Document 5LddQ5Me2KZdn50Ey2Z2GNNXR

FILE NAME: German Articles - Some with English Translation (GER) DATE: 1953 Feb DOC#: GER013 DOCUMENT DESCRIPTION: Medical Journal Article - Pulmonary Carcinoma in Pulmonary Asbestosis From: Medizinische Monatsschrift 7:77-81, February 1953 From the Pathological Institute of the Municipal Hospitals, Dortmund (Director: Prof. Dr. Fr. Boemke) Pulmonary carcinoma in pulmonary asbestosis By Fr. Boemke with 3 illustrations While, in the case of numerous other kinds of dust, the macroscopic morphological substratum of the dust does not have to be, by any means, immediately and unequivocally characteristic of a certain type of dust, the finding of asbestosis (!) corpuscles in the sputum or, post mortem, in the lungs, generally justifies a diagnosis of pulmonary asbestosis. It is true, that there are certain exceptions from that rule, inasmuch as the formations designated as asbestosis corpuscles occasionally even though rarely - are found in the lungs of subjects who demonstrably have never been exposed to asbestos dust. Nordmann reported such find ings and spoke, in such cases, of pseudo-asbestosis corpuscles. Recently, Langer reported the presence of asbestosis corpuscles in a worker who was employed in the glass wool industry. Doerr also mentioned recently, in an oral discussion, the case of a woman in whose lungs asbestosis corpuscles were found, and in whom, without any doubt, no occupational activity entailing any action of asbestos doubt had been present. But, despite those reservations, it may, indeed, be stated in a general way that, as a rule, the demonstration of asbestosis corpuscles makes for a diagnosis of asbestos pneumo-coniosis (pulmonary asbestosis), and that the afore-mentioned unusual observations of occurrence of asbestosis corpuscles without any action of asbestos dust are rare, isolated cases. 2/ It is well known that pneumoconiosis caused by asbestos dust, when there is a considerable amount and when the action of the dust continues over a considerable period of time, may lead to fibrosis of pulmonary tissue; that fibrosis is a disease for which indemnity is established legally. Recently, Behrens demonstrated by means of animal experiments that this asbestos-fibrosis is to be considered a partial phenomenon of a connective-tissue encapsulation of foreign bodies, and that asbestosis corpuscles as such have no specific significance in the fibrosis of pulmonary tissue. According to his investigations, that fibrosis rather appears to be the reaction of the tissue to foreign bodies containing long fibers. In this connection, we may point out, on the basis of our activities as medical expert, that not every pulmonary asbestosis as such is a disease legally to be indemnified. The proof of the presence of asbestosis corpuscles in the sputum alone is not sufficient for granting a disability pension, but the afore-mentioned connective-tissue-like changes, the fibrosis of extensive parts of the pulmonary tissue with loss of their function for respiration and circulation are required. We do not intend here to go into any further details about the propagation of the asbestos dusts in pulmonary tissue and on the type and spread of fibrosis in asbestos lung. We make reference to the pertinent communications in the literature - Nordmann and others. Beger recently characterized the mineralogical and chemical nature of asbestosis corpuscles in detail in several papers - lately in a lecture presented at the Meeting of the German Association of Pathology at Kiel in 1949. Pneumoconiosis due to asbestos dust entails, however, not only a 3/ fibrosis of the pulmonary tissue^ under certain conditions a pulmonary carcinoma may also develop, in connection with asbestosis. This fact makes pneumoconiosis due to asbestos stand out among the group of pneumo conioses. It is well known that only a few conioses are associated with frequent development of lung cancer; among them, the so-called Schneeberg miners' disease, is probably best known. For the sake of completeness, we want to point out here that, according to more recent investigations, lung cancer is found also in workers handling chromium. At this point, a general statement is required. Pulmonary cancer associated with silicosis are not, by any means, frequent. Rather, it has been determined by means of statistical surveys that, percentage-wise, the number of lung cancers in workers suffering from silicosis does not exceed the number of lung cancers without silicosis (W. Fischer, Spdrlein, and many others). When giving an esqjert opinion on a pulmonary carcinoma, one will be able to assume a connection only in the very rare cases, in which it can be demonstrated that it originated in a decay cavity within a silicotic nodule (di Biasi). Things are different, inasmuch as lung cancer associated with asbestosis is concerned. The connection between the pathogenesis of this type of cancer and the action of that particular type of dust has been confirmed by animal experiments (Nordmanr} and has been recognized legally for the purpose of insurance claims. Pertinent observations, partly with reviews of communications published up to the time of those obser vations, have been reported, among others, by Normann, Wedler and Linzbach, Gloyne, and Boemke. In any case, lung cancer associated with 4/ asbestos is rare when related to the number of cases published. Up to the time of a first pertinent case, which I reported in 1943, I was able to find only 17 cases in the literature; for that reason, a comprehensive discussion of three observations of my own appears to be justified. Inasmuch as the facts of my first case are concerned, I can be brief since I have discussed it in this journal, in 1947. It was the case of a man of 71 years who had been employed as comber in an asbestos plant over a period of 11 years, and in whom grave pulmonary asbestosis had been diagnosed 6 years before his death. Shortly before his death, a pulmonary carcinoma was found during a hospital stay. The autopsy showed asbestos fibres of the pulmonary tissue and diffuse cancerous penetration of the lower right lobe of the lungs. In other lobes of the lungs too, cancerous proliferations were found. In addition, an extensive carcinomatosis existed in the right pleura. Cancer metastases were found in the intra-thoracic and intra-abdominal lymph nodes, in the spleen, in both kidneys, in the left adrenal gland, in the liver, in the wall of the large intestines, in the ribs, in the vertebral column,in the left femur, and in the skin of the head. Inasmuch as the proliferation of cancerous growths in the right lower lobe of the lungs and the chronological and spatial con nections of asbestosis and pulmonary carcinoma are concerned, I make reference to the following over-all discussion of the three cases. The two additional observations have not yet been reported by me in any detail. They have to do with a woman who died at the age of 57 years, and with a man of 53 years. 5/ The woman of 57 years was admitted to the Medical Clinic of the St. Johannes Hospital at Dortmund in October 1950. She suffered from considerable breathing difficulties and bloody sputum, high temperature and nocturnal perspiration. Before admission, she had lost 6.5 Kg in a short period of time. The history of earlier illnesses is of no importance in the contest of this discussion. At the time of admission, her strength and nutritional state were at a very low ebb. There was an area of dullness with humid rattles sounding like small or medium-sized vesicles above the right lobe of the lungs. The erythrocyte sedimentation rate was 51/78 mm. During her stay at the clinic, continuous temperatures around 38C were measured at first. The patient suffered from sputum that was lumpy, light red, partially similar to raspberry jelly. No tubercle hecilli could be demonstrated at any time. The X-ray picture showed a striped-spotty shadow in the lower part of the left lobe of the lungs with formation of transverse strands. The shadow filled the left sinus phrenico-costalis. In October 1950, the sputum of the patient was sent to me to be tested for the presence of tumor cells (Test # 7,191/50). In the sputum, numerous typical asbestosis corpuscles were found (see Fig. 1). Fig. 1. Asbestosis corpuscles in sputum (Test # 7,191/50, 57 years old female) 6/ During the further course of her hospital stay, the patient gradually became fever-free, but at the same time, an increasing dyspnea developed. The dullness in the region of the lower right lobe of the lungs persisted, as did the 3 copious sputum which amounted to 50 to 250 cm per day. Associated with increasing cachexia, increasing cardiac insufficiency developed. Death occurred in March 1951. From the report on the autopsy (Autopsy #109/51), only those findings shall be mentioned here that are most essential in the context of this presentation. Both lungs, and in particular the lower part of the left lobe, showed accretions to their environment. The left lung was volumi nous and heavier than normal. The lower lobe presented, on the cutting surfaces of the over-all densified tissue, regularly distributed, whitish, partly rough, partly pulpy areas with small black spots and stripes. In the rough, whitish, thick ened pleura of the lower left lobe of the lungs, too, pulpygrey strands and foci could be demonstrated. The consistency of the left upper lobe contained excessive air in the marginal areas. In part, central sections proved to be extensively densified and tough. Here,too, rough grey-whitish segments could be found, but they did not contain any pulpy foci. The marginal regions were coarsely meshed and collapsed when an incision was made. The right lung was also voluminous, but lighter in weight. The pleura showed rests of accretions, 7/ in the form of grey-whitish, thickened shreds. In regions free of accretion, the pleura was light grey-red, with interspersed black spots and stripes. The marginal regions of the lung were partly inflated like air-cushions. In other regions, the consistency of the right lung was uneven, characterised partly by dense foci, partly rather by doughy densifications. On the cutting surfaces, the marginal regions corresponded to those of the upper part of the left lobe, while all the other pulmonary tissue was partly whitish, partly greyish-red to dark red, altogether unevenly spotted and interspersed with small black spots and stripes. . The bronchi in both lungs could be cut open up to the immediate vicinity of the pleura. No circumscribed tumor as origin of the pulpy, greyish-white regions which were described above and which appeared to us macroscopically to be neoplastic growths, could be found. The lymph nodes of the radix pulmonis which were somewhat larger than peas, were also partly tough-elastic, greyish-red with black inclusions. The pericardium adhered to the thick ened pleura of the lower part of the left lobe on the one hand and to the heart on the other hand. Upon incision, the tissue in that region was found to be partly tough, greyish-white, partly pulpy-grey. After cutting the accretions on the rear wall of the left chamber, we found here that pulpy, greyish- white areas rested firmly on the epicardium and extended into the superficial muscle segments of the wall of the left chamber 8/ of the heart. All cardiac cavities were enlarged. The left half of the diaphragm was also comprised within the pleural accretions and had degenerated into tough, greyish-white tissue with smaller pulpy, greyish-white areas. Those pulpy, greyish-white areas extended beyond the diaphragm into the left lobe of the liver, the upper pole of the spleen, the left adrenal gland, and the serosa of the stomach wall. The other findings of the autopsy are of no interest in connection with this discussion. During histological examination, very large alveolar spaces with thin, elongated or torn septa were found in the marginal regions of the lungs. At other locations, all lobes presented rather extensive, hyaline, connective-tissue containing regions with irregular boundaries. Part