Document JvrjxGDvOQBYqYg49aVEBXJkr

. -- f t.n tti-w iliti ii-irrv n rfi^ff * W m* teKAtSwNAL w oture to throw e significant heep watch facilities, oratay t o holim any more c back and leave to make t o t e people exam ine their provision is made ' 'o f plant, ovestm ent .having given p tit iay neck on v e x in a very good W here do 'g tM B P to * * have done jtil >' [ one thinks, how "* to improve J t Q uestion, i Of w ater are 'S8I^an w ith over the I m anner that /f in d the need i chooses to get v|^ -e n d it is o f the , .-.fi rticulariy o f the *er w eri^ sem e ' id p b ut wonder - M k k Into our `liestta w hich is ^ t o s t a t o t i w ith the ' V fJ us less m indful ' ;-C preventive side ? 1 * P ttd m o t it - i , ir to atpend, and V* ten arranged for me op us in this "?v. v : 25 July 1964 211 Exposure to Asbestos and M esotheliom a of P. B. S. FOWLER,* DJ*., F.R.CJP.; J. C. SLOPER,t M4., mjlop. ; B. C WARNER,* mj., BM .C*. Brit, m ti.3 ; 1964, g, 211-213 Tw o cases of mesothelioma were the subjects of fairly recent coroners' inquests. In neither instance was it accepted th at the tum our was attributable to inhalation o f asbestos fibre ; yet in one egae there was a known and severe occupational hhrory of exposure to asbestos, while in both cases " asbestos bodies" were found in the lung. A point made a t b oth Inquests was the difficulty o f attributing a tum our to asbestos-inhalatio in t o b w ee o f die pulm onary to ro sis so long tceo g n to d (M urray, 1907) as characteristic of " asbestoses." Recently, however, it has become d ear, a t least in South A frica (W agner, Stegga, and M archaad, 1960; T hom son, K aschula, and M acD onald, 1963), th at the association between m esotoU om ata an d asbestos-inhalation can scarcely b e to tuitous. T h e studies initiated by W agner in G reat B ritain (1963, unpublished) suggest th at the same m ay apply here. O ur tw o cases of th is rare tum our illustrate th e practical im plications of his in vesti^tions. Case 1 A man born in 1902 was investigated in Charing Cross Hospital in 1957 for mfid hypertension. During a routine medical examina tion he denied shortness of breath, cough, or other symptoms, and a chest x-ray film, even when studied retrospectively, showed no evidence of lung disease. He was somewhat poiycythaesmc (Ho 122%--18.1 gyiOO ml. ; R.B.C. 5,870,000 j packed ceB volume 53% ). Over the next two years he lost weight and complained of abdominal distension after meals. In February 1961 he became q m n% % [ 4jot t& asaens ***** l> of w m seen a n d b o w e d a very thickened pletta tnwr t o w h ^ p f t o right to s t, with a nodular outline (Fig. 1) which suggested a meeothdiotna -, on biopsy res' anaplastic growth smt found. Despite dse absence of evidence of fibrosis in dse coutrataeerilang.aad o f iofr fibrosi fa the chest radiograph of f95?, was consSdered. No asbesto bodta were found in the sputum, but questioaing^eato t t o t o i ip to h M J l^ d b a g s jn an asbestos partly as dcaaer, p a rty as a c s tm ta a M S ant, anifl W B . Bor th en en 2 0 y ear h ew a* n otm o s lto asb e o a Despite treatment involving t o tarectiM m tadtoadive .p i t t o ., t o pleural cavity, his cooditian deteriorated and he died at home. This waa performed fo r H M . Coroner by D r. B. H . Knight at I ta to c e u to Hospital, K ent, t o right lung and diaphragm being given to us f o r -- Flo. 1.