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The roentgenographic findings associated with neuroblastoma
The Journal of Pediatrics VOL. 5 1
DECEMBER, 1 9 5 7
NO. 6
THE ROENTGENOGRAPHIC FINDINGS ASSOCIATED WITH NEUROBLASTO1KA CHARLOTTE F . H A N S M A N , )/I.D. AND BERTRAM R . GIRDANY, M.D.
PITTSBURGH, PA. H E diagnosis of neuroblastoma is
the course of the disease. MeCrorie and Smith 4 in 1953 reported a child with neuroblastoma whose initial complaints and roentgen findings were confined to the extremities. A palpable abdominal mass and characteristic skeletal changes a p p e a r e d later.
T based on a combination of factors.
This p a p e r reviews the chief complaints, physical findings, and laborat o r y data and emphasizes the roentgen findings associated with neuroblastoma in a group of 30 children seen at the
Children's Hospital of Pittsburgh in the five-year period between 1951 and 1955.
DATA
These observations are based on 30 children in each of whom the diagnosis of neurob]astoma or ganglioneuroblastoma was confirmed histologically. Sixteen patients were boys and 14 were girls. Ages ranged f r o m I month to 10 years, 1 month, with 15 children in the 1 to 4 y e a r age group. The average age was 3 years, 9 months. (Table I.)
REVIEW OF LITERATURE
I n 1941 W y a t t and F a r b e r 1 reviewed the roentgen changes and t r e a t m e n t of neurob]astoma. They concluded that there was no characteristic radiographic picture associated with the p r i m a r y tumor. T h e y discussed the type and extent of metastases. I n 1937 Rypins 2 reported 3 cases of neuroblastoma with proptosis, hydrocephalus, and destructive and productive lesions in the skeleton. Abdominal masses were not p a l p a t e d . Sherman and Learning 3 in 1953 described the roentgen findings in 50 histologically proved cases of neuroblastoma. They emphasized the skeletal changes late in
TABLE I.
AGE ]:NCIDENCE AND SEX DISTRIBUTION
AGE GROUP ( YEARS)
Under 1 1-4: 5-9 10 Total
l
IvIALES
3 7 6 16
FEI~ALES
3 8 2 1 14
Abdominal masses were p a l p a t e d in 24 instances. F e v e r was the chief complaint in 12 children; 9 complained of
From the D e p a r t m e n t of Radiology, Children's Hospital of Pitsburgh, and the Departm e n t of Pediatrics, University of Pittsburgh, School os lYiedic~.ne.
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pain in the legs, 8 were anoretic, and 7 were tired and listless. Table I I lists the signs and symptoms in order of their frequency. TABLE I~. FREQUENCY OF PHYSICAL SIGNS AND SYMPTOMS IN 30 :PATIENTS Mass palpable in abdomen without complaints referable thereto Fever Pain in legs Anorexia Fatigue and listlessness PaiiL in abdomen :Big liver or spleen Vomiting Irritability and restlessness Cough Swelling of abdomen Weight loss
24 5 ]2 9 8 7 5 5 4 4 3 3 2
All patients had x,ray films of the abdomen, urinary tract, and skeleton. An intra-abdominal soft tissue mass was visualized in 26 cases. In 25 the mass displaced adjacent structures (:Figs. 1 and 2). Shadows of ealcimn density were seen in the region of an adrenal gland in 5 instances (Figs. 3 and 4), and an enlarged liver shadow was present in 5 others. Dilatation and blunting of the renal calyces indicated obstruction to drainage of the upper urinary tract b y the mass in one child (Fig. 5). A large kidney shadow with attenuation of the pelvocalyeeal system suggested renal infiltration in one instance. In 2 cases there was evidence of ascites and associated generalized edema of the lower extremities. Two children had mediastina] masses (Fig. 6) and 3 had extradural tumors. (Table III.) Fourteen of the 26 abdominal masses originated in an adrenal gland. A definite site of origin could not be ascertained for any of the other 12 masses. (Table IV.)
TABLE I I I . ROENTGEN FINDINGS ASSOCIATED WITIt THE PRIMARY TU~mR Abdominal mass Displacement of adjacent structures Calcification, abdomen only Enlarged liver Ascites and edema I:[ydronephrosis Renal infiltration IntestinaI obstruction Mediastinal mass Obstruction on myelography TABLE IV.
26 25 5 5 2 1 1 0 2 2
SITE O~ PRIMA~Y TUMOIr
Abdomen Adrenal gland Retroperitoneal Unknown Mediastinum Spine
26 14 5 7 2 3
Bony or soft tissue changes of metastatic neuroblastoma were seen in 11 children. In 3 cases the bones alone were affected and in 2 the changes were limited to the lungs and meninges. Six children had combined bony and soft tissue metastases. Pulmonary metastases were present in 4 of these cases (Fig. 7). Seven children had metastatic lesions in the skull. Four of these also had roentgen signs of increased intracranial pressure. In one instance changes in the skull were limited to signs of increased intracranial pressure. (Figs. 8 and 9.) Eight children had lesions in the femurs and 4 showed changes in tile bony pelvis (Figs. 10 and 11). In one case femoraI involvement was unilateral (Fig. 12). In 3 children both tibias were affected; in 2 children only one tibia showed metastases (Figs. 13 and 14). Both humeri were affected in 2 children; in 2 others only one was involved (Fig. 15). A pathologic fracture occurred through the proximal humerus of one child (Fig. 16). There were metastases to the bones Of both
HANSMAN
Fig.