of the alveolar septa are widened considerably by connective tissue formation. Every where, in the alveoli as well as in the connective tissue, asbestosis corpuscles of typical structure were found - partly shaped like dumbbells, partly in the form of rolls of coins, partly in spear-shaped or splinter-shaped formations that look as if they were broken off and are of a brownish-shiny color; in the Prussian-blue test, they reacted positively. In sections from the lower part of the left lobe of the lungs, epithelial cells of the type of plate epithelium could be shown every where they grew in irregularly infiltrating formations, and it was possible to observe numerous atypical 9/ mitoses. Typical asbestosis corpuscles of the structure as described above lay also between those epithelial formations (see Pig. 2). Fig. 2: Asbestosis corpuscles within the plate-epithelial carci nomatous growths in the lower part of the left lobe (Serial # 109/51, 57 years old female). Asbestosis corpuscles = a. Cancer cells with mitoses = b The histological examination of the other organs had the following important results: epithelial growth in the left chamber of the heart also, they spread to the muscle and are found also in the region of the left lobe of the liver, of the left adrenal gland, of the upper tip of the spleen, of the serosa of the stomach, of the left pleura, and of the left diaphragm. Consequently, on the basis of the pathological-anatomical findings with which agree with the clinical ones, we have to do/a typical asbestos fibrosis of the pulmonary tissue with extensive growths of plateepithelial carcinoma in the lower left lobe of the liver, without any circumscribed point of origin, and with a carcinosis of the left pleura with invasion of the cancerous growth into the pericardium, the heart, the left half of the diaphragm with penetration of that half and further spread of the cancerous neoplasms to the liver, 10/ the spleen, and the serosa of the stomach wall. Lastly, we want to mention that, in this case, connective tissue areas that were poor in nuclei and included some asbestosis corpuscles could be found, a finding that is observed but rarely, because the asbestosis corpuscles - very likely because of their size - do not pass through the lymphatic pathways of the lungs as easily as other kinds of dust (see Fig. 3). Fig. 3; Asbestosis corpuscles in a lymph node from the hilus of a lung (Serial # 109/51. 57 years old female) Asbestosis corpuscles = a. Anthracotic pigment = b. The occupational history showed that the patient worked from her 17th to her 20th year in an asbestos factory on a pull-test machine. The raw material which arrived in the form of bales, was pulled apart there, and that caused the development of much dust which was eliminated by the fans that were available in the work room, only in a very unsatisfactory manner. As we have mentioned before, the third case is that of a foreman who, at the time of his death, was 53 years old. He was gravely ill hen he was admitted to the 1st Medical Clinic of the Municipal Hospital at Dortmund, in August 1951. He said that he had felt ill only during the last 3 weeks before his admission to the Clinic. 11/ His illness began with increasing dyspnea and swelling of the feet as well as with pain in the upper part of the right arm. At the time of admission, we found a considerable cyanosis of the lips associated with severe dyspnea and frequent coughing. Both lungs presented the picture of congestion. The borders of the heart were broader than normal on both sides. The liver could be palpated, in a width of two fingers' breadth above the right lower costal arch. The abdomen was tympanous. Both lower legs showed edematous swell ings. The patient made the impression of a gravely ill person, so that it was necessary to do without any additional clinical exam inations. He died during the night after his admission to the clinic, and the obduction took place at the Pathological Institute of the Municipal Hospitals Dortmund on the following day (Protocol #305/51). We shall, once more, present only the findings that are most important in the present context. Both lungs presented extensive accretions to the thoracic wall and and to the diaphragm. They were partly superimposed on the peri cardium and were very voluminous and heavy. Their free margins were blunt or rounded. The pleura had extensive whitish-grey vestiges of accretions and rough-whitish, thickened areas, in particular in the region of the base and of parts of the tip. The interlobar fissures had also coalesced. The consistency of both lungs was rough, elastic, partly inflated, within circumscribed marginal areas only, in the manner of air-cushions. On the cutting surfaces, the lung tissue presented, on both sides, diffuse yellow-brown-reddish, 12/ spots and isolated small, soft, black spots and stripes which, altogether, were not very extensive. Particularly, in the lower lobes, the cutting surfaces presented an extensive, grey-whitish net. Circumscribed formations of nodes could not be demonstrated. to be The bronchi appeared to have thick walls and/more or less compressed by the surrounding rough-elastic pulmonary tissue. But, it was possible to cut them open up to the immediate vicinity of the pleura, reaching into their more delicate ramifications. Their mucosa was greyish-red to darkened, covered by a greasy reddish-grey, toughslimy fluid. The vessels of the lungs were empty, the lymph nodes of the hilus of the lungs had the size of two beans; they were soft, partly black, partly whitish-grey and spotty. Since the findings in the lungs in combination with earlier observa tions appeared to me to justify a suspicion of asbestosis, native preparations were made during the autopsy. In the press-juice from the cutting surfaces of the lungs, numerous typical asbestosis corpuscles could be demonstrated microscopically. In addition, pulpy whitish-grey regions were found in both adrenal glands; next to them, only scanty vestiges of adrenal parenchyma were present. The heart was enlarged and expanded; in particular, the wall of the right ventricle was thickened, and the clearance of the right ventricle was enlarged considerably. The weight of the heart was 465 g. Lastly, there was an abundance of blood of the inner organs, due to congestion, with an ascites 3 of 300 cm . 13/ We want to mention one additional finding that is of lesser importance in this connection, but is important as a contributing cause of death, viz., an arteriosclerosis of the coronary arteries of the heart, associated with the formation of small callosities in the muscles of the heart. In the histological examination, we found, once more, alveolar septa thickened by connective tissue and partly infiltrated by asbestosis corpuscles, in all lobes of the lungs. Likewise, we found in many alveolar clearances groups of asbestosis corpuscles of widely varying shapes, partly of the type of the coin-roll or dumb-bell shapes, partly of the type of spear-or splinter-shaped formations; they were of a brownish-brilliant hue. In the lower lobes, irregularly bordered, extensive areas of connective tissue were present. Between those stretches of connective tissue, especially in the lower lobes and less extensively in the other lobes of the lungs, there were irregularly arranged epithelial cell groups and steins which, in part, filled the alveoli completely and, in many cases showed cells with atypical mitoses and polymorphous nuclei. A circumscribed point of,orgin of those epithelial formations could not be demonstrated. Between those epithe lial groups of cells, there were likewise a great many asbestosis corpu scles to be found. Lastly, very wide alveoli with thinly elongated or torn septa could be domonstrated in sections from marginal areas of the lungs. The lymph nodes of the hilus of the lungs also presented, besides vestiges of lymphatic tissue, an irregular and diffuse infiltration of 14/ epithelial cell groups of the described structure* among connective tissue areas, again, we were able here, too, to find asbestosis corpuscles. The adrenal gland presented, likewise, a diffuse infiltration of epithelial growths with many atypical mitoses. Accordingly, we had to do in this case, too, with asbestosis complicated by fibrosis of pulmonary tissue and extensive cancerous growths in the lungs. The latter ones had caused metastasization into the lymph nodes of the hilus of the lungs and into both adrenal glands. Later, an attempt was made, on the basis of the observations made, to look into the history of the subject's occupation. But, since he was a refugee, it was- not possible to-get any exact information as to his past activities. It could be ascertained only that he was supposed to have worked a long time in an asbestos plant. But, the duration and nature of his employment could not be determined. Especially in the diagnosis of cancer in an asbestos-dust lung, the collection of data concerning former employment is of essential importance. Nordmann has pointed out certain laws governing the occurrence of cancers in asbestosis. In some of those who died of asbestosis complicated by carcinoma, the pulmonary carcinoma appeared when they were relatively young. It is true that in the cases which I have observed, that statement does not apply, particularly inasmuch as bronchial or lung cancers occuring without the presence of asbestosis are now observed in younger people more frequently. But, another finding seems to me to be of particular interest. In the majority of subjects suffering from lung cancer complicating asbestosis, 15/ a certain rather identical period of time passes between the beginnings of their employment in an asbestos establishment and the time of their deaths due to lung cancer. That period of time amounts, according to Nordmann, to 18 years, and unequivocally applies to my first case, too. It is true that, in the 2nd case, a time period of no fewer than 37 years elapsed between the beginning of occupation in an asbestos plant and death due to lung cancer associated with an asbestos-dust lung, while in my third case the period cannot be calculated, for the reasons given above. Of course, the figure calculated by Nordmann is to be considered an average period only. As in my second case, upward and downward variations occur. Bauer gives the period elapsed between the onset of the action of the asbestos dust and the appearance of the carcinoma as ranging from 12 to 42 years. It does not matter whether the ejqposure to the dust was continuous up to the time of the development of the can cer, or whether a dust-free interval occurred between the exposure and the development of the cancer. But, it is a matter that, besides the cancer, an infiltration of the pulmonary tissue by asbestosis corpuscles must be present if lung cancer associated with asbestosis is to be the diagnosis. Data concerning the calculated percentage of lung cancer complica ting asbestosis vary. In 50 autopsies of asbestosis cases, Gloyne observed lung cancers in 6 cases, i.e., 12%. In a smaller number of asbestosis deaths, Nordmann arrives at 17% of lung cancers. On the basis of my cases, I can confirm also additional regular phenomena as shown by Nordmann, i.e., the preference of the primary carcinoma for a 16/ lower lobe of the lungs. We may assume that, in accordance with the kind of spread in the male of 71 years, the cancer started in the lower right lobe of the lungs. In the case of the female of 57 years, the cancer growtte also had their primary location in the lower left lobe of the lungs. In the last case described, extensive carcinoma growths in both lower lobes could be demonstrated. It is true that, in that case, no preferred involvement of one or the other lower lobe could be shown. Lastly, it is a notable fact that, in the majority of all cases, plateepithelial carcinomas are present - as is true of my two first cases while, in the third case, the cancerous growths were less differentiated even though they contained giant cells. It is of special significance and downright typical