TERATOMA IN HORSESHOE M. RENATE RICHARD
DISCHE, JOHNSTON,
M.D.,
KIDNEYS
PH.D.
M.D.
From the Department of Pathology, The Hospital Sick Children, Toronto, and the Soldiers’ Memorial Hospital, Orillia, Canada
for
ABSTRACT -Renal tumors are uncommon, but they are signijicantly increased in horseshoe kidneys. Although nephroblastomas frequently occur in horseshoe kidneys of children, no teratoma has been observed in the past. A teratoma in the horseshoe kidney of a child with unusual congenital anomalies is described.
Horseshoe kidneys, the most common form of renal fusion, occur in about one of 400 persons.’ They may be associated with neoplasia. One hundred eleven malignant tumors, mostly adenocarcinomas and carcinomas of the renal pelvis, have been reported in horseshoe kidneys
between 1895 and 1976.2 Nephroblastoma, the third most common associated tumor, is of embryonal origin. It is, therefore, of interest that teratoma, another type of embryonal tumor, rarely occurs in the kidney and has never been observed in a horseshoe kidney.
(A) lnfant with low-set ears, FIGURE 1. micrognathia, webbed arms, and single digit. (B) X-ray film showing single forearm bone (radius) and single digit (thumb) with absent metacarpal.
UROLOGY
/ APRIL 1979 / VOLUME
XIII,
NUMBER 4
435
We report a teratoma in the horseshoe kidney of an infant born with unusual congenital anomalies and discuss the implication of our findings.
FIGURE 2. Posterior view of fused adrenals, horseshoe kidneys, and malposition of inferior vena cava to left of aorta (arrows).
Case Report A severely malformed female infant was born after thirty-eight weeks of uneventful pregnancy to a nineteen-year-old healthy primigravida. The baby died at birth although the fetal heart was heard just prior to delivery. The body was small for gestational age. It weighed 1,675 Gm. and measured 43 cm. from crown to heel. There was bilateral absence of the ulna and digits in the rigidly flexed and webbed arms, but the radius and a well-formed thumb were present bilaterally (Fig. 1). The legs were normal except for flexion at the knees. The face was abnormal with a small receding mandible and malformed lowset ears. Internal examination disclosed many minor anomalies including pancreatic heterotopia in the stomach, accessory spleens, Meckel diverticulum, notching of the liver, posterior vaginal ridge, and bicomuate uterus. More significant anomalies were hypoplastic lungs (17 Gm., normal for weight 39 Gm.), abnormal relationship of the inferior vena cava to the aorta reminiscent of the asplenia syndrome, fusion of the adrenals in front of the aorta, and horseshoe kidneys (Fig. 2). A small cystic bar of tissue 0.5 cm. wide and 1.0 cm. long connected the two main renal masses. The right kidney was rotated with the pelvis facing anteriorly, the left kidney was lower and more medial than normal. Cortical cysts up to 0.3 cm. in diameter were present in both main renal masses. The pelves, ureters, and urinary bladder were normal. Microscopic examination of the right and left portions of the horseshoe kidney disclosed numerous cortical cysts, malformed tubules, and
FIGURE 3. (A) Renal teratoma featuring metanephric blastema and uroepithelium. (B) Gliu and ganglion cells (arrows), components of the teratoma (original magnification x 270). (Hematoxylin and eosin stain.)