AND GIRDANY:
ROENTGEN
FINDINGS
IN
NEUROBLA_STOMA
1.--Anteroposterior and lateral films of the abdomen of a 16-month-old child show p l a c e m e n t of t h e l e f t r e n a l p e l v i s a n d c a l y c e s b y a l a r g e s u p r a r e n a l m a s s .
623
dis-
Fig. 2 . - - E x c r e t o r y u r o g r a p h i c film s h o w s d i s p l a c e m e n t of the air-filled s t o m a c h b y a m a s s in t h e r e g i o n o f t h e l e f t k i d n e y in a 5 - y e a r - o l d c h i l d . N o t e t h e a b s e n c e o f v i s u a l i z a t i o n of r e n a l p e l v i s a n d c a l y c e s on t h i s side, i n d i c a t i n g p o o r f u n c t i o n of t h e k i d n e y .
624
Fig.
T H E J O U R N A L OF P E D I A T R I C S
3.~nteroposterior a n d l a t e r a l e x c r e t o r y u r o g r a p h i e films s h o w a r o u n d e d s h a d o w c a l c i u m d e n s i t y in t h e r e g i o n of t h e r i g h t a d r e n a l g l a n d in a 4 ~ - y e a r - o l d girl.
of
F i g . 4 . - - E x c r e t o r y u r o g r a p h i c film s h o w s diffuse s h a d o w s of c a l c i u m d e n s i t y ( a r r o w s ) in t h e r e g i o n of t h e left a d r e n a l g l a n d in a n 8 - y e a r - o l d girl. T h e l e f t r e n a l p e l v i s is d i s p l a c e d caudad.
HANSMAN
Fig.
AND GIRDANY:
ROENTGEN FINDINGS IN NEUROBLASTOMA
5 . - - E x c r e t o r y u r o g r a p h s s h o w m a r k e d d i l a t a t i o n a n d l a t e r a l d i s p l a c e m e n t of t h e pelvis and calyces associated with a large overlying neuroblastoma.
625
renal
F i g . 6. P o s t e r o a n t e r i o r f i l m o f t h e t h o r a x s h o w s a w i d e s u p e r i o r m e d i a s t i n a l s h a d o w a s weI1 a s p a r a v e r t e b r a l soft tissue shadows associated with involvement of the mediastinal a n d p a r a v e r t e b r a l s t r u c t u r e s in a 7 - y e a r - o l d c h i l d .
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THE JOURNAL OF PEDIATRICS
forearms in 2 instances. Three children showed evidence of skeletal metastases without skull metastases; one child with skull lesions had no demonstrable roentgen changes in tile long bones. (Table V.) TABLE V.
DISTRIBUTION OF METASTASES
Lungs Meninges Skull Femurs, bilateral unilateral Pelvis Tibias, bilateral unilateral Humeri, bilateral unilateral Forearm, bilateral L o n g bones w i t h o u t skull S k u l l w i t h o u t l o n g bones
4 5 7 7 1 4 3 2 2 2 2 3 ]
teristic. The intra-abdominal soft tis~ sue mass most commonly lies in the region of an adrenal gland, displacing adjacent structures. U r i n a r y tract obstruction may result. The rctroperitoneal tumor mass displaces the air- or barium-filled gastrointestinal tract ventrad. Intestinal obstruction is rare. Calcification within the mass suggests neuroblastoma2 Calcification did not occur in the mediastinal tumors. Nenroblastoma is a malignant tumor which metastasizes the bony and nonbony structures. Small, poorly defined rounded shadows of water density in the lungs represent metastases (Fig. 7). Another roentgen indication of
Fig. 7 . - - P o s t e r o a n t e r i o r film of the t h o r a x in a 3-year-old child shows a wide s u p e r i o r m e d i a s t i n a l s h a d o w a n d tiny, poorly defined n o d u l a r m e t a s t a s e s in the lungs. Metastatic n e u r o b l a s t o m a w a s proved a t necropsy. DISCUSSION
The adrenal gland is the most common p r i m a r y site of ncuroblastoma. The tumor may originate in any of the sympathetic ganglia. Mediastinal and spinal cord tumors are probably ganglionic in origin. The radiographic picture associated with the p r i m a r y tumor is not charac-
soft tissue involvement is widening of the cranial sutures due to masses of tumor tissue between the dura and the calvarium. The tumor invades the dura, which seems to act as a barrier to invasion of the brain. A roentgenogram of the skull showing widened sutures and destruction of the bones of the cranial vault is
A.