of pulmonary carcinoma complicating asbestosis and as a sequel of asbestosis, that the cancerous growths in the lungs have a multi-centric pathogenesis. In such cases, it is never possible to demonstrate a circumscribed point of origin, as is the case, e.g., in bronchial carcinoma. The cancerous formations are rather present in the form of a completely irregular distribution within the affected regions of the lungs, so that multiple metaplastic carcinoma has to be called characteristic of asbestosis. In view of the undoubted connection of asbestosis and lung cancer, there arises - as a matter of course - the question which factors are of decisive importance for the pathogenesis of the carcinoma. We have to think of the fact that a coarse-mechanical trauma of the relatively large asbestos dust structures must be considered; when that effect is 17/ continuous, it may lead, in the end, to a precipitate regeneration and to epithelial metaplasias with subsequent cancerous degeneration. There is no doubt that that explanation alone does not solve the problem, inasmuch as it is likely that chemical processes have a determining influence in this type of cancer also. Summary On the basis of the author's observations, the connection between pulmonary asbestos fibrosis and lung cancer is discussed. The particular laws that are characteristic of this special form of cancer - in particular, the preferred location in the lower lobes and the multi centric origin of plate-epithelial cancerous growths in the lungs are stressed. f certify that the staff member who translated the foregoinq is thoroughly familiar with theCS--- and English languages and that it is a true and complete translation of the corresponding<S^S=ae; document. f Franklin W . Clark, President Language Service Bureau, Ine Dupont Circle Building W ashington, D.C. 20036 EDIZ1N Zeitschrift fr allgemeine Medizin und Therapie Schriftleitung: CU RR. Ll> i iviL-U. ' Priy.-Doz. Df. med. habil. Hans Braun, Mnchen W issenschaftlicher B eirat: 'Beratdes, Mannheim K . Blumberger, Dsseldorf A . von Braunmhl, Haar bei Mnchen fl. Eymer, nchen A . W.Forst, Mnchen J.Fuchs, Stuttgart R. Geiendrfer, Frankfurt a. M. A. Hahn, Mnchen ^ Heilmeyer, Freiburg IF. Hneck, Mnchen IF. Knierer, Mnchen J \ Kuhlmann, Essen ||jf; lAndemann, Roltach a. Tegernsee 0. Lorenz, Dortmund //. Malluche, Falkenstein IF. Mahoff, ^Tbingen Meggendorfer. Erlangen iFA. Naegeli, Tbingen //. Schloberger, Frankfurt a. M. J. Schiiller, Dsseldorf * IF. Seitz, Mnchen F. Steigerwaldt, M nchen .4. Sturm, Wuppertal O. Ullrich. Bonn (7. IIVW, Mnchen INHALTSVERZEICHNIS bersichten -- rztliche Fortbildung Z>r., Dr. P . G, Seeger: ber die Bedeutung > des Vitamins A fr die Prophylaxe ver schiedener Krankheiten, insbesondere die ; Krobsprophylaxe.......................................... - Dr. Gnther Wolff:Neues berdas Hyalurongiiure-Hyaluronidaao-Systoni ................. Originallen Prof. Dr. Fr. Boemke: Das Lungonkarzinom in der Asbest-Staublunge.............................77 Dr. Viktor Tobiasch: ber die schworo Vor- laufsforin dos Erythema exsudativum multifo rm o .......................................................... 82 Prof, Dr. Peter Dohr: Indirekte Vaterschal'ts- aussohlioliung bei der lilutgruppon-Bostirnmung mittels Untersuchung bluts verwandter Personen................................. Dozent Dr. Georg Heuchet: ber eine Sonderform der subakuten Glomerulonephritis . 89 Dozent Dr. Paul Bernhard: Die einzeitige Utenisdilatation mit Hilfe langsporfo- rierter M eta llstifte......................... .... 03 Dr. N . Goossens: Zura Problem der porkutanen Thrombo-Embolie-Prophylaxo . . . t)4 Dr. U. Martin u.K.Gralzl: Ein Versuch, den neurovegetativon Status graphisch darzus t e l l e n .......................................................... 100 Dr. Hermann Heizer: Zur Therapie der Dys menorrhoe..........................................................105 Dr. Benedikt Babel: Zur Behandlung des Darms bei gaatrokardialen Strungen und bei Lobor-Gallen-Baschworden.................... 108 Kasuistik Priv.-Doz. Dr. Hans Braun: Zur Begutach tung innerer Krankheiten......................... 11 i Dr. A. Drassdo: Ein Fall von spontaner ex-7 ' tomer G a llen fisto l..................................... 112 Grenzgebiete Dr. Jaromir Lhotsky: Gesprche mit dom U n b o w u te n .................................................. 114 Geschichte der Medizin Erwin Dichter: Einwirkung des I'aracelsisinua auf die Entwicklung dt Votivwesens 115 Rechtsfragen Dr. M. Lehmann: ,,Zustellung" von .Schrift stcken .......................................................... 1 1 9 Therapeutische Rundschau.....................................119 Dag R e z e p t .......................................................... 121 Buchbesprechungen.............................................. 121 Referate nach Fachgebieten ............................. 126 Tagungsberichte..................................................... 134 Ilochschuliiachriehton..........................................137 Kleino Mitteilungen..............................................138 iahrgang Februar 1953 Heft 1 H S S E N S C H A F T L I C H E V E R L A C S H F C F i f r M a c t u u u c t u t t p !.' Boemke: Das Lungenkarzinom in der Aslx.\stStaublunge d 77 4 eindringen knnen. Man hat- nun auch versucht vor- y 9hiodene Formen der mnnlichen Sterilitt, dio auf ttnen Hyaluronidasemangel zurckzufhren sind, durch Substitutionstherapio anzugehen. Kurzrock55 und Mit I arbeiter wiesen schon 1946 nach, da ein Teil der un 1 fruchtbaren Ehen auf einen llyaluronidasetnangel im Sperma zurckzufhren ist. Sie konnten durch Beigabe von Hyaluronidase zum Sperma eine Graviditt erzielen. Pas Medikament wird hierbei frischem Sperma beigefgt 15. D aran-H eyn als: Proc. Soc. exp. Med. JJiol. 38, 763 (1938) 16. M eyer und Cheffee: .1. Idol. Chem. 138, 401, (1941) 17. Sehoen: D tseh. Med. W schr. 77. 17, 558 (1952) 18. Hfling: rztl. W schr. 6, 29, 686 (1951) 19. Kppinger: Pcrm eahillttspathologie, Springer W ien 20. Forrest: J . o f Pharm , ami Pharm acol. 1952 ,4, 231 21. (libiun: Hoppe Seylers Z. f. phys. Chem. 289 (1951) 22. M ahaux: Acta clin. bei. 7, 338 (1952) 23. Schiirch: Schweiz Med. W schr. 80, 711 (1950) Hartmann: Z. f. Rheuinaforsehg. 11, 23, (1952) 24. Laves: Klin. W schr. 534 (1948) 25. Langecker: Klin. W schr. 30, 9/10, 222 (1952) und in den Zervikalkaual -- oder einige Zeit ante eohnbitationem in denselben -- injiziert. Spielt die Hyaluro nidase beim Befruchtungsvorgang zumindest eine nicht unerhebliche tiologische Kollo55, so war es naheliegend auch das Gegenstck hierzu, eine Hyaluronidasehemmung als Antikonzipiens zu untersuchen. Martin und Heiler57 fanden, da Hesperidin als Hyaluronidaseinhibitor wirkt. Im Tierexperiment konnten sie durch diese Hyaluroni daseblockierung eine vorbergehende Sterilitt erzielen. Inwieweit diese Methoden ohne eine gesundheitsschdi gende Wirkung auch beim Menschen anwendbar sind, ist augenblicklich noch eine offene Frage. 26. Flerker: rztl. W schr. 5, 34. 638 (1950) 27. Doyens: T her. d. (iegenw. S<), 6, 169, (1950) 28. Schwartzmann: X.Y. J . Med. 51, 215 (1951) 29. Koslowski: r/.tl. Praxis 4, t> (1952) 30. Weidenbach: Therapiew oche 2. 189, (1952) * 31. Sim on-W eidner: 1). Chir. 23, 10, 464 (1952) 32. Dammann: D. Med. 22. 765 (1952) Rosenthal: A naesthcsist 1, 75. (1952) 33. Saiterwein: Z ahn- M und- u. Kieferheilk. 12, 189 (1952) 34. Raum: Am. J . obstetr. Gyn 62, 658 (1951) 35. Erhard und Rauh: M nch, m ed. W schr. 9 1, 2019 (1952) 36. Po ruf: La presse linM. 60, 22, 474 (1952) 37. Maschas: Hull, e t Mt'im. Soc. mod. Hop. Paris 67, 1097 (1951) 38. Ehievt: Med. K lin. 40, 716 (1951) 39. Husch und H rinkm ann: Mnch. Med. W schr. 94, 533 (1952) Lass: lic itr. klin. Tbk. J00, 101 (1951) An dieser Stelle konnten aus Raummangel nur die wichtigsten Ergebnisse aufgezeigt worden. Sicher be stehen bei vielen Krankheiten engere Beziehungen tio M ansm ann: Die Therapiewoche 2, 468 (1952) 40. Hrcsyen: M nch. Med. W schr. 93, 13, 657 (1951); Verb. Tun. Med. Wie baden 1952 41. Fiebelkorn und Mkesch: Med. Msehr. 6, f>16 (1952) logischer und pathogenetischer Art zum HyaluronsureHyaluronidase-System, als man bisher angenommen hat. Damit erffnen sich auch neue therapeutische Mglich Mller-Meernach und Hudniok: r/.tl. W schr. 6, 1187 (1951) 42. Halt und llauser: Press, med. 60, 5, 106 (1952) Huit: The J . o f Urolog. 67, 4. (1952) 43. Lebewson: An. J . ophtlialm . 33, 865 (1950) keiten. Weitere Literaturangaben ber das Hyaluron sure-Hyaluronidase-System finden sicli in den Medizi nischen Mitteilungen von S c h e r in g sowie in den ausge K ey: Texas S ta te J . Med. 40, 31 (1950) 44. Heinberg: Kar etc. Mt hl. 30, 31 (1951) 45. Vlger: IINO 3, 142 (1952) 46. Keining: D enn. W schr. 120. 633 (1952) zeichneten Arbeiten von Gibian4 und Billerbeck5. Keil: H autarzt 3, 321 (1952) Langhof: D enn. W schr. 126, 764 (1952) Braun Falco: Derm. W schr. 124, 796 (1951) Literaturverzeichnis Rosm an: X .Y . S ta te J . M. 50, 1939 (1950) 47. Tuchmann: Am. J . Med. Sei. 219, 147 (1950) 1. Klcmperer: A ,, J . P a th . 4, 503 (1050) 2. Daran-Reynals: La Sem. des H op. 2$, 25, 1047 (1952) $. Conference o f th e grottnd su b sta n c e.o f th e m esenchyuir an d H yaluro nidase: Am. X .Y . A rad. Sei. 52, 043, (1050) 4, Gibian: Angew. Chem. 63, 5, 105 (1951) 5. BUirrbfrk: rz tl. Forsohg. 6. 5, 107 (1952) & fcyer: J . bioi. Chem. 107, 629 (1934) f, baetpre: La presso intu. 67, 1400 (1051) 8; Durati-Keynais: ,1. Kxp. Mod. 50, 327, (1929) 9, Chain, D uthie: Tlrit. Exp. P a th . 21, 324 (1940) Uli Stroder und X igyemeyer: Z. f. d. ges. exp. Med. 119, 301 (1952) * Uggenteyer: Msohr. f. K inderhoilk. 9S, 2, 67 11, Favelli: W ien klin. W schr. 64, 33, 405 (1952) Gibian: Hoope Seylers Z. f. phys. Chem. 2S9. 165 (1952) 48. Richter: T herap. d. Gcgcrnv. 91, 9, 333, (1952) Fllickingcr. Praxis 41, 25, 536 (1952) Henschrn: Schweiz. Med. W schr. 82, 7, 173 (1952) Lacepre: La presse md. 67, 1400(1951) Hagedorn und Rosenthal: Z. f. Chir. 77, 20, 834 (1952) Ilunkit: Z. G eburtsh. 136, 192 (1952) Ehrhardt und Rauh: Mnch. Med. W schr. 94, 2019 (1952) M in k und Lang: Dtseh. Med. W schr. 75. 43. 1328 (1952) de Rudder: Dtseh. Med. W schr. 75, 313 (1950) Kursrock: Am. J . Med. 1, 491, (1946) Wallenfels: Angew. Chem. 63, 9, (1951) Kiendorf: Arch. Gyn. ISO. 234 (1951) M artin und Heiler: Science 115, 402 (1952) 58, Schering AG. B erlin: Medizinische M itteilungen 1951, 1952 l Daran-Heynais: Ann. In st. P asteu r 57, 597 (1936) 14. ____ Science (New Y ork) 83, 286 (1936) Anschrift des Verfassers: Ansbach, J ildtstrac 11. Wk im ggf ORI Gl NA LI EN r E-i Aus dem Pathologischen Institut der Stadt. Krankenanstalten Dortmund (Direktor: Prof. Dr. Fr. lioemke) m il-v: ISSi m ,,, ! Das Lungenkarzinom in der Asbeststaublunge \ Von F r. \Bonn ke i'-iAir Ai it 3 Textabbildungen fkjjh Whrend hei zahlreichen anderen Stauharten das fctti|iohe morphologische Substrat, des Staubes zunchst g^^fcjjies'vegs eindeutig typisch fr eine bestimmte StaubHitsei*1mu, gestattet die Feststellung von AsbestosisPPjmerchen im Sputum oder nach dem Tode in der Blftlg *u der Regel die Diagnose einer Asbeststaub||fefopg<c Allerdings gelten auch fr diese Regel gewisse pSttsnahmeu, da die als Asbestosiskrperchen bezeich n te n Gebilde gelegentlich, wenn auch selten in den langen von Menschen zur Beobachtung gelangen, die piyAweishar nicht mit Asbeststaub in Berhrung gejommen sind. Xordmann hat entsprechende Befunde Hjitgeteilt und in solchen Fllen von Pseudoashestosis- krperehen gesprochen. Langer berichtete krzlich ber das Vorkommen von Asbestosiskrperchen bei einem Arbeiter, der in der Glaswollindustrie ttig war. Auch Doerr hat letzthin in einer mndlichen Diskussionsbemerkung einen Fall mit Beobachtung von Asbesto siskrperchen in den Lungen einer Frau erwhnt, hei der mit Siehcrheit keine Berufsttigkeit mit Asbest staubeinwirkung Vorgelegen hatte. Man kann aber trotz dieser Einschrnkungen insgesamt wohl die Fest stellung treffen, da in der Regel der Nachweis von Asbestosiskrperchen auch die Diagnose einer Asheststauhlunge gestattet und da die erwhnten ungewhn lichen Beobachtungen des Vorkommens von Asbestosis- i.s Ikunike: Das Lungenkarzinoin in der Asbeslstaubiungo Med. Mschr. 