Document Z1oR0bMgQ7pmXQKvVEOG5L5L

FILE NAME: German Articles - Some with English Translation (GER) DATE: 1960 DOC#: GER026 DOCUMENT DESCRIPTION: Medical Journal Article - Asbestosis Kk'JSI-.'fei^P *. OEH Code No 2 228 10 Ci J 5 O<r c Archiv fur Gewerbepatholcgie und Gewerbehygiene, volume 18, pages 159-20^, 1960 ASBESTOSIS* Knig, J. Pathological Institute, St. Georg ospitai, Hamburg it- * ^ -O' v xV *Ddicated to Professor Heine in gratitude and respect on the occasion of his 65th birthday. INTRODUCTION In 1951, KBnig presented a report at a meeting of North-West German pathologists concerning the histogenesis of asbestosis and asbestosis carcinoma of the lung, based on 16 cases of the Patholo gical Institute of the St. Georg Hospital in Hamburg. The investi gation was aided by the fact that most of the cases were subjected to autopsy, mainly for diseases other than asbestosis. In many of them, the asbestosis was discovered in the course of the pathological and anatomical examination. The available material of this type has now increased to 36 cases, which demonstrate soma of the problems dis cussed in the clinic from the standpoint of the pathologist. Through a more profound knowledge of the histogenetic problems, they may be brought nearer to a solution. For this reason, the author feels that publication is necessary. ASBESTOSIS IS A DISEASE OF CIVILIZATION In view of the rarity of asbestosis, it appears to be desirable to present briefly certain data concerning its importance as a disease of civilization, the conditions of its development and asbestos itself. The date of the initial appearance of asbestosis is not known. Asbestos as a refractory and spir.nable material, has been used and des cribed in antiquity (Cooke, 1924; a detailed presentation by Frank, 1952), but on an industrial scale, it has been processed only since the middle of the past century. Its most important products are It-plates, asbes tos cardborad, asbestos concrete plates and tubes, brake linings and -1- bands, gaskets, seals, filter- and gasket naterials for acids. Modern technology is unthinkable without asbestos. The disease of asbestosis was observed initially in England (Montague Murray 1900), then in Canada (1912, Wedler) and in Germany (Fahr and Feigl, 1914). The literature of asbestosis itself began in England in 1924 (Cooke). In 1927, numerous English and South-African papers were published; in 1930, asbestosis was recognized as an occupa tional disease in England. In 1951, Gloyne reviewed 121 autopsy cases of the period from 1920-1949. No such numbers were available'.in Germany, where papers on. asbestosis did net appear until 1931 (BUttner-Wobst and Trillitsch, Kurger, Rostoski and Saupe). By 1943, Wedler had collected 29 autopsy cases, of which 18 were published. A few other cases were added in the meantime (Welz, Boemke, Werber, Weiss). According toWedler, there must have been approximately 500 asbestosis patients in Germany, to which about 200 doubtful cases should be added. In 1939, Baader counted approximately 8,600 employees in the asbestos processing industry. Jacob and Bohlig estimated that there are about 4,000 asbes tos workers in Germany at the present time, but this figure must be too low, because in the area of Dresden alone there are at least 2,000 asbes tos workers. In Finland, Wegelius found 126 cases of asbestosis by radio logical examinations of 476 asbestos workers. Since .1936, severe cases of asbestos pneumoconiosis are being recognized as occupational diseases eligible for disability benefits. In 1952, the restricting qualification of "severity" was eliminated (M. Bauer). Since 1938, lung carcinoma qualifies for workman's Compen sation even in cases of slight asbestosis. The severity of the clinical -2- syndrome is evaluated differently in Canada than in Europe and South Africa (Cartier 1949). The prognosis of European and South African asbestosis is much less favorable than that of the Canadian disease. This is due perhaps to the type of asbestos. Different exposure condi tions must also be considered. Not only the type and form of the asbestos, which differ widely, but also-- as determined by experimental investigations (Vorwald, Durban and Pratt), the factors of dust density, exposure, period and particle size are important. ASBESTOS The fibrous mineral, major deposits of which are located in the Urals, in Canada, in South Africa, and Northern Italy -- lays in veins, crystallizes mostly transversely to the axis and consists of magnesium silicates and nonuniform components of lime, mica, various ores, quartz, clay-like substances, rutile (TiO^,) and talcum. Two principal types are distinguished: serpentine asbestos, mainly in the form of chrysotile asbestos which is primarily mined and processed in Canada and amphibole, which originates in South -Africa and is added to the European asbestos. Both types are highly- heat-resistant, but are very different chemically and physically. The monograph of Frank presents an excellent and encompassing review. Table 1 summarizes some of the most important data. ASBESTOS DUST The dust is generated during the opening up of the mulled (crushed) raw material, the mixing with binders (e.g. cotton), carding (combing) and during spinning, threading and weaving. The thickness of the dust particles is 0.05-3 y (Gardner and Cummings, Sundius and Bygden), the length of the particles inhaled 85-200 y maximum (Beger, Beintker, Gardner and Cummings, Noro) or only up to 26 y according to Knox and Beatties. In addition, irregular particles of other minerals with diameters of 0.5-10 y may be found in the lungs. ASBESTOS PARTICLES Asbestos needles inhaled by humans are usually converted to particles in a few months. Only isolated needles remain permanently unchanged. The asbestos particles are generated by the formation of a so-called gel envelope around the needles; the envelope is brownish in color and contains much iron (Prussian blue reaction). The variety of shapes is great; piniform, claviform and dumbbell forms are found with segmental constrictions. Highly detailed investigations were performed of the genesis, the physical and chemical properties, and the fate of these formations, in the hope that the knowledge of the histogenesis and thus the cause of the. progression of asbestosis can be emphasized (Beger, Sundius and Bygden, Holzapfel). According to more recent investigations by Holzapfel, the gel envelopes are created by the primary adsorption of carbohydrates, to which proteins are added. The primary bonding of OH-containing components, but not of amino groups, takes place with the release of the cations magnesium and iron from the lattice of silicon oxide chains, so that this cation exchange creates high-molecular organic silicon compounds, wThich are highly resistant to dissolution. It has been ascertained that the asbestos particles of amphibole survive decades in the lungs. Sundius and Bygden, also Ruska, found only amphibole -4- in the lungs but not chrysotile asbestos, which belongs to the serpentine type. In an investigation of the cause of carcinoma developing on a foundation of asbestosis, these are the particles that must be considered. TABLE 1. Summary of the components and properties of important asbestos types (K. Frank, "Asbestos," Hamburg, Becker and Haag 1952). Components: silica Magnesia Ferrous oxide Iron oxides Alumina Water Alkalis Acid resist ance Heat resist ance Properties: Texture <? Flexi bility Spinnability Impurities Chrysotile asbestos (Canada, Russia, Rhodesia, Cyprus) Amphibole asbestos Blue Asbestos (Cape) Amo sit (Transvaal) , Tremolite (Finland-, Italy) 39.0-43% 35.1-42.6% 51.1% 2.3% 35.8% 0-4.9% 0-3.5% 14.0-16.5% ---- -3.9% 6.9% soluble to 57% good brittle soft to rough, nostly silky very flexible good resistant good-low melting soft to rough, rather rough favorable flexible very good ?e, Cr, Ni favorable Fe 50.24% -- 32.0% .7.8% -- 3.0% 2.12% favorable resistant good brittle rough, but somewhat yielding poor com pared to chrysotile favorable Fe 55.1-62.02% 27.2-29.5% 3.54-4.6% -- 2.08-3.4% 5.0-5.04% 0.71-2.4% CaO good resistant favorable to good mainly rough, sometimes soft flexible to varying degrees poor lime Anthophylite (USA) 57.6% 31.2% 5.8% -- 0.9% 4.5% good resistant very good rough, hard ' brittle, not flexible poor Fe -5- FINDINGS 1. Material . Our report is based on 36 cases(*)- In 20 of these, the occupa tional history .was known. For the sake of clarity, these have been compiled in Table 2, while the remaining cases, where the history is incomplete, have been listed in Table 2. 2. Autoptic Findings. The lungs. In summary, the picture that emerged was the following: most lungs were voluminous, heavy, of a more or less solid consistency that offered a noticeable resistance to the knife. The parenchyma appeared diffusely dense, tough, inelastic, especially subpleurally, and peri bronchially. The reddish-brown section-showed a fine, greyish-white to greyish-green net-like pattern and often felt rough, almost, like fine sand or foam rubber. These changes were more marked in the apico-basal direction. In milder cases, they were slight and frequently limited to the lower lobes. Besides these diffuse changes, there were also focal ones in a num ber of cases. There were areas containing air and compacted or callous ones, ,,the latter especially basal, dorsal, and subpleural. Frequently observed were callous greyish-green to black nodules the size of pepper corns with star-shaped contours increasing in density in the apico-basal direction. (*) My thanks for making the clinical data available go to Professors Bansi, Diebold, Hesse, Holthusen (General Hospital St. Georg , Hamburg), Dr. Belicke (General Hospital Wandsbeck, Hamburg), Professor Budelmann (General Hospital Rissen, Hamburg) and Professor Engelmann, Hamburg. Dr. Seiberg (Path. Inst, of the General Hospital Bambeck, Hamburg) made two cases available, for which I wish to express my gratitude. For the collection of cases since 1952, I wish 'to thank Dres. H. Hilsselmann, E. KUhl, J. Schlosshauer (Pathological Institute of the General Hospital St. Georg.., Hamburg. -6- The bronchi, in particular the snail ones, were frequently more or less dilated. Catarrhal and putrefacient bronchitides were often seen. The large branches of the pulmonary artery showed a smooth intima in most cases. The lymph nodes at the hilus and at the bifurcation were in most cases slightly enlarged and brownish-grey. The pleural membranes had in many instances grown together, often with callouses. The most important autoptic findings in these cases have been com piled in Table 4, with special consideration of the morphological degree of severity of the asbestosis. A classification of the morphological pulmonary changes according to their severity is possible only with reservations. We have largely forgone an evaluation of the histological sections, since they could not always be identified with both of the whole lungs, as can be seen from the description of the_macroscopic pulmonary findings. The histo logical preparations represent a selected material, the finding being in most cases too severe rather than too mild in comparison to the macroscopic total finding. Diagnosis during autopsy was always the task of one person only (Professor Heine). Thus, a classificaton was made on the basis of the macroscopic find ing. Cases which were macroscopically inconspicuous and which were diagnosed only during histological examination, were called mild ( = 1) . Severe ( = 3) were those cases, where the autoptic diagnosis permitted the conclusion that extensive and marked changes were present. All othe -7- cases were evaluated as being moderately severe ( = 2). In the few cases, where the autoptic diagnosis did not permit a classification, but where unambiguous radiological findings were available, the latter were considered in the sense of raising or lowering the grade ( = 2-3) . The findings from four cases were sent to us so that the histological findings had to be used as a basis for evaluation. 3. H istological Findings. a) Lungs. Slight magnification revealed at. first four structural characteristics: 1) deposits of small heaps of asbestos particles in the walls of the bronchioles, and of a few asbestos particles in the alveolar end-sacs, 2) peribronchiolar and peribronchial and subpleural calloused areas, in part, radiating into the parenchyma or reaching it with finger-like formations, 3) a diffuse or focal dystelectasis and fibrosis of the alveolar skeleton, and 4) focal, substantial emphysema and bronchiectasis. The asbestos particles, which attracted attention by their bright yellow to dark brown coloration when subjected to the customary staining methods, have already been described in the introduction. A detailed examination is required by the deposits of asbestos needles and asbestos particles. A stronger magnification revealed, even in cases where years without symptoms had passed, asbestos particles and asbestos needles in small numbers. The tissue in which they buried themselves, was entirely without reaction. It was noteworthy that an occasional asbestos particle was found in a giant cell with its end protruding from the cell as a naked needle. The heaps of asbestos -8- particles were scattered in the alveo of the respiratory bronchioles (Figure 1) and the alveolar ducts (Figure 2), or they were found in peribronchiolar callouses of calloused tissue (Figure 3). Appropriate cutting sometimes showed that the asbestos particles completely filled the alveoli. They were lying topsy-turvy, in most cases densely packed Penetrated among them were macrophages and giant cells, or a granulation tissue had formed that surrounded and penetrated the cumulation of asbestos particles, forming a fine network of fibers (Figure 4). Some times, the asbestos particles were arranged radially-- especially in the callosities-- with the button-shaped, thicker end pointing toward the periphery (Figure 5). Despite not inconsiderable cumulations, the alveolar walls were still found to have remained quite fine, almost all had thickened and had become infiltrated with microcells. The bronchiole and alveolus duct were often barely recognizable where a granulation tissue with microcell infiltrations had developed in the mucosa and become fibrous. This narrowed the lumen and cut the filled alveolus off from the lumen so that compact cumulations of asbestos particles lay completely isolated in a callosity-transformed alveolar wall (Figure 3). The lumen, as far as it still existed in these sections, was stripped of mucous membrane and contained a few asbestos particles and ample quantities of desquamated macrophages. The granulation tissue penetrated into the cell-filled lumen. The resulting picture was that of bronchiolitis obliterans (Figure 4). Both in the bronchioli and, especially clearly, in the alveolar ducts, the smooth muscles had coarsened considerably (Figures 1 and 2). These areas were still visible even in the calloused tissue. -9- TABLE 2 , Survey of the cases with a known occupational previous history No. Serial Age Sex No. u lOHi/39 fi:l ? I ]999/30 41 ? 0 G 200:1/41 .79 <$ 0 191/lS 53 0 10 8.17/4S *17 0 . n 993/42 19 9 12. 43G/5U 75 J i:i ! S23/50 39 9 M | 227/51 Gl ? | 15 I 27(1/51 55 ? j Period of Date 1910-- 19:13 1918-- 1930 exons. Free First symptoms Jura- Inter Years val :ion Date >efore (vrs'. ) yrs. death Disabled 17 0 with asthma G in 1933 12 9 llroncliili.i 1930 9 ? 15 7 7 -- 1924-- 1918 ! 24 0 1930 IS 1 1922-- 1037 15 11 1935 13 1 1927-- 1933 Ci 15 Before'194 ? 7 30 7 7 -- 1920-- 1937 1007-- 1912 1927-- 1930 1925-- 1030 11 13 .935: as thru 15 ifter a cold 15 .938:bronch. $1b 21 'asbestos 13 >artitles r ixpectorate) ... . < G 21 j 31)50 1-2 Clinical diagnosis Suspicion 1939 1933 yes 70% dis abled 1938 30% reduc tion of ~ ability to work 1917 No to 1949 :rio 1950: suspici on Confirmed since 1938 No . Radiological finding Negative Probably positive positive Probable. 1938 positive posi H vc .1.94g positive but no diagnosis 1959: negative 1950: suspiclo ? positive, bur no. diagnosis TABLE 2 . (Continued) a \ Ili 5(17/5 J 45 M 1 1023-- 1031 -7 i 17 G3 0 /5 1 44 $ 1023-- 1035, s } 15 1011-- 1040 Jo 351/52 (0 2 1010-- 1017 7 *w 0 2 3 /5 2 5!) 2 lO Ifi-- 1 0 52( 7) 0 j:i 103/53 41 i? 1 0 2 0 -- 1.TJ 10 1 24 0(17/51 45 tf 1 0 2 3 -- 1035) H ! !--1 20 1 3 1 3 /5 5 55 d 1037-- 1055 13 H I :io M 23/53 54 d 1 037-- 101(5 0 31 M I3/5G 72 ? 7 25 34 303/57 47 $ 102S-- 1032, 1047 }5 20 inno No, although 1 occupational Probably inamnesis negative /as known 2 't :tii 1.951 1 0 Prob . none : -- M from 1939 li ned. superv for Tbc suspicion /ecause of /ccup .his to Probably negative No ? No -- No Presumably negative IK none 0 1952 9 1952 -- 2-- :j 2~:\ No 1955 abilty to .work eclu^gfj by __ No______ 1911, 19 5 1 ,1 9 5 :1 : negative, 1955 l i a s J.Live______ 1955 susp,. because of negative previous occupn tiona 1 Ins Lory ? 195G 10 weeks suspicion nospitaliz. 1956: ior1 dust,, suspicion lull R jr> 1950 9 7 1950 Presumably positive TABLE . Survey of cases with incomplete previous histories Serial N o . N. Age Sex G 200/30 46 G 2110/30 2070/30 G 1685/48 48 109/43 67 IS 15/52 46 JO 24S->- 62 21 353/52 1051/5-1 60 1122/54 56 2S S70/55 63 32 15/57 61 33 J5 1063/57 65 3G 1039/57 'irst Years symptoi efore death 1935 "lung disease' None linicafL Radioliagnos 3-s logical findings 2 wks. positive before death 1 probably no Yes 1923(1): Dry Pleuritis 20( ?) No m & t 24 No 1940: 12 No Plfurith None No Presumably No None Asthma., date?. No None No No 1955 10 weeks No No No No No No i 4 No > , = OJO c. tn uts> (46 ?) a. -HXia gCO-AW OUr-rOO * : ocupen *dCJ Sj i uiSo-io . 0\G)CiHCiO ' t-HC/lCCCKf As bestoSis negative?. S in ce 1928 'callosi-/ ties1' No Presumably' negative negative negative negative negative positive, but no diagnosis -12- TABLE 4 . Listing of the most important autoptie findings. Degree of asbestosis: 1 = slight, 2 = moderate, 3 = severe (for details, cf. text); degree of anthracosis: - = not mentioned in autoptie diagnosis; moderate:- all cases which were not expressly termed severe, serious, etc,, in the diagnosis. Main disease, No. cause of death 1 Material sent in (probably asbes tosis) 2 Material sent in (probably asbes tosis) 3 Tuberculosis, right cardiac insufficiency Degree of asbestosis Probably 3 Pulmonary carcinoma --~ Probably 3 2 ! i 4 Asbestosis, right cardiac insuffi ciency 5 Sepsis 6 Pulra. carcinoma (material sent in) 7 Material sent in (probably asbes tosis) co CN1 3 1 2-3 -- -- Left lower lobe Pulmonary tuberculosis -- -- Degree of anthracosis ? ? Severe scarification of the upper lobes, middle lobe and of apical sec tions of the lower lobes I'Yeaher <'(i!JeiiLion In right lower Jobe, pleuritis right "*-- -- -- -- ? ? TAULE 4 (Continued) Hain disease No. cause of death 8 TuberculosiSj pulmo nary embolism 9 Pulmonary carcinoma 10 Pulmonary carcinoma 11 Stomach carcinoma 12 Hydronephrotic atrophic kidney, uremia 13 Pleural endothelioma 14 Asbestosis 1.5 Glomerulonephritis uremia 16 Pleural endothelioma Cl I CM Degree of asbestosis 2 3 3 1 1 3 3 2 3 2 Pulmonary carcinoma Pulmonary tuberculosis Degree of Anthracosis Left lower lobe with diffuse in filtration, nodu lar mtastass in right lower lobe Right lower lobe, invasion of medi astinum -- Indurating tuberculosis of the right upper lobe with some exudative foci empyema 1000 cm , cavern and chronic pneumonia in right lower lobe -- Moderate Severe Severe -- Slate-like induration -- of right upper lobe Over right lower -- lobe, also in 'right lower lobe -- -- -- -- Over left lung, extensive invasioi subpleural and in the hilus ------------ Severe Moderate Moderate TABLE 4. (Continued) No . Main disease cause of death 17 Peritoneal carcinoma 18 Peritoneal carcinoma 19 Ca. of the urinary bladder, uremia 20 Stomach carcinoma, cardiac infarct Degree of asbestosis 2-3 2-3 1 1 21 Cardia carcinoma 1 22 Esophageal carcinoma 1S. 23 Pulmonary ca. 1 ' 24 Pulmonary embolism -J after- urethral injury 25 Bronchial asthma, 1 insufficiency-of right heart 26 Pulmonary carcinoma 1 27 Pleural endothelioma Presumably 1 Pulmonary carcinoma -- -- -- -- -- Right lower lobe Left upper lobe in tuberculous induration Over right lung Pulmonary tuberculosis -- -- -- Degree of Anthracosis Moderate Severe Moderate Camifying and scari fying tuberculosis of both upper lobes w/ 'chalky foci. -- Chalky focus in right upper lobe Chronic-cirrhotic tuberculosis of both tips w/ minimal caverns Bilateral slate-like scars in tips Scars in tips of both upper lobes Moderate Severe Moderate Severe Severe Indurated Tbc of tip w/ fresh caseation Moderate Moderate TABLE 4. (Continued) Main disease No. cause of death Degree of asbestosis 28 Peritoneal ca. Tbc , . Probably cardiac infarct 3 29 Pancreas ca, 30 Pulmonary ca. 31 Ashes tosis 32 Pleural endothelioma 33 Ca. of sigmoidal colon 34 Dermoid of left ovary stomach ca. 35 Pulmonary ca. 2-3 2 3 . 