Document 3QwVb4EGrYEQvwyNXxQq20o4E

- ex - 3 o ///- n*mm 211 Exposure to Asbestos and Mesothelioma of the Pleura P. B. S. FOWLER,* d.m., f.r.c.?. ; J. C. SLOPER,f m.o., v..a.c.r.; E. C. WARNER,* M.n., F.A.c.r. ir,,. mrJ.J., 19M, 2, 2U-Jn Tiro eases tif mesothelioma were the subjects of fairly recent . jroners' inquests. In neither instance was it accepted that ::e tumour was attributable to inhalation of asbestos fibre ; yet one ease there was a Unown and severe occupational history .f exposure to asbestos, while in both eases " asbestos bodies ** ere found in the lung. A point made at both inquests was -e difficulty of attributing a tumour to asbestos-inhalation in .he absence of the difluse pulmonary fibrosis so long recognized ..Murray, 1907) as characteristic of " asbestosis.'* Recently, however, it has become clear, at least in South fries .(Wapner, Sleeps, and Marchand, 1960 ; Thomson, -faschula, and MacDonald, 1963), that the association between -icsothcliomata and asbestos-inhalation can scarcely be for-iious. The studies initiated by Wagner in Great Britain !063, unpublished) suggest that the same may apply here. Our two eases of this rare tumour illustrate the practical -r.plicitions of his investigations. Cose 1 A man born in 1902 was investigated in Charing Cress Hospital 1957 for mild hypertension. During a routine medical cxamir.aj.a he denied shortness of breath, cough, or other symptoms, and chest r-ray film, even when studied retrospectively, showed no tider.ee of lung disease. Ke was somewhat poiyrythscmic (Hb 12%--1S.1 g./100 ml.; R.B.C J.S70.000 ; packed ceil volume Over the nett cwo years he lost weight and complained of bdominal distension after meals. In February 1961 he became e'.inicr.l examination was essentially negative, except for an an.icmu CTIts ~3%). Hi* chest was aspirated nr.J two pints (1.14 1.) rsf slightly blood-stained fluid was withdrawn. No .Tuliitr.an; cells were seen and culture was sterile. Radiograph* at this suae .tlvwed a very thickened pleura over the whole of the rielit chest, with a nodular outline (Tie. 1) which suggested a mesoihclionta ; on hinp:.y 'an anaplastie growth was found. Despite tlte absence of evidence of fibrosis in the contralateral lung, and of any fibrosis in the chett radiograph of 19S7, the possibility of asccstos-inhalation was considered. No asbestos bodies-were found in the sputum, but questioning revealed that this patient had cleaned bags in an a.'-heuns - factory from 1926 to 1929, and had continued with the same fi.-rn. partly as a cleaner, partly as a canteen attendant, until 1942. l;or the next 20 years he was not exposed to asbestos. Despite treatment involving the insertion of radioactive geld into the pleural cavtty, his condition deteriorated and he died at home. i j ` ' \ i | j Necropsy This was performed for H.M. Coroner by Dr. B. H. Kn.gr.t at Faraberough Hospital, Kent, the right lung and diaphragm being gives to us for examination. PLAINTIFF'S EXHIBIT S' ir' v ! r f- i s r e " . 1;. . i: . tb-. v. a - . i \ li !vt t Ftc. 1iladiccraph of chest in Case 1. The nodular npsciues on ihe mediasnnat sr.J latent surfaces of the right pleura suggest s mesothelioma. fr. of breath or. exertion and had a slight esug h with scanty cm. in .May he had developed the s:gr.s of a !a rge rtght-sided .:at effusion and was again admitted. By thit time-be wit: .-.oric but waited. There was co clubbing, i.be rest cf the . .v.-iician, Charing Cross Hospital- . .-..-lorary Consultant Pathologur, Charing Cross Hospital. Ftc. 2.---Photrgrsph of slice of rich: lung from Case 1 ta show cuirass-like sheet of pieuraJ growth. MejofhJlono of P!;ura.--It was noted that the tumour r.-.-.s confined :o the right siue of the chest and did not penetrate the dtsphragm. There was no growth in the lett lung or elsewhere in the body. The rig.'it fung was largely enveloped by a shell of fi.-r.i white growth (Fig. Z'j varying in general between 0.5 and 1.7 cm. _/> in thickness, be: thickened up to S cm. on its lower surface, which G* inrlndrd the '  *' rjter.v.ie. Elsewhere (trowth bulged into the substance * :iit turf;, bu: nowhere were there dee? islands of growth within 0-r iuhe. r.ar, despite prolonged search, could a bronchial primary - .i.soma be fsur.d. Pour ar.thraeotie glands were /ound at the ..an' and also a white ovoid mass (2x 1 cm.; which proved to be r ruroiibrcma. eulty in dun (<-.) paraffin sections, but readily m tl-.ick (30-.0 frozen sections. These bodies lay either in alveolar .'paces or ,n areas of slight interstitial fibrosis ; they were not found in mony sections taken from the pleural growth. Paraffin and frncen sections 'of a hilar gland did not reveal asbestos bodies. There were sreas of slight interstitial fibrosis, the latter especially in the partly collapsed righ: Ipwer lobe. Picroscojsy Smears .'rom she unfixed lens revealed asbestos bodies. These .