7. JgSlBtfHel krperchen ohne As hcxtstauhciii Wirkung seltene Einzelfiille (larstellen. Bekanntlich kann die Verstaubung des Lungen* gewebes mit Asbeststauh bei entsprechender Menge und Dauer zu einer Fibrose des Lungengewebes fhren, die auch unter die entsehiidigungspfliehtigen Lungenerkrankungen aufgenommen ist. Behrens hat krz'ich auf Grund von Tierversuchen nachgewiesen, da diese Ashestfibrose als Teilerscheinung einer bindegewebigen Abkapselung von Fremdkrpern anzusehen'ist und da den Aauestosiskrperchen an sieh keine spezifische Bedeutung fr die Fibrose des Lungen gewebes zukommt. Diese Fibrose stellt nach seinen Untersuchungen vielmehr die Reaktion des Gewebes auf langfaserige Fremdkrper dar. Es sei in diesem Zusammenhang der sich aus der Gutachterpraxis ergebende Hinweis gestattet, da nicht etwa jede Asbeststaublunge an sich eine entschdigungspfliehtige Erkrankung darstellt. Fr die Gewhrung einer Rente gengt nicht allein der Nach weis von Asbestosiskrperchen im Sputum, vielmehr ist dazu die erwhnte bindegewebige Umwandlung, die Fibrose ausgedehnterer Lungengewebsanteile mit Aus fall ihrer Funktion fr Atmung und Kreisluferforder lich. ber die. Ausbreitung des Asbeststaubes im Lungengewebe, und ber Art und Ausdehnung einer Fibrose in einer Asbeststaublunge sollen hier keine weiteren Ausfhrungen gemacht werden. Es wird auf die einschlgigen Mitteilungen im Schrifttum -- Nordmann u. a. -- verwiesen.'Die mineralogische und chemische Natur der Asbestosiskrperchen hat Beyer in mehreren Arbeiten und zuletzt ausfhrlich in einem Referat auf der Tagung der Deutschen Gesellschaft fr Pathologie 1941) in Kiel gekennzeichnet. Die Verstaubung des Lungengewebes mit Ashcststaub hat nun aber unter Umstnden nicht nur eine Fibrose des Lungengewebes zur Folge. Im Zusammen hang mit einer Asbestoais kann sich auch ein Lungen karzinom entwickeln. Diese Tatsache hebt die Asbest staublunge aus dem Kreise der Staubluugenerkrankungen besonders hervor. Bekanntlich sind nur ein zelne bestimmte Staublungenerkrankungen mit der ge huften Entstehung von Lungenkarzinomen verbun den, unter denen der sogenannte >Schneeberger Lungen krebs, der bei Arbeitern im Schneeberger Revier auftreten kann, wohl der bekannteste, ist. Der Vollstndig keit halber sei hier daraufhingewiesen, da nach neue ren Untersuchungen auch Lungenkrebse bei Chromat arbeitern Vorkommen knnen. Hier ist eine generelle Feststellung erforderlich. Lungenkarzinome in Ver bindung mit einer Silikose treten keineswegs gehuft auf. Durch statistische Feststellungen ist vielmehr er wiesen. da Lungenkarzinome bei Arbeitern, die an einer Silikose erkrankt sind, die Zahl der Lungenkrebse ohne Silikose prozentual nicht bertrifft ( !F. Fischer, Sprlein u.v.aj. Man wird bei der Begutachtung eines Lungenkarzinoms bei einer Silikose sich nur in den sehr seltenen Fllen zu der Annahme eines Zusammen hanges entschlieen drfen, bei denen das Karzinom nachweisbar in einer Zerfallshhe innerhalb einer silikotischen Schwiele entstanden ist (di fiiasi). Anders liegen die Verhltnisse bei den Lungen karzinomen bei einer Asbostosis. Der Zusammenhang der Entstehung dieser Karzinomformen mit der Ein wirkung der besonderen Staubart ist durch Tierver suche erhrtet ( Xordmann) und auch versieherungs-f rechtlich anerkannt. Entsprechende Beobachtungen! z. T. mit bersichten ber die bisher erfolgten Ver-| ffentliehungen sind unter anderem von XnrdinansXi Wedler und lAnzlmch. Oloyne und von Boemke mit*! geteilt. Immerhin sind Lungenkarzinome hei AsliesUr | sis im Verhltnis zur Zahl der im Schrifttum verffeut- lichten Flle offen har selten. Bis zu einem ersten von f mir mitgeteilten einschlgigen Fall im Jahre 1943 konnte ich im Schrifttum insgesamt nur 17 Flle fest- ' stellen, so da eine zusammenfassende Besprechung von drei eigenen Beobachtungen berechtigt ei-scheint. Hinsichtlich der Angaben ber meinen ersten Fall kann ich mich kurz fassen, da ich denselben in dieser Zeitschrift im Jahre 1047 bereits besprochen habe. Es handelt sich dabei um einen bei seinem Tode 71 Jahre alten Mann, der 11 Jahre in einer Asbestfabrik als Krempier ttig war und bei dem 0 Jahre vor dem Tode eine schwere Asbeststaubhmge festgestellt wurde. Kurz vor seinem Ableben wurde whrend eines Krankenhausuu (enthalte ein Lungenkurzinom diagnostiziert. Bei der Obduktion bestand eine Asbestfibrse des hungongewebes und eine diffuse karzinomatse Durchsetzung des rechten Lungenunterlappens. Auch in den brigen Lungenlappen waren Karzinomwueherungoti vorhanden. Weiterhin fand sich eine aus gedehnte rechtsseitige Pleurakarzinose. In den intra thorakalen und intraabdominellen Lymphknoten, in der Milz, in beiden Nieren, in der linken Nebenniere, in der Leber, in der Diekdnrmwand, in den Rippen, in der Wir belsule, im li. Femur und in der Kopfsehwarte fanden sich Karzinommotnstasen. Zur Frage der Ausbreitung der Karzinomwucherungen im rechten Lungenunterlappen und des zeitlichen und rtlichen Zusammenhanges zwi schen Asbostosis und Lungenkarzinom verweise ich auf die nachfolgende gemeinsame Besprechung der drei Flle. Die beiden weiteren Beobachtungen wurden von mir noch nicht, ausfhrlicher mitgeteilt. Es handelt sich da bei einmal um eine hei ihrem Tode 57 Jahre alte Frau, zum anderen um einen 53 Jahre alten Mann. Die 57 Jahre alte Frau wurde in der Medizinischen Klinik des St.-Johaimes-Hospitals in Dortmund im Ok tober 1950 aufgenommen*. Sie litt an erheblicher Atem not, blutigem Auswurf, Temperaturerhhungen und Nachtsehwei. Vor der Klinikaufnahme hatte sie in kur zer Zeit 6,5 kg an Gewicht abgenornmon. Die Anamnese ber frhere Erkrankungen ist im Zusammenhang dieser Ausfhrungen unwesentlich. Bei der Aufnahme waren der Krfte- und Ernhrungszustand sehr stark herabgesetzt. ber der re. Lunge lag basal eine Dmpfung mit feuchten kloin- bis mittelblasigen klingenden Rasselgeruschen vor. Die Blutkrperchcnsonkungsgeschwindigkcit betrug 51/78 nun. Whrend des Klinikaufenthaltes bestanden zunchst dauernd Temperaturen um 38a C. Dabei litt die Patientin an Auswurf, der geballt, hellrot, z. T. leicht hiinbeergeleeartig war. Tuborkolbazillen lieen sich nie nachwcison. Rntgenologisch lag einostreifig-fleekige Ver schattung im Untergescho der linken Lunge mit Aus fllung des linken Sinus phrenico-costalis und mit queren Stmngbildungen vor. Im Oktober 1950 wurde mir Sputum der Patientin zur Untersuchung auf Tumorzellen ber sandt (E. Nr.7 191/50). Darin fanden sich zahlreiche ty pische A s b e sto sisk r p e r c h e n (s. Ahb. 1). Im weiteren Verlauf des Klinikaufenthaltes wurde die Patientin allmhlich fieberfrei. Dabei entwickelte sich jedoch eine zunehmende Dyspnoe. Die Dmpfung im Be reich des rechten Lungenunterlappens blieb bestehen, weiterhin auch der reichliche Auswurf in einer Monge von 50--250 ccm pro die. Unter zunehmender Kachexie ent wickelten sich steigende Beschwerden im Sinne einer Herzinsuffizienz. Im Mrz 1951 trat, der Exitus ein. Aus dem Befundbericht ber die am Todestag durch gefhrte O b d u k tio n (S. Nr. 109/51) sollen hier nur die H errn C hefarzt I)r. m cd. habil. .Vogel danke, ich filr di freur.dliehe f brrlnaKung ausfhrlicher klinischer Angaben. eft 2/1953 Boemia: Das Lungonkarzinorn in clor Asboststaublungo 70 I ;j Zusammenhang dieser Ausfhrung wesentlichsten Be rnde genannt werden. Beide Lungen zeigten fliiehenhufto erwachsimgen mit ihrer Umgebung, besonders der linke ungenunterlappen. Die linke Lunge war volumins und hwerer als normal. Der Unterlappen zeigte auf den shnitt flachen des insgesamt verdichteten Gewebes regol ai verteilte weiliche, z. T. derbe, i . T. auch markigo Bo rke mit schwarzen Fleckchen und Streifen. Auch in der jrben weilich verdickten Pleura des linken Lungenaierlappens lieen sich markig-grau-weie Strnge und 'oster naohwoisen. Die Konsistenz des linken Uberlappens ar in den Randbozirken vermehrt lufthaltig. Zentrale bschnitte erschienen z. T. ziemlich ausgedehnt zh vericht^ *U if den Schnittflchen lieen sich auch hier derbe rau-weiliche Abschnitte, jedoch ohne murkigo Herde achweisen. Die Randbezirke waren grobmaschig und Ulken bei Einschnitt zusammen. -- Die rechte Lunge ar gleichfalls volumins, dabei aber leichter. flJie Pleura eigte Verwachsungsreste in Form grauweilieuer fetziger 'erdiekungen. In von Verwachsungen freien Bezirken eribie die Pleura hellgraurot, von schwarzen Flocken und treifen durchsetzt. Die Randbezirke der rechten Lungo ,rcn z. T. luftkissenartig geblht. Im brigen war die Konsistenz der rechten Lunge ungleichmig, z. T. herdirmig dicht bis derb, ?.. T. auch ober teigig verdichtet, uif den Schnittflchen entsprachen die Randbezirke enon des linken Lungenoberlappens, whrend das brige .ungengewebe z. T. weilich, z. T. graui-ot bis dimkolrot, nsgesamt nngleiclnnig fleckig erschien und von schwr en Fleckchen und Streifen durchsetzt wurde. Die Rren inoli waren in beiden Lungen bis dicht unter die Pleura ufschneidbar. Ein umschriebener Tumor als Ursprungsrt der beschriebenen markig-grauweien makroskopisch 1s Tumorwucherungen imponierenden Bezirke im li. .ungenunterlappen lie sieh nicht feststellen. Die"uberrbsgroen Lungenwurzellymphknoten waren z. T. auch .ah-elastisch jgraurot. mit schwarzen Einlagerungen. Der lorzbeutel war mit der verdickten Pleura des linken uingenuntci lappens einerseits und mit dem Herzen and erseits verwachsen. Bei Einschnitt war das Gewebe in liesem Bereich z. T. derbe, grau-weilich, z. T. auch mar- mit dnn ausgezogenen oder eingerissonon Sopten riachweisen. An anderen Stellen fanden sich in allen Lappen ausgedehntere unregelmig bogrenzto hyalin bindege webige Bezirke. ZumToil waren die Alvoolarsopton stark bindegewebig verbreitert. Sowohl in den Alveolen wie auch im Bindegewebe lagen berall Asbestosiskrperohon vom charakteristischen Aufbau, z. T. von liantoihnlichon Formen, z. '1'. von Geldrollenform, z. T. in wie abgebro chen erscheinenden spie- oder splittorfrmigen Gebilden von brunlich glnzender Farbe vor, die bei der Berliner | Abb. 2. A sbi'stosisknrperchen innerhalb von l 'laU cnepithelkarzinom - wiichcnmgcii im linken liungenunterlappen (S. Nr. 109/51 57 J. $). Asbc-atrisiskiirpcrchen -- a, KaizinoinzeHeii m it Mitosen = b Blaureaktion positiv reagierten. In Schnitten aus dem linken Lungonuntcrlappon lieen sich in regelloser An ordnung berall epitheliale Zellen vom Plattonopitlioltyp naohweison, die in unregelmig infiltrierenden Verbnden Wuchsen und zahlreiche atypische Mitosen erkennen lieen. Auch zwischen diesen epithelialen Formationen lagen typische Asbostosiskrporchon des beschriebenen Aufbaues vor (s. Abb. 2). Die b ist e le g is c h e Gut e rsu ch u n g der brigen Or gane ergab an wesentlichen Befunden in der linken Herz kammer gleichfalls epitheliale Wucherungen, die vom Kpikard auf die Muskulatur bergriffen, ebenso im Be reich des linken Lebcrlappens, der linken Nebenniere, des oberen Milzpoles, der Serosa des Magens, der linksseitigen Pleura und der linken Zwerchfellhalfte. JhbTT. A sbestosii*k(ri>mhrn im S putum (nV (K. ?>r. 71lH/."0, f7 .1, kig-grau. Nach Lsung der Verwachsungen an der Hinterwaiid der linken Kammer saen hier dem Kpikard markiggrauweiliche Bezirke fest auf, die auf die oberflchlichen Muskelubschnitte der linken Her/.kiunmerwand ber griffen, Die Herzhhlen waren insgesamt erweitert. Auch die linke ZwerchfeHlmlfto war in die Pleuraverwachsungen cinbezogen und in ein derbes, grau-weiliches Uewobo mit kleineren markig-gniuweilielien Nestern limgewaudelt. Diese markig-grauweilichen Bezirke glitten ber das Zwerchfell hinaus auf den linken Leherlnppcn, den oberen Milzpol, die linke Xebonniere und die Serosa der Magentrund ber. Die brigen bei der Obduktion erhobenen Be funde sind im Zusammenhang dieser Ausluiinmgon ohne Interesse. Bei den feingeweblichen loitersuehimgon lieen sicli in den Lungen in Raadbe/.ii keil sehr weite Alveolarriiumo Es handelt sich also nach den pathologisch-anato mischen Erhebungen in bereinstimmung mit dem klinischen Befund um eine ty p isc h e A sb e stfib r o se des L ungengew ebes m it ausgedeh nteil P latten ep ith elk a rzin o m W u ch eru n g en im linken Limgenunteiiappon ohne umschriebenen Ausgangspunkt und um eine linksseitige P le u r a k a r z in o se mit bergreifeu der Karzinom Wucherungen auf den Herzbeutel, das Herz, die linke Zwerchfelllnilftc mit Durchbruch derselben und weiterem bergreifen der k a rzin o m atsen F orm ationen auf L eber, MHz, linke N e b e n n iere und auf die S ero sa der M agenw and. Es sei hier schlielich noch erwhnt, da sich in diesem Falle auch in den Lungenwurzellymphknoten kernanue Bindegewehshezirke mit einzelnen Asbestosiskrporohen naclnveisen lieen, ein Befund, der sel tener zur Beobachtung gelangt, da die Asbestosiskrperehen offenbar wegen ihrer Gre die Lvmplihalmen der Lunge nicht so leicht passieren wie andere Stauharten (siehe Abb. 3). Die Besehiiftigmigsanamneso ergab, da die Patien tin von ihrem 17.