436
UROLOGY
/ APRIL 1979 / VOLUME
XIII,
NUMBER 4
occasional malformed glomeruli. The grossly cystic connecting bar contained masses of immature renal tissue (Fig. 3A) and rare normal glomeruli. The cysts were lined by squamous and uroepithelium. Cartilage was present in their walls. In addition there was skeletal muscle and glia containing clusters of ganglion cells (Fig. 3B). The capsule was intact. Postmortem skin fibroblast culture disclosed a normal chromosome pattern of 46 XX. Comment Malignant renal tumors are uncommon and are found in only 0.3 per cent of all autopsies3 The incidence of malignant tumors is increased in horseshoe kidneys, but statistical studies are not available to the best of our knowledge. In the past twenty-five years there were 43 horseshoe kidneys in 13,063 autopsies at The Hospital for Sick Children in Toronto. The incidence of this malformation in our experience is therefore 0.33 per cent which compares well with the predicted value of 0.25 per cent calculated from the incidence of 1 in 400. Two of the 43 horseshoe kidneys contained intrarenal tumor. One was the teratoma described, the other an adenocarcinema at the right lower pole of a hydronephrotic horseshoe kidney in a sixty-eight-year-old man. The incidence of tumors in horseshoe kidneys from this admittedly insufficient sampling is 4.65 per cent. This represents a sixty-two-fold increase over the expected 0.075 per cent incidence of tumors in horseshoe kidneys if this association were coincidental and strongly suggests a causal relationship. The frequency of various types of malignant tumor in horseshoe kidneys follows their general incidence. There is, however, an interesting difference in their distribution within the horseshoe kidney. Blackard and Mellinger in their review of 72 malignant tumors in horseshoe kidneys noted 24 per cent of all adenocarcinomas and 33 per cent of nephroblastomas in the isthmus, while squamous carcinoma of the renal pelvis was never present in this location. The equal distribution of nephroblastoma in all parts of the horseshoe kidney indicates that this tumor has no preferential site of origin. This is not unexpected from its embryonic derivation, while renal pelvis carcinoma and perhaps also adenocarcinoma may be linked to the frequent chronic obstruction and inflammation encountered in horseshoe kidneys. In view of the frequency of nephroblastomas it is surprising that teratomas which are also
UROLOGY
/
APRIL 1979
/
VOLUME XIII,
NUMBER 4
tumors of embryonal or germ cell origin, should be extremely rare in kidneys. Only 3 intrarenal teratomas have been previously described and all occurred in children. 5-7 Two of the tumors in young infants closely resembled our own case in their histologic make-up and featured nephroblastic elements. None of these children with intrarenal teratomas had any extrarenal anomalies, as in our case. The relationship of tumors and tumorous malformations to multiple congenital anomalies and chromosomal abnormalities is indeed of great interest because of the bearing on the etiology of neoplasia. Nephroblastoma is known to occur with extrarenal anomalies such as aniridia and hemihypertrophy* and teratoma has been noted in trisomy 13.’ Extrarenal anomalies are commonly associated with horseshoe kidneys, particularly in infants and children. Fatalities among these children are usually caused by the severity of the extrarenal anomalies rather than the renal disease, as stated by Campbell and Harrison.” In our series of 4.2 horseshoe kidneys in children this proved to be the sole anomaly in only 7. These children died of newborn infections, effects of prematurity, and other acquired nonrenal diseases. Two children had minor additional anomalies. The reMajor extrarenal anomalies associated with horseshoe kidneys in 33 children*
TABLE I.
Anomaly1
Number
Congenital heart disease Complex CHD VSD t Coarc. Coarc. + Turner Valve anomalies Anomalies of large vessels EFE
19
Central nervous system disease Hydrocephalus and/or meningomyelocele
10
Miscellaneous Omphalocele T-E fistula GI stenosis and atresia Cleft palate Subglottic stenosis Hypoplasia of lungs
12
4 7 2 3 2 1
10
2 3 3 2 1
1
*Eight children with two major extrarenal anomalies. t KEY: CHD = congenital heart disease; VSD = ventricular septal defect; Coarc. = coarctation of aorta; T-E fistula = tracheoesophageal fistula; and EFE = endocardial fibroelastosis.
