Document evkzVRZOyrZo5g71dMaQyynx4

.imosnt teoy'asric were of which became sarcomatous. net D. L. Thomson for valuable sugaaaatwns and prejxtritt* {he illustra- solutions. Mr. C. Larsen rendered . Tie aether wishes. a!so. to express iilbaum Company, to Sobering (Can*, schiria? Corporation, for the supply autre 135: 65, 1953. acet t: 775, 1956. jjC. Soc. Ssper. Biol. & Med. 40: 241, rt7: 3S9,1933. * acerSO: 70, 1937, :ux Cancer and Prccancer, published by ^mc. Sac. Sxper. Biol. & Med. 34: 201, ,?noc Soc. Esper. Biol. $; Med 35: 56, PULMONARY ASBESTOSIS V. A Report of Bronchial Carcinoma and Epithelial Metaplasia 1 KENNETH M. LYNCH. M.O- axa \V. ATSIAR SMITH. 1LD. {Froos the Departments of Pathology ctul 5tcdia'nr, Medlrai CofU'&e i-f the State of South Cutouku) Following our report In 1935 (l), seme further interest m the occurrence of lung cancer in asbestosis has been manifested. Six cases have been re corded, by Gloyne (2, 3), Egbert and Geiger (4) and Xordmann (3). The present report brings the total to 8. Nordmann believes that these cases should be classified as occupational cancers. In 193$ Anderson and Bible (6) studied the silica content of the lungs and the histologic evidence of pneumonoconiosis in 70 persons who died of pul monary carcinoma and in 50 non-cancer subjects. A greater incidence of silicosis and a greater lung silica content were found among those who had cancer than fn the control series, from which the authors conclude that the role of' the silicosis is etiological. * Vorwald and Karr (7), also in 193$, renewed the reports of carcinoma of the lungs in subjects of pulmonary dust disease and reached the conclusion that no relationship has been shown between the inhalation, of d:;si and the occurrence of cancer and that, except as it contains known carriages!. fac tors-, such as tar or radium, dust cannot be considered as of til .,,n:c s.gulAcance in malignant disease of the lungs. In 1939 Klotz (8) reported that from 1925 to 1936 there c^.:..rred in his necropsy service 50 cases of silicosis, among which were 4 inscanc - of brohehiogenic carcinoma, an incidence of S per cent,* while in his total of - '*00 necrop sies for that period there were 53 primary cancers of the lung, an incidence of only 1.18 per cent. It was soon after reporting the first case that the writers encountered a second. A white man first presented himself in the dispensary at the age of forty-two. He had then been employed os a weaver in an asbestos null' for seven years. HU complaints were shortness of breath and lassitude. No other significant symptoms were elicited. There were somewhat diminished expansion of the left chest and culncss in the left axilla and in the right base posteriorly. A few riles were heard ia these areas and in the upper right axillary region and the left base posteriorly. The roentgen report at that time is as follows: ~ Bron chial lines slightly hoarier in the left chest but not sumeica; to warrant a diagnosis of tuberculosis.'' No tubercle bacilli were found in the sputum and serologic tests for syphilis were negative. * The patient was not seen again until six'years later, when he was complaining of short ness of breath and soredess in the chest. He had continued to work in the asbestos mill, giving him a total of thirteen years' exposure to asbestos dust. He stated that he bad been gradually becoming weaker, more easily fatigued, and shorter of breath for about two years, and bad developed a cough, productive of thick phlegm but no blood. For about a year he Read before the American Society for Cancer Research. Richmond, Va^ April 5, 1939. 5/ti-li c a. JV zt'.3 & '-ft.; '20-*-' 7~ , / 9 s 568 KENNETH It. LYNCH AND W. ATHAR SMITH had experienced pain In scattered anu over the chest. At this time he had stopped work oa account of weakness. He had lost ten or twelve pounds in weight in the last few years. After thirty days in the hospital the patient was discharged, having shown progressive Improvement. 