2 , \ 2 3 1 36 Asbestosis 3 . Pulmonary carcinoma -- Left lower lobe -- Bilat., especi ally right lower lobe " -- Pulmonary tuberculosis Chron. cavernous Tbc of both lungs carnifying pneumonia in left lower lobe, fresh scattering -- -- Old indurating Tbc with fresh activity --*~' -- Left lower lobe, spread into both pleural cavities Slatey focus in right tip ---- --- Degree of Anthracosis Moderate Severe Severe Moderate Severe Moderate Moderate Severe Severe Figure 1 . Respiratory bronchioles vith cumulations of asbestos par ticles in the alveoli' (case 4, hematoxylin^-eosin, oc. 10 , lens 10). Figure 2 . Alveolar duct with cumulations of asbestos particles in the alveoli (case 5, hematprcylin-eosin, oc. 10, lens 10). -17- Figure 3. Peribronchiolar indurated tissue with cumulations of asbestos particles (case 6, hematoxylin-eosin, oc. 10. lens 10). S- % 40 I v *r-j :~n Jf.ww)*. h '. ) ri > 4 `S T-.'.V .7.id * </> }'Ji>-.' - ;o Figure 4 . Bronchiolitis obliterans. Cumulations of asbestos particles in the lumen, partially enclosed by giant cells and par tially infiltrated by a granulation tissue (case 7, Tibor-Pap, oc. 10, lens 40). Because of the addition of fibrous-collagenous material tending toward hyalinization in the loose, peribronchial connective tissue layers, a structural definition of the bronchiolar wall as distinct from the adjoining parenchyma was no longer possible. The severely fibrous tissue radiated into the alveolar structure; which was itself more or less fibrous. The whole peribronchial tissue was infiltrated at varying degrees by small cells and shewed some asbestos particles. In a few cases, dilated lymph paths were found within the peribronchial fibrotic areas, in which lay macrophages and short asbestos particles. Figure 5 . Radially arranged asbestos particles in a band-like callo sity (case 5, hematoxylin-eosin, o c . 10, lens 40). In advanced cases, the parenchyma contained scattered roundish and band-like callous areas (Figure 6). There were no structural indications as to the location where these foci had formed. Some showed a few char acteristics of hyperplastic, smooth muscles and cumulations of asbestos -19- Figure 6. Marked emphysema, hand-shaped callosity and obliteration of the parenchyma (case 24, hematoxylin-eosin, oc. 10, lens 10). particles strung up in a rosette shape, sometimes capped by large plasms.-rich giant foreign body cells (Figure 5) ,, In other layers of the callous tissue, some particles and frequently rows of dust cells. Ying in the alveolar terminal sacs were'short asbestos particles in small numbers. These alyeoli showed desquamation of alveolar epi thelium and also giant.cells. While in the early stages, the parenchyma showed a mild emphysema, the advanced stages, where the bronc-hiolar and peribronchiolar processes of callous formation increased, were character ized by dystelectasis, sometimes of a very marked degree. Also present were an alveolar desquamative catarrh, small-celled infiltrates in the interstitial space and finally also a lattice fiber hyperplasia and extensive fibroses. The sclerosis of the alveolar septum sometimes reached a considerable degree of severity. Thus, there were pictures -20- pointing to a collapse induration. Instead of the desquamated alveolar epithelium, a granulation then blocked the remainder of the lumen. Finally, in a few cases, connective tissue obliterations of whole areas of the parenchyma were observed, combined with the wasting of the elastic fibers. These obliterations involved primarily the subpleural and peribronchial areas. The vessels that supplied such sections, showed swelling and hyaiinizatioa of their walls, loss of the tunica elastica int., intima proliferations and fibrous-hyaline densification of the adventitia. In cases where the changes were nila, only a portion of the bronchioli were involved in the above-describec manner, while some appeared unchanged. No asbestos particles were seen in these cases. The j.rregular involve ment was not bound to relatively large areas, such as perhaps a lobe, but was evidently circumscribed by one cr several alveoli. These systems revealed a tendency toward the development of ^ r k e d emphysema at an early stage. At advanced stages of the changes, such emphysematous foci were found between indurating, fibrous sections of the parenchyma (Figure 6). In extensive indurations, there were occasionally multi-chambered systems of spaces separated from each other only by trabecular structures of fibrous tissue. These contained air, mucus, expelled epithelial cells, leukocytic exudate or mushroom-shaped granulation tissue although generally speaking no asbestos particles. Frequently, they were lined with epithelium. This was in part flattened, such as in mucus-filled spaces, but partly also cubic or cylindrical so that this picture resembled that of a glandular structure, such as the prostate. The phenomenon was -21- Figure 7 . Callosities and rearrangement; epithelial destruction and re-formation, mucus retention (case 7, hematoxylin-eosin, oc. 10. lens 10). that of an adenomatous restructuring (Figure. 7)^ The original struc tures of the airways were no longer recognizable. The bronchial epithelium must be examined, ,by itself. In the respiratory bronchioli, where asbestos particles and processes in the sense of bronchiolitis obliterans were found, there was frequently no epithelium. In the unchanged sections of the bronchioli, the epithelium was intact. Hyperplastic formations were found here in some cases, where cubic epithelium had become multi-layered or irregularly proliferating in bundles in the manner of a cylinder epithelium. Atypical develop ments of a few or several cellular characteristics were registered and there were some findings of a rich, intracanalicular epithelial prolifer-, ation, which could not be interpreted as carcinomatous only because of its sharply basal outlines. This applies in particular to formations -22- which recall squamous cell . carcinomas. The nature of the atyp ical feature nay differ greatly even in one and the same case. The described epithelial changes were most marked in the adenoma-like transformation areas that have already been described. The picture of pulmonary asbestosis as described here must yet be supplemented by a summarizing description of the carcinomatous findings. These did not offer a uniform picture; small- to polymorphous large- celled carcinomas were just as frequent as uniform microcellular car cinomas. In case 35, squamous cell carcinoma appeared. Locally, there were some formal relationships to the described . adenomatous transformation process. In case 6, for example, there was a polymorphous large-celled carcinoma in callous areas of connective tissue adjoining bronchiectases, in which atypical epithelial prolifer ations were conspicuous. In two cases, a microcellular carcinoma showed transitional stages either to a large-celled carcinoma (case 10), or to formations resembling squamous cell carcinoma, enclosed by callosities (case 9). But, these callosities enclosed open areas lined with cylinder epithelium, which tended on the one hand to atypical intra-can- ilicular proliferations and marked invasions of the connective tissue wall, on the other hand, so that it was not possible to make a reliable distinction between carcinoma and the atypical, hyperplastic epithelium. While these open areas were generally free from asbestos particles, there were large numbers of them in the callous tissue. Similar relations between carcinoma, atypical hyperplastic epithelium and callous tissue were also discerned in other cases. They were observed, in particular, in cases of pleural endotheliomas. -2 3- Concerning the parallel existence of astestosis and tuberculosis, no peculiarities were observed. Asbestos particle-s may occur in all tuberculous structures, be it in areas of cheesy degeneration, be it in unspecific, perifocal connective tissue. Giant foreign body cells containing asbestos particles were found lying next to giant Langerhans cells. b) Lymph nodes. In regional lymph nodes of the hilus and the bifurcation, small asbestos particles were found. They were usually located in circumscribed areas of the peripheral sinus, but occasionally also in the central sinuses. Giant cells did occur. Other findings were a marked sinus catarrh and histiocytic proliferations. The pro liferated endothelial cells of the sinuses give the Prussian blue reaction. Small callosities were seen in some cases. Besides asbestos particles, brownish or blackish clods and lumps were also found frequently, often phagocytized by giant cells. Judging by their shapes, these were evi dently fragments of old segmented asbestos particles. These fractions also gave the Prussian blue reaction. The traqheo-bronchial lymph nodes almost always contained asbestos particles and their fragment in relatively large, numbers sometimes also needles measuring up to about 70 y in length. In some cases, a few such fragments were determined in the lymph.nodes of the neck (Figure 8). The degree of involvement of the lymph nodes appeared to correspond to the degree of severity of the pulmonary ashestosis. c) Paranasal Sinuses(*). In one case, the maxillary sinus, the frontal sinus, and the sphenoidal sinus were examined. All sections (*)These studies were performed by Dr. JH. Hilssalmann and Dr. J. Schlcsshauer Figure 8 . Lymph nodes of the neck: sinus containing asbestos particles (case 4, hematoxylin-eosin, oc. 10, lens 10). 'Y ** . showed short asbestos particles up to a length of about 40 p and. also small to moderate numbers of fragments. But in addition to these, highly edematous, submucous tissue was found to contain ample amounts of coarse particles containing iron, which were obviously fragments of disinte grated asbestos particles. There was no tissual reaction apart from a slight microcellular infiltration. Irregularly distributed asbestos particles lying singly or in groups were also determined in the tonsil and pharyngeal tonsil. Their lengths reached 70 to 90 y. Likewise, there were fragments, some with giant foreign body cells* which appeared to have enclosed some of these parti cles. Close to some of the particles were the beginning of fibrous scarification. -25- d) Systemic Organs. In the livers, kidneys, and myocardiums of the nine cases that were examined in this respect, no asbestos particles were found. But, of 13 spleens that were dissected, nine showed asb.estos particles of lengths of up to about 50 u, or large fragments of such particles, still clearly recognizable as such. Most of them were isolated, only sometimes they were arranged in small groups, often in the peripheral sinuses at the trabeculae or otherwise sparsely distributed throughout the whole organ. In some cases, a very slight anthracosis of the spleen was diagnosed. DISCUSSION First, we shall discuss the casuistic data reported above. They confirmed much of what is known today of asbestosis. A detailed screen ing, however, also uncovered a number of facts, which are still being discussed or which have not yet been sufficiently recognized. This raises questions that direct our attention to the histiogenesis of asbestosis. For this reason, the concepts presented at Lbeck (Knig) shall be presented in greater detail. These permit a discussion of the questions that have remained open with respect to these case histories. The result, in our opinion, leads to certain consequences in the fields of occupational hygiene and official medical evaluations. The discus sion thus consists 'of four parts. 1. Case Histories. . a) Selection. Our patient material consisted of 13 men and 23 women. This ratio becomes understandable if- it is realized that in this area, more women than men are employed in various manufacturing processes of the asbestos industry. In the material, of Gloyne, the female sex also -26- predominated. The age at the time of death-was 58.5 years for the men and 54.3 years for the women. These ages were thus much higher than those determined by Gloyne (men = 38.5 years, women = 33.5 years). These figures suggest that the severity and progressive nature of asbes- tosis were less in our cases than in those of Gloyne. Table 5 provides a survey of' the cases classified by us as mild ( = 1), moderately severe ( = 2), or severe ( = 3). The Table shows that all degrees of the disease were rather equally present. There was no difference between the sexes in this respect. The distribution indicates already that in our material, asbestosis was often a secondary finding. Thus, our patient material was selected on a different basis than that of a group with pneumoconiosis. It appears necessary to emphasize this fact without proceeding further. Since the number of our cases is much higher than those in studies published so far in Germany, we feel justified in considering our collective as a representative one. It appears permissible- to compare 25 of the 36 cases to cases from the general autoptic material at the St. Georg Hospital, from which they differed in only one respect: the presence of some degree of asbestosis. Whether all cases without exception that occurred since 1939 have actually been included remains questionable, however, since mild cases were recognized only when the lungs were subjected to histological examinations. ________________ Degree of Men severity n Table 5. Survey of the cases classified as mild ( = 1), moderately severe ( = 2) J and severe ( - 3). 15 21 2-- 3 3 34 3S 1(-.*f0,.o S; 23 \ 31 j'54?? Women /V 6 25 5 22 j-43% 3 13 r03" 0 "0 f 27- uncharacteristic and gradual onset, a determination of dates is objectively difficult. The dates are, therefore, frequently, but not always, related to some remembered event, such as a -medical treatment, a determination of disability, or a similar circumstance. It can be assumed that in many cases, the symptomatology goes- back further in time than was reported. Those anamnestic data that could be' related to a possibly existing pulmonary tuberculosis, were not considered. On the other hand, cases of pulmonary carcinoma were included, since the history, as far as it was dictated by the carcinoma, can only have been important for a short time. Logically included in this category were those cases, where another pathological condition led to shortness of breath a rela tively short time before the death of the patient. A study of the relationship between the duration of the complaints and the severity of the asbestosis shows that the cases where the pulmo nary changes were minor (1) went back on the average for a period of 0.14 years, that moderately severe cases (2) had a history of 3.3 years and that in the severe-cases (2-3 and 3), the corresponding plriod was 7.6 years on the average. Figure 9 shows that a positive cor relation between the duration of the shortness of breath and the severity of the pulmonary finding exists only in some of the cases. In a considerable portion of the severe and moderately severe cases, no symptoms were reported Figure -9 . Relationship between the duration of the symptoms and the degree of asbestosis. years 2t 22 - 20 io- s * . 1 1 1 1 1 1 n - 12 .1 a - s 6 - ( # 2- Degree of asbestosis -29- or only these of a relatively short duration. The morphological degree of severity is thus not simply identical with the duration of the .sub jective disorder of the respiratory function. This and a. symptomatology that lacks characteristic aspects explains th.at a clinical diagnosis was established in only some of these cases. Table 6 provides a survey of.the extent to which these cases appeared to be clinically suspicious or were definitely recognized and to which cate gory of severity they belonged. It becomes evident that of the 23 moderately severe and. severe cases, ten were net diagnosed. Of these ten cases, four had a previous history with symptoms. In the group of the cases which were recognized only shortly before death or which were considered suspicion at that stage, there were four, whose previous history mentioned revealing symptoms. Only in one-fifth of the moderately severe and severe cases had the asbestosis been known to exist for several years. These considerations lead us to one of the. most important problems in connection with asbestosis, which is the discrepancy between the clini cal and the morphological pictures. Using the autoptic experiences, wre add yet another aspect to this problem. The morphological finding may be more severe than the clinical picture or the duration of the previous history would lead one to expect in regard to the symptomatology. From the viewpoint cf the clinical experience, the opposite impression is in the foreground; the subjective condition is frequently much worse than is suggested by the objective physical signs of the disease (Sparks 1938, Baader 1939, Luton et al. 1953, Behrens 1956). A negative radiological finding was obtained by Wood and Gloyne in 9 of 53 cases, by Alvens in 13 of 38, although all other clinical signs of asbestosis were present. -30- Tile same experience was reported by.Garnis and Ucko. Cases which radio logically correspond to dust lung of the first and second degrees (Schulte), may reveal such severe functional disorders that they would, without hesitation, be evaluated as the most severe cases of dust lung (Di Bissi). Totally different-- and evidently in agreement with our concepts developed in relations to the work at the autopsy table-- are the experiences of Cartier, who described the clinical aspect in Canadian asbestos workers by saying that in uncomplicated and even in advanced asbestosis, the symptoms were more often missing than pressent. TA3L5 6 . Number of clinically diagnosed cases arranged according to the degree of severity of the asbestosis (Cases 2, 6, and 7 could not be considered). > Year preceding death . . . . < Year preceding death . . . . Suspicion shortly before_death No . . . . . . . . . . . . . . Degree of severity of the asbestosis 1 2 2 - 3 3 1 4 1 3 1 1 2 10 4 3 3 The different experiences as far as our cases are concerned, can be explained by the selection of the material, depending bn whether the clinical or the pathologico-anatomical observer supplies the comment. The contrast is only an apparent one, since the same principle is expressed by both kinds of experiences. From the pathological and anatomical viewpoint, we can confirm the clinically important experience, "that the roentgenological picture is more-a yardstick, for the intensity of the reaction on the part of the pulmonary tissue than for the severity of the dust lung disease," as 3aader emphasized. This raises the ques tion as to which possibilities exist for understanding this discrepancy from the histological point of view. c) Which conditions determine the degree of severity of the mor phological finding in the light of our data? First, the exposure time must be examined. It is known in 20 cases. On the average, it amounted to 7.7 years in the cases where the pulmonary changes were mild (1), to 9.1 years in the cases with moderately severe changes (2), and in the severe cases (2-3 and 3), the exposure time averaged 14.5 years. Figure 10 shows that the increasing severity of the asbestosis was combined with increasingly longer exposure periods, although there was no positive correlation in a number of severe cases. Relatively short exposure times were reported for these. It can be assumed that added to the exposure period is the dust concentration as the second essential factor. In. the individual case, this factor remained largely unknown. Soma insight into this might be gained from exa mining the relationships between the sex of the patients and the degree of severity of the asbestosis. Severe asbestosis was not more frequent in men than in women, although Yea'ts.' Ji' 23 i2S . r 2- L22 . ZC 3 - IS n 12 tor a 6 { 2 - 0/ !i . . . Ii 1 iiI 2 2-i the exposure period for the men was 16.1 years and for the women, Figure 10. Relationsnip between exposure time and degree of sever ii;y of the asbestosis. 