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Neuroblastoma sympatheticum with metastases
Case Reports NEUROBLASTOMA SYMPATHETICUlVI WITH
METASTASES
I~EPORT OF A CASE WITH APPARENT RECOVERY
DAVID GOLDRING,M.D. ST. LOUIS, !VI0. N
E U R O B L A S T O M A is a highly malignant t u m o r t h a t metastasizes early and widely as is well-demonstrated in numerous published reports in which there were no recoveries}, ~, 3 Farberr ~ however, was the first to point out that the prognosis in this t y p e of tumor, while serious, is not always hopeless. Reports in the literature of recovery are few, and the possible mechanisms in such recovery as listed by F a r b e r 4 are as follows: 1. The neuroblastoma m a y undergo spontaneous hemorrhage and necrosis and disappear without a n y treatment. 2. The neuroblastoma m a y undergo spontaneous m a t u r a t i o n or metaplasia and become a benign ganglioneuroma. Cushing 6 reported this phenomen in a patient f r o m whom he removed a ganglioneuroma f r o m the p a r a v e r t e b r a l region at the level of the sixth dorsal vertebral body where ten years previously he has f o u n d a neuroblastoma. Chandler and Nareross 7 have reported two similar cases. 3. The neuroblastoma m a y be treated successfully by a combination of surgical removal of the t u m o r followed by irradiation. L e h m a n s, 9 r e p o r t e d a case of neuroblastoma with recovery a f t e r surgical removal of the tumor, while Kerley ~~ reported one five-year survival and one twelve-year survival. F a r b e r * was the first to report the recovery in two p a t i e n t s who h a d liver metastases and in eight other patients without metastases who have remained alive and well f o r a n u m b e r of years a f t e r surgical removal of the tumor. The case to be reported here is one in which there were definite metastatic From the Department of Pediatrics, Washington University School of Medicine. and the St. Louis Children's Hospital. 231
lesions in the liver, demonstrated during an exploratory laparotomy, and probable metastatic involvement of the skeletal system by x-ray, i t was found impo,ssible to remove the o r i g i n a 1 tumor, and so the patient was treated with small doses of x-ray irradiation a n d with supportive t h e r a p y in the f o r m of whole blood transfusions. This patient is still alive two years a f t e r the discovery of the t u m o r and has no a p p a r e n t sign of the disease. CASE R E P O R T
G. S., a white male, was first seen on March 4, 1947, because of a mild u p p e r r e s p i r a t o r y infection and was found to have a mild otitis and phaITngitis. Physical examination was otherwise negative. The p a r e n t s were healthy, and the p r e g n a n c y had been nomnal. B i r t h weight was 6 pounds, 7 ounces, a n d on feedings of evaporated milk supplemented with vitamins, his weight at 4 months of age was 13 pounds and his height 241/2 inches. H e was again observed a month later, at age 5 months, with a mild rhinitis but no other abnormality. Three weeks later, however, on April 28, 1947, he suddenly developed bilateral hemorrhages of the eyelids and, when examined, in addition to the periorbital ecchymoses, was found to be definitely anemic and to have a palpable mass in the u p p e r right abdomen. This was firm, not too sharply outlined, but slightly movable, and a p p e a r e d to be beneath the liver which was pushed somewhat u p w a r d and forward. On fluoroscopy, a radiopaque mass was seen in the right u p p e r abdomen, and the right d i a p h r a g m was considerably higher t h a n the left. A f t e r admission to the St. Catheri n e ' s Hospital, Whiting, Ind., for
232
THE
J O U R N A L OF P E D I A T R I C S
t~ig. 1 . - - T h e b a b y a s he a p p e a r e d a t t i m e of t h e e x p l o r a t o r y o p e r a t i o n . N o t e t h e p e r i o r bital ecchymosis, bulbar conjunetival hemorr h a g e , a n d p r o p t o s i s . ( P h o t o g r a p h c o u r t e s y of Dr'. J o h n K e e l e y , C h i c a g o , :Ill.)