B~
F i g . 8 . - - A a n d B, A n t e r o p o s t e r i o r a n d l a t e r a l films of t h e s k u l l s h o w m a r k e d l y c r a n i a l s u t u r e s a n d fine m o t t l i n g in t h e b o n e s of t h e c r a n i a l v a u l t c h a r a c t e r i s t i c destruction. T h e c o m b i n a t i o n of t h e s e f i n d i n g s is p a t h o g n o m o n i c os n e u r o b l a s t o m a .
widened of b o n e
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OF P E D I A T R I C S
pathognomonic of metastatic neuroblastoma (Figs. 8 and 9). The roentgen picture of metastases in neurob]astoma reflects combined destruction and proliferation of bone. The earliest evidences of metastases are tiny areas of radio]ueence in either long or fiat bones representing bone destruction and invasion of the marrow cavity by tumor cells. It should be emphasized that tumor cells may be
Fig. 9.--Lateral productive
film of the skull in a 5-year-old and destructive lesions (arrow)
detected in the bone marrow before there is roentgen evidence of their presence. Evidence of cortical destruction is another early finding. The cortices of the medial, distal metaphyses of the femurs and the lateral aspects of the proximal tibias are frequently affected (Fig. 13). A later manifestation is subperiosteal new bone reaction as evideneed by parallel lines of ealeimn density along the margins of the bones. Perpendicular spiculation and exten-
sion of new bone into the surrounding soft tissue may occur (Fig. 17). Bony metastases occurred most frequently in the skull and the femurs. The bones of the lower legs and upper extremities were late sites of involvement. In all eases of long bone involvement both metaphyses and diaphyses of the bones were affected. In no eases were the bones of the hands or feet affected.
boy terminally ill with neuroblastoma shows as well as markedly widened sutures.
DIFFERENTIAL
DIAGNOSIS
The palpable abdominal mass is, of itself, rarely diagnostic. Neuroblastoma, Wilms's tumor, hydronephrosis, polyeystic k i d n e y, lymphosareoma, mesenteric cyst, and renal vein thrombosis must be considered in the differential diagnosis. An occasional infant with neuroblastoma is referred with the diagnosis of enlarged spleen. Preoperative differential diagnosis between Wilms's tumor and neuroblastoma may not be possible. Indeed,
HANSMAN
AND
GIRDANy:
ROENTGEN
FINDINGS
Fig. lO.~Anteroposterior f i h n of t h e f e m u r s of a p r o d u c t i v e a n d d e s t r u c t i v e c h a n g e s in n e u r o b l a s t o m a . tion ( a r r o w s ) a s well a s the diffuse m o t t l i n g .
Fig. ll.--Anteroposterior
IN
NEUROBLASTOIKA
629
5 - y e a r - o l d b o y s h o w s ~/ell t h e e x t e n s i v e Note the subperiosteal new bone forma-
film o f t h e p e l v i s of t h e s a m e p a t i e n t and productive changes.
shows the
diffuse destructive
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OF P E D I A T R I C S
F i g . 1 2 . - - A n t e r o p o s t e r i o r f i l m o f t h e p e l v i s in a n 8 - y e a r - o l d c h i l d s h o w s d o m i n a n t l y u n i l a t e r a l c h a n g e s on t h e r i g h t side. N o t e t h e s u b p e r i o s t e a l n e w b o n e p r o d u c t i o n i n f e r i o r to the lesser troehanter (arrow) as well as the diffuse destructive changes.
~'ig. 1 3 . - - A n t e r o p o s t e r i o r a n d l a t e r a l f i l m s of t h e k n e e in a 6 - y e a r - o l d c h i l d s h o w well t h e d e p o s i t i o n o f s u b p e r i o s t e a l n e w b o n e a b o u t t h e p r o x i m a l p o r t i o n of t h e s h a f t o f t h e t i b i a . S o - c a l l e d " C o d m a n ' s t r i a n g l e " is i n d i c a t e d b y t h e a r r o w .
F i g . 1 4 . - - L a t e r a l f i l m of t h e r i g h t k n e e s h o w s a s m a l l a m o u n t formation about the distal Portion of the shaft of the femur, deep s o f t - t i s s u e lesion ( a r r o w s ) .
of s u b p e r i o s t e a l n e w b o n e T h i s film s h o w s well the
HANSMAN
AND G I R D A N Y :
Fig. 15.---The h u m e r u s
Fig.
R O E N T G E N F I N D I N G S I N NEUROBLAST05~IA
of a 5 - y e a r - o l d b o y s h o w s diffuse, t i n y r o u n d e d a r e a s density reflecting bone destruction.