10 years. In six men and seven women suffering from severe asbestosis, -32- the average exposure time was calculated at 18.3 and at 11.3 years. This could be considered as the expression of a greater exposure of the women, but also that of a stronger disposition. Besides the duration and the intensity of the exposure, another factor that must be taken into account is the time as a whole, i.e., the exposure, period plus the free interval. Knox and. Beattie have proven the importance of this fact or for the degree of the pulmonary changes in their quantitative studies. Such relationships did not become apparent in our material, since the time from the beginning of the exposure to the fatal outcome did not indicate any reliable differ ences for the moderatley severe and the severe cases. Again, the diffi culty of evaluating this lies in the fact that we do not know the intensity of the exposure (time x absorbed dust quantity). If Knox and Beattie are right, we should have to assume that the patients whose exposure time was shorter, have absorbed more dust. Let us examine the seven severe cases^of asbestosis in Table 7. The time between the beginning of -the exposure and death (the whole history) is approximately of the same order of magnitude. The exposure time varies. TT*e results in the lungs of these patients were about- the same. If the time from, the beginning of the exposure to the appearance of the first symptoms is taken as a yardstick for the progress of the disease, case 4, 10, 13, and 29 permit the 'assumption that relatively more dust was absorbed in the cases where the exposure period was shorter. And in cases 11, 15, and 24, we must, on the contrary, assume that the amount of dust that was absorbed during the relatively brief exposure period, was not sufficient to cause symptoms soon thereafter, although it did affect a -33 TABLE 7. Comparison of exposure times to the time that passed between the start of the exposure and the appearance of the first, symptoms in cases of severe asbestosis. Case 13 4 10 29 11 15 24 _____----------Exposure time 11 12 .15 18 6 5 8 1st symptom-years after beginning of exposure 9 12 13 15 19 25 -- Free Duration of the intex*val total history 13 24 9 21 11 26 0 18 15 21 21 26 18 26 progression of a gradual character that reached far into the free inter val, i.e., into the time between the end of the exposure and death. The importance of the time factor, for the development of the pulmonary process is particularly well illustrated, by these cases. The differences- of the reactions in the individual case, whether they be of a chronological or a quantitative nature, however, are cer tainly not attributable to differences of the exogenous factors, which are only partly known or estimated. This is also the conclusion of Knox and Beattie. There can be no doubt as to the participation of an indi vidual disposition, although its importance has not yet been elucidated (Baader, Wedler). The anamnestic data are insufficient for an evaluation of this factor. A more detailed investigation of the type and the development of the pulmonary process is, thus, in the final analysis restricted to the picture presented by the lungs and to its chronological arrangement, i.e., to the study of the histogenesis. d) Which pulmonary findings of general importance were combined in our cases with the asbestosis? Mixed pneumoconioses in the strict sense of the term did not occur in our material. Only one case showed histo logically small callosities or indurations that aroused the suspicion of silicosis. The distribution of anthracosis among our cases is shown in Table 8.. Accordingly, the men showed a severe anthracosis more often than the women. The degree of severity of the asbestosis was not parallel to that of the anthracosis. TABLE 8 . Relationship between the degree of severity of the asbestosis and anthracosis. Sex Mala Female Degree of severity of tbe asbestosis i 2 2-3 3 1 2 2-3 ,,o> Degree of severit y of the anthracosis Mild and moder-' Severe not mentioned ate n cases n cases n cases 1 2 2 1 1 1 1 3 4 1 1 2 2 1 2 1 1 3 2 3 v Tuberculous changes were determined in 12 cases. Seven of these were old processes that had largely healed and had involved, more or less, the apical segments of the upper lobes. In this group, the number of cases with mild asbestosis was disproportionally large, (n = 5). In another three cases, there were fresh foci, twice (cases 3 and 31) in indurative tuberculosis of the upper lobes and once (case 28) in double cavernous tuberculosis. The remaining two cases,presented a relatively new tuberculosis with cheese degeneration that involved both lungs in -35- case 26 and the right lower lobe, in case 3, which showed marked indur ation in both upper lobes. In these five cases where the tuberculosis was still active, two (8 and 26) had a mild, one (case 3) a moderately severe and two (28 ana 31) a severe asbestosis. In cases 3,' 8, and 28, the tuberculosis was probably an important contributing factor in regard to the fatal outcome. The age of these patients at the time of death was 63, 63, and 67 years. In the remaining two cases, the cause of death was once the asbestosis (case 31) and once a scar (?) carcinoma of the lung (case 26). The ages at the time of death were 72-and 56 years. This compilation does in our opinion not permit a conclusion as to a mutual dependence of pulmonary tuberculosis and asbestosis. The dependence on general time factors is probably of some importance. Using comprehensive statistics, Wedler proved that tuberculosis of the lungs is not more frequent in asbestos workers than in the general population. The last broad-based survey of Gloyne showed that in the autoptic material from his cases of pneumoconioses, the group with asbestosis had almost the lowest incidence of tuberculosis. e) Pulmonary carcinoma in asbestosis. Pulmonary carcinoma in asbes tosis is of . practical and theoretical importance. The carcinoma of the asbestos lung, observed in the past by Gloyne (1933, 1935), Lynch and Smith (1935) and by- Egbert and Geiger (1936), has been recognized as an occupational cancer by all authors except Cureton, ever since Nordaann convincingly explained the relationship on the. basis of four cases from the literature and two observations of his ow n . The number of cases has greatly increased during the past ten years. According -36- to Wedler (1943), 6 cases (=2 %) of the 29 of asbestosls that were autopsied and published in Germany, showed a pulmonary carcinoma, as did 14 cases (=16%) of the 92 cases of asbestosls that were reported in the whole literature. Wedler included in his figure two cases of pleural endothelioma, arguing that the pleura was involved in the transformation process. In 1947, Boerake studied a collective of almost the same sice and found 17 cases and in 1953, he added two more cases to his one of 1947. Also to be. mentioned are the cases of Weiss (one pleural endothe lioma), Welz, and Werber. In 1950, Merewether reviewed 235 cases of autoptically confirmed asbestosls and determined that 13.2% of these had pulmonary carcinomas. Gloyne contributed 121 cases where 14.1% suffered from a carcinoma. Isselbacher, et al. determined a rate of carcinoma of 13.8% in a group of 603 cases of asbestosis (1953). In groups of living asbestos workers, a cumulation of lung cancers was also determined (Doll 1955). In recent years, Bohlig and Jacob (1955, 1958) have raised objec tions to these statistics. By relating the figures for pulmonary carcino mas from, autoptic statistics to the group of living asbestos workers, they arrived at the conclusion that lung cancer is no more frequent in asbestos workers than in the general mala population. This is a surpris ing finding since Bohlig and Jacob consider the causal relationship between pulmonary asbestosis and bronchial carcinoma as a proven fact. In the very recent past, Bhme has in this archive cast doubt on the general validity of the results of Bohlig and Jacob. He not only used recent figures from the literature, but also studies of his own. In 92 asbestos patients from a certain asbestos plant, who had been continuously -37 examined, six had developed'pulmonary carcinomas in 1959. In 125 cases of asbestosis registered by an occupational! association, Bhme found 15 cases of lung cancer (=12%), 14 of whom have since died. Regarding the.total number of deaths (n = 31), lung cancer with fatal outcome stands at 45%. Of the 20 cases which had been studied pathologicoanatomically, 11 had lung cancer. These figures demonstrate the depend ence of statistical results on the selection of the reference system. In the material of Bohlig and Jacob, 34 patients have died since 1958, . .11 of whom were autopsied. Among these, five asbestos carcinomas were found. We object in principle to the assumption that autoptic material and the living population are comparable collectives. The sources of error inherent in such a situation become evident when one considers the ques tion of the incidence of occupational cancers with a short life and a long latency period, Bhme has indicated this with respect to the asbestos carcinoma. A prerequisite for a comparison is that the groups are distinguished by only one'characteristic. Pathologico-anatonical collectives must also meet this requirement as much as possible. In this light, our collection of cases acquires particular interest. / At 11 of 36 cases (=30.7%), the percentage of carcinomas of the lung and / the pleura in our asbestosis group is higher than was expected in the light of the data in the literature. But a comparison to other statistics appears problematical, because the selection of the groups might be based on different principles as has already been said. But, if we use our general autoptic material from the years 1948 - 1358 (Nassehi) for the comparison and deduct all cases where death occurred before the age of 38- 30 years and all cases of asbestosis, we ratian 13,307 autcpsied cases with 1,018 (=7.8%) pulmonary carcinomas (including pleural endotheliomas). Since 10 of our 36 cases of asbestosis did not belong to the same autoptic material, it appears that sources of error of selection might interfere with equating our whole collection of cases with the group of the above 13,307 cases. In the remaining 26 cases, only 6 cases of asbestosis were clinically known and 4 were suspected. In 3 cases, the asbestosis was the cause of death. There is no argument against con sidering this autoptic group of 26 cases as being representa tive of the general asbestosis group as the simultaneously examined, general autoptic collective with regard to the general population of the area that supplied all of these cases. Among the 26 cases were 9 of lung cancer, i.e., 34.6%. This per centage can likewise not as yet be simply compared to that in the general autoptic material, since the ratio between men and women in the asbestos group was 1:1.9, while it is only 1:0.7 in the general autoptic material. If we examine the rate of lung cancer separately for the sexes, the men in the general autoptic material had 11.6% and those in the asbestos col lective, 44.4% of lung carcinomas. For the women apply, correspondingly, rates were 2.1% and 29.4%. Table 9 gives a survey of these conditions. Regardless of which relationship is selected, it illustrates the increased incidence of cancer in the asbestosis group. This was especially evident for the female sex, an observation that was conceded by Jacob and Bohlig. The large number of pleural endotheliomas that exceeded all expecta tions, confirms the assumption of Wedler. -We also consider our cases as a.sbestosis carcinomas. Although we leave open the question as to the soil \ TABLE 9'. Comparison of the rate of incidence of pulmonary carcinoma in the autoptic material from asbestos is cases and in the. general autoptic material of the Pathological Institute of the St. Georg Hospital, Hamburg. All cases pulmonary carcinoma. pleural endotheliomas All cases in men lunc cancer All cases in women lung cancer i <d -U GJ i c/) *d d -c c o o g 4 J Oe CJ O 4-1 0 ) 4-J u * H CD oC U 4-4 r H CO d o 4 J V ) 4 - i o p <D d C/3 a) d * .c : !--- 1 u 4-J d ?> w CO <rju r --! d 4-J 0) 2 c a o u rCHO H 6 CO LO Ch rH i CO KT Oh tH *- /*%, oCO 4-J aCO o H *H AJ r CO O Cl aj 1C d CE d C' rH V) d -H CO (0 CD r H L O A3J d <D d *H Oh i--i X CJ) d i a CJ CO ^--i GJ -U v T j r d Gh < AJ g i-- 1 CO a) Ch CO C O da Ch rH 4-J CO d- CO <D M H CJ co e C o *H rd o AJ CO AJ CO ccS (D 03 d 3 f'H O rO CO CD> ai-- d AJ CD AJ co r H CO AJ C*-J 0do 13 307 1 OiS 102 7 S17 903 5400 115 ion.o'. 7,i% 0.77% 100,0% 11.6% 100.0% 2.1% 20 100.0% 9 34,6% 4 1:7,4% 0 100.0% 1 44.4% 17 100.0% 5 29,4% 1 30 100,0% 11 30,6% -* 11. 1% 13 100.0% 6 45,2% 23 100,0% 5 21,7% from which the pleural endothelioma came , it St ill appears suf ficient to us for a justification of the occupational relationship that the above is a malignant tumor of the lung surface. It is this area that constitute a site of predilection for the pulmonary reaction, as is indicated by the tendency toward a subpleural densification and the frequency of pleural callosities or indurations in uncomplicated cases of asbestosis. Among the carcinomas listed in Table 9, six were located in the lower lobes, four, were pleural endotheliomas, and one an upper carcinoma (case 26), which because of its location and its close relationship to a tuberculous scar, might also be interpreted as a scar carcinoma. The increased danger of cancer in asbestosis is manifested not only by the rate, of incidence, but also-- in accordance with the concepts of -40- Sc'hinz -- by the shift of the ages at which the patients died toward the younger ages. In our material, the average age was 51.6 years and, thus, corresponded well to the age of 52 years reported by Wedler. Compared to this, Schenck deter-mined an average age of 59 years for the patients who died of lung carcinoma and were autopsied at St. Georg . If one compares the data of Nassehi on the age distribution for lung carcinoma in the autoptic material at St. Georg, during the past 50 years (16-68 cases) to our figures by using summation curves, the proportions are the same (Figure 11). FIGURE 11. Age distribution for lung cancer in 1,668 cases of the general autoptic material of the Path. Inst, of St. Georg Hospital (using the data of Nassehi) and in 11 cases from autopsied patients who had asbestosis. a) general autoptic material, and b) asbestosis autoptic material. But, the hazard cannot be evaluated by using the duration of the exposure, as can be seen from Table 10. There is a certain constancy-- ip agreement with previously published cases-- regarding the period from the beginning of the exposure until death. We would like to call this period the latency period. Our own case, No. 16, is surpassed by one of Owen, where the exposure time was one year and the latency period was 20 years. It also appears that the cancer hazard does not increase with the degree of severity of the asbestosis, as shown in Table 4, which is a -41- * TABLE 10. Comparison of exposure time. and latency period in six cases of asbestos carcinoma. surprising observation. When he studied the files of the occupa- C cLS Q. No. 9 10 13 16 23 30 years Age Exposure Latency time period 53 24 24 47 15 26 39 11 24 45 2-1/2. 23 41 10 24 54 9 18 tional association, Bijhme also arrived at the conclusion that the autopsied. cases had apparently not suffered clearly from more severe asbestos!s, a result that contrasted xxdth the observations made in our ox-m six cases. We shall return to this problem later with consideration of the histo genesis . The male sex appears to be more endangered than the female one. Of the 13 men in our collection, 6 = 46.2% had a lung carcinoma, while of the 23 women, 5 = 21.7% were in the same position. Gloyna also found that a greater hazard exists for men: while in 19.6% of the male patients, a lung cancer was determined, this was the case in only 9.7% of the women. Wedler had already pointed to .this sex distribution. The otherwise already sexual disposition in the case of lung cancer is here clearly demonstrated by the asbestos carcinoma. Of special interest in this connection is that the pleural endothelioma occurred only in female patients. Hera also, a sexual predisposition is evident. For comparison, a look at the lung carcinomas that were autopsied from July 1, 1957 to December 31, 1958 at the St. Georg Hospital: of 133 carcinomas in men, 15 (=11.3%) x^ere pleural endotheliomas; of 29 carcinomas in women, 11 were of this type (=38%). -42- The thought suggests itself that the asbestos carcinoma can in principle not be distinguished from carcinomas of unknown etiology- appearing in the sane location. This is supported by the fact that our material did by no means consist only of squamous cell . car cinomas, as has been practically postulated in the past. Besides large-celled and pavement epithelial forms, there were also transitional types toward small-celled structures or clearly microcellular bronchial carcinomas. Transitions toward large cells or pavement epithelial cells were also observed in small-celled bronchial carcinomas of unknown etiology. Still, the forms that do not consist of small cells did pre dominate in our material. Another criterion of asbestos carcinoma, the multicentric development, is difficult to evaluate by macroscopic, examin ation. The histologically varied pictures could mean just this, with a certain degree of probability in case 9. The site in the lower lobe of the carcinoma that has been emphasized in the literature, was clearly preferred in our material. It was striking, as has already been said, that pleural endotheliomas were so frequent. In two' of four cases, it was limited to the lower lobes. If we look at the group as a whole, the special position that has been assigned morphologically to the asbestos carcinoma is, after all, supported. But, if wa examine only the individual case, then this, special position would be justified only by the fact that we believe we know the etiology through statistical experience. If, according to K. H. Bauer, i< occupational cancers of the various organs cannot be dis tinguished from "spontaneous" cancers of the sane organs, an opinion upheld by Hueck in connection with the Schneeberg lung cancer, the -A3- asbestos carcinoma must gain our very special interest from the view point of general pathology. If we succeed in defining the importance of the exogenous factor, our understanding of the conditions that attend upon the development of pulmonary carcinoma should improve. f) Other carcinomas in asbestosis. The discussion of the relation ship between asbestosis and pulmonary carcinoma should not exclude the fact that among the cases without lung cancer, there were 11 cases of other carcinomas. The high percentage of asbestosis carcinomas in our material, thus, did not come about at the expense of other malignant tumors with a different genesis. Found were: 4 stomach carcinomas, 3 peritoneal carcinomas, one esophageal carcinoma, one of the pancreas, one of the bladder, and one of the sigmoid colon. If we again use the general autoptic material for comparison, as we have done for the lung carcinomas, the data listed in Table 11 emerge. The rate of extrapulmon- ary carcinomas is, thus, relatively markedly raised despite the incidence of pulmonary carcinomas, a situation to which the stomach carcinoma con tributed. - - What, is conspicuous is the number of peritoneal carcinomas. The tumor in these cases was especially strongly developed. The diaphragm was always extended and shot through with proliferations. In one case, the tumor had invaded the right lower lobe on a broad front. We should not dismiss this occurrence of peritoneal carcinomas as coinci dental. The coincidence of two such rare findings suggests a causal relationship. We refer to the case of Leicher. Since it has been proven that a generalization of asbestos particles can occur via the circulation, the suspicion^vo.iced for the first time by Leicher) of an interrelationship -44- TABLE 11. Comparison of the frequency of extrapulmonary carcinomas in the general autoptic material and in .the material of the asbestosis cases of the Path. Inst, of the St. Georg Hospital, Hamburg. i a C r* o 4-4 o o CJ >4 0 ) *r-t 4-1 44 co i--1 - U CJ co co o 0) CO 4-1 CO 44 a 3 cO o c0 a a 0 ft --i i 4J ;-- cO 1 M CO CO 0 -H 4J 3 <*3h S-i CO 01 GH 4-1 C O E CO 1-0 CO --o > T! CO 1 4o--'c c CO CTv CJ r--1 .a CO cO All cases All carcinomas except monary carcinomas Stomach carcinomas Peritoneal carcinomas pul 13307 3135 SO7 1 22 100,0O/'O 23,GOt'o 6,1 % 0,16% c c H AJ Q-. CO o 0 -U CO 3 cO CO a \--! CO m CO CO cn I--1 u -- CO 0 1 { 4o-J G 0 co C O co fcO 4 GT\ 0 0 1--i CD 4-J CO r; cO < 4~1 E 26 100,0% 11 2,3% 4 15,4% 3 11,5% CO 0 G> CO c O (X i--1 cO O h - U CO 0 CO o c cs CO 0 M CJ CO G 6o o H rC u 4-J CO 4-1 o CO CO 0 0 ra P h & CO 0 > 0 c0 V-irG 4-J rH 0 A J U2 CO i--! 