study, the :following laboratory findings were obtained. Blood: hemoglobin 7.4 Gin., erythroeytes 3,040,000, platelets 60,800, leucocytes 7,500 with a differential of 1 basophile, 2 eosinophiles, 1 juvenile, 2 stab eel.Is, 26 segmented cells, 68 lymphocytes, and 5 normoblasts p e r 100 leucocytes. Bleeding time was 11 minutes and clotting time 41/2 minutes. Blood chemistry: nonprotein nitrogen 38 nag., chlorides 569 mg., total serum protein 6.6 Gm., with albumin 5.3 Gin. and globulin 1.3 Gm. per 100 e.c. An intravenous pyelogram showed the right kidney pelvis much lower than the left, and x-rays revealed, in addition to the mass in the right u p p e r q u a d r a n t noted on fluoroscopy, an area of localized r a r e f a c t i o n in the u p p e r right humerus and a suggestion of similar areas in the skull. The patient was given three whole blood transfusions of 100 c.c. each while in the hospital and six deep x-ray treatments to the right kidney region in divided doses of 200 roentgens for a total of 1,200 roentgens. The patient was then t r a n s f e r r e d to Mercy H o s p i t a l in
Chicago for surgical exploration. At this time, the periorbital and eonjunetival hemorrhage and proptosis were r a t h e r marked (Pig. 1). The p a t i e n t ' s abdomen was explored on May 24, 1947, by Dr. J o h n Keeley, a member of the surgical staff of Mercy tIospitM, and the liver was found to be extensively involved with nodular masses--some soft, some h a r d - - w h i c h varied in color from light yellow to orange. Some were whitish in color. There were nodules up over the dome of the right lobe of the liver, and upon palpating' the region of the right kidney, the lower and middle portions of the kidney were entirely normal. The u p p e r portion of the kidney was in continuity with a retroperitoneal mass which seemed to come u p w a r d and anteriorly to involw~ the liver in a nodular manner. A biopsy wedge of the liver was taken. Microseopic examination of this tissue showed the liver to be involved by extensive t u m o r deposits of a neuroblastoma. The t u m o r revealed very well-defined rosette formation over wide areas, and elsewhere it grew in more solid or cordlike closely packed masses of cells in a fibrous stroma (Figs. 2 and 3). The patient was given two more blood transfusions of 120 c.c. each and was discharged to be followed at home. D u r i n g the month of June, he was given five more sessions of x - r a y t h e r a p y to the r i g h t kidney region for a total of 750 roentgen units. X - r a y t h e r a p y was stopped because he developed a marked leueopenia and anemia. Also during this month he was given two blood transfusions of 120 c.c. each. The patient, however, seemed to be getting more marked proptosis, so that celluloid protective shields had to be constructed for his eyes. D u r i n g the month of July, he was given two whole blood transfusions of 120 c.c., but his condition remained grave. H e was seen again on Aug. 16, 1947, and, surprisingly enough, showed r a t h e r striking improvement. His weight was 15 pounds, 8 ounces. The mass in the right side of his abdomen was smaller, and the proptosis was not as marked. He showed no evidence of anemia. H e
GOLDRING:
NEUROBLASTOMA
SYMPATHETICUI~I WITH
Fig. 2.
METASTASES
233
Fig. 3.
Fig'. 2 . - - P o s i t i o n o f t h e I 4 i d n e y s in s~tu_ N o t e s i z e a n d p r o x i m i t y to o n e a n o t h e r . formation. M a g n i f i c a t i o n p o w e r X10. Fig. 3.--Typical rosette formation of cells. Magnification power X95.
was seen again one month later, and he had gained two pounds. The proptosis was very slight, and the mass in the right side of his abdomen was smaller. The p a t i e n t was followed at periodic intervals and continued to show improvement, and when he was seen on Sept. 8, ]948, at 23 months of age, his weight was 25 pounds, and his height 34 inches (Fig. 4). A t the time he showed no clinical evidence of the original tumor. His proptosis was abse~:t as was the right-sided abdominal mass. X - r a y s of his skeletal system takerl on Nov. 24, ]94%, and Sept. 15, 1949, revealed no metastases. An examination of his peripheral blood was withh~ normal limits. I t is difficult to explain the favorable outcome in this p a r t i c u l a r case. One might assume that the topical x-ray t h e r a p y which, a 1 t h o u g h small in amount, produced necrosis and destruction of the t u m o r and possibly also t h a t of the metastatic lesions in the liver. I t would be extremely difficult to explain the disappearance of the meta-
static lesions in the skeletal system and periorbital regions. Again, it is worthy of emphasis that the prognosis in this
Fig. 4.--The patient as he appeared Sept. 8, 19~48, a t w h i c h t i m e he s h o w e d e v i d e n c e of o r i g i n a l t u m o r .
on no
234
THE JOURNAL OF PEDIATRICS
t y p e of t u m o r is s e r i o u s means hopeless.
but
by
no
The helpful advice of Dr. J e a n V. Cooke and Dr. Alexis F. H a r t m a n n is gratefully acknowledged.