631
of d i m i n i s h e d
1 6 . - - - A n t e r o p o s t e r i o r film of t h e h u m e r u s in a 6 - y e a r - o l d b o y s h o w s p~tth01ogie f r a c t u r e t h r o u g h a n a r e a of b o n e d e s t r u c t i o n .
at surgery, accurate identification of the nature of the tumor may not be made. The final diagnosis awaits histologic proof. Wilms's tumor is an intrinsic renal mass. Nonexcretion of opaque material during excretory urography suggests Wilms's tumor. Neuroblastoma tends to displace the
renal pelvis and calyces downward and laterally. In either instance neuroblastoma and Wilms's tumor may simulate one another (Fig. 2). Wilms's tumor metastasizes to the lungs and rarely to the skeleton. The major value of the excretory urogram lies in the identification of the normalcy of
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THE JOURNAL OF PEDIATRICS
the contralateral kidney. Delay films may serve to identify hydronephrosis and kindred conditions. When the tumor has metastasized and leg or back pain brings the patient to the physician, leukemia, scurvy and malignant bone tumors must be ruled out. Tuberculosis of the spine, osteomyelitis, acute rheumatic fever, and poliomyelitis often enter the differential diagnosis. The skeletal changes of leukemia and metastatic neuroblastoma are radiographically indistinguishable. Involvement of the skull is less common in leukemia.
marrow smears which were positive for tumor cells did not show abnormal roentgenographic changes in their bones. SUMMARY AND CONCLUSIONS
1. The roentgen findings, chief complaints, and physical signs associated with 30 microscopically proved cases of neuroblastoma are presented. 2. An intra-abdominal mass is the most frequent finding on both physical and x-ray examination. The mass is a nonspeeifie finding and involves the differential diagnosis of all intraabdominal masses.
Fig, 1 7 . - - A n t e r o p o s t e r i o r film of the m a n d i b I e in a 5-year-old boy shows p e r p e n d i c u l a r spieulation a s s o c i a t e d w i t h deposition of n e w bone a t the sites of m e t a s t a s i s .
Bone marrow aspiration is useful in establishing a diagnosis which otherwise depends upon the microscopic examination of tissue obtained at surgery. Roentgen changes in the long bones may dictate an optima] site of bone marrow study. Marrow study may reveal tumor cells in the presence of radiographica]ly normal bone. Four of the 11 children having bone
3. Roentgenograms of the skull showing widened sutures and evidence of destruction of the bones of the cranial vault are pathognomonie of metastatic neuroblastoma. 4. The differential diagnosis of neuroblastoma is presented. The r a d i o g r a p h i c i l l u s t r a t i o n s in t h i s p a p e r are L o g E g r a m s p r o d u c e d f r o m the LogEtronie printer. The a u t h o r s a r e i n d e b t e d
HANSMAN AND GIRDANY:
ROENTGEI'~ FINDINGS IN NEUROBLASTOMA
to Dr. Elmer O. St. J o h n of Binghamton, I~ew York, and to LogEtronics Inc., for making these reproductions. REFERENcEs I. W y a t t , Geo. 1Vs and Farber, Sidney: Neuroblastoma Sympathetieum Roentgenological Appearances and Radiation Treat~ ment, Am. ,i. Roentgeno]. 46: 485, 19r
633
2. Rypins, E. L. : The l~oentgen Diagnosis of Neuroblastoma in Children, Am. ,i. Roentgenol. 37: 325~ 1937. 3. Sherman, Robert S., and Leaming, Robert: The Roentgen Findings in Neuroblastoma, Radiology 60: 837, 1953. 4. 1VicCrorie, W. D. C., and Smith, A.: Sympathicoblastoma (Adrenal lqeuroblastoma) With Report of a Case, B r i t . . I . Radio]. 26: 207, 1953.
Enlargement o f the Breast in the Newly Born I n f a n t I t occasionally happens, t h a t children newly born are found to have their breasts swollen, and e v i d e n t l y inflamed. This exists in various degrees, from a slight tumefaction, to one t h a t t h r e a t e n s suppuration. There is a v u l g a r opinion, t h a t these enlargements proceed from a q u a n t i t y of milk w i t h i n these little bodies, which must be squeezed or milked out, t h a t mischief may not follow. This absurd opinion, has, unfortunately~ led to the preposterous, and mischievous practice j u s t alluded to; in consequence of which, the parts have become so :irritated, as to occasion much pain, a n d increase of inflammation. The little turnout has been violently pressed, w i t h the view to force out impacted milk; but being disappointed in its not appearing~ the pressure is renewed again, and again, and each effort with an increase of force; since, agreeably to them, if the cause be not removed, serious consequences will follow to the parts, and, perhaps, in females for ever, destroy their usefulness. In thus pursuing a bad theory, by a worse practice, the consequences wllieh they so much dreaded, have absolutely taken place: suppuration has sometimes followed these rude manoeuvres, and has for ever destroyed the organization of these most useful parts. It eannot~ therefore, be too peremptorily forbidden, that these parts should be meddled with; for all that is necessary to their restoration, is a little time; or the application of a piece of linen, moistened with a little sweet oil~ unless the tumours be unusually ]arge~ and the inflammation very considerable. In this case~ a bread and milk poultice~ renewed every three or four hours, will be almost sure to restore them to health in a few days. WILLIAM DEWEES~ ON CHILDI%EN, 1834.