-- It. Lebensjahr in einer A.-U-tfahrik an einer Zerreimaschine gearbeitet hatte. Das Ml Bocmke: Das Lungenkarzinom in dar Asbestsfuuhhmgo Med. Mwclir. in Hallen eintreffende Rohmaterial wurde dort zer rissen. wobei es zu einer erheblichen Staubentwicklung kam, die durch die im Arbeitsrauin vorhandenen Venti latoren nur unzulnglich beseitigt wurde. Der dritte Hall betrifft, wio oben bereits erwhnt, einen bei seinem Tode 53 Jahre alten Werkmeister, der in sehwerkrnnkoiu Zustand im August 1951 in der I..Medizi nischen Klinik der Stadt. Krankenanstalten Dortmund aufgenommen wurde*. Er fhlte sich angeblich erst seit, drei Wochen vor der Klinikaufnaluno krank. Seine Er krankung begann mit stndig zunehmender Atemnot und einer Schwellung der Flle sowie mit Schmerzen im rechten Oberbauch. bei der Aufnahme bestand eine erhebliche Lippen zyanose mit hochgradiger Dyspnoe und hufigen Hustensten. beide Lungen zeigten das Uild einer Stauung. Die Herzgrenzen waren bds. verbreitert. Die Leber war zweifingerbreit ber dem rechten unteren Kippenbogen rand tastbar. Das Abdomen war meteoristiseh geblht, beide Unterschenkel waren demats geschwollen. Der Patient machte einen schwerkrankon Eindruck, so da ,\lib . .\slH 'H l'istakni'|ii'iT l,i`ii in t-im-ni l. y iiip lik iiii in i vom tiiu m ciitiiliiH . (S . N r. tO il/: I. :>7 .1. j ) A s lii-tiln s ls k iiriirri'ln-n n. A n tlin ik n tiiu 'h rs l*ig-- m ent -- li von weiteren klinischen Erhebungen abgesehen werden mute. Er starb in der Nacht nach der Klimkaufnahmo und wurde am nchsten Tilge im Pathologischen Institut der Stiidt. Krankenanstalten Dortmund obduziert (S. Nr. 305/01). Aus dein L e ic lie iu iffn u n g sb e fu iid b e r ie lit sollen liier wiederum nur die im Zusammenhang dieser Ausfhrungen wichtigsten Befunde wiedergegeben werden. beide Lungen waren flchcnhaft ausgedehnt mit der bnistwand und dem Zwerchfell verwachsen. Sie ber lagerten den Herzbeutel zum Teil und waren sehr volumi ns, dabei schwer. Ihre freien Rnder waren stumpf, bzw. abgerundet. Das Lungenfell zeigte ausgedehnte grauweilielie Yerwuulisungsresto und derbe grau-weiliche Verdickungen, hesonders im bereich der bnsis und der Spitzcnanteile. Auch die Interlobiiispalten waren uutereinander verwachsen. Die Konsistenz beider Lungen war derb elastisch, nur in umschriebenen Kandbezirkyii iuftkissenartig geblht. Auf den Schnittflchen war das l.imgengewebe bds. diffus fleckig graubraun-rtlieli, mit ver einzelten kleinen, weichen, schwarzen FleckolieiVmul Streifen, die insgesamt, nicht sehr ausgedehnt warenSYor allem in den Untcrlappen zeigten die .Schnittflchen weiterhin ein ausgedehntes feines, grauweiliehes Xetzlmd Maschenwelk. l.nisehiicheiic Knntenhilduiigen waren nicht nachweisbar. Die Bronchien erschienen derhwandig, vom umgehenden xidi-elastsehen Lungcngewelie ic eingeengt. Sie wuren jedoch bis nahe unter die Pleura in ihm feineren Verzweigungen hinein aulselmeidlmr. Ihre. Sehleimlmut war graurnt Ins duukelmt. \nn sehmierig-graurtlieher, zh-schleimiger Flssigkeit bedeckt. Die Lungengefe waren leer, die Llingeiiliilus- Hi'Nii t ItH ar/t l 'rolrssor h r. Wnt'urklunm il.inkt* ich fr li* lus-'Uiii' <!! klinischen Angaben. lyinphknoten duppelbohnongro, weich, z. 'I'. schwrt.) z. rL'. fleckig grau-weilieh. Da mir bereits hei der Obduktion auf ( rund der frhe1 reu Beobachtungen der Lungenbefund fr eine Asbostosis | vordiiebtig erschien, wurden Nutivpriiparate bei der Sek- J ; tion angefertigt. Im von den Schnittflchen iler Lungen;; ausgopreten ( ewobesaft lieon sieb mikroskopisch zahl- > ` reiche typische A sb e sto sisk r p e r e h e n michweiaen. ^ r Weiterhin fanden sieh in beiden Nebennieren markig-, i grauweilicho bezirke, neben denen nur noch sprliche M 5 Reste von Neheimierenparonehym Vorlagen. Das Het* I war vergrert und erweitert, besonders die rechte Hers- kamrnerwand war verdickt und die Lichtung der rechten Herzkammer stark erweitert. Das Herzgewieht betrug 465 Gramm. Schlielich bestand eine Stauungsblutflle der inneren Organe mit einem Aszites von 300 ccm. An in diesem Zusammenhang weniger wichtigen, aber fr den Eintritt des Todes wesentlichen Befunden, ist noch eine Arteriosklerose der Herzkranzarterien mit kleinen Scliwielenbildungcn in der Herzmuskulatur zu erwhnen. Bei der fe in g e w e b lic h e n U n te r su c h u n g fanden sich wiederum in allen Lungonlappen bindegewebig ver breiterte Alveolarseptum die z. T. von Asbestosiskrper- elion durchsetzt waren. Ebenso lagen in zahlreichen Alveolnrlicbtungen Gruppen von Asbestosiskrperehen der verschiedensten Form vor, teils nach Art der schon oben erwhnten charakteristischen Hantel- oder Geld- rollenform, teils auch in spie- fixier splitterfrmigen brunlich glnzenden Gebilden.f ln den Unterlappen waren regellos begrenzte ausgedehntere Bindegewebs- bezirke vorhanden. Zwischen diesen bindegewebszgen fanden sieb vor allem in den Untcrlappen, weniger aus gedehnt in den brigen Limgenluppon regellos ungeordnete epitheliale Zellnester lind -strnge, die z. T. die Alveolen vllig ausfllten und vielfach Zellen mit atypischen Mi tosen und polymorphen Keinen erkennen lieen. Ein um schriebener Ausgangspunkt dieser epithelialen Forma tionen lie sieb nicht imehweison. Zwischen diesen epi thelialen Zelluestern waren gleichfalls massenhaft As- bostosiskrpcrelicn vorhanden. In Schnitte aus den Kund- bezirken der Lungen lieen sieh schlielich sehr weite Al veolen mit dnn ausgez.ogenen oder eingerissenen Septeu naeliwoisen. Die Luiigenbiiiislvmplikiioten zeigten gleiebtTilfs neben Kesten lymphatischen Gewebes eine regellose und diffuse Durchsetzung mit epithelialen Zellverbnden des be schriebenen Aufbaues zwischen bindegewehsbezirken. Vereinzelt lieen sieh auch hier wiederum Asbestosis- krpercheti fest-steilen. ^ Auch die Nebennieren zeigten eine diffuse Durchsetzung mit epithelialen Wucherungen mit zahlreichen atypischen Mitosen. Es handelt sich also auch in diesem Falle um eine A sb o sto sis m it F ib r o se d es L u n g en g ew eb es und ausgedehnten K a rzin o m W u c h e r u n g e n in d en L u n gen. Letztere hatten zur Metastasierung in den Lungen- hiluslymphknoten und in beiden Nebennieren gefhrt. Es wurde nachtrglich auf Grund des erhobenen Be fundes versucht, eine Anamnese ber die berufliche Ttigkeit des Verstorbenen zu erhellen. Da es sich um einen Flchtling handelte, war es jedoch unmglich, eine genaue Auskunft ber seine frhere Ttigkeit zu erhalten. Es lie sich lediglich feststellen, da er frher angeblich lange Zeit in einem Asbestwerk gearbeitet hatte. Die Dauer und Art der Ttigkeit lie sielt jedoch nicht mehr in Erfahrung bringen. Gerade bei der Diagnose eines Karzinoms in einer Asbeststaublunge ist die Erhebung einer Arbeit* an am nette von wesentlicher Bedeutung. Xordmann hat, auf gewisse Gesetzmigkeiten bei dem Auftreten von Karzinomen bei einer Asbostosis hingewiesen. Bei einem 'feil der au Asbostosis und Karzinom Verstor benen trat das Lungenkarzinom in einem relativ jugendlichen Alter auf. ln den von mir beobachteten Fllen ist. allerdings eine solche Feststellung nicht zu treffend, zumal die ohne Asbostosis vorhandenen *!J- 2/1 l*3 lloernke: Das Lungenkarzinom in iler Asbeststaublunge Sl: Bronchial- bzw. Lungcnknrzinome jetzt auch hufiger schon bei jngeren Menschen beobachtet werden. Da gegen'erscheint mir eine andere Feststellung von be sonderem Interesse. Bei der Mehrzahl der an einem Lungenkarzinom mit einer Asbestosis erkrankten Men schen liegt ein ziemlich gleichmiger Zeitraum vom Beginn ihrer Arbeit in einem Asbestbotrieb bis zum Eintritt des Todes an einem Lungenkarzinom vor. Dieser Zeitraum ist von Xonlmumt mit IS Jahren an gegeben und trifft auch bei meinem ersten Fall ein deutig zu. Im zweiten Fall ist allerdings ein Zeitraum von immerhin 37 Jahren zwischen dem Beginn der beruflichen Ttigkeit in einer Asbestfabrik und dem Tod als Folge eines Lungenkarzinoms bei einer Asbest staublunge vergangen, whrend in meinem dritten Fall aus den obengenannten Grnden dieser Zeitraum sieh nicht berechnen lt. Natrlich ist die von A'unimann errechnete Zahl lediglich als Durchschnittszahl zu werten. Schwankungen nach oben und nach unten kommen, wie auch in meinem zweiten Fall, durchaus vor. Die Zeit zwischen dem Beginn der Einwirkung von Asbeststaub und der Krebsentwicklung wird von Bauer mit 12--42 Jahre angegeben. Dabei spielt es keine Rolle, ob die Staubexposition fortlaufend bis zur Entwicklung des Krebses vorhanden war, oder ob zwischen dieser und der Entwicklung des Lungen krebses ein staubfreies Intervall vorlag. Selbstver stndlich mu aber, wenn man einen Lungenkrebs in Zusammenhang mit einer Asbestosis annehmen will, histologisch auch neben dem Krebs eine Durchsetzung des Lungengewebes mit Asbestosiskrperehen vor handen sein. Die Angaben ber die crrechneten F r o z e n tz a h le n von L u n g en k a rzin om en bei A sb e sto sis schwan ken. Gloyne hat bei 50 Obduktionen von Asbestosis in 6 Fllen, also in 12%. einen Lungenkrebs beobachtet. Xnrdmarni errechnet bei einer geringeren Zahl von Asbestosistodosfiillen 17%, bei denen gleichzeitig ein Lupgtffikarzinom bestand. Weitere von Xordnutnn aufgezeigte Gesetzmig keiten ber die Bevorzugung des primren Karzinom eintritts in einem Lungenunterlappen kann ich auf Grund meiner Flle auch besttigen. Man kann wohl annehmen, da nach der Art der Ausbreitung bei dem 71 Jahre alten Mann das Karzinom vom rechten Lungenunterlappen seinen Ausgang genommen hat. Auch hei der 57 Jahre alten Frau hatten die Karzinom wucherungen ihren Kitz primr im linken Lungen unterlappen. Im letzten Falle lieen sich ausgedehnte KarzinomWucherungen in beiden Unterlappen nachweisen. Allerdings war dabei keine bevorzugte Be teiligung des einen oder anderen Unterlappens vor handen. Bemerkenswert ist schlielich die Tatsache, da es sieh bei der Mehrzahl aller Beobachtungen um P la tte n e p ith e lk a r z in o m e handelt, so auch in meinen beiden ersten Fallen, whrend in dem dritten Fall die Karzinomwuehcrungen undifferenzierter, wenn auch grozellig waren. Von besonderer Bedeutung und geradezu typisch fr das Lungenkarzinom hei einer Asbestosis und als Folge einer solchen ist vor allem die multizentrische Ent stehung der Kurzinoimvueherungen in den Lungen. Man kann in solchen Fllen nie einen umschriebenen Ausgangspunkt etwa wie hei einem Bronehialkarzinom nachweisen. Die krebsigen Formationen sind vielmehr in vllig unregelmiger Verteilung in den betroffenen Lungenbezirken vorhanden, so da man das m u ltip le m e ta p la s tis c h e K arzin om als c h a r a k te r is tis c h fr eine A s b e s to s is bezeichnen mu. Bei der sicheren Kenntnis des Zusammenhanges von Asbestosis und Lungenkarzinom erhebt sich natr lich die Frage, welche Faktoren fr die; Karzinoment stehung von mageblicher Bedeutung sind. Man mu daran denken, da durch die relativ groen Asheststaubgebilde eine grob-mechanische Schdigung der Alveolardeckzellen in Frage kommt, die hei stndiger Einwirkung schlielich zu einer berstrzten Regene ration und zu Epithelmetaplasien mit nachfolgenden' krehsiger Entartung fhren kann. Sicher wird eine solche Erklrung dem Problem der Karzinoment stehung jedoch nicht allein gerecht, da auch hei dieser Karzinomform wohl chemische Prozesse von mageb licher Bedeutung sind. - /jusainme.njussnntj Auf Grund von drei eigenen Beobacht,ungen wird der Zusammenhang von Asbestfibrosen der Lunge mit Lun- genkatv.inom besprochen. Die dieser besonderen Kar zinomform eigentmlichen Gesetzmigkeiten vor allem der bevorzugte Befall der Untcrlappcn und die multizentrische Entstehung von Plattoncpitholkarzinuinwuehenmgen in den Lungen werden hervorgelinhen. Literal iirvcrzeichniu Hmnlt'r. K. I!'