1.
2. 3. 4.
REFERENCES Redman, J. L., Agerty, ]-I. A , Barthmaier, O. F., and Fisher, It. R. : Adrenal Neuroblastoma--Review of Literature, Am. J. Dis. Child. 50: 1097, 1938. Rypins, E. L.: Roentgen Diagnosis of Neuroblastoma in Children, Am. J. Roentgen. 37: 325, 1937. Boyd, ~Vm.: Three Tumors Arising From Neurob]asts, Arch. Surg. 12: 1031, 1936. Wyatt, G. M., and Farber, S.: Neuroblastoma Sympatheticnm : Roentgeno-
5.
6.
7. 8. 9. ]0.
logical Appearances and Radiation Treatment, Am. J. Roentgenol. 46: 485, 1941. Ladd, W. E., and Gross, R. E." Abdominal Surgery of I n f a n c y and Childhood, Philadelphia~ 1941, W. B. Saunders Co, Chap. 36. Cushing, It., and Wolbaeh, S. B.: The Transformation of a Malignaat Paravertebral Sympathieoblastoma Into a Benign Ganglioneuroma~ Am. J. Path. 3: 203, 1927. Chandler, F. A., and Nareross, J. R.: Sympathicoblastoma, J. A. M. A. 114: 113~ 1940. Lehman~ E . P . : J. M. Research 36: 309, 1917. I~bid.9 Adrenal Neuroblastoma in Infancy - - F i f t e e n Year Survival~ Ann. Surg. 95: 473, 1932. Farber, S.- Neuroblastoma, Am. J. Dis. Child. 60: 749, 1940.
METASTASES
I~EPORT OF A CASE WITH APPARENT RECOVERY
DAVID GOLDRING,M.D. ST. LOUIS, !VI0. N
E U R O B L A S T O M A is a highly malignant t u m o r t h a t metastasizes early and widely as is well-demonstrated in numerous published reports in which there were no recoveries}, ~, 3 Farberr ~ however, was the first to point out that the prognosis in this t y p e of tumor, while serious, is not always hopeless. Reports in the literature of recovery are few, and the possible mechanisms in such recovery as listed by F a r b e r 4 are as follows: 1. The neuroblastoma m a y undergo spontaneous hemorrhage and necrosis and disappear without a n y treatment. 2. The neuroblastoma m a y undergo spontaneous m a t u r a t i o n or metaplasia and become a benign ganglioneuroma. Cushing 6 reported this phenomen in a patient f r o m whom he removed a ganglioneuroma f r o m the p a r a v e r t e b r a l region at the level of the sixth dorsal vertebral body where ten years previously he has f o u n d a neuroblastoma. Chandler and Nareross 7 have reported two similar cases. 3. The neuroblastoma m a y be treated successfully by a combination of surgical removal of the t u m o r followed by irradiation. L e h m a n s, 9 r e p o r t e d a case of neuroblastoma with recovery a f t e r surgical removal of the tumor, while Kerley ~~ reported one five-year survival and one twelve-year survival. F a r b e r * was the first to report the recovery in two p a t i e n t s who h a d liver metastases and in eight other patients without metastases who have remained alive and well f o r a n u m b e r of years a f t e r surgical removal of the tumor. The case to be reported here is one in which there were definite metastatic From the Department of Pediatrics, Washington University School of Medicine. and the St. Louis Children's Hospital. 231
lesions in the liver, demonstrated during an exploratory laparotomy, and probable metastatic involvement of the skeletal system by x-ray, i t was found impo,ssible to remove the o r i g i n a 1 tumor, and so the patient was treated with small doses of x-ray irradiation a n d with supportive t h e r a p y in the f o r m of whole blood transfusions. This patient is still alive two years a f t e r the discovery of the t u m o r and has no a p p a r e n t sign of the disease. CASE R E P O R T
G. S., a white male, was first seen on March 4, 1947, because of a mild u p p e r r e s p i r a t o r y infection and was found to have a mild otitis and phaITngitis. Physical examination was otherwise negative. The p a r e n t s were healthy, and the p r e g n a n c y had been nomnal. B i r t h weight was 6 pounds, 7 ounces, a n d on feedings of evaporated milk supplemented with vitamins, his weight at 4 months of age was 13 pounds and his height 241/2 inches. H e was again observed a month later, at age 5 months, with a mild rhinitis but no other abnormality. Three weeks later, however, on April 28, 1947, he suddenly developed bilateral hemorrhages of the eyelids and, when examined, in addition to the periorbital ecchymoses, was found to be definitely anemic and to have a palpable mass in the u p p e r right abdomen. This was firm, not too sharply outlined, but slightly movable, and a p p e a r e d to be beneath the liver which was pushed somewhat u p w a r d and forward. On fluoroscopy, a radiopaque mass was seen in the right u p p e r abdomen, and the right d i a p h r a g m was considerably higher t h a n the left. A f t e r admission to the St. Catheri n e ' s Hospital, Whiting, Ind., for