'During his hospital residence his temperature remained normal, his pube varied from SO to HO, respirations ranged between 20 and 30. and the blood pressure was around 2*2 systolic and 96 diastolic. - At this time chest expansion was diminished bilaterally, tactile fremitus was alike over the two sides, and no abnormal areas of dulness were found. The breath sounds were Fk*h !. Lotto Sttowoc Asustqso with Cascucoha or tire Lower Lose vesicular over the greater portion of both lungs, but broochovcsicular in the bases. Fine rales were heard in both apices anteriorly and in the lower right base posteriorly. Coarse rales were audible in both bases posteriorly and over the lower left side anteriorly. The hemoglobin was $S per cent (Dare.). Neither tubercle bacilli nor asbestos bodies were found in several examinations of sputum. ' Tae next admission to the hospital was eight months Later. Although the patient had not returned to work, all of his previous complaints had recurred with increased severity. The chvit pain was worse on the righL Chest expansion was slight on both sides, and the blood pressure was down to ICS systolic and 6$ diastolic. Physical findings in the chest tR surrh hi* time he Hod *tup(>o( work n weight in the las; few years; ged, having shown progressive re remained normal, his pulse iO, and the blood pressure was tactile fremitus was alike over tad. The breath sounds were PvLilONARY ASBSSIOSIa. V 569 were about as before, and the f.nger tips were now dubbed. Sputum coronations again showed no tubercle bacilli or asbestos bodies. Roentgenograms revealed no definite changes ia the lung field* as previously noted. A pellagrous skin eruption disappeared under appro* prate treatment. After seventy-seven days in the hospital the patient was again discharged, improved as ' to weight and general condition, hut his dyspnea or. exertion did not improve. At the time of this man's death, sixteen months Liter, he was not a hospital patient and had not been under close observation tor the intervening period. Necropsy (232jT-35-3j> & . . ~ -'V .'**.* V- .''// *v*' . -v *... >i. > -T- ua o to* Lnwt Uwk tchoveskular in the loses. Hue . right base posccrhrly. Coarse lower left side anteriorly. The Ui nor asbestos bodies were found later. Although the patient had recurred with increased Severity, was stijgiic on hpeh sides, and the Physical findings in the chest . 7a 2. SouAicous-cua ax GtAxoctA* Cascxxosca wrm Assocxatco Asssstos Boots*. X J50 was limited to the chest. The body was greatly emaciated and the finger tip* were clubbed : and cyanotic. . There was no free fluid in either pleural sac but the pleural surfaces were so thick and : um as to make removal of the lungs dfiScult. There was a Arm dense mass in the upper mediastinum, surrounding the large vessels as they arose from the aorta. r Both visceral and parietal pleurae were thick, nodular, and almost cartilaginous in dca\ dry, reaching a thickness of 1 cm. over the left lung posteriorly and laterally. In addition ; chare were a number of discrete white arm nodules, l to 2 cm. is diameter and aboue 0.5 cm. thick scattered over both lungs. Section of the right lung revealed a dense consolidated area m the upper part of che lower lobe, with less complete solidification of the lower part of this lobe. In the axillarv sere of the lobe a firm, fealty, cor.c-ihaped mass based on the pleura extended to the hilus. ' There was marked fibrosis about the bronchi in this region until some stenosis. Several ant ' white nodules were present in the hilar nodes here, while other nodes were black and of the turn! consistency. The lower part of the lobe contained numerous coalesces but seoarate white nodules. The upper lobe was soft and crepitant, showing nothing mote than a* m>dcote emphysema beneath the pleura. In the left lung there was a single circumscribed sodule beneath the pleura in the axillary region, with slight infiltration of the adjacent lung 'issue. . 