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Intrathoracic tumours of the sympathetic nervous system
INTRATHORACIC
INTRATHORACIC
TUMOURS
TUMOURS
OF
OF THE SYSTEM
THE
SYMPATHETIC
SYMPATHETIC
275
NERVOUS
WITH A R E P O R T OF TWO C A S E S
BY P. JACOBS, M.B., Ch.B., M.R.C.S., M.R.C.P., D.M.R.(D) SENIOR REGISTRAR IN DIAGNOSTIC RADIOLOGY, LONDON HOSPITAL
REPORTS of tumours occurring in various parts of the body arising from cells of the sympathetic nervous system appear in the literature from time to time. The best known are those arising from the suprarenal medulla divided into the two main clinical types, the Pepper type, in which a primary suprarenal neoplasm metastasizes to the liver, and the Hutchison type, in which metastases occur in the skull, orbit, and long bones. Many of these tumours present a mixed picture, so modern opinion is against retaining these watertight compartments. Tumours may arise from sympathetic nerves elsewhere. They have been reported arising from such structures as the abdominal sympathetic nerves, sacrococcygeal gland, in the mesentery, jejunum, liver, uterus, cavity of the nose, ciliary ganglion, skin, scapular region, spinal canal, and cervical and thoracic sympathetic chain. The present paper is concerned with sympathetic nerve tumours arising within or presenting in the thorax. For the most part these turnouts arise from the thoracic sympathetic chain situated in the paravertebral gutter on either side. Therefore, their origin is not strictly mediastinal, but they soon enlarge to occupy the posterior mediastinum pushing the mediastinal pleura forwards. They extend more to one side than the other, though some may appear on both sides of the midline and may extend cvcn to occupy part of the anterior mediastinum. PATHOLOGY The sympathetic nervous system is developed by a ]~rogressive growth of and differentiation from the pluripotential mother cells, the sympathogonia. Tumours may contain cells of varying maturity and, in fact, rarely contain a single-cell type. Various transitions between the different forms are reported. Numerous classifications are suggested and there is much confusion. The simplest and probably the most useful is the one proposed by Bielschowsky. O F T U M O U R S O F S Y M P A T H E T I C S Y S T E M (after Bielschowshy) (The turnours and their synonyms are in brackets) Sympathogonia (sympathogonioma)
CLASSIFICATION
\
sympathoblastoma ]sympathicoblastoma \ Sympathoblast ~neuroblastoma ~neurocytoma f
Phaeochromoblast (phaeochromoblastoma)
Sympathetic ganglion cells (ganglioneuroma)
Chromaffin cells (phaeochromocytoma)
The sympathogonioma and chromaffin tumours occur extremely rarely in the thorax. For the main part roughly 25 per cent of intrathoracic sympathetic nerve tumours consist of the neuroblastoma (sympathoblastoma) and 75 per cent consist of the more differentiated, more mature, and less malignant ganglioneuromata. Although ganglioneuromata are regarded generally as benign tumours, Stout (1947) has described metastases occurring from them. Tumours are encountered in which varying numbers of ganglion cells are present in a growth which otherwise has the criteria of a fibrous tissue growth--these are known as gang/ionated
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neurofibromata. Both the benign and malignant tumours may assume a dumb-bell form, occurring both in the spinal canal and in the thorax. Ineidenee.--Wyatt and Farber (i94i) traced 40 cases of neuroblastoma over a io-year period at the Boston Children's Hospital. In the same period they traced 3° cases of Wilms' tumour. They did not state, however, how many of their cases were primarily intrathoracic. Sherman and Leaming (1953) , in an analysis of 5o cases of neuroblastoma, did not record with certainty a primary intrathoracic example ; io of their 50 patients had intrathoracic lesions which they regarded as metastatic, though they said that the radiographs in a few cases suggested that the primary tumour might have arisen there. Wittenborg (195o) regarded 7 per cent of 73 cases to be primarily intrathoracic. Ganglioneuromata, as indicated, are more common. Rogers and Keogh (195o) reported that up to 195o they were able to trace in the literature 9° cases of intrathoracic ganglioneuroma. The present two cases are primary intrathoracic neuroblastomata, no evidence of metastases being found from either. CLINICAL F E A T U R E S The great majority of the patients are infants and young children. Some of the ganglioneuroma cases, however, are found in adults. Patients may be referred for radiological examination on account of the following groups of symptoms : - i. Intrathoracic Symptoms. Patients may complain of vague pains or fullness in the chest. They may suffer from symptoms arising from pressure on structures such as the trachea, main bronchi, recurrent laryngeal nerve, (esophagus, or superior vena cava. Examples of such symptoms and signs are dyspn~ea, stridor, unproductive brassy cough, hoarseness with paralysis of a vocal cord, dysphagia, and distended veins of the neck and trunk. Homer's syndrome from involvement of the sympathetic trunk may be found, and it may occur after surgical removal of the tumour. 2. Spinal Symptoms.--Some of these tumours arise within the intervertebral foramina and extend both to the spinal canal and outwards into the thorax. They are often called ' dumb-bell ' or ' hourglass, tumours '. They are uncommon but very interesting. A good example is reported in the present paper. 3. Symptoms due to Metastases.TThe patient may present on account of the effects of metastases. These may occur in soft tissues, such as in the orbits, producing exophthalmos, or in other soft tissues, such as the scalp, when the lumps will be palpable. They may occur in bone, and the diagnosis of neuroblastoma will be kept in mind when unexpected osteolytic areas or periosteal reaction causing radiating spicules or perpendicular striations are seen. Bony metastases from neuroblastoma tend to be bilaterally symmetrical. Hartung and Rubert (~935) described 2 patients with primary intrathoracic neuroblastomata in whom bony metastases were demonstrated. At that time they regarded their cases as unique, but subsequently other cases of this nature have been reported. 4. Fortuitous Finding.--Probably with the ever-increasing routine chest examinations in children, tuberculin surveys, and similar investigations necessitating chest radiography, more of these tumours, and particularly the ganglioneuromata, will be discovered unexpectedly. One of the two patients referred to, presented on account of spinal symptoms, the other on account of a chronic unproductive cough at first thought to be whooping-cough.