232
THE
J O U R N A L OF P E D I A T R I C S
t~ig. 1 . - - T h e b a b y a s he a p p e a r e d a t t i m e of t h e e x p l o r a t o r y o p e r a t i o n . N o t e t h e p e r i o r bital ecchymosis, bulbar conjunetival hemorr h a g e , a n d p r o p t o s i s . ( P h o t o g r a p h c o u r t e s y of Dr'. J o h n K e e l e y , C h i c a g o , :Ill.)
study, the :following laboratory findings were obtained. Blood: hemoglobin 7.4 Gin., erythroeytes 3,040,000, platelets 60,800, leucocytes 7,500 with a differential of 1 basophile, 2 eosinophiles, 1 juvenile, 2 stab eel.Is, 26 segmented cells, 68 lymphocytes, and 5 normoblasts p e r 100 leucocytes. Bleeding time was 11 minutes and clotting time 41/2 minutes. Blood chemistry: nonprotein nitrogen 38 nag., chlorides 569 mg., total serum protein 6.6 Gm., with albumin 5.3 Gin. and globulin 1.3 Gm. per 100 e.c. An intravenous pyelogram showed the right kidney pelvis much lower than the left, and x-rays revealed, in addition to the mass in the right u p p e r q u a d r a n t noted on fluoroscopy, an area of localized r a r e f a c t i o n in the u p p e r right humerus and a suggestion of similar areas in the skull. The patient was given three whole blood transfusions of 100 c.c. each while in the hospital and six deep x-ray treatments to the right kidney region in divided doses of 200 roentgens for a total of 1,200 roentgens. The patient was then t r a n s f e r r e d to Mercy H o s p i t a l in
Chicago for surgical exploration. At this time, the periorbital and eonjunetival hemorrhage and proptosis were r a t h e r marked (Pig. 1). The p a t i e n t ' s abdomen was explored on May 24, 1947, by Dr. J o h n Keeley, a member of the surgical staff of Mercy tIospitM, and the liver was found to be extensively involved with nodular masses--some soft, some h a r d - - w h i c h varied in color from light yellow to orange. Some were whitish in color. There were nodules up over the dome of the right lobe of the liver, and upon palpating' the region of the right kidney, the lower and middle portions of the kidney were entirely normal. The u p p e r portion of the kidney was in continuity with a retroperitoneal mass which seemed to come u p w a r d and anteriorly to involw~ the liver in a nodular manner. A biopsy wedge of the liver was taken. Microseopic examination of this tissue showed the liver to be involved by extensive t u m o r deposits of a neuroblastoma. The t u m o r revealed very well-defined rosette formation over wide areas, and elsewhere it grew in more solid or cordlike closely packed masses of cells in a fibrous stroma (Figs. 2 and 3). The patient was given two more blood transfusions of 120 c.c. each and was discharged to be followed at home. D u r i n g the month of June, he was given five more sessions of x - r a y t h e r a p y to the r i g h t kidney region for a total of 750 roentgen units. X - r a y t h e r a p y was stopped because he developed a marked leueopenia and anemia. Also during this month he was given two blood transfusions of 120 c.c. each. The patient, however, seemed to be getting more marked proptosis, so that celluloid protective shields had to be constructed for his eyes. D u r i n g the month of July, he was given two whole blood transfusions of 120 c.c., but his condition remained grave. H e was seen again on Aug. 16, 1947, and, surprisingly enough, showed r a t h e r striking improvement. His weight was 15 pounds, 8 ounces. The mass in the right side of his abdomen was smaller, and the proptosis was not as marked. He showed no evidence of anemia. H e
GOLDRING:
NEUROBLASTOMA
SYMPATHETICUI~I WITH
Fig. 2.