.: D tsrli. Me<!. \V'!ir. 1. 407 (10:10) inner, IC. II.: Das K rebsproblem, Springer-V erlag HMD Heuer, /'. .1.: Yirchowa Areh. 200, 2H0 (1033) -- Med. Klm. 1943 11 -- Yirehows Areh. 203, 530 (1043) -- Arch. f. G ew erbepath. (i, 341) (1935) -- Verhdl. Dtaeli. Ges. f. Pall. 33. Tgg. Kiel (HMD) Hehren, H'.; Schweiz, Z. All. Pall. 14, 275 207 (1051) Hoemke, Fr.: Frankf. ZeitHchr. f. Pathologie, 57, 500 (1013) -- Med. Msclir. lie ft 1. S. 2 (1047) liriihje: Ann. liep. Sen. Med. Inspector o f F aetones 1031, S. 74 d i Hiait ll\; Arch. f. G ew rrbepath. 8, 130 (1038) -- Boitr. z. silikoselbrHchg. H eft 3 (1040) Doerr, 11'.; Mndl. DiskussioiiHbomorkg. Silikosetgg. Boehnm Sept. Fischer, U \; Zll. P ath. 85, 103 -212 (1040) (Hof/ne: Tuherele 17, 5 (1035) Kopprnhfer: Arch. f. Gewerbepath. 0, 3s (1935) -- Virohmvs Areli. 2D7, 271 (1030) Lanner. F.: ZI>1. P ath. HS, 137 (1051) Linzhaeh und Wr.Hrr; Virehows Areh. 307. 3.87 (HMD Xordnnmn: Z. K rcbsforseh. 47, 2SS (103s) -- S. internat. Kongr. U ufalimed. it. Berufskrankheiten. Frankfurt 103.8, s. 083 -- Verhdlg. Dtaeli. Ges. f. Path. 33. Tgg. K id (ID 10) XnnhnuiiH und St.rye: /,. Krelmforneh. 51, 10S (HMD .Sietfmund II.: Arch. f. Geworhepath. 0, l (1035) -- .!Kurse arztl. Fortbild. 30, II. 1 (1030) Sprh in , S.: ZM. P ath. HD, 1D7 200 (1052) Funtlius und limithin: Areh. f. G ewerhepatli. 8, 20 (1038) Wrdler: Klinik der Lungennsbestose, Leipzig 1030 - - Dtseh. Areh. klin. Med. 10!. ISO (1043) Welz, A .: Areh. f. G ew erbepath. 11, 530(1042) 1052, a. M. W eitere ausfhrliche Litera tu ranga bei siehe auch bei Heger und Xordmann /f/7 - <\ J 3 E 8 F Med. Mschr., volume, 7, No. 6, pages 77-81, February 1953 LUNG CARCINOMA IN PATIENTS SUFFERING FROM ASBESTOS PNEUMOCONIOSIS Fr. Boemke Pathological Institute of the Dortmund Municipal Hospital (Director: Dr. Fr. Boemke, Professor) Although with other types of dust the main morphological substrate of the dust at first does not appear uniformly typical of any specific type of dust, the identification of asbestos particles in the sputum or in the lungs after death usually leads to a diagnosis of asbestos pneumoconiosis. However there are exceptions to this rule since the .formations defined as asbestos particles are sometimes, though rarely, found in the lungs of persons never having come in contact with asbestos dust. Nordmann. reported similar observations in which he spoke of pseudo-asbestos particles. Langer published a short report on the presence of asbestos particles in an employee of the glass wool industry. More recently during a verbal discussion, Doerr also mentioned one case where asbestos particles were observed in the lungs of a woman who had never been exposed to the effects of asbestos dust on an occupational basis. In spite of these exceptions, however, we can come to the conclusion that the detection of asbestos particles generally does warrant a diagnosis of asbestos pneumoconiosis and that these unusual observations of asbestos particles without previous exposure to asbestos dust are really exceptional. . As we know, the dusting of the lung tissue with a given quantity of asbestos dust for a given duration can lead to fibrosis of said lung tissue. This fibrosis also belongs to the lung diseases subject to compensation. Behrens recently determined through animal experimentation that asbestos fibrosis should be considered as a secondary symptom of a connective tissue encystment of foreign bodies and that the asbestos particles as such have no special significance as far as the lung tissue fibrosis is concerned. According to his studies, this type of fibrosis is much more a reaction of the tissue to long and fibrous foreign bodies. - 1- On this point, expert, experience has shown that not just any case of asbestos pneumoconiosis represents a disease subject to compen sation. To qualify for a pension, it is not sufficient to determine the presence of asbestos particles in the sputum but also the previously mentioned connective tissue changes, fibrosis of distended lung tissue parts with functional respiratory and circulatory disorders. No addi tional information will be given here on the distribution of the asbestos dust in the lung tissue and on the type and extent of fibrosis in cases of asbestos pneumoconiosis. Please refer to the individual reports contained in the literature (Nordmann, etc.). The mineralogical and chemical nature of asbestos particles was defined by Beger in several of his works and more recently in a report on the meeting of the German Pathological Association in Kiel in 1949. Under certain conditions, however, the dusting of the lung tissue with asbestos dust does not result exclusively in fibrosis of the lung tissue. Asbestosis can also be accompanied by carcinoma of the lungs This fact is particularly emphasized by the inclusion of asbestos pneumo coniosis among pneumoconiosis diseases. As we know, only a few types of pneumoconiosis diseases are accompanied by the appearance of lung carcinoma. These include the so-called and best known Schneeberg lung cancer with a high incidence among workers of the Schneeberg region. For purposes of completeness, let us add that more recent studies have also indicated the high incidence of lung cancer among chromate workers. This requires a general specification. The incidence of lung carcinoma in connection with silicosis is definitely low. Statistical studies have shown that the number of lung carcinoma cases among workers suffering from silicosis did not proportionally exceed the number of lung cancer cases in persons not suffering from silicosis (W. Fischer, Sporlein and many others). During the expert examination of lung carcinoma in persons .suffering from silicosis, there are very few cases where a correlation can be drawn and where the carcinoma can be shown to have originated within the frame of a silicotic callosity (bi Biasi). The conditions are different as far as lung carcinoma with asbestosis i i I is concerned. The correlation between the. appearance of this type of cancer and the effects of the specific type of dust was demonstrated through animal experimentation (Nordmann) and recognized by legal insur ance regulations. Related observations with partial reviews of previous publications were reported by Nordmann, Wedler and Linzbach., Gloyne and Berger among others. Still the number of lung carcinoma cases among patients suffering from asbestosis is evidently small as compared to the number of cases reported in the literature. With the exception of one isolated case which I personally reported in the year 1943, I was only able to find 17 such cases in the literature, and I feel that this justifies my discussing three additional observations of my own. Information with regards to my first case was already published in the present journal in the year 1947. This was a case of a man who died at the age of 71. He had b.een employed as carder in an asbestos plant for a period of 11 years and had been found to be suffering from severe asbestos pneumoconiosis six years prior to his death. During a period of hospitali - 3- zation shortly prior to his death, a diagnosis of lung carcinoma was given. The autopsy revealed the presence of asbestos fibrosis of the lung tissue and diffuse carcinomatous infiltration of the right lung lower lobe. Carcinomatous growths were also present in the other lung lobe, as well as extensive pleural carcinosis on the right. Cancerous metastases were found in the intrathoracic and intra-abdominal lymph nodes, the spleen, both kidneys, the left suprarenal gland, the liver, the large intestinal wall, the ribs, the vertebral column, the left femur and the scalp. Please see the following discussion of three of my own cases with regards to the distribution of the carcinomatous growth in the right lung lower lobe and the time/localization relationship between asbestosis and lung carcinoma. I had not as yet reported on the two following cases. One of these concerns a woman who died at the age of 57, the other a man who died at the age of 53. The 57-year-old female was hospitalized in the Medical Clinic of the St. Johannes Hospital in Dortmund in October of 1950.* She was complaining of extreme shortness of breath, bloody expectoration, high temperature and night-sweat. Prior to her admission, she had lost 6.5 kg within a very short period of time. Her medical history did not reveal *1 wish to thank Dr. Nagel, head physician, for providing us with detailed clinical information on the case. - 4- any significant information with regards to her disease. Upon her admission, she was in extremely bad. physical and nutritional condition. Over the right lung towards the base was an area of suppression with small to moderately vesicular rattling sounds. The blood sedimentation rate was 51/78 mm. During her hospitalization, her temperature first remained around 38C. During that time, the patient had expectorations which were round and light red in color and sometimes closely resembled raspberries. There were no tubercle bacilli to ever be detected. On the X-rays, there was a striped and spotty shadow in the under part of the left lung with filling of theileft Sinus phrenico-costalis and the transversal formation of strands. In October of 1950, the patient's sputum was sent for analysis in the search for tumor cells (E. No. 7 191/50). The latter was found to contain numerous typical asbestos particles (Fig. 1). The patient's fever gradually disappeared during the rest of her hospitalization, but she developed increasing dyspnea. The area of suppression in the right lung lower lobe persisted as well as abundant expectoration of 50-250 ccm per day. With increasing cachexia, her complaints increased and took the form of a cardiac insufficiency. The patient finally died in March of 1951. As far as the report of the autopsy performed on the day of death is concerned (see No. 109/51), only the relevant points will be given here. Both lungs were found to have superficially grown together with the adjacent parts, particularly the left lower lobe. The left lung was larger and heavier than normal. On the surface cut of the entire thickened tissue, the lower lobe showed partly firm, and partly marrowy irregularly distributed whitish areas with black spots and stripes. 'Marrowy gray and white strands - 5- and nests-could also be found in the thickened whitish pleura. The consistency of the left upper lobe in the peripheral areas contained large amounts of air. Parts of the central sections appeared extensively thickened. The edges were coarsely, meshed and decomposed when cut.. The right lung was equally large but lighter. The pleura showed growth rests in the form of grayish white particle thickening. In the areas free of any growths, the pleura appeared light grayish-red in color, covered with black spots and stripes. The peripheral areas of the right lung were partly inflated in the form of a cushion. The general consistency of the right lung was irregular with some dense to firm or even paste-like thickening. On the sections, the peripheral areas corresponded to those of the left lung upper lobe, but the remaining lung tissue was partly whitish and partly grayish-red to dark red in color, had an irregular spotty appearance and was covered with black spots and stripes. The bronchia could be dissected in both lungs up to right underneath the pleura. There was no evidence of a circumscribed tumor being at the origin of the. described marrowy and grayish-white macroscopic areas having the appearance of tumor growths in the left lung lower lobe. The p-like pulmonary route lymph nodes were also partly viscous and elastic and grayish-red in color with black infiltrations. The pericardium had grown together with the thickened pleura of the left lung lower lobe on the one side and with the heart on the other side. Upon incision, the tissue within this area was. partly firm, grayish-white in color and sometimes marrowy gray. - 6- FIGURE 1. Asbestos particles in sputum (a). (see No.7191/50, 57-year-old female) a After releasing the growth on the inner well of the left chamber, we found marrowy grayish-white areas which adhered to the epicardium and also attacked the superficial muscle sections of the left cardiac chamber wail. On the whole the cardiac cavities were all distended. The left half of the diaphragm was also involved in the pleural growth and had converted into a firm grayishwhite tissue with small grayish-white marrowy nests. These grayishwhite marrowy areas extended beyond the diaphragm onto the left lower lobe, the upper tip of the spleen, the left suprarenal gland and the stomach wall serosa. Additional findings during the autopsy are of no interest with regards to the question at hand. Examination, of the fine tissue showed the presence of wide alveolar spaces around the peripheral areas of the lung with thin continuous or torn septa. In other areas, all the lobes contained extensive irregularly-defined hyalin connective tissue areas. There was partial thickening of the connective tissue of the alveolar septa.