--Radiograph of chest in Case 1. The nodular cities on the mediastinal and Unreal surfaces ef the right pleura suggest a mesothelioma. . t o r t of breads on exertion and had a slight rough with scanty sp am s, Jn M ay he had developed the aigns of a targe right-tided pleural e to d o n and wa again retained. By this tim e he m s plethoric but watted. There was no clubbing. The rest of the phyddan, Charing Cross Hospital. f Honorary Consultant Pathologist, Charing Cross Hospital. I |N v d l M tsotkM tm a o f itoM ^ v ^ :hnrour was . sto n ri to Oh right to ,;o f t o t o e t ; ( t o p | t o penetiate t o , diaphragm T T to wm no |p o w * to the left lung o r d s e to re fa vmisc inw iu i v*v< -4/ fMfiBift'm w> nus 1.7 cot. in thfcfcncsa, but thickened up to 8 cm. on its lower su rfs , which included the diaphragm. In several areas the growth was jifUPJiuryya L*. * 212 25 July 1964 Mesothdioma--Fowler et al. soft Mid necrotic. Elsewhere growth bulged into the substance of the lung, b a t nowhere were there deep islands of growth within tbs lung, nor, despite prolonged search, could a bronchial primary carcinoma be found. Four anthraootic glands were found at the titan and also a white ovoid a n ( 2 x i cm.) which proved to be a neurofibroma. M icroscopy Smears from the unfixed lung revealed asbestos bodies. These ware found ooiy with great difficulty to dito (S-t*> paraffin sections, but wece rto ia y deBwnstrated to thick (lO-v) frozen sections. Typically, fhey ineasured lSO (* to bogth, wad lay to loos fibrous - tissue. T u m b le d intensely forhaemosiderin w ith Peris's ftu ssb n - bhw technlijue. - . T h o e sections of tw ig revealed focal collapse of alveoli with Seme increase to interstitial collagen s whedier tbis redected the con densation of satana o r a slight focal fibrosis could not be deter* to ta l. Soim broachlolea emitatoed purulent emidate, but evidence of chronic brencfcltis--M M m ple, die toes o f submucosal d e sto -' was lacking. Arterioles showed fibroelsjtic M M 'bypaidasto. The m m tM iam a was compared to aome areas o f sheas and ttobecBbc of coboidal and pergonal cells. In places these cells ttoed delta, to places diey were papdlasy to arrangement. to m any. areas these o d b were se tto a diffuse and densely collagenous stroma. T his tum oui was stained fairly tottnady by A ldan tone. It con tained no asbestos bodies. There was growth in one of the hilar glands, which also contained asbestos bodies. CM 2 A man bom in 1889 was fin t seen in M arch 1961, when he psmented With the typical symptoms and signs of temporal arteritis. T his was confirmed by biopsy (see below), which also relieved the symptoms. H e remained w dl until May 1962, when he presented with a two-weeks history of eongh and pato in the left side of the chest, worse on breathing. He. had toat Id lb. (4.S kg.) to weight to one year. O n exuntoMton he was thin, pale, and iU-loaking- Movement of the right tower ebestw as. restricted, the percussion note was impaired, end breath sounds were diminished. There was a Urge mass in the epigastrium. A chest x-ray film showed nodular shadows along thc lateral wall of the right efaest with appearances suggesting a tnesothd hm a. A pleural biopsy confirmed only that (his was a malignant growth. His eendhton steadSy deteriorated. He was given a paB btivt eousse of tadtotherapy, which gave M e t. He toed on 2 October 1962. Subsequently k was discovered tbat he had worked for a laundry company Urn 1918, first as van-driver, but from 1938 as a general hand. His ctoties toctoded lagging pipes with asbestos and the main tenance of the laundry presses; this latter jab involved the occasional reinsertion of sheets of asbestos. Necropsy Post-mortem examination was performed for H M . Coroner. Mesothelmma o f Pleura and Peritoneum.