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Pulmonary alveolar proteinosis presenting with pneumothorax
Clin. RadioL (1967) 18, 428-431 PULMONARY
ALVEOLAR PROTEINOSIS PNEUMOTHORAX H. C. A N T O N
and BRENDA
PRESENTING
WITH
GRAY*
From the Department of Radiodiagnosis and the Department of Pathology, Stobhill General Hospital, Glasgow, N.1
A 32-year-old m a n who presented with p n e u m o t h o r a x was f o u n d at a u t o p s y to have p u l m o n a r y alveolar proteinosis. Chest x - r a y showed a h o n e y c o m b a p p e a r a n c e a n d rupture o f a subpleural bulla is suggested as the p r o b a b l e cause. V a r i a t i o n s in radiological • patterns a n d in their distribution are discussed.
ABOUT 100 cases o f p u l m o n a r y alveolar proteinosis have been r e p o r t e d since the original account (Rosen, Castleman a n d Liebow, 1958). This case is described because o f its hitherto u n r e p o r t e d clinical presentation with p n e u m o t h o r a x a n d l y m p h a d e n o p a t h y . I n addition, x - r a y e x a m i n a t i o n o f the chest showed a h o n e y c o m b appearance. T h e original account o f the disease was comprehensive. L a r s o n a n d G o r d i n i e r , (1965) reviewed 85 cases, 6 o f which were new. O f u n k n o w n aetiology, the disease is characterised b y a p r o t e i n a c e o u s m a t e r i a l filling the p u l m o n a r y alveoli. Symptoms may be absent b u t m o r e often there is cough, d y s p n o e a o f insidious onset a n d low-grade fever. Cyanosis a n d finger clubbing m a y develop in severe cases, a n d death occurs in a b o u t one quarter o f cases. O n examination, rales m a y or m a y n o t b e found. I n d e e d suspicion m a y be a r o u s e d ~b y the striking absence o f positive signs despite extensive x-ray changes. The diagnosis is usually established b y lung b i o p s y o r at autopsy, b u t it m a y also be m a d e b y finding the characteristic m a t e r i a l in s p u t u m (Carlson a n d M a s o n , 1960). The disease m a y remit spontaneously or be c o m p l i c a t e d b y either bacterial o r fungal infection ( L a r s o n a n d G o r d i n i e r , 1965). A reliable m e t h o d o f t r e a t m e n t is n o t yet established, a l t h o u g h relief has been o b t a i n e d following i n t r a b r o n c h i a l infusion o f heparin in saline (Ramirez-R, N y k a a n d M c L a u g h l i n , 1963).
The E.S.R. was 53 mm. in the first hour. Initial treatment included water-seal drainage of the left pleural cavity, and Tetracycline 250 mg. q.i.d. There was an occasional pyrexia, rarely exceeding 101°F. Laboratory investigations: serum albumin 2.8 gm.%, globulin 3.2 gin.%; electrophoresis, reduced albumin, slight increase in ~2, and ~1 globulins; serum alkaline phosphatase elevated, 16 K.A. units %; other liver function tests normal. One day before death there was slight acidosis (Micro Astrup--Blood pH 7.31, pCO2 43 rnm. Hg, Standard bicarb. 20 m.eq./1, plasma). Haematotogical findings: Hb. 13.7 gin.%; W.B.C. 4,300-8,300 per c.mm.; slight relative neutrophilia. Bacteriological examination of sputum, including culture for Mycobacterit~m tuberculosis, negative. Pulmonary alveolar proteinosis was not suspected. Biopsy of right axillary node, non-specific inflammatory changes. Mantoux and Kveim tests, negative. The left lung expanded fully for short periods, the degree of pneumothorax being very variable. Ampicillin 250 mg. q.i.d, was started 2 weeks after admission and Prednisolone 15 rag. q.i.d. 1 week later. He gradually deteriorated, requiring oxygen for dyspnoea at rest and for peripheral cyanosis, dying 4 weeks after admission. Radiological findings.