-re found only with sreat difficulty in thin (5-/*) paraffin sections, -..t were readily demonstrated in thick (30-/*) frozen sections, /picsilv, they measured ISO / in length, and lay in loose fibrous ' me. They stained intensely for hacstosidcrin with Peril's Prussian* ' sc technique. These sections of lung revealed focal collapse of alveoli with r.e increase in interstitial eollagcn ; whether this reflected the eon* -.notion of stroma or a slight focal fibrosis eould not be deter* .neX Some hronehiolcs contained purulent exudate, but evidence chronic bronchitis--for example, the loss of submucosal elastics-- -, lacking. Arterioles showed fibrdelastic intimal hyperplasia, The mesothelioma was very similar to that in Case 1, and in places penetrated into the lung through the pleural eiastica. It stained fairly intensely with Alcian blue, jhc reacting material being removed by hyaluronidasc. ' Other findings at necropsy included bronchopneumonia, a thrombotic embolus in a pulmonary artery, and partial occlusion of the left-renal vein by thrombus. A biopsy of the tempera! art::-/ (1961 ; courtesy of Or. Jones Williams, Mount Vernon Hospital, Middlesex) revealed changes consistent with temporal arteritis ; the single paraffin section we examined was devoid of asbestos bodies. Discussion "he metatheiloma was composed in some areas of sheets and ..ieeulac of cuboidal and polygonal cells. In places these cells . ird clefts, in places they were papillary in arrangement. In many rtas these ceils were sec in a diffuse and densely collagenous stroma, '-.is tumour was stained fairly intensely by Alcian blue. It con-' : .ted no asbestos bodies. There was growth in one of the hilar . .r.ds, which also contained asbestos bodies. Plcurai mcsothcliomata, primarily on account of their remarkable appearance both on radioscopy anti aiso a: necropsy, have come to be regarded by many (MeCaughey, 19.'X ; Wagner, Sicggs, and Marchand, 1960) as a clinical and patho logical entity distinct from carcinoma of the bronchus. In both cur cases the manner in which growth enveloped and compressed the lung led to the radioscopic diagnosis of meso- 'thclioma ; and at necropsy the cuirass-likc _ shell of plcurai Cass 2 . growth was quite unlike rhe usual appearance of the carcinoma of the bronchus. Detailed examination of the iung failed, to * man Com in 1339 was firs: seen in March 1961, when he reveal a primary bronchial carcinoma, although, as in ail such . -cr-ented with the typical symptoms and signs of temporal arteritis, cases, it must oc admitted that such a primary could be missed i nis was confirmed by biopsy (see below), which also relieved the. (Willis, I94S ; Smart and Hinson, 1957). Microscopy is of nrptoms. Kc remained well until'May 1962, when he presented less value in distinguishing mcsothcliomata, for these tumours th a two-wcak* history of cough and pain in the left side of the worse or. breathing. He had lost 10 lb. (4.5 kg.) in weight* or.e year. arc anaplastic and vary in their histological appearance, forming in some areas large amounts of dense collagenous tissue con ^AOn cx.wnir.stion he was thin, pale, and ill-looking. Movement the right lower chest was restricted, the percussion note was taining clefts lined by cubical and. columnar epithelium, .whereas in other areas they arc composed of sheets of polygonal -paired, s.-.e hreath sounds were diminished. There was a ic.-ge undifferentiated ceils (McCaughcy, 1953). Wagner, Munday, - .-.i in the epigastrium. A chest x-ray film showed nodular shadows and Harington (1962) claim that such tumours, when fixed in - . *.g the lateral wall of the right chest with appearances suggesting formol-aicohol-acctic mixtures, secrete material which stains as - .esotheiior.-.a. A pleural biopsy confirmed only that this was a acid mucopolysaccharide, a feature which helps in their histo .. 'iignant growth.- His condition steadily deteriorated. He was logical difTcrentiation from peripheral pulmonary adcnccarcino- -'cn a palliative course of radiotherapy, which gave relief. He -mata. Our cytcchcmicai observations, because they are made on 2 October 1962. on materia! fixed in formol-salinc, are of limited value in this .lubscguently it was discovered that he had worked for a laundry . 'respect. , .i.moany ainca 1913, first as a van-driver, but from 1933 as a general --.nd. His duties included lagging pipes with asbestos and the main- The pathogenesis of pleural mcsochciiamata is still obscure. -. nance of the laundry presses ; this latter job involved the occasional Comparable tumours'have been produced in mice after the --insertion of sheets of asbestos. y' intrapleural inoculation both of silica and of two of the three 'varieties of asbestos in use--namely, crocidoliic and citrysoulc . <ccropsy (Wagner, 1962).' More recently a carcinogenic hydrocarbon, 3:4-benzpyrcnc, has been identified among the oils adsorbed to t'osi-msrtcm examination was performed for H.M. Coroner. Mesolhelsauu of Pleura and Peritoneum.--Confluent, partly .erotic white plaques of fibrous growth up to 5 cm. thick enveloped : posterior and medial aspects of the lower lobe of the right /uf, :.d there were diffuse plaques on the adjacent parietal pleura. There r-.s no growth ir. the deep lung parenchyma, and the hilar glands ::e spared; numerous noculcs and plaques (up to 2.5x2 by up 0.3 cm. thick; were distributed throughout the pjcritoiuel cavity, r.ring the pelvis. The apices of both lungs showed slight emphy-na and both lur.gs contained areas of bronchopneumonia. The ,*u lung,' compressed by pleural growth, showed sreas of partul . .-llapsc. Thera were occasional fibrous pleural adhesions oyer both but tha pleura was not markedly thickened, save where veived by the fibrous growth. crncidoiitc and, to a less extent to amositc, the third form of . asbestos fibre (Harington aod Cilliers, 1963). Wagner (1963) believes crocidolitc to be the fibre particularly associated with mesothelioma of the pleura. Incidentally, wc could find no evidence by autoradiography of any radioactivity in asbestos bodies present ir. smears prepared from the lung of our second case. This study was made in the light of the possibility tits: the supposeJ carcinogenic properties of asbestos migit: be due to its association with radioactive ores (Professor A. G. Hcpplcston, personal communication). Indirect evidence linking asbestos fibres with the dcvciop. mer.t of mcsothcliomata can be sought by determining whether the association noted in human patients is fortuitous or not. It is necessary to know the incidence of mcsothcliomata in the Microscopy general population, the extent to which the general population is exposed to asbestos fibres, and the proportion of cases of smears from the right lung revealed asbeatos bodies. ' Aiitoradio. tphs prepared fra.-n such bodies and exposed for 42 day; revealed .o local radioacitviry. Asbestos bodies were found with great vlifTi- mesothelioma of the pleura similarly exposed. The disease is clearly much rarer than, for example, primary carcinoma of the bronchus. Thus only one of :j:c IS instances i i ! 1f i 1 \ I i i I t ) .yj July 1964 Mesothelioma--Fodder it cl. V* * *. i * Riiwh MiMtw h*M****t 21 'of lung cc.-cinoms reported by Doit (1935) in patients known (30-/0 froecn sections of lung be prepared and trc-ueit wr :o luve been severely exposed to asbestos was described as a Peris': potassium fcrrieyar.idc technique. Asbestos bn.hes e~ . mcjotliclinma ('`endothelioma**). Again, Saccone and Coblciu then readily be recognized by their shape and content of (1943) calculated the incidence ot this cur.umr as 1 per 1,1 CO siderin. It thin (5-/t) paraffin sections arc ured, rigid .-.`heshv necropsies in the U.S.A.; but comparable figures for this bodies, measuring some 130 /* in length, must often he toni country are lacking. out snd lost. Little is known, too, about the risk of the inhalation of asbestos fibres here. In this respect specific information con cerning. air-pollution to windward and leeward of asbestos Summary \ factories would be of value. More immediate evidence, how* ever, is likely to be derived from the study* of sputum in the general population, and particularly of lung smears made in large series of necropsies. By this latter method Thomson ex rJ. (1963) found evidence of exposure in over 23% of 300 necropsies made in an urban area in South Africa. The)* also