--Confluent, partly necrotic white plaques of fibrous growth up to 5 cm. thick enveloped the posterior and m e^hl **Pt of the lower lobe of the right tong, and there were diffuse plaques on the adjacent parietal pleura. There was no growth to hf deep lung parenchyma, and the hilar glands were spared } aw netfus nodules and plaques (up to 2 .5 x 2 by up to 0.3 cm. tokfc) n j distributed throughout (be peritoneal cavity, (toifejg the p d v k . The aptoes of both lungs showed slight emphy- ` ' lung* contained areas of brondwpnemnbni*. The to ld % pleural growth, showed afees of partoti . . . . . .......... wet occasional fibwaa pleural sdhesiana over both lung, bnt ttoe pleura g j t markedly thickened, save where involved b y fe e fibrous growth. cutty to thin (S-r parafln sections, but resdfly to thiek (3#w) frozen sections. These bodies b y either to i to a t e spates m to , m u of slight interstitial fibroshi they were not fotmd to rnsoy sections taken from the pleural growth. Paraffin and frozen sectionj of a hilar gland did not reveal asbestos bodies. There wwe areas of slight interstitial fibrosis, toe latter eapedafly to toe partly Otdbpaed right lower toto> T b s mesothelioma wm very rimSar to toat to Case I , sad to places penetrated into die h o g through to e pleural elastica. ~ removed by hyataroatoato O ther flntoags a t . . ............................ . ...... thrombotic embolus to a pubnenary artery, and partial i . .. of the left renal veto by tom atoes. .A biopsy a t the torniporal artery (1961 j courtesy of D r. Jones WSiiauM, M ount Vernon Hospital, Middlesex) revealed d m consistent whh temporal a tte rith ; die single paraffin section we examined was devoid o f sbeetes bodies. P feuni mesotbehotMta, primarily -to t aoodant of th e! remarkable appearance boto on raefioaeppy and aboataecropty, bave come to be rep n fett by ttw ty (McGstigbey, 1 9 j W agnet, Segga, and M erdmiid, I960) as a ciittical and patho logical entity distinct from carctooma f the bronchus. to both our cases the m anner to which growth enveloped M l compressed the lung led to the radtoseppiedtognosis oftneso- tbelioma ; and at oetotopey the cuirass-like t M at plenral growth was quite unlike toe usual appearance of toe carcinoma of the bronchus. Detailed examination of die tan g failed to revcgl a primary bronchial carcinoma, although, as in all such cases, it must be admitted th at snob a primary could be missed (W illis, 194* t Sm art and Hinson, 1957). Microscopy is of 1686 yrivtg ^S8S tQ&&Sn are anaplastic mid v ary to to eir histological appearance,forming in gonne asesa im e g f ifa w if -tlty co&~ Hitag (efts fey pvyf dfrffoffrTjfrtftf whereas m otoer areas they are composed of sheets o f polygonal undifferentiated ceBs (McCaughey, 19S*). Wagner, Muncby, and Harmgton (1962) daim that such tumours, when tend to fmrrool-fllcohol-acetic mixtures, secrete material which sato s as acid mueopdyssocharidfr * feature which helps to foeit histo logical differentiation from peripteral pulmonary adenocarcino m a. O ur cytochemical observations, because they ate, made on material fiieed in fomad-saltoe, are of limited value to this ' T h e pathogenesis of pleural m esotheilam ata to tint obscure. Com parable tum ours la v e been produced to m ice after toe intrapleural inoculation both of silica and of tw o o f the three varieties of asbestos to use--nam ely, crocidoiite and chrysolite (W agner, 1962). M ore recently a carcinogenic hydrocarbon, 3 : 4-benzpyrene, has been identified among the oils adsorbed to crocidoiite and, to a less extent tn am osite, th e th ird form of asbestos fibre (H arington and C dliers, 1963). W agner (1963) believes crocidoiite to be th e fin e particularly associated w ith m esotheliom a o f thy pleura. Incidentally, we could find no evidence by autoradiography o f an y radioactivity to asbestos bodies present in sm ears prepared ftw irfo e lu n g o f o u r second case., T h issttttiy vras r a M in th e lig to o f th ep o sjib ility foat th e supposed