RADIOLOGICAL ASPECTS As stated, the tumour is seen most frequently in young children. It presents usually as a smooth, rounded, well-circumscribed, homogeneous opacity. Slight lobulation of the borders may be seen. The tumours appear most frequently at the apex and in the upper half of the hemithorax and are found always to be posteriorly situated. However, some may occur in the lower part of the hemithorax and others may be paraspinal in position, being seen as extra shadows thrgugh the cardiac silhouette.
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Earlier writers stated that sympathetic nerve tumours in general occurred more frequently on the left side of the body. Stout (1947) could find no statistical difference as to the side of the body affected. That author, however, was discussing sympathetic nerve tumours occurring in all sites. The majority of the reported intrathoracic cases occurred on the left side. For example, Hollingsworth (i946) reported 7 intrathoracic cases, of which 6 were left-sided. The present 2 examples are both left-sided. The neuroblastomata appear to be left-sided more frequently than the ganglioneuromata. However, since cases of both types of tumour have been found on the right side, little diagnostic help may be expected from the consideration of the side of the thorax involved. Both in ganglioneuroma and in neuroblastoma, bony erosion either of the ribs or of the vertebral column may be found. Intervertebral foramina may be enlarged, though in the upper thoracic region this may be difficult to demonstrate. Bony erosions are caused usually by the effects of pressure and do not necessarily indicate the presence of metastases. In one of the present examples, well-marked erosion of the posterior part of the left 5th rib with widening of the left 5-6th interspace was found. In the other, erosion of the posterior part of the 3rd left rib, with widening of the 3rd-4th interspace, was similarly seen. In both the present cases an important and interesting feature is the presence of calcification. Calcification occurring in neuroblastomata of the suprarenal is, of course, well known. Calcification in sympathetic nerve tumours in other sites is not so well recognized. Mandeville (1949) studied all reported instances in which calcification had been seen in sympathetic nerve tumours in all sites. Only 3 intrathoracic examples were discovered. In one, the calcification was found by the pathologist after removal of the tumour. In another, the neuroblastoma presented as a partially calcified opacity to the right of the lower thoracic spine. In this type there is a resemblance to a tuberculous abscess, the differential diagnosis being made by the lack of the typical bony changes of tuberculosis. The third example was reported by Startz and Abrams (x938). One of their patients had a tumour in the right apex and upper zone in which calcification was seen. The radiograph was published and it is the only one discovered which is comparable with those of the present two patients. In addition, HoUingsworth (i 946) reported 7 patients with intrathoracic tumours of sympathetic nerves. He reported 2 cases showing calcification, but the radiographs were not published. Of interest is the fact that his 2 examples demonstrating calcification were histologically ganglioneuromata. One of the present cases was a neuroblastoma, the other a neuroblastoma differentiating towards a ganglioneuroma. More recently, Sherman and Learning (1953) have published a comprehensive paper on the radiological findings in neuroblastoma. They reported io cases with intrathoracic manifestations, but in only I case was calcification found, and this was in an extension upward through the diaphragm of a mass from the suprarenal area. Metastases to the lungs may occur from neuroblastomata elsewhere. They appear as rounded opacities with indistinct borders, but they have no diagnostic features and cannot be differentiated by their appearances from other metastases such as, for example, those from a Wilms' tumour. They may, incidentally, be very radiosensitive. Metastatic mediastinal tumours and pleural deposits and effusions may also be found. The radiological appearances of bony metastatic lesions have been described well elsewhere by other writers and will not be repeated. One should emphasize, nevertheless, the importance of radiographing all bones in a search for metastatic deposits in the presence of a chest lesion, such as has been described. Other diagnostic radiological methods ,include screening the chest to investigate possible displacement of the barium-filled oesophagus, diaphragmatic movements, and the like. Tomography may be helpful in demonstrating bony erosions. It was used in one of the present patients. No evidence of bony erosion was found other than that demonstrated by the straight films and none subsequently at operation was discovered. Diagnostic pneumothorax will enable one to determine
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whether an opacity is intrapulmonary or mediastinal. It is felt tl~at with increasing knowledge of the pattern of mediastinal tumours, this investigation will comparatively seldom be necessary.
