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\ \ --s ! Canrul. Med. Ass. J 1 Dec. 3, 1966. voi. 95 963 and January is of neutralizing e noted in 29 of tenatal sera were history of rubellidies characteristic in the offspring, tasles virus in 33 >30, parainfluenza iza virus 3 in 209 d by detectable throat of five of the "rubella synof these seven *ctive serological y during th first tot no rash de ed pooled human posure to known ( Hat., 3 i 35. 1941. 'Hi-. 6 6 1 341. 591, Met, 12 1, 1958. 56.. 1964. lu r., 2 i 647. 737, i* Ar t en st ein . M. I 225, 1962 , t i l l 215. 1962. . R . G. : J . A . M. Asa. J ., 8 6 1 128, sixer, T. H . : H e w . J ., 931 80. 1965. ncet, 2: 935, 1959. !61, 1962. le w JUnff. J. M ed., 95Jt. Sit 351, 1966. Ada m s, p ., J r. : . 1966 . J ., 94: 905, 1966 l, A . J . : Ib id ., 92: 843, 1965. 66. 1965. '965. irtality Weekly 1 . ttO i 444, 1965. ' i * 9* Caad Med. Ass. J. Dec 3, 1966, vol. 95 1179A n j i l v e l a n d T h u r l b e c k : I n c i d e n c e o f A s b e s t o s B o d ie s The Incidence of Asbestos Bodies in the Lungs at Random Necropsies in Montreal LILY ANJILVEL, M.B., B.S.* and W. M. THURLBECK, M.B., Ch.B., M.C.Path.,t Montreal Tile incidence of asbestos bodies in the lungs of adult patients selected at random, who died in four Montreal hospitals, was studied by examining fresh unstained smears of lungs obtained at necropsy. Two techniques were used for preparation of the smears and an arbi trary grading system was developed to estimate the degree of contamination of the lungs by asbestos bodies. Asbestos bodies were present in 48 out of 100 necropsies; they were found in 32 of 56 men (57%) and in 16 of 44 women (34%). Men were more heavily contaminated. The proportion of positive smears de pended on the technique used and the amount of lung sampled. No particular association was noted between asbestos bodies in the lungs and the presence of cancer in the 33 patients in this scries with malignant disease. The high incidence in this random series suggests that asbestos is a significant air contaminant in Montreal. THE occurrence of asbestos bodies in the lungs of patients with diffuse pleural mesothelioma has now been well documented.1, 2 Wagner, Sleggs and Marchand1 encountered 33 histologically proved cases of diffuse pleural mesothelioma in a four-year .period in the Northwestern Cape Prov ince, South Africa, a large asbestos-mining area. Asbestos bodies were found in eight of the 33 by sputum examination, lung biopsy or necropsy, and this was accepted as pathological evidence of as bestos exposure. In the remaining 25 cases, there was circumstantial evidence of asbestos exposureOnly one of the seven patients with mesothelioma reported by Thomson2 from Cape Town. South Africa, had a history of asbestos exposure, but on. histological examination asbestos bodies and fibrosis were found in the bases of the lungs in all cases. Following these observations, the frequency of asbestos bodies in the lungs was studied in routine necropsies in a hospital in Cape Town.3 Since then, similar studies have been reported from Pittsburgh4 and Miami.3 In Pittsburgh, the incidence was 41%; in Miami, 27.9%; and in Cape Town, 26.4%. The present paper reports a similar study on the inci dence of asbestos bodies in the lungs of patients who died in four hospitals in Montreal. In addition, we evaluated various sampling methods and studied the prevalence of asbestos bodies in pa tients with malignancy. Prom the D epartm ent of Pathology, Pathological Institute, McGill U niversity, M ontreal, Quebec. R esearch Fellow in Pathology, D epartm ent of Pathology, M cGill U niversity, M ontreal. tP ro feeso r of Pathology, D epartm ent of P athology, M cGill U niversity, M ontreal. Supported by a g ra n t from th e M edical R esearch Council of Canada. R eprint requests t o : D r. W illiam M. Thurlbeck, P athological In stitu te, M cGill U niversity, M ontreal. Quebec. La frquence cte la prsence de particules d'amiante dans les poumons de malades adultes pris au hasard et qui sont morts dans des hpitaux montralais, a t tudie en examinant des frottis frais non colors, prlevs l'autopsie. On a utilis deux techniques pour la prparation des frottis et on a mis au point un systme arbitraire d'chelle pour valuer le degr de contamination des poumons par des particules d'amiante. Ces particules ont t decouvertes dans 48 autopsies sur 100; elles ont t constates chez 32 