carcinogenic propertfes o f asbestos night be due to tot association w ith radioactive ore* (Professor A G. H cpplcston, personal com m unication). ' . *' I t k a e o e s m f toknow Smears from the right tong revealed asbestos bodies. Autoradio graphs prepared from such bodies and exposed for 42 days revealed no local radioactivity. Asbestos bodies were found with great diffi- to exposed to, iw opw rion trf rosoi of mesotheKoma o f th e t* m ra sim ilarly exposed. T h e disease is clearly m uch rarer than, fo r exam ple, prim ary carcinom a of the bronchus. T hus only one of th e 18 instances 25 July 196 of lung carcino: to have been sc mesothelioma (" (1943) calculatenecropsies to t country are lacl L ittle is kno asbestos fibres f cem ing air-poli factories would ever, is likely tc general populat large serics of et at. (1963) fbi necropsies made m entioned that Florida. Alton m tctochem cal lungs--a step v. Gloyne, 1951; reasonable, nar asbestos bodies to asbestos. Sc asbestos, and it is ta high. W ith regard t patients suffer attention by to and his co-wo presence in 8 o. examined, in w able fo r examin be accounted f< to asbestos and in four o f the gt 0.0003). Indent B ritain were sh presence of sue fortuitous (P = convincing whfi referred has bee M eantim e it sought in the 1 search should b history of expc evidence of sev In searching be prepared fro m ended, for ex those u n its whi tion of thick w g . . V. WMOkl rruonmai KiMilini i.i,r.i<nillSM ttin i Air - ! bronchas. la , ; enveloped and ' "Z 0 g n o siso f meso , ja M l of . J p f th e carenon -`t S : lung failed to as i naU such 'i | " *" BBBBEBHBBBHfl.* tflf polygonal j n e r, Munday, f , w hen fined in J w hich stains as J || i in M b -U n o ^ ||l adenocarcino' m? : they n e -made :A | sd value in th is ia stffl obscure, m ice after the ;J|f wof thefitasee j : an d chrysotile jg g le hydrocarbon, :> oils adsorbed to iJh s th ird form of W agner (1963) 1 associated w ith I could find no i *y i 25 July 1964 Mesothelioma- Fowler et al. tu eS S U t 213 of lung carcinom a reported by D oll (1955) in patients known to have been severely exposed to asbestos was described as a mesothelioma (" endotheliom a "). A gain, Saccone and Coblenz (1943) calculated the incidence of this tum our as 1 per 1,100 necropsies in the U.S.A. ; but comparable figures for this country are lacking. L ittle is know n, too, about the risk o f the inhalation of asbestos fibres here. In th is respect specific inform ation Con cerning air-pollution to w indw ard and leew ard of asbestos factories would be of value. M ore immediate evidence, how ever, is likely to be derived from the study of sputum in the general population, and particularly of lung smears m ade in large series of necropsies. By th is latter m ethod Thom son et al. (1963) found evidence of exposure in over 25% o f 500 necropsies made in an urban area in South A frica. T hey also m entioned th at high figures had been obtained in M iam i, Florida. A lthough th eir findings were not checked by the mkarochemical identification of asbestos bodies in affected lungs--a step w hich, where possible, should be attem pted (see G loyne, 1951 ; G ough, 1959)--the im plied proposition seems reasonable, nam ely th at the histological identification of asbestos bodies provides a guide to the incidence of exposure to asbestpa. S outh A frica, however, is a prim ary producer of asbestos and i t seems unlikely th at exposure in G rm t B ritain isa s-b ig h - W fih regard to the presence of asbestos bodies in the lungs of patients suffering from m esotheliom ata, th is was given little attention by those investigating these tum ours u n til W agner and his co-worfcers in South A frica (1960) repotted their presence