- Email: [email protected]
Congenital Mesoblastic Nephroma (Leiomyomatous Hamartoma): First Adult Case
THE ,JOURNAL OF UROLOGY
Vol. 110, October
Copyright © 1973 by The Williams & Wilkins Co.
Printed in U.S.A.
CONGENITAL MESOBLASTIC NEPHROMA (LEIOMYOMATOUS HAMARTOMA): FIRST ADULT CASE NORMAN L. BLOCK, HARRY G. GRABSTALD
AND
MYRON R. MELAMED
From the Departments of Surgery (Urology) and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
Congenital mesoblastic nephroma is an unusual renal tumor, similar in some respects to Wilms tumor and heretofore reported only in infants. We report herein a case of congenital mesoblastic nephroma in an adult. CASE REPORT
C. F., MH 61 43 31, a 31-year-old white woman, was referred to us with a 6-month history of intermittent left flank pain diagnosed as pyelonephritis and previously treated with sulfisoxazole. Six days before hospitalization she had pyuria and albuminuria but no hematuria. Excretory urograms (IVPs) and nephrotomograms revealed a previously unsuspected space-occupying lesion of the lower pole of the right kidney (fig. 1, A). Physical examination was within normal limits. Blood pressure was 110/70, the kidneys were not palpable and there was no lymphadenopathy or sign of masculinization. Hemoglobin, hematocrit, total and differential white blood count, blood urea nitrogen, fasting blood sugar, serum creatinine, potassium, sodium, chloride, carbon dioxide content, calcium, alkaline phosphatase, glutamic oxaloacetic transaminase, 5' -nucleotidase and prothrombin time were normal. Urinalysis was normal, with only rare white blood cells in the sediment and no albuminuria. Urine culture yielded no pathogenic bacteria. Urinary 17-ketosteroids and 17 to 21-dihydroxysteroids were normal. Multiple urine cytology specimens were negative for malignant cells. Chest roentgenography and skeletal survey were normal. A percutaneous transfemoral abdominal aortogram and selective right renal arteriogram revealed the right kidney to be supplied by 2 arteries. A sharply demarcated, space-occupying lesion measuring 4 cm. in diameter was demonstrated in the lower pole (fig. 1, B). Within the lesion there was an abnormal distribution of vessels with tumor staining noted on delayed films. The mass protruded from the medial aspect of the lower pole, elevated the renal pelvis on that side and displaced the lower pole infundibulum laterally. The tortuous dilated vessels, characteristic of renal cell cancer, were not seen. Hamartoma or adenoma was considered as diagnosis. The left kidney was normal. Right nephrectomy was performed on July 30, 1969. Bisection of the kidney revealed the tumor as Accepted for publication May 4, 1973.
380
described in the angiogram (fig. 2). It was 38 mm. in diameter, firm, round, tan, homogeneous and discrete and compressed adjacent renal parenchyma. The calices were distorted. The tumor extended to the renal capsule, bulging it slightly but not invading it. Microscopically, the tumor was comprised almost entirely of interwoven bands of spindle cells. In some areas these were tightly compacted, thin and elongated, while in others they were plump, loosely arranged and formed numerous slits and spaces. Interspersed within the tumor but more numerous peripherally were tubules and small cysts lined by a single layer of cuboidal or flattened epithelium (fig. 3, A). No well-formed glomerular structures were found but a very convoluted tubule did suggest a disorganized nephron (fig. 3, B). There was no invasion through the renal capsule. Most of the tumor was non-encapsulated (fig. 4). Representative histologic sections of the tumor were reviewed by Dr. R. P. Eolande who agreed with the diagnosis of mesoblastic nephroma. He noted that the tumor was more collagenized than in the infantile form. Convalescence was uneventful and the patient was discharged from the hospital 8 days postoperatively. She is in excellent health 4 years postoperatively with no evidence of recurrence. DISCUSSION
In 1967 Eolande and associates coined the term "congenital mesoblastic nephroma" for a small group of unique renal tumors that had been found in infants. 1 These tumors were characterized by a histologic pattern of spindle cells with numerous vascular slits or spaces and occasional cystic or imperfectly formed tubules and glomeruli. Some tumors also had nests of cartilage and foci of hematopoiesis. The tumors were clinically benign although they were non-encapsulated and penetrated surrounding renal parenchyma or perirenal and hilar fat. The mixture of mesenchymal and epithelial derivatives resembled Wilms tumor but was distinguished from it by the benign cytology of all components. Their choice of names for these tumors was somewhat unfortunate since mesoblastic nephroma is one of the many synonyms that have 1 Eolande, R. P., Brough, A. J. and Izant, R. J., Jr.: Congenital mesoblastic nephroma of infancy. A report of eight cases and the relationship to Wilms' tumor. Pediatrics, 40: 272, 1967.