hommes sur 56 (soit 57%) et chez 16 femmes sur 44 (soit 34%). La contamination tait beaucoup plus prononce chez les hommes que chez les femmes. La proportion de frottis positifs dpendait de la technique employe et de la grandeur du spcimen pulmonaire. On n'a mis en lumire aucune relation particulire entre les particules d 'amiante dans les poumons et le caucer pulmonaire chez les 33 malades de cette srie qui avaient une noplasie. La grande frquence de l'exis tence de particules d'amiante dans des cas pris au hasard permet de croire que l'amiante est une sub stance contaminante notable Montral. M a t e r ia l s a n d M eth o d s The material consisted of random adult necrop sies from the Royal Victoria Hospital, the Montreal Neurological Institute, the Montreal General Hos pital and St. Mary's Hospital, all in Montreal. The age, sex and occupation of the patients were determined from the hospital charts. In all cases the pathological diagnosis was recorded, and in cancers, special attention was paid to bronchogenic and gastrointestinal carcinomas. The presence of asbestos bodies was deter mined by examining fresh unstained smears from the lungs. Two methods were used to prepare the smears. In the first, the "scraping" method, the whole left lung was bisected and the cut surface was scraped with the narrow edge of a 75 x 38 mm. glass slide. The material which accumulated on this narrow edge was spread by another slide. The resulting smear, which looked like a thick bone marrow film, was air dried and cover-slipped using Permount (Fisher Scientific Co.). Two to four slides were prepared from each lobe, depend ing upon the amount of fluid obtained, which was related to the degree of pulmonary congestion and edema. If markedly edematous lungs were left refrigerated for a few hours after cutting, the fluid diminished considerably and thicker smears were obtained. One hundred lungs were prepared in this way. The second, the "squeezing" method, was origi nally used when the lung had to be preserved for subsequent inflation with formalin. The base of the lung was incised and the surrounding tissue was squeezed gently and the fluid collected on a USO A n j i e v e l a n d T h u r l b e c k : I n c i d e n c e o f A s b e s t o s B o d ie s r C aad. Med Asa. J. D ec 3, 1966, voi 95 * ' ./A. . U v --- * Fg. 1.-- T y p ical a s b e s to s b odies (u n s ta in e d lu n g s m e a r ). slide, as in the first method. Thick even smears vyth one or two macrophages per low-power field were considered satisfactory. Smears showing only blood were discarded. Eighty lungs were examined by this method. In 45 patients, one lung was examined by the scraping technique, and the other by the squeezing method. Asbestos bodies, recognized on morphologic grounds only, were identified by their typical orange-brown colour and by their segmented or beaded bodies, with club-shaped ends (Fig. 1). Only typical asbestos bodies were counted. It should be emphasized that these bodies were mor phologically identical with the asbestos bodies en countered in asbestosis. All doubtful or atypical bodies or "pseudoasbestos bodies"'5-6 were ex cluded. Atypical bodies, seen especially in pig mented lungs, resembled asbestos bodies in that they were linear but were jet black, and none had the orange-yellow beading of typical bodies. In addition, other "bodies" had club-shaped ends which were orange-yellow with a prominent black centre and were smooth, but did not have the seg mentation seen in typical asbestos bodies. These were termed "pseudoasbestos bodies" (Fig. 2) by Thomson and Graves.6 The smears were examined by the method customarily used to study cytology smears using a low-power field (16 mm. objective). The follow ing arbitrary grading system was used to estimate the degree of contamination: Less than five asbestos bodies per slide . Average of five to 10 asbestos bodies per slide . + + Over 10 asbestos bcdies per slide .. +++ Average five asbestos bodies per low-power field + + + + I '} /' . 1 _/ ' . /_+ : ; % * * t '. - ` * L .ti* m- I. a + K ii s ii ,, ..a . ..1 , -- , . ..4 Fig. 2.