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Nephroblastoma in Adults
0022-534 7/84/1321-0108$02.00 /00
THE
Vol. 132, July Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright© 1984 by The Williams & Wilkins Co.
NEPHROBLASTOMA IN ADULTS DAVID R. ROTH, JOHN WRIGHT, C. DAVID CAWOOD, JR.
AND
DONALD W. PRANKE
From the Roy and Lillie Cullen Department of Urologic Research, Department of Urology, Baylor College of Medicine and Department of Pathology, St. Luke's Episcopal Hospital, Houston, Texas
ABSTRACT
Nephroblastoma, or Wilms tumor, is the most common renal neoplasm in children and accounts for approximately a fifth of all malignant growths in this age group. However, the incidence of Wilms tumor in adults is much less common, with less than 200 cases having been reported in the literature. In addition, since there are at least 53 synonyms for this tumor an adequate computer search for articles relating to this subject is difficult. Because of the scarcity of this disease in adults definite treatment modalities have not been accepted thoroughly until recently. The rationale for the present treatment modalities is based largely on the National Wilms Tumor Study groups 1 to 3. We present radiologic and histologic findings of this tumor in 2 additional cases. The current treatment modalities, consisting of chemotherapy with or without adjunctive radiotherapy, are discussed. Nephroblastoma traditionally is a disease of young children, with 85 per cent of the cases being reported in individuals <6 years old. 1 The first case was reported in the early nineteenth century and, until recently, the outlook for individuals with this disease has been dismal, with cure rates ranging from Oto 30 per cent. 2- 5 With the advent of modern chemotherapy and the National Wilms Tumor Study groups the over-all survival rate has increased to approximately 85 per cent during 3 years. 6 These children are treated aggressively with either a combination of radiotherapy and chemotherapy or chemotherapy alone, depending on the stage of the disease. Prognosis in children has been shown to be related to histology and stage. In the first National Wilms Tumor Study prognosis was believed to be related to age. However, in subsequent study groups it has been shown that age is not important once aggressive chemotherapy is used. However, nephroblastomas in adults are much less common, accounting for <1 per cent of Wilms tumors. Because of the scarcity of this lesion treatment protocols on the scale of the National Wilms Tumor Study have not been done. Since the advent of the chemotherapeutic era only a handful of cases has been treated aggressively in an attempt to improve the dismal results. Still, the prognosis for adults with this disease is markedly worse than that for children.7 Accordingly, an aggressive course of combination chemotherapy and radiotherapy has been suggested as treatment for these individuals. 7- 9 CASE REPORTS
Case 1. A 46-year-old white woman presented in June 1980 with a 2-week history of right upper quadrant and flank pain associated with a 10-pound weight loss. The patient specifically denied hematuria. Examination was unremarkable, with no evidence of a flank mass. The patient promptly sought medical attention for this symptom and an excretory urogram (IVP) revealed a large right renal mass. Arteriography showed an 11 cm. right lateral renal mass with neovascularity. Epinephrine injections were consistent with tumor vessels. No arteriovenous malformations were noted despite significant vascularity (fig. 1). Preoperative diagnosis was renal cell carcinoma and appropriate preoperative evaluation revealed no evidence of metastatic spread. Right radical nephrectomy was performed. A large, ovoid mass measuring 8 cm. in diameter occupied the lower pole of the kidney. No perforation through the capsule was encountered. The tumor did not involve vascular structures Accepted for publication March 20, 1984.
FIG. 1. Case 1. Arteriogram with epinephrine injection shows typical tumor vessels unaffected by epinephrine.