--A large left pneumothorax was shown on the initial film of the chest and an x-ray a few days after admission (Fig. 1) showed considerable absorption of the pneumothorax with water-seal drainage of the left pleural cavity. There was extensive pulmonary infiltration, confluence of which had produced consolidation at the periphery of both mid-zones. Adjacent portions of the lungs showed numerous small translucencies, forming a honeycomb pattern with the infiltration. The cyst-like translucencies were most obvious at the subpleural part of the left lung (Fig. 2), when the pneumothorax had later relapsed. Autopsy Findings.--No free air could be demonstrated in the left plenral cavity which contained a small quantity of clear straw-coloured fluid; there were fine fibrous adhesions over the apices of both upper lobes. On separating the left apical adhesions a small area of roughening on the surface of the lung was noted, suggesting a ruptured bulla; there were several subpleural builae in this region, varying from a few millimetres to 1 cm. in diameter. Over the remainder of the lung surfaces there was a fine shaggy fibrinous exudate, extending into the interlobar fissures. Together, the lungs weighed 2645 g. (normal 900-1300 g.); they were bulky and firm particularly in the lower lobes, at first suggesting pneumonic consolidation. Section showed a fine honeycomb
CASE REPORT Male aged 32. Admitted to hospital with 2 day history of pain in the left chest and epigastrium after 3 weeks breathlessness with an unproductive cough. In the previous winter he had persistent colds and an occasional cough, with loss of appetite and tiredness. He was a plumber, often working in a dusty atmosphere, and he smoked 20-30 cigarettes daily. On examination he was dyspnoeic with rapid shallow respirations. Palpable nodes were present in the right 'side *Present address, Department of Pathology, Royal of the neck, both axillae and both groins. There was a left pneumothorax and the blood pressure was 170/95 ram. Hg. Northern Infirmary, Inverness. 428
PULMONARY
ALVEOLAR
PROTEINOSIS
PRESENTING
WITH
PNEUMOTHORAX
429
FIG. 1 Chest x-ray a few days after admission, showing pneumothorax. Fio. 3 Section of lung, stained FL and E., x i00, showing granular material filling alveoli, and foamy macrophages.
FIG. 2 Cyst-like intrapulmonary translucencies, most marked in the sub-pleural region. appearance in both upper lobes, with numerous small cystic spaces, ranging from 1 ram. to 1 cm. and solid, rather granular, greyish intervening lung tissue. Some cysts connected with bronchial passages and were thought to be dilated bronchioles. In the lower lobes, the lung tissue was much more solid and cystic spaces were relatively fewer and smaller. The trachea and main bronchi contained a little thin mucopus. The tracheo-bronchial and mediastinal lymph nodes were enlarged to a maximum size of 3 x 2 × 1 cm. Their cut surfaces were greyish black. The heart weighed 280 g. The wall of the right ventricle was slightly thickened. The remaining organs showed no abnormality. Histology.--Lung sections (haematoxylin and eosin) showed a striking distension of almost all the alveolar spaces with granular eosinophilic material (Fig. 3) which was found also in a few small bronchioles. The alveolar walls
FIo. 4
Large section of lung, stained H. and E., x 2 -5, to show numerous cysts. were intact; there was no inflammatory reaction and no consolidation in the lOWer lobes. There was lymphocytic infiltration in the walls of several bronchioles and bronchi. Special staining showed that the intra-alveolar material was P.A.S. positive after diastase digestion and metachromatic with toluidine blue. Trichrome and reticulin stains showed preservation of the alveolar walls with focal areas of fibrosis.
