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Bilateral Wilms' tumors in children
Volume 65
Number 3
T h e J o u r n a l o[ P E D I A T R I C S
3 7 1
Bilateral Wilms' tumors in cbildren Ten per cent o[ children who have Witms' tumor will have bilateral disease. I t is often unsuspected and proper evaluation may not be made at the time o[ surgery. I[ not present in both kidneys concurrently, the tumor most #equently occurs in the remaining kidney between 6 and 15 months alter initial diagnosis. Considerations as to whether or not bilateral tumors are separate primary tumors or metastatic disease are presented.
K. H. Jagasia, M.D., ~' W. G. Thurman, M.D., k* Elizabeth Pickett, M.D., and Harry Grabstaldt, M.D. NE'gV Y O R K ~
N,
Y.
T H E first case of Wilms' tumor recorded was bilateral and subsequent publications have stressed both the occurrence and overall incidence?, s-16 As Wilms' tumor is one of the more c o m m o n abdominal neoplasms in children, second only to neuroblastoma in frequency, and 5.6 per cent of all renal cancers proved at autopsy or surgery are Wilms' tumor, it is not surprising that it can occur bilaterally. T h e true incidence of bilateral Wilms' tumor, however, is not well documented. Considerable debate has arisen regarding the nature of these bilateral tumors: Are they two separate p r i m a r y tumors, or is one kidney secondarily involved, i.e., a metastatic lesion ? T h e purpose of this brief study is to delineate some of the possibilities in
From the Department o[ Pediatrics and the Urology Service, Department o[ Surgery, Memorial Hospital [or Cancer and Allied Diseases. ~Fellow in Pediatrles. *'xChairman, Department o] Pediatrics. Address, 444 1~. 68th Street, N e w York, N. Y. 10021.
these two theories and to detail the incidence and clinical and pathologic characteristics of the bilateral Wilms' tumors seen in one institution between 1949 and 1963. CASE M A T E R I A L During the 14 years from June, 1949, to June, 1963, 130 patients with Wilms' tumor were admitted to Memorial Hospital. The age ranged f r o m 8 months to 65 years with 14 cases (10.7 per cent) occurring in adults (18 years or over); the remaining 116 were children. O f these one hundred and thirty, 12 patients (9.2 per cent), 7 males and 5 females, ranging in age from 8 months to 9 years, had bilateral disease (Table I). None of the fourteen adults had bilateral renal involvement. Thus, the corrected incidence of bilateral Wilms' tumor in children in this series is 10.3 per cent. Table I I compares this with the incidence as reported by other authors. Of the twelve cases diagnosed clinically, histologic confirmation of bilateral disease was obtained in 9. T h e remainder were
372
Jagasia et al.
September 1964
Table I. Details of study group
Age
Biopsy site
Clinical examinations
X-ray diagnosis
Interval between first lesion and second lesion
Patient
Sex
1. T . S .
M
8 months Bilateral Mass bilateral
Yes
Right nephrectomy Irradiation to left kidney
Concurrent
2. R. C,
F
5 years
Yes
Exploration and biopsy-both kidneys
Concurrent
3. K . K .
F
Mass in right flank 3 weeks later mass in left flank
Yes
Right nephrectomy
Three weeks
4, S.J.
M
2 years
Bilateral
Mass in both flanks
Yes
Right nephrectomy Biopsy left kidney
Concurrent
5. S.A.
M
9 years
Bilateral Hematuria, mass in left flank
IVP revealed Left "horseshoe k~d- nephrectomy hey" with tumor on left side
6. D . C .
F
3 years
Bilateral Loss of appetite Mass in left flank
IVP indicated tumor on left only
Biopsy of both I V P abnormal kidneys 9 one side Both kidneys involved at operation
7. P . T .
M
2 8 9 years Bilateral Mass in right flank Mass in left flank 19 months later
First I V P - lesion in right kidney only
Right nephrectomy 19 months later excision of lower pole of left kidney
19 months
8. j . o .
M
1 year
Yes
Left nephrectomy Excision of tumor in right kidney
9 months
9, A.S.
M
Left nephrectorny Biopsy right kidney
6 months
I0. C.S.