or the collecting system. Microscopically, the tumor was formed of rounded masses of polygonal cells with high nuclear-cytoplasmic ratios (fig. 2). The nuclei were hyperchromatic with evenly dispersed chromatin and occasional prominent nucleoli. Mitotic figures averaged 1 per high power field. Strands and sheets of basophilic cells alternated with broad bands of dense fibrous connective tissue with focal areas showing myxomatous change. Individual aggregates of tumor cells showed a varying mixture of a sheet-like arrangement of tumor cells alternating with areas of gland formation. The glands tended to be organized around the periphery, whereas the sheets tended to be placed centrally. No glomeruloid structures were encountered. Convalescence was uneventful. The patient began a course of chemotherapy in September, consisting of 500 mg. actinomycin D daily for 5 days every 6 weeks and 2 mg. vincristine every week for 7 weeks. Chemotherapy was completed in March 108
109 and intermediate clear with a central mulation of epithelioid Unlike normal glomeruli central structure was not vascularized. An additional difference from case 1 was that the blastematous elements proliferated focally in a monomorphous fashion to the exclusion of the tubular and stromal components. Light microscopic findings in both cases were typical for Wilms tumor. Convalescence was uneventful. Chemotherapy, consisting of vincristine, doxorubicin and actinomycin D, in association with radiotherapy to the tumor bed is planned as recommended in more recent studies. DISCUSSION
FIG. 2. Case L Blastema and tubules. Reduced from X400
FIG. 3. Case 2. A, IVP shows large left lower pole renal mass displacing and distorting collecting system. B, renal arteriogram shows avascular mass with abnormal parasitic vessels draping along its periphery.
1981. Since then the patient has been seen regularly. Appropriate laboratory and radiologic evaluations, including computerized tomography scan, bone scan, serum electrolytes, liver function tests, complete blood counts and IVPs, have been within normal limits. The patient has done well for 3 years and appears to be cured. Case 2. A 32-year-old white woman presented in July 1983 after an episode of gross, painless hematuria. On physical examination the was noted to have a left renal mass. An IVP showed superior displacement and distortion of the collecting system. Arteriography revealed an 11 X 9 cm. avascular lesion in the left lower pole. Abnormal parasitic vessels Metastatic evalwere found draping around the mass (fig. uation, including liver function tests and chest x-rays, was within normal limits. Preoperative diagnosis was renal cell carcinoma, and left thoracoabdominal incision and radical nephrectomy were performed. As in case 1 a Wilms tumor was not suspected at operation and biopsy of the contralateral kidney (as recommended for childhood Wilms tumor) was not performed. The multilobulated tumor originated at the inferior pole of the kidney and varied in color from white to yellow-tan. The maximum dimensions of the tumor were 13 X 7.5 X 7.5 cm. Probable breach of the capsule was encountered posteriorly. Microscopically, the tumor was similar to that described in case L One difference was the presence of abundant glomeruloid structures (fig. 4) that mimicked normal glomeruli, being approximately the same size, and containing a peripheral capsule
N ephroblastoma originates from the totipotential cells of the metanephrogenic blastema. 10 The neoplasm occurs most commonly in young children, although it has been reported in all age groups extending to the ninth decade of life. 11 The occurrence of this tumor in adults is unusual, with <200 cases being reported in the literature. Recently, Kilton and associates suggested rigid criteria for an adult Wilms tumor: 1) primary renal neoplasm, 2) primitive blastematous spindle or round cell component, 3) formation of abortive or embryonal, tubular or glomeruloid structures, 4) no area of tumor diagnostic of a renal cell tumor, 5) pictorial confirmation of histology and 6) age > 15 years. 9 With these criteria they reported only 35 cases of well documented adult Wilms tumor. Presenting signs and symptoms included pain in approximately two-thirds of the cases, while a mass and/or hematuria was present in 25 of 33 patients. Additionally, some patients presented with either sciatica or constitutional symptoms. The staging of the tumor conforms with the National Wilms Tumor Study: group 1-tumor limited to the kidney and excised completely, group 2-tumor extending beyond the kidney but resected completely, group 3-residual nonhematogenous tumor confined to the abdomen, group 4-hematogenous metastases and group 5-bilateral nephroblastoma. Preoperative staging of this tumor is similar to that of renal cell carcinoma. No single test distinguishes one disease from the other. An IVP often will suggest a mass. Calcification will be present in 10 to 30 per cent of the individuals 12 and always is subtle, never extensive or dense. In approximately half of these individuals calcification is curvilinear in nature and in the others it is punctate. Arteriography often is performed in an adult with a solid renal mass. Unfortunately, few, if any, features will distinguish a Wilms tumor from a renal cell carcinoma. Both tumors may be hypovascular, avascular or hypervascular. One of the few distinguishing characteristics may be fine nodularity of vessels as described by Farah and Lofstrom. 13 Additionally, no arteriovenous malformations have been found in patients with Wilms tumors despite rich vascularity. 18 An operation
FIG. 4. Case 2. Note blastema, tubules, glomeruloid structures and stroma. Reduced from XlOO.
