- Email: [email protected]
Bilateral neonatal Wilms' tumor with B-C chromosomal translocation
98
B r i e f clinical and laboratory observations
Medical Records Request Attached is a copy of the discharse summary on your patient. Should you need a complete copy of all or parts of the medical record, please check those desired and return this form to: MEDICAL RECORDS DEPARTMENT Upstate Medical Center 750East Adams Street Syracuse, New York 13210
(
I Physician's Notes [
l
J Laboratory Data
(Includi~ns x-rays,
[ N..... 'Notes
~
Entire Rec.ord
EEG, EKG, etc.)
Physlcian's Name Address
Fig. 2 A working copy of the discharge form is included in the chart of each pediatric patient at the time of his admission to the hospital. Problems which are present at the time of admission are immediately entered. New problems are entered as they alirpear. At the time of discharge, the form is completed by the house officer, then
Bilateral neonatal Wilms' tumor with B-C chromosomal translocation
The Journal of Pediatrics January 1975
reviewed and counter-signed by the attending physician. The summary is then transported to the record room, typed, and returned within 24 hours to the unit secretary. The secretary is responsible for obtaining signatures o f t h e house officers and attending physicians and for mailing summaries to the appropriate physicians. A small card (Fig. 2) is sent along with the discharge s u m m a r y to the referring physician. This card may be returned if the physician wishes photocopies of additional portions of the hospital chart. Our new system has now been employed for a period of 15 months. It has been viewed favorably by house officers, faculty, and the referring physicians. Only seven requests for additional information have been received during the past year. In order to assess the efficiency of the new system, the n u m b e r of charts awaiting summary at the end of each m o n t h for the period March, 1973, to February, 1974, was compared with the same period in 1972-1973. A total of 662 charts had not been summarized in the year 1972-1973, while only six had not been completed in the year 1973-1974. Other approaches to the problem may work equally well. We have been pleased with the efficiency of this particular approach and the satisfaction it has engendered on the part of both the sender and the recipient.
described by Bolande and associates I which is benign. Isolated case reports of mesoblastic n e p h r o m a in the n e w b o r n i n f a n t have a p p e a r e d s p o r a d i c a l l y , a n d 30 cases have been summarized recently2; the n u m b e r o f proved cases of bilateral Wilms' tumor in the neonate is even less.
Joseph Giangiacomo, M.D.,* Lila Penehansky, M.D.,** Patrieia L. Monteleone, M.D., and Jay Thompson, M.D. St. Louis, Mo. TRUE WlLMS' TUMOR of the newborn infant is rare. In the past, there has been confusion between Wilms' tumor in the neonate and the mesoblastic n e p h r o m a From the Departments o f Pediatrics, Pathology, and Radiology, St. Louis University Medical School Cardinal Glennon Memorial Hospital.for Children. Supported in part by the Bidwill Memorial R esearch Fund and the National Foundation-March o f Dimes. *Reprintaddress:1465S. GrandBlvd., St. Louis, Mo. 63104. **DriscollFellow.
L
Abbreviation used IVP: intravenous pyelogram
Miller a n d associates 3 f o u n d a s s o c i a t e d c o n g e n i t a l anomalies in 66 (15%) of 440 patients with Wilms' tumor. C h r o m o s o m a l a b n o r m a l i t i e s with t r i s o m y 18 and pseudohermaphroditism with X X / X Y mosaicism have also been described with Wilms' tumor. 4,s The following is a report of a newborn infant with bilateral Wilms' tumor and B-C translocation, an association not previously reported. The child exhibited striking Potter's facies, which has been associated with a n u m b e r of congenital anomalies including unilateral or bilateral renal agenesis, hypoplastic or dysplastic kid-
Volume 86 Number 1
Brief clinical and laboratory observations
99
Fig. 1. Potter's facies.