-- A p sem lo asb esto s body (u n s ta in e d lung- s m e a r). N ote the centra] black core. Statistical comparison between groups was made using chi-square tables and the null hypothesis. Finally, routine histological sections of 67 lungs from the Royal Victoria Hospital and the Montreal Neurological Institute that had been examined by the scraping method were examined for pulmonary fibrosis and asbestos bodies. The sections were stained with HPS (hematoxylin, phloxine and safranine) stain and with Perl's stain for iron. R esults Asbestos bodies were found in 48 of 100 necrop sies in which smears were obtained by the scraping method. Asbestos bodies were found in 32 (57%) of the 56 males in this series, and in 16 (36'V ) of the 44 females. The difference is significant at less than 1 in 20 (P < .05). Table I shows the average number of asbestos bodies in these cases. Asbestos bodies were generally scanty. Men were more heavily contaminated than women. TABLE I . --A sb e st o s B o d ie s in M en- a n d W om en Asbestos bodies Total Males Females "h - 4*+ +++ . + -f- + T*. 35 20 15 98 1 3 3-- .1 1-- The age distribution by sex ol those with posi tive smears ("positives") is shown in Table II, and the lobar distribution of positives is shown in Table III. Using the chi-square test, the observed difference does not reach conventional levels of Age (yre.) 26-45... . 46 - 65 .. 66 + .. .. TABLE I I .-- I n cid en ce o f Asbesto s B o d ies by A ge and S ex Males Females Total Positive c/c Total Positive O'0' . 6 2 33 4 23 12 52 13 . 27 18 67 27 1 25 6 46 9 33 Males and females Total Positive % 10 3 30 36 18 50 54 27 50 - JU.IJMJU O anud Moti. Dec 3, 1966, TABLE II] No of left 1 Xo. of left i Aibe->tos bo Positive m 1 Positive m 1 Total positi Total positi significane or clistribt Table 1 using the by scrap positive, < of less th TABLE Methods wsi Smears by Smears by Tables tive sme category of the h lymphom the majo significan Pathologies All types c Other dise: In the ferree! to sistent w TABLE V Typfs of n Bronchogf carnnor Carcinomi stomaci Cai cinomi colon. . Carcinomi pancrea Carcinomi breast. All other cancer. To' Caad. Med. Ass j Dec. 3,1966, vol FT.! I I *t 4 - * ' i. -lUiu am ed lung sm ear). roups was made ill hypothesis, ions of 67 lungs nd the Montreal en examined by 1 for pulmonary sections were phloxine and am for iron. of 100 necropby the scraping d in 32 (57%) n 16 (36'7 ) of jnificant at less >ws the average cases. Asbestos en were more *and W omen ales Fenlates 20 15 8T 3-- 1-- ose with posiTable II, and is shown in , the observed onal levels of and females ositive 3 30 18 50 27 50 Caad Med. Ass. J. pec. 3, 1966, vol 95 1181A n j i l v e i . a n d T h u r l b e c k : I n c i d e n c e o f A s b e s t o s B o d i e s TABLE I I I .--T h e D ist r ib u t io n ' o f A sb e s t o s B o d ie s in U pper and Low er Lobes Xo. of left lower lobes examined Xo. of left upper lobes examined. . Asbestos bodies in both lobes. . Positive in lower lobes alone Positive in uppci lobes alone Total positive m lower lobes Total positive upper lobes 100 . 100 31 - 0 -8 ' 40 39 significance (P is approximately 0.1 for either age or distribution). Table IV shows the difference that results from using the two techniques. In the smears collected by scraping, almost twice as many cases were positive, and the difference is significant at the level of less than one in 1000 (P < .001). TABLE IV.--R e su l t s by T w o D if f e r e n t S a m pl in g M ethods Method vsed Positive for asbestos % Total bodies positive Smears by scraping.............. 100 Smears by squeezing........ SO 48 17 48 21 Tables V and VI show the percentage of posi tive smears among those with malignancy. The category "other types of cancer" includes carcinoma of the larynx, liver and testes, astrocytoma and lymphomas. In all instances the malignancy was the major cause of death. The difference is not significant at conventional levels (P < 0.1). cases, asbestos bodies were found with great diffi culty in routine sections stained with HPS and in sections stained with Perl's stain. There was no reaction around these bodies. No asbestos bodies could be found in the other cases even on diligent searching. Sections of the lungs in which the pseudoasbestos body shown in Fig. 2 was found, showed silicoanthrocotic nodules with fibrosis. Asbestos bodies were also found in this case. Since 36 of the 56 men were "retired--previous occupation unknown" and the women were generally designated as housewives, data were not available to establish the relationship between occupation and the incidence of asbestos bodies. D isc u ssio n In this study in Montreal, the prevalence of asbestos bodies in the lungs is high, the overall incidence being 48%. This is comparable to the findings of a survey in Pittsburgh4 where the over all incidence was 41%. In Montreal the incidence among women (36%) is almost identical with the Pittsburgh incidence (34%). In Vlontrcal the in cidence among men is 57%, while in Pittsburgh it was 47%. Thomson-' reported an overall incidence of 26.4% in Cape Town and a similar incidence. 