- In the alveoli as well as in the connective tissue, there were characteristic asbestos particles which were partly dumbbell-shaped, coin roll shaped and shiny brown spear or splinter shaped formations which reacted positively to the Berlin blue reaction. - 7- FIGURE 2. Asbestos particles inside squamous cell carcin omatous growth in the left lung lower lobe (see No. 109/51 57-year-old female). Asbestos particles = a, carcinomatous cells with mitoses - b. Sections of the left lung lower lobe showed irregularly arranged pavement epithelial cells growing in irregularly infiltrating series and numerous atypical mitoses. Typical asbestos particles as described also grew between these epithelial formations (Fig. 2). Other significant findings obtained during the histological exam ination of the remaining organs also showed epithelial growth in the left cardiac chamber which attacked the musculature from the epicardium and in the area of the left hepatic lobe, the left suprarenal gland, the upper tip of the spleen, the stomach serosa, the left pleura and the left half of the diaphragm. Based on the pathological-anatomical findings which are in agreement with the. clinical findings, this is a typical case of asbestos fibrosis of the lung tissue with extensive growth of the squamous cell carcinoma in the left lung lower lobe without a circumscribed point of origin accom panied by pleural carcinosis on the left with the carcinomatous growth affecting the pericardium, the heart, the left half of the diaphragm with -8 rupture of the latter and further attacks by carcinomatous formations on the liver, spleen, left suprarenal gland and stomach serosa. Let us finally mention that in this case the pulmonary root lymph nodes also contains almost coreless connective tissue areas with indi vidual asbestos particles; this is rarely observed since the size of the asbestos particles generally does not allow them to pass through the lymph tract of the lungs as easily as other types of dust (Fig. 3). The occupational history showed that the patient had operated a tearing machine in an asbestos plant between the ages of 17 and 20. The raw material received in the form of balls was torn producing consid erable amounts of dust, part of which remained in the working room due to the lack of ventilation. FIGURE 3. Asbestos particles in lymph node of lung hilus (see No. 109/51, 57-yearold female). Asbestos par ticles = a, anthracotic pigment - b. ' . * '-V-5K ^ ^ C-v a*, v a v> * ' * & * * & ? . * ` v "uh*- ,,w - As mentioned above, the. third case concerns a foreman who died at the age of 53. He was severely ill and died in August of 1951 in the First Medical Clinical of the Dortmund Municipal Hospital.* *1 wish to Dr. Woenckhaus, professor and head physician, for providing us with relevant clinical information. - 9- He had apparently -begun to feel ill only three weeks prior to his hospitalization. The disease began with constantly increasing shortness of breath and swelling of the foot as well as pain on the right side of the upper abdomen. Upon his admission, he had a severe cyanosis of the lips with marked dyspnea and frequent coughing spells. Both lungs appeared congested. The cardiac edges were distended bilaterally. The liver was palpable approximately two fingers above the right lower side of the rib cage. The abdomen was meteorestically inflated., Both tibias were swollen by edemas. The patient was in such a poor condition that further clinical studies could not be made. He died during the night following his hospitalization and was autopsied shortly thereafter in the Pathological Institute of the Dortmund Municipal Hospital (see No. 305/51). Again, only the most important observations made during the autopsy will be reported here. Both lungs were distended and had superficially grown together with the thoracic wall and the diaphragm. It thus overloaded the pericardium and had become very voluminous and thus heavy. Their free edges were flat or round. The visceral pleura showed large amounts of grayish-white growth residue and firm grayish-white thickening, particularly around the base and the tip. Even the intralobar spaces had grown together. The consistency of both lungs was -firm and elastic and inflated in the circumscribed peripheral edges. On the cut surface, the lung tissue had diffuse grayish-brown-red spots with isolated small, soft, black spots and stripes which were not altogether extensive. In the lower lobes, - 10- particularly, the cut surface also showed an extensive fine, grayish- white mesh or network. There were no circumscribed nodular formations to be seen. The walls of the bronchia appeared firm and somewhat com pressed by the surrounding viscous and elastic lung tissue. These could however be removed by cutting their fine branching all the way under neath the pleura. Their mucous membrane was grayish-red to dark red in color and covered with a glutinous grayish-red tough slimy fluid. The lung messels were empty and the pulmonary hilar lymph nodes were about the size of two beans, soft, partly black and partly with gray and white spots. Since even during the autopsy I already suspected asbestosis due to earlier observations of lungs, an untreated specimen was prepared. The tissue fluid obtained from the cut surface of the lung was microscopically found to contain numerous typical asbestos particles. The two suprarenal glands also contained grayish-white marrowy areas as well as some small rests of the suprarenal parenchyma. The heart was enlarged and distended and the right cardiac chamber wall was particularly thickened while the right cardiac chamber orifice was highly distended. The heart weighed 465 g. Finally, the inner organs were filled with congested blood with 300 ccn ascites. One point of lesser importance with regards to this question but which played a significant role in promoting the patient's death was arteriosclerosis of the coronary arteries with small callosity formations in the cardiac musculature. ' . - 11- A study of the fine tissue again showed alveolar septa with distended connective tissue in all lung lobes, with said septa partly covered with asbestos particles. Several alveolar spaces also contained numerous groups of asbestos particles of various forms with some of them having the above-mentioned characteristic dumbbell or coin roll shape, others in the form of glossy brownish spear or splinter-shaped forma tions. Large, irregularly-defined connective tissue areas were present in the lower lobes. Between these connective tissue processes and more particularly in the lower lobe, there were smaller epithelial cell nests and strands irregularly distributed throughout the other lung lobes. These cell nests and strands sometimes totally filled the alveolesand often showed the presence of atypical mitoses and polymorphic cores. There was no circumscribed point of origin of these epithelial formations to be found. Numerous asbestos particles were also present between these epi thelial cell nests. Finally, sections of the peripheral areas of the lung showed very large alveoles with thin continuous or torn septa. In addition to residues of lymphatic tissue, the pulmonary hilar lymph nodes showed an irregular and diffuse infiltration of epithelial cells with the above structure between the connective tissue areas. There were also isolated asbestos particles to be found here. The suprarenal glands also showed a diffuse infiltration of epithelial growth with numerous atypical mitoses. This case is therefore also a case of asbestosis with fibrosis of the lung tissue and extensive carcinomatous growth in the lungs. This - 12- led to the formation of metastases in the pulmonary hilar lymph nodes and in both suprarenal glands. Based on these findings, we attempted to obtain an occupational history of the patient. This was unfortunately impossible since the patient was a refugee and no information was available on his previous occupations. We did find out that he had been employed in an asbestos plant for a long period of time but could not obtain any information with regards to the duration and nature of his work. The occupational anamnesis is of great importance in diagnosing carcinoma in a patient suffering from asbestos pneumoconiosis. Nordmann pointed out some legal points which apply to the presence of carcinoma in a case of asbestosis. In a number of patients who died from asbestosis and carcinoma, lung carcinoma had originated at an early age. This, however, did not apply to my observations, especially since cases of bronchial or lung carcinoma without asbestosis are now more frequently seen among the lung population. On the other hand, one other point appears of significant interest. In the majority of cases of lung carcinoma with asbestosis, thefe seemed to be an equal period of time between the. time of employment in an asbestos plant and the time of death due to lung carcinoma. Nordmann found this period of time to be 18 years; this also applies to my first case. In my second case, however, there was a period of 37 years between the time of employment in an asbestos plant and the time of death as a result of lung carcinoma in a case of asbestos pneumoconiosis; the latency period could not be determined in my third case due to the above-mentioned reasons. 