Pediatric Radiology
•
Angiography and Histopathology of Nephroblastomatosis 1
Robert E. Brantley, M.D., and Laurence R. Simson, Jr., M.D. A case of nephroblastomatosis (diffuse bilateral Wilms' tumor) in association with congenital hemihypertrophy is reported and the angiographic findings presented. Serial angiograms and tissue biopsies documented the transition from nodular renal blastema to Wilms' tumor. INDEX TERMS:
Kidney neoplasms. Kidney neoplasms, angiography
Radiology 120: 151-154, July 1976
ILMS - TUMOR (nephroblastoma) has been reported to . be bilateral in 3-11 % of cases (10). Whether unilateral or bilateral, the masses are generally well defined. Rarely, however, there may be diffuse involvement of both kidneys without a discrete or dominant local mass, a condition termed "nephroblastomatosis" by Hou and Holman (3). We wish to describe the angiographic findings in one such case, together with the histopathological correlation provided by serial tissue biopsies. The evolution from so-called "nodular renal blastema" (1) to diffuse bilateral Wilms' tumor is illustrated.
W
CASE REPORT A white female infant weighing 2.3 kg (5 lb. 2 oz.) was delivered spontaneously at 34 weeks gestation. Hemihypertrophy was evident, involving primarily the left leg and thigh and to a lesser degree the left arm and hemithorax. Hypertrophy of the right side of the tongue made it somewhat difficult for her to swallow. Associated anomalies included clitoral prominence with sexual ambiguity, a relatively small head, weakness of the abdominal musculature, and patent ductus arteriosus. Both kidneys were palpable and abnormally large, particularly on the left. Because of the association of Wilms' tumor with hemihypertrophy (8), serial urograms were obtained soon after birth and at approximately 3-month intervals thereafter. Cardiac catherization and abdominal aortography were performed when she was 7 weeks old. Although the nephrogram phase was not optimal for renal visualization (Fig. 1), it did show a distinct corticomedullary zone outlining most of the perimeter of the right kidney. At 15 weeks, an open biopsy of the left kidney revealed multiple tiny aggregates of primitive cells beneath the renal capsule (Fig. 2), so-called "nodular renal blastema" (1). When the patient was one year old, a progress urogram was interpreted as showing further calyceal deformity in addition to bilateral renal enlargement. Angiography demonstrated multiple areas of slight vascular displacement; however, tumor vessels were questionably present in only one nodular area in the right upper pole. The right kidney had a single renal artery, while the left had a dual supply. Selective injection of each vessel (Fig. 3) yielded a nephrogram with innumerable defects, not unlike a polycystic kidney. A peculiar rind of subcapsular tissue measuring 0.5-1.2 em was present at the perimeter of each kidney but exhibited no nephrogram effect. The inner aspect of each rind was irregularly contoured, but the outer margin was quite smooth. Both kidneys were clearly larger than normal.
Fig. 1. Nephrogram phase of the abdominal aortogram at 7 weeks demonstrates the intact upper pole and lateral boundaries of the right kidney (arrowheads). The left kidney is obscured by intestinal gas. Fig. 2. Biopsy specimen of the left kidney, obtained at 15 weeks of age. Nodular aggregates of primitive cells ("nodular renal blastema") are seen immediately beneath the capsular connective tissue, together with a few mitotic figures. The adjacent glomeruli and tubules are normal for a child this age. (XBO)
The roentgenographic differential diagnosis included diffuse infiltrating neoplasm and adult-type polycystic kidney disease. In view of the histopathological pattern seen in the initial renal biopsy, it was concluded that the islands of renal blastema cells had grown dramatically and coalesced. Since such uncontrolled growth is characteristic of a malignant neoplasm, a roentgenographic diagnosis of diffuse bilateral Wilms' tumor was submitted. When the patient was admitted to the hospital for open renal biopsy, she was found to be hypertensive, with blood pressures ranging up to 240/120. At operation, both kidneys were grossly enlarged, notably the left. The left kidney was frankly nodular, while the right had a fissured surface. Tissue
1 From the Departments of Radiology (R. E. B.) and Laboratories (L. R. S.), Edward W. Sparrow Hospital, Lansing, Mich. Accepted for publication in November 1975. sjh
151
Fig. 3. A and B. Selective right and main left renal arteriograms at one year of age. The kidneys are enlarged, with multiple areas of mild vessel displacement. A tumor nodule is seen in the upper pole (open arrows). C and D. Right and left nephrogram phases show innumerable defects, with an unopacified sheath of subcapsular tumor (arrows) encompassing both kidneys.