570 KENNETH il. LYNCH AND VT. ATilAR SMITH Xo lesions of the inner parts of the trachea or large bronchi were found, although there was considerable dense white infiltration about them, especially is the upper mediastinum. This infiltration surrounded the upper portion of the aorta also. The right side of the heart was moderately dilated. Dense cartilaginous white tissue infiltrated the entire unjwr mediastinum, holding aH structures there rigidly, and extended into the neck as far as could he reached. This was continuous with the thickening of the mediastinal pleura and with the thickening about the bronchi on the right. It was densely adherent to the vertebrae and had to be cut away. Sections from the right lower lobe, the lower part of the uj>pcr left lobe, the pleural nodules, and the mediastinal mass and nodes reveal advanced malignant neoplastic disease, composed in the main of infiltrating masses and cords of stratified squamous epithelium, the cells of which vary in their differentiation from young forms with little squamous cell pro* fts. 3. IsTttnwnojr or SocUxoes Guczxosca sr Fistocs Tissrs wrm Asassros Bootes. X 350 /fwffrn fa the looser tissues to large many-layered masses with polygonal and squamous differentiation and keratinous pearly body production in the denser tissues, such as the pleural nodules. Xo definite focus of origin can be positively determined, so extensive is the infiltration about bronchi, peribronchial tissues, pulmonary parenchyma, and in the sev eral aspects of the pleura. Within the walls of several bronchi, intermingled with mucous gfaw>u but not upon the mucosa so far as this was examined, the carcinomatous process is actively infiltrating. It permeates the lymph channels widely, infiltrates peribronchial lymph nodes, am! has produced dense infiltration about the respiratory tubes and great vessels of the upper mediastinum. It has invaded the walls of the large veins within the lungs and seems actually to have penetrated to the lining. ' In certain uktee*. notably in some of the pleural extensions and in the large mediastinal growth, the cancer structures are not epidermoid in fom but tubular, with a lining of cuboids1, or colt^nrar epithelium, like that of the bronchioles. These tubular structures arr seen occasionally in other cancerous areas. ' 52SSSSS ijjU*n WJggfggg ifTinrrqjTii ^ V. ARtAft swift: trge bronriu were u:. :. ..hlsouuh there t. especially t" *.hc a; mediastinum. aorta alio.' The ri. #: the heart : entice upper r.*.cv;;. v.hvurv., holding ail ;uri} csu;d r.,v.. This was tlous and with the i:`.iv-ier.ir.j about the te vertebrae and hue : i he cut away. part of the upper U* kV**C. the pleural U advanced malip^a.r. r.voplasric disease, rds of scorified :>'u* epithelium, the suag forms witfc.lkt'.e * .uor.ous ceU pro- rc;t,.uo.xARv a^bestos:^ y It appears chat the primacy growth ts probably {? the lower right lobe and chat fr5o7m1 this has occurred the wide pulmonary, mediastinal and pleural extension. The pleural tis sue* are generally ^uice thick, densely fibrous ar.d hyaline. Xo asbestos products occur within the pleural tissues pn>:<r. ' diffusely but irregularly throughout both lungs. mve marked in the lower than in the upj>c? lobes, is a widespread old hut still progressive fibrosis, increasing ths immew-ork and thickening the wall* ot' bronchiole* and many alveoli, although la some areas these walls are not thickened and the alveoli are emphysematous. In alveoli are derow<*A -- --------- ` *" ' v .. i' Sa> . 4 v - j \y-- '*-4.' vV* V: s.?... "*** ;'-w - --- '~S\ v-^ V * Ex . : .. i . *+ ` \ * * '** , i * *'-T. 4 f S:(^r l^ ' - c' Vt K%*S ^ Vr.r . ... -V .r `0\ * a" C* ' V . > 6'* i ; * S" h^ > X . v -v .-1 ^v is* , .y <s.- * s. :^i '{ -=, .i .i ; ?'.4 ^ .. .v Fcnocs Ttsict wrru .V3?os Boots*. fw. 4*. PxnRxxusmaxocxