Acute pleurisy in asbestos exposed persons

ENVIRONMENTAL

RESEARCH

Acute

5, 380-392

Pleurisy G. K.

National

Research Institute

( 1972)

in Asbestos SLULS-CXEMER

AND

Exposed I.

Persons

WEBSTER

Occupational Diseases, of the South African Council, P.O. Box 4788, Johannesburg

for

Medical

Research

Received January 25, 1972 It has been clinically observed that pleural effusion occurs, not infrequently, in asbestos exposed persons with or without evidence of asbestosis. Nine such cases are presented, in seven of these, pleural biopsy has been carried out by needle or by open thoracotomy. The histological features are described. The suspicion of mesothelioma of the pleura necessarily arises in such cases. This problem is discussed. It is well known that a chronic pleural reaction of both the visceral and parietal pleura is common in asbestosis and frequently the dominating clinical feature. Webster ( 1970) for instance has found a very high incidence of chronic pleurisy (that is, fibrous thickening of the visceral pleura-usually diffuse-sometimes localised) in asbestos exposed persons.

Hyaline and calcified pleural plaques of the parietal pleura are well known in asbestos exposed persons, though they are not pathognomonic of asbestosis occurring as they do in talc and mica exposed persons as well, and sometimes without adequate explanation (Rous and Studeny, 1970). Lamellar pleural thickening along the lateral chest wall is also a fairly characteristic roentgenological sign of asbestosis and may occur in the absence of parenchymal radiological signs of asbestosis. Uncalcified pleural plaques may also be due to asbestosexposure (Mattson and Ringqvist, 1970). It is less well appreciated that acute pleural reactions may occur in asbestos exposed persons. Eisenstadt ( 1964) reported a case under the heading of asbestos pleurisy. This case had acute pleurisy with effusion which did not respond to anti-tuberculous drugs. Eventual thoractomy revealed considerable thickening of the visceral pleura with dense connective tissue (with infiltrates of lymphocytes and eosinophils). There was evidence of asbestosisin the underlying lung. The patient recovered after decortication and remained in good health. McNulty (1968) reports eight patients with bilateral pleural effusion in a small group of Australian asbestos miners and Ringqvist (1970) seven patients with pleural effusion one of whom was probably due to a pleural mesothelioma. Gaensler ( 1970) also mentions asbestosisas a cause of pleural effusion. CASE

REPORTS

Case 1 J.P.C., a Caucasian, is aged 35. He had worked in an amosite mine from 1950 as a miner, He developed a cough with chest pain in 1966-this was accompanied by listlessnessand 20 lb weight loss. In 1969 a pleural rub was heard in the left 380 Copyright All rights

@ 1972 by of reproduction

Academic in any

Press, Inc. form reserved.

ACUTE

PLEURISY-ASBESTOS

:381

EXPOSURE

lower thorax-16 ounces of blood-strained fluid was aspirated which contained numerous lymphocytes, red cells and ocassional serosal cells. Mycobacterium tuberculosis was absent. Erythrocyte sedimentation rate ( E.S.R. ) ( Wintrobe) was 13 mm/l hr. Blood count was normal. Mantoux was positive to l/1000 old tuberculin ( 1.5 cm). The pleural biopsy specimen consisted of a small core of tissue which had been removed with a Vim Silverman needle. Histological examination showed wellformed collagen fibres which had been cut longitudinally. Occasional linear clefts were present and these lined by flattened cells. It was noted that there was no the clefts did not atypism of the nuclei of the collagen fibres and the cells lining show any evidence of metaplasia to the cuboidal type. There was no evidence, beyond the presence of an occasional lymphocyte of round cell infiltration. The histological features were considered to suggest that the specimen had been derived from a chronic fibrous pleurisy. He was put on anti-tuberculosis therapy but despite this, after 2 months he developed a right-sided pleural

the

FIG. 1. Low pmver thickened pleura.

( X12)

of the

pleural

biopsy

(5135/69)

showing

the

dense

fibrosis

of

382

SLUIS-CREMER

AND

WEBSTER

effusion; E.S.R. was now 10 mm/l hr. The blood count was normal. Six cultures of sputum for M. tuberculosis were negative. The Latex test for Lupus erythematosus was negative; urine was normal; serum protein electrophoresis was normal; Latex test for rheumatoid arthritis was negative; virus complement fixation tests including those for psittacosis and herpes were negative. Pleural biopsy on the right side failed. The patient remained well after 15 months, though still on anti-tuberculosis treatment. Case 2 A.C.P.C., was aged 57 in 1964-he is a Caucasian. From 1928 through 1955 he was a carpenter at an amosite mine where at times he had to work in the crushing plant. In 1956 he developed pleural plaques and by 1964 he had extensive calcified pleural plaques. In that year he developed bilateral pleural effusions and was admitted to hospital. Pleural fluid contained moderate numbers of polymorphonuclear leukocytes and lymphocytes and a few plasma cells and serosal cells. Malignant cells were not observed. Culture of the fluid for M. tuberculosis was negative after 8 weeks.

FIG. bundles

2. Higher power ( X60) of the biopsy with an occasional cleft-like space.

shown

in Fig.

1 shows

the well-formed

collagen

ACUTE

PLEURISY-ASBESTOS

33833

EXPOSURE

Culture of three speciments of sputum for M. tuberculosis were negative. Mantoux test with old tuberculin l/1000 was positive (1.2 cm); E.S.R. was 53 mm/l hr. Hemoglobin was 11.1 g. Sections of the pleural biopsy specimen which was removed with a Vim Silverman-type needle showed bundles of dense hyaline collagen bundles which had been cut longitudinally. Clefts of varying sizes were seen in between some of thca collagen fibres and although these were mainly lined by flattened cells, an occasional cell was seen. There was no evidence of proliferation of these lining ~11s. An occasional lymphocyte and plasma cell was present in the sections. None of the nuclei of the collagen fibres nor those lining the clefts showed any evidence of variation iu staining reaction. The histological features were consistent with but not completely typical of tissue derived from an asbestotic plaque. There was no evidence of malignancy in the sections examined. The patient has been lost sight of.

A Bantu labourer, 5135/69, aged 35 had worked on a blue asbestos mine from 1963 through 1970. He d eveloped a left-side pleural effusion in October 1969. S-ray of chest shows only an effusion.

FIG,

3.

Section

showing

the papillary

type

of thickened

visceral

pleura

of HAS

( ~60

).

384

SLUIS-CREMER

AND

WEBSTER

Sections of the pleural biopsy specimen showed the presence of dense interlining collagen bundles with areas in which the collagen bundles are lying parallel to one another. Although throughout the sections the collagen bundles were thick and well-formed areas of more mature collagen can be seen. An occassional cleft can be seen and there are a few capillaries lined by swollen epithelial cells. Neither the cells lining the clefts nor the swollen endothelial cells nor the nuclei of the collagen fibres show any atypism. It is considered that the histological features are consistent with a chronic pleurisy associated with the inhalation of asbestos or that the specimen has been derived from a pleural plaque. Culture of sputum was three times negative for M. tuberculosis (Figs. 1 and 2).

Case 4 H.A.S., aged 49-Mill fitter and carpenter at asbestos mines in North West Cape for 16 years. Smoked 15 cigarettes per day. Developed pain at right base posteriorally. A pleural rub was heard and X-ray showed slight thickening of the right interlobar fissure and of the pleura over the right lower lobe. Thoracotomy done on February 18, 1970. At thoracotomy the parietal pleurae was thickened and the visceral pleurae over the lower lobe was white in colour and slightly thickened, but there was no

FIG. 4. Section showing

the cellular type of thickened

parietal pleura of HAS ( X60).

ACUTE

PLEURISY-ASBESTOS

EXPOSURE

385

evidence of nodulation. Biopsy specimes of both pleura and lung tissue were taken. Sections of the parietal and visceral pleurae showed the presence of a papillary thickening of the pleurae in which the connective tissue consisted of a loose arrangement of collagen fibres and a few reticulin fibres in an oedematous matrix. A moderate number of cells were present and although a few lymphocytes and plasma cells were present together with an occasional eosinophilic leukocyte, other cells not usually found in a reactive pleurisy were found. These cells were found scattered throughout the sections but in a few foci had aggregated into an irregular follicle formation. The nuclei of these cells were large and contained a moderate amount of nuclear plasma. The chromatin stained faintly but the nuclear membrane was easily visible. Although the nucleus tended to be elliptical, some appeared folded. The cytoplasm stained blue with Romanowsky dyes which together with the nuclear appearance suggested that these cells were mesothelial in origin. Although a reactive pleurisy could not be completely excluded it was suggested that the histological appearances indicated that the specimens, particularly that from the visceral pleura could have been derived from a mesothelioma of the pleura.

FIG. 5. Sectionshowingthe desquamativealveolitiswith coatedasbestos fibres in the lung parenchymaof HAS ( X60).

386

SLUIS-CREMER

AND

WEBSTER

Sections of the underlying lung tissue showed the presence of thickening of the walls of the lower respiratory tract which could have been caused by the atelectasis produced by the pleural change. In some areas the thickening of the walls of the lower respiratory tract was associated with the presence of asbestos needles and ferruginous bodies and it was thought that there was evidence of asbestosis (Figs. 3-5). Patient remains well to date (January 1971). Case 5 H.J.S., aged 28-8 years a miner in a Northern Transval asbestos mine. In 1935 he developed a right pleural effusion and a calcified plaque in the left midzone. There were no subjective complaints. Straw-coloured fluid was recovered from the right side posteriorally. Thick pleura was encountered-no biopsy was done. Mantoux test was negative and culture of three sputa negative for M. tuberculosis. He remained well in 1970. Pleural plaques have become more numerous and well defined and extensive calcification of the pleura has appeared in the right midzone (Fig. 6). Case 6 D.J.V.-a Caucasian aged 36 had worked for 7.5 years in blue asbestos mills in the North West Cape region. He developed a right-sided pleural effusion with breathlessness in 1955. Fluid was aspirated (40 cc) and found to be blood stained.

FIG.

6. X-ray

of H.J.S.

showing

thickened

pleura

on right

and

calcified

plaque

on left.

ACUTE

PLEURISY-ASBESTOS

EXPOSURE

387

Bronchoscopy was normal and bronchial washing negative for malignant cells and a lung biopsy was done. The parietal pleura was found to be thick and opaque and there were areas adherent to the diaphragm by oedematous friable adhesions which were easily separated. Sections of this specimen show the presence of lung parenchyma covered by a chronic fibrous pleurisy. In the lung parenchyma there is evidence of an interstitial fibrosis associated with the presence of asbestos bodies indicating that asbestosis is present. The chronic fibrous pleurisy consists of mature collagen fibres lying parallel to the lung. Occasional aggregates of lymphocytes are present in the thickened pleura and occasional lymphocytes can be seen. The patient has been lost to follow-up (Figs. 7 and 8). Case 7 T.N.J., a Caucasian, aged 34, had worked for a blue asbestos mine, in the mill, store and offices from 1958 through 1969. In June 1969 dyspnoea, lassitude, right-sided chest pain and 20 lb weight loss developed. Right-sided pleural effusion was diagnosed clinically. X-ray in October 1969, showed bilaterial pleural effusion more marked on the

388

FIG. 8. Higher power of the collagen fibers.

SLUIS-CREMER

( x60)

of the thickened

AND

WEBSTER

pleura showing

the longitudinal

arrangement

right. The fluid was negative for tubercle bacilli on culture as was the sputum. Pleural biopsy was unsuccessful. By March 1970 the effusions had receded leaving both costophrenic angles obliterated with an appearance of coarse fibrosis at both bases. [ U2/2 both lower zones according to UICC/Cincinnati classification ( 1970) .] Asbestosis was diagnosed. This patient had two cousins who were being treated for pulmonary tuberculosis. Mantoux test to l/1000 old tuberculin was positive (1 cm); E.S.R. was 17 mm/ 1 hr-blood count was with normal limits (Figs. 9 and 10). Case 8 A.G.B., aged 50, a Caucasian, had 15 years service on chrysotile mines and had also worked in gold and copper mines. He was diagnosed on radiological evidence of fibrosis to have asbestosis in 1965-there was little disability. The X-ray reading was T l/l in both lower zones [according to the UICC/Cincinnati classification ( 1970) 1. Bilateral pleural rubs were detected early in 1969 and on X-ray there was an effusion on the left side and obliteration of the right costophrenic angle. A pleural biopsy specimen was taken from the left side. Histological sections

ACUTE

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EXPOSURE

389

FIG. 9. Low power study of pleural biopsy showing loose and dense connective tissue with serosal cell proliferation, and lymphocytic cell infiltration.

of this specimen showed the presence of hyaline connective tissue in which there are foci of lymphocytes. An occasional area in which there is marked serosal cell profileration can be seen. There is however no evidence of malignant neoplasia in the sections examined. The left-side effusion subsided spontaneously and he remains well (January 1971) (Fig. 11). Case 9 A Bantu labourer, 1089/70, aged 45 had worked in 1963 in an amosite mine. He developed a right-sided pleural effusion in October 1969. Pleural biopsy was carried out. Sections of this specimen of pleural biopsy show the presence of dense collagen bundles in which there are a moderate number of capillaries. Some of the capillaries are lined by swollen endothelial cells. At the free edge of the pleural surface there is evidence of fibrin deposition and in places the fibrin has been incorporated in the connective tissue. The presence of a moderate number of lymphocytes and the fibrin suggeststhat the biopsy specimen has been derived from a chronic inflammatory pleural reaction. The presence of the very dense mature collagen bundles however indicates that the pleura has been thickened for a considerable time (Fig. 12).

390

SLUIS-CREMER

AND

WEBS’IEB

FIG. 10. High power study of biopsy specimen showing serosal cell proliferation and lymphocytic cell infiltration. The serosal cells show the characteristic vesicular nuclei and prominent nucleali.

DISCUSSION

The aetiology of a pleural effusion is always difficult to determine and suspicion of a tuberculous origin will always linger despite a negative fluid examination or pleural biopsy. In cases l-3 the gross hyaline connective tissue proliferation with clefts lined by flattened cells in the absence of tuberculous granuloma, granulation tissue, or lymphocyte or other cell infiltration is a fairly characteristic picture. TABLE INCIDENCE

OF CHRONIC

PLEURISY

(VISCERAL

I PLEURA)-C.ZSES

Gold miners Whites/col:)rlreds

172 13.2(‘/;,

Ban tu

992

Asbestos

16.97< a Number * Asbestos

of cases given miners include

EX.%MIWED

in upper row for each race group. the group with asbestosis.

miners*

46 t34.1yo 74 75.80/

DURING Asbestosis 20 83. “7; 33 69.37;

1969’

ACUTE

FIG 11. LOW power )f the cellular infiltration.

FIG.

12. Higher

power

( X12)

( X60)

PLEUBISY-ASBESTOS

of the pleural

showing

the

biopsy

dense

391

EXPOSURE

specimen

collagen

of 1089/70

bundles

with

showing

cleft

the

formation.

extent

392

SLUIS-CREMER

AND

WEBSTER

In cases 2, and 4-8 radiological or histological evidence of asbestosis was present. In case eight radiological evidence of asbestosis preceded the effusion by 4 years. The E.S.R. when done is normal or slightly raised except in case 2 where an E.S.R. of 53 associated with a hemoglobin of 11.1 raises the possibility of another aetiology for the effusions. The evidence of asbestosis, viz., extensive pleural ca!cification and the pleural biopsy specimen features which are identical to other cases however, strongly suggest asbestosis as the aetiology. In case 7 there is also some doubt. A roentgen photograph in 1959 was normal. Since then he had no films taken till the onset of his acute illness. On subsidence of the pleural effusions without anti-tuberculous treatment, basal radiological changes consistent with asbestosis were revealed, Some doubt however remains, particularly in view of the history of tuberculosis in his cousins. Case 4 is particularly intriguing as the suspicion of mesothelioma of the pleura must necessarily be roused. His effusion however spontaneously subsided and he remains well after a follow-up period of 1 year. Long-term follow-up is however required in this case in order to finally exclude this possibility. In case 8 the appearances are also very suspicious of a mesothelioma but the patient remains clinically well nearly 2 years from biopsy. Eisenstadt (1964) re f ers to two cases of mesothelioma of the pleura in one of whom unilateral pain was present for 12 years before onset and in the other bilateral benign pleural eifusions had occurred 10 years before the final illness. Mesothelioma of the pleura must be borne in mind in all such pleural effusions-especially as a needle biopsy may miss the malignant tissue and reveal only “fibrous pleuritis” (Heller, Janower and Weber, 1970). REFERENCES EISENSTADT, H. B. ( 1964). Asbestos pleurisy. Dis. Chest 46, 78-81. “Idiopathic” pleural effusion. New Eng. J. Med. 283, 816-817. GAENSLER, E. A. (1970). GILSON, J. C., BOHLIG, H., BRISTOL, L. J., CARTIER, P. H., FELSON, B., GRAINGER, T. R., JACOBSEN, G., KIVILUOTO, R., LAINHART, W. S., MCDONALD, J. C., PENDERGRASS, E. P., ROSSITER, C. E., SELIKOFF, I. J., SLUIS-CRE~R, G. K., AND WRIGHT, G. W. (1970). UICC/Cincinnati classification of the radiographic appearances of penumoconiosis. Chest

58, 57-67. HELLER, R. M., JANOWER, M. L., AND WEBER, A. L. ( 1970). The radiological manifestations of malignant pleural mesothelioma. Amer. J. Roentgen. 108, 53-59. MCNULTY, J. C. ( 1968). Asbestos mining, Wittenoom, Western Australia. In “Proceedings of the First Australian Pneumaconiosis Conference,” pp. 447-466, Sydney. ( 1970). Pleural plaques and exposures to asbestos. MATTSON, S. B., AND RINGQVIST, T. Stand. J. Resp. Dis. Suppl. 75, 41pp. Rous, V., AND STUDENY, J. ( 1970). Aetiology of pleural plaques. Thorax 25, 270-284. The role of animal experimentation in asbestosis. Paper presented at WEBSTER, I. ( 1970). the Symposium on the Tissue Response to Asbestosis, Cardiff.