110
ROTH AND ASSOCIATES
Statistics showing poorer over-all and stage-for-stage survival for adults compared to children7
Over-all survival: 2 yrs. 3 yrs. 3-yr. survival: Low stage Ca Stage IV
Adults
Children
(%)
(%)
54 24
75 74
48
87 53
11
usually is performed on the basis of suspicion of a renal cell carcinoma. As in renal cell carcinoma, the lungs are the most common site of metastases. Other sites have included the liver, bone, skin, bladder, sigmoid colon, orbit brain, spinal cord and contralateral kidney. 8 Therefore, the preoperative metastatic evaluation is the same for either neoplasm. Radical nephrectomy often is performed without considering biopsy of the contralateral kidney. Childhood Wilms tumor is known to occur bilaterally in 6 to 10 per cent of the cases. 14• 15 However, only 1 case of bilateral Wilms tumor has been reported in an adult who presented with widely metastatic disease, with the diagnosis being made at autopsy. 16 Accordingly, it is doubtful that biopsy of the contralateral kidney is indicated in adults with Wilms tumor. The prognosis of patients with Wilms tumor before the era of chemotherapy was dismal, with cure rates ranging from O to 27 per cent. 2 This trend persisted through the mid 1960s. At that time the National Wilms Tumor Study was incorporated to arrive at a comprehensive method of treating these individuals. Current statistics for children with Wilms tumor are encouraging, with cure rates approaching 95 per cent. 12 Unfortunately, adults with Wilms tumor have not fared as well. Recent series on combination chemotherapy and radiotherapy have revealed cure rates of approximately 25 per cent. 7 Even with aggressive therapy survival lags significantly behind that for children with Wilms tumor. Adults present with more advanced tumors, with 50 per cent having either stage 3 or 4 disease. 7 This finding is in contradistinction to children, of whom approximately a fifth will present with stage 3 and approximately 11 per cent with stage 4 disease. 17 Additionally, there continues to be a significant mortality rate for adults with Wilms tumors >2 years. This is not the case for children in whom >90 per cent of recurrences are noted within the first 2 years. 6 • 18 Therefore, in children but not adults 2-year survival is a reasonable approximation of total survival. In the initial Wilms Tumor Study Group age was suggested as one of the important determinants of prognosis, along with histology and stage. 18 However, the second Wilms Tumor Study Group did not confirm this finding and it is believed that with aggressive chemotherapy age no longer has a role in the determination of prognosis. 17 It may be that the poorer prognosis in adults relates to a higher percentage of patients with unfavorable histology. 18 Unfortunately, the adult subsection of the National Wilms Tumor Study did not address this parameter. Because of the rarity of this lesion definite treatment modalities have not been accepted firmly. In 1980 Babaian and associates suggested treatment based on the National Wilms Tumor Study protocol. 8 With these guidelines they reported on 3 patients: 1 had no evidence of tumor after 24 months, 1 died of disease at 3 months and 1 died of side effects of the chemotherapy 5 months postoperatively. On the other hand, Kilton and associates suggested the same treatment for all stages, that is an operation for diagnosis and debulking with definition of the tumor bed for radiation. 9 They believe that all patients should receive 3,500 to 4,000 rad radiotherapy with additional whole lung radiotherapy if pulmonary metastases are present. Adjunctive chemotherapy, including vincristine and actinomycin D, should be given as with childhood Wilms tumor. The rationale is that radiotherapy has documented activity against Wilms tumors and, therefore,