CONGEi~ITAL MESOBLASTIC NEPHROrviA
381
FIG. 1. A, IVP demonstrates mass in medial portion of lower pole of right kidney. B, capillary phase of aortogram demonstrates sharply demarcated space-occupying lesion in right lower pole.
Our case is the first example of this benign tumor in adults. Other investigators have reported what appears to be the same tumor but under a variety of names. •- 11 This tumor has been found in siblings, has been bilateral and may be more common in infants than was first suspected. 12 It is strange that these tumors have not been previously recognized in an adult and that relatively few have been found in older children. The oldest patient previously reported was a 15-year-old girl. 12 A review of the literature on renal tumors in the pediatric age group reveals individual cases that could probably be reclassified as congenital mesoblastic nephromas. Wigger reported 5 cases of a tumor which he called fetal hamartoma of the kidney.• His patients were less than 1 year old and 3 had an initial diagnosis of Wilms tumor. These tumors were all benign and their pathologic deFIG. 2. Gross tumor measures 38 mm. in diameter and is firm, round, homogeneous and. discrete, compressing adjacent renal parenchyma.
been applied to true Wilms tumor. 2 Culp and Hartman used the same term as Bolande for a different group of tumors. Those reported and Hartman are a variety of malignant mixed renal tumorn, some that we would now call malignant Wilms tumor.2 None of these tumors corresponds to the benign tumor that we report herein. A recent article Mostofi and associates concerns the tumor that we are reporting and the name !eiomyomatous hamartoma is used. 3 2 Culp, 0. S. and Hartman, F. W.: Mesoblastic nephroma in adults: a clinico-pathologic study of Wilms' tumors and related renal neoplasms. J. Urol., 60: 552, 1948. 'Bogdan, R., Taylor, D. E. M. and Mostofi, F. K.:
Leiomyomatous hamartoma of the kidney. A clinical and pathologic analysis of 20 cases from the kidney tumor registry. Cancer, 31: 462, 1973. 'Wright, E. S.: Congenital Wilms' tumour: case report. Brit. J. Urol., 42: 270, 1970. 5 Bachma.nn, K. D. and Kroll, W.: Der Wilms-Tumor im ersten Lebensja.hL Deutsch. Med. Wschr., 94: 2598, 1969. 'Favara, B. E., Johnson, W. and Ito, J.: Renal tumors in the neonatal period. Cancer, 22: 845, 1968. 7 Kay, S., Pratt, C. B. and Salzberg, A. M.: Hamartoma (leiomyomatous type) of the kidney. Cancer, 19: 1825, 1966. 'Wigger, H. J.: Fetal hamartoma of kidney. A benign symptomatic congenital tumor, not a form of Wilms' tumor. Amer. J. Clin. Path., 51: 323, 1969. • Burkholder, G. V., Beach, P. D. and Hall, R.: Fetal renal hamartoma. J. Urol., 104: 330, 1970. ''Richmond, H. and Dougall, A. J.: Neonatal renal tumors. J. Pediat. Surg., 5: 413, 1970. 11 Waisman, J. and Cooper, P.H.: Renal neoplasms of the newborn. J. Pediat. Surg., 5: 407, 1970. 12 Bolande, R. P.: Personal communication.