4-1 *44 < o CO o n 5 100,0% 11 30,6% 4. 11,1% 3 S,3% receives further support. The question would have to be investigated, with more evidence, whether the rate of extrapulmonary cancers is raised in asbestosis. In view of the present findings, dne should at any rate con sider an increased responsiveness of the peritoneum to a carcinogenic stimulus. One may draw a parallel with the lungs. ,, In examining the case histories, we encountered some problems for which there do not seem to be any solutions as yet. They concern the dis crepancy between the clinical and the morphological picture, the importance of the time factor, especially that of the so-called free interval, for the progress of the lung changes, and of the substrate of the individual disposition. The question of the development of asbestosis carcinoma, whether caused by direct or indirect carcinogenic stimulus, remains 'open for the time being. Such questions lead to the study of the histogenesis of asbestosis. . ? -45- 2 . Histogenesis. Our histological findings in the lungs have essentially confirmed the morphological characteristics of asbestosis which prompted Fahr and Feiglj for example, to speak of a chronic indurating pneumonia, while Lhschcke used the term cirrhosis of the lungs. These are characteris tics which have been described in the detailed studies of Strobe and, especially, Di Biasi. Commenting on a case, Di Biasi wrote: "Judging by the experiences that have been gathered so far and which have again been confirmed by the present case, asbestosis of the lungs consists of interstitial, indurating changes, a diffuse fibrosis of the lungs which involves both lungs, starting at the top and increasing downward." This statement agrees with the radiological findings. But what precedes, this radiologically discernible fibrosis? In view of the findings, the ques tion must be investigated whether the development of the diffuse fibrosis is the pulmonary process, as Nordmann believed: "Thus one must assume a diffuse, chronic irritation that causes the diffuse proliferation of the lungs." At the meeting of pathologists in Kiel in 1949, Nordmann explained that in asbestosis, all of the enormous expanse of the organ offers itself as-a surface for the dust to settle, since the particle size of the asbestos needles prevents the dust5s being dispersed by the lymph tract. In 1949, at the dust lung meeting in MUnster, Siegmund made this distinction: "Where the dust is concentrated, a silicotic granuloma or a silicotic induration develops, but where, as in asbestosis or aluminosis, the inhaled dust particles are diffusely distributed, throughout the lungs, diffuse scleroses are the consequence." The German literature contains some statements that seem to con tradict this opinion and raise the question of whether a diffuse fibro sis exists from the beginning in all cases, or whether, possibly, local reactions at specific points and of another type precede the diffuse one. Nordmann has pointed out expressly that the asbestos lung is fibrous only in parts. In a brief histological description of a case of Wedler, he said that the asbestos particles are found in the bronchi, the alveolar ducts and also in the callous tissue, i.e., that they are not diffusely- distributed. Behrens emphasized the finding of a peribronchial fibrosis. Numerous experiences have been reported in the Anglo-American liter ature. Gloyne and Wood observed in 22 cases that the first histological changes occurred at the respiratory bronchioles and at the alveolar ducts, where mononuclear phagocytes and giant asbestos'cells were found. This was followed by reticular fibrosis. Sparks (.1938) described, the same processes. In experiments with guinea pigs, rabbits, and rats, Gardener and Cummings (1931-1933) had seen that the process began pri marily at the respiratory bronchiole. In the English literature, the respiratory bronchiolus is called the "crucial site" for asbestosis. o The attempt of a chronological analysis of our findings must start with the fact that the asbestos particles are the permanent form of the asbestos needles in the lungs and that they are not diffusely distributed, but deposited at preferred sites. These preferred sites are the alveoli of the respiratory bronchioles and the alveolar ducts. We can confirm the observations of the British authors. Physical, anatomical, and func tional considerations explain that deposition and reaction take place primarily at these sites. -47- Physical reasons: The dust passes through a system of ducts that is long in relation to the lumen. Such systems are suitable traps for dust whose components are needle-shaped or fibrous. The same principle of dust removal is used by the asbestos-processing industry, where air is pumped from the work rooms through long felt hoses along whose walls the dust adheres. The dedusting of the air in the bronchial space takes place along wall areas of different composition of different, design. In the bronchi and in the bronchioles, which are equipped with a ciliated epithelium and mucous glands, the asbestos needles are gripped by the cilia of the mucous layer which then slowly migrates toward the. trachea ("like a rolling carpet," Hayek). In none of my cases have I been able to determine asbestos particles and needles in the walls of these sections of the air passages. Conditions are totally different in succeeding sections, in the terminal bronchioles, respiratory bronchioles, and the alveolar ducts. Here, conditions for catching the asbestos needles are particularly favorable. Because of the widening of the lumina in the area of the respiratory bronchioles and alveolar ducts, direction and velocity of the airstream are changed. The. increasing numbers of needles that are deposited come in direct contact with the epithelium, without a mucous layer and a coat of cilia. But, the distribution is not even" there are cumulations in the alveoli which interrupt the wall of the duct like niches. The negative pressure that develops there during inspiration deflects the airstream that has so far been straight, and turbulences form. The tendency of the needle-shaped particles to deviate in their flight from the longitudinal direction of the bronchioles, is decisively -48- promoted at this point. Thus, these alveoli become the depositories for the dust. The dust that has not been held by the alveoli. of the respiratory bronchioles enters the initial portion of the alveolar ducts and remains there, under the sane circumstances . This explains that only a few, and only the shortest, asbestos needles can be found in the alveolar sacs. Moreover, these dust deposits taka place in a contractile system of tubes. We must anticipate spastic occlusions even in the initial stages of asbestosis. The frequent finding of hyperplastic smooth muscles, also mentioned by D.i Biasi arid others, permits us to conclude such processes. ' An expression of this functional disturbance of ventilation, is the rather diffuse emphysema that is observed in mild cases, a fact that was also pointed out by Eickhoff and Bander, among others. The bronchial spasms presumably force the needles into the tissue. The first functional disorders in the sense of spasms of the bron chioles can, thus, take place in the respiratory bronchioles and the alveolar ducts. The first morphic reaction occurs: fixation of the asbestos needles that are transformed into asbestos particles by giant cells, which wander into the lumen, and by a granulation tissue that leads to a gradual narrowing of the lumen in the sense of an obliterating bron chiolitis. The spear-like nature of the foreign bodies, the shrinking that takes place as a consequence of the fibrous conversion of the granu lation tissue and the walls, and the respiratory movements of the adjoinin free alveolar parenchyma, permit the foreign bodies to enter into the surrounding areas of primary contact. Peribronchiolar fibroses result and a shrinking process again develops. The masses of asbestos particles that lie in this fibrous connective tissue can then be found.after decades without exposure to dust, surrounded by giant foreign body cells in callosities. The consequence of endo- and peribronchial fibrosis is a rigid fixation of the adjoining parenchyma, first in the longitudinal direction of the bronchiolus, which leads to a progressive ventilation v disorder. As a secondary change-- because of the ventilation disorders, which initially show an emphysemal character, but then increasingly turn into a telectases-- there develops a diffuse fibrosis with atelectatic induration and ending -in an obliteration of the parenchyma. The fate of the bronchi in this situation differs. Either they become obliterated because of a progressive obliterating bronchiolitis, or they become dilated, sometimes in connection with the development of small, circumscribed foci of a highly substantive emphysema so that large-chambered systems are formed. In some cases, these show consider able post-infectious, mesenchymal proliferations and processes of rearrangement. 'Epithelial regeneration takes place and presents all transitional forms from regular to metaplastic or atypical epithelium. In. these sections, adenoma-like elements develop with all transitional forms toward carcinoma. But, undoubtedly, .the small bronchiolar lumina, which have remained intact in various segments of obliterated bronchioles, may also provide the. ground for a carcinoma. The concept that a diffuse distribution of the dust requires a diffuse stimuluSjwhich then leads to a diffuse fibrosis, must be abandoned. The -50- diffuse fibrosis develops secondarily, as we have seen, without direct contact with asbestos particles, following a circumscribed, peribron chial fibrosis which stands.in a definite local relationship to the described intracanalicular cumulation of dust. The objection could be raised with respect to the above that dust elements whose size is below the line of visibility, enter the lungs in masses, a phenomenon which Nordnann felt is highly probable. According to Sundius and Bygden, et a l ., however, the fiber must be. of a certain length in order to be able to induce fibrosis. Vorwald, Durban and Pratt also arrived at this position, as 'did Behrens via animal experi ments. The hypothesis of the effect of invisible dust particles can probably be neglected, in our opinion, because the development of the fibrosis can easily be read from visible findings, as is shown b y an examination of the formal genesis. If one examines the process as a vdnole, two phases can be distin guished, as was rightly emphasized by Eickhoff* the phase of the functional and morphic reaction at the bronchiolus and the subsequent phase of the diffuse fibrosis. The first, the bronchiolar phase, already results in the decisive ventilatory disorder. The parenchymatous phase in the form of the. diffuse fibrosis is the second chronological phase. It is not the cause of the ventilatory disorder, but its result. 3. Conclusions from the histogenesis. These histogenetic concepts can contribute to finding the answers to the questions that have arisen from our examination of the material. Thus, they can help explain some peculiarities inherent in the clinical picture and the course of asbestosis. *' -51- a) Referring to the histogenesis, we can understand the discrep ancy that arises between the clinical picture and the radiological and anatomical picture of the disease. The functional and morphological changes at the bronchioles and the alveolar ducts do not appear at all in the radiological picture initially^ and later, they occur as barely recognizable signs. This happens at a time, as was also emphasized by Eickhoff, when the disorder of pulmonary ventilation has already begun to develop, which in turn leads to parenchymatous fibrosis. It is understandable, that the morphological changes one awaits in such cases in order to support the diagnosis, already belong to a relatively late phase of the disease at the time they become radiologicaily visible. Whether the symptoms appear early depends on the intensity of the bronch- iolar reaction. We cannot decide to what extent late symptoms must be attributed to the bronchiolar process or to its sequelae, the diffuse fibrosis. b) In accordance with our histogenetic ideas, the time factor (and thus also the. free interval^is of great importance for the final develop ment of the pulmonary changes. The amount of dust that has been deposited and the time are important factors that determine the extent of the progress of the disease. Our findings indicate that the peribronchiolar induration under the effect of the presence of the asbestos particles does not cease even in the course of decades. This is indicated by fragments, pieces that he.ve separated from the particles, transformations at the gel sheath and rearrangements of the particles in rosette-like structures, all of which _ are typical of old and advanced asbestoses. It. would be difficult to bold that these deposits, which must be considered as oz- typical amphibole derivatives, are irrelevant to the progres sion of the disease. We agree entirely with Beger that the asbestos particles maintain the fibrotic development indirectly via the peri bronchiolar fibrosis, without wishing to belittle the importance of the asbestos needles for the initial processes. The nature of the fibro- genous irritation at any rate requires a long period of time, mid it is possible that besides the mechanical irritation (Sundius and Bygden), a chemical one is added (Beger, Knox, and Beattie). c) The histogenetic concepts also permit a better understanding of the role of individual disposition, as it became evident to us in our material, for example, as different degrees of intensity of the symptoms. If the pulmonary parenchyma were from the beginning affected by the dust over its whole expanse, we would have to settle for those long- discussed factors enumerated in the recent past by Wedler, to which the decisive influence of individual disposition has been attributed. These are the manner of breathing and the removal of the dust by the respective nature and reactions of the upper respiratory paths. The t validity of these ideas has already been doubted, for silicosis by Gessler and for asbestosis by Baader, who examined several hundred asbes tos workers. Wedler likewise was not satisfied with them. If the dust is deposited primarily in the bronchioles and if the first functional and morphic reactions take place in this area, we are inclined to view them as the basis for the Individual disposition. It appears'logical to assume that the reasons for an individual disposition -53- nust lie especially i n .the intensity of the motor reaction of the respiratory bronchioles. The shortness of breath, after all, developed in our cases after six years at the earliest (case 9) so that the first morphic reactions had presumably already taken place. But they are certainly coupled with a bronchioiar spasm of individual intensity, which determines the clinical picture. This spasm, in turn, may again be' an important prerequisite for the transmural expansion of the morphic reaction in the bronchioiar wall. d) The study of the formal genesis of asbestosis also provides us with some ideas relating to the question of the role of asbestosis in the. development of a carcinoma. It seemed justified that carcinogenic properties were attributed to the asbestos particles after it had become evident that carcinomas were frequently associated with asbestosis. The problem was to find out whether the cause was irritation from some foreign body or the effect of a chemical noxa that had dissolved (Baader). Among the most impor tant chemical noxae, Hueper counted the anthracenes, the aromatic amines, tar, arsenic, etc., and asbestos (1950). That this effect could not be bound tc free silicic acid was demonstrated, however, by the experiences gathered, in connection with silicosis (,. . . illegible, Baader, Merevether Vorwald and Karr, Leicher, Ehrhardt, . . , [illegible], Mittmann). Likewise, carcinogenic activities of such metals as magnesium, aluminum, and titanium have not become known, as was determined by Nordmann and . .. . [illegible] . , According to Frank, et al., chryso- tile asbestos contains as an impurity chrome, and nickel. That such admixtures are not of great importance as carcinogens may perhaps be concluded from the fact that in the countries where these asbestos types are. obtained, asbestos carcinomas are not particularly.frequent. The question cannot be answered whether chrysotiles with these impuri ties played any role at all in the histories of our cases. However, such a possibility has so far not been sufficiently considered. It is best to base our considerations of the causal genesis on the concept that the carcinogenesis'is the result of an interplay,of dif ferent complementary factors