DECEMBER, 1 9 5 7
NO. 6
THE ROENTGENOGRAPHIC FINDINGS ASSOCIATED WITH NEUROBLASTO1KA CHARLOTTE F . H A N S M A N , )/I.D. AND BERTRAM R . GIRDANY, M.D.
PITTSBURGH, PA. H E diagnosis of neuroblastoma is
the course of the disease. MeCrorie and Smith 4 in 1953 reported a child with neuroblastoma whose initial complaints and roentgen findings were confined to the extremities. A palpable abdominal mass and characteristic skeletal changes a p p e a r e d later.
T based on a combination of factors.
This p a p e r reviews the chief complaints, physical findings, and laborat o r y data and emphasizes the roentgen findings associated with neuroblastoma in a group of 30 children seen at the
Children's Hospital of Pittsburgh in the five-year period between 1951 and 1955.
DATA
These observations are based on 30 children in each of whom the diagnosis of neurob]astoma or ganglioneuroblastoma was confirmed histologically. Sixteen patients were boys and 14 were girls. Ages ranged f r o m I month to 10 years, 1 month, with 15 children in the 1 to 4 y e a r age group. The average age was 3 years, 9 months. (Table I.)
REVIEW OF LITERATURE
I n 1941 W y a t t and F a r b e r 1 reviewed the roentgen changes and t r e a t m e n t of neurob]astoma. They concluded that there was no characteristic radiographic picture associated with the p r i m a r y tumor. T h e y discussed the type and extent of metastases. I n 1937 Rypins 2 reported 3 cases of neuroblastoma with proptosis, hydrocephalus, and destructive and productive lesions in the skeleton. Abdominal masses were not p a l p a t e d . Sherman and Learning 3 in 1953 described the roentgen findings in 50 histologically proved cases of neuroblastoma. They emphasized the skeletal changes late in
TABLE I.
AGE ]:NCIDENCE AND SEX DISTRIBUTION
AGE GROUP ( YEARS)
Under 1 1-4: 5-9 10 Total
l
IvIALES
3 7 6 16
FEI~ALES
3 8 2 1 14
Abdominal masses were p a l p a t e d in 24 instances. F e v e r was the chief complaint in 12 children; 9 complained of
From the D e p a r t m e n t of Radiology, Children's Hospital of Pitsburgh, and the Departm e n t of Pediatrics, University of Pittsburgh, School os lYiedic~.ne.
621
622
THE JOURNAL OF PEDIATRICS
pain in the legs, 8 were anoretic, and 7 were tired and listless. Table I I lists the signs and symptoms in order of their frequency. TABLE I~. FREQUENCY OF PHYSICAL SIGNS AND SYMPTOMS IN 30 :PATIENTS Mass palpable in abdomen without complaints referable thereto Fever Pain in legs Anorexia Fatigue and listlessness PaiiL in abdomen :Big liver or spleen Vomiting Irritability and restlessness Cough Swelling of abdomen Weight loss
24 5 ]2 9 8 7 5 5 4 4 3 3 2
All patients had x,ray films of the abdomen, urinary tract, and skeleton. An intra-abdominal soft tissue mass was visualized in 26 cases. In 25 the mass displaced adjacent structures (:Figs. 1 and 2). Shadows of ealcimn density were seen in the region of an adrenal gland in 5 instances (Figs. 3 and 4), and an enlarged liver shadow was present in 5 others. Dilatation and blunting of the renal calyces indicated obstruction to drainage of the upper urinary tract b y the mass in one child (Fig. 5). A large kidney shadow with attenuation of the pelvocalyeeal system suggested renal infiltration in one instance. In 2 cases there was evidence of ascites and associated generalized edema of the lower extremities. Two children had mediastina] masses (Fig. 6) and 3 had extradural tumors. (Table III.) Fourteen of the 26 abdominal masses originated in an adrenal gland. A definite site of origin could not be ascertained for any of the other 12 masses. (Table IV.)
TABLE I I I . ROENTGEN FINDINGS ASSOCIATED WITIt THE PRIMARY TU~mR Abdominal mass Displacement of adjacent structures Calcification, abdomen only Enlarged liver Ascites and edema I:[ydronephrosis Renal infiltration IntestinaI obstruction Mediastinal mass Obstruction on myelography TABLE IV.
26 25 5 5 2 1 1 0 2 2
SITE O~ PRIMA~Y TUMOIr
Abdomen Adrenal gland Retroperitoneal Unknown Mediastinum Spine
26 14 5 7 2 3
Bony or soft tissue changes of metastatic neuroblastoma were seen in 11 children. In 3 cases the bones alone were affected and in 2 the changes were limited to the lungs and meninges. Six children had combined bony and soft tissue metastases. Pulmonary metastases were present in 4 of these cases (Fig. 7). Seven children had metastatic lesions in the skull. Four of these also had roentgen signs of increased intracranial pressure. In one instance changes in the skull were limited to signs of increased intracranial pressure. (Figs. 8 and 9.) Eight children had lesions in the femurs and 4 showed changes in tile bony pelvis (Figs. 10 and 11). In one case femoraI involvement was unilateral (Fig. 12). In 3 children both tibias were affected; in 2 children only one tibia showed metastases (Figs. 13 and 14). Both humeri were affected in 2 children; in 2 others only one was involved (Fig. 15). A pathologic fracture occurred through the proximal humerus of one child (Fig. 16). There were metastases to the bones Of both
HANSMAN
Fig.