437
maining 33 children all had severe lifethreatening extrarenal malformations (Table I). A constellation of malformations reminiscent of the present case has been described by syndrome. HowWeyersrr as the oligodactyly ever, he found horseshoe kidneys only when deformities of both upper and lower extremities were present, and no renal tumor has been observed so far. It is difficult in the present case to assess the future malignant potential of the tumor. The hisappearance resembled a welltologic differentiated Wilms tumor, but capsular invasion was not present. Toronto, Ontario, Canada (DR. DISCHE) References 1. Warkany J: In: Congenital Malformations, Publishers, Inc., 1971, p. 1050.
438
Yearbook
Medical
2. Buntley D: Malignancy associated with horseshoe kidney, Urology 8: 146 (1976). 3. Lucke B, and Schlumberger HG: Tumors of the kidney, renal pelvis and ureter, In: Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, 1953, sect. VIII, fast. 30. 4. Blackard CE, and Mellinger GT: Cancer in a horseshoe kidney, Arch. Surg. 97: 616 (1968). 5. Dehner LP: Intrarenal teratoma occurring in infancy: report of a case with discussion of extragonadal germ cell tumors of infancy, J. Pediatr. Surg. 8: 396 (1973). 6. McCurdy GA: Renal neoplasms in childhood, J. Pathol. Bacteriol. 39: 623 (1934). 7. Bilger F, St011 G, and Raiga JC: Teratome kystique complete de la loge renale, J. Urol. Med. (Paris) 58: 861 (1952). 8. Miller RW, Fraumeni JF, and Manning MD: Association of Wilms tumor with aniridia, hemihypertrophy and other congenital malformations, N. Engl. J. Med. 270: 922 (1964). 9. Dische MR, and Gardner HA: Mixed teratoid tumors of the liver and neck in trisomy 13, Am. J. Clin. Pathol. 69: 631 (1978). 10. Campbell MF, and Harrison JH: In: Urology, Philadelphia, W. B. Saunders Co. 1970, p. 1448. 11. Weyers H: Das Oligodaktilie-Syndrom des Menschen und seine Parallelmutation bei der Hausmaus, Ann. Paediat. 189: 351 (1957).
UROLOGY
/
APRIL
1979
/
VOLUME
XIII.
NUMBER
4
DISCHE, JOHNSTON,
M.D.,
KIDNEYS
PH.D.
M.D.
From the Department of Pathology, The Hospital Sick Children, Toronto, and the Soldiers’ Memorial Hospital, Orillia, Canada
for
ABSTRACT -Renal tumors are uncommon, but they are signijicantly increased in horseshoe kidneys. Although nephroblastomas frequently occur in horseshoe kidneys of children, no teratoma has been observed in the past. A teratoma in the horseshoe kidney of a child with unusual congenital anomalies is described.
Horseshoe kidneys, the most common form of renal fusion, occur in about one of 400 persons.’ They may be associated with neoplasia. One hundred eleven malignant tumors, mostly adenocarcinomas and carcinomas of the renal pelvis, have been reported in horseshoe kidneys
between 1895 and 1976.2 Nephroblastoma, the third most common associated tumor, is of embryonal origin. It is, therefore, of interest that teratoma, another type of embryonal tumor, rarely occurs in the kidney and has never been observed in a horseshoe kidney.
(A) lnfant with low-set ears, FIGURE 1. micrognathia, webbed arms, and single digit. (B) X-ray film showing single forearm bone (radius) and single digit (thumb) with absent metacarpal.
UROLOGY
/ APRIL 1979 / VOLUME
XIII,
NUMBER 4
435
We report a teratoma in the horseshoe kidney of an infant born with unusual congenital anomalies and discuss the implication of our findings.
FIGURE 2. Posterior view of fused adrenals, horseshoe kidneys, and malposition of inferior vena cava to left of aorta (arrows).