382
BLOCK, GRABSTALD AND MELAMED
FIG. 3. A, tumor is comprised of interwoven bands of spindle cells with interspersed tubules and small cysts. Thin vascular slits and spaces are evident between cell bundles. H & E, reduced from x350. B, unusually convoluted tubule is seen which suggests disorganized nephron. Epithelial formations of this kind are considered intrinsic part of tumor. H & E, reduced from x 140.
scription is similar to that of the tumor described by Eolande. Wigger concluded that there may not be a true congenital Wilms tumor. He thinks that all of the tumors may be this benign variant called fetal hamartoma or mesoblastic nephroma. Bove and associates demonstrated persistence of renal blastema in the renal cortex. 13 Whether this represents in situ congenital Wilms tumor or the benign variant is unknown. Eolande pointed out the possibility of sarcomatous transformation occur-
ring in this tumor after many years but this has never been reported. 12 The young age of most children with this tumor, as well as its mixed histology, has suggested a congenital origin and some relationship to Wilms tumor. Possibly it represents the benign counterpart of that neoplasm, as suggested by Liban 1 • and Eolande.' Eolande has even considered that it may represent spontaneous or induced maturation and differentiation of Wilms tumor. He described 2 cases of suspected Wilms tumor in which large renal masses shrunk to half their size when treated by irradiation. The excised tumors then showed the mesoblastic pattern. On a number of occasions we have seen metastatic Wilms tumor in the lung decrease in size under treatment and, when subsequently excised, be comprised largely of mature spindle cells or fibrous stroma with a cystic or tubular epithelial component not unlike the mesoblastic nephroma (fig. 5). If one assumes that the benign mesoblastic nephroma represents maturation of a Wilms tumor, then continued maturation could explain its rarity in the adult. As the epithelial elements give way to the spindle cell component the tumor might eventually become a fibroma. Tubular inclusions are commonly present within fibromas and they may be remnants of the original epithelial structures. Such a thesis would explain the origin of some fibromas in the adult kidney and provide a reason why the benign mesoblastic nephroma would be found in children and not adults. The primary clinical significance of this tumor is
" Bove, K. E., Koffler, H. and McAdams, A. J.: Nodular renal blastema. Definition and possible significance. Cancer, 24: 323, 1969.
14 Liban, E. and Kozenitzky, I. L.: Metanephric hamartomas and nephroblastomatosis in siblings. Cancer, 25: 885, 1970.
FIG. 4. At low magnification sharp demarcation between tumor and adjacent renal parenchyma is demonstrated and thin fibrous capsule is present. Within tumor vascular spaces are prominent. Tubules and small epithelial lined cysts tend to be more numerous near periphery of tumor. H & E, reduced from x35.
383
CONGENITAL rvlESOBLASTIC NEPHROivIA
FIG. 5. Metastatic Wilms tumor resected from lung of child treated with actinomycin D and radiotherapy prior to thoracotomy. Several tumors which were visible in chest x-ray grew smaller or disappeared during course of chemotherapy and irradiation. Remaining tumors were resected; one showed typical Wilms tumor and another is illustrated here. Pattern of spindle cell and fibrous stroma with occasional cysts and tubules closely resembles mesoblastic nephroma. It is presumed to be an example of tumor maturation under therapy. A, H & E, reduced from x35. B, H & E, reduced from x140.
in its close histologic resemblance to Wilms tumor. This resemblance may lead to paradoxical survival statistics for Wilms tumor and to over-treatment of patients with a benign tumor. Several investigators have pointed out that Wilms tumor is associated with better survival rates in children less than 1 year old. 1 • 15 One would ordinarily expect that the earlier manifesting tumors would be faster and implication rnore malignant. Eolande has that as many as 50 per cent of the renal tumors initially diagnosed as Wilms tumor in children less than 1 year old to be ta! mesoblastic nephromas.
Despite the non-encapsulated growth pattern of this tumor, it is identification would elirni.nste the morbidity and mortality associated with mappropriate irradiation and chemotherapy.
"Kiapproth, H.J.: Wilms tumor: a and an analysis of 1,351 cases literature from 1940 to 1958. J.
Dr. R. P. Bolande reviev,1ed the siiri.es of this and comments.