n e y s , cystic renal disease, a n d a variety o f e x t r a r e n a l defects. 6 O l i g o h y d r a m n i o s is possibly r e s p o n s i b l e for features of Potter's syndrome. 7 CASE PRESENTATION B. M. was a one-day-old, white male with multiple congenital anomalies. His mother was gravida I, para I, aborta O. Her pregnancy was complicated by a 16 kg weight gain and she had taken diuretics and vitamins during the fifth month of pregnancy. The infant had a normal vertex delivery at 33 weeks' gestation and a normal amount of amniotic fluid was present. Birth weight was 2.7 kg; head circumference of 33.0 cm, chest circumference of 30.0 cm. The optic fundi were unremarkable. The ears were low set, the nose flattened and beaklike, and mild micrognathia was present, characteristic of a Potter's facies (Fig. 1). The lungs were clear and no cardiac murmurs were heard. The abdomen was protuberant with smooth masses palpable bilaterally in the flanks. The testes could not be palpated. The hands were broad and spadelike, with a skin tag attached to the fifth digits. There were bilateral talipes equinovarus deformities, with polydactaly and webbing of the toes. The baby had good Moro, grasp, and suck reflexes, but had a somewhat weak and high-pitched cry. Initial hematologic values were normal as was the urinanalysis. Blood urea n i t r o g e n was-10 mg, and s e r u m creatinine was 0.9 mg/dl. The chest radiograph was unremarkable. An initial intravenous pyelogram revealed bilateral renal enlargement with marked distortion of the pelvocalyceal collecting systems. On the right side, a collection of contrast medium in the superior pole of the kidney was thought to be in dysplastic tubules rather than in a definable superior pole calyx. The kidneys were not considered to be hydronephrotic.
Fig. 2. Bilateral retrograde pyelogram. Attempts to pass a retrograde catheter into the left renal pelvis were unsuccessful with the catheter coiling upon itself in the proximal ureter. The left kidney was hydronephrotic. The distal left ureter was deviated to the right and was compressed by the enlarging lower pole of the left kidney. A large polypoid mass was demonstrated occupying the entire right renal pelvis and causing severe distortion of the pelvocaiyceal collecting system. At 3 weeks of age, the left kidney had increased markedly in size. Another IVP showed severe hydronephrosis of the left kidney but no change of the right one. Cystoscopy and retrograde pyelograms at this time revealed a large polypoid mass which occupied the pelvocalyceal collecting system of the right kidney. On the left, marked hydronephrosis was present secondary to partial obstruction of the ureteropelvic junction. The left ureter was deviated to the right by the enlarged lower p01e of the left kidney (Fig. 2). At laporatomy a large u n r e s e c t a b l e mass filled the pelvocalyceal collecting system of the left kidney, causing proximal obstruction of the left ureter. On the right side, a similar mass was found but without obstruction. Frozen sections of the masses were diagnosed as bilateral Wilms' tumor. The extent of the tumor precluded any definitive surgery. Bilateral nephrostomy tubes were inserted and the abdomen was closed. Later routine examination of tissues from both kidneys confirmed the diagnosis. On the ninth postoperative day there was a gastrointestinal hemorrhage requiring transfusions with fresh whole blood.
100
Brief clinical and laboratory observations
The Journal of Pediatrics January 1975
Fig. 3. A, Polypoid projection into the pelvis covered by pelvic epithelium. (Hematoxylin-eosin x 2.5.) B; Islet of epithelial separated by myxomatous tissue. (Hematoxylin-eosin • 10.) C, Epithelial tissue cell with scanty cytoplasm round nuclei with fine chromatic pattern. (Hematoxylin-eosin • 40.) D, Neoplastic tubular formation. (Hematoxylin, eosin • 40.) E, Myxomatous tissue with elongated cells and plump nuclei. (Hematoxylin-eosin • 40.) F, Pseudocapsule separating the tumor (upper part) from renal parenchyma. (Hematoxylin-eosin x 25.) Despite continuing supportive care, the child died at 5 weeks of age. PATHOLOGY The pathologic changes were limited to the kidneys. The left kidney was enlarged; it weighed 51 gin. Bisection revealed a hemorrhagic mass which occupied the entire upper renal pole and the midportion of the renal parenchyma; there were polypoid projections into the pelvis. The right kidney contained a mass similar to the one on the left. The right pelvic mucosa was grossly normal. M i c r o s c o p i c a l l y the t u m o r and r e n a l p a r e n c h y m a were clearly separated in the medulla by bands of connective tissue which had the characteristics of a tumor pseudocapsule (Fig. 3, F ) . Normal renal tubules were engulfed by neoplasm at the junction of the tumor (Fig. 3, F). The mass was edematous, papillomatous, hemorrhagic, and focally necrotic. The external tumor surface
was entirely covered by pelvic epithelium (Fig. 3, A). The tumor was composed of islets of hematoxophilic epithelial tissue with scanty cytoplasm separated mainly by myxomatous or occasionally more cellular fibroblastic tissue (Fig. 3, B). N o cartilage was seen. The cells of the epithelial areas possessed hyperchromic nuclei (Fig. 3, C) with a fine chromatic pattern, and occasional nucleoli. In some areas, these cells formed primitive t u b u l e s with a c e n t r a l l u m e n (Fig. 3, D), b u t no neoplastic glomerular formations were seen. The tissue t h a t s u r r o u n d e d t h e a b o v e islets was c o m p r i s e d of elongated cells, with scarcely visible eosinophilic cytoplas m and with larger, less h e m a t o x o p h i l i c n u c l e i than the epithelial cells (Fig. 3, E ) . No intravascular tumor was seen in any of the multiple sections examined. The normal renal parenchyma showed variable mat u r i t y o f the g l o m e r u l i , b u t w i t h o u t tissue characteristics of Wilrns' tumor.