CONCLUSION It is seen that these tumours may produce a variable picture. However, there is a tendency for them to occur in the upper zones of the hemithorax. Calcification in both the present cases was
Fig. 235.--Case I. A.P. radiograph of chest. Note areas of calcification within the opacity and also erosion of .posterior part of left 5th rib, with widenmg of 5th-6th interspace.
very marked and microscopically was found to be scattered throughout the tumour. It is felt that in the presence of a rounded Fig. 236.--Case i. Left lateral radiograph showingrounded turnout posteriorly situated, tumour, showing evidence of calcification, situated posteriorly in the hemithorax of a child, the diagnosis of a sympathetic nerve tumour may confidently be made, as indeed it was in the present two patients. Calcification has not been recorded in other posteriorly situated tumours such as neurofibroma. Wyatt and Farber (1941) considered that there was no characteristic picture of a primary neuroblastoma. Sherman and Leaming (1953) believe this to be true, except when the radiologist can reliably identify the presence of a mass in the suprarenal region with calcification. To this I would add that primary intrathoracic sympathetic nerve tumours may produce an absolutely characteristic picture.
CASE
REPORTS
Case I . - - L a w r e n c e B., aged ten m o n t h s , was a d m i t t e d to hospital on Sept. 24, 1953, on account of suspected m e n i n g i t i s or poliomyelitis. T h e m o t h e r ' s p r e g n a n c y was normal, the d e l i v e r y normal, the b a b y sat up at five m o n t h s and stood w i t h assistance at six and a half m o n t h s . Seven weeks before a d m i s s i o n he h a d an attack
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of diarrhoea and vomiting f r o m w h i c h he soon recovered, except that his parents noticed that his legs seemed weak and were not supporting h i m as before. T h i s weakness worsened, and the m o t h e r said that he had not moved his legs for two days before admission. O n examination, there was marked neck rigidity, knee and ankle reflexes were brisk and abdominal reflexes absent. T h e r e was a sustained ankle clonus on the right side and a positive Kernig sign. An area of par~esthesia was noticed just above the umbilicus on drawing a pin down the body. A diagnosis of spinal compression was suggested and for that reason the spine and chest were radiographed. CHEST RADIOGRAPHS(Figs. 235, z 3 6 ) . - - A n opacity was seen in the left u p p e r and mid zones extending from the xst to the 3rd left interspaces, spreading f r o m the mediastinal surface of the lung to half-way across the left
Fig. 237.--Case z. P.A. radiograph, Areasofcalc~ficatian are seen within the opacity. Erosion of the mferior surface of the medial part of the left 3rd rib is also noted,
Fig. 238.--Case 2. Left lateral radiograph showing rounded posteriorly mtuated tumour.
hemithorax at its widest point. T h e edges were clear-cut and no infiltration of s u r r o u n d i n g lung was seen. T h e mass was seen to be posteriorly situated in the lateral film and extended from the 3rd to the 7th thoracic vertebra. Mottled areas of calcification were clearly seen within the opacity, the calcified areas becoming confluent in places. Erosion of the posterior part of the 5th left rib, with widening of the 5-6th intercostal " space, was found. AT OPERATION (Sept. e8, I 9 5 3 ) . - - L a m i n e c t o m y by Mr. D. W. C. Northfield. T h e dorsal spine was explored and a large extradural mass of t u m o u r removed. It protruded into the 4th, 5th, and 6th spaces, at which points the t u m o u r was incised. MICROSCOPICAL EXAMINATION (Professor D. S. Russelt).--Pieees of extensively calcified solid neoplasm of small spheroidal cells, in anatomical continuity with a sympathetic ganglion. T h e appearances are those of an undifferentiated neurohlastoma. X-RAY THERAPY.--Later he was given a course of deep X°ray t h e r a p y - - 3 o a o r, 2oo kv., i6 treatments, 6 × 8 cm. right angle wedge pair--overall time ei days. PRoaRESs.--Following operation and radiotherapy he made a very satisfactory recovery and was using his legs normally on discharge f r o m hospital on Nov. 29. Jan. I4, I954 : He was re-admitted. At the time of admission leg m o v e m e n t s were good and no abnormal physical signs were found.