AND GIRDANY:
ROENTGEN
FINDINGS
IN
NEUROBLA_STOMA
1.--Anteroposterior and lateral films of the abdomen of a 16-month-old child show p l a c e m e n t of t h e l e f t r e n a l p e l v i s a n d c a l y c e s b y a l a r g e s u p r a r e n a l m a s s .
623
dis-
Fig. 2 . - - E x c r e t o r y u r o g r a p h i c film s h o w s d i s p l a c e m e n t of the air-filled s t o m a c h b y a m a s s in t h e r e g i o n o f t h e l e f t k i d n e y in a 5 - y e a r - o l d c h i l d . N o t e t h e a b s e n c e o f v i s u a l i z a t i o n of r e n a l p e l v i s a n d c a l y c e s on t h i s side, i n d i c a t i n g p o o r f u n c t i o n of t h e k i d n e y .
624
Fig.
T H E J O U R N A L OF P E D I A T R I C S
3.~nteroposterior a n d l a t e r a l e x c r e t o r y u r o g r a p h i e films s h o w a r o u n d e d s h a d o w c a l c i u m d e n s i t y in t h e r e g i o n of t h e r i g h t a d r e n a l g l a n d in a 4 ~ - y e a r - o l d girl.
of
F i g . 4 . - - E x c r e t o r y u r o g r a p h i c film s h o w s diffuse s h a d o w s of c a l c i u m d e n s i t y ( a r r o w s ) in t h e r e g i o n of t h e left a d r e n a l g l a n d in a n 8 - y e a r - o l d girl. T h e l e f t r e n a l p e l v i s is d i s p l a c e d caudad.
HANSMAN
Fig.
AND GIRDANY:
ROENTGEN FINDINGS IN NEUROBLASTOMA
5 . - - E x c r e t o r y u r o g r a p h s s h o w m a r k e d d i l a t a t i o n a n d l a t e r a l d i s p l a c e m e n t of t h e pelvis and calyces associated with a large overlying neuroblastoma.
625
renal
F i g . 6. P o s t e r o a n t e r i o r f i l m o f t h e t h o r a x s h o w s a w i d e s u p e r i o r m e d i a s t i n a l s h a d o w a s weI1 a s p a r a v e r t e b r a l soft tissue shadows associated with involvement of the mediastinal a n d p a r a v e r t e b r a l s t r u c t u r e s in a 7 - y e a r - o l d c h i l d .
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THE JOURNAL OF PEDIATRICS
forearms in 2 instances. Three children showed evidence of skeletal metastases without skull metastases; one child with skull lesions had no demonstrable roentgen changes in tile long bones. (Table V.) TABLE V.
DISTRIBUTION OF METASTASES
Lungs Meninges Skull Femurs, bilateral unilateral Pelvis Tibias, bilateral unilateral Humeri, bilateral unilateral Forearm, bilateral L o n g bones w i t h o u t skull S k u l l w i t h o u t l o n g bones
4 5 7 7 1 4 3 2 2 2 2 3 ]
teristic. The intra-abdominal soft tis~ sue mass most commonly lies in the region of an adrenal gland, displacing adjacent structures. U r i n a r y tract obstruction may result. The rctroperitoneal tumor mass displaces the air- or barium-filled gastrointestinal tract ventrad. Intestinal obstruction is rare. Calcification within the mass suggests neuroblastoma2 Calcification did not occur in the mediastinal tumors. Nenroblastoma is a malignant tumor which metastasizes the bony and nonbony structures. Small, poorly defined rounded shadows of water density in the lungs represent metastases (Fig. 7). Another roentgen indication of
Fig. 7 . - - P o s t e r o a n t e r i o r film of the t h o r a x in a 3-year-old child shows a wide s u p e r i o r m e d i a s t i n a l s h a d o w a n d tiny, poorly defined n o d u l a r m e t a s t a s e s in the lungs. Metastatic n e u r o b l a s t o m a w a s proved a t necropsy. DISCUSSION
The adrenal gland is the most common p r i m a r y site of ncuroblastoma. The tumor may originate in any of the sympathetic ganglia. Mediastinal and spinal cord tumors are probably ganglionic in origin. The radiographic picture associated with the p r i m a r y tumor is not charac-
soft tissue involvement is widening of the cranial sutures due to masses of tumor tissue between the dura and the calvarium. The tumor invades the dura, which seems to act as a barrier to invasion of the brain. A roentgenogram of the skull showing widened sutures and destruction of the bones of the cranial vault is
A.