430
CLINICAL R A D I O L O G Y
Foamy macrophages were present in the eosinophilic material in some alveoli; acicular spaces were also seen which contained anisotropic crystals on examination with polarised light. Sudan IV stain for fat showed that many of the foamy macrophages contained fine lipid droplets and these were also seen in the alveolar walls. A few cystic spaces were formed partly by distended bronchioles and partly by terminal air sacs but the majority had no fibrous tissue wall and no epithefial lining. On the contrary, the alveoli opened directly off the cystic spaces, and almost completely surrounded them, the alveoli themselves being filled with the proteinaceous material. The subpleural cysts had only a thin fibrous septum between them and the serous surface (Fig. 4). The bronchial and mediastinal lymph nodes showed sinus hyperplasia, similar to that in the axillary lymph node. No P.A.S. positive material was present. DISCUSSION Pathology.---The diagnostic pathological features of pulmonary alveolar proteinosis have been fully described by a number of authors but in fact little has been added to the original histological description of Rosen et al. (1958), to which the present case conforms. Various theories of pathogenesis have been postulated and discussed by Scadding (1963). Rosen et al. (1958) suggested that the cause was an abnormal proliferation of septal cells which sloughed into the alveolar spaces and the resulting debris accumulated to form the proteinaceous material. Larson and Gordinier (1965) considered that the hyperplasia of the alveolar cells resulted in hypersecretion of material which accumulated in the alveoli. Ray and Salm (1962) thought that the material was inspissated serum transudate and some cases reverted to normal if this material was removed by phagocytosis and absorption. The histochemical observations of Stanisfer and Bourgeois (1965) led them to support the view that the material was derived from extravasation of serum through injured capillary walls. The nature of the specific factor which operates in pulmonary alveolar proteinosis is not clear. Scadding (1963) notes that there is no evidence of an abnormal serum protein. Inhalation of noxious agents has been suggested as the most likely cause but none has ever been positively incriminated. In our patient, emphysematous areas in the intervening parenchyma, described by Rosen et al. (1958), were present particularly in the upper lobes. This feature was more pronounced than in previously described cases, which accounts for the unusual clinical presentation and striking radiological picture. The pneumothorax was almost certainly the result of rupture of one of the many subpleural bullae. The mechanism of formation of the cyst-like translucencies in staphylococcal pneumonia is described by Spencer (1962). Valvular
obstruction in the smaller bronchi leads to the formation of tension cavities, and, owing to the consolidation surrounding the cavities, collateral ventilation cannot remove the excess air, causing further distension. Such a pneumatocele may rupture producing a pneumothorax. Similar conditions prevail in pulmonary alveolar proteinosis, the proteinaceous material extending to the bronchioles and smaller bronchi, with consolidated numerous groups of alveoli and it is therefore not surprising that tension cysts may also develop in pulmonary alveolar proteinosis. Translucencies in a staphylococcal pneumonia may also be due to abscess cavities, which are not found in uncomplicated pulmonary alveolar proteinosis. The fatal outcome in our patient was attributable in part to the additional respiratory embarrassment consequent upon pneumothorax, but perhaps mostly to the fact that there was such extensive involvement of the lungs by the disease process that there was virtually no lung parenchyma left for normal gaseous exchange. Radiologieal Findings.--The description of the chest x-ray appearances by Rosen et al. (1958) was of a 'fine, diffuse, perihilar, radiating, feathery or vaguely nodular, soft density, resembling in its butterfly distribution the pattern seen in severe pulmonary oedema'. Hilar lymphadenopathy was absent. Most subsequent authors have repeated this description though their illustrations do not always conform to it. We feel that too rigid an adherence to the original description could lead to failure to recognise the condition radiologically. Several authors have called attention to variations in the radiological picture. Lull, Beyer, Maier and Morss (1959) point out that in their 2 patients, the feathery densities were mainly basal in distribution, and a peripheral as well as a basal distribution is shown in 1 of the illustrations of a patient reported by Ford and Hackett (1965). Peripheral