Two eases of mesothelioma of the pleura are report;J. Despite the absence of severe pulmonary fibrosis, the lungs; * in both contained "asbestos bodies"; in both, too, there wav an occupational history of exposure to asbestos, although in the ' second this was obtained with ditficuity and after death. mentioned that, high figures had been obtained in Miami, ` The association between mesothelioma of the pleura and Florida. Although their' findings were not checked by the --exposure to asbestos is unlikely to oc fortuitous ; but to establish microchcmical identification of asbestos bodies in afleeted * this point all cases of mesothelioma, whatever their occupa lungs--a step which, where possible, should be attempted (see tional history, should be sredied with this possibility in maitl ;; Glovne, 1931 ; Gough, 1939)--the implied proposition seems for evidence is now accumulating that this disease, is an, reasonable, namely that the histological identification of industrial hazard. asbestos bodies provides a guide to the incidence of exposure to asbestos. South Africa, however, is a primary producer of asbestos, and it seems unlikely that exposure in Great Britain is as high. APOENOUM.--Since the submission of this paper an analysis of the material collected in the Bernhard Baron Institute o; i Pathology of the London Hospital between 1917 and 1962 has With regard to the presence of asbesros bodies in the lungs of confirmed the frequency with which asbestos fibres occur in the patients suffering from mesorhdiomara, this was given little * lungs of patients with mesothelioma ta (Kourihar.e, 19641. attention by those investigating these tumours untH Wagner and his co-workers in South Africa (1960) reported their presence in S out of the 10 eases of pleural mesothelioma they examined, in which lung tissue as well as tumour was avail able for examination. It seems to us that the figures could not be accounted for by the chance association between exposure to esocstos and the development of mcsorhcliomata, even if one Particular thanks arc due to Dr. Gavin Thurston, Qee:r.\ Coroner for Westminster, for his comments, snd Dr. B. N- rCaigh: ; for his help with the first ease. :. i' ! S 1 Rercaexczs - in four of the general population were exposed to asbcs:os*(P =0.0003). Indeed, even if one in ten of the population in Great Britain were shown to have asbestos bodies in'their lungs, the presence of such bodies in both pur eases could searcely be fortuitous (P0.0l). Our evidence, however, will be more convincing when the larger series to which Wagner (1963) has referred has been published. Meantime it must be stressed that asbestos bodies should be sought in the lungs of all patients with mcsochciiomata: this search should lie pursued even though there is no occupational history of exposure to asbestos and even though there is no evidence of severe pulmonary fibrosis. In searching for these bodies it is suggested, first, that smears be prepared from the fresh cut surface.of the lung, as recom mended, for example, by Thomson eX af. (1963). Second, in those units which lack the facilities necessary for the prepara tion of thick whole-lung sections, we suggest that small thick Doll, R. (19331. tint. J. induitr. Aled.. 12, 81. ' Clo>-ne, S. R. (1931). Lontti, I, $10. 1 Cnueh, J. (1939). " Occupational Pulmonary D;aease>._" In .'.ioJem Trendt in Pji'neion, edited by D. K. Collins, p. ZSa. Eutterworth, London. Harinetnn. J. S.. and Ci!licrs, J. J. le R. (1963). Ceoehim. MimKk. Acta. St. ll. Hourihanc, D. O'R. (19641. Thorax, 19, 26S. 1 McCausher, 97. T. F_*(l93i). 7. Path. Pact.. *75. 317. * Murray, r. At. (19071. Report of the Oeporimuttal^Com/niuec or. Com- ; pen.anon for l/uiuuriai Disrate, para. 4176--104, K-Md.O. London. ~ . . Saccnr.e. A., and Cubtens, A. (19431. /inter. J. e.'in. Posh.. !3. 186. Smart, J., and Hinson. K. F. W. (1937). Prit. J. Tuoerc.. SI. 319. Thomson, J. G.. Kaschuia, R. O., and .MacDonald, 3. R. (1963). S. Afr. nted. 7,, 37. 77. Wiener. I. C. (1962). Haitire (Lorn!.), 196, ISO. -- (1963). Author's unpublished summary of rape.- read at Fourteenth International Congress an Occupational Health, .Madrid. Sepu. 1963. -- .Monday, D. S-, and Hatinpton, J. S. (1962). J. Path. Sect., d. 73. -- Sleees, G. .A., and Marehand, ?. (I960). Srit. 7- indutir. .Vied.. 17, 260. WilU.-.. R. A.-(1948). Pathology af Lung Tumours. 1st ed.. pp. 1$4, 1S3. SuttcrA-ords, London. 1 \