of various degrees of importance, which all come together and produce the result-- conditionally-- roughly in the sense of a syncarcinogenesis (K. H. Bauer). From this viewpoint, iron must be mentioned. The iron that is determined in the Prussion blue reaction is by itself probably meaning less .regarding the development of pulmonary cancer as is revealed by the brown induration in the lungs. But in a table listing carcinogenic noxae, K. H. Bauer has also listed iron. From,the literature, ws know of the. two cases of Dreyfuss (1936). The patients were siblings who both developed pulmonary carcinomas at the ages of 36 and 44 years. This cancer was related to the inhalation of iron oxide in the youth of the patients (clockmaking as a cottage industry). The only three cases of pulmonary carcinoma among a very large group of radiologically con firmed pneumoconioses (without asbestosis), came from an iron mine (VorwTald and Karr 1938), Otherwise, however, there have been no reports to my knowledge of lung cancer in workers employed in mining iron. In 1940, Campbell was able to induce cancer in animal experiments by iron oxide inhalation. These observations might mean that a combination of various effects of foreign bodies, where the effect of iron is not yet -55- known to us, might create suitable conditions for carcinogens, as has been discussed in connection with a case of pulmonary carcinoma caused by a splinter .of a bullet that remained in the organism (KiJnig) . The documentation that indicates carcinogenic importance of these two conditions are undoubtedly too sparse to justify any binding conclu sions as to a carcinogenic activity of asbestos particles.. A review shows that the hypothesis of a chemical induction of cancer by asbestos cannot be sufficiently supported, a fact that has again been confirmed in the recent past by Behrens (1956). Linzbach felt that the cause for the development of an asbestosis carcinoma lies in the disorder of tissue relationships. Our findings have made it clear that- epithelial proliferations of a regenerative nature can provide the matrix for the carcinoma on the basis of rearrangement processes at bronchi ectases and constricted and dilated alveolar ducts. Sections of the respiratory tract, seem to have been involved, whose epithelium has not had any contact with asbestos dust. The formation of an asbestos carcinoma can thus be explained by Virchow's irritation theory or by the regenera tion theory of Fischer-Wasel. The chronic state of irritation has already been considered by Lynch and Smith a.s the cause of the asbestos carcinoma. Isselbacher, et al. have also held that chronic mechanical irritation is the essential carcinogenic factor. The objection that under such cir cumstances, tuberculosis or silicosis would have to lead to cancer more often, was refuted by Nordmann, who pointed to the fundamental difference of the morphological conditions in asbestosis on the one hand and the above-described pulmonary changes on the other. We must realize that to the diffuse process of asbestosis that spreads over the whole lungs -56- belong innumerable such regenerative foci. 'This makes it understandable, that the probability that at any one of these sites a sudden change takes place that results in an autonomous proliferation of a malignant character is much greater than in lungs where the basis for such a development can lie only in one corresponding focus.. Thus, we approach concepts that apply to the genesis of pulmonary carcinoma as such. The importance of a chronic irritation for the' development of a pulmonary carcinoma,, according to Berkhan, can be recognized by the greater incidence of carcinoma in the right lung. He assumed that as a consequence of the straight course of the right main bronchus, the right .lung inhales more dust than the left. W. Fischer attributed the differences in the incidence of carcinoma to the dif ferent volumes of the right and the left lung and, thus, introduced yet another aspect. The probability of the development of a cancer grows with the increase of a substrate. These general considerations are impor tant for our observation that there is no relationship between the degree of severity of the asbestosis and pulmonary carcinoma. We must count on a quantitative factor, which is constituted by the extent of the process. O We must assume that the chronic state of irritation at the respiratory bronchiole, distributed ubiquitously over the lungs, is sufficient for the growth of a carcinoma. But we must not settle for this exogenous factor. "That we are thus still far from a full understanding of the more complex relationships is a fact that this problem in asbestosis shares with that of carcinogenesis as such" (Wedler). That asbestos is only one factor was also emphasized by Hueper in 1957. -57- Further impulses that still elude our awareness must be assumed. "There are more endogenous and exogenous factors than one can dream of" (W. Fischer). The type of the inhaled asbestos, individual habits, general circumstances of life dictated by geography ate, as far as can be judged, just as important participating factors as dispositional individual ones, which need the outside stimulus in the sense of a pro liferative stimulus of sufficient duration, intensity, and, perhaps, type, in order to lead to cancer. At the 28th meeting of pathologists, Fischer-Wasel said, "Only if the. typical special general disposition, the general readiness for cancer, is added, can a regenerative prolifer ation form the beginnings of a tumor, a malignant tumor." We refer in this context to the noteworthy sexual distribution of the asbestos car cinoma in our material, which corresponds to the general sexual disposition toward pulmonary carcinoma. 4. Conclusions resulting for the evaluating physician. The findings presented above and their interpretation seem to bring us closer to the answers to some questions, particularly clinical ones and those that concern the genesis of the asbestosis carcinoma. Thus they may also acquire some importance for occupational medicine, indivi dual prophylaxis and medical opinions. The discrepancy between the clinical picture in.its subjectivity^ and the radiological (clinico-morphological) finding, creates a difficult situation for the .physician who must give an opinion. Any expert opinion will always seek an objective foundation for the classification of the severity of a disease^. and will strive to express its judgments in a standardized manner in order to be generally under-, standable to the extent that the measur-e of help needed by the patient-- -58- be it prophylactic, therapeutic or social in nature-- can be determined. I refer to the classifications of Kruger, P<.ostoski and Saupe, Lanza and Buresch. Any critique of such an endeavor leads one to the recog nition that a determination of degree cannot do justice to the clinical and radiological and pathologico-anatomical facts (Winkler). In his last communication on pneumoconioses, Gloyne wrote that all attempts at classifying pulmonary changes have failed. They had to fail as long as one tried to correlate the severity of the clinical picture with the radiological one. Therefore, for example, it is not permissible to grant workmen's compensation only at the time when "the connective tissue transformation, the fibrosis of extensive parts of the pulmonary tissue with a cessation of their function for respiration and circulation" have been proven (Boemke). The preceding, long-lasting clinical disorders can then conceivably be neglected as warning signals and early indicators of asbestosis. In 1959, at the dust lung meeting at Miinster, Jotten stated: "The functional examination is today, in contrast to the'past, considered to be much more decisive than the radiological picture, which should be evaluated only as a criterion." The 5th regulation on occupa tional diseases of February 26, 1952, has largely taken this new concept into account. Since the morphological"examination of comprehensive autoptic material that contained pulmonary changes of all phases has shown that the pulmonary process is initiated by the functional and morphic reactions at the respiratory bronchiole and also that the fate of the further course is already decided in this bronchiolar phase, we wish to raise the question -59 alarming symptoms. This development can be ascertained at. a time when there is not yet a sufficient radiological indication. In conclusion, I wish to refer to the findings of carcinoma. The greater danger of carcinoma that threatens the asbestos lung in the central European area can^in our opinion be considered to be largely factual. The retreat to a "in dubio pro aegroto" (Oettel) does not seem necessary if one uses comparable samples from the central European region as a foundation of judgment. Pleural endothelium, can also be included among asbestos lung cancers. A case from the literature (Leicher) , a cumulation of cases in our material and the proof that a hematogenous generalization of asbestos particles is possible, raise the question of whether the peritoneal carcinoma in asbestosis is to be recognized as a complication of asbes- tosis and, thus,.as an indemnifiable occupational disease. SUMMARY 1. This is a report on 36 cases of asbestosis which were examined at the Pathological Institute of the General Hospital St, Georg in Hamburg. Data on asbestosis as a disease of civilization, on asbestos, its processing, on the dust and the intrapulmonary asbestos particles, as' they are needed for a general understanding, precede the. report. 2. Tables list the histories and most important clinical and autoptic findings. The macroscopic and microscopic findings of the lungs and the regional lymph nodes are described. A brief report follows on the findings which indicate a hematogenous distribution of the asbestos, particles. 3. The autoptic material, stemming from 13 male and 23 female patients, includes all morphological degrees of severity of asbestosis. -61- In 7 cases, the asbestosis was presumably the main disorders in another 11, a carcinoma was found, 4 of which were pleural endotheliomas. In 18 cases, the chief disorders were other conditions. In a number of cases, the asbestosis was recognized only at autopsy. 4. The opinion held in Germany^ that the diffuse effect of dust on the respiratory parenchyma in its totality leads directly to a diffuse fibrosis, cannot be confirmed. Rather, most of the dust is deposited in the respiratory bronchiole, as has long been described by British authors. The functional and morphic reactions at the bronchiole introduce the first phase, which we would like to call the bronchiolar one. It leads to peribronchiolar fibrosis. The rigid fixation of the elastic parenchyma begins the second, parenchymatous phase, which finally leads to diffuse fibrosis. Besides an obliterating bronchiolitis, bronchiolec tasLs also develop. Under the conditions of post-infectious states of irritation and functional losses, considerable processes of epithelial regeneration get..under way and these,are the prerequisite for the development of a pulmonary carcinoma. " 5. The knowledge of the histogenesis moves us close to answers con cerning some problems of asbestosis. a) The discrepancy between the severe clinical picture and the more or less negative radiological picture can be explained through the peculiarity of the bronchiolar phase. The functional disorders in this phase may be considerable, while there still need not be any radiological symptoms. Unelucidated remains the discrepancy that can exist in the parenchymatous phase between a sparse symptomatology and a more or less marked morphological finding. -62- b) The degree of severity of pulmonary changes depends not only on the exposure time and the (mostly unknown) dust concentration at the work place, but also on the time. The histological findings make it probable that the disease progresses gradually even during the course of the free interval. c) A substrate of individual disposition can be seen in the respiratory bronchiole. The intensity, differing from one case to the next in the functional and morphic reactions that influence each other, determines the clinical picture and the time frame of the pro gression and, thus, it also affects the degree of severity of the lung changes. 6. The opinion voiced during recent years that pulmonary carcinoma is no more frequent in asbestos workers than in the general population, is contradicted. Of 13 man in our sample, 6 (= 46.2%) and of 23 women, 5 (= 21.7%) showed a pulmonary carcinoma (or a pleural endothe lioma). If we consider, in the interest cf a statistically acceptable comparison, only the cases seen at the St. Georg Hospital among the autoptic material between 1948 and 1958, the higher expectation of can cer compared to the. general autoptic material during this period becomes quite clear: in the men at the rate of 44.4% (compared to 11.6% in the general autoptic material), in the women at'29.4% (compared to 2.1% in the general autoptic material). Among the 11 lung carcinomas were 4 pleural endotheliomas. The average age at the time of death and. the duration of the latency periods agreed with the data in the literature. There was no relationship in our material between pulmonary cancer and the degree of severity of the pulmonary changes. This appears understand able if one considers the histogenesis. - 63~ 7 The percentage of extra-pulmonary carcinoma was likewise raised. Stomach carcinoma occurred at the rate of 11.1% (or 15.4%, related to the asbestosis autoptic material from 1948 to 1958), compared to 6.1%. The suspicion, voiced by Leicher, of a relationship between peritoneal carcinoma and asbestosis was supported by our findings, since three peritoneal carcinomas were found in our material, i.e., 8.3% (or 11.5%, related to the autoptic material with asbestosis from 1948 to 1958), compared to 0.16% in the general autoptic material. 8. The conclusions to be drawn from our results for the authors of medical expert opinions are discussed. In view of the difficulty of reconciling the clinical and radio logical pictures, it Is proposed that a distinction be made between asbestosis and asbestos lung. BIBLIOGRAPHY Alwens, W . : On pulmonary asbestosis. Munch, med. Wschr. 1935, 1797. Annotations: Lung cancer in Asbestos. 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Beattie: Mineral content of the lungs after expo sure to asbestos dust. Arch, i'ndustr. Med. 10, 23 (1954). Knox, J. F,, and Beatti: Distribution of mineral particles and fibers in the lung after exposure to asbestos dust. Arch, industr. Med. 10, 30 (1954). - 68- Knig, J.: The histogenesis of pulmonary asbestosis. Proc. 2nd Sei. Meet. Pathol. Northern Germany, 1951. Ref. Zbl. allg. Path, path. Anat. 88, 220 (1952). Knig, J.: Lung carcinoma caused by an indwelling bullet splinter. Zbl. allg. Path. Path. Anat. 88, 271 (1952). Krusler, J., and P. Seyss: Early diagnosis of asbestosis using greatly enlarged x-ray pictures. Z. Unfallrned. Berufskr. 47, 59 (1954). Kruger, E . , 0. Rostoski and E. Saupe: Pulmonary asbestosis. Arch. GewerbepatVi. Gewerbehyg. 2, 558 (1931). Lanza, A. J.: Asbestosis. J. Amer. med. Ass. 1936, 368. Leicher, F.: Primary pavement cell tumor of the peritoneum in asbes tosis. Arch. Gewerbepath. Gewerbehyg. 13, 382 (1954). Linzbach, A. J., and H. W. 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Nassehi, P.: On pulmonary carcinomas with special consideration of netastases in the brain and adrenals. Thesis, Hamburg 1958.. Nordmann, M.: Occupational cancers in asbestos workers. Z. Krebs- forsch. 47, 288 (1938). Nordmann, M.: Pulmonary asbestosis and cancer. Report, 8th Intemat. Cong. Accid. Med. & Occup. Dis., Frankfurt/Main. Leipzig: Georg Thieme 1939. t Nordmann, M.: Occupationally acquired pulmonary fibroses. Proc. Germ. Path. Soc., 33rd Meeting, 1949. Stuttgard: Piscator 1950. Nordmann, M . , and A. Sorge: Lung cancer induced by asbestos dust in animal experiments., Z. Krebsforsch. 51,. 168 (1941). Noro, L.: The histology of asbestosis. Acta path, microbiol. scand. 23, 53 (1946). - ' Oettel, H . : The problem of occupational cancers caused by chemical agents. Proc. Germ. Path. Soc., 43rd Meeting, 1959. Stuttgart: Piscator. 1959. Owen; Carcinoma and asbestosis of the lung: Report of a case. Brit. J. Cancer 5, 382 (1951). / Ruska, H.: Microscopic studies of asbestos dust and asbestos lungs. Arch. Gewerbepath. Gewerbehyg. 11, 575 (1942). Sc'nenck, S.: The increase of lung cancer in the "autoptic material of the General Hospital St. Georg Thesis, Hamburg 1951. -70- Schinz, H. R., and Th. Reich: Changes in the cancer hazard in Eng land, Wales, and Japan. Dtsch. med. Wschr. 1959, 1328. Siegmund, H.: The fate, of the lungs and respiratory tract after inhalation of various types of dust. In: Dust lung diseases. Darmstadt': Steinkopff 1950. Sparks, J. V.: Pulmonary asbestosis. Radiology 17, 1249 (1931). Sparks, J. V.". Some further observations on pulmonary asbestosis Brit. J. Radio. 5, 75 (1932). Sparks, J. V,: Asbestosis. Brit. J. Radiol. 11, 371 (1933). Stroebe, H. : Report on a case of pulmonary asbestosis that provided the basis for the study of Prof. Beger. Virchows Arch, path. Anat. 290, 354 (1933). Sundius, N., and A. Bygden: The dust content of an asbestosis lung and the consistency of the so-called asbestosis particles. Arch. Gewerbepath. Gewerbehyg. 8, 25 (1938). Vorwald, J. A., Th. M. Durban and ?. C. Pratt: Experimental studies of Asbestosis. Arch, industr. Hyg. 3, 1 (1951). Vorwald, A. J., and J. W. Karr: Pneumoconiosis and pulmonary carcinoma. Amer. J. Path. 14, 49 (193S). Wedler, H. W . : The clinic of pulmonary asbestosis. Leipzig: Georg Thieme 1939. Wedler, H. W . : On lung cancer in asbestosis. Dtsch. Arch, k lin, Med. 191, 189 (1943). Wedler, H. W . : Pulmonary tuberculosis in asbestosis. Leipzig: Johann Ambrosius Barth 1947. -71- Wegelius, C.: Changes in the lungs in 126 cases of ashestosis observed in Finland. Acta radiol. (Stockh.) 28, 139 (1947). Weiss, A.: Pleural cancer in pulmonary ashestosis morphologically confirmed in vivo. Medizinische 1953, 93. Welz, A.: More observations on the occupational cancers in asbesto- sis workers. Arch. Gewerbepath. Gewerbehyg. 11, 536 (1942). Werber, M,,: Pulmonary asbestosis and carcinoma. Zbl. Arbeitsmed. 2, 179 (1952). Winkler, A.: On a classification of the nomenclature of the dusts arid the organicchanges caused by dust. Munch, med. Wschr. 1955, 1114 Wood, W. B., and S. R. Gloyne: Pulmonary asbestosis. Lancet 1930y 445 Wood, W. B., and S. R. Glyone: Pulmonary asbestosis complicated by pulmonary tuberculosis. Lancet 1931 II, 954. Wood, W. B., and S. R. Gloyne: Pulmonary asbestosis. Lancet 1934 II, 1383. (Author's address:) Joachim KBnig, M. D. Hamburg 34 ir Rennbahnstr. 22 -72- r** u K 8 ;; RV I'' if g I pvt. % / 1 5 8 W . E r s i i s c h , G. H a y d n und H . W T t t g e x s : Lrmschden und Lrmschutz J a n k o w s k i, W .: Deterioration of hearing in industrial workers. Med. Praey 3 1 ^ (1952). K l e y , W .: ber die Schwerhrigkeit whrend und nach intensiver Lrmeimvjr. kung. Arch. Ohrenheilk: 156. 471 (1949/50). K l e y . W.. u . R. Z i s s i . e e : Untersuchungen ber das Hren im Lrm. Z. 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T s e M jO S , C. 0 .: Deafness due to vitamin A deficiency. Cyprus med. J. 5,876 (1952). Wheeler. D. E.: Detection of noise susceptible ears. Laryngoscope (St. Louis) 59, 1328 (1949). Willemse, Ch. : Protection contre la surdite professionelle. Role de la vitamine A. Acta oto-laryng. (Stockh.) 6, 319 (1952). WIT T G E N S , H .: Untersuchungen ber Lrmarbeiten und Lrmschutz bei der Deutschen Bundesbahn. Berufsgenossenschaft H. 1, 3 (1953). Z w iS L O C K lj J . : New types of ear protectors. Zit. nach Excerpta med. (Amst.), Sect. X I 6, 1297 (1953). Dr. m e d . H. W it t g e n s , Arbeitsschutzarzt der Deutschen Bundesbahn, Frankfurt a. M., Karlstrae 4--6 fr Gewerbepathologie und Gewerbehygiene 18, 159--204 (I960) MM , -i> vp- us dem Pathologischen Institut des Allgemeinen Krankenhauses S|t. Georg in Hamburg (Prosektor: Prof. Dr. J. H e in e ) ber die Asbestose* Von J. K nig, H am burg Mit 11 Textabbildungen (Eingegangen am 22. A pril 1960) E in leitu n g 1951 k o n n t e Knig a u f d e r T a g u n g d e r n o r d w e s t d e u t s e .ie n P a t h o logen an H a n d v o n 16 F llen d es P a th o lo g isch en In stitu tes; S t. G eorg, H a m b u r g , b e r d ie Histogenese der Asbestose u n d d e s A s b c ,t o s e - C a r c inom s in der L un ge b erich ten . D ie U n tersu ch u n gen w aren d adu rch gefrd ert, d a d ie b eo b a ch teten F lle b erw iegen d n ich t m it ein er A sb estose als H au p tleid en zu r S ek tion gek om m en w aren . In e: rem gro en T eil d er F lle w u rd e d ie A sb esto se erst b ei d er p a th o lo g isch -a n a to m i schen U n tersu ch u n g a u fg ed eck t. D ieses so geartete, M aterial ist in zw ischen au f 36 F lle an gew ach sen . E s b ietet ein ig e der k lin isch errterten P rob lem e in d er S ich t d es P a th o lo g en . S ie k n n en au f G ru n d der v ertieften K en n tn isse d er H isto g en ese ein er L su n g m .h ergeb rach t w erden. D esh alb glau b en w ir u n s zu ein er V erffen tlich u n g verp flich tet. D ie A sbestose als Z ivilisa tio n sk ra n k h eit A n gesich ts d er S elten h eit d er A sb estose ersch ein t es zw eck m ig, z u r E in f h r u n g k u r z e A n g a b e n b e r ih r e B e d e u t u n g a ls Zivilisations k ran kh eit, b er ihre E n tsteh u n gsb ed in gu n gen u n d ber den A sb est vorau szu sch ick en . Wann die Asbestose zuerst aufgetreten ist, wissen wir nicht. -- Als feuerfestes, verspinnbares Material bereits im Altertum verwendet und beschrieben 'fC o o K E 1924, ausfhrliche Darstellung bei F r a n k , 1952), wurde Asbest doch erst seit der Mitte des vorigen Jahrhunderts im Sinne der modernen Industrie verarbeitet. Die wichtigsten Produkte sind It-Platten, Asbestpappen, Asbestzementplatten und -rhren, Bremsbnder und -belge, Dichtungen, Packungen. Filter und Dichtungsmaterial bei Suren. Die moderne Technik ist ohne den Asbest nicht denkbar. Die Asbestose wurde zuerst in England beobachtet (M o n t a g c e M u r r a y 1900), dann in Kanada (1912, W e d l e r ) und in Deutschland ( F a h r u n d F e ig e 1914), Das eigentliche Schrifttum der Asbestose begann in England 1924 (C o o k e ). 1927 erschienen zahlreiche englische und sdafrikanische Arbeiten; 1930 wurde in England die Asbestose als Berufskrankheit anerkannt. 1951 gab G l o y n e einen*1 * Herrn Prof. H e in e in Dankbarkeit und Verehrung zum 35. Geburtstag. 1 11* / s?' ; \ \\ Tabelle 2. bersicht ber die Flle mU bekannter beruflicher Vorgeschichte E x p o sitio n sz cit Freies Lfd. N r. S Nr. A lter Ge schlecht Dauer In te r vall Datum in in Jahren Jahren 1. Symptome Datum Jahre vor dem Tod K linische Diagnose R ntgen befund ;i 1016/39 63 4 1999/39 41 6 G 2053/41 59 9 491/48 53 10 835/48 47 11 993/48 49 12 436/50 75 13 823/50 39 14 227/51 61 15 276/51 55 ? 1916--1933 17 ? 1918--1930 12 <f V 15 <? 1924--1948 24 <? 1922--1937 15 $ 1927--1933 6 cJ 1 30 $ 1926--1937 11 ? 1907-- 1912 1927-- 1930 !} 9 1925--1930 5 6 invalidisiert 6 wegen Asthma 1933 9 Bronchitis 1930 9 9 9 -- 0 1930 18 li 1935 13 15 vor 1947 9 ? ? -- 13 1935: Asthma 15 im Anschlu an Erkltung 15 1938: Bronchitis 13 21 (Asbestkrper chen im Aus wurf) 21 1950 1-- 2 Verdacht 1939 negativ 1933 verm utlich p o sitiv ja p o s itiv 70% Invaliditt vermutlich 1938 1938 30% Erwerbs positiv w minderung OUi: (,,Silikose") 0 1937 1947 positiv 1948 nein positiv, aber keine Diagnose bis 1949: nein, 1949: negativ, 1950: Verdacht 1950: Verdacht sicher seit 1938 9 noin 1 positiv, ahor 1 U i 'i t n Dirt^nofw 16 567/51 45 ? 1928--1931 **/. 20 1950 1 nein, obwohl vermutlich berufliche negativ Anamnese bekannt 17 630/51 44 ? 1928--1935, 2 ? Verdacht wegen beruflicher vermutlich negativ etwa 1941-- 1949 s }15 Anamnese 20 851/52 60 $ 1910--1917 7 35 1951 1 nein V 22 923/52 59 $ 1946--1952( ?) 6 0 vermutlich keine -- nein -- 9 23 198/53 41 <s 1929--1939 10 14 LwuenggeennfTbrscoargbe 14 nein vermutlich 05 negativ 4 Bt 1939 24 967/54 45 <? 1928--1936 8 18 29 1318/55 55 3 1937--1955 18 0 keine 1952 -- 2--3 nein nein er 30% Erwerbs 1944,1951,1953: CO minderung 1955 negativ, 1955: positiv 30 1428/55 54 3 1937--1946 9 9 1952 2--3 1955 Verdacht wegen beruf licher Vor geschichte negativ 31 1493/56 72 9 ? 25 ? 1956 10 Wochen Verdacht, Ein 1956: Verdacht weisung wegen ,,Staublunge" 34 393/57 47 1928--1932, 15 1950 ? 1947 3* 9 7 1950 vermutlich positiv oCn r*T * rV *J, '-*7Y -r-i -1-* Him-**- ; ' *- * ; .`V *' rw -f? j ir ^ *?>' *' -:*.<r;ut^mmtrni ... ...... :,.... -V-, J 1 ' Wt* 166 J.K mig: ber die Asbestose 167 Tabelle 3. bersicht ber die Flle mit unvollstndiger Vorgeschichte Z S Nr. Alter Ge 1. Symptome schlecht Datum Jahre vor Klinische Diagnose dem Tode Rntgen. befund Tabelle 4. bersicht ber die wichtigsten Sektionsbefmde Orad der Asbestose: 1 = gering, 2 = mittelschwer, 3 = schwer (Nheres s. ' Qra(j der Anthrakose: -- = in der Sektionsdiagnose nicht erwhnt; mig '"alle Flle, die in der Diagnose nicht ausdrcklich als schwer, stark usw. hervor- .rboben sind. ______ 1 G 209/39 46 2 G 2110/39 55 5 2076/39 52 7 G 1665/48 48 8 109/48 67 18 15/52 46 9 1935: ,,Lungen leiden" 9 9 9 keine 2 9 OA 1928 (?): trockene Pleuritis 9 1928: Kur, 1940: Pleuritis 4 - - -- 20 ( ?) 24 12 14 Tage vor dem Tode positiv S r - !:.m.! H auptleiden Todesursache 9 9 1 Emsendungsgut (vermutlich schweainhlrich -- EmAssebnedsutonsges)gut nein (vermutlich ja -- Asbestose) nein Ansebgeasttoivse b I nein seit 1928 I nein ,,Ver I schwartung" Tuberkulose, R echtsinsuffizienz Asbestose- G rad ver mutlich 3 ver mutlich 3 19 248/52 62 21 852/52 79 25 1051/54 60 26 1122/54 56 27 558/55 52 28 879/55 63 32 15/57 61 33 296/57 57 35 1063/57 65 36 1089/57 77 O keine -- nein 9 vermutlich -- nein keine S Asthma, 9 nein Datum ? O keine -- nein ? 9 -- nein 1955 10 Wochen nein 9 nein -- nein 9 nein -- nein S 9 -- nein Ofi 1953: ,,Em 4 nein physem (46?) bronchitis" angeblich schon ein mal vor 46 Jahren nein -- vermutlich negativ negativ ? -- negativ negativ negativ positiv aber keine Diagnose Asbestose, Rechtsinsuffizienz Sepsis Lungencarcinom (Einsendungsgut) Einsendungsgut (vermutlich AsbeBtose) Tuberkulose, Lungenembolie 2--3 2--3 Lungencarcinom erk en n en , d a d ie A sb estk rp ereh en d ie A lv eo len vollk om m en aus sto p fen . S ie lieg en w irr d u rch ein a n d er, m eist ziem lich d ich t. Z w ischen sie sin d M a k r o p h a g e n u n d R ie se n z e lle n e in g e d r u n g e n , o d e r e s lie g t ein G ran u lation sgew eb e vor, d as in fein ster A u fsp litteru n g d as H ufchen d u rch d rin gt u n d ein zartes G itterfasern etz b ild et (A b b . 4). D ie A sbest k r p e r c h e n s i n d g e l e g e n t l i c h --- b e s o n d e r s i n d e n S c h w i e l e n -- r a d i r g eo rd n et, d era rt, d a d a s k n o p ff rm ig v er d ic k te E n d e peripher lieg t (A b b . 5). D ie A lveorlarw an d k an n tro tz n ich t u nb etrchtlicher 10 Lungencarcinom ir Magencarcinom 12 Hydronephrotische Schrumpfniere, Urmie 2--3 L u n g e n c a rc in o m Lungentuberkulose Antk ra - koseG rad Starke Verschwie lung der Oberlap pen, des Mittel lappens und der apikalen Abschnitte der Unterlappen. Erischere Verksun gen im re. Unter lappen, Pleuritis re. li. Unterlappen li. Unterlappen mit diffuser Infiltra tion, knotige Metastasen im re. Unterlappen re. Unterlappen, Einbruch in das Mediastinum Indurierende Tuber kulose im re. Ober lappen mit einzel nen exsudativen Herden. Empyem 1000 cm3, Kaverne und chronische Pneumonie im re. Unterlappen mig stark stark Schiefrige Indura tion des re. Ober lappens 168 J. K nig: 1 ber die Asbestose 169 Tabelle 4 (Fortsetzung) f Tabelle 4 (Fortsetzung) Lfd Nr Hauptleiden Todesursache As bestose- Lungencarcinom Lungentuberkulose . Grad 13 Pleura endotheliom 3 ber dem re. Unterlappen, ausgedehnte Aus breitung auch im re. Unterlappen 14 Asbestose 2 _ _ Glomerulonephritis, 3 Urmie 16 Pleura 2 ber der li. Lunge, -- endotheliom ausgedehnte Ein brche subpleural und im Hilus 17 Peritoneal careinom 18 Peritoneal- carcinom 19 Harnblasen carcinom, Urmie 20 Magenearcinom, Herzinfarkt 21 Kardiaearcinom 22 Oesophagus- carcinom 23 Lungen oarcinom 2--3 i __ _ i -- Karnifizierende und vernarbende Spitzentuberkulose beider Oberlappen mit Kreideherden i -- -- i -- Kreideherd im re. berlappen i re. Unterlappen Chronisch-cirrhoti- sehe Spitzentuber kulose bds. mit kleinsten Kavernen 24 Lungenembolie 3 nach Harnrhren verletzung -- Schiefrige Spitzen narben bds 25 Asthma bronchiale, 1 Rechtsinsuffizienz -- Spitzennarben in beiden Oberlappen 26 Lungencarcinom 1 li. Oberlappen Schwielige Spitzen innerhalb einer tuberkulose mit tuberkulsen frischen Ver Verschwielung ksungen 27 Pleura ver ber der re. Lunge -- endotheliom mutlich 1 Ay." thru. ko*? GfU stari r1 k Iv mi r ? ma,. - mi. " stark mi: ?. mi: 1 f ; stark $ k mi: ^ stark i i stark * | . s mig . S mi? | | Hanpt leiden Todesursache As bestose- Grad Lungencarcinom Lungentuberkulose A ll" tliriikoseGrad & PerTitounbeearlkcualrocsien,om, wohl 3 Herzinfarkt at Pankreascareinom ;o ---L--ung"encarci:nom :>i Asbestose 2--3 2 3 > Pleura- 2 endotheliom 33 Carcinom des 2 Colon sigmoid. :i4 Dermoid des li. 3 Ovars, Magen- eareinom 35 Lungenoarcinom 1 % Asbestose 3 -- li. Unterlappen bds.. besonders re. Unterlappen -- -- li. Unterlappen, Ausbreitung in Pleuraschwarten bds. -- Chron -kavernse Tuberkulose beider Lungen, karnifizie rende Pneumonie im li. Oberlappen. frische. Streuung -- -- Alte indurierende Tuberkulose mit frischer Aussaat -- ' stark stark mig stark -- mig -- mig Schiefiger Spitzen- stark herd re. -- stark Ansammlung noch ziem lich zart sein. M eist ist sie aber verdickt und M1.1cmzeImT g. limJVMi Lj. i*ierJt.. B ron ch iolu s und D uctus a lveo la ris sind oft nur andeutungsw eise zu ernennen, w enn sicn ein ivieinzemg u n n tn eives vxtjiiiuictnuiigevveue m der Sch leim h au t en tw ick elt h a t und fibrs wird. H ierbei w ird die Lichtung eingeengt und die vollgestopfte A lveole von der Lichtung abgeschnrt, so da kom pakte Hufchen von Asbestkrperchen vllig isoliert in schw ielig um gew andelter Bronchiolenw and liegen knnen (Abb. 3). D ie L ichtung, so w eit sie in diesen A b sch n itten noch vorhanden ist, ist von Schleim haut en tb l t und en th lt einzelne A sbestkrperchen und reichlich desquam ierte M akrophagen. D a s G ranulationsgew ebe dringt in die zellerfllte L ich tu n g vor. E s zeigen sich B ilder einer Bronchiolitis obliterans (Abb. 4). Sowohl in den Bronchiolen als auch besonders deutlich in den D u ctu s alveolares finden sich erhebliche Verdickungen der glatten M uskulatur (Abb. 1 und 2). Sie sind selb st im Schwielengewebe teilw eise noch deutlich nachweisbar. Durch den Anbau von fibrs-kollagenem , zur H yalinisierung neigendem M aterial in den lockeren p e rib ro n c h io l re n B in d e g ew e b ssch ic h te n ist tpisipwr*1 182 J. K n ig : d ie F lle 4 , 10, 13 u n d 29 d ie A n n ah m e, d a in d en F llen m it kurzen E xp osition szeit verh ltn ism ig m ehr S tau b au fgen om m en w urde ] d e n F lle n 1 1 , 1 5 , 2 4 m s s e n w ir d a g e g e n a n n e h m e n , d a d ie in rjrela tiv k u rzen E x p o sitio n szeit au fgen om m en e S ta u b m en g e n ich t au reich en d w ar, u m in b ald iger F olge S ym p tom e zu verursach en b eein flu te ab er ein en p rogred ien ten P roze vo n sch leich en dem Charat ter, d er w eit in d as freie In terv a ll, d . h. in d ie Z eit v o m E n d e d er E xpo t i o n b i s z u m T o d e , r e i c h t e . D i e B e d e u t u n g d e r Z e i t f r d ie E n t w i c k l e '., d es L u n gen p rozesses w ird a n d iesen F llen b eson d ers augenscheinlid, Tabelle 7. Vergleich von Expositionszeiten mit der Zeitdauer vom Beginn der Exposition bis zum'Auftre ten erster Symptome bei Fllen mit schwerer Asbestose Ex 1. Symptom. F all positions Jahre nach Freies Bauer der zeit Beginn der E x p o sitio n In te rv a ll gesam ten Anamnese 13 h 9 13 24 4 12 12 9 21 10 15 13 11 26 29 18 15 0 18 11 6 e tw a 19 15 21 15 5 etw a 25 21 26 24 8 -- 18 26 D ie Unterschiede jr, d er R e a k tio n d es E ie. ze lfa lle s, seie n sie zeit, lich er, seien sie quaiiti. ta tiv e r N a tu r, sind aber sich er n ic h t allein auf d ie U n te r s c h ie d e der (n u r zu m T eil bekannter, od er abschtzbaren: exogen en F ak toren zu r c k z u f h r e n . Zud iesem E rgeb n is k om m en auch der M itw irk un g ein er in dividuellen D is p o s itio K n knaonxn unn di cBhEt AgTe Tz wiEe i.f eAlnt w e r d e n , w e n n a u c h i h r e B e d in g u n g e n n o c h u n g e k l r t s i n d (Baadib. zWu en dg ldeire s).e s DF iaek tao nr sa mn inc ehstt ias cu hs .e n U n t e r l a g e n r e i c h e n fr d i e A b s c h t - E in e ein geh en d ere B etra ch tu n g d er A rt u n d d er E n tw ick lu n g des L u n gen p rozesses k an n sich also letztlich n u r au f d as L un gen b d und se in e z e i t l ic h e O r d n u n g s t t z e n , d . h . a u f d a s S t u d i u m d e r Histogenese. d ) W eich e L u n gcn b cfu n d e von allgem ein er B ed eu tu n g sind in unseren 1 allen m it d er A sb estose zu stzlich k om b in iert? M ischp neum okon iosen im en geren S in n e liegen in u n serem M aterial n ich t vor. E in F all nur w eist h isto lo g isch k le in e h y a lin e S ch w ielen , d ie V e rd a ch t a u f Silikose e r w e c k e n , a u f. D ie V e r te ilu n g d e r Anthrakose a u f u n s e r e F lle g ib t T ab elle 8 w ied er. D an ach zeigen d ie M n n er h u figer ein e schw ere A n th rak ose als d ie b rau en . D er S ch w eregrad d er A sb estose geh t dem d er A n th rak ose n ich t p arallel. < Tuberkulse Vernderungen w u r d e n i n 1 2 F l l e n g e f u n d e n . In 7 F llen h an d elte es sich u m ltere, w eitgeh en d ab geh eilte Prozesse, d ie m eh r od er m in d er d ie ap ik alen O b erlap p en ab sch n itte betrafen- In d ieser G ru p p e w ar d er A n teil d er F lle m it leich ter A sb estose un v e r h ltn is m ig g r o (n = 5 ). I n w e ite r e n 3 F lle n fa n d e n w ir- ein frische S treuu n g, zw eim al (F all 8, 31) b ei ein er in d u rativen T uber- ber die Asbestose 183 , [oib e r O J b e r la p p e n , e in m a l ( F a ll 2 8 ) b e i e in e r d o p p e ls e it ig e n k a v e r - *!! * T u b erk u lo se. In d en r e stlich en 2 F lle n b esta n d ein e frisch ere _ e T u b erk u lose, im F a ll 26 in b eid en L u n gen , im F a ll 3, d er ein e 's-irke V ersch w ielu n g b eid er O b erla p p en ze ig te, im rech ten U n terla p p en . H d iesen 5 F llen n och a k tiv er T u b erk u lose zeig ten zw ei (F all 8, 26) qie leich te , ein er (F a ll 3 ) ein e m ittelsch w er e, u n d zw ei (F a ll 2 8 , 31) `!in e s c h w e r e A s b e s t o s e . I n d e n F l l e n 3 , 8 u n d 2 8 w a r d ie T u b e r k u lo s e w ah rschein lich w esen tlich a n d er T o d esu rsa ch e b eteilig t. D a s S terh e- dter b etru g 63, 63 u n d 67 Jah re. In d en b eid en b rigen F llen w ar ,, i n m a l d i e A s b e s t o s e Tabelle 8. Die Beziehung zwischen dem Schweregrad Fall 3 1 ), d a s a n d ere M al der Asbestose und der Anthrakose ,.j,, X a r b e n ( ? )-C a rcin o m Schweregrad der A nthrakose der L un ge (F all 26) die T o d e su r sa ch e; d a s Ge schlecht Schw ere - grad der A sbestose leicht m ittel schwer n ic h t erw hnt Sterbealter w ar 72 u n d n Flle n Flle n Flle "di J a h re. D ie se Z u i 2 2 s a m m e n s t e l l u n g l t u n <? i 2 1 seres E rach ten s kernen Schlu a u f ein e g eg e n 2-- 3 3 i 1 i 3 s e it ig e A b h n g i g k e i t v o n $ 21 4 2 1 2 i i L un gen tu berk ulose u n d to COl 2 1 i A sbestose zu. D ie A b 3 3 2 3 hn e nn g Zi gekiet ui tmv os tn na dl leg ne m we iir d e i n i g e B e d e u t u n g h a b e n . A n H a n d g r o e r S ta tistik e n k o n n te Wedler n a c h w e is e n , d a d ie L u n g e n tu b e r k u lo s e bei A sb estarb eitern n ich t h u figer ist als in d er allgem ein en B evlk eru n g. D ie le t z te g r o e b e r s ie h t v o n Gloyne z e ig t, d a im S e k tio n s g u t seiner P rcn m n lm n in sp n d ie A sb esto seg ru p p e fa st d ie g erin g ste H u fig keit an T u b g ck ^ ssiiS iiiiw ies. ig s L u n g e n c a r cinom b e i A s b e s t o s e ^ E in e g a n z b e s o n d e r e B e - d e u tu H g ln p r a k tis c h e r u n d th a o rctm c-h tn H in s ic h t h a t d a s Lungen- carcinom bei A sb esto se. Das Careinom der Asbestlunge, schon frher von G l o y n e (1933, 1935), von Lynch und Sm it h (1935) und von E g b e r t und G e ig e r (1936) beobachtet, gilt, seit N o r d m a n n mit 4 Fllen der Weltliteratur und zwei eigenen Beobachtungen berzeugend den Zusammenhang mit der Lungenasbestose dargelegt hatte, unwider sprochen als Berufskrebs, wenn man von Einwnden C u r e t o n s absieht. I d den letzten 10 Jahren ist die Zahl der Flle wesentlich vermehrt worden. Nach W e d l e r (1943) zeigten von den 29 in Deutschland sezierten und bekannt gewordenen Fllen von Asbestose 6 (20%) und von 92 im Weltschrifttum mitgeteilten Fllen 14 Flle (16%) ein Lungencarcinom. W e d l e r rechnete zu seinen Fllen auch - Heuraendotheliome mit der Begrndung, die Pleura sei in den Umbauproze mit einbezogen. B o e m k e stellte 1947 bei einem fast gleich, groen Kollektiv 17 Flle fest und fgte 1953 seinem Fall von 1947 zwei weitere Fe hinzu. Es mssen weiterhin die Flle von W e is s (ein Pleuraendotheliom), W e l z und W e r b e r 184 J. Knig: erwhnt werden. Me r e w e t h e r bersah 1950 235 Flle autoptiseh gesieh*. Asbestosen mit 13,2% Lungenearcinom, G l o y n e 121 Flle mit 14,1%. j , ! * * b a ch e r ii. Mitarb. fanden bei 603 Fllen des Schrifttums eine Hufigkeit*'1" 13,8 % (1953): Auch in Gruppen von lebenden Asbestarbeitem konnte eine Huf des Lungencarcinoms beobachtet werden ( D o l l 1955). Lt' I n d e n l e t z t e n J a h r e n s i n d v o n Bohlig u n d J acob ( 1 9 5 5 , j g - s B ed en k en g eg en d iese S ta tistik en erh o b en w o rd en . In d em sie d ie dunl S ek tion sstatistik en erm ittelten Z ahlen von L un gen earcin om auf K o l le k t iv d e r l e b e n d e n A s b e s t a r b e i t e r b e z ie h e n , k o m m e n s ie z u <]*- F e ststellu n g , d a d er L u n g en k reb s b ei A sb esta r b e item n ich t hufjo, , sei als in d er allgem ein en m n n lich en B evlk eru n g. D as ist ber r a s c h e n d , d a Bohlig u n d J acob u r s c h l i c h e Z u s a m m e n h n g e zw is c h e : L u n g e n a s b e s to s e u n d B r o n c h ia lc a r c in o m a ls e r w ie se n a n seh en . ].. j n g s t e r Z e it h a t Bhme in d ie s e m A r c h iv d ie A llg e m e in g ltig k e it di E r g e b n is s e v o n Bohlig u n d J acob i n Z w e i f e l g e z o g e n . E r s t t z t sie l n ic h t n u r a u f n eu ere Z a h len u n terla g en d es S ch rifttu m s son d ern auch a u f eig e n e E rh eb u n g en . S o e n tsta n d e n b ei 9 2 A sb esto se k r a n k en , die au s ein em b estim m ten A sb estw erk stam m en d -- laufen d untersuch w u r d e n , b is 1 9 5 9 6 L u n g e n c a r e in o m e . W e i t e r h i n f a n d Bhme in 125 b eru fsgen ossen sch aftlich erfa ten F llen 15 L u n gen k reb se (=12% ). v o n d en en 14 gestorb en sin d . In b ezu g au f d ie G esam tzah l der Ver s to r b e n e n (n -- 3 1 ) e r g ib t sic h f r d e n L u n g e n k r e b s m it t d lic h e m A us g a n g ein e R a te v o n 4 5 % . U n te r d en 2 0 F llen , d ie pathologischa n a to m isc h b e a r b e ite t w a r en , z e ig te n 11 e in e n L u n g en k r eb s. D iese Z ah len zeigen d ie A b h n g ig k eit sta tistisch er E rgeb n isse v o n d er Auswahl d e s B e z u g s s y s t e m s . I n d e m M a t e r i a l v o n Bohlig u n d J acob situ : b rigen s b is 1958 34 F lle verstorb en , v o n d en en 11 seziert wurden u n ter d iesen w u rd en 5 A sb estosecarein om e festg estellt. W ir h ab en gru n d stzlich e B ed en k en , S ek tion sgu t u n d leb en de Be v lk eru n g a ls v erg leich b a re K o llek tiv e a n zu seh en . D ie Fehlerquellen w e rd en a llein sch o n a u g en sch ein lich , w e n n es sich u m d ie F ra g e der H u fig k e it v o n B er u fsk re b se n m it k u r zer L e b e n sd a u e r u n d langer L a t e n z z e it h a n d e lt . Bhme h a t d a s f r d a s A s b e s to s e c a r c in o m an g ed eu te t. D ie V o ra u ssetzu n g ein es V erg leich s ist, d a sieh d ie K ollektive n u r in ein em M erk m al u n tersch eid en . A u ch p ath ologisch -an atom isch e K o llek tiv e m ssen d ieser F ord eru n g m g lich st n aeh k om m en . In d ieser H in sich t g ew in n t u n sere F aU sam m lu n g b eson d eres Inter esse. M it 11 von 36 F llen (= 3 0 ,7 % ) ist d er A n teil d es L ungen- und d es P leu racarcin om s an u n serem A sb esto sek o llek tiv gr er als nach d em S ch rifttu m zu erw arten w ar. E in V ergleich m it an d eren Statistiken ersch ein t jed och p rob lem atisch , w eil d ie A u sw ah l d er K ollek tive unter sch ied lich sein k n n te, w ie sch on b eto n t. Z ieh en w ir ab er zu m Ver g l e i c h u n s e r a l l g e m e i n e s S e k t i o n s g u t v o n 1 9 4 8 -- 1 9 5 8 h e r a n (NasseHI)- ber die Asbestose 185 ben sich n ach A b zu g aller F lle m it ein em L eb en salter b is zu Jahren u nd der A sb estoseflle 13307 S ek tion en m it 1018 (= 7 ,8 % ) v igen carcin om en (ein sch lie lich d er P leu raen d oth eliom e). * p a j o v o n u n s e r e n 3 6 A s b e s t o s e f l l e n n ic h t d e m g le ic h e n S e k t io n s t a,,geh ren, ersch ein t ein e G leich setzu n g unserer gesam ten F a ll e n d u n g m it d em K o llek tiv d er 1 3307 F lle d u rch d ie F eh lerm glieh e ,, ,n Jer A u sw ah l b ela stet. In d en verb leib en d en 26 F llen w aren n u r 6 A sb estose k lin isch b ek an n t, in 4 F llen b estan d ein V erd ach t. In i F llen w ar d ie A sb esto se T od esu rsach e. E s sp rich t n ich ts d a g eg en , 1It.w m S e k tio n s k o lle k t iv v o n 2 6 F lle n d ie g le ic h e R e p r s e n ta n z f r l-i a llg e m e in e A sb e sto se k o lle k tiv z u z u sp r e c h e n , w ie d e m g le ic h z e itig (K 'ohachteten a llg em ein en S ek tio n sk o llek tiv f r d a s a llg em ein e K o lle k tiv j.