27.9%, in Miami. The observed differences in incidence are probably not meaningful, since the surveys were conducted by different observers using different techniques. The smears in the Cape Town and Miami studies were obtained from the base of the lower lobe only by the scraping TABLE V.--I n c id e n t e o f A s b e s t o s B o d ie s in P a t ie n t s W it h and W it h o u t M a l ig n a n t D is e a s e Males Females Pathological diagnosis Total Positive % Total Positive % Total Positive All types of c a n c e r................................. 33 Other diseases.......................................... 67 12 36 36 1? 54 38 10 22 55 15 58 29 2 14 % 13 48 In the histological examination of 67 lungs, re ferred to above, interstitial pulmonary fibrosis con sistent with asbestosis was not seen. In two of these TABLE V I,-- T h e I ncid en ce o f Asbestos B od ies by T ype of M alignancy Males Females Types of malignancy Total Positiie Total Positive Bronchogenic carcinoma . 42 Carcinoma of the stomach .. 2 _ _ __ Carcinoma of the colon.......... 3 2 1 __ Carcinoma of the pancreas. . . 1 __ 4 __ Carcinoma of the brea&t. . . . . . . . _ __ 42 All other types of cancer.................. 8 6 6-- Total. .. 18 10 15 2 method.7 Cauna, Totten and Gross,4 on the other hand, made an incision into the lung tissue and squeezed a small quantity of blood on to a glass slide. It is quite clear that the same observer using different methods may produce different prevalence rates. This is well shown in our own study where asbestos bodies were found in 48% of lungs ex amined by the scraping method but in only 21.5% by the squeezing method. This difference is par ticularly striking since in 45 of the cases one lung was sampled by squeezing and the other by scraping. The scope of sampling within the lung also may affect the result: if only lower or upper lobes were sampled, only 39 or 40% of lungs would be positive by the scraping technique (Table III). It is also possible that if both lungs were sampled, instead of only the left lung as was done here, the incidence of asbestos bodies would have been increased. 1182 A n j i l v e l a n d T h u r l b e c k : ; x c i d e n c e o f A s b e s t o s B o d i e s C aad. Med. Asa. J. D ec. 3. 1966, vol. 95 This survey confirms the findings of others4,0 tensive uses in brake linings, electrical insulation, that asbestos bodies are more common in men than cement, roofing, pipe covering and numerous house women, and that men0 are more heavily con hold articles. Industrial exposure occurs in plants taminated. In our study the effect of age was in where asbestos products are manufactured, and the conclusive. In men there .was an increase in inci widespread use of these products exposes a high dence in the groups ranked according to age, but proportion of the non-industrial population. It has in women the intermediate age group (46-65 been claimed"1that chrysolite, the type of asbestos years) had the greatest incidence. In the series as mined in Quebec, has fewer impurities--natural a whole, age did not appear to affect the incidence oils--than crocidohte and amosite fibres, the types of asbestos bodies. No real difference was noted found in South African and Australian mines. Ca between upper and lower lobes, in contrast to nadian asbestos fibres may not be carcinogenic. In other reports3, r' * that asbestos bodies tend to be 1958 Braun and Truan11 did a survey in Canada found more frequently in the bases of the lower and could not demonstrate an increased incidence lobes. of cancer in asbestos workers. Unfortunately, the clinical histories were inade Recently the relation of true asbestos bodies and quate and did not permit the assessment of occupa "pseudoasbestos" bodies has been examined and tional exposure. However, one patient, whose lung the possibility has been raised that minerals, other t smears showed + + + asbestos bodies, had worked than asbestos, may form asbestos bodies. Accord as a steam-boiler operator for several years. Rou ing to Thomson0 other substances may occasion tine histological examination of his