152
Vol. 120
ANGIOGRAPHY AND HISTOPATHOLOGY OF NEPHROBLASTOMATOSIS
Fig. 4. A. Biopsy specimen of the left kidney at one year. Sheets of slightly elongated primitive cells, resembling renal blastema cells, are associated with tubules lined by columnar epithelium. This biphasic pattern is characteristic of Wilms' tumor (nephroblastoma). (X80) B. Biopsy specimen of the right kidney at one year. This undifferentiated area of Wilms' tumor illustrates the high mitotic rate seen throughout the biopsy material. (X 128)
from both kidneys had a morphologic pattern diagnostic of Wilms' tumor (Fig. 4). The patient has been treated with actinomycin 0 and vincristine. Selective renal angiography at 22 months of age showed a bilateral reduction in renal size and only minimal residual cortical defects (Fig. 5). At this writing, the child, now 27 months old, remains well and is free of demonstrable metastatic neoplasm. DISCUSSION The roentgenographic distinction in this case was between infiltrating malignant neoplasm and adult-type polycystic renal disease. The possibility of diagnostic confusion has been cited previously (2). In this case the correct diagnosis was possible because the progression of nodular renal blastema to nephroblastoma could be inferred. It has long been thought that Wilms' tumor evolves from the metanephric blastema (6); this concept has been strongly supported by the experimental work of Javadpour and Bush (5), who observed the development of such tumors following transplantation of renal blastema in adult mice. It is not surprising, therefore, that the tiny islands of renal blastema tissue observed on initial biopsy should grow and coalesce to form diffuse Wilms' tumor. The hypertension which developed in this patient was far
153
Pediatric Radiology
Fig. 5. Selective right renal angiogram at 22 months of age, following chemotherapy, indicates reduction of renal size and considerable return toward normal renal architecture. The left kidney showed similar improvement.
in excess of that explainable by the patent ductus arteriosus and was probably due to a renovascular hypertensive component. The peripheral rind of neoplasm sheathing both kidneys may have restricted renal blood flow, resulting in a situation analagous to the capsular scar-induced hypertension described by Page (7, 9). Following antihypertensive medication and a course of antitumor chemotherapy, which resulted in marked reduction of renal size to palpation, blood pressure stabilized at 115/60/50. Many authors have discussed the question of whether autochthonous foci or metastases account for the occasional bilaterality of Wilms' tumor (4). Clearly, in this case a multitude of discrete foci in each kidney coalesced to form bilateral primary tumors. Thus this case documents the evolution of nodular renal blastema to Wilms' tumor in terms of both gross anatomy (angiography) and histopathology. Department of Radiology Edward W. Sparrow Hospital 1215 E. Michigan Avenue P.O. Box 480 Lansing, Mich. 48902
REFERENCES 1. Bove KE, Koffler H, McAdams AJ: Nodular renal blastema. Definition and possible significance. Cancer 24:323-332, Aug 1969 2. Gyepes MT, Burko H: Diffuse bilateral Wilms' tumor simulating multicystic renal disease. Radiology 82: 1029-1 031, Jun 1964
154
ROBERT E. BRANTLEY AND LAURENCE
3. Hou LT, Holman RL: Bilateral nephroblastomatosis in a premature infant. J Pathol Bacteriol 82:249:-255, Oct 1961 4. Jagasia KH, Thurman WG, Pickett E, et al: Bilateral Wilms' tumors in children. J Pediatr 65:371-376, Sep 1964 5. Javadpour N, Bush 1M: Induction and treatment of Wilms' tumor by transplantation of renal blastema in a new experimental model. J UroI107:931-937, Jun 1972 6. Lucke B, Schlumberger HG: Tumors of the kidney, renal pelvis and ureter. Atlas of Tumor Pathology, Sect 8, Fasc 30. Washington DC, AFIP, 1957, P 80