Case Report A severely malformed female infant was born after thirty-eight weeks of uneventful pregnancy to a nineteen-year-old healthy primigravida. The baby died at birth although the fetal heart was heard just prior to delivery. The body was small for gestational age. It weighed 1,675 Gm. and measured 43 cm. from crown to heel. There was bilateral absence of the ulna and digits in the rigidly flexed and webbed arms, but the radius and a well-formed thumb were present bilaterally (Fig. 1). The legs were normal except for flexion at the knees. The face was abnormal with a small receding mandible and malformed lowset ears. Internal examination disclosed many minor anomalies including pancreatic heterotopia in the stomach, accessory spleens, Meckel diverticulum, notching of the liver, posterior vaginal ridge, and bicomuate uterus. More significant anomalies were hypoplastic lungs (17 Gm., normal for weight 39 Gm.), abnormal relationship of the inferior vena cava to the aorta reminiscent of the asplenia syndrome, fusion of the adrenals in front of the aorta, and horseshoe kidneys (Fig. 2). A small cystic bar of tissue 0.5 cm. wide and 1.0 cm. long connected the two main renal masses. The right kidney was rotated with the pelvis facing anteriorly, the left kidney was lower and more medial than normal. Cortical cysts up to 0.3 cm. in diameter were present in both main renal masses. The pelves, ureters, and urinary bladder were normal. Microscopic examination of the right and left portions of the horseshoe kidney disclosed numerous cortical cysts, malformed tubules, and
FIGURE 3. (A) Renal teratoma featuring metanephric blastema and uroepithelium. (B) Gliu and ganglion cells (arrows), components of the teratoma (original magnification x 270). (Hematoxylin and eosin stain.)
436
UROLOGY
/ APRIL 1979 / VOLUME
XIII,
NUMBER 4
occasional malformed glomeruli. The grossly cystic connecting bar contained masses of immature renal tissue (Fig. 3A) and rare normal glomeruli. The cysts were lined by squamous and uroepithelium. Cartilage was present in their walls. In addition there was skeletal muscle and glia containing clusters of ganglion cells (Fig. 3B). The capsule was intact. Postmortem skin fibroblast culture disclosed a normal chromosome pattern of 46 XX. Comment Malignant renal tumors are uncommon and are found in only 0.3 per cent of all autopsies3 The incidence of malignant tumors is increased in horseshoe kidneys, but statistical studies are not available to the best of our knowledge. In the past twenty-five years there were 43 horseshoe kidneys in 13,063 autopsies at The Hospital for Sick Children in Toronto. The incidence of this malformation in our experience is therefore 0.33 per cent which compares well with the predicted value of 0.25 per cent calculated from the incidence of 1 in 400. Two of the 43 horseshoe kidneys contained intrarenal tumor. One was the teratoma described, the other an adenocarcinema at the right lower pole of a hydronephrotic horseshoe kidney in a sixty-eight-year-old man. The incidence of tumors in horseshoe kidneys from this admittedly insufficient sampling is 4.65 per cent. This represents a sixty-two-fold increase over the expected 0.075 per cent incidence of tumors in horseshoe kidneys if this association were coincidental and strongly suggests a causal relationship. The frequency of various types of malignant tumor in horseshoe kidneys follows their general incidence. There is, however, an interesting difference in their distribution within the horseshoe kidney. Blackard and Mellinger in their review of 72 malignant tumors in horseshoe kidneys noted 24 per cent of all adenocarcinomas and 33 per cent of nephroblastomas in the isthmus, while squamous carcinoma of the renal pelvis was never present in this location. The equal distribution of nephroblastoma in all parts of the horseshoe kidney indicates that this tumor has no preferential site of origin. This is not unexpected from its embryonic derivation, while renal pelvis carcinoma and perhaps also adenocarcinoma may be linked to the frequent chronic obstruction and inflammation encountered in horseshoe kidneys. In view of the frequency of nephroblastomas it is surprising that teratomas which are also
UROLOGY
/
APRIL 1979
/
VOLUME XIII,
NUMBER 4
tumors of embryonal or germ cell origin, should be extremely rare in kidneys. Only 3 intrarenal teratomas have been previously described and all occurred in children. 5-7 Two of the tumors in young infants closely resembled our own case in their histologic make-up and featured nephroblastic elements. None of these children with intrarenal teratomas had any extrarenal anomalies, as in our case. The relationship of tumors and tumorous malformations to multiple congenital anomalies and chromosomal abnormalities is indeed of great interest because of the bearing on the etiology of neoplasia. Nephroblastoma is known to occur with extrarenal anomalies such as aniridia and hemihypertrophy* and teratoma has been noted in trisomy 13.’ Extrarenal anomalies are commonly associated with horseshoe kidneys, particularly in infants and children. Fatalities among these children are usually caused by the severity of the extrarenal anomalies rather than the renal disease, as stated by Campbell and Harrison.” In our series of 4.2 horseshoe kidneys in children this proved to be the sole anomaly in only 7. These children died of newborn infections, effects of prematurity, and other acquired nonrenal diseases. Two children had minor additional anomalies. The reMajor extrarenal anomalies associated with horseshoe kidneys in 33 children*
TABLE I.