F
Left nephrectomy ; biopsy right kidney
7 months
Bilateral Loss of activity and appetite Mass bilateral
11 months Right
Bilateral Mass in right flank~pallor
2 3 m o n t h s Bilateral Mass in left Mass in lower flank oole left kidney Mass in right Bilateral hydroside 6 months nephrosis--no later bladder neck obstruction 3 years
Bilateral Mass in left flank Enlarged right kidney 7 months later
1st I V P ~ m a s s left kidney 2nd I V P - - e n larged right kidney
Treatment
Less than two months
Volume 65
Number 3
Bilateral Wilms" tumors
3 73
Table I. C o n t ' d
Age
Biopsy site
Clinical examinations
X-Taft diagnosis
Treatment
Interval between l~rst lesion and second lesion
Patient
Sex
iI. T.C.
M
4 ~ years Right
Mass in right abdomen
First I V P - mass in right kidney Later I V P - displacement of lower pole of left kidney
Right nephrectomy
4 months
12. R.C.
F
2 years
Swelling of right abdomen Tumor in left kidney 9 months later
IVP--lesions in right kidney only
Right nephrectomy
9 months
Right
diagnosed by surgical palpation and x-ray studies. T h e second intravenous pyelogram showed changes from the original study consisting of evidence of expanding lesions with distortion of the calyces (Table I). A solitary lesion was present in both kidneys in 10 cases; in Patient 5, a solitary lesion was present in the left kidney and multiple lesions were found on the right. T h e most recent patient (No. 6) h a d multiple lesions in both kidneys; the renal vessels were not involved. Clinical data. Clinically, a mass was felt in both kidneys at the time of initial diagnosis in 3 patients 1' ~' 4; this was confirmed by I V P . I n one patient (No. 3), a mass was felt only in the right flank, a n d there is no record of palpation of the left kidney during operation; however, a mass in the left kidney was palpated 3 weeks after the operation. Patient 5 had a t u m o r palpable in the left flank; I V P indicated that the t u m o r was confined to the left side, but at operation it was found that the right side of a "horseshoe kidney" was also studded with multiple tumor nodules. One can easily conjecture that the right kidney represented metastatic lesions. Patient 6 had a mass palpable in the left kidney; this was confirmed by IVP, but at operation both kidneys had multiple tumor nodules and cysts. Grossly, the arteries and veins of both kidneys were uninvolved. Patient 7 had a mass felt in the right kidney;
there was no evidence of disease in the left kidney by I V P or at surgery. Nineteen months later a left renal mass was felt. There was no evidence, grossly or by palpation, of renal vessel involvement. Patient 8 had a left nephrectomy for a Wilms' tumor; the renal vessels appeared normal. Nine months later the patient developed anemia, and a mass was palpable in the region of the right kidney which on exploration proved to be another Wilms' tumor. Patient 9 had a mass palpable on the left side; I V P earlier had revealed bilateral hydronephrosis; 6 months after initial nephrectomy a mass was noted in the right kidney. There is no record as to whether the right kidney was palpated during operation. Patient 10 developed a mass on the left side, the right side being normal. Eight months later the patient presented with a mass on the right; the I V P revealed a distorted calyceal system. Patient 11 had a mass in the right flank; I V P confirmed the existence of the mass. At surgery, the right kidney was removed but the left kidney was not palpated. Fifteen months later a mass was palpated in the area of the left kidney and again the I V P confirmed that the mass was intrarenal. Patient 12 had a swelling in the abdomen on the right side confirmed as a renal mass by IVP. At laparotomy the left kidney was not palpated. Nine months later a swelling in the left side of the abdomen was detected,
3 74
September 1964
]agasia et aI.