SUMMARY
The first case of 1n
clinical tumor resemblance to WHms tumor and danger of radica 1 disease.
con2iequent
Vol. 110, October
Copyright © 1973 by The Williams & Wilkins Co.
Printed in U.S.A.
CONGENITAL MESOBLASTIC NEPHROMA (LEIOMYOMATOUS HAMARTOMA): FIRST ADULT CASE NORMAN L. BLOCK, HARRY G. GRABSTALD
AND
MYRON R. MELAMED
From the Departments of Surgery (Urology) and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
Congenital mesoblastic nephroma is an unusual renal tumor, similar in some respects to Wilms tumor and heretofore reported only in infants. We report herein a case of congenital mesoblastic nephroma in an adult. CASE REPORT
C. F., MH 61 43 31, a 31-year-old white woman, was referred to us with a 6-month history of intermittent left flank pain diagnosed as pyelonephritis and previously treated with sulfisoxazole. Six days before hospitalization she had pyuria and albuminuria but no hematuria. Excretory urograms (IVPs) and nephrotomograms revealed a previously unsuspected space-occupying lesion of the lower pole of the right kidney (fig. 1, A). Physical examination was within normal limits. Blood pressure was 110/70, the kidneys were not palpable and there was no lymphadenopathy or sign of masculinization. Hemoglobin, hematocrit, total and differential white blood count, blood urea nitrogen, fasting blood sugar, serum creatinine, potassium, sodium, chloride, carbon dioxide content, calcium, alkaline phosphatase, glutamic oxaloacetic transaminase, 5' -nucleotidase and prothrombin time were normal. Urinalysis was normal, with only rare white blood cells in the sediment and no albuminuria. Urine culture yielded no pathogenic bacteria. Urinary 17-ketosteroids and 17 to 21-dihydroxysteroids were normal. Multiple urine cytology specimens were negative for malignant cells. Chest roentgenography and skeletal survey were normal. A percutaneous transfemoral abdominal aortogram and selective right renal arteriogram revealed the right kidney to be supplied by 2 arteries. A sharply demarcated, space-occupying lesion measuring 4 cm. in diameter was demonstrated in the lower pole (fig. 1, B). Within the lesion there was an abnormal distribution of vessels with tumor staining noted on delayed films. The mass protruded from the medial aspect of the lower pole, elevated the renal pelvis on that side and displaced the lower pole infundibulum laterally. The tortuous dilated vessels, characteristic of renal cell cancer, were not seen. Hamartoma or adenoma was considered as diagnosis. The left kidney was normal. Right nephrectomy was performed on July 30, 1969. Bisection of the kidney revealed the tumor as Accepted for publication May 4, 1973.
380
described in the angiogram (fig. 2). It was 38 mm. in diameter, firm, round, tan, homogeneous and discrete and compressed adjacent renal parenchyma. The calices were distorted. The tumor extended to the renal capsule, bulging it slightly but not invading it. Microscopically, the tumor was comprised almost entirely of interwoven bands of spindle cells. In some areas these were tightly compacted, thin and elongated, while in others they were plump, loosely arranged and formed numerous slits and spaces. Interspersed within the tumor but more numerous peripherally were tubules and small cysts lined by a single layer of cuboidal or flattened epithelium (fig. 3, A). No well-formed glomerular structures were found but a very convoluted tubule did suggest a disorganized nephron (fig. 3, B). There was no invasion through the renal capsule. Most of the tumor was non-encapsulated (fig. 4). Representative histologic sections of the tumor were reviewed by Dr. R. P. Eolande who agreed with the diagnosis of mesoblastic nephroma. He noted that the tumor was more collagenized than in the infantile form. Convalescence was uneventful and the patient was discharged from the hospital 8 days postoperatively. She is in excellent health 4 years postoperatively with no evidence of recurrence. DISCUSSION
In 1967 Eolande and associates coined the term "congenital mesoblastic nephroma" for a small group of unique renal tumors that had been found in infants. 1 These tumors were characterized by a histologic pattern of spindle cells with numerous vascular slits or spaces and occasional cystic or imperfectly formed tubules and glomeruli. Some tumors also had nests of cartilage and foci of hematopoiesis. The tumors were clinically benign although they were non-encapsulated and penetrated surrounding renal parenchyma or perirenal and hilar fat. The mixture of mesenchymal and epithelial derivatives resembled Wilms tumor but was distinguished from it by the benign cytology of all components. Their choice of names for these tumors was somewhat unfortunate since mesoblastic nephroma is one of the many synonyms that have 1 Eolande, R. P., Brough, A. J. and Izant, R. J., Jr.: Congenital mesoblastic nephroma of infancy. A report of eight cases and the relationship to Wilms' tumor. Pediatrics, 40: 272, 1967.