should be used in all patients. Based on the adult subgroup of the National Wilms Tumor Study, D'Angio thought that aggressive chemotherapy in conjunction with radiotherapy is necessary. 19 It is known that adults have a poorer prognosis stage-for-stage and over-all compared to children (see table). Radiotherapy in adults is less morbid dose-for-dose than in children and, although there are no clear data to guide a dosage schedule for these patients, it is suggested that the highest dose reported in the National Wilms Tumor Study (that is 4,500 rad at 180 rad per day to fields as outlined in the study) should be used. In addition, D'Angio thought that 3 drugs should be used, since the National Wilms Tumor Study showed improved results when doxorubicin was added to vincristine and actinomycin D. 19 To date aggressive treatment with combination chemotherapy and radiotherapy is indicated in adults with Wilms tumor. The prognosis for adults with nephroblastoma lags behind that in children and, accordingly, aggressive chemotherapy with vincristine, doxorubicin and actinomycin D should be used. Cases of this disease, including histology, should be reported to the National Wilms Tumor Study groups so that effective therapy can be determined and the controversy concerning current treatment modalities can be resolved. REFERENCES 1. Exelby, P. R.: Retroperitoneal malignant tumors: Wilms' tumor
and neuroblastoma. Surg. Clin. N. Amer., 61: 1219, 1981. 2. Klapproth, H. J .: Wilms' tumor: a report of 45 cases and an analysis of 1,351 cases reported in the world literature from 1940 to 1958. J. Urol., 81: 633, 1959. 3. Culp, 0. S. and Hartman, F. W.: Mesoblastic nephroma in adults: a clinicopathologic study of Wilms' tumors and related renal neoplasms. J. Urol., 60: 552, 1948. 4. Foot, N. C., Humphreys, G. A. and Whitmore, W. F.: Renal tumors: pathology and prognosis in 295 cases. J. Urol., 66: 190, 1951. 5. Smith, K. H.: Wilms' tumour in the adult. Brit. J. Surg., 47: 397, 1960. 6. Beckwith, J. B. and Palmer, N. F.: Histopathology and prognosis of Wilms tumors: results from the First National Wilms' Tumor Study. Cancer, 41: 1937, 1978. 7. Byrd, R. L., Evans, A. E. and D'Angio, G. J.: Adult Wilms tumor: effect of combined therapy on survival. J. Urol., 127: 648, 1982. 8. Babaian, R. J., Skinner, D. G. and Waisman, J.: Wilm's tumor in the adult patient: diagnosis, management, and review of the world medical literature. Cancer, 45: 1713, 1980. 9. Kilton, L., Matthews, M. J. and Cohen, M. H.: Adult Wilms tumor: a report of prolonged survival and review of literature. J. Urol., 124: 1, 1980. 10. Denes, F. T., Nahas, W. C. and Alfer, V.: Adult Wilms tumor. Treatment with surgery, radiotherapy, and chemotherapy. Urology, 19: 187, 1982. 11. Kaushik, S. P., Sachdeva, H. S. and Dutta, B. N.: Renal embryoma in the adult. Ann. Surg., 38: 468, 1972. 12. Cope, J. R., Roylance, J. and Gordon, I. R.: The radiologic features of Wilms' tumour. Clin. Rad., 23: 331, 1972. 13. Farah, J. and Lofstrom, J. E.: Angiography of Wilms's tumor. Radiology, 90: 775, 1968. 14. Cromie, W. J. and Duckett, J. W.: Wilms' tumor. Weekly Urology Update Series, vol. 1, lesson 21, 1978. 15. Malcolm, A. W., Jaffe, N., Folkman, M. J. and Cassady, J. R.: Bilateral Wilm's tumor. Int. J. Rad. Oncol. Biol. Phys., 6: 167, 1980. 16. Bettendorf, U.: Doppelseitiger Wilms-Tumor bei einem Erwachsenen. Zentralbl. Allg. Path., 117: 394, 1973. 17. D'Angio, G. J., Evans, A., Breslow, N., Beckwith, B., Bishop, H., Farewell, V., Goodwin, W., Leape, L., Palmer, N., Sinks, L., Sutow, W., Tefft, M. and Wolff, J.: The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study. Cancer, 47: 2302, 1981. 18. Breslow, N. E., Palmer, N. F., Hill, L. R., Buring, J. and D'Angio, G. J.: Wilms' tumor: prognostic factors for patients without metastases at diagnosis: results from the First National Wilms' Tumor Study. Cancer, 41: 1577, 1978. 19. D'Angio, G. J.: Wilms' tumor. Curr. Concepts Oncol., 4: 3, summer 1982.