B~
F i g . 8 . - - A a n d B, A n t e r o p o s t e r i o r a n d l a t e r a l films of t h e s k u l l s h o w m a r k e d l y c r a n i a l s u t u r e s a n d fine m o t t l i n g in t h e b o n e s of t h e c r a n i a l v a u l t c h a r a c t e r i s t i c destruction. T h e c o m b i n a t i o n of t h e s e f i n d i n g s is p a t h o g n o m o n i c os n e u r o b l a s t o m a .
widened of b o n e
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pathognomonic of metastatic neuroblastoma (Figs. 8 and 9). The roentgen picture of metastases in neurob]astoma reflects combined destruction and proliferation of bone. The earliest evidences of metastases are tiny areas of radio]ueence in either long or fiat bones representing bone destruction and invasion of the marrow cavity by tumor cells. It should be emphasized that tumor cells may be
Fig. 9.--Lateral productive
film of the skull in a 5-year-old and destructive lesions (arrow)
detected in the bone marrow before there is roentgen evidence of their presence. Evidence of cortical destruction is another early finding. The cortices of the medial, distal metaphyses of the femurs and the lateral aspects of the proximal tibias are frequently affected (Fig. 13). A later manifestation is subperiosteal new bone reaction as evideneed by parallel lines of ealeimn density along the margins of the bones. Perpendicular spiculation and exten-
sion of new bone into the surrounding soft tissue may occur (Fig. 17). Bony metastases occurred most frequently in the skull and the femurs. The bones of the lower legs and upper extremities were late sites of involvement. In all eases of long bone involvement both metaphyses and diaphyses of the bones were affected. In no eases were the bones of the hands or feet affected.
boy terminally ill with neuroblastoma shows as well as markedly widened sutures.
DIFFERENTIAL
DIAGNOSIS
The palpable abdominal mass is, of itself, rarely diagnostic. Neuroblastoma, Wilms's tumor, hydronephrosis, polyeystic k i d n e y, lymphosareoma, mesenteric cyst, and renal vein thrombosis must be considered in the differential diagnosis. An occasional infant with neuroblastoma is referred with the diagnosis of enlarged spleen. Preoperative differential diagnosis between Wilms's tumor and neuroblastoma may not be possible. Indeed,
HANSMAN
AND
GIRDANy:
ROENTGEN
FINDINGS
Fig. lO.~Anteroposterior f i h n of t h e f e m u r s of a p r o d u c t i v e a n d d e s t r u c t i v e c h a n g e s in n e u r o b l a s t o m a . tion ( a r r o w s ) a s well a s the diffuse m o t t l i n g .
Fig. ll.--Anteroposterior
IN
NEUROBLASTOIKA
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5 - y e a r - o l d b o y s h o w s ~/ell t h e e x t e n s i v e Note the subperiosteal new bone forma-
film o f t h e p e l v i s of t h e s a m e p a t i e n t and productive changes.
shows the
diffuse destructive
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F i g . 1 2 . - - A n t e r o p o s t e r i o r f i l m o f t h e p e l v i s in a n 8 - y e a r - o l d c h i l d s h o w s d o m i n a n t l y u n i l a t e r a l c h a n g e s on t h e r i g h t side. N o t e t h e s u b p e r i o s t e a l n e w b o n e p r o d u c t i o n i n f e r i o r to the lesser troehanter (arrow) as well as the diffuse destructive changes.
~'ig. 1 3 . - - A n t e r o p o s t e r i o r a n d l a t e r a l f i l m s of t h e k n e e in a 6 - y e a r - o l d c h i l d s h o w well t h e d e p o s i t i o n o f s u b p e r i o s t e a l n e w b o n e a b o u t t h e p r o x i m a l p o r t i o n of t h e s h a f t o f t h e t i b i a . S o - c a l l e d " C o d m a n ' s t r i a n g l e " is i n d i c a t e d b y t h e a r r o w .
F i g . 1 4 . - - L a t e r a l f i l m of t h e r i g h t k n e e s h o w s a s m a l l a m o u n t formation about the distal Portion of the shaft of the femur, deep s o f t - t i s s u e lesion ( a r r o w s ) .
of s u b p e r i o s t e a l n e w b o n e T h i s film s h o w s well the
HANSMAN
AND G I R D A N Y :
Fig. 15.---The h u m e r u s
Fig.
R O E N T G E N F I N D I N G S I N NEUROBLAST05~IA
of a 5 - y e a r - o l d b o y s h o w s diffuse, t i n y r o u n d e d a r e a s density reflecting bone destruction.