CONGEi~ITAL MESOBLASTIC NEPHROrviA
381
FIG. 1. A, IVP demonstrates mass in medial portion of lower pole of right kidney. B, capillary phase of aortogram demonstrates sharply demarcated space-occupying lesion in right lower pole.
Our case is the first example of this benign tumor in adults. Other investigators have reported what appears to be the same tumor but under a variety of names. •- 11 This tumor has been found in siblings, has been bilateral and may be more common in infants than was first suspected. 12 It is strange that these tumors have not been previously recognized in an adult and that relatively few have been found in older children. The oldest patient previously reported was a 15-year-old girl. 12 A review of the literature on renal tumors in the pediatric age group reveals individual cases that could probably be reclassified as congenital mesoblastic nephromas. Wigger reported 5 cases of a tumor which he called fetal hamartoma of the kidney.• His patients were less than 1 year old and 3 had an initial diagnosis of Wilms tumor. These tumors were all benign and their pathologic deFIG. 2. Gross tumor measures 38 mm. in diameter and is firm, round, homogeneous and. discrete, compressing adjacent renal parenchyma.
been applied to true Wilms tumor. 2 Culp and Hartman used the same term as Bolande for a different group of tumors. Those reported and Hartman are a variety of malignant mixed renal tumorn, some that we would now call malignant Wilms tumor.2 None of these tumors corresponds to the benign tumor that we report herein. A recent article Mostofi and associates concerns the tumor that we are reporting and the name !eiomyomatous hamartoma is used. 3 2 Culp, 0. S. and Hartman, F. W.: Mesoblastic nephroma in adults: a clinico-pathologic study of Wilms' tumors and related renal neoplasms. J. Urol., 60: 552, 1948. 'Bogdan, R., Taylor, D. E. M. and Mostofi, F. K.:
Leiomyomatous hamartoma of the kidney. A clinical and pathologic analysis of 20 cases from the kidney tumor registry. Cancer, 31: 462, 1973. 'Wright, E. S.: Congenital Wilms' tumour: case report. Brit. J. Urol., 42: 270, 1970. 5 Bachma.nn, K. D. and Kroll, W.: Der Wilms-Tumor im ersten Lebensja.hL Deutsch. Med. Wschr., 94: 2598, 1969. 'Favara, B. E., Johnson, W. and Ito, J.: Renal tumors in the neonatal period. Cancer, 22: 845, 1968. 7 Kay, S., Pratt, C. B. and Salzberg, A. M.: Hamartoma (leiomyomatous type) of the kidney. Cancer, 19: 1825, 1966. 'Wigger, H. J.: Fetal hamartoma of kidney. A benign symptomatic congenital tumor, not a form of Wilms' tumor. Amer. J. Clin. Path., 51: 323, 1969. • Burkholder, G. V., Beach, P. D. and Hall, R.: Fetal renal hamartoma. J. Urol., 104: 330, 1970. ''Richmond, H. and Dougall, A. J.: Neonatal renal tumors. J. Pediat. Surg., 5: 413, 1970. 11 Waisman, J. and Cooper, P.H.: Renal neoplasms of the newborn. J. Pediat. Surg., 5: 407, 1970. 12 Bolande, R. P.: Personal communication.