THE
Vol. 132, July Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright© 1984 by The Williams & Wilkins Co.
NEPHROBLASTOMA IN ADULTS DAVID R. ROTH, JOHN WRIGHT, C. DAVID CAWOOD, JR.
AND
DONALD W. PRANKE
From the Roy and Lillie Cullen Department of Urologic Research, Department of Urology, Baylor College of Medicine and Department of Pathology, St. Luke's Episcopal Hospital, Houston, Texas
ABSTRACT
Nephroblastoma, or Wilms tumor, is the most common renal neoplasm in children and accounts for approximately a fifth of all malignant growths in this age group. However, the incidence of Wilms tumor in adults is much less common, with less than 200 cases having been reported in the literature. In addition, since there are at least 53 synonyms for this tumor an adequate computer search for articles relating to this subject is difficult. Because of the scarcity of this disease in adults definite treatment modalities have not been accepted thoroughly until recently. The rationale for the present treatment modalities is based largely on the National Wilms Tumor Study groups 1 to 3. We present radiologic and histologic findings of this tumor in 2 additional cases. The current treatment modalities, consisting of chemotherapy with or without adjunctive radiotherapy, are discussed. Nephroblastoma traditionally is a disease of young children, with 85 per cent of the cases being reported in individuals <6 years old. 1 The first case was reported in the early nineteenth century and, until recently, the outlook for individuals with this disease has been dismal, with cure rates ranging from Oto 30 per cent. 2- 5 With the advent of modern chemotherapy and the National Wilms Tumor Study groups the over-all survival rate has increased to approximately 85 per cent during 3 years. 6 These children are treated aggressively with either a combination of radiotherapy and chemotherapy or chemotherapy alone, depending on the stage of the disease. Prognosis in children has been shown to be related to histology and stage. In the first National Wilms Tumor Study prognosis was believed to be related to age. However, in subsequent study groups it has been shown that age is not important once aggressive chemotherapy is used. However, nephroblastomas in adults are much less common, accounting for <1 per cent of Wilms tumors. Because of the scarcity of this lesion treatment protocols on the scale of the National Wilms Tumor Study have not been done. Since the advent of the chemotherapeutic era only a handful of cases has been treated aggressively in an attempt to improve the dismal results. Still, the prognosis for adults with this disease is markedly worse than that for children.7 Accordingly, an aggressive course of combination chemotherapy and radiotherapy has been suggested as treatment for these individuals. 7- 9 CASE REPORTS
Case 1. A 46-year-old white woman presented in June 1980 with a 2-week history of right upper quadrant and flank pain associated with a 10-pound weight loss. The patient specifically denied hematuria. Examination was unremarkable, with no evidence of a flank mass. The patient promptly sought medical attention for this symptom and an excretory urogram (IVP) revealed a large right renal mass. Arteriography showed an 11 cm. right lateral renal mass with neovascularity. Epinephrine injections were consistent with tumor vessels. No arteriovenous malformations were noted despite significant vascularity (fig. 1). Preoperative diagnosis was renal cell carcinoma and appropriate preoperative evaluation revealed no evidence of metastatic spread. Right radical nephrectomy was performed. A large, ovoid mass measuring 8 cm. in diameter occupied the lower pole of the kidney. No perforation through the capsule was encountered. The tumor did not involve vascular structures Accepted for publication March 20, 1984.
FIG. 1. Case 1. Arteriogram with epinephrine injection shows typical tumor vessels unaffected by epinephrine.