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Jan. 18 (Removal of mediastinal tumour by Mr. G. Flavell) : A firm flat'oval mass was found lying on the vertebral bodies centred on the 5th, 3 cm./2 cm./o" 5 cm. T h e sympathetic chain was divided above and below and the mass with the overlying pleura was removed without difficulty. Discharged on Feb. i to be followed up by Radiotherapy Department. Sept. 12 : No evidence of metastases was discovered clinically or after radiography of the entire skeleton. Case 2 . - - N o r m a R., aged 3 years, was admitted on July 7, I954. History of chronic .unproductive cough for ten months. T h e cough resembled whooping-cough. Apart from a urinary infection, the child had no previous history of illness. She produced no sputum of hmmoptysis and was not dyspnoeic. On examination, no abnormal physical signs were found except for dullness to percussion and diminished breath-sounds over the upper half of the left hemithorax posteriorly. CHEST RADIOGRAPHS (Figs. 237, 238).--A well-demarcated rounded opacity was seen. On the posteroanterior film it extended from the mediastinal surface of the left lung field right across the upper left hemithorax. It was found in the lateral film to be posteriorly situated. Quite extensive calcification was found within the opacity. T h e posterior part of the left third rib with widening of the left 3rd-4th interspace was noted. No evidence of metastases in other bones was found after radiography of the entire skeleton. AT OPERATION (Mr. Geoffrey Flavell).--A tumour was found in the posterior mediastinum to the left. It was an ovoid mass measuring 21 × 2 × 3 in. It extended up to the thoracic inlet. Part of it was adherent to the aortic arch and great vessels, and it was not possible to remove it completely. MICROSCOPICAL EXAMINATION (Professor D. S. Russell).--Neuroblastoma differentiating towards ganglioneuroma with a few definite ganglion cells. There is focal calcification of the stroma. (July 27, 1954.) Aug. 6, 1954 : Discharged and referred to Radiotherapy Department for treatment as an out-patient. SUMMARY i. T w o cases of p r i m a r y i n t r a t h o r a c i c t u m o u r s of t h e s y m p a t h e t i c n e r v o u s s y s t e m are p r e s e n t e d . 2. T h e p a t h o l o g y a n d clinical f i n d i n g s of t h e s e t u m o u r s are briefly r e v i e w e d a n d t h e r a d i o logical a p p e a r a n c e s d i s c u s s e d in detail. 3- T h e i m p o r t a n c e of calcification in t h e diagnosis of t h e t u m o u r is stressed. 4. T h e t u m o u r s are r a r e a n d t h o u g h t h e y m a y p r o d u c e a v a r i e t y of a p p e a r a n c e s , it is felt t h a t t h e radiological p i c t u r e , as in t h e t w o cases described, m a y b e p a t h o g n o m o n i c . M y t h a n k s are d u e to M r . G e o f f r e y Flavell for p e r m i s s i o n to p u b l i s h t h e case r e c o r d s ; to M r . D. W . C. N o r t h f i e l d , w h o also o p e r a t e d o n t h e first p a t i e n t ; a n d to P r o f e s s o r D. S. Russell for p e r m i s s i o n to p u b l i s h t h e m i c r o s c o p i c a l findings. I w o u l d also like to t h a n k D r . M . H . Jupe, D i r e c t o r , a n d D r . R. S. M u r r a y , A s s i s t a n t D i r e c t o r , of t h e R a d i o d i a g n o s t i c D e p a r t m e n t , for t h e i r keen interest and encouragement. BIBLIOGRAPHY ALLISON, P. R., and CARMICHAEL,R. (I939) , Brit. J. Surg., 27, 175. BIGLER, J. A., and HOYNE, A. (I932), Amer. ft. Dis. Child., 43, 1552. CHANDLER, F. A., and NORCROSS, J. R. (I94O), ft. Amer. reed. Ass., 114. 112. GODWIN, J. T., WATSON, W. L., POOL, J. L., CAHAN, W. G., and NARDIELLO, V. A. (195o), J. thorac. Surg., 2o, 169. HARTUNG, A., and RUBERT, S. R. (I935) , Radiology, 24, 607. HOLLINGSWORTH, R. K. (I946), Surg. Gynec. Obstet., 82, 682. JuPE, M. H. (I938), Brit. J. Radiol., I24, 242. KENT, E. M., BLADES, B., VALLE, A. R., and GRAHAM, E. A. (I944),J. thorac. Surg., 13, 116. MANDEVlLLE, F. B. (1949), Radiology, 53, 4o3. MURRAY, M. R., and STOUT, A. P. (1947), Amer. J. Path., 23, 429. PATBESON, D., and PILeHBR, R. S. (I94I), Brit. J. Surg., 28, 608. POTTER, E. L., and PAI~RISH, J. M. (I942), Amer. J. Path., 18, 141. RODRBGUEZ, C., BUTO, A., and POTENZA, L. (195I), Dis. Chest., 19, 690. RO~ERS, J. G., and KEOGH, J. P. (I95o), Ibid., 17, 532. SHERMAN, R. S., and LEAMINO, R. (I953), Radiology, 60, 837. STARTZ, I. S., and ABRAMS, J. (I938), Ibid., 3o, 232. STOUT, A. P. (I947), Surg. Gynec. Obstet., 84, ioi. WlTTENBORG, M. H. (I95O), Radiology, ~4, 679. WYATT, G. M., and FARBEI~, S. (I94I), Amer. J. Roentgenol., 46, 485 .