R. SIMSON, JR.
July 1976
7. Marshall WH Jr, Castellino RA: Hypertension produced by constricting capsular renal lesions. ("Page" kidney). Radiology 101:561-565, Dec 1971 8. Miller RW, Fraumeni JF Jr, Manning MD: Association of Wilms' tumor with aniridia, hemihypertrophy and other congenital malformations. N Engl J Med 270:922-927,30 Apr 1964 9. Page IH: A method for producing persistent hypertension by cellophane. Science 89:273-274,24 Mar 1939 10. Ragab AH, Vietti TJ, Crist W, et al: Bilateral Wilms' tumor. A review. Cancer 30:983-988, Oct 1972
•
Angiography and Histopathology of Nephroblastomatosis 1
Robert E. Brantley, M.D., and Laurence R. Simson, Jr., M.D. A case of nephroblastomatosis (diffuse bilateral Wilms' tumor) in association with congenital hemihypertrophy is reported and the angiographic findings presented. Serial angiograms and tissue biopsies documented the transition from nodular renal blastema to Wilms' tumor. INDEX TERMS:
Kidney neoplasms. Kidney neoplasms, angiography
Radiology 120: 151-154, July 1976
ILMS - TUMOR (nephroblastoma) has been reported to . be bilateral in 3-11 % of cases (10). Whether unilateral or bilateral, the masses are generally well defined. Rarely, however, there may be diffuse involvement of both kidneys without a discrete or dominant local mass, a condition termed "nephroblastomatosis" by Hou and Holman (3). We wish to describe the angiographic findings in one such case, together with the histopathological correlation provided by serial tissue biopsies. The evolution from so-called "nodular renal blastema" (1) to diffuse bilateral Wilms' tumor is illustrated.
W
CASE REPORT A white female infant weighing 2.3 kg (5 lb. 2 oz.) was delivered spontaneously at 34 weeks gestation. Hemihypertrophy was evident, involving primarily the left leg and thigh and to a lesser degree the left arm and hemithorax. Hypertrophy of the right side of the tongue made it somewhat difficult for her to swallow. Associated anomalies included clitoral prominence with sexual ambiguity, a relatively small head, weakness of the abdominal musculature, and patent ductus arteriosus. Both kidneys were palpable and abnormally large, particularly on the left. Because of the association of Wilms' tumor with hemihypertrophy (8), serial urograms were obtained soon after birth and at approximately 3-month intervals thereafter. Cardiac catherization and abdominal aortography were performed when she was 7 weeks old. Although the nephrogram phase was not optimal for renal visualization (Fig. 1), it did show a distinct corticomedullary zone outlining most of the perimeter of the right kidney. At 15 weeks, an open biopsy of the left kidney revealed multiple tiny aggregates of primitive cells beneath the renal capsule (Fig. 2), so-called "nodular renal blastema" (1). When the patient was one year old, a progress urogram was interpreted as showing further calyceal deformity in addition to bilateral renal enlargement. Angiography demonstrated multiple areas of slight vascular displacement; however, tumor vessels were questionably present in only one nodular area in the right upper pole. The right kidney had a single renal artery, while the left had a dual supply. Selective injection of each vessel (Fig. 3) yielded a nephrogram with innumerable defects, not unlike a polycystic kidney. A peculiar rind of subcapsular tissue measuring 0.5-1.2 em was present at the perimeter of each kidney but exhibited no nephrogram effect. The inner aspect of each rind was irregularly contoured, but the outer margin was quite smooth. Both kidneys were clearly larger than normal.
Fig. 1. Nephrogram phase of the abdominal aortogram at 7 weeks demonstrates the intact upper pole and lateral boundaries of the right kidney (arrowheads). The left kidney is obscured by intestinal gas. Fig. 2. Biopsy specimen of the left kidney, obtained at 15 weeks of age. Nodular aggregates of primitive cells ("nodular renal blastema") are seen immediately beneath the capsular connective tissue, together with a few mitotic figures. The adjacent glomeruli and tubules are normal for a child this age. (XBO)
The roentgenographic differential diagnosis included diffuse infiltrating neoplasm and adult-type polycystic kidney disease. In view of the histopathological pattern seen in the initial renal biopsy, it was concluded that the islands of renal blastema cells had grown dramatically and coalesced. Since such uncontrolled growth is characteristic of a malignant neoplasm, a roentgenographic diagnosis of diffuse bilateral Wilms' tumor was submitted. When the patient was admitted to the hospital for open renal biopsy, she was found to be hypertensive, with blood pressures ranging up to 240/120. At operation, both kidneys were grossly enlarged, notably the left. The left kidney was frankly nodular, while the right had a fissured surface. Tissue
1 From the Departments of Radiology (R. E. B.) and Laboratories (L. R. S.), Edward W. Sparrow Hospital, Lansing, Mich. Accepted for publication in November 1975. sjh
151
Fig. 3. A and B. Selective right and main left renal arteriograms at one year of age. The kidneys are enlarged, with multiple areas of mild vessel displacement. A tumor nodule is seen in the upper pole (open arrows). C and D. Right and left nephrogram phases show innumerable defects, with an unopacified sheath of subcapsular tumor (arrows) encompassing both kidneys.