382
BLOCK, GRABSTALD AND MELAMED
FIG. 3. A, tumor is comprised of interwoven bands of spindle cells with interspersed tubules and small cysts. Thin vascular slits and spaces are evident between cell bundles. H & E, reduced from x350. B, unusually convoluted tubule is seen which suggests disorganized nephron. Epithelial formations of this kind are considered intrinsic part of tumor. H & E, reduced from x 140.
scription is similar to that of the tumor described by Eolande. Wigger concluded that there may not be a true congenital Wilms tumor. He thinks that all of the tumors may be this benign variant called fetal hamartoma or mesoblastic nephroma. Bove and associates demonstrated persistence of renal blastema in the renal cortex. 13 Whether this represents in situ congenital Wilms tumor or the benign variant is unknown. Eolande pointed out the possibility of sarcomatous transformation occur-
ring in this tumor after many years but this has never been reported. 12 The young age of most children with this tumor, as well as its mixed histology, has suggested a congenital origin and some relationship to Wilms tumor. Possibly it represents the benign counterpart of that neoplasm, as suggested by Liban 1 • and Eolande.' Eolande has even considered that it may represent spontaneous or induced maturation and differentiation of Wilms tumor. He described 2 cases of suspected Wilms tumor in which large renal masses shrunk to half their size when treated by irradiation. The excised tumors then showed the mesoblastic pattern. On a number of occasions we have seen metastatic Wilms tumor in the lung decrease in size under treatment and, when subsequently excised, be comprised largely of mature spindle cells or fibrous stroma with a cystic or tubular epithelial component not unlike the mesoblastic nephroma (fig. 5). If one assumes that the benign mesoblastic nephroma represents maturation of a Wilms tumor, then continued maturation could explain its rarity in the adult. As the epithelial elements give way to the spindle cell component the tumor might eventually become a fibroma. Tubular inclusions are commonly present within fibromas and they may be remnants of the original epithelial structures. Such a thesis would explain the origin of some fibromas in the adult kidney and provide a reason why the benign mesoblastic nephroma would be found in children and not adults. The primary clinical significance of this tumor is
" Bove, K. E., Koffler, H. and McAdams, A. J.: Nodular renal blastema. Definition and possible significance. Cancer, 24: 323, 1969.
14 Liban, E. and Kozenitzky, I. L.: Metanephric hamartomas and nephroblastomatosis in siblings. Cancer, 25: 885, 1970.
FIG. 4. At low magnification sharp demarcation between tumor and adjacent renal parenchyma is demonstrated and thin fibrous capsule is present. Within tumor vascular spaces are prominent. Tubules and small epithelial lined cysts tend to be more numerous near periphery of tumor. H & E, reduced from x35.
383
CONGENITAL rvlESOBLASTIC NEPHROivIA
FIG. 5. Metastatic Wilms tumor resected from lung of child treated with actinomycin D and radiotherapy prior to thoracotomy. Several tumors which were visible in chest x-ray grew smaller or disappeared during course of chemotherapy and irradiation. Remaining tumors were resected; one showed typical Wilms tumor and another is illustrated here. Pattern of spindle cell and fibrous stroma with occasional cysts and tubules closely resembles mesoblastic nephroma. It is presumed to be an example of tumor maturation under therapy. A, H & E, reduced from x35. B, H & E, reduced from x140.
in its close histologic resemblance to Wilms tumor. This resemblance may lead to paradoxical survival statistics for Wilms tumor and to over-treatment of patients with a benign tumor. Several investigators have pointed out that Wilms tumor is associated with better survival rates in children less than 1 year old. 1 • 15 One would ordinarily expect that the earlier manifesting tumors would be faster and implication rnore malignant. Eolande has that as many as 50 per cent of the renal tumors initially diagnosed as Wilms tumor in children less than 1 year old to be ta! mesoblastic nephromas.
Despite the non-encapsulated growth pattern of this tumor, it is identification would elirni.nste the morbidity and mortality associated with mappropriate irradiation and chemotherapy.
"Kiapproth, H.J.: Wilms tumor: a and an analysis of 1,351 cases literature from 1940 to 1958. J.
Dr. R. P. Bolande reviev,1ed the siiri.es of this and comments.
SUMMARY
The first case of 1n
clinical tumor resemblance to WHms tumor and danger of radica 1 disease.
con2iequent