Volume 86 Number 1
Brief clinical and laboratory observations
101
Fig. 4. Translocation between a C chromosome to a B chromosome. CYTOGENETIC STUDIES Peripheral lymphocytes were cultured for chromosome analysis. Thirty cells were analyzed and in all the cells the modal chromosome n u m b e r was 46 with an increase in length of the long arm of one of the B group chromosomes. In one of the C group chromosomes there was a deletion of portions of the long arms (Fig. 4). The mother refused to have chromosomal analysis; the father is u n k n o w n . The cytogenetic findings in the patient were interpreted as a translocation between one of the long arms of a B chromosome and the long arms of a C chromosome (Fig. 4). Giemsa banding techniques, in an attempt to identify the specific chromosome involved, were inconclusive. DISCUSSION The pathologic features that differentiate W i l m s ' tumor from benign mesoblastic hephroma have been clarified by Bolande and associates I Differentiation between the two neoplasms is of obvious therapeutic and prognostic importance. This infant had bilateral congenital Wilms' tumor, B-C chromosomal translocation, Potter's facies, a n d talipes e q u i n o v a r u s , polydactaly, webbing of the toes, and broad, spadelike hands without oligohydramnios.
There has b e e n little data to suggest c o n s i s t e n t chromosomal abnormalities in association with Potter's facies. P a s s a r g e a n d S u t h e r l a n d 8 f o u n d a n o r m a l chromosomal pattern in three patients with Potter's facies. T h e r e are two reports of a b n o r m a l c h r o m o somes in infants with Pottei"s facies, one with a Y-21 translocation9 and one with XX sex chromosomes and male external genitals; :~ our patient is the third case with c h r o m o s o m a l a b n o r m a l i t i e s . This paucity of chromosomal studies may reflect the u n c o m m o n occurrence of the syndrome or the frequency of stillbirth or of early death. Our patient may represent an isolated combination of chromosomal abnormalites of Wilms' tumor or may suggest a more common association. The authors are indebted to Dr. Roland Triska for referral of the patient, the technical assistance of Miss Joan Grzegocki, Mr. Michael Tietjens, and Sr. Leo Rita Volk, and the secretarial assistance of Mrs. Catherine Camp. REFERENCES
1. Bolande R, Brough A, and Izant R: Congenital mesoblastic nephroma of infancy, Pediatrics 40: 272, 1967. 2. Bolande R: Congenital mesoblastic nephroma of infancy, in Perspectives in Pediatric Pathology, Vol 1, Chicago, 1973, Year Book Medical Publishers, Inc., p 227.