or the collecting system. Microscopically, the tumor was formed of rounded masses of polygonal cells with high nuclear-cytoplasmic ratios (fig. 2). The nuclei were hyperchromatic with evenly dispersed chromatin and occasional prominent nucleoli. Mitotic figures averaged 1 per high power field. Strands and sheets of basophilic cells alternated with broad bands of dense fibrous connective tissue with focal areas showing myxomatous change. Individual aggregates of tumor cells showed a varying mixture of a sheet-like arrangement of tumor cells alternating with areas of gland formation. The glands tended to be organized around the periphery, whereas the sheets tended to be placed centrally. No glomeruloid structures were encountered. Convalescence was uneventful. The patient began a course of chemotherapy in September, consisting of 500 mg. actinomycin D daily for 5 days every 6 weeks and 2 mg. vincristine every week for 7 weeks. Chemotherapy was completed in March 108
109 and intermediate clear with a central mulation of epithelioid Unlike normal glomeruli central structure was not vascularized. An additional difference from case 1 was that the blastematous elements proliferated focally in a monomorphous fashion to the exclusion of the tubular and stromal components. Light microscopic findings in both cases were typical for Wilms tumor. Convalescence was uneventful. Chemotherapy, consisting of vincristine, doxorubicin and actinomycin D, in association with radiotherapy to the tumor bed is planned as recommended in more recent studies. DISCUSSION
FIG. 2. Case L Blastema and tubules. Reduced from X400
FIG. 3. Case 2. A, IVP shows large left lower pole renal mass displacing and distorting collecting system. B, renal arteriogram shows avascular mass with abnormal parasitic vessels draping along its periphery.
1981. Since then the patient has been seen regularly. Appropriate laboratory and radiologic evaluations, including computerized tomography scan, bone scan, serum electrolytes, liver function tests, complete blood counts and IVPs, have been within normal limits. The patient has done well for 3 years and appears to be cured. Case 2. A 32-year-old white woman presented in July 1983 after an episode of gross, painless hematuria. On physical examination the was noted to have a left renal mass. An IVP showed superior displacement and distortion of the collecting system. Arteriography revealed an 11 X 9 cm. avascular lesion in the left lower pole. Abnormal parasitic vessels Metastatic evalwere found draping around the mass (fig. uation, including liver function tests and chest x-rays, was within normal limits. Preoperative diagnosis was renal cell carcinoma, and left thoracoabdominal incision and radical nephrectomy were performed. As in case 1 a Wilms tumor was not suspected at operation and biopsy of the contralateral kidney (as recommended for childhood Wilms tumor) was not performed. The multilobulated tumor originated at the inferior pole of the kidney and varied in color from white to yellow-tan. The maximum dimensions of the tumor were 13 X 7.5 X 7.5 cm. Probable breach of the capsule was encountered posteriorly. Microscopically, the tumor was similar to that described in case L One difference was the presence of abundant glomeruloid structures (fig. 4) that mimicked normal glomeruli, being approximately the same size, and containing a peripheral capsule
N ephroblastoma originates from the totipotential cells of the metanephrogenic blastema. 10 The neoplasm occurs most commonly in young children, although it has been reported in all age groups extending to the ninth decade of life. 11 The occurrence of this tumor in adults is unusual, with <200 cases being reported in the literature. Recently, Kilton and associates suggested rigid criteria for an adult Wilms tumor: 1) primary renal neoplasm, 2) primitive blastematous spindle or round cell component, 3) formation of abortive or embryonal, tubular or glomeruloid structures, 4) no area of tumor diagnostic of a renal cell tumor, 5) pictorial confirmation of histology and 6) age > 15 years. 9 With these criteria they reported only 35 cases of well documented adult Wilms tumor. Presenting signs and symptoms included pain in approximately two-thirds of the cases, while a mass and/or hematuria was present in 25 of 33 patients. Additionally, some patients presented with either sciatica or constitutional symptoms. The staging of the tumor conforms with the National Wilms Tumor Study: group 1-tumor limited to the kidney and excised completely, group 2-tumor extending beyond the kidney but resected completely, group 3-residual nonhematogenous tumor confined to the abdomen, group 4-hematogenous metastases and group 5-bilateral nephroblastoma. Preoperative staging of this tumor is similar to that of renal cell carcinoma. No single test distinguishes one disease from the other. An IVP often will suggest a mass. Calcification will be present in 10 to 30 per cent of the individuals 12 and always is subtle, never extensive or dense. In approximately half of these individuals calcification is curvilinear in nature and in the others it is punctate. Arteriography often is performed in an adult with a solid renal mass. Unfortunately, few, if any, features will distinguish a Wilms tumor from a renal cell carcinoma. Both tumors may be hypovascular, avascular or hypervascular. One of the few distinguishing characteristics may be fine nodularity of vessels as described by Farah and Lofstrom. 13 Additionally, no arteriovenous malformations have been found in patients with Wilms tumors despite rich vascularity. 18 An operation
FIG. 4. Case 2. Note blastema, tubules, glomeruloid structures and stroma. Reduced from XlOO.