and an I V P revealed an enlarged left kidney with flattening of the middle calyceal group. Time interval. O n e patient (3) had a mass in the remaining kidney palpated within 3 weeks after the initial nephrectomy. The time interval between the initial diagnosis in one kidney and the appearance ot involvement in the remaining kidney in the other patients was from 6 to 15 months, with a median of 9 months (Table I). Renal vein involvement. I n only Patients 3 and 9 was the renal vein involved with tumor. Four patients (1, 2, 4, 6) had both kidneys involved concurrently, yet none of these had renal vein involvement, grossly or by palpation. Autopsy data. Of the 130 patients reviewed, 20 patients are living (15.4 per cent). Autopsies were obtained in 45 of the other 110 patients (40.9 per cent). All patients autopsied, including 3 with bilateral tumors, had metastases in various parts of the body. It is interesting, and probably significant, that none of the other 42 patients autopsied had metastases in the remaining kidney. DISCUSSION In paired organs, if one undergoes malignant change it is reasonable to assume that similar potentialities at least exist for the opposite organ to do the same. Certain evidence suggests that, insofar as Wilms' tumor is concerned, the occurrence of separate primaries rather than metastases best explains the presence of bilateral tumors. These include:
1. Embryologic evidence of origin of Wilms' t u m o r from blastemal cells in both kidneysY -5 2. T u m o r s in both kidneys consisting mostly of clumps of primitive blastema cells. an indication of abnormal growth in situ. z 3. Both tumors detected simultaneously with no evidence of metastases to other sites. 4. N o other metastases found at the time of detection of second tumor. 5. Solitary t u m o r in remaining kidney (except in Patient 5). 6. No evidence of direct tumor extension across midline either during operation or at autopsy. 7. T h e smallest t u m o r in the kidney at the time of operation larger than demonstrable metastases in other areas. Conversely, metastatic origin for the occurrence of t u m o r in the remaining kidney is Supported by the following: 1. T h e frequency with which blood-borne metastases are seen in all patients with Wilms' tumor, assuming that the theory of blood-borne metastases will account for the spread of tumor beyond a local area. 2. Theoretical direct extension of tumor in a congenital anomalous kidney such as the "horseshoe" kidney. 3. Multiple lesions in the remaining kidney as seen in Patient 5. More than one distinct lesion in the kidney which first became enlarged has not been reported so if multiple lesions are found in the remaining kidney, it is logical to presume that they are metastatic.
Table II. Review of previous reports
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
Author or source
No. o[ Wilms' tumor reported
Cincinnati Children's Hospltal 8 Boston Children's Hospital s Walker, J. B. (1897) s~ Scott1~ (Urology Survey) Reiser and Creevy (Urology Survey) Dean, A. L. 2 Kretschner and Hibbs 18 Great Ormond Street Hospital, London14 Gross and Neuhauser ~8 Rickham 1~ Memorial Hospital, New York (1963)
39 139 141 906 117 100 17 80 96 25 I16
No. of bilateral cases
3 6 10 33 28 -
-
2 -4 2 t2
"~Diagnosis was made only by palpation. Hence hydronephrosis or polycystic kidneys may have existed,
Percentage
7.7 4.3 7.0 3.6 2.3 -
-
11.7 -4.1 8.O 10.3
Volume 65
Number 3
Metastatic lesions have been commonly reported in lungs and other tissues, but the lack of involvement of the remaining kidney is striking in the material reviewed. On the basis of these autopsy studies, it is thus reasonable to conclude that Wilms' tumor rarely metastasizes to the other kidney. Tumors of t h e kidney represent complex problems in that their histogenesis is controversial , their structure variable, and their behavior capricious. If a tumor is present at birth, it is usually considered to be embryonic and congenital. Wilms' tumor is thought to be congenital, arising from a renal analage, and m a y show either a multiplicity of cellular components or else very few. The tumors are mesodermal in origin, arising from metanephric blastema cells, presumably at different stages of embryonal development. The embryonic nature of Wilms' tumor has been discussed by Hou and Holman 2 in their description of a premature infant, delivered at 32 weeks, who had complete "replacement" of both kidneys by Wilms' tumor; they concluded that the tumor must be an embryonic metanephric tumor. They suggested that these represented separate primary tumors, rather than metastases, because of the symmetrical and uniform involvement of both kidneys in the same stage of development. Similar findings were reported by Barrett and McCague 