involvement was well shown in the present case (Fig. 1) and also confluence of the lesions producing a homogeneous consolidation, a fairly common finding in other reports. Of particular interest in our case is the presence of cyst-like translucencies which stand out clearly against the consolidated background (Fig. 2). Varying in size up to 1 cm. they are thus considerably larger than the pinpoint translucencies described by Kerley (1962). Ramirez-R (1964) also mentions radiolucent cysts, which he attributes to bronchiolar obstruction. He stresses particularly the distinctive appearance of individual lesions which he describes as mottled or granular densities, sometimes like rosettes, due to aggregates of alveolar-occupying densities. This
PULMONARY ALVEOLAR PROTEINOSIS PRESENTING WITH PNEUMOTHORAX
appearance, however, is not pathognomonic of pulmonary alveolar proteinosis, since it may occur in other conditions, including haemosiderosis. Moreover, such distinctive opacities are not always present, rounded nodules of non-specific character being a common finding. Thus the 3rd patient recorded in this country (Ray and Salm, 1962) was a tin miner whose chest x-ray showed for a considerable period, a diffuse nodulation indistinguishable from that of pneumoconiosis. Alterations in the position and extent of the areas of lung affected by pulmonary alveolar proteinosis were observed in one case by Phillips and Constance (1963), the shifting nature of the densities suggesting pulmonary eosinophilia. The variants in the radiological picture include (1) Feathery appearance of individual lesions, (2) Butterfly distribution, (3) Mainly basal opacities, (4) Mainly peripheral opacities, (5) Homogeneous eonsolidation, (6) Diffuse nodulation, (7) Radiolucent cysts, and (8) Shifting nature of lesions. Any combination may occur, and the pattern may alter in the course of the disease. Differential Diagnosis.--When only the butterfly distribution is taken into account, the diagnosis is usually acute pulmonary oedema, although a similar appearance is described in Pneumocystis carinii pneumonia. Pneumothorax may occur in the latter due to rupture of a bulla (Kerley, 1962). When pulmonary alveolar proteinosis presents as a diffuse nodulation the differential diagnosis is widened to include nodulation due to infection, especially miliary tuberculosis, pneumoconiosis, metastatic tumour, haemosiderosis, the collagen diseases and sarcoidosis. Unlike pulmonary alveolar proteinosis, sarcoidosis is usually accompanied by mediastinal lymphadenopathy. The honeycomb pattern in our patient is similar to that found in the honeycomb lung defined as cystic translucencies in association with interstitial granulomata or fibrosis (Heppleston, 1956); under-
lying lesions include sarcoidosis, scleroderma, tuberose sclerosis and eosinophilic granuloma. The last condition was suggested as a possibility in the present case because of its association with pneumothorax in a quarter of all cases (Lewis, 1964). Other diseases not conforming to the pathological criteria of honeycomb lung may show a similar honeycomb pattern on chest x-ray especially if associated with an inflammatory process, e.g. some forms of emphysema, congenital cystic disease, and bronchiectasis. Consolidation, as seen in pneumonia, has not yet been reported as an isolated feature of pulmonary alveolar proteinosis. The main differential diagnoses therefore include other causes of a butterfly pattern, a diffuse nodulation, and a honeycomb appearance. Aeknowledgements.--We are grateful to Dr. J. G. Macarthur for allowing us to use the clinical records, and to Mr. P. S. Waldie for the photographic reproductions. REFERENCES CARLSON, D. J. t~ MASON, E. W. (1960). Amer. J. clin. Path., 33, 48. FORD, R. M. & HACKETT, E. (1965). Dis. Chest, 47, 446. HEPPLESTON, A. G. (1956). Thorax, 11, 77. KERLEY, P. (1962). A Textbook of X-Ray Diagnosis by British Authors, edited by Shanks, S. C. & Kerley, P., 3rd ed., Vol. II, p. 657 and p. 704. London: Lewis. LARS0N, R. K. & GORDINIER, R. (1965). Ann. intern. Meat., 62, 292. LEWIS, J. G. (1964). Quart. Y. Med., 33, N.S., 337. LULL, G. F., Jr., BEYER, J. C., MAIER, J. G. & MORSS, D. F. (1959). Amer. J. RoentgenoL, 82, 76. PHILLIPS, W. J. E. & CONSTANCE, T. J. (1963). Med. or. Aust., 2, 357. RAMIREz-R, J. (1964). Amer. J. RoentgenoL, 92, 571. RAMmEz-R, J., NYKA, W. & McLAUGHLIN, J. (1963). New Engl. J. Med., 268, 165. RAY, R. L. t~ SALM, R. (1962); Thorax, 17, 257. ROSEN, S. H., CASTLEMAN, B. • LIEBOW, A. A. (1958). New Engl. J. Med., 258, 1123. SCADDING, F. H. (1963). Current Medicine and Drugs, 4, 3. SPENCER, I-I. ( 1 9 6 2 ) . Pathology of the Lung, p. 112. Pergamon Press. STANISEER,P. D. & BOURGEOIS,C. (1965). Amer. J. Clin. Path., 44, 539.