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of d i m i n i s h e d
1 6 . - - - A n t e r o p o s t e r i o r film of t h e h u m e r u s in a 6 - y e a r - o l d b o y s h o w s p~tth01ogie f r a c t u r e t h r o u g h a n a r e a of b o n e d e s t r u c t i o n .
at surgery, accurate identification of the nature of the tumor may not be made. The final diagnosis awaits histologic proof. Wilms's tumor is an intrinsic renal mass. Nonexcretion of opaque material during excretory urography suggests Wilms's tumor. Neuroblastoma tends to displace the
renal pelvis and calyces downward and laterally. In either instance neuroblastoma and Wilms's tumor may simulate one another (Fig. 2). Wilms's tumor metastasizes to the lungs and rarely to the skeleton. The major value of the excretory urogram lies in the identification of the normalcy of
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the contralateral kidney. Delay films may serve to identify hydronephrosis and kindred conditions. When the tumor has metastasized and leg or back pain brings the patient to the physician, leukemia, scurvy and malignant bone tumors must be ruled out. Tuberculosis of the spine, osteomyelitis, acute rheumatic fever, and poliomyelitis often enter the differential diagnosis. The skeletal changes of leukemia and metastatic neuroblastoma are radiographically indistinguishable. Involvement of the skull is less common in leukemia.
marrow smears which were positive for tumor cells did not show abnormal roentgenographic changes in their bones. SUMMARY AND CONCLUSIONS
1. The roentgen findings, chief complaints, and physical signs associated with 30 microscopically proved cases of neuroblastoma are presented. 2. An intra-abdominal mass is the most frequent finding on both physical and x-ray examination. The mass is a nonspeeifie finding and involves the differential diagnosis of all intraabdominal masses.
Fig, 1 7 . - - A n t e r o p o s t e r i o r film of the m a n d i b I e in a 5-year-old boy shows p e r p e n d i c u l a r spieulation a s s o c i a t e d w i t h deposition of n e w bone a t the sites of m e t a s t a s i s .
Bone marrow aspiration is useful in establishing a diagnosis which otherwise depends upon the microscopic examination of tissue obtained at surgery. Roentgen changes in the long bones may dictate an optima] site of bone marrow study. Marrow study may reveal tumor cells in the presence of radiographica]ly normal bone. Four of the 11 children having bone
3. Roentgenograms of the skull showing widened sutures and evidence of destruction of the bones of the cranial vault are pathognomonie of metastatic neuroblastoma. 4. The differential diagnosis of neuroblastoma is presented. The r a d i o g r a p h i c i l l u s t r a t i o n s in t h i s p a p e r are L o g E g r a m s p r o d u c e d f r o m the LogEtronie printer. The a u t h o r s a r e i n d e b t e d
HANSMAN AND GIRDANY:
ROENTGEI'~ FINDINGS IN NEUROBLASTOMA
to Dr. Elmer O. St. J o h n of Binghamton, I~ew York, and to LogEtronics Inc., for making these reproductions. REFERENcEs I. W y a t t , Geo. 1Vs and Farber, Sidney: Neuroblastoma Sympathetieum Roentgenological Appearances and Radiation Treat~ ment, Am. ,i. Roentgeno]. 46: 485, 19r
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2. Rypins, E. L. : The l~oentgen Diagnosis of Neuroblastoma in Children, Am. ,i. Roentgenol. 37: 325~ 1937. 3. Sherman, Robert S., and Leaming, Robert: The Roentgen Findings in Neuroblastoma, Radiology 60: 837, 1953. 4. 1VicCrorie, W. D. C., and Smith, A.: Sympathicoblastoma (Adrenal lqeuroblastoma) With Report of a Case, B r i t . . I . Radio]. 26: 207, 1953.
Enlargement o f the Breast in the Newly Born I n f a n t I t occasionally happens, t h a t children newly born are found to have their breasts swollen, and e v i d e n t l y inflamed. This exists in various degrees, from a slight tumefaction, to one t h a t t h r e a t e n s suppuration. There is a v u l g a r opinion, t h a t these enlargements proceed from a q u a n t i t y of milk w i t h i n these little bodies, which must be squeezed or milked out, t h a t mischief may not follow. This absurd opinion, has, unfortunately~ led to the preposterous, and mischievous practice j u s t alluded to; in consequence of which, the parts have become so :irritated, as to occasion much pain, a n d increase of inflammation. The little turnout has been violently pressed, w i t h the view to force out impacted milk; but being disappointed in its not appearing~ the pressure is renewed again, and again, and each effort with an increase of force; since, agreeably to them, if the cause be not removed, serious consequences will follow to the parts, and, perhaps, in females for ever, destroy their usefulness. In thus pursuing a bad theory, by a worse practice, the consequences wllieh they so much dreaded, have absolutely taken place: suppuration has sometimes followed these rude manoeuvres, and has for ever destroyed the organization of these most useful parts. It eannot~ therefore, be too peremptorily forbidden, that these parts should be meddled with; for all that is necessary to their restoration, is a little time; or the application of a piece of linen, moistened with a little sweet oil~ unless the tumours be unusually ]arge~ and the inflammation very considerable. In this case~ a bread and milk poultice~ renewed every three or four hours, will be almost sure to restore them to health in a few days. WILLIAM DEWEES~ ON CHILDI%EN, 1834.