Anomaly1
Number
Congenital heart disease Complex CHD VSD t Coarc. Coarc. + Turner Valve anomalies Anomalies of large vessels EFE
19
Central nervous system disease Hydrocephalus and/or meningomyelocele
10
Miscellaneous Omphalocele T-E fistula GI stenosis and atresia Cleft palate Subglottic stenosis Hypoplasia of lungs
12
4 7 2 3 2 1
10
2 3 3 2 1
1
*Eight children with two major extrarenal anomalies. t KEY: CHD = congenital heart disease; VSD = ventricular septal defect; Coarc. = coarctation of aorta; T-E fistula = tracheoesophageal fistula; and EFE = endocardial fibroelastosis.
437
maining 33 children all had severe lifethreatening extrarenal malformations (Table I). A constellation of malformations reminiscent of the present case has been described by syndrome. HowWeyersrr as the oligodactyly ever, he found horseshoe kidneys only when deformities of both upper and lower extremities were present, and no renal tumor has been observed so far. It is difficult in the present case to assess the future malignant potential of the tumor. The hisappearance resembled a welltologic differentiated Wilms tumor, but capsular invasion was not present. Toronto, Ontario, Canada (DR. DISCHE) References 1. Warkany J: In: Congenital Malformations, Publishers, Inc., 1971, p. 1050.
438
Yearbook
Medical
2. Buntley D: Malignancy associated with horseshoe kidney, Urology 8: 146 (1976). 3. Lucke B, and Schlumberger HG: Tumors of the kidney, renal pelvis and ureter, In: Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, 1953, sect. VIII, fast. 30. 4. Blackard CE, and Mellinger GT: Cancer in a horseshoe kidney, Arch. Surg. 97: 616 (1968). 5. Dehner LP: Intrarenal teratoma occurring in infancy: report of a case with discussion of extragonadal germ cell tumors of infancy, J. Pediatr. Surg. 8: 396 (1973). 6. McCurdy GA: Renal neoplasms in childhood, J. Pathol. Bacteriol. 39: 623 (1934). 7. Bilger F, St011 G, and Raiga JC: Teratome kystique complete de la loge renale, J. Urol. Med. (Paris) 58: 861 (1952). 8. Miller RW, Fraumeni JF, and Manning MD: Association of Wilms tumor with aniridia, hemihypertrophy and other congenital malformations, N. Engl. J. Med. 270: 922 (1964). 9. Dische MR, and Gardner HA: Mixed teratoid tumors of the liver and neck in trisomy 13, Am. J. Clin. Pathol. 69: 631 (1978). 10. Campbell MF, and Harrison JH: In: Urology, Philadelphia, W. B. Saunders Co. 1970, p. 1448. 11. Weyers H: Das Oligodaktilie-Syndrom des Menschen und seine Parallelmutation bei der Hausmaus, Ann. Paediat. 189: 351 (1957).
UROLOGY
/
APRIL
1979
/
VOLUME
XIII.
NUMBER
4