110
ROTH AND ASSOCIATES
Statistics showing poorer over-all and stage-for-stage survival for adults compared to children7
Over-all survival: 2 yrs. 3 yrs. 3-yr. survival: Low stage Ca Stage IV
Adults
Children
(%)
(%)
54 24
75 74
48
87 53
11
usually is performed on the basis of suspicion of a renal cell carcinoma. As in renal cell carcinoma, the lungs are the most common site of metastases. Other sites have included the liver, bone, skin, bladder, sigmoid colon, orbit brain, spinal cord and contralateral kidney. 8 Therefore, the preoperative metastatic evaluation is the same for either neoplasm. Radical nephrectomy often is performed without considering biopsy of the contralateral kidney. Childhood Wilms tumor is known to occur bilaterally in 6 to 10 per cent of the cases. 14• 15 However, only 1 case of bilateral Wilms tumor has been reported in an adult who presented with widely metastatic disease, with the diagnosis being made at autopsy. 16 Accordingly, it is doubtful that biopsy of the contralateral kidney is indicated in adults with Wilms tumor. The prognosis of patients with Wilms tumor before the era of chemotherapy was dismal, with cure rates ranging from O to 27 per cent. 2 This trend persisted through the mid 1960s. At that time the National Wilms Tumor Study was incorporated to arrive at a comprehensive method of treating these individuals. Current statistics for children with Wilms tumor are encouraging, with cure rates approaching 95 per cent. 12 Unfortunately, adults with Wilms tumor have not fared as well. Recent series on combination chemotherapy and radiotherapy have revealed cure rates of approximately 25 per cent. 7 Even with aggressive therapy survival lags significantly behind that for children with Wilms tumor. Adults present with more advanced tumors, with 50 per cent having either stage 3 or 4 disease. 7 This finding is in contradistinction to children, of whom approximately a fifth will present with stage 3 and approximately 11 per cent with stage 4 disease. 17 Additionally, there continues to be a significant mortality rate for adults with Wilms tumors >2 years. This is not the case for children in whom >90 per cent of recurrences are noted within the first 2 years. 6 • 18 Therefore, in children but not adults 2-year survival is a reasonable approximation of total survival. In the initial Wilms Tumor Study Group age was suggested as one of the important determinants of prognosis, along with histology and stage. 18 However, the second Wilms Tumor Study Group did not confirm this finding and it is believed that with aggressive chemotherapy age no longer has a role in the determination of prognosis. 17 It may be that the poorer prognosis in adults relates to a higher percentage of patients with unfavorable histology. 18 Unfortunately, the adult subsection of the National Wilms Tumor Study did not address this parameter. Because of the rarity of this lesion definite treatment modalities have not been accepted firmly. In 1980 Babaian and associates suggested treatment based on the National Wilms Tumor Study protocol. 8 With these guidelines they reported on 3 patients: 1 had no evidence of tumor after 24 months, 1 died of disease at 3 months and 1 died of side effects of the chemotherapy 5 months postoperatively. On the other hand, Kilton and associates suggested the same treatment for all stages, that is an operation for diagnosis and debulking with definition of the tumor bed for radiation. 9 They believe that all patients should receive 3,500 to 4,000 rad radiotherapy with additional whole lung radiotherapy if pulmonary metastases are present. Adjunctive chemotherapy, including vincristine and actinomycin D, should be given as with childhood Wilms tumor. The rationale is that radiotherapy has documented activity against Wilms tumors and, therefore,