8 in a 61~ month fetus. Paul 4 has suggested :that Wilms' tumors are metanephric in the full meaning of the w o r d - - t h a t like all tumors they are malformations. Similarly, Nicholson '~ concluded that Wilms' tumor is metanephric and essentially a malformation in his study of the kidneys of full-term and stillborn fetuses. CampbelP has described a 24-day-old infant with "situs inversus" in whom each kidney was enlarged. Histologically in each kidney there was an "embryonal adenocarcinoma" associated with polycystic kidneys. There was no comment regarding metastases. It is imperative to keep in mind the possibility of involvement of both kidneys, particularly at surgery, in order to detect the lesion as early as possible. Management of
Bilateral Wilms' tumors
3 75
the patient can then be planned to best advantage. The lesion in the other kidney may be small so that it m a y be possible to extirpate it without sacrificing too much normal kidney tissue. If the lesions are extensive and surgery is not feasible, there are two possible plans of management: 1. If one kidney has been previously removed or if bilateral involvement is noted, small doses of radiotherapy to the remaining or least involved kidney supplemented by actinomycin D or vincristine or both should be given. The lesions may regress enough to be approached surgically. 2. Homotransplantation of a normal kidney with removal of diseased kidneys is the ultimate goal. This is now under investigation. It is thus recommended that thorough examination of the opposite kidney be done during operation in order not to overlook a tumor even if evidence of involvement is not present clinically or by IVP. Based on this small series, it appears that the lesion in the second kidney usually becomes manifest 6 to t5 months after initial surgery. In order to detect these lesions, it is suggested that pyelograms be routinely obtained in all patients at the sixth and twelfth month after nephrectomy for unilateral disease. The prognosis is very poor in children with bilateral tumors. The mortality in this series is 100 per cent and a review of the reported series in the literature reveals mortality figures between 73 to 100 per cent. More aggressive therapy is indicated in the hope that survival can be increased. SUMMARY
A review of 130 cases of Wihns' tmnor diagnosed during a 14-year period has demonstrated the incidence of bilateral tumors in children to be 10.3 per cent. Clinical data is presented relative to the time of diagnosis of tumor in the second kidney. The suggestion that repeat intravenous pyelograms at 6 and 12 months as well as adequate examination of remaining kidney at the time of surgery would improve the diagnosis is derived from the data. The mortality
376
]agasia et al.
in b i l a t e r a l t u m o r s in this series cent. A r e v i e w of the l i t e r a t u r e e m b r y o n i c c o n g e n i t a l origin for m o r . T h e q u e s t i o n of w h e t h e r or are bilateral p r i m a r y lesions or lesions has b e e n discussed.
September 1964
is 100 p e r favors a n W i l m s ' tun o t lesions metastatic
REFERENCES 1. Rance, T. F.: Cited in M. Physiol. J. 32: 19, 1814. 2. Hou, L. T., and Holman, R. L.: Bilateral nephroblastoma in a premature infant, J. Path. & Bact. 82: 249, 1961. 3. Barrett, W. A., and McCague, E. J.: Histopathology in prognosis of kidney tumors, J. Urol. 71: 684, 1954. 4. Paul, F. T.: Quoted in Transactions of Pathology Society, London, 37: 292, 1886. 5. Nieholson, G. W.: An embryonic tumor of the kidney in a foetus, J. Path. & Bact. 34: 711, 1931. 6. Campbell, M. F.: Bilateral embryonal adenosarcoma of kidney (Wilms' Tumor), J. Urol. 59: 567, 1948.
7. Bodian, M., and White, L. R.: Personal communication to Rickham, P. P., quoted in Bilateral Wilms' tumor, Brit. J. Surg. 44: 492, 1957. 8. Martin, L. W., and Kleocker, R. J.: Bilateral nephroblastomas, Pediatrics 28: 101, 1961. 9. Walker, G.: Sarcoma of kidney in children: A critical review of the pathology, symptomatology, prognosis and operative treatment as seen in one hundred and forty-five cases, Ann. Surg. 26: 529, 1897. 10. Scott, L. S.: Bilateral Wilms' tumor, Brit. J. Surg. 42: 513, 1955. 11. Reiser, M. P., and Creevy, C. D.: Wihns' tumor, Urology Survey 2: 413, 1953. 12. Dean, A. L.: Wilms' tumor, New York j. Med. 45: 1213, 1945. 13. Kretsehner, W. C., and Hibbs, B. A.: Mixed tumors of kidney in infancy and childhood, Surg., Gynec. & Obst. 52: 1, 1931. 14. White, L. L. R.: Personal communication to Rickham, P. P., Quoted in Bilateral Wilms' tumors, Brit. J. Surg. 44: 492, 1957. 15. Gross, R. E., and Neuhauser, E. B. D.: Treatment of mixed tumors of the kidney in childhood, Pediatrics 6: 843, 1950. 16. Rickham, P. P.: Bilateral Wilms' tumor, Brit. J. Surg. 44: 492, 1957.