lungs showed ally produce bodies that mimic asbestos bodies, no fibrosis. This was one of the two cases iiT which but these must be very uncommon because such asbestos bodies were found on routine histological substances are rare to begin with. The only criteria sections. In the remaining cases asbestos bodies used in the present study for the recognition of were not found in such sections despite careful asbestos bodies was their morphological appear search. Since routine paraffin sections represent a ance. These bodies arc the same morphologically very small portion of the lung, the likelihood of as those in asbestosis, and are quite easy to dis finding asbestos bodies is small. tinguish from pseudoasbestos bodies and other In our series, there seemed to be no particular association between malignancy and the presence of asbestos bodies. This is of interest because the atypical bodies in deeply pigmented lungs. It may be that these structures are not formed by asbestos fibres at all, although this does not appear likely incidence of malignancy among asbestos workers at the present time. Whatever their origin or struc is higher than among the general population. Ham ture, asbestos bodies are common in a high propor mond, Selikoff and Clung3 in the United States tion of cadavers in Montreal. For this reason, have reported an increased incidence of carcinoma asbestos is probably a significant air contaminant. among asbestos workers, particularly that of the lung and gastrointestinal tract. Reports from Bri Summary tain3 also indicate that there is a significant rela tion between carcinoma and asbestos. However, this association was seen in surveys of people work ing with asbestos, such as insulation workers. Since it is unlikely that more than a very small propor tion of our patients worked with asbestos, the Asbestos bodies were found in the lungs of 48 of 100 random adult necropsies performed in four hospitals in Montreal. The proportion of positive smears depended on the technique and amount of lung sampled; this m ade comparison with other similar surveys difficult. As bestos bodies were more common in men, whose lungs increased incidence of malignancy noted` in as were also more heavily contaminated. No association bestos workers would not be apparent in our cases. was noted between the presence of asbestos bodies and It is clear, however, that asbestos bodies are not death from malignant disease. more common in patients with malignant disease in the autopsy populations we have studied, and thus casual exposure to asbestos is not an impor tant cause of malignancy in the general population. We wish to thank the staff of the Department of Path ology, the Montreal General Hospital, and the staff of the Department of Pathology, St. Mary's Hospital, for their co-operation in this investigation. The number of cases that we have studied is very small, and we are now conducting a survey in all R eferences patients who die of malignant disease. For some years, Canada has been the world's largest producer of asbestos. Much of this comes l. W a g n er, J. C . S leggs, C. A and M a rch a n d , P . : B rit. J. In d u s tr . M ed.r 17: 260, 1960 2 T h o m s o n , J. G .: S. A fr. M ed J , 36: 759, 1962 3. T h o m s o n , J . G.. K a s c h u l a , r . o . C. a n d M a c D o n a ld . R . R : Ib id , 37: 77. 1963. from the Eastern Townships of the Province of Quebec, but important deposits are being mined in British Columbia and Newfoundland. Further 4. C a o n a , D . T o t t e n , R . S a n d G r o ss, P . : J . A . 31. A ., 192: 371, 1965. 6. T h o m s o n , J. G .: A nn. X .Y . A cad. S e t , 132: 196. 1965. 6. T h o m s o n , J . G a n d G raves. W . M ,, J r. : A rc h . P a th . (C hicago), 81: 458. 1966. developments are under way in the Yukon, North West Territories, the Ungava region of northern Quebec and northern Ontario, which already is a 7. T h o m s o n , J . G .: P e rs o n a l co m m u n ic atio n 8. H a m m o n d , E C ., S e l ik o k f , I. J . a n d C h u r g , J . . A n n . X . r . A cad. Set., 132: 519. 1965. 9. B u c h a n a n , W . D . : rin d ., 132: 507, 1965 10. H a b in o t o n , J . S. a n d R oe, F . J . C .: Ib id ., 132: 439, 1966. significant producer. Asbestos has varied and ex 11. B r a u n , D C a n d T r u a n , T . D . : A M .A . A rc h . In d u s tr . H e a lth , 17: 634. 1958. XX2 i t 1 I i C \ i. r s t: n t; n ti h ii n ii d FiG*;i. U VSi fR?(t HR.