-r B e v lk e r u n g d e s E in z u g s g e b ie te s . U n ter d en 26 F llen fin d en sich 9 L u n gen carein om e, d as sin d 3 4,6% . M ich d ie ser P r o z e n tsa tz is t n o ch n ic h t o h n e w e iter es m it d em d es d lgem ein en S ek tio n sk o llek tiv s zu v erg leich en , d a d as V erh ltn is d er M nner zu d en F rau en im A sb estosek ollek tiv 1:1 ,9 , im allgem ein en Sektionsgut a b e r n u r 1 : 0 , 7 b e t r g t . V e r g l e i c h e n w i r d i e H u f i g k e i t Ics L un gen carcinom s f r d ie G esch lech ter getren n t, so fin d en sich b ei T a b e l l e 9 . Vergleich der Hufigkeit von Lungenearcinom im Sektionsgut der Asbestose- llle und im allgemeinen Sektionsgut des Pathol. Instituts des Krankenhauses St. Georg Allgemeines Sektionsgut Asbestoseflle Alle Asbestoseflle, die se it 1939 r (Flle vom des allgemeinen im P ath . In stitu t 31. L ebensjahr an, minus Asbestoseflle) Sektionsgutes 1948-- 1958 von .St. Georg beobachtet wurden 1948-- 1958 L Alle F lle .................... 13307 h Lungencareinome . 1018 100,0 % 7,7% 26 100,0% 9 34,6% 36 100,0% 11 30,6% davon Pleuraendotheliome . . . . 102 0.77% 4 15,4% 4 11,1% Alle mnnlichen Flle r1 Lungencareinome . t Alle weiblichen Flle . - Lungencareinome . 7 817 903 5490 115 100,0 % 11,6 % 100,0 % 2,1 % 9 100,0% 4 44,4% 17 100,0% 5 29,4% 13 100,0% 6 46,2% 23 100,0% 5 21,7% iden M n n ern d es a llg em ein en S ek tio n sg u tes 11,6% , b ei d en en d es A sb estosegu tes 44,4% L u n g en ca rein o m e. F r d ie F ra u en g elten en t sprechend d ie S tze 2,1 % u n d 2 9 ,4 % . E in e b ersich t b er d ie V erh lt nisse g ib t T a b e lle 9. S ie m a c h t, w e lc h e n B ez u g m a n a u ch w h lt, d ie erhhte K reb sb elastu n g d es A sb estosek ollek tivs d eu tlich . B eson d ers *deu tlich ersch ein t d a s f r d a s w eib lich e G esch lech t, ein e B eo b a ch tu n g , d ie a u c h J acob u n d Bohlig e i n r u m e n d h e r v o r h e b e n . D ie b er jed e E rw artu n g h in au sgeh en d e H u fu n g vo n P leu rae n d o th e lio m e n b e s t tig t d ie A n n a h m e v o n Wedler. W ir b e tr a c h te n a u ch u n sere F lle als A sb esto se-C a rcin o m e. W en n g leich w ir d ie Jj* w e lc h e m M u tte r b o d e n d a s P le u r a e n d o th e lio m e n tsta m m t, o ffen las**, so ersch ein t u n s f r d ie th eo retisch e B eg r n d u n g d er gew ebliche B ezieh u n g d och au sreichend , da es sich u m ein en m alignen T um or 4 L u n g en o b erfl ch e h a n d elt; g era d e d ieser B ereich ist ein P rdilek tiou*,.. d e r L u n g en re a k tio n , w ie d ie N e ig u n g zu su b p le u r a ler V erd ich tu n g u d ie H u fig k e it v o n P le u ra v e rsch w a r tu n g e n in u n k o m p liz ie rten Flli v o n A sb estose zeigen . U n te r d e n in T a b e lle 9 a n g e f h r te n L u n g e n c a r c in o m e n fin d e t sir* n eb en d en 6 U n terlap p en -C arein om en u n d d en 4 P leuraendotheliom '-; e in O b e rla p p e n -C a re in o m (F a ll 2 6 ), d a s w e g en se in e s S itz e s u n d sein, en g en B ezieh u n g zu ein er tu b erk u l sen N a rb e a u ch a ls N arbencarcim m ged eu tet w erden knnte. "D ie g r ere K re b sg e f h r d u n g b ei A sb e sto se k o m m t n ic h t nur d e r H u f ig k e it s o n d e r n a u c h -- e n ts p r e c h e n d d e n V o r s te llu n g e n vi>; Sohixz -- in d e r V e r s c h ie b u n g d e s S t e r b e a lt e r s in R ic h t u n g d e r j n g ere J a h rg n g e zu m A u sd ru ck . D a s D u rch sch n ittsa lter b etr g t in unserer: M a t e r i a l 5 1 . 6 J a h r e u n d e n t s p r i c h t d a m i t r e c h t g u t d e m v o n Wedle: a n g e g e b e n e n A l t e r v o n 5 2 J a h r e n . D e m g e g e n b e r f a n d Schenck fr d as L u n gen earcin om im S t. G eorger S ek tio n sg u t ein D urchschnitt a l t e r v o n 5 9 J a h r e n . V e r g le ic h e n w ir d ie A n g a b e n v o n Nassehi bed ie A lte rsv er te ilu n g f r d a s L u n g en ea rcin o m im S t. G eorger Sektionm aterial d er letzten 50 Jah re (1068 F lle) m it u n seren Z ahlen an H an; v o n S u m m a tio n sk u rv en . so erg eb en sich en tsp rech en d e V erhltnis-(A bb . 11). D ie G efh rd u n g lt- sich ab er n ich t, an s d er D a u er d er E xpositio! ab leiten , w ie T ab elle 10 zeigt. E in e g ew isse K o n sta n z lieg t -- in ber e in stim m u n g m it d e n b e r e its v e r ffe n tlic h te n F lle n -- in d em Zeit r a u m v o m B e g in n d e r E x p o sitio n b is z u m T o d e . W ir m c h te n diesen Z eitrau m als L a ten zzeit b ezeich n en . U n ser eigen er F all 16 w ird nod v o n d e m F a l l Owens b e r t r o f f e n , h e i d e m d ie E x p o s i t i o n s z e i t 1 J a h r d ie L aten zzeit 20 Jah re d au erte. D ie G ef h r d u n g sch ein t, a u ch n ic h t m it d em S ch w ereg ra d der A sb esto se zu zu n eh m en , w ie T ab elle 4 zeig t, ein e b errasch en d e Fest s t e llu n g . A u c h Bhme kam auf G r u n d s e in e s S t u d iu m s d e r b eru feg e n o s s e n s c h a ftlic h e n A k te n z u dem S c h lu , d a b e i d e n s e z ie r te n F llen ein d e u tlic h e s b e r w ie g e n d e r sc h w e r e n A sb e sto se n a n sc h e in e n d nicht b eob ach tet w ord en w ar, ein E rgeb n is, d as im G egen satz zu d en Beob a ch tu n g en d er eig en en 6 F lle sta n d . W ir w erd en a u f d ieses Problem n och ein m al u n ter B er ck sich tigu n g d er H istogen ese zurckkom m en D a s m n n lic h e G e sc h le c h t is t o ffe n b a r m e h r g e f h r d e t a ls d a s w eib lich e. V o n 13 M n n ern u n serer S a m m lu n g h a b en 6 , d . h . 46,2% eff L u n g en ea rcin o m , w h ren d von d en 2 3 F ra u en 5, d . h . 21,7% betroffen .,, J E in e st r k e r e K r e b sg e f h r d u n g d e s m n n lic h e n G e sc h le c h ts s te llte } -n falls Glovne fe st: w h ren d b ei M n n ern in 19,6% d er F lle ein L aiw en carcinom g efu n d en w u rd e, w ar d ies b ei F rau en n u r in 9,7 % d er i'3ll S ch o n W e d t .e r w e is t a u f d ie se G e se h le e h tsv e r te ilu n g h in . D ie son st b ek an n te G esch lech tsd isp osition f r d as L u n gen earcinom .-d t u ns d a m it d eu tlich b eim A sb esto seca rcin o m en tg eg en . V o n b einderem In teresse ist in d iesem Z u sa m m en h a n g , d a d a s P leu ra- ioth elio m n u r b e i d e n w e ib lic h e n F lle n a u fg e tr e te n is t. A u c h h ie r 4jrd ein e G esch leeh tsd isp o sitio n deu tlich. B etra ch ten w ir zu m V er gleich etw a d ie L u n g en ca rcin o m e. io v o m 1. J u li 1 9 5 7 b is 3 1 . D e z e m !l(.r 1 9 5 8 in S t. G e o r g s e z ie r t w u r den:von 133 C areinom en h eim M an n Tabelle 10. Vergleich von Exposilions zeit und Latenzzeit in 6 Fllen von Asbestose-Cardnom Jahre F11 Ex- Nr. Alter positions- Latenzzeit zeit 9 53 24 24 10 47 15 26 13 39 11 24 16 45 27* 23 23 41 10 24 30 54 9 18 -19 ~39 - -SS -59 -73 -35 Altersklassen Abb. 11. Die A ltersverteilung des Lungencarcinoms bei 1668 F llen des allgem ei nen Sektionsgutes des P ath. Institutes St. Georg (unter Verwendung der Angaben von N a s s e h i) u n d b e i 11 F llen des Asbestose-Sektion-gutes, a Allgemeines Sektionsgut; t) A sbestose-Sektionsgut w aren 15 (= 1 1 ,3 % ) P leu raen d oth eliom e, von 29 C areinom en b ei d er Frau 11 (= 3 8 % ). E s d rn gt sich d ie V orstellu n g au f, d a d as A sb estosecarcin om prinzipiell n ich t v o n C arein om en m it u n b ek an n ter tio lo g ie in gleich er L okalisation u n tersch ied en w erd en k an n . In d iesem S in n e sp rich t, d a unser M aterial d u rch au s n ich t n u r P latten ep ith elcarcin om e zeig t, w ie frher gerad ezu p o stu liert w u rd e. E s fin d en sich in ein igen F llen neben gro zelligen u n d p latten ep ith elia len W u ch sform en au ch b er gnge zu k lein zelligen S tru k tu ren od er d as au sgesp roch en e B ild d es k leinzelligen B ron ch ialcarcin om s. b erg n g e zu g ro zellig en od er p latten ep ith elialen S tru k tu ren k an n m an au ch in k lein zelligen B ro n ch ia l careinom en u n b ek an n ter tio lo g ie b eob ach ten . Im m erh in steh en d ie n ich tk lein zelligen W u eh sfo rm en in u n serem M aterial m eh r im V ord er grund. E in w eiteres K riteriu m d es A sb estosecarcin om s, d ie m u ltizen trische E n tsteh u n g , ist m ak rosk op isch sch w er zu b eu rteilen . D ie jf- , 192 J. Knig: a lv eo l re n P a ren ch y m s b ew irk en ein b er tre ten d er F rem d k rp er in ^ N a c h b a r s c h a f t ih r e s p r im r e n K o n t a k t e s . E s e n t s t e h e n peribronchiola,, Fibrosen u n d w ie d e r u m -.S c h r u m p fu n g e n . D ie in d ie s e m fib r s e n B in d e, g e w e b e lieg en d en A sb estk rp erh a u fen k n n en d a n n n a ch Jahrzehnt-, la n g e m , sta u b fre ie m In te r v a ll v o n F r em d k rp erriesen zellen um schloss.--, in n erh alb von S ch w ielen gefu n d en w erd en . D ie F olge der endo- und p e r ib r o n c h io l r e n F ib r o s e is t e in e starre Fixierung d e s b en a ch b a r ter . P a r e n c h y m s z u n c h s t in der Lngsrichtung d e s B r o n c h io lu s , d ie e in e r fo r ts c h r e ite n d e n B e l f tu n g s s t r u n g f h r t. A ls sekundre V cr n d e r u n g -- in fo lg e d er B e l ftu n g sst r u n g e n , d ie a n f n g c h noci; E m p h y se m ch a ra k te r zeig en , d a n n a b er zu n eh m en d in D ystelektas. b e r g e h e n -- e n t w ic k e l t s ic h e i n e diffuse Fibrose m it Kollapsinduratm u nd A usgang in V erdung des P arenchym s. D ie B ro n ch io len erleid en d a b ei ein v ersch ied en es S ch ick sal. Entw e d e r v er d e n sie in fo lg e ein er fo rtsch re iten d e n B ro n ch io litis obliterans. od er sie erw eitern sich , gelegen tlich im Z u sam m en h an g m it d er E ntw ick lu n g k lein er u m sch rieb en er H erd e ein es h o ch grad igen substantiellen E m p h y se m s, so d a g ro k a m m erig e S y ste m e e n tste h e n . D iese zeigen d a n n in m an ch en F llen erh eb lich e p o st-in fek ti se m esenchym ale P r o l i f e r a t i o n e n u n d o Umbauv r g n g e . H i e r b e i k o m m t e s z u e p it h e lia le n R eg en era tio n en , d ie a lle b erg n g e v o n reg elrech tem zu m etap lastischein o d er a ty p isch em E p ith el a u fw eisen . In d iesen A b sch n itten entw ickeln s ie h a d e n o m a r t ig e B ild e r m it a lle n b e r g n g e n z u m Garcinom. Z w e ife l lo s k n n en a b er a u ch d ie k lein en B ro n ch io le n lich tu n g e n , d ie in einzelnen A b sch n itten verd eter B ron ch iolen erh alten geb h eb en sind , d en Boden f r ein C areinom b ereiten . D ie V o r stellu n g , ein e d iffu se V e rte ilu n g d es S ta u b e s setze einen d iffu se n R e iz , d ie se r f h r e d a n n z u e in e r d iffu se n F ib r o se , m ssen wir a u f g e b e n . D i e d if f u s e F ib r o s e e n t w ic k e l t s ic h , w i e w ir s e h e n , sekundr, oh n e selb st ein en K o n ta k t m it A sb estk rp erch en au fzu w eisen , im An sch lu a n ein e u m sch rieb en e, p erib ro n ch io l r e F ib r o se, d ie in einer sich eren rtlich en B ezieh u n g zu d er g esch ild erten intracanalicu lren A nhufung des Staubes steht. Gegen diese berlegung knnte eingewendet werden, da Staubelemente, deren Gre unter der Grenze der Sichtbarkeit liegt, in Mengen in die Lungen a .geraten, was N o u. mu aber r b m a n n fr sehr wahrscheinlich hlt. Nach die Faser eine bestimmte Lnge haben, um Sun d eine i u s und Fibrose B vgden' erzeugen zu knnen. Zu diesen Vorstellungen kamen auch V o r w a l d , D u r b a n und P r a k sowie B e h r e n s auf tierexperimentellem Wege. Die Hypothese der Wirkung unsichtbarer Staubteilchen kann unseres Erachtens wohl auch deshalb vernach lssigt werden, weil sich, wie eine Betrachtung der formalen Genese ergibt, die Ent wicklung der diffusen Fibrose zwanglos aus den sichtbaren Befunden ablesen lt- E s s in d , b e r b lic k t m a n d e n g a n z e n P r o z e , zwei Phasen z u u n ter s c h e id e n , w ie Eickhoff s c h o n m i t R e c h t h e r v o r g e h o b e n h a t , d ie P h a s e ber die Asbestose 193 |?r fu n k tion ellen u n d m orp h isch en R eak tion am B ron ch iolu s u n d d ie ^ s c h lie e n d e P h a s e d e r d if f u s e n F ib r o s e . D ie e r s t e , d ie branchiolre `hiise, f h r t b e r e i t s z u d e r e n t s c h e i d e n d e n B e l f t u n g s s t r u n g ; d i e p iire n ch y m a t se Phase in F o r m d e r d if fu s e n F ib r o s e is t d ie z w e ite , seitlich n a c h g e o r d n e te P h a se . S ie is t n ic h t U r sa c h e d er B e l ftu n g s,,trung son d ern ihre F olge. t 3. F olgerun gen a u s der H istogenese D iese V orstellu n gen von d er H istogen ese sin d geeign et, zu r L su n g der F ragen , d ie sich h ei d er B etra ch tu n g u n seres M aterials ergab en , b eizutragen u n d d a m it ein ige E igen t m lich k eiten , d ie am k lin isch en B ild u n d a m V erla u f d er A sb e sto se a u ffa llen , v er st n d lich zu m a ch en . a ) A u f d ie s e m W e g e v e r s te h e n w ir d ie Diskrepanz z w is c h e n d e m klinischen B e f u n d u n d d e m rntgenologischen u n d anatom ischen B i l d . D ie fu n k tio n ellen u n d m o rp h o lo g isch en V er n d eru n g en a m B ro n ch io lu s und am A lveolargan g w erd en an fn glich k ein e u n d sp ter relativ schw ach erk enn b are Z eich en im R n tgen b ild geb en k n n en , w ie au ch Etckhoff b e t o n t , w h r e n d s i e s c h o n j e n e B e l f t u n g s s t r u n g d e r L u n g e einleiten, d ie ih rerseits zu r P aren ch ym fib rose f h rt. E s ist v erst n d lich , da d ie m orp h ologisch en V ern d eru n gen , au f d ie m a n in so lch en F llen zur E rh rtu n g d er D iagn ose w artet, sch on ein er verh ltn ism ig sp ten Phase d es K ran k h eitsverlau fes an geh ren m ssen , u m rn tgen ologisch sichtbar zu w erd en . V on d er In ten sit t d er b ron ch iolren R eak tion hngt es ah , ob eia F a ll fr h zeitig S ym p tom e zeigt. W ir k n n en n ich t en tsch eid en , w iew eit S p tsy m p to m e d em b ron ch iolren P ro ze od er seinen F o lg en , d er d iffu sen F ib ro se, zu zn seh reib en sin d . b ) D e m Zeitfaktor u n d d a m i t a u c h d e m freien Intervall k o m m t n a c h unseren h istogen etiseh en V orstellu n gen ein e erh eb lich e B ed eu tu n g f r die en d g ltig e A u sb ild u n g d er L u n g en v er n d er u n g en zu . D ie ein m a l ab gelagerte S tau b m en ge u n d d ie Z eit sin d w ich tige B ed in gu n gen f r das M a d er P rogred ien z. U n sere B efu n d e sp rech en d af r, d a d ie I p erib ron ch iolre V ersch w ielu n g u n ter d em E in flu d er A sb estk rp ereh en auch im L au fe vo n Jah rzeh n ten n ich t zur R u h e k om m t. D af r sp rechen B rche, A bsprengungen von den K rperchen, U m form ungen an der G elhlle u n d U m gru p p ieru n gen d er K rp erch en zu R o setten stru k tu ren , alles B efu n d e, d ie f r a lte u n d fo rtg esch ritten e A sb esto sen ty p isch sin d . E s fllt sch w er, d iese A b lageru n gen , d ie als ty p isch e H orn b len d en d erivate an zu seh en sin d , als b elan glos f r d ie P rogred ien z au fzu fassen . W ir s in d m it Begeh v llig e in ig , d a d ie A s b e s tk r p e r c h e n d ie F ib r o s e B ild un g m ittelb a r b er d ie p erib ro n ch io l re F ib ro se u n terh a lten , o h n e d ie B ed eu tu n g d er A sb estn a d eln f r d ie in itia len P ro zesse sch m lern zu w ollen . D ie N a tu r d es fib rogen en R eizes ist jed en falls au f ein en 196 J. Knig: en tk rftet. V ergegen w rtigen w ir u n s, d a d em d iffu sen , be; d ie g an ze L u n ge v erb reiteten P ro ze d er A sb esto se u n z h lig e solch R egen eration sh erd e zu geh ren , d an n w ird oh n e w eiteres verstand lieh , d a d ie W a h rsch ein lich k eit, d a a n irg en d ein er S telle der U m sc h la g in ein e a u to n o m e W u ch eru n g m a lig n en C h a ra k ters erfolgt g r e r is t a ls in j e n e n L u n g e n , i n d e n e n d e r B o d e n z u ein solch en E n tw ick lu n g n u r in ein em en tsp rech en d en E in zelh erd ai su ch en ist. W ir n h ern u n s d am it V orstellu n gen , d ie f r d ie G en ese d es Lungenca rcin o m s b erh a u p t g elten . D ie B ed eu tu n g ein es ch ro n isch en B eize; f r d ie E n t s te h u n g d e s L u n g e n c a r c in o m s g la u b t Berkhan in dein strk eren B efall d er rech ten L u n ge m it C arcinom erk en n en zu knnen, w o b ei er a n n im m t, d a in fo lg e d es grad lin igen V erlau fes d es rechten H a u p tb ro n ch u s d ie re ch te L u n g e m eh r S ta u b e in a tm e t a ls d ie linke. A V e n n AAT. Fischer d ie U n t e r s c h ie d e in d e r H u f ig k e it s v e r t e ilu n g au f d ie U n tersch ied e d es V olu m en s d er rech ten u n d lin k en L u n ge zurckf h rt, so w ird d a m it ein w eiterer G esich tsp u n k t b er ck sich tig t; es w ch st d ie A A 'h rschein lichk eit d er K reb sen tsteh u n g m it d er Z unahm e d es M u tterb od en s. D iese allgem ein en b erlegu n gen sin d f r unsere B eob