in 8 o u t of the 10 Cases of pleural m esothelioma they m am ined, in w hich lung tissue as well as tum our was avail able fo r exam ination. I t seem s to us th at th e figures could not be accounted fo r by the chance association between exposure to asbestos and the developm ent of m esotheliom ata, even if one in four of the genera! population were exposed to asbestos (P = 0.0003). Indeed, even if one in ten of the population in G reat B ritain were show n to have asbestos bodies in th eir lungs, the presence of such bodies in both our cases could scarcely be fortuitous (P = 0 .0 I). O ur evidence, however, w ill be m ore convincing w hen the larger series to which W agner (1963) has referred has been published. M eantim e it m ust be stressed th at asbestos bodies should be sought in the lungs of all patients w ith mesot heliomata : th is search should be pursued even though there is no occupational history of exposure to asbestos and even though there is no evidence of severe pulm onary fibrosis. In searching for these bodies it is suggested, first, th at smears be prepared from the fresh cut surface of the lung, as recom m ended, for exam ple, by Thom son et al. (1963). Second, in those units w hich lack the facilities necessary for the prepara tion of thick w hole-lung sections, we suggest th at sm all thick (39-J) frozen sections of lung be prepared mad m ated w ith Perls's potassium ferricyanide technique. A sbesioe bodies can th en readily be recognized by their shape and content o f haemo- siderin. If th in (5-/*) paraffin sections m e used, rigid asbestos bodies, m easuring some 150 p in length, m ust often be torn o u t an d tost. '. . T w o o n e s o f m esotheliom a of th e p te u n are reported. D espite th e absence of severe pulm onary S iro sis, the lungs in both Contained " asbestos bodies " ; in boffi, too, th ere was an oscnpat ional history of exposure to asbestos, although in the second tiffs was obtained w ith difficulty end a fte r death. T h e association between m esothelioma of the pleura and exposnte asbestos is unlikely to be fo rtu ito u s; b u t to establish th is point aR cases of m esotheliom a, whatever j$rr occupa tional history, should be studied w ith th is possibility in m ind ; fo r evidence is now accum ulating th at th is disease is an industrial hazard. Addendum.--Since the subm ission of th is paper an analysis of the m aterial collected in th e Bernhard Baron In stitu te of Pathology of th e London H ospital between 1917 and 1962 has confirm ed the frequency w ith w hich asbestos S u e s occur in the lungs o f patients w ith mesotheliomata (H ourihane, 1964). Particular thanks are due to D r. Gavin Thurston, Queen's Coroner for W estminster, for his comments, and D r. B. N. Knight for his help with the first case. RSPgKSHCES Doll, R. (1955). Brit. % industr. M ed., 12, 81. Ctojae, 4 R. M S lk im e n , I, *18. , Gough, J. (1959). " Occupational Pulmonary Diseases. In Modem Trends m N M w , edited by D. H . Collins, p. 296. Bunerworth, H ariagttm Tj. S_ and Ciffiers, j.' J. le R. (1963). Qeoctim. eg cosmock. HouritoM , D . ffB . (1964). T konx, 19, 268. -------k 9581. f. Posh. Beet., in. s n . on ComH J4 S .O , P a rk .,. , 1*6. , SL 319. i, MJ. Gjjj.-, Kaschn. la, R. O., and MacDonald, R. R. (1963). S . Afr. W agner.J.C . (1962). Nature (Lond.), 19, 180. ------(1963). Author's onpublished summary of paper read at Fourteenth International Congress on Occupational H ealth Madrid, Sept., 1963. ------M n n d W o . R ., ra d H aringm o, J. S. (1962). J. PetKBeraTM , 73. C. A., and Marchand, P. (1960). Brit. J. industr. Med., WUt1h%. RT A. (1948). Petholoty of Lung Tumours, 1st ed., pp. 184, 185. BooenratA , London. "NWMMSW .UUHll*! c. f .'"''sniw pi.i 2