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431
ALVEOLAR PROTEINOSIS PNEUMOTHORAX H. C. A N T O N
and BRENDA
PRESENTING
WITH
GRAY*
From the Department of Radiodiagnosis and the Department of Pathology, Stobhill General Hospital, Glasgow, N.1
A 32-year-old m a n who presented with p n e u m o t h o r a x was f o u n d at a u t o p s y to have p u l m o n a r y alveolar proteinosis. Chest x - r a y showed a h o n e y c o m b a p p e a r a n c e a n d rupture o f a subpleural bulla is suggested as the p r o b a b l e cause. V a r i a t i o n s in radiological • patterns a n d in their distribution are discussed.
ABOUT 100 cases o f p u l m o n a r y alveolar proteinosis have been r e p o r t e d since the original account (Rosen, Castleman a n d Liebow, 1958). This case is described because o f its hitherto u n r e p o r t e d clinical presentation with p n e u m o t h o r a x a n d l y m p h a d e n o p a t h y . I n addition, x - r a y e x a m i n a t i o n o f the chest showed a h o n e y c o m b appearance. T h e original account o f the disease was comprehensive. L a r s o n a n d G o r d i n i e r , (1965) reviewed 85 cases, 6 o f which were new. O f u n k n o w n aetiology, the disease is characterised b y a p r o t e i n a c e o u s m a t e r i a l filling the p u l m o n a r y alveoli. Symptoms may be absent b u t m o r e often there is cough, d y s p n o e a o f insidious onset a n d low-grade fever. Cyanosis a n d finger clubbing m a y develop in severe cases, a n d death occurs in a b o u t one quarter o f cases. O n examination, rales m a y or m a y n o t b e found. I n d e e d suspicion m a y be a r o u s e d ~b y the striking absence o f positive signs despite extensive x-ray changes. The diagnosis is usually established b y lung b i o p s y o r at autopsy, b u t it m a y also be m a d e b y finding the characteristic m a t e r i a l in s p u t u m (Carlson a n d M a s o n , 1960). The disease m a y remit spontaneously or be c o m p l i c a t e d b y either bacterial o r fungal infection ( L a r s o n a n d G o r d i n i e r , 1965). A reliable m e t h o d o f t r e a t m e n t is n o t yet established, a l t h o u g h relief has been o b t a i n e d following i n t r a b r o n c h i a l infusion o f heparin in saline (Ramirez-R, N y k a a n d M c L a u g h l i n , 1963).
The E.S.R. was 53 mm. in the first hour. Initial treatment included water-seal drainage of the left pleural cavity, and Tetracycline 250 mg. q.i.d. There was an occasional pyrexia, rarely exceeding 101°F. Laboratory investigations: serum albumin 2.8 gm.%, globulin 3.2 gin.%; electrophoresis, reduced albumin, slight increase in ~2, and ~1 globulins; serum alkaline phosphatase elevated, 16 K.A. units %; other liver function tests normal. One day before death there was slight acidosis (Micro Astrup--Blood pH 7.31, pCO2 43 rnm. Hg, Standard bicarb. 20 m.eq./1, plasma). Haematotogical findings: Hb. 13.7 gin.%; W.B.C. 4,300-8,300 per c.mm.; slight relative neutrophilia. Bacteriological examination of sputum, including culture for Mycobacterit~m tuberculosis, negative. Pulmonary alveolar proteinosis was not suspected. Biopsy of right axillary node, non-specific inflammatory changes. Mantoux and Kveim tests, negative. The left lung expanded fully for short periods, the degree of pneumothorax being very variable. Ampicillin 250 mg. q.i.d, was started 2 weeks after admission and Prednisolone 15 rag. q.i.d. 1 week later. He gradually deteriorated, requiring oxygen for dyspnoea at rest and for peripheral cyanosis, dying 4 weeks after admission. Radiological findings.