u r concept o f the spectrum o f renal morphogenesis is summarized in Figure 5.
References
1. Bolande, R. P., Brough, A.J., and lzant, R.J.: Congenital mesoblastic nephroma of infancy. Pediatrics, 40:272, 1967. 2. Bolande, R.P.: Congenital mesoblastic nephroma of infancy. Persp. Peal. PathoI_, 1:227, 1973. 3. Joshi, V. V., Kay, S., Milsten, R., Koont2, W. W., and McWilliams, N.: Congenital mesoblastic nephroma of infancy. Am. J. Clin. Path., 60:811, 1973. 4. Fu, Y., and Kay 5.: Congenital mesoblastic nephroma and its recurrence. Arch. PathoL, 96:66, 1973. 5. Walker, D., and Richard G. A.: Fetal hamartoma of the kidney: recurrence and death of patient. J. Urol., 110:359, 1973. 6. Richmond, ll_, and Dougall, A.J.: Neonatal renal tumors. J. Ped. Surg., 5:413, 1979. 7. Bogdan, R., Taylor, D. E. hi., and Mostofi. F. K.: Leiomyomatus hamartoma of the kidney. Cancer, 31:462, 1973. 8. Uson, A. C., Del Rosario, C., and Melicow, M. M.: Wilms' tumor association ~'ith cystic rena! disease: report of two cases. J. Urot., 83:262, 1960. 9. Datnow, B., and Daniel, W. W., Jr.: Polyc}stic nephroblastoum. J.A.M.A., 236:2528, 1976. 10. Christ, M. L.: Polycystic nephroblastoma. J. Urol., 98:570, 1968. 11. Blank, E., Nerhout, R. C., and Burr)', R.A.: Congenital mesoblastic nephroma and polyhydramnios. J.A.M.A., 240:1504, 1978. 12. Shen, S. C., and Yunis, E. J.: A stud)" of the cellularity and uhrastructure of congenital mesoblastic nephroma. Cancer, 45:306, 1980. 13. Crocker, J. F. S., and Vernier, R. L.: Congenital nephroma of infancy. Induction of renal structures by organ culture. J. Pediatr., 80:69, 1972. 14. Young, G., L'llereux, P., and Dehner, L. P.: Cystic nephroma (so-called polycystic Wilms' tumor) of childhood. A CT-pathologic study. Am. j. Ped. Hem. Oncol., 1:i79, 1979. 15. Joshi, V. V., Banerjee, A. K., Yadav, K., and Pathak., I. C.: Cystic partially differentiated nephroblastoma. Cancer, 40:789, 1977. 16. Boggs, L. K., and Kimmelstiel, P.: Benign muhilocular cystic nephroma: report of t~'o cases of so-called multilocular cyst of the kidney. J. Urol., 76:530, 1956. 17. Frazier, T. tl_: Multilocular cysts of the kidney. J. Urol., 65:351, 1951. 18. Baldauf, M. D., and Schulz, D. M.: Multilocular cyst of the kidney. Am. J. Clin. Path., 65:93, 1976. 19. Fowler, M.: Differentiated nephroblastoma: solid cystic or mixed. J. Path., 215, 1971. 20. Potter, E. L.: Wilms' tumor: nephroblastoma. In Normal and Abnormal Development of the Kidney. Chicago, Year Book Medical Publishers, Inc., 1972, p. 262. 21. Bore, K. E., and McAdams, A.J.: The nephroblastomatosls complex and its relationship to Wilms" tumor: a clinical pathologic treatise. Persp. Ped_ Pathol., 3:185, 1976.
Department of Pediatrics Marshall University Huntington, W_ Va. 25701 (Dr. Ganick)
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