13- Of course the figure quoted by Nordmann is merely an average and there can be increasing and decreasing variations. Twelve to 42-year periodswere quoted by Bauer between the initial exposure to asbestos dust and.the development of cancer, regardless of whether there was constant exposure to the dust prior to the development of.cancer or whether there was a dust-free interval in between. Of course if we are to speak of lung cancer in conjunction with asbestosis, histologi cally there must necessarily be an infiltration of the lung tissue with asbestos particles in addition to cancer. The reports received on the calculated rate of lung carcinoma among asbestosis patients fluctuates. Out of 50 autopsies of asbestosis cases, Gloyne found six cases or 12% accompanied by lung cancer. In a small number of patients who died of asbestosis, Nordmann calculated an average of 17% in which lung carcinoma was present simultaneously. Based on my own cases, I am also in a position to confirm addi tional legalities pointed out by Nordmann on the higher number of primary carcinomas originating in a lower lobe of the lung. Given the nature of the carcinomatous spread in the 71-year-old male, we can assume that the said carcinoma originated from the right lung lower lobe. The carcin omatous growth in the 57-year-old female also had its primary seat in the left lung lower lobe. In the last case there, was extensive carcinomatous growth in both lower lobes. Finally, one interesting point is that the majority of observations concerns squamous cell carcinomas; this also applies to my first two cases whereas the third involved carcinomatous growths of non-differentiated large cells. - 14- Particularly significant and typical of lung carcinoma in con junction with asbestosis or as a result of the latter is the multicentric origin of the carcinomatous growth in the lungs. In such cases, there is never any circumscribed point of origin to be found as would be the case with bronchial carcinoma. The cancerous formations are very irregularly distributed in the affected areas of the lungs so that we can consider multiple metaplastic carcinoma as characteristic of asbestosis. In view of the undisputable correlation between asbestosis and lung carcinoma, we can now question exactly which factors can be of any significance for the development of carcinoma. We must consider the fact that the relatively large asbestos dust formation could promote coarse mechanical injuries to the alveolar stigmata which, under con tinued effect, could finally lead to excessive regeneration and epithelial metaplasia followed by cancerous degeneration. Surely this simple explanation does not in itself solve the problem of carcinoma development since this type of carcinoma also involves important and significant chemical processes. SUMMARY This is a discussion of the' correlation between asbestos fibrosis of the lungs and lung carcinoma based on three of my own observations. Legalities relevant to this particular type of carcinoma are given, primarily with regards to the origin in the -lower'lobes and the multi centric development of squamous cell carcinomatous growth in the lungs. - 15- LITERATURE REFERENCES Baader, E. W . : Dtsch. Med. Wschr. 1, 407 (1939). Bauer, K. H . : Des Krebsproblem. Springer-Verlag 1949. Beger, P. J.: Virchows Arch. 290, 280 (1933). ________ : Med. Klin. 1943 II. ________ : Virchows Arch. 293, 530 (1943). ______ : Arch. f. Gewerbepath. 6, 349 (1935). ________ : Verhdl. Dtsch. Ges. f. Path. 33, Tgg. Kiel (1949). Behrens, W . : Schweiz. Z. Allg. Path. 14, 275-297 (1951). Boemke, Fr.: Frankf. Zeitschr. f. Pathologie, 57, 569 (1943). ________ : Med. Mschr. Heft 1, p. 2 (1947). Bridge: Ann. Rep. Sen. Med. Inspector of Factories 1931, p. 74. di Biasi, W. : Arch. f. Gewerbepath. 8, 139 (1938). ________ : Beitr. z. Silikoseforschg. Heft 3 (1949). Doerr, W. : Mundl. Diskussionsbemerkg. Silikosetgg. Bochnm Sept. 1952 Fischer, W . : Zbl. Path. 85, 193-212 (1949). Gloyne: Tubercle 17, 5 (1935). Koppenhofer: Arch. f. Gewerbepath. 6, 38 (1935). ________ : Virchows Arch. 297, 271 (1936). Langer, E. : Zbl. Path. 88, 137 (1951). Linzbach and Wedler: Virchows Arch. 307, 387 (1941). Nordmann: Z. Krebsforsch. 47, 288 (1938). ________ : 8. internat. Kongr. Uhfallmed. u. Berufskrankheiten, Frankfurt a.M. 1938, p. 983. - 16- Nordmann: Verhdlg. Dtsch. Ges. f. Path. 33, Tgg. Kiel (1949) Nordmann and Sorge: Z. Krebsforsch. 51, 168 (1941). Siegmund H: Arch. f. Gewerbepath. 6, 1 (1935). ________ : Jkurse ar2 tl. Fortbild. 30, H. 1 (1939). Sprlein, S.: Zbl. Path. 89, 197-200 (1952). Sundius and Bygden: Arch. . Gewerbepath. 8, 26 (1938). Wedler: Klinik der Lungenasbestose, Leipzig 1939. ________ : Dtsch. Arch. klin. Med. 191, 180 (1943). Welz, A . : Arch. f. Gewerbepath. 11, 536 (1942). For additional literature references, see Beger and Nordmann. - 17- American Chemical Society Volume 47 April m --Jty W: 2)0 Q,t&9 (Columns -?2S) 1953 Editor: E. j. CRANE Executive Assistant to the Editor: ELMER HOCICETT Associate Editors: H elen G am e Cr a n e , L eonard T. C abell, G ertrude G ibbons, M ary A. M a g il l , C harles L. Be r n ie r , A ud rey D u d l ey , R ussell St e m e n , A lice E. P ad a n , R uth J ones, R obert L. M essier, Cecil C . L an g h a m , M el v il l e F. R avely, D ale B. Ba k e r , a n d R ichard D . H anks The Ohio State University Columbus 10, Ohio 4471 Chemical Abstracts 4472 W >' rcabsorption which are independent of filtered Na load. while the water content was normal. Following lint* 35 references. Theresa McKee with insulin and 0.85% NaCl soln. the patients-.h... Study of mast-cells in human subjects with relation to rapidclinicalimprovementandreturnoftheplasmar: atheroma, heparin and cholesterol. D. P. Basu. Indian carbonate and water to normal. Undesirablesideo'- Heart J. 4, 65-71(1952).-- Mast cellsoccur in the human ;were occasional hypernatremia, const, transient In.,, aorta, coronary artery, and lungs. Fewer occur in athero- chloremia, and hypokalemia, which persisted scvn.it matusvesselsandundertheseconditionsruptureofthecells With treatmenttheerythrocyteslostnofurtherh.t,.- occurs. Few mast cells occur in the lung when there is lose water and Na. Na reaccumulated in the cell pulmonary hypertension and the pulmonary artery has rapidly than did K or water. In most patients, I.,.., undergoneatheromatouschanges. A largeno.ofmastcells"-water and K were lower than normal at thetime occur inlung tissue when there ispulmonary tuberculosis charge from the hospital. There isa parallelismI., with no atheromatous changes in the pulmonary artery. waterandbaseshiftsintheerythrocytesandintheint,., These findings suggest a close connection between mast mass during recovery from diabeticacidosis. 28reli'in,- cells,'atheromatous changes, and cholesterol. It is sug John T. M .n gested thatthestresson arterialwalls,which iscaused by ' The cholate:cholesterol relationship in clinicalmut generalized or pulmonary hypertension, damages the mast perunental nephrosis. Ray H. Rosenmau, Meyer h,., cells with a subsequent reduction in heparin production; man, and Sanford O. Byers (Mt. Zion Hosp., San ft,,, the power to rupture the globulin lipide bond then de cisco,Calif.). J. Clin. Invest. 32,121-4(1953).--Alien-, creases. This agrees with the view that an increase in the. -accumulation of bile acid (hypercholatemia) wits Inurv:,i no.ofmast cellsproducesextraheparinand thusproduces thebloodofhuman subjectswithnephrosisandinthe a lowered plasma cholesterol concu. Theresa McKee ofratsinwhichexptl.nephrosishad beeninducedlit-. Lung carcinoma caused by asbestos inhalation. Fr. tioti of antirat-kidney serum when hypercholostrK.-., Boetnke (Stdt. Krankc-.'.anstalteu, Dortmund, G-er.). was also present. The nephrotic rat also showed ,i.' . Med. Momtsschr. 7, 77-5i(1953).---The relation between 1ished ability to rid his blood of excess injected fibroticchangescausedby asbestosdepositsinthelungand Feedingofcholatetonephroticratsappearedtopm, -,iit,, carcinoma isdiscussed. The lowerlobe isthe siteof pre decrease of plasma cholesterol, which usually a,.., dilection. Characteristic are the multicentered develop followingthe initialrise. John T, M .f?, ments of flatepithelium carcinoma. A. E. Meyer _ Pulmonary hypertension. I. Pulmonary circulate? Determination of 17-kstosteroids in acne rosacea. Ro namics in patients with pulmonary emphysema st dolfo Nstor Corti and Pedro H. Magnin. Semana, m d . Paul N. G. Yu, Frank Lovejoy, Jr., Howard A (Buenos Aires) 9S3, I, 113-15.-- The values found were Robert E. Nye, Jr.,WilliamS.McCann, S.JohnV.- normalinrosacea,higherincommon acne,whichdifference elli,and Caro!Gouverneur(Univ.ofRochester,!(.!,,,.. is of diagnostic importance. A.E.Meyer I N.Y.). J. Clin. Invest. 32, 130-7(1953).-- Thy d-v. Altered liverfunction or chronic congestive heart failure. pulmonary hypertension varied directly with the John M. Evans, Hyman J. Zimmerman, J. Grjmt Wilmer, of emphysema, hypercapnia, and anoxia. The 0 Lawrence J. Thomas, and Clayton B. Etheridge (George arterial blood varied inversely with the mean puln Washington Univ., Washington D.C.). Am. J. Med. 13,._arterypressure,butdidnotparalleltheothertlott-m- 704-12(1952).-- Impairment of the hepatic excretory ca "The O tension of arterial blood did not vary pn>,:. , pacity for Bromsulphalein was often marked, generally withanyofthedeterminants. The COatensionniot paralleling the severity of heart failure. Flocculation and blood correlated closely with mean pulmonary artm turbidity tests were less frequently abnormal, the latter sure,totalpulmonary resistance, and arteriolarre-.ui-, usually in assocn. with the hyperglobulinemia found in ; but not with "pulmonary capillary" pressure. Th, ,, some ofthe patients. Serum bilirubin conens. were mod ofresidualvol.tototalcapacityvarieddirectlywith.... eratelyincreasedinabout25% ofthepatients,particularly pulmonary arterypressureand totalpulmonary.. in those with higher levels of venous pressure. The serum The role of anoxia in the pathogenesis ofpulntonma albuminconcn.was lessthan3.5g./100ml.in35of56 pa tensionisconfirmed. CO retentionisprobablyim;- tients; theserum globulinwas 3.59% orabove in 15of56 "inraisingpulmonary arterypressureandininert*,iMi.j ,. patients. -TheimpairedexcretionofBromsulphaleinshowed inonaryvascularresistance. 33references. J,r y a pos. correlationwith theheight ofthevenous pressures; The effeetofthyrotropichormone on themctnlioH.- no significantcorrelation was observed with the degree of radioiodineineuthyroid,hyperthyroidand acromi**!;!* arterial O unsatn. 34 references. Barbara R. Murray f dividuals. David V. Becker, J. E. Rail,Wendell lVy,,, Autoimmune hemolyticdiseaseand cryoglobulinemiaas andRulonW. Rawson(Sloan-KetteringInst,uni\l< , sociated with chronic lymphocytic leukemia. Hemato Center, New York, N.Y.j. J. Clin. Invest. 12.H,, logic and metabolic studies. Albert B. Craig, Christine (1953).-- The effect of a single intramuscular hike . Waterhouse, and Lawrence Young (Univ. of Rochester, thyroid-stimulating hormone (TSH) on the 1 ti-tiilmi,. , Rochester, N.Y.). Am. J. Med. 13,793-804(1952).-- , "tracerdoseofI131wasstudiedin3euthyroid,:v,-ir--Iw Reductionsintheno.ofcirculatinglymphocytes,hithesize and 3 acromegalicpatients. When administered i1 ofthe peripherallymph nodes, and intherate ofred cell afterthetracerI131,TSH increasedthelevelofprotcif1...., destructionweresustainedfor9months followingadminis Im andI1=7inthebloodandofI131intheurine. Mith,u , tration of 1250 mg. adrenocorticotropic hormone (ACTH) _ presented for the estn. of the total thyroid hurmn... . in15days. A 2ndcourseofACTH producedalessmarked ' chargedfromthethyroidafterTSH andforcaley.th. but stillwell-sustainedresponse. The expected lossof N, I content of the thyroid. Following a standardy . P,andK occurred. 82references. BarbaraR. Murray TSH, euthyroid patientsappeared tosecrete111011*th.-. Observations pon the absorption ofurinary constituents hormone than did liyperthyroid patients. The in.n , afterureteroaigmoidostomy. Theimportanceofrenaldam -of TSH appeared in the first24 hrs. intheh\ age. C.D. CreevyandM. P.Reiser(Univ.ofMinnesota, patients,andnotuntil48hrs.ineuthyroidpatient., , Minneapolis). Surg., Gynecol. Obstet. 95, 589-96(1952).-- hyperthyroid patientsdemonstrated an unusual Absorption of urinary chlorides through the mucosa of the handling radio-I, which was characterized by avet. colonafterureterosigmoidostomycancausehyperchloremia ,turnoverrateofIby thethyroidwithabnormally,|tl.. and acidosis. BarbaraR. Murray 1 serumprotein-boundradio-Iandurinaryradio-!ieui- Systemic lupus erythematosus. A review ofthe litera references. John T. ture. S. William Ross and Benjamin B. Wells (Univ. of Histamine sensitivity and anaphylaxis inthev*-.1.... Arkansas, LittleRock). Am. J. Clin. Pathol. 23, 139-GO vaccinatedrat. SaulMalkieland Betty J.Hunts-1 (1953).-- The reviewincludeschanges intheblood chemis _we,. Univ. Med. School, Chicago). tryand the "L.E." factor. 193references. J.T.M. B id. 81,689-91(1952).-- Inoculation h- Electrolyte equilibria n erythrocytes during diabetic with Hemophilias pertussis increased its scns'iivu nr:dosis. George Nichols. Jr and Nancy Nichols (New mine. Pertussis, organism mixed with hors? h , H -gland Deacone s Hosp.. 'o on, Mass.) J. Cl;}-. enhanced the ability of the horse serum u. -., Invest. 32. I'8-20(1953).-- Yalt.tw.or am and erythro- anaphylacticsensitivity. Richard . yte Na, K, r.d water during dietben anacsis are com- Electrophoretic studies of the serum -.or a"'" h- va'uc .21norma'subjects. Duringacido- with exp-...', -.unta? infectious anemia.