--A large left pneumothorax was shown on the initial film of the chest and an x-ray a few days after admission (Fig. 1) showed considerable absorption of the pneumothorax with water-seal drainage of the left pleural cavity. There was extensive pulmonary infiltration, confluence of which had produced consolidation at the periphery of both mid-zones. Adjacent portions of the lungs showed numerous small translucencies, forming a honeycomb pattern with the infiltration. The cyst-like translucencies were most obvious at the subpleural part of the left lung (Fig. 2), when the pneumothorax had later relapsed. Autopsy Findings.--No free air could be demonstrated in the left plenral cavity which contained a small quantity of clear straw-coloured fluid; there were fine fibrous adhesions over the apices of both upper lobes. On separating the left apical adhesions a small area of roughening on the surface of the lung was noted, suggesting a ruptured bulla; there were several subpleural builae in this region, varying from a few millimetres to 1 cm. in diameter. Over the remainder of the lung surfaces there was a fine shaggy fibrinous exudate, extending into the interlobar fissures. Together, the lungs weighed 2645 g. (normal 900-1300 g.); they were bulky and firm particularly in the lower lobes, at first suggesting pneumonic consolidation. Section showed a fine honeycomb
CASE REPORT Male aged 32. Admitted to hospital with 2 day history of pain in the left chest and epigastrium after 3 weeks breathlessness with an unproductive cough. In the previous winter he had persistent colds and an occasional cough, with loss of appetite and tiredness. He was a plumber, often working in a dusty atmosphere, and he smoked 20-30 cigarettes daily. On examination he was dyspnoeic with rapid shallow respirations. Palpable nodes were present in the right 'side *Present address, Department of Pathology, Royal of the neck, both axillae and both groins. There was a left pneumothorax and the blood pressure was 170/95 ram. Hg. Northern Infirmary, Inverness. 428
PULMONARY
ALVEOLAR
PROTEINOSIS
PRESENTING
WITH
PNEUMOTHORAX
429
FIG. 1 Chest x-ray a few days after admission, showing pneumothorax. Fio. 3 Section of lung, stained FL and E., x i00, showing granular material filling alveoli, and foamy macrophages.
FIG. 2 Cyst-like intrapulmonary translucencies, most marked in the sub-pleural region. appearance in both upper lobes, with numerous small cystic spaces, ranging from 1 ram. to 1 cm. and solid, rather granular, greyish intervening lung tissue. Some cysts connected with bronchial passages and were thought to be dilated bronchioles. In the lower lobes, the lung tissue was much more solid and cystic spaces were relatively fewer and smaller. The trachea and main bronchi contained a little thin mucopus. The tracheo-bronchial and mediastinal lymph nodes were enlarged to a maximum size of 3 x 2 × 1 cm. Their cut surfaces were greyish black. The heart weighed 280 g. The wall of the right ventricle was slightly thickened. The remaining organs showed no abnormality. Histology.--Lung sections (haematoxylin and eosin) showed a striking distension of almost all the alveolar spaces with granular eosinophilic material (Fig. 3) which was found also in a few small bronchioles. The alveolar walls
FIo. 4
Large section of lung, stained H. and E., x 2 -5, to show numerous cysts. were intact; there was no inflammatory reaction and no consolidation in the lOWer lobes. There was lymphocytic infiltration in the walls of several bronchioles and bronchi. Special staining showed that the intra-alveolar material was P.A.S. positive after diastase digestion and metachromatic with toluidine blue. Trichrome and reticulin stains showed preservation of the alveolar walls with focal areas of fibrosis.