102
Brief clin&al and laboratory observations
3. 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. 4. Gieser CF, and Schindler AM: Long-term survival in a male with 18-trisomy syndrome and Wilms' tumor, Pediatrics 44: 111, 1969. 5. Denys P, Mal Vaux P, Van den Berghe H, Tanghe W, and Proesman W: Association d'un syndrome anatomopathologique de pseudohermaphrodisme masculin, d'une tumeur de Wilms', d'une nephropathie parenchymateuse et d'un mosaicisme XX/XY, Arch Franc Pediatr 24: 729, 1967. 6. Kissane JM~ and Smith, MG: Pathology of infancy and
The glucagon infusion test and growth hormone secretion Theodore W. AvRuskin, M.D., F.A.A.P., F.R.C.P.(C),* Shiu-Ching Tang, M.D., and Christina S. Juan, B.S. Chem., New York, N. Y.
The Journal of Pediatrics January 1975
childhood, St. Louis, 1967, The C. V. Mosby Company. 7. Thomas IT, and Smith DW: Oligohydramnios, cause of the nonrenal features of potter's syndrome, including pulmonary hypoplasia, J PEDIATR84:811, 1974. 8. PassargeE, and Suther.land JM: Potter's syndrome, Am J Dis child 109: 80, 1965. 9. Hillman LS, Sekhon GS, Kaufman RL, and Ho C: Y/21 Translocation with gonadal and renal dysgenesis and cardiac rupture, Am J Dis Child (.in press). 10. Schlegel RJ, Aspillage MJ, Lew RL, Cameiro-Lesno J, and Gardner LI: An XX sex chromosome complement in an infant having male-type external genitals, renal agenesis and other anomalies, J PEDIATR69: 812, 1966.
cantly altered by prior administration of tolbutamide. 6,7 S u b s e q u e n t l y , similar I R G H responses following glucagon i n f u s i o n s have b e e n n o t e d in j u v e n i l e diabetes mellitus.8 The present study was designed to investigate the effects on G H release of 30 minute infusions of glucagon, and whether 30 minute infusions altered the subsequent time course of the GH peak when compared to our original investigations: MATERIAL
PROVOCATIVE TESTS of G H secretion in infants a n d c h i l d r e n h a v e b e e n p r i n c i p a l l y l i m i t e d to responses to exogenous insulin and arginine 1, 2 and more recently to administration of propranolol 3 and L - d o p a . 4 S y m p t o m a t i c h y p o g l y c e m i a following ins u l i n testing, p a r a d o x i c a l G H s e c r e t i o n after IV glucose, and nausea, p a l p i t a t i o n , and v e r t i g o after arginine are all reported. We originally reported that glucagon* administration, IM or as a rapid IV bolus, in normal infants and children consistently increased serum I R G H concentrations and that these responses were not signifiFrom the Division of Pediatric Endocrinology and Metabolism and The Hanid Endocrinology Laboratory, Department of Pediatrics, The Brookdale Hospital Medical Center, New York UniversitySchool of Medicine. Supported by The A rnoMSchwartz Foundationfor Medical Research and Education and The Hanid Foundationfor Diabetes Mellitus and Endocrinology Research. *Reprint address: Division o f Pediatric Endocrinology and Metabolism, Department of Pediatrics, The Brookdale Hospital Medical Center, Linden Blvd. at Brookdale Plaza, Brooklyn, IV. Y. 11212. *Glucagon for injection, U.S.P., Eli Lilly and Co., Indianapolis, Ind. The insulin concentration has been reported5 to be less than 0.05 U/rag by mouse convulsion assay and 0.04-0.08 U/mg by immunoassay.
AND METHODS
Clinical. Forty-one patients were studied. Twentythree children with genetic short stature, three adults and one adolescent who had acromegaly, and two Abbreviations used GH: growth hormone IRI: immunoreactive insulin IRGH: immunoreactive growth hormone IM: intramuscular IV: intravenously children with hypopituitarism were given IV glucagon. The five girls and 18 boys were 3 6/12 to 15 9/12 years of age. None was obese. Bone maturation was assessed by the standards of Greulich and Pyle. Skeletal age excluded evidence of hypothyroidism. Growth velocity curves (calculated in cm/year) excluded evidence of growth hormone deficiency. All patients had normal adrenal and thyroid functions. Twelve other patients (10 boys, 2 girls) had IM glucagon tests. Chronologic ages ranged from 1 3/12 to 10 8/12 years. Bone ages were comparable to height ages. None was obese or malnourished. Growth velocities ranged from 2.4-9.0 cm/year. The four acromegalic patients consisted of one 13year-old girl, reported elsewhere, 9 and three adult pa-
B r i e f clinical and laboratory observations
Medical Records Request Attached is a copy of the discharse summary on your patient. Should you need a complete copy of all or parts of the medical record, please check those desired and return this form to: MEDICAL RECORDS DEPARTMENT Upstate Medical Center 750East Adams Street Syracuse, New York 13210
(
I Physician's Notes [
l
J Laboratory Data
(Includi~ns x-rays,
[ N..... 'Notes
~
Entire Rec.ord
EEG, EKG, etc.)