Number 3
T h e J o u r n a l o[ P E D I A T R I C S
3 7 1
Bilateral Wilms' tumors in cbildren Ten per cent o[ children who have Witms' tumor will have bilateral disease. I t is often unsuspected and proper evaluation may not be made at the time o[ surgery. I[ not present in both kidneys concurrently, the tumor most #equently occurs in the remaining kidney between 6 and 15 months alter initial diagnosis. Considerations as to whether or not bilateral tumors are separate primary tumors or metastatic disease are presented.
K. H. Jagasia, M.D., ~' W. G. Thurman, M.D., k* Elizabeth Pickett, M.D., and Harry Grabstaldt, M.D. NE'gV Y O R K ~
N,
Y.
T H E first case of Wilms' tumor recorded was bilateral and subsequent publications have stressed both the occurrence and overall incidence?, s-16 As Wilms' tumor is one of the more c o m m o n abdominal neoplasms in children, second only to neuroblastoma in frequency, and 5.6 per cent of all renal cancers proved at autopsy or surgery are Wilms' tumor, it is not surprising that it can occur bilaterally. T h e true incidence of bilateral Wilms' tumor, however, is not well documented. Considerable debate has arisen regarding the nature of these bilateral tumors: Are they two separate p r i m a r y tumors, or is one kidney secondarily involved, i.e., a metastatic lesion ? T h e purpose of this brief study is to delineate some of the possibilities in
From the Department o[ Pediatrics and the Urology Service, Department o[ Surgery, Memorial Hospital [or Cancer and Allied Diseases. ~Fellow in Pediatrles. *'xChairman, Department o] Pediatrics. Address, 444 1~. 68th Street, N e w York, N. Y. 10021.
these two theories and to detail the incidence and clinical and pathologic characteristics of the bilateral Wilms' tumors seen in one institution between 1949 and 1963. CASE M A T E R I A L During the 14 years from June, 1949, to June, 1963, 130 patients with Wilms' tumor were admitted to Memorial Hospital. The age ranged f r o m 8 months to 65 years with 14 cases (10.7 per cent) occurring in adults (18 years or over); the remaining 116 were children. O f these one hundred and thirty, 12 patients (9.2 per cent), 7 males and 5 females, ranging in age from 8 months to 9 years, had bilateral disease (Table I). None of the fourteen adults had bilateral renal involvement. Thus, the corrected incidence of bilateral Wilms' tumor in children in this series is 10.3 per cent. Table I I compares this with the incidence as reported by other authors. Of the twelve cases diagnosed clinically, histologic confirmation of bilateral disease was obtained in 9. T h e remainder were
372
Jagasia et al.
September 1964
Table I. Details of study group
Age
Biopsy site
Clinical examinations
X-ray diagnosis
Interval between first lesion and second lesion
Patient
Sex
1. T . S .
M
8 months Bilateral Mass bilateral
Yes
Right nephrectomy Irradiation to left kidney
Concurrent
2. R. C,
F
5 years
Yes
Exploration and biopsy-both kidneys
Concurrent
3. K . K .
F
Mass in right flank 3 weeks later mass in left flank
Yes
Right nephrectomy
Three weeks
4, S.J.
M
2 years
Bilateral
Mass in both flanks
Yes
Right nephrectomy Biopsy left kidney
Concurrent
5. S.A.
M
9 years
Bilateral Hematuria, mass in left flank
IVP revealed Left "horseshoe k~d- nephrectomy hey" with tumor on left side
6. D . C .
F
3 years
Bilateral Loss of appetite Mass in left flank
IVP indicated tumor on left only
Biopsy of both I V P abnormal kidneys 9 one side Both kidneys involved at operation
7. P . T .
M
2 8 9 years Bilateral Mass in right flank Mass in left flank 19 months later
First I V P - lesion in right kidney only
Right nephrectomy 19 months later excision of lower pole of left kidney
19 months
8. j . o .