430
CLINICAL R A D I O L O G Y
Foamy macrophages were present in the eosinophilic material in some alveoli; acicular spaces were also seen which contained anisotropic crystals on examination with polarised light. Sudan IV stain for fat showed that many of the foamy macrophages contained fine lipid droplets and these were also seen in the alveolar walls. A few cystic spaces were formed partly by distended bronchioles and partly by terminal air sacs but the majority had no fibrous tissue wall and no epithefial lining. On the contrary, the alveoli opened directly off the cystic spaces, and almost completely surrounded them, the alveoli themselves being filled with the proteinaceous material. The subpleural cysts had only a thin fibrous septum between them and the serous surface (Fig. 4). The bronchial and mediastinal lymph nodes showed sinus hyperplasia, similar to that in the axillary lymph node. No P.A.S. positive material was present. DISCUSSION Pathology.---The diagnostic pathological features of pulmonary alveolar proteinosis have been fully described by a number of authors but in fact little has been added to the original histological description of Rosen et al. (1958), to which the present case conforms. Various theories of pathogenesis have been postulated and discussed by Scadding (1963). Rosen et al. (1958) suggested that the cause was an abnormal proliferation of septal cells which sloughed into the alveolar spaces and the resulting debris accumulated to form the proteinaceous material. Larson and Gordinier (1965) considered that the hyperplasia of the alveolar cells resulted in hypersecretion of material which accumulated in the alveoli. Ray and Salm (1962) thought that the material was inspissated serum transudate and some cases reverted to normal if this material was removed by phagocytosis and absorption. The histochemical observations of Stanisfer and Bourgeois (1965) led them to support the view that the material was derived from extravasation of serum through injured capillary walls. The nature of the specific factor which operates in pulmonary alveolar proteinosis is not clear. Scadding (1963) notes that there is no evidence of an abnormal serum protein. Inhalation of noxious agents has been suggested as the most likely cause but none has ever been positively incriminated. In our patient, emphysematous areas in the intervening parenchyma, described by Rosen et al. (1958), were present particularly in the upper lobes. This feature was more pronounced than in previously described cases, which accounts for the unusual clinical presentation and striking radiological picture. The pneumothorax was almost certainly the result of rupture of one of the many subpleural bullae. The mechanism of formation of the cyst-like translucencies in staphylococcal pneumonia is described by Spencer (1962). Valvular
obstruction in the smaller bronchi leads to the formation of tension cavities, and, owing to the consolidation surrounding the cavities, collateral ventilation cannot remove the excess air, causing further distension. Such a pneumatocele may rupture producing a pneumothorax. Similar conditions prevail in pulmonary alveolar proteinosis, the proteinaceous material extending to the bronchioles and smaller bronchi, with consolidated numerous groups of alveoli and it is therefore not surprising that tension cysts may also develop in pulmonary alveolar proteinosis. Translucencies in a staphylococcal pneumonia may also be due to abscess cavities, which are not found in uncomplicated pulmonary alveolar proteinosis. The fatal outcome in our patient was attributable in part to the additional respiratory embarrassment consequent upon pneumothorax, but perhaps mostly to the fact that there was such extensive involvement of the lungs by the disease process that there was virtually no lung parenchyma left for normal gaseous exchange. Radiologieal Findings.--The description of the chest x-ray appearances by Rosen et al. (1958) was of a 'fine, diffuse, perihilar, radiating, feathery or vaguely nodular, soft density, resembling in its butterfly distribution the pattern seen in severe pulmonary oedema'. Hilar lymphadenopathy was absent. Most subsequent authors have repeated this description though their illustrations do not always conform to it. We feel that too rigid an adherence to the original description could lead to failure to recognise the condition radiologically. Several authors have called attention to variations in the radiological picture. Lull, Beyer, Maier and Morss (1959) point out that in their 2 patients, the feathery densities were mainly basal in distribution, and a peripheral as well as a basal distribution is shown in 1 of the illustrations of a patient reported by Ford and Hackett (1965). Peripheral involvement was well