INTRATHORACIC
TUMOURS
TUMOURS
OF
OF THE SYSTEM
THE
SYMPATHETIC
SYMPATHETIC
275
NERVOUS
WITH A R E P O R T OF TWO C A S E S
BY P. JACOBS, M.B., Ch.B., M.R.C.S., M.R.C.P., D.M.R.(D) SENIOR REGISTRAR IN DIAGNOSTIC RADIOLOGY, LONDON HOSPITAL
REPORTS of tumours occurring in various parts of the body arising from cells of the sympathetic nervous system appear in the literature from time to time. The best known are those arising from the suprarenal medulla divided into the two main clinical types, the Pepper type, in which a primary suprarenal neoplasm metastasizes to the liver, and the Hutchison type, in which metastases occur in the skull, orbit, and long bones. Many of these tumours present a mixed picture, so modern opinion is against retaining these watertight compartments. Tumours may arise from sympathetic nerves elsewhere. They have been reported arising from such structures as the abdominal sympathetic nerves, sacrococcygeal gland, in the mesentery, jejunum, liver, uterus, cavity of the nose, ciliary ganglion, skin, scapular region, spinal canal, and cervical and thoracic sympathetic chain. The present paper is concerned with sympathetic nerve tumours arising within or presenting in the thorax. For the most part these turnouts arise from the thoracic sympathetic chain situated in the paravertebral gutter on either side. Therefore, their origin is not strictly mediastinal, but they soon enlarge to occupy the posterior mediastinum pushing the mediastinal pleura forwards. They extend more to one side than the other, though some may appear on both sides of the midline and may extend cvcn to occupy part of the anterior mediastinum. PATHOLOGY The sympathetic nervous system is developed by a ]~rogressive growth of and differentiation from the pluripotential mother cells, the sympathogonia. Tumours may contain cells of varying maturity and, in fact, rarely contain a single-cell type. Various transitions between the different forms are reported. Numerous classifications are suggested and there is much confusion. The simplest and probably the most useful is the one proposed by Bielschowsky. O F T U M O U R S O F S Y M P A T H E T I C S Y S T E M (after Bielschowshy) (The turnours and their synonyms are in brackets) Sympathogonia (sympathogonioma)
CLASSIFICATION
\
sympathoblastoma ]sympathicoblastoma \ Sympathoblast ~neuroblastoma ~neurocytoma f
Phaeochromoblast (phaeochromoblastoma)
Sympathetic ganglion cells (ganglioneuroma)
Chromaffin cells (phaeochromocytoma)
The sympathogonioma and chromaffin tumours occur extremely rarely in the thorax. For the main part roughly 25 per cent of intrathoracic sympathetic nerve tumours consist of the neuroblastoma (sympathoblastoma) and 75 per cent consist of the more differentiated, more mature, and less malignant ganglioneuromata. Although ganglioneuromata are regarded generally as benign tumours, Stout (1947) has described metastases occurring from them. Tumours are encountered in which varying numbers of ganglion cells are present in a growth which otherwise has the criteria of a fibrous tissue growth--these are known as gang/ionated
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neurofibromata. Both the benign and malignant tumours may assume a dumb-bell form, occurring both in the spinal canal and in the thorax. Ineidenee.--Wyatt and Farber (i94i) traced 40 cases of neuroblastoma over a io-year period at the Boston Children's Hospital. In the same period they traced 3° cases of Wilms' tumour. They did not state, however, how many of their cases were primarily intrathoracic. Sherman and Leaming (1953) , in an analysis of 5o cases of neuroblastoma, did not record with certainty a primary intrathoracic example ; io of their 50 patients had intrathoracic lesions which they regarded as metastatic, though they said that the radiographs in a few cases suggested that the primary tumour might have arisen there. Wittenborg (195o) regarded 7 per cent of 73 cases to be primarily intrathoracic. Ganglioneuromata, as indicated, are more common. Rogers and Keogh (195o) reported that up to 195o they were able to trace in the literature 9° cases of intrathoracic ganglioneuroma. The present two cases are primary intrathoracic neuroblastomata, no evidence of metastases being found from either. CLINICAL F E A T U R E S The great majority of the patients are infants and young children. Some of the ganglioneuroma cases, however, are found in adults. Patients may be referred for radiological examination on account of the following groups of symptoms : - i. Intrathoracic Symptoms. Patients may complain of vague pains or fullness in the chest. They may suffer from symptoms arising from pressure on structures such as the trachea, main bronchi, recurrent laryngeal nerve, (esophagus, or superior vena cava. Examples of such symptoms and signs are dyspn~ea, stridor, unproductive brassy cough, hoarseness with paralysis of a vocal cord, dysphagia, and distended veins of the neck and trunk. Homer's syndrome from involvement of the sympathetic trunk may be found, and it may occur after surgical removal of the tumour. 2. Spinal Symptoms.--Some of these tumours arise within the intervertebral foramina and extend both to the spinal canal and outwards into the thorax. They are often called ' dumb-bell ' or ' hourglass, tumours '. They are uncommon but very interesting. A good example is reported in the present paper. 3. Symptoms due to Metastases.TThe patient may present on account of the effects of metastases. These may occur in soft tissues, such as in the orbits, producing exophthalmos, or in other soft tissues, such as the scalp, when the lumps will be palpable. They may occur in bone, and the diagnosis of neuroblastoma will be kept in mind when unexpected osteolytic areas or periosteal reaction causing radiating spicules or perpendicular striations are seen. Bony metastases from neuroblastoma tend to be bilaterally symmetrical. Hartung and Rubert (~935) described 2 patients with primary intrathoracic neuroblastomata in whom bony metastases were demonstrated. At that time they regarded their cases as unique, but subsequently other cases of this nature have been reported. 4. Fortuitous Finding.--Probably with the ever-increasing routine chest examinations in children, tuberculin surveys, and similar investigations necessitating chest radiography, more of these tumours, and particularly the ganglioneuromata, will be discovered unexpectedly. One of the two patients referred to, presented on account of spinal symptoms, the other on account of a chronic unproductive cough at first thought to be whooping-cough.
RADIOLOGICAL ASPECTS As stated, the tumour is seen most frequently in young children. It presents usually as a smooth, rounded, well-circumscribed, homogeneous opacity. Slight lobulation of the borders may be seen. The tumours appear most frequently at the apex and in the upper half of the hemithorax and are found always to be posteriorly situated. However, some may occur in the lower part of the hemithorax and others may be paraspinal in position, being seen as extra shadows thrgugh the cardiac silhouette.
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Earlier writers stated that sympathetic nerve tumours in general occurred more frequently on the left side of the body. Stout (1947) could find no statistical difference as to the side of the body affected. That author, however, was discussing sympathetic nerve tumours occurring in all sites. The majority of the reported intrathoracic cases occurred on the left side. For example, Hollingsworth (i946) reported 7 intrathoracic cases, of which 6 were left-sided. The present 2 examples are both left-sided. The neuroblastomata appear to be left-sided more frequently than the ganglioneuromata. However, since cases of both types of tumour have been found on the right side, little diagnostic help may be expected from the consideration of the side of the thorax involved. Both in ganglioneuroma and in neuroblastoma, bony erosion either of the ribs or of the vertebral column may be found. Intervertebral foramina may be enlarged, though in the upper thoracic region this may be difficult to demonstrate. Bony erosions are caused usually by the effects of pressure and do not necessarily indicate the presence of metastases. In one of the present examples, well-marked erosion of the posterior part of the left 5th rib with widening of the left 5-6th interspace was found. In the other, erosion of the posterior part of the 3rd left rib, with widening of the 3rd-4th interspace, was similarly seen. In both the present cases an important and interesting feature is the presence of calcification. Calcification occurring in neuroblastomata of the suprarenal is, of course, well known. Calcification in sympathetic nerve tumours in other sites is not so well recognized. Mandeville (1949) studied all reported instances in which calcification had been seen in sympathetic nerve tumours in all sites. Only 3 intrathoracic examples were discovered. In one, the calcification was found by the pathologist after removal of the tumour. In another, the neuroblastoma presented as a partially calcified opacity to the right of the lower thoracic spine. In this type there is a resemblance to a tuberculous abscess, the differential diagnosis being made by the lack of the typical bony changes of tuberculosis. The third example was reported by Startz and Abrams (x938). One of their patients had a tumour in the right apex and upper zone in which calcification was seen. The radiograph was published and it is the only one discovered which is comparable with those of the present two patients. In addition, HoUingsworth (i 946) reported 7 patients with intrathoracic tumours of sympathetic nerves. He reported 2 cases showing calcification, but the radiographs were not published. Of interest is the fact that his 2 examples demonstrating calcification were histologically ganglioneuromata. One of the present cases was a neuroblastoma, the other a neuroblastoma differentiating towards a ganglioneuroma. More recently, Sherman and Learning (1953) have published a comprehensive paper on the radiological findings in neuroblastoma. They reported io cases with intrathoracic manifestations, but in only I case was calcification found, and this was in an extension upward through the diaphragm of a mass from the suprarenal area. Metastases to the lungs may occur from neuroblastomata elsewhere. They appear as rounded opacities with indistinct borders, but they have no diagnostic features and cannot be differentiated by their appearances from other metastases such as, for example, those from a Wilms' tumour. They may, incidentally, be very radiosensitive. Metastatic mediastinal tumours and pleural deposits and effusions may also be found. The radiological appearances of bony metastatic lesions have been described well elsewhere by other writers and will not be repeated. One should emphasize, nevertheless, the importance of radiographing all bones in a search for metastatic deposits in the presence of a chest lesion, such as has been described. Other diagnostic radiological methods ,include screening the chest to investigate possible displacement of the barium-filled oesophagus, diaphragmatic movements, and the like. Tomography may be helpful in demonstrating bony erosions. It was used in one of the present patients. No evidence of bony erosion was found other than that demonstrated by the straight films and none subsequently at operation was discovered. Diagnostic pneumothorax will enable one to determine
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whether an opacity is intrapulmonary or mediastinal. It is felt tl~at with increasing knowledge of the pattern of mediastinal tumours, this investigation will comparatively seldom be necessary.