M
1 year
Yes
Left nephrectomy Excision of tumor in right kidney
9 months
9, A.S.
M
Left nephrectorny Biopsy right kidney
6 months
I0. C.S.
F
Left nephrectomy ; biopsy right kidney
7 months
Bilateral Loss of activity and appetite Mass bilateral
11 months Right
Bilateral Mass in right flank~pallor
2 3 m o n t h s Bilateral Mass in left Mass in lower flank oole left kidney Mass in right Bilateral hydroside 6 months nephrosis--no later bladder neck obstruction 3 years
Bilateral Mass in left flank Enlarged right kidney 7 months later
1st I V P ~ m a s s left kidney 2nd I V P - - e n larged right kidney
Treatment
Less than two months
Volume 65
Number 3
Bilateral Wilms" tumors
3 73
Table I. C o n t ' d
Age
Biopsy site
Clinical examinations
X-Taft diagnosis
Treatment
Interval between l~rst lesion and second lesion
Patient
Sex
iI. T.C.
M
4 ~ years Right
Mass in right abdomen
First I V P - mass in right kidney Later I V P - displacement of lower pole of left kidney
Right nephrectomy
4 months
12. R.C.
F
2 years
Swelling of right abdomen Tumor in left kidney 9 months later
IVP--lesions in right kidney only
Right nephrectomy
9 months
Right
diagnosed by surgical palpation and x-ray studies. T h e second intravenous pyelogram showed changes from the original study consisting of evidence of expanding lesions with distortion of the calyces (Table I). A solitary lesion was present in both kidneys in 10 cases; in Patient 5, a solitary lesion was present in the left kidney and multiple lesions were found on the right. T h e most recent patient (No. 6) h a d multiple lesions in both kidneys; the renal vessels were not involved. Clinical data. Clinically, a mass was felt in both kidneys at the time of initial diagnosis in 3 patients 1' ~' 4; this was confirmed by I V P . I n one patient (No. 3), a mass was felt only in the right flank, a n d there is no record of palpation of the left kidney during operation; however, a mass in the left kidney was palpated 3 weeks after the operation. Patient 5 had a t u m o r palpable in the left flank; I V P indicated that the t u m o r was confined to the left side, but at operation it was found that the right side of a "horseshoe kidney" was also studded with multiple tumor nodules. One can easily conjecture that the right kidney represented metastatic lesions. Patient 6 had a mass palpable in the left kidney; this was confirmed by IVP, but at operation both kidneys had multiple tumor nodules and cysts. Grossly, the arteries and veins of both kidneys were uninvolved. Patient 7 had a mass felt in the right kidney;
there was no evidence of disease in the left kidney by I V P or at surgery. Nineteen months later a left renal mass was felt. There was no evidence, grossly or by palpation, of renal vessel involvement. Patient 8 had a left nephrectomy for a Wilms' tumor; the renal vessels appeared normal. Nine months later the patient developed anemia, and a mass was palpable in the region of the right kidney which on exploration proved to be another Wilms' tumor. Patient 9 had a mass palpable on the left side; I V P earlier had revealed bilateral hydronephrosis; 6 months after initial nephrectomy a mass was noted in the right kidney. There is no record as to whether the right kidney was palpated during operation. Patient 10 developed a mass on the left side, the right side being normal. Eight months later the patient presented with a mass on the right; the I V P revealed a distorted calyceal system. Patient 11 had a mass in the right flank; I V P confirmed the existence of the mass. At surgery, the right kidney was removed but the left kidney was not palpated. Fifteen months later a mass was palpated in the area of the left kidney and again the I V P confirmed that the mass was intrarenal. Patient 12 had a swelling in the abdomen on the right side confirmed as a renal mass by IVP. At laparotomy the left kidney was not palpated. Nine months later a swelling in the left side of the abdomen was detected,
3 74
September 1964
]agasia et aI.