shown in the present case (Fig. 1) and also confluence of the lesions producing a homogeneous consolidation, a fairly common finding in other reports. Of particular interest in our case is the presence of cyst-like translucencies which stand out clearly against the consolidated background (Fig. 2). Varying in size up to 1 cm. they are thus considerably larger than the pinpoint translucencies described by Kerley (1962). Ramirez-R (1964) also mentions radiolucent cysts, which he attributes to bronchiolar obstruction. He stresses particularly the distinctive appearance of individual lesions which he describes as mottled or granular densities, sometimes like rosettes, due to aggregates of alveolar-occupying densities. This
PULMONARY ALVEOLAR PROTEINOSIS PRESENTING WITH PNEUMOTHORAX
appearance, however, is not pathognomonic of pulmonary alveolar proteinosis, since it may occur in other conditions, including haemosiderosis. Moreover, such distinctive opacities are not always present, rounded nodules of non-specific character being a common finding. Thus the 3rd patient recorded in this country (Ray and Salm, 1962) was a tin miner whose chest x-ray showed for a considerable period, a diffuse nodulation indistinguishable from that of pneumoconiosis. Alterations in the position and extent of the areas of lung affected by pulmonary alveolar proteinosis were observed in one case by Phillips and Constance (1963), the shifting nature of the densities suggesting pulmonary eosinophilia. The variants in the radiological picture include (1) Feathery appearance of individual lesions, (2) Butterfly distribution, (3) Mainly basal opacities, (4) Mainly peripheral opacities, (5) Homogeneous eonsolidation, (6) Diffuse nodulation, (7) Radiolucent cysts, and (8) Shifting nature of lesions. Any combination may occur, and the pattern may alter in the course of the disease. Differential Diagnosis.--When only the butterfly distribution is taken into account, the diagnosis is usually acute pulmonary oedema, although a similar appearance is described in Pneumocystis carinii pneumonia. Pneumothorax may occur in the latter due to rupture of a bulla (Kerley, 1962). When pulmonary alveolar proteinosis presents as a diffuse nodulation the differential diagnosis is widened to include nodulation due to infection, especially miliary tuberculosis, pneumoconiosis, metastatic tumour, haemosiderosis, the collagen diseases and sarcoidosis. Unlike pulmonary alveolar proteinosis, sarcoidosis is usually accompanied by mediastinal lymphadenopathy. The honeycomb pattern in our patient is similar to that found in the honeycomb lung defined as cystic translucencies in association with interstitial granulomata or fibrosis (Heppleston, 1956); under-
lying lesions include sarcoidosis, scleroderma, tuberose sclerosis and eosinophilic granuloma. The last condition was suggested as a possibility in the present case because of its association with pneumothorax in a quarter of all cases (Lewis, 1964). Other diseases not conforming to the pathological criteria of honeycomb lung may show a similar honeycomb pattern on chest x-ray especially if associated with an inflammatory process, e.g. some forms of emphysema, congenital cystic disease, and bronchiectasis. Consolidation, as seen in pneumonia, has not yet been reported as an isolated feature of pulmonary alveolar proteinosis. The main differential diagnoses therefore include other causes of a butterfly pattern, a diffuse nodulation, and a honeycomb appearance. Aeknowledgements.--We are grateful to Dr. J. G. Macarthur for allowing us to use the clinical records, and to Mr. P. S. Waldie for the photographic reproductions. REFERENCES CARLSON, D. J. t~ MASON, E. W. (1960). Amer. J. clin. Path., 33, 48. FORD, R. M. & HACKETT, E. (1965). Dis. Chest, 47, 446. HEPPLESTON, A. G. (1956). Thorax, 11, 77. KERLEY, P. (1962). A Textbook of X-Ray Diagnosis by British Authors, edited by Shanks, S. C. & Kerley, P., 3rd ed., Vol. II, p. 657 and p. 704. London: Lewis. LARS0N, R. K. & GORDINIER, R. (1965). Ann. intern. Meat., 62, 292. LEWIS, J. G. (1964). Quart. Y. Med., 33, N.S., 337. LULL, G. F., Jr., BEYER, J. C., MAIER, J. G. & MORSS, D. F. (1959). Amer. J. RoentgenoL, 82, 76. PHILLIPS, W. J. E. & CONSTANCE, T. J. (1963). Med. or. Aust., 2, 357. RAMIREz-R, J. (1964). Amer. J. RoentgenoL, 92, 571. RAMmEz-R, J., NYKA, W. & McLAUGHLIN, J. (1963). New Engl. J. Med., 268, 165. RAY, R. L. t~ SALM, R. (1962); Thorax, 17, 257. ROSEN, S. H., CASTLEMAN, B. • LIEBOW, A. A. (1958). New Engl. J. Med., 258, 1123. SCADDING, F. H. (1963). Current Medicine and Drugs, 4, 3. SPENCER, I-I. ( 1 9 6 2 ) . Pathology of the Lung, p. 112. Pergamon Press. STANISEER,P. D. & BOURGEOIS,C. (1965). Amer. J. Clin. Path., 44, 539.
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