METASTASES
233
Fig. 3.
Fig'. 2 . - - P o s i t i o n o f t h e I 4 i d n e y s in s~tu_ N o t e s i z e a n d p r o x i m i t y to o n e a n o t h e r . formation. M a g n i f i c a t i o n p o w e r X10. Fig. 3.--Typical rosette formation of cells. Magnification power X95.
was seen again one month later, and he had gained two pounds. The proptosis was very slight, and the mass in the right side of his abdomen was smaller. The p a t i e n t was followed at periodic intervals and continued to show improvement, and when he was seen on Sept. 8, ]948, at 23 months of age, his weight was 25 pounds, and his height 34 inches (Fig. 4). A t the time he showed no clinical evidence of the original tumor. His proptosis was abse~:t as was the right-sided abdominal mass. X - r a y s of his skeletal system takerl on Nov. 24, ]94%, and Sept. 15, 1949, revealed no metastases. An examination of his peripheral blood was withh~ normal limits. I t is difficult to explain the favorable outcome in this p a r t i c u l a r case. One might assume that the topical x-ray t h e r a p y which, a 1 t h o u g h small in amount, produced necrosis and destruction of the t u m o r and possibly also t h a t of the metastatic lesions in the liver. I t would be extremely difficult to explain the disappearance of the meta-
static lesions in the skeletal system and periorbital regions. Again, it is worthy of emphasis that the prognosis in this
Fig. 4.--The patient as he appeared Sept. 8, 19~48, a t w h i c h t i m e he s h o w e d e v i d e n c e of o r i g i n a l t u m o r .
on no
234
THE JOURNAL OF PEDIATRICS
t y p e of t u m o r is s e r i o u s means hopeless.
but
by
no
The helpful advice of Dr. J e a n V. Cooke and Dr. Alexis F. H a r t m a n n is gratefully acknowledged.
1.
2. 3. 4.
REFERENCES Redman, J. L., Agerty, ]-I. A , Barthmaier, O. F., and Fisher, It. R. : Adrenal Neuroblastoma--Review of Literature, Am. J. Dis. Child. 50: 1097, 1938. Rypins, E. L.: Roentgen Diagnosis of Neuroblastoma in Children, Am. J. Roentgen. 37: 325, 1937. Boyd, ~Vm.: Three Tumors Arising From Neurob]asts, Arch. Surg. 12: 1031, 1936. Wyatt, G. M., and Farber, S.: Neuroblastoma Sympatheticnm : Roentgeno-
5.
6.
7. 8. 9. ]0.
logical Appearances and Radiation Treatment, Am. J. Roentgenol. 46: 485, 1941. Ladd, W. E., and Gross, R. E." Abdominal Surgery of I n f a n c y and Childhood, Philadelphia~ 1941, W. B. Saunders Co, Chap. 36. Cushing, It., and Wolbaeh, S. B.: The Transformation of a Malignaat Paravertebral Sympathieoblastoma Into a Benign Ganglioneuroma~ Am. J. Path. 3: 203, 1927. Chandler, F. A., and Nareross, J. R.: Sympathicoblastoma, J. A. M. A. 114: 113~ 1940. Lehman~ E . P . : J. M. Research 36: 309, 1917. I~bid.9 Adrenal Neuroblastoma in Infancy - - F i f t e e n Year Survival~ Ann. Surg. 95: 473, 1932. Farber, S.- Neuroblastoma, Am. J. Dis. Child. 60: 749, 1940.