and an I V P revealed an enlarged left kidney with flattening of the middle calyceal group. Time interval. O n e patient (3) had a mass in the remaining kidney palpated within 3 weeks after the initial nephrectomy. The time interval between the initial diagnosis in one kidney and the appearance ot involvement in the remaining kidney in the other patients was from 6 to 15 months, with a median of 9 months (Table I). Renal vein involvement. I n only Patients 3 and 9 was the renal vein involved with tumor. Four patients (1, 2, 4, 6) had both kidneys involved concurrently, yet none of these had renal vein involvement, grossly or by palpation. Autopsy data. Of the 130 patients reviewed, 20 patients are living (15.4 per cent). Autopsies were obtained in 45 of the other 110 patients (40.9 per cent). All patients autopsied, including 3 with bilateral tumors, had metastases in various parts of the body. It is interesting, and probably significant, that none of the other 42 patients autopsied had metastases in the remaining kidney. DISCUSSION In paired organs, if one undergoes malignant change it is reasonable to assume that similar potentialities at least exist for the opposite organ to do the same. Certain evidence suggests that, insofar as Wilms' tumor is concerned, the occurrence of separate primaries rather than metastases best explains the presence of bilateral tumors. These include:
1. Embryologic evidence of origin of Wilms' t u m o r from blastemal cells in both kidneysY -5 2. T u m o r s in both kidneys consisting mostly of clumps of primitive blastema cells. an indication of abnormal growth in situ. z 3. Both tumors detected simultaneously with no evidence of metastases to other sites. 4. N o other metastases found at the time of detection of second tumor. 5. Solitary t u m o r in remaining kidney (except in Patient 5). 6. No evidence of direct tumor extension across midline either during operation or at autopsy. 7. T h e smallest t u m o r in the kidney at the time of operation larger than demonstrable metastases in other areas. Conversely, metastatic origin for the occurrence of t u m o r in the remaining kidney is Supported by the following: 1. T h e frequency with which blood-borne metastases are seen in all patients with Wilms' tumor, assuming that the theory of blood-borne metastases will account for the spread of tumor beyond a local area. 2. Theoretical direct extension of tumor in a congenital anomalous kidney such as the "horseshoe" kidney. 3. Multiple lesions in the remaining kidney as seen in Patient 5. More than one distinct lesion in the kidney which first became enlarged has not been reported so if multiple lesions are found in the remaining kidney, it is logical to presume that they are metastatic.
Table II. Review of previous reports
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
Author or source
No. o[ Wilms' tumor reported
Cincinnati Children's Hospltal 8 Boston Children's Hospital s Walker, J. B. (1897) s~ Scott1~ (Urology Survey) Reiser and Creevy (Urology Survey) Dean, A. L. 2 Kretschner and Hibbs 18 Great Ormond Street Hospital, London14 Gross and Neuhauser ~8 Rickham 1~ Memorial Hospital, New York (1963)
39 139 141 906 117 100 17 80 96 25 I16
No. of bilateral cases
3 6 10 33 28 -
-
2 -4 2 t2
"~Diagnosis was made only by palpation. Hence hydronephrosis or polycystic kidneys may have existed,
Percentage
7.7 4.3 7.0 3.6 2.3 -
-
11.7 -4.1 8.O 10.3
Volume 65
Number 3
Metastatic lesions have been commonly reported in lungs and other tissues, but the lack of involvement of the remaining kidney is striking in the material reviewed. On the basis of these autopsy studies, it is thus reasonable to conclude that Wilms' tumor rarely metastasizes to the other kidney. Tumors of t h e kidney represent complex problems in that their histogenesis is controversial , their structure variable, and their behavior capricious. If a tumor is present at birth, it is usually considered to be embryonic and congenital. Wilms' tumor is thought to be congenital, arising from a renal analage, and m a y show either a multiplicity of cellular components or else very few. The tumors are mesodermal in origin, arising from metanephric blastema cells, presumably at different stages of embryonal development. The embryonic nature of Wilms' tumor has been discussed by Hou and Holman 2 in their description of a premature infant, delivered at 32 weeks, who had complete "replacement" of both kidneys by Wilms' tumor; they concluded that the tumor must be an embryonic metanephric