ach tu n g, d a k ein e B ezieh u n g zw isch en S ch w eregrad d er A sbestose u n d L u n g en ca rcin o m b este h t, v o n B ed eu tu n g . W ir m ssen m it einem q u an titativen F ak tor rech n en , d er in d er A u sd eh n u n g d es Prozesses liegt. AW r m ssen an n eh m en , d a d er ch ron isch e R eizzu stan d am B ro n ch io lu s resp ira to riu s, u b iq u it r in d er L u n g e v e r te ilt, f r d ie C arcin om en tsteh u n g au sreicht. A b er w ir d rfen u n s m it d em exogen en Faktor n ich t b egn gen . ,,D a w ir d am it n och w eit v on ein em vollen V erstndnis d er fein eren B ezieh u n gen en tfern t sin d , h a t d ieses P rob lem b ei der A s b e s t o s e m i t d e m d e r K r e b s e n t s t e h u n g b e r h a u p t g e m e i n s a m " (Wedler). D a d e r A s b e s t n u r ein F a k t o r i s t , b e t o n t e 1 9 5 7 a u c h H ueper. E s m s s e n w e ite r e I m p u ls e , d ie sic h u n s e r e m AA7is s e n n o c h en tz ieh en , an gen om m en w erden. ,,E s gib t m ehr en d ogen e u nd exogen e F aktoren a l s s i c h t r u m e n l t " ( W . F ischer). D i e A r t d e s i n h a l i e r t e n A s b e s t e s , in d iv id u elle L eb en sg ew o h n h eiten , a llg em ein e g eograp h isch b ed in gte L eb en su m st n d e sin d , so w eit zu b erseh en , v o n eb en so m itw irk en d er B ed eu tu n g w ie an lageb ed in gte in d ivid u elle F ak toren , F ak toren , d ie erst d es u eren A n sto es im S in n e d es P roliferation sreizes v o n gengender D au er, S trk e und vielleich t b estim m ter A rt bedrfen, u m zu m K rebs z u f h r e n . S c h o n ' Fischer-Wasels s a g t e a u f d e r 2 8 . P a t h o lo g e n T a g u n g : ,,A b er n ur, w enn d ie ty p isch e b eson d ere A llgem ein d isp osition , d ie allgem ein e K reb sb ereitsch aft n och h in zu k om m t, b ild et ein e R egen e ration sw u ch eru n g ein e G esch w u lstk eim an lage, ein e b sartige G e sch w u lst." In d iesem Z u sam m en h an g verw eisen w ir a u f d ie b em erk en s w erte G esch lech tsverteilu n g d es A sb estose-C arcinom s in unserem ber die Asbestose 197 Material, d i e d e y a l l g e m e i n e n G e s c h l e c h t s d i s p o s i t i o n f r d a s L u n g e n sjreinom en tsp rich t. 4. Schlujolgerungen f r d ie B egutachtung P ie vorgelegten B efu n d e u n d ih re D eu tu n g sch ein en geeign et, F ragen vor allem von k lin isch er S eite u n d jen e, d ie d ie G en ese d es A sb esto seC arcinom s b etreffen , ein er L su n g n h erzu b rin g en . S ie g ew in n en damit v i e l l e i c h t a u c h e i n e g e w i s s e B e d e u t u n g f r d i e A r b e i t s m e d i z i n , die in d iv id u elle P r o p h y la x e u n d d ie B e g u ta c h tu n g . P ie D isk rep an z zw isch en d em k lin isch en B ild in sein er su b jek tiven Frbung u n d d em rn tgen ologisch en (k lin isch -m orp h ologisch en ) B efu n d .teilt d en B eg u ta ch te r v o r ein e sch w ierig e E n tsch eid u n g . Pie Begutachtung wird immer nach objektiven Unterlagen einer Klassifizierung der Schwere einer Erkrankung suchen und bestrebt sein, ihre Urteile in genormter Ausdrucksweise zu formulieren, um soweit allgemein verstndlich zu sein, da das Ma der Hilfeleistung fr den Betroffenen -- sei es eine prophy laktische, eine therapeutische oder eine soziale -- festgelegt weiden kann. Es sei auf die Ein teilungen von Krger, Rostoski und Saupe, von Lanza und von Buresch hingewiesen. Die Kritik an diesen Bemhungen fhrt immer wieder zu der Fest stellung, da eine Gradeinteilung den klinischen und rntgenologischen und' patho logisch-anatomischen Gegebenheiten nicht gerecht werden kann (V/ixkler). Gloyne s c h r i e b i n s e i n e r l e t z t e n M i t t e i l u n g b e r d i e P n e u m o k o n i o s e n , da alle K lassifizieru n gen d er L u n gen vern d eru n gen gesch eitert sin d . Sie m ten sch eite rn , so la n g e m a n d ie S ch w ere d es k lin isc h e n B ild e s m it ein em R n tg en b ild zu id en tifizieren v ersu ch te. E s ist d a h er z. B . nicht a n g n g ig , ein e R e n te im m er erst d a n n zu gew h ren , w en n d ie ,,b in d egew eb ige U m w an d lu n g, d ie F ib ro se au sged eh n ter L u n gen gew eb santeile m it A u sfall ih rer F u n k tio n f r A tm u n g u n d K reislau f" n a ch g e w ie s e n i s t (Boemke). D i e v o r a u s g e h e n d e n , l a n g a n h a l t e n d e n k l i n i s c h e n S trungen w erd en d am it u n ter U m st n d en als A larm zeich en u n d fr h zeitige In d ica to ren d er A sb esto se v llig vern a ch l ssig t. 1949 stellte Jtten a u f d e r S t a u b l u n g e n t a g u n g i n M n s t e r f e s t : ,, D i e f u n k t i o n e l l e U n tersuchu n g w ird jetzt im G egen satz zu fr h er w esen tlich h h er bew ertet als d as R n tgen b ild , d as n u r als ein K riteriu m b ew ertet w erden so ll." D ie 5. B eru fsk ran k h eiten -V erord n u n g v o m 26. F eb ru ar 1952 tru g d ieser n eu en A u ffassu n g sch on w eitgeh en d R ech n u n g. N ach d em u n s n u n d ie m orp h ologisch e U n tersu ch u n g! ein es gr eren S ek tion sm aterials, d as -- ein h eitlich g esich tet -- L u n gen vern d eru n gen aller P h a sen en th lt, g ezeig t h a t, d a d er L u n gen p roze d u rch d ie fu n k tion ellen u n d m orp h isch en R ea k tio n en am B ron ck ioiu s resp iratoriu s ein geleitet w ird , fern er d a sich in d ieser b ron ch iolre.n P h a se b ereits das S ch ick sal d es w eiteren V erlau fes en tsch eid et, m ch ten w ir d ie F rage au iw erfen , ob es g u ta ch tlich rich tig ist, erst d a n n v o n ein er A sb esto se 211 sp rech en , w e n n im R n tg e n b ild d ie V er n d eru n g en d er F ib r o se ' t : - . 198 J. KOTG: sich tb a r w erd en . Z w eifellos w ird d ie A n tw ort a u f d iese F rage von u. E n tw ick lu n g d er R n tg e n te ch n ik b eein flu t sein ; so etw a von deM g lie lik e it. d u rch -,V e r g r e r u n g sa u fn a h m e n F r h d ia g n o se n zu steij,,. ( K n .A r s i .E R u n d Seyss). A b e r d a m i t w i r d d i e D i s k r e p a n z z w is c -ij d em m orp h ologisch en B efu n d u n d d em k lin isch en B ild n ich t gerin g D as E rgeb n is u nserer U n tersu ch u n g h efert u n seres E rach ten s d en B ew e, d a Bvrksth r e c h t h a t t e , a ls e r b e r e it s 1 9 3 1 s c h r ie b : ,, D ie s e U n t!-, s d ie id u n g v o n S ta u b lu n g e u n d S ta u b k r a n k h e it er sch ein t a ls durchs!., g l c k l i c h g e w h l t . ' "' D a m i t h a t Bttkesch z w e i B e g r i f f e u n t e r s c h i e d , d ie b lic h e r w e is e , g e m e in s a m m it d e r B e z e ic h n u n g A s b e s t o s e besam w erden. Eine Voraussetzung, die Schwierigkeiten der Beurteilung und der Bei,;: achtnng zu berwinden, sind klare Begriffe, die einem objektiven Denken zugrg. lieh sind, die deutlich und nicht vertauschbar sind. Begriffe bedrfen eindeun:;.-: Benennung. Zur Erreichung einer eindeutigen Nomenklatur auf dem Gebiei <i<* Pneumokoniosen hat der englische Arbeitsmediziner M e r e w e t h e b die Bildm; internationaler Gremien gefordert. D e m V o r s c h l g e v o n Baader. Goralewski, H agen, H olstein u n s K o e i.sc h , d a s O r g a n u n d d i e s c h d i g e n d e N o x e i n d e r B e z e i c h n u n g zt v erein en , fo lg en d , m ch te ich d ie d u rch A sb est m orp h ologisch verndert: L u n g e a ls A sb e stlu n g e b e z e ic h n e n . H ie r n a c h k a n n je m a n d a n eine: A$benfsifie l e i d e n , o h n e d a m i t d e n M i t t e l n d e r k li n i s c h e n M o r p h o lo g ie w en n m a n v o n d em N a ch w eis d er K rp ereh en im S p u tu m ab sieh e i n e Ashe.fttlunae n a c h g e w i e s e n w i r d . E b e n s o s o l l t e m a n a b e r a u c h m r d er M g lich k eit re ch n e n , d a sieh ein e m itte l- o d er so g a r hochgradig A s b e s th r a g e o h n e a la r m ie r e n d e S y m p to m e e n tw ic k e ln k a n n ; dies: E n tw ick lu n g k an n zu ein em Z eitp u n k t festg eleg t w erd en , zu der. rn tgen ologisch n och k ein au sreich en d er A n h alt gegeb en ist. A b sch lie en d m ch ten w ir au f u n sere .S resb efn n d e h in w eisen . B lt h ere K reb sg ef h rd u n g d er A sb estlu n g e im m itteleu ro p isch en R aun k a n n u n seres E ra ch ten s n a ch w ie v o r als w eitg eh en d sich ergestel a n g e s e h e n w e r d e n . D e r R c k z u g a u f e in ,, in d u b io p r o a e g r o to " (Oettei: sch ein t n ich t, erford erlich , w en n m an v erg leich b a re K o lle k tiv e d es m ittel e u r o p i s c h e n R a u m e s z u r G r u n d l a g e d e r U r t e i l s b i l d u n g m a c h t . Zoe K reb s d er A sb estlu n ge ist auch d as P leu raen d oth eliom zu zh len . E in F a au s d em S ch rifttu m (L e ic h e r ), ein e H u fu n g v o n F llen is u n serem M aterial u n d d er N a ch w eis, d a ein e h m a to g en e G en eralisatiffi v o n A sb estk rp erch en m glich ist, w erfen d ie F rage au f, ob au ch das Peritoneal-Carcirt&m b e i A s b e s t o s e a ls K o m p lik a t io n -d e r A s b e s t o s e ffl d a m it als en tsoh d igu n gsp flicb tige B eru fsk ran k h eit an zm erk en oen ist. Ensaismciifassimg 1. E s w ird b er 3 6 F a lle v o n A sb esto se , d ie im A rb eitsb ereich 6 P ath ologisch en In stitu tes d es A llgem ein en K ran k en h au ses S h G eorg ber die Asbestose 199 Hiiahufg .untersucht w u r d e n , b e r i c h t e t . E i n i g e z u m a l l g e m e i n e n V e r gdnis n o tw en d ig e A n g a b en b er d ie A sb esto se a ls Z iv ilisa tio n sk ra n k -s b er d en A sb e st, se in e V e ra rb eitu n g , b e r d en S ta u b u n d d ie ,,^ p u lm on al geb ild eten A sb estk rp erch en w erd en voran gestellt. > p je A n am n ese, d ie w ich tigsten k lin isch en u n d S ek tion sb efu n d e s:- den sie l1 in T a b e lle n . D ie m a k r o sk o p isc h e n u n d m ik r o sk o p isc h e n hm de d er L u n gen u n d d er regionren L ym p h k n oten w erd en zu sam m en -. fa t d a r g e ste llt. E s fo lg t e in k u r zer B e r ic h t b e r B e fu n d e , d ie ein e hmatogene S t r e u u n g d e r A s b e s t k r p e r c h e n e r k e n n e n l a s s e n . 3. D as S ek tio n sg u t, d as v o n 13 m n n lich en u n d 23 w eib lich en F llen .m im t, e n th lt a lle m o r p h o lo g isc h e n S ch w er eg ra d e d er A sb esto se iii inlich g leich m ig . In 7 F llen ist d ie A sb esto se v erm u tlich d a s H auptleiden, in 11 w eiteren F llen b esteh t ein L u n gen carein om , d avon ... 4 F lle n e in P le u r a e n d o th e lio m . I n 1 8 F lle n s in d a n d e r e B e fu n d e ,|s H au p tleid en zu b ezeich n en . In ein er R eih e v o n F llen w u rd e d ie A sbestose erst p a th ologisch -an atom isch erk an n t. D ieses M aterial sch ien g eeig n et, d ie V orstellu n g en v o n d er H isto jenese zu b erp r fen , au f d ieser G ru n d lage ein ig e k lin isch e P rob lem e einer K l ru n g n h erzu b rin g en u n d er n e u t S tellu n g zu d er in d en letzte n Jahren w ied er au fgew orfen en F rage d es A sb estose-C arcin om s zu n eh m en . 4. D ie in D eu tsch la n d vertreten e A u fassu n g, ein e d iffu se S tau b iM invirkung a u f d a s a tm e n d e P a r en ch y m in sein er G e sa m th e it f h re u nm ittelb ar zu r d iffu sen F ib ro se, k a n n n ich t b est tig t w erd en . D er Staub w ird vielm eh r b erw iegen d im B ron ch iolu s resp iratoriu s abgefangen, w ie es d ie en glisch en A u toren sch on seit lan gem b esch reib en . D ie fu n k tio n ellen u n d m o rp h isch en R e a k tio n en a m B ro n ch io lu s leite n die 1. P h a se, d ie w dr d ie b ro n ch io l r e n en n e n m c h te n , ein . S ie f h rt zur p erib ron ch iolren F ib rose. D ie starre F ix ieru n g d es elastisch en P arenchym s am in d u rierten B ron ch iolu s leitet d ie 2 ., d ie p aren ch ym atse Phase ein , d ie sch lie lich zu r d iffu sen F ib rose f h rt. N eb en ein er B ron ch iolitis o b litera n s en tw ick eln sich a u ch B ro n eh io lek ta sen . H ier w ie d ort k o m m t es u n ter d en B ed in g u n g en p o stin fek ti ser R e iz zu st n d e und fu n k tion eller A u ssch altu n g zu erh eb lich en ep ith elialen R egen era tionen. S ie sin d d ie V o ra u ssetzu n g f r d a s L u n g en ca rcin o m . 5. D ie K en n tn is der H istogen ese b rin gt ein ige F ragen zu r A sb estose ner K lru n g n her. a) D ie D isk rep an z zw isch en d em sch w eren k lin isch en B ild u n d d em W ehr od er m in d er n egativen R n tgen b ild k an n m it d er E igen art d er b ron ch iolren P h a se erk lrt w erd en . In d ieser P h a se k n n en d ie fu n k tio ellen S t ru n g en erh eb lich sein , w h ren d r n tg en o lo g isch e Z eich en n o ch fehlen m ssen . U n k la r b leib t d ie D isk rep a n z, d ie in d er p a ren ch y m a t sen P hase zw isch en ein er d rftigen S y m p tom atologie u n d ein em m eh r od er m inder a u sgep rgten m orp h ologisch en B efu n d b esteh en k an n . 200 J. K nig: b) D er S ch w eregrad d er L u n gen vern d eru n g ist n ich t n u r abhng v o n d e r E x p o s i t i o n s z e i t u n d d e r ( m e i s t n i c h t b e k a n n t e n ) Staubkorn? tr a tio n a m A rb eitsp la tz so n d ern a u ch v o n d er Z eit. D ie histologischB efu n d e m ach en d ie A n n ah m e ein er sch leich en d en P rogred ien z au? im V erlau fe d es freien In tervalls w ah rsch ein lich . c ) E i n S u b s t r a t d e r i n d i v i d u e l l e n D i s p o s i t i o n k a n n i m Bronchiole resp iratoriu s geseh en w erd en . D ie v o n P a ll zu F a ll unterschiedlich In ten sit t d er sich gegen seitig b eein flu ssen d en fu n k tion ellen u n d morph seh en R e a k tio n en b estim m t d a s k lin isc h e B ild u n d d a s Z eitm a dt; P rogred ien z u nd b eein flu t d am it au ch d en S ch w eregrad d er Lunow. V ernderung. d ) V ir leh n e n -- in b er ein stim m u n g m it d em S c h r ifttu m _ i,, u n m ittelb a re can cerogen e W irk u n g d es A sb estes ab : d ie U b iq u itt voi H erd en m it ep ith elialen R egen eration en erh h t allein sch o n d ie V ale sch ein lieh k eit f r d ie E n tsteh u n g ein es L un gen carcin om s. 6. D er in d en letzten Jah ren geu erten A n sich t, da d as Lungenca rein o m b eim A sb esta r b e iter n ic h t h u fig e r a ls in d er allgem einen m n n lich en B ev lk eru n g sei, k n n en w ir n ich t zu stim m en . V o n 13 Mann ern z e ig e n in u n se rer S a m m lu n g 6 ( = 4 6 ,2 % ), v o n 2 3 F r a u e n 5 ( = 21.7,ein L u n gen carein om (b zw . ein P leu ra en d o th elio m ). B ercksichtige!: w ir, u m ein en sta tistisch ein w an d freien V ergleich d u rch zu f h ren , nur d ie F lle d es S t. G eorger S ek tion sgu tes v o n 1948-- 1958, so ist di h h e r e K r e b se r w a r tu n g g e g e n b e r d e m a llg e m e in e n S e k tio n sg u t dieseZ e it a b s c h n it t e s u n v e r n d e r t e in d e u t ig : b e i d e n M n n e r n m it 4 4 .4 "s (g e g e n b e r 1 1 ,6 % im a llg e m e in e n S e k tio n sg u t), b e i d e n F r a u e n mit 2 9 ,4 % (g eg en b er 2.1 V im a llg em e in en S ek tio n sg u t). U n ter den 11 L u n gen careinom en fin den sieh 4 P leu raen d oth eliom e. D as durch sc h n ittlic h e S ter b e a lter u n d d ie D a u er d er L a te n z z e it en tsp re ch en den A n g a b e n in d er L itera tu r. In u n serem M a teria l b este h t k ein e B eziehung zw isch en L u n g en k reb s u n d S ch w ereg ra d d er L u n g en v er n d eru n g . U nter B er ck sich tigu n g d er H istogen ese ersch ein t d as verstn d lich . 7. D er A n teil d er ex tra p u lm o n a len C arcin om e ist eb en fa lls erhht. D a s M a g en ca rcin o m k o m m t m it 11,1% (od er 15,4% , b ezo g en au f das A sb esto se-S ek tio n sg u t v o n 1948-- 1958) g eg en 6,1% g eh u ft vor. H e s c h o n v o n Leioher a u s g e s p r o c h e n e V e r m u t u n g e in e s Z u s a m m e n h a n g e s v o n P e r ito n e a lc a r c in o m u n d A s b e s to s e e r h lt e in e S t tz e , d a sich in u n serem M a teria l 3 P e rito n ea lca r cin o m e fin d e n , d . h . 8 ,3 % (o d er 11,5; b ezogen au f das A sb estose-S ek tion sgu t von 1948-- 1958) gegenber 0,16% im allgem ein en S ek tion sgu t. 8. S ch lu folgeru n gen au s u n seren E rgeb n issen f r d ie B egutachtung w erden besprochen. ber die Asbestose 201 W ege d er S ch w ierigk eit, k lin isch e u n d rn tg en o lo g isch e (an atom i- .!,,) B ild e r z u r D e c k u n g z u b r in g e n , w ir d v o r g e s e h la g e n , in d e r gpgutachtung b egrifflich zw isch en A sb estose u n d A sb estlu n ge zu u nterscheid en . L iteratu r BSS, : ber Asbestose der Lungen. Mnch, med. Wschr. 1935, 1797. V Mtiorw: Lung cancer in Asbestosis. Lancet 19551, 1163. iUiUKR. E. W .: Asbestose. Dtsch. med. 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Gl y o n e : Pulmonary asbestosis complicated by pul monary tuberculosis. Lancet 1931II, 954. W ood, W. B., and S. R. Gl o y n e : Pulmonary asbestosis. Lancet 193411, 1383. I)r. med. J oachim K oine. Hamburg 34, Rennbahnstr. 22 yrekiv fr Gewerbepathologie und Gewerbehygiene 18, 205--219 (1960) y' dem Pathologischen und Bakteriologischen Institut der Hauptstadt Hannover *a (Leit. Arzt: Prof. Dr. N ordmann) Asbest-Zementstaufo-Lunge (P n eu m ok on iose b ei M ischstau b oder gem isch tem S tau b ?) u n d H a n n o v e r Martin Nordmaxx Von H ermann Sonnenberg, Mit 5 Textabbildungen (Eingegangen am 14. Juni 1960) D ie K om b in ation von A sb est u n d Z em en t k om m t b ei d er H erstellu n g von P latten , d ie zu W n d en u n d D ch ern b en u tzt w erd en od er au ch von B eh ltn issen u n d Isolierk rp ern vor, d ie in d er E lek tro in d u strie V er w endung fin d en . B eid er B earb eitu n g von A sb est-Z em en t k an n es sta u b en , w enn d ie geh rteten P la tten zersgt w erd en . Z em en tstau b g ilt als u n gefh rlich , jed en falls steh t d ie Z ah l d er M enschen, d ie au sn ah m sw eise d u rch Z em en tstau b gesch d igt w erd en , in keinem V erh ltn is zu d er M en ge d er in d er Z em en tin d u strie B esch ftig ten . A sb est b ew irk t b ek an n terw eise ein e A sb eststau b -L u n ge (A sb estosis), die erst n a ch v ie le n J a h ren ein e B ee in tr ch tig u n g d er A tm u n g so rg a n e bew irkt u n d d u rch K o m b in a tio n m it rezid iv ieren d en L u n g en en tz n dungen, T u b erk u lose u n d K reb s d as L eh en gefhrdet. D ie K om b in ation v o n A sb est u n d Z em en t als U rsach e ein er S tau b lunge m it a u to p tisch er B est tig u n g ist im b ish erigen S ch rifttu m n och n icht b esch rieb en w ord en . E in e E rk ra n k u n g u n d gar ein T o d esfa ll n a ch E xposition v o n A sb est-Z em en tstau b sin d offen b ar selten ; an gesich ts der verm ein tlich en H a rm lo sig k eit d es Z em en tes w re n u r ein e A sb estlu n ge zu erw arten gew esen. D er von u ns b eh an d elte F all h a t n och ein e d ritte S tau b art im W erk stoff: T alk u m , allerd in gs in ein em seh r gerin gf gigen P ro zen tsa tz, d er trotzdem n ich t u n b ea ch tet gelassen w erd en soll. B ei unserer B eob ach tu n g h an d elt es sich u m d en 68jh rigen N ., d er sehr lan ge Z eit in ein er k lein en F a b rik m it ein em seh r k lein en P eT sonenkreis g ea rb eitet h a t, d ie au s eig en er A n sch a u u n g zu n ch st b esch rieb en w erden soll. Die Arbeitssttte D er F ab rik ation sb etrieb -- ein k lein er F am ilien b etrieb im H in ter hof ein es m eh rstck igen W oh n h au ses -- b esch ftigt 6 A rb eiter u n d luft in ein em n ied rigen S ch u p p en ab , d er in 2 R u m e g eteilt ist, in denen d ie M asch in en steh en . Im ersten R au m w ird ein erd feu eh tes G em isch v o n A sb est u n d Z em en t an ger h rt u n d in ein er D ru ck p resse Aich, p.wprhpnot.h pwfirhphvff Uri IS 1/1