should be used in all patients. Based on the adult subgroup of the National Wilms Tumor Study, D'Angio thought that aggressive chemotherapy in conjunction with radiotherapy is necessary. 19 It is known that adults have a poorer prognosis stage-for-stage and over-all compared to children (see table). Radiotherapy in adults is less morbid dose-for-dose than in children and, although there are no clear data to guide a dosage schedule for these patients, it is suggested that the highest dose reported in the National Wilms Tumor Study (that is 4,500 rad at 180 rad per day to fields as outlined in the study) should be used. In addition, D'Angio thought that 3 drugs should be used, since the National Wilms Tumor Study showed improved results when doxorubicin was added to vincristine and actinomycin D. 19 To date aggressive treatment with combination chemotherapy and radiotherapy is indicated in adults with Wilms tumor. The prognosis for adults with nephroblastoma lags behind that in children and, accordingly, aggressive chemotherapy with vincristine, doxorubicin and actinomycin D should be used. Cases of this disease, including histology, should be reported to the National Wilms Tumor Study groups so that effective therapy can be determined and the controversy concerning current treatment modalities can be resolved. REFERENCES 1. Exelby, P. R.: Retroperitoneal malignant tumors: Wilms' tumor
and neuroblastoma. Surg. Clin. N. Amer., 61: 1219, 1981. 2. Klapproth, H. J .: Wilms' tumor: a report of 45 cases and an analysis of 1,351 cases reported in the world literature from 1940 to 1958. J. Urol., 81: 633, 1959. 3. Culp, 0. S. and Hartman, F. W.: Mesoblastic nephroma in adults: a clinicopathologic study of Wilms' tumors and related renal neoplasms. J. Urol., 60: 552, 1948. 4. Foot, N. C., Humphreys, G. A. and Whitmore, W. F.: Renal tumors: pathology and prognosis in 295 cases. J. Urol., 66: 190, 1951. 5. Smith, K. H.: Wilms' tumour in the adult. Brit. J. Surg., 47: 397, 1960. 6. Beckwith, J. B. and Palmer, N. F.: Histopathology and prognosis of Wilms tumors: results from the First National Wilms' Tumor Study. Cancer, 41: 1937, 1978. 7. Byrd, R. L., Evans, A. E. and D'Angio, G. J.: Adult Wilms tumor: effect of combined therapy on survival. J. Urol., 127: 648, 1982. 8. Babaian, R. J., Skinner, D. G. and Waisman, J.: Wilm's tumor in the adult patient: diagnosis, management, and review of the world medical literature. Cancer, 45: 1713, 1980. 9. Kilton, L., Matthews, M. J. and Cohen, M. H.: Adult Wilms tumor: a report of prolonged survival and review of literature. J. Urol., 124: 1, 1980. 10. Denes, F. T., Nahas, W. C. and Alfer, V.: Adult Wilms tumor. Treatment with surgery, radiotherapy, and chemotherapy. Urology, 19: 187, 1982. 11. Kaushik, S. P., Sachdeva, H. S. and Dutta, B. N.: Renal embryoma in the adult. Ann. Surg., 38: 468, 1972. 12. Cope, J. R., Roylance, J. and Gordon, I. R.: The radiologic features of Wilms' tumour. Clin. Rad., 23: 331, 1972. 13. Farah, J. and Lofstrom, J. E.: Angiography of Wilms's tumor. Radiology, 90: 775, 1968. 14. Cromie, W. J. and Duckett, J. W.: Wilms' tumor. Weekly Urology Update Series, vol. 1, lesson 21, 1978. 15. Malcolm, A. W., Jaffe, N., Folkman, M. J. and Cassady, J. R.: Bilateral Wilm's tumor. Int. J. Rad. Oncol. Biol. Phys., 6: 167, 1980. 16. Bettendorf, U.: Doppelseitiger Wilms-Tumor bei einem Erwachsenen. Zentralbl. Allg. Path., 117: 394, 1973. 17. D'Angio, G. J., Evans, A., Breslow, N., Beckwith, B., Bishop, H., Farewell, V., Goodwin, W., Leape, L., Palmer, N., Sinks, L., Sutow, W., Tefft, M. and Wolff, J.: The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study. Cancer, 47: 2302, 1981. 18. Breslow, N. E., Palmer, N. F., Hill, L. R., Buring, J. and D'Angio, G. J.: Wilms' tumor: prognostic factors for patients without metastases at diagnosis: results from the First National Wilms' Tumor Study. Cancer, 41: 1577, 1978. 19. D'Angio, G. J.: Wilms' tumor. Curr. Concepts Oncol., 4: 3, summer 1982.