152
Vol. 120
ANGIOGRAPHY AND HISTOPATHOLOGY OF NEPHROBLASTOMATOSIS
Fig. 4. A. Biopsy specimen of the left kidney at one year. Sheets of slightly elongated primitive cells, resembling renal blastema cells, are associated with tubules lined by columnar epithelium. This biphasic pattern is characteristic of Wilms' tumor (nephroblastoma). (X80) B. Biopsy specimen of the right kidney at one year. This undifferentiated area of Wilms' tumor illustrates the high mitotic rate seen throughout the biopsy material. (X 128)
from both kidneys had a morphologic pattern diagnostic of Wilms' tumor (Fig. 4). The patient has been treated with actinomycin 0 and vincristine. Selective renal angiography at 22 months of age showed a bilateral reduction in renal size and only minimal residual cortical defects (Fig. 5). At this writing, the child, now 27 months old, remains well and is free of demonstrable metastatic neoplasm. DISCUSSION The roentgenographic distinction in this case was between infiltrating malignant neoplasm and adult-type polycystic renal disease. The possibility of diagnostic confusion has been cited previously (2). In this case the correct diagnosis was possible because the progression of nodular renal blastema to nephroblastoma could be inferred. It has long been thought that Wilms' tumor evolves from the metanephric blastema (6); this concept has been strongly supported by the experimental work of Javadpour and Bush (5), who observed the development of such tumors following transplantation of renal blastema in adult mice. It is not surprising, therefore, that the tiny islands of renal blastema tissue observed on initial biopsy should grow and coalesce to form diffuse Wilms' tumor. The hypertension which developed in this patient was far
153
Pediatric Radiology
Fig. 5. Selective right renal angiogram at 22 months of age, following chemotherapy, indicates reduction of renal size and considerable return toward normal renal architecture. The left kidney showed similar improvement.
in excess of that explainable by the patent ductus arteriosus and was probably due to a renovascular hypertensive component. The peripheral rind of neoplasm sheathing both kidneys may have restricted renal blood flow, resulting in a situation analagous to the capsular scar-induced hypertension described by Page (7, 9). Following antihypertensive medication and a course of antitumor chemotherapy, which resulted in marked reduction of renal size to palpation, blood pressure stabilized at 115/60/50. Many authors have discussed the question of whether autochthonous foci or metastases account for the occasional bilaterality of Wilms' tumor (4). Clearly, in this case a multitude of discrete foci in each kidney coalesced to form bilateral primary tumors. Thus this case documents the evolution of nodular renal blastema to Wilms' tumor in terms of both gross anatomy (angiography) and histopathology. Department of Radiology Edward W. Sparrow Hospital 1215 E. Michigan Avenue P.O. Box 480 Lansing, Mich. 48902
REFERENCES 1. Bove KE, Koffler H, McAdams AJ: Nodular renal blastema. Definition and possible significance. Cancer 24:323-332, Aug 1969 2. Gyepes MT, Burko H: Diffuse bilateral Wilms' tumor simulating multicystic renal disease. Radiology 82: 1029-1 031, Jun 1964
154
ROBERT E. BRANTLEY AND LAURENCE
3. Hou LT, Holman RL: Bilateral nephroblastomatosis in a premature infant. J Pathol Bacteriol 82:249:-255, Oct 1961 4. Jagasia KH, Thurman WG, Pickett E, et al: Bilateral Wilms' tumors in children. J Pediatr 65:371-376, Sep 1964 5. Javadpour N, Bush 1M: Induction and treatment of Wilms' tumor by transplantation of renal blastema in a new experimental model. J UroI107:931-937, Jun 1972 6. Lucke B, Schlumberger HG: Tumors of the kidney, renal pelvis and ureter. Atlas of Tumor Pathology, Sect 8, Fasc 30. Washington DC, AFIP, 1957, P 80
R. SIMSON, JR.
July 1976
7. Marshall WH Jr, Castellino RA: Hypertension produced by constricting capsular renal lesions. ("Page" kidney). Radiology 101:561-565, Dec 1971 8. Miller RW, Fraumeni JF Jr, Manning MD: Association of Wilms' tumor with aniridia, hemihypertrophy and other congenital malformations. N Engl J Med 270:922-927,30 Apr 1964 9. Page IH: A method for producing persistent hypertension by cellophane. Science 89:273-274,24 Mar 1939 10. Ragab AH, Vietti TJ, Crist W, et al: Bilateral Wilms' tumor. A review. Cancer 30:983-988, Oct 1972