CONCLUSION It is seen that these tumours may produce a variable picture. However, there is a tendency for them to occur in the upper zones of the hemithorax. Calcification in both the present cases was
Fig. 235.--Case I. A.P. radiograph of chest. Note areas of calcification within the opacity and also erosion of .posterior part of left 5th rib, with widenmg of 5th-6th interspace.
very marked and microscopically was found to be scattered throughout the tumour. It is felt that in the presence of a rounded Fig. 236.--Case i. Left lateral radiograph showingrounded turnout posteriorly situated, tumour, showing evidence of calcification, situated posteriorly in the hemithorax of a child, the diagnosis of a sympathetic nerve tumour may confidently be made, as indeed it was in the present two patients. Calcification has not been recorded in other posteriorly situated tumours such as neurofibroma. Wyatt and Farber (1941) considered that there was no characteristic picture of a primary neuroblastoma. Sherman and Leaming (1953) believe this to be true, except when the radiologist can reliably identify the presence of a mass in the suprarenal region with calcification. To this I would add that primary intrathoracic sympathetic nerve tumours may produce an absolutely characteristic picture.
CASE
REPORTS
Case I . - - L a w r e n c e B., aged ten m o n t h s , was a d m i t t e d to hospital on Sept. 24, 1953, on account of suspected m e n i n g i t i s or poliomyelitis. T h e m o t h e r ' s p r e g n a n c y was normal, the d e l i v e r y normal, the b a b y sat up at five m o n t h s and stood w i t h assistance at six and a half m o n t h s . Seven weeks before a d m i s s i o n he h a d an attack
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of diarrhoea and vomiting f r o m w h i c h he soon recovered, except that his parents noticed that his legs seemed weak and were not supporting h i m as before. T h i s weakness worsened, and the m o t h e r said that he had not moved his legs for two days before admission. O n examination, there was marked neck rigidity, knee and ankle reflexes were brisk and abdominal reflexes absent. T h e r e was a sustained ankle clonus on the right side and a positive Kernig sign. An area of par~esthesia was noticed just above the umbilicus on drawing a pin down the body. A diagnosis of spinal compression was suggested and for that reason the spine and chest were radiographed. CHEST RADIOGRAPHS(Figs. 235, z 3 6 ) . - - A n opacity was seen in the left u p p e r and mid zones extending from the xst to the 3rd left interspaces, spreading f r o m the mediastinal surface of the lung to half-way across the left
Fig. 237.--Case z. P.A. radiograph, Areasofcalc~ficatian are seen within the opacity. Erosion of the mferior surface of the medial part of the left 3rd rib is also noted,
Fig. 238.--Case 2. Left lateral radiograph showing rounded posteriorly mtuated tumour.
hemithorax at its widest point. T h e edges were clear-cut and no infiltration of s u r r o u n d i n g lung was seen. T h e mass was seen to be posteriorly situated in the lateral film and extended from the 3rd to the 7th thoracic vertebra. Mottled areas of calcification were clearly seen within the opacity, the calcified areas becoming confluent in places. Erosion of the posterior part of the 5th left rib, with widening of the 5-6th intercostal " space, was found. AT OPERATION (Sept. e8, I 9 5 3 ) . - - L a m i n e c t o m y by Mr. D. W. C. Northfield. T h e dorsal spine was explored and a large extradural mass of t u m o u r removed. It protruded into the 4th, 5th, and 6th spaces, at which points the t u m o u r was incised. MICROSCOPICAL EXAMINATION (Professor D. S. Russelt).--Pieees of extensively calcified solid neoplasm of small spheroidal cells, in anatomical continuity with a sympathetic ganglion. T h e appearances are those of an undifferentiated neurohlastoma. X-RAY THERAPY.--Later he was given a course of deep X°ray t h e r a p y - - 3 o a o r, 2oo kv., i6 treatments, 6 × 8 cm. right angle wedge pair--overall time ei days. PRoaRESs.--Following operation and radiotherapy he made a very satisfactory recovery and was using his legs normally on discharge f r o m hospital on Nov. 29. Jan. I4, I954 : He was re-admitted. At the time of admission leg m o v e m e n t s were good and no abnormal physical signs were found.