Physlcian's Name Address
Fig. 2 A working copy of the discharge form is included in the chart of each pediatric patient at the time of his admission to the hospital. Problems which are present at the time of admission are immediately entered. New problems are entered as they alirpear. At the time of discharge, the form is completed by the house officer, then
Bilateral neonatal Wilms' tumor with B-C chromosomal translocation
The Journal of Pediatrics January 1975
reviewed and counter-signed by the attending physician. The summary is then transported to the record room, typed, and returned within 24 hours to the unit secretary. The secretary is responsible for obtaining signatures o f t h e house officers and attending physicians and for mailing summaries to the appropriate physicians. A small card (Fig. 2) is sent along with the discharge s u m m a r y to the referring physician. This card may be returned if the physician wishes photocopies of additional portions of the hospital chart. Our new system has now been employed for a period of 15 months. It has been viewed favorably by house officers, faculty, and the referring physicians. Only seven requests for additional information have been received during the past year. In order to assess the efficiency of the new system, the n u m b e r of charts awaiting summary at the end of each m o n t h for the period March, 1973, to February, 1974, was compared with the same period in 1972-1973. A total of 662 charts had not been summarized in the year 1972-1973, while only six had not been completed in the year 1973-1974. Other approaches to the problem may work equally well. We have been pleased with the efficiency of this particular approach and the satisfaction it has engendered on the part of both the sender and the recipient.
described by Bolande and associates I which is benign. Isolated case reports of mesoblastic n e p h r o m a in the n e w b o r n i n f a n t have a p p e a r e d s p o r a d i c a l l y , a n d 30 cases have been summarized recently2; the n u m b e r o f proved cases of bilateral Wilms' tumor in the neonate is even less.
Joseph Giangiacomo, M.D.,* Lila Penehansky, M.D.,** Patrieia L. Monteleone, M.D., and Jay Thompson, M.D. St. Louis, Mo. TRUE WlLMS' TUMOR of the newborn infant is rare. In the past, there has been confusion between Wilms' tumor in the neonate and the mesoblastic n e p h r o m a From the Departments o f Pediatrics, Pathology, and Radiology, St. Louis University Medical School Cardinal Glennon Memorial Hospital.for Children. Supported in part by the Bidwill Memorial R esearch Fund and the National Foundation-March o f Dimes. *Reprintaddress:1465S. GrandBlvd., St. Louis, Mo. 63104. **DriscollFellow.
L
Abbreviation used IVP: intravenous pyelogram
Miller a n d associates 3 f o u n d a s s o c i a t e d c o n g e n i t a l anomalies in 66 (15%) of 440 patients with Wilms' tumor. C h r o m o s o m a l a b n o r m a l i t i e s with t r i s o m y 18 and pseudohermaphroditism with X X / X Y mosaicism have also been described with Wilms' tumor. 4,s The following is a report of a newborn infant with bilateral Wilms' tumor and B-C translocation, an association not previously reported. The child exhibited striking Potter's facies, which has been associated with a n u m b e r of congenital anomalies including unilateral or bilateral renal agenesis, hypoplastic or dysplastic kid-
Volume 86 Number 1
Brief clinical and laboratory observations
99
Fig. 1. Potter's facies.