tumor. They suggested that these represented separate primary tumors, rather than metastases, because of the symmetrical and uniform involvement of both kidneys in the same stage of development. Similar findings were reported by Barrett and McCague 8 in a 61~ month fetus. Paul 4 has suggested :that Wilms' tumors are metanephric in the full meaning of the w o r d - - t h a t like all tumors they are malformations. Similarly, Nicholson '~ concluded that Wilms' tumor is metanephric and essentially a malformation in his study of the kidneys of full-term and stillborn fetuses. CampbelP has described a 24-day-old infant with "situs inversus" in whom each kidney was enlarged. Histologically in each kidney there was an "embryonal adenocarcinoma" associated with polycystic kidneys. There was no comment regarding metastases. It is imperative to keep in mind the possibility of involvement of both kidneys, particularly at surgery, in order to detect the lesion as early as possible. Management of
Bilateral Wilms' tumors
3 75
the patient can then be planned to best advantage. The lesion in the other kidney may be small so that it m a y be possible to extirpate it without sacrificing too much normal kidney tissue. If the lesions are extensive and surgery is not feasible, there are two possible plans of management: 1. If one kidney has been previously removed or if bilateral involvement is noted, small doses of radiotherapy to the remaining or least involved kidney supplemented by actinomycin D or vincristine or both should be given. The lesions may regress enough to be approached surgically. 2. Homotransplantation of a normal kidney with removal of diseased kidneys is the ultimate goal. This is now under investigation. It is thus recommended that thorough examination of the opposite kidney be done during operation in order not to overlook a tumor even if evidence of involvement is not present clinically or by IVP. Based on this small series, it appears that the lesion in the second kidney usually becomes manifest 6 to t5 months after initial surgery. In order to detect these lesions, it is suggested that pyelograms be routinely obtained in all patients at the sixth and twelfth month after nephrectomy for unilateral disease. The prognosis is very poor in children with bilateral tumors. The mortality in this series is 100 per cent and a review of the reported series in the literature reveals mortality figures between 73 to 100 per cent. More aggressive therapy is indicated in the hope that survival can be increased. SUMMARY
A review of 130 cases of Wihns' tmnor diagnosed during a 14-year period has demonstrated the incidence of bilateral tumors in children to be 10.3 per cent. Clinical data is presented relative to the time of diagnosis of tumor in the second kidney. The suggestion that repeat intravenous pyelograms at 6 and 12 months as well as adequate examination of remaining kidney at the time of surgery would improve the diagnosis is derived from the data. The mortality
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in b i l a t e r a l t u m o r s in this series cent. A r e v i e w of the l i t e r a t u r e e m b r y o n i c c o n g e n i t a l origin for m o r . T h e q u e s t i o n of w h e t h e r or are bilateral p r i m a r y lesions or lesions has b e e n discussed.
September 1964
is 100 p e r favors a n W i l m s ' tun o t lesions metastatic
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7. Bodian, M., and White, L. R.: Personal communication to Rickham, P. P., quoted in Bilateral Wilms' tumor, Brit. J. Surg. 44: 492, 1957. 8. Martin, L. W., and Kleocker, R. J.: Bilateral nephroblastomas, Pediatrics 28: 101, 1961. 9. Walker, G.: Sarcoma of kidney in children: A critical review of the pathology, symptomatology, prognosis and operative treatment as seen in one hundred and forty-five cases, Ann. Surg. 26: 529, 1897. 10. Scott, L. S.: Bilateral Wilms' tumor, Brit. J. Surg. 42: 513, 1955. 11. Reiser, M. P., and Creevy, C. D.: Wihns' tumor, Urology Survey 2: 413, 1953. 12. Dean, A. L.: Wilms' tumor, New York j. Med. 45: 1213, 1945. 13. Kretsehner, W. C., and Hibbs, B. A.: Mixed tumors of kidney in infancy and childhood, Surg., Gynec. & Obst. 52: 1, 1931. 14. White, L. L. R.: Personal communication to Rickham, P. P., Quoted in Bilateral Wilms' tumors, Brit. J. Surg. 44: 492, 1957. 15. Gross, R. E., and Neuhauser, E. B. D.: Treatment of mixed tumors of the kidney in childhood, Pediatrics 6: 843, 1950. 16. Rickham, P. P.: Bilateral Wilms' tumor, Brit. J. Surg. 44: 492, 1957.