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Jan. 18 (Removal of mediastinal tumour by Mr. G. Flavell) : A firm flat'oval mass was found lying on the vertebral bodies centred on the 5th, 3 cm./2 cm./o" 5 cm. T h e sympathetic chain was divided above and below and the mass with the overlying pleura was removed without difficulty. Discharged on Feb. i to be followed up by Radiotherapy Department. Sept. 12 : No evidence of metastases was discovered clinically or after radiography of the entire skeleton. Case 2 . - - N o r m a R., aged 3 years, was admitted on July 7, I954. History of chronic .unproductive cough for ten months. T h e cough resembled whooping-cough. Apart from a urinary infection, the child had no previous history of illness. She produced no sputum of hmmoptysis and was not dyspnoeic. On examination, no abnormal physical signs were found except for dullness to percussion and diminished breath-sounds over the upper half of the left hemithorax posteriorly. CHEST RADIOGRAPHS (Figs. 237, 238).--A well-demarcated rounded opacity was seen. On the posteroanterior film it extended from the mediastinal surface of the left lung field right across the upper left hemithorax. It was found in the lateral film to be posteriorly situated. Quite extensive calcification was found within the opacity. T h e posterior part of the left third rib with widening of the left 3rd-4th interspace was noted. No evidence of metastases in other bones was found after radiography of the entire skeleton. AT OPERATION (Mr. Geoffrey Flavell).--A tumour was found in the posterior mediastinum to the left. It was an ovoid mass measuring 21 × 2 × 3 in. It extended up to the thoracic inlet. Part of it was adherent to the aortic arch and great vessels, and it was not possible to remove it completely. MICROSCOPICAL EXAMINATION (Professor D. S. Russell).--Neuroblastoma differentiating towards ganglioneuroma with a few definite ganglion cells. There is focal calcification of the stroma. (July 27, 1954.) Aug. 6, 1954 : Discharged and referred to Radiotherapy Department for treatment as an out-patient. SUMMARY i. T w o cases of p r i m a r y i n t r a t h o r a c i c t u m o u r s of t h e s y m p a t h e t i c n e r v o u s s y s t e m are p r e s e n t e d . 2. T h e p a t h o l o g y a n d clinical f i n d i n g s of t h e s e t u m o u r s are briefly r e v i e w e d a n d t h e r a d i o logical a p p e a r a n c e s d i s c u s s e d in detail. 3- T h e i m p o r t a n c e of calcification in t h e diagnosis of t h e t u m o u r is stressed. 4. T h e t u m o u r s are r a r e a n d t h o u g h t h e y m a y p r o d u c e a v a r i e t y of a p p e a r a n c e s , it is felt t h a t t h e radiological p i c t u r e , as in t h e t w o cases described, m a y b e p a t h o g n o m o n i c . M y t h a n k s are d u e to M r . G e o f f r e y Flavell for p e r m i s s i o n to p u b l i s h t h e case r e c o r d s ; to M r . D. W . C. N o r t h f i e l d , w h o also o p e r a t e d o n t h e first p a t i e n t ; a n d to P r o f e s s o r D. S. Russell for p e r m i s s i o n to p u b l i s h t h e m i c r o s c o p i c a l findings. I w o u l d also like to t h a n k D r . M . H . Jupe, D i r e c t o r , a n d D r . R. S. M u r r a y , A s s i s t a n t D i r e c t o r , of t h e R a d i o d i a g n o s t i c D e p a r t m e n t , for t h e i r keen interest and encouragement. BIBLIOGRAPHY ALLISON, P. R., and CARMICHAEL,R. (I939) , Brit. J. Surg., 27, 175. BIGLER, J. A., and HOYNE, A. (I932), Amer. ft. Dis. Child., 43, 1552. CHANDLER, F. A., and NORCROSS, J. R. (I94O), ft. Amer. reed. Ass., 114. 112. GODWIN, J. T., WATSON, W. L., POOL, J. L., CAHAN, W. G., and NARDIELLO, V. A. (195o), J. thorac. Surg., 2o, 169. HARTUNG, A., and RUBERT, S. R. (I935) , Radiology, 24, 607. HOLLINGSWORTH, R. K. (I946), Surg. Gynec. Obstet., 82, 682. JuPE, M. H. (I938), Brit. J. Radiol., I24, 242. KENT, E. M., BLADES, B., VALLE, A. R., and GRAHAM, E. A. (I944),J. thorac. Surg., 13, 116. MANDEVlLLE, F. B. (1949), Radiology, 53, 4o3. MURRAY, M. R., and STOUT, A. P. (1947), Amer. J. Path., 23, 429. PATBESON, D., and PILeHBR, R. S. (I94I), Brit. J. Surg., 28, 608. POTTER, E. L., and PAI~RISH, J. M. (I942), Amer. J. Path., 18, 141. RODRBGUEZ, C., BUTO, A., and POTENZA, L. (195I), Dis. Chest., 19, 690. RO~ERS, J. G., and KEOGH, J. P. (I95o), Ibid., 17, 532. SHERMAN, R. S., and LEAMINO, R. (I953), Radiology, 60, 837. STARTZ, I. S., and ABRAMS, J. (I938), Ibid., 3o, 232. STOUT, A. P. (I947), Surg. Gynec. Obstet., 84, ioi. WlTTENBORG, M. H. (I95O), Radiology, ~4, 679. WYATT, G. M., and FARBEI~, S. (I94I), Amer. J. Roentgenol., 46, 485 .