n e y s , cystic renal disease, a n d a variety o f e x t r a r e n a l defects. 6 O l i g o h y d r a m n i o s is possibly r e s p o n s i b l e for features of Potter's syndrome. 7 CASE PRESENTATION B. M. was a one-day-old, white male with multiple congenital anomalies. His mother was gravida I, para I, aborta O. Her pregnancy was complicated by a 16 kg weight gain and she had taken diuretics and vitamins during the fifth month of pregnancy. The infant had a normal vertex delivery at 33 weeks' gestation and a normal amount of amniotic fluid was present. Birth weight was 2.7 kg; head circumference of 33.0 cm, chest circumference of 30.0 cm. The optic fundi were unremarkable. The ears were low set, the nose flattened and beaklike, and mild micrognathia was present, characteristic of a Potter's facies (Fig. 1). The lungs were clear and no cardiac murmurs were heard. The abdomen was protuberant with smooth masses palpable bilaterally in the flanks. The testes could not be palpated. The hands were broad and spadelike, with a skin tag attached to the fifth digits. There were bilateral talipes equinovarus deformities, with polydactaly and webbing of the toes. The baby had good Moro, grasp, and suck reflexes, but had a somewhat weak and high-pitched cry. Initial hematologic values were normal as was the urinanalysis. Blood urea n i t r o g e n was-10 mg, and s e r u m creatinine was 0.9 mg/dl. The chest radiograph was unremarkable. An initial intravenous pyelogram revealed bilateral renal enlargement with marked distortion of the pelvocalyceal collecting systems. On the right side, a collection of contrast medium in the superior pole of the kidney was thought to be in dysplastic tubules rather than in a definable superior pole calyx. The kidneys were not considered to be hydronephrotic.
Fig. 2. Bilateral retrograde pyelogram. Attempts to pass a retrograde catheter into the left renal pelvis were unsuccessful with the catheter coiling upon itself in the proximal ureter. The left kidney was hydronephrotic. The distal left ureter was deviated to the right and was compressed by the enlarging lower pole of the left kidney. A large polypoid mass was demonstrated occupying the entire right renal pelvis and causing severe distortion of the pelvocaiyceal collecting system. At 3 weeks of age, the left kidney had increased markedly in size. Another IVP showed severe hydronephrosis of the left kidney but no change of the right one. Cystoscopy and retrograde pyelograms at this time revealed a large polypoid mass which occupied the pelvocalyceal collecting system of the right kidney. On the left, marked hydronephrosis was present secondary to partial obstruction of the ureteropelvic junction. The left ureter was deviated to the right by the enlarged lower p01e of the left kidney (Fig. 2). At laporatomy a large u n r e s e c t a b l e mass filled the pelvocalyceal collecting system of the left kidney, causing proximal obstruction of the left ureter. On the right side, a similar mass was found but without obstruction. Frozen sections of the masses were diagnosed as bilateral Wilms' tumor. The extent of the tumor precluded any definitive surgery. Bilateral nephrostomy tubes were inserted and the abdomen was closed. Later routine examination of tissues from both kidneys confirmed the diagnosis. On the ninth postoperative day there was a gastrointestinal hemorrhage requiring transfusions with fresh whole blood.
100
Brief clinical and laboratory observations
The Journal of Pediatrics January 1975
Fig. 3. A, Polypoid projection into the pelvis covered by pelvic epithelium. (Hematoxylin-eosin x 2.5.) B; Islet of epithelial separated by myxomatous tissue. (Hematoxylin-eosin • 10.) C, Epithelial tissue cell with scanty cytoplasm round nuclei with fine chromatic pattern. (Hematoxylin-eosin • 40.) D, Neoplastic tubular formation. (Hematoxylin, eosin • 40.) E, Myxomatous tissue with elongated cells and plump nuclei. (Hematoxylin-eosin • 40.) F, Pseudocapsule separating the tumor (upper part) from renal parenchyma. (Hematoxylin-eosin x 25.) Despite continuing supportive care, the child died at 5 weeks of age. PATHOLOGY The pathologic changes were limited to the kidneys. The left kidney was enlarged; it weighed 51 gin. Bisection revealed a hemorrhagic mass which occupied the entire upper renal pole and the midportion of the renal parenchyma; there were polypoid projections into the pelvis. The right kidney contained a mass similar to the one on the left. The right pelvic mucosa was grossly normal. M i c r o s c o p i c a l l y the t u m o r and r e n a l p a r e n c h y m a were clearly separated in the medulla by bands of connective tissue which had the characteristics of a tumor pseudocapsule (Fig. 3, F ) . Normal renal tubules were engulfed by neoplasm at the junction of the tumor (Fig. 3, F). The mass was edematous, papillomatous, hemorrhagic, and focally necrotic. The external tumor surface
was entirely covered by pelvic epithelium (Fig. 3, A). The tumor was composed of islets of hematoxophilic epithelial tissue with scanty cytoplasm separated mainly by myxomatous or occasionally more cellular fibroblastic tissue (Fig. 3, B). N o cartilage was seen. The cells of the epithelial areas possessed hyperchromic nuclei (Fig. 3, C) with a fine chromatic pattern, and occasional nucleoli. In some areas, these cells formed primitive t u b u l e s with a c e n t r a l l u m e n (Fig. 3, D), b u t no neoplastic glomerular formations were seen. The tissue t h a t s u r r o u n d e d t h e a b o v e islets was c o m p r i s e d of elongated cells, with scarcely visible eosinophilic cytoplas m and with larger, less h e m a t o x o p h i l i c n u c l e i than the epithelial cells (Fig. 3, E ) . No intravascular tumor was seen in any of the multiple sections examined. The normal renal parenchyma showed variable mat u r i t y o f the g l o m e r u l i , b u t w i t h o u t tissue characteristics of Wilrns' tumor.
Volume 86 Number 1
Brief clinical and laboratory observations
101
Fig. 4. Translocation between a C chromosome to a B chromosome. CYTOGENETIC STUDIES Peripheral lymphocytes were cultured for chromosome analysis. Thirty cells were analyzed and in all the cells the modal chromosome n u m b e r was 46 with an increase in length of the long arm of one of the B group chromosomes. In one of the C group chromosomes there was a deletion of portions of the long arms (Fig. 4). The mother refused to have chromosomal analysis; the father is u n k n o w n . The cytogenetic findings in the patient were interpreted as a translocation between one of the long arms of a B chromosome and the long arms of a C chromosome (Fig. 4). Giemsa banding techniques, in an attempt to identify the specific chromosome involved, were inconclusive. DISCUSSION The pathologic features that differentiate W i l m s ' tumor from benign mesoblastic hephroma have been clarified by Bolande and associates I Differentiation between the two neoplasms is of obvious therapeutic and prognostic importance. This infant had bilateral congenital Wilms' tumor, B-C chromosomal translocation, Potter's facies, a n d talipes e q u i n o v a r u s , polydactaly, webbing of the toes, and broad, spadelike hands without oligohydramnios.
There has b e e n little data to suggest c o n s i s t e n t chromosomal abnormalities in association with Potter's facies. P a s s a r g e a n d S u t h e r l a n d 8 f o u n d a n o r m a l chromosomal pattern in three patients with Potter's facies. T h e r e are two reports of a b n o r m a l c h r o m o somes in infants with Pottei"s facies, one with a Y-21 translocation9 and one with XX sex chromosomes and male external genitals; :~ our patient is the third case with c h r o m o s o m a l a b n o r m a l i t i e s . This paucity of chromosomal studies may reflect the u n c o m m o n occurrence of the syndrome or the frequency of stillbirth or of early death. Our patient may represent an isolated combination of chromosomal abnormalites of Wilms' tumor or may suggest a more common association. The authors are indebted to Dr. Roland Triska for referral of the patient, the technical assistance of Miss Joan Grzegocki, Mr. Michael Tietjens, and Sr. Leo Rita Volk, and the secretarial assistance of Mrs. Catherine Camp. REFERENCES
1. Bolande R, Brough A, and Izant R: Congenital mesoblastic nephroma of infancy, Pediatrics 40: 272, 1967. 2. Bolande R: Congenital mesoblastic nephroma of infancy, in Perspectives in Pediatric Pathology, Vol 1, Chicago, 1973, Year Book Medical Publishers, Inc., p 227.
102
Brief clin&al and laboratory observations
3. 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. 4. Gieser CF, and Schindler AM: Long-term survival in a male with 18-trisomy syndrome and Wilms' tumor, Pediatrics 44: 111, 1969. 5. Denys P, Mal Vaux P, Van den Berghe H, Tanghe W, and Proesman W: Association d'un syndrome anatomopathologique de pseudohermaphrodisme masculin, d'une tumeur de Wilms', d'une nephropathie parenchymateuse et d'un mosaicisme XX/XY, Arch Franc Pediatr 24: 729, 1967. 6. Kissane JM~ and Smith, MG: Pathology of infancy and
The glucagon infusion test and growth hormone secretion Theodore W. AvRuskin, M.D., F.A.A.P., F.R.C.P.(C),* Shiu-Ching Tang, M.D., and Christina S. Juan, B.S. Chem., New York, N. Y.
The Journal of Pediatrics January 1975
childhood, St. Louis, 1967, The C. V. Mosby Company. 7. Thomas IT, and Smith DW: Oligohydramnios, cause of the nonrenal features of potter's syndrome, including pulmonary hypoplasia, J PEDIATR84:811, 1974. 8. PassargeE, and Suther.land JM: Potter's syndrome, Am J Dis child 109: 80, 1965. 9. Hillman LS, Sekhon GS, Kaufman RL, and Ho C: Y/21 Translocation with gonadal and renal dysgenesis and cardiac rupture, Am J Dis Child (.in press). 10. Schlegel RJ, Aspillage MJ, Lew RL, Cameiro-Lesno J, and Gardner LI: An XX sex chromosome complement in an infant having male-type external genitals, renal agenesis and other anomalies, J PEDIATR69: 812, 1966.
cantly altered by prior administration of tolbutamide. 6,7 S u b s e q u e n t l y , similar I R G H responses following glucagon i n f u s i o n s have b e e n n o t e d in j u v e n i l e diabetes mellitus.8 The present study was designed to investigate the effects on G H release of 30 minute infusions of glucagon, and whether 30 minute infusions altered the subsequent time course of the GH peak when compared to our original investigations: MATERIAL
PROVOCATIVE TESTS of G H secretion in infants a n d c h i l d r e n h a v e b e e n p r i n c i p a l l y l i m i t e d to responses to exogenous insulin and arginine 1, 2 and more recently to administration of propranolol 3 and L - d o p a . 4 S y m p t o m a t i c h y p o g l y c e m i a following ins u l i n testing, p a r a d o x i c a l G H s e c r e t i o n after IV glucose, and nausea, p a l p i t a t i o n , and v e r t i g o after arginine are all reported. We originally reported that glucagon* administration, IM or as a rapid IV bolus, in normal infants and children consistently increased serum I R G H concentrations and that these responses were not signifiFrom the Division of Pediatric Endocrinology and Metabolism and The Hanid Endocrinology Laboratory, Department of Pediatrics, The Brookdale Hospital Medical Center, New York UniversitySchool of Medicine. Supported by The A rnoMSchwartz Foundationfor Medical Research and Education and The Hanid Foundationfor Diabetes Mellitus and Endocrinology Research. *Reprint address: Division o f Pediatric Endocrinology and Metabolism, Department of Pediatrics, The Brookdale Hospital Medical Center, Linden Blvd. at Brookdale Plaza, Brooklyn, IV. Y. 11212. *Glucagon for injection, U.S.P., Eli Lilly and Co., Indianapolis, Ind. The insulin concentration has been reported5 to be less than 0.05 U/rag by mouse convulsion assay and 0.04-0.08 U/mg by immunoassay.
AND METHODS
Clinical. Forty-one patients were studied. Twentythree children with genetic short stature, three adults and one adolescent who had acromegaly, and two Abbreviations used GH: growth hormone IRI: immunoreactive insulin IRGH: immunoreactive growth hormone IM: intramuscular IV: intravenously children with hypopituitarism were given IV glucagon. The five girls and 18 boys were 3 6/12 to 15 9/12 years of age. None was obese. Bone maturation was assessed by the standards of Greulich and Pyle. Skeletal age excluded evidence of hypothyroidism. Growth velocity curves (calculated in cm/year) excluded evidence of growth hormone deficiency. All patients had normal adrenal and thyroid functions. Twelve other patients (10 boys, 2 girls) had IM glucagon tests. Chronologic ages ranged from 1 3/12 to 10 8/12 years. Bone ages were comparable to height ages. None was obese or malnourished. Growth velocities ranged from 2.4-9.0 cm/year. The four acromegalic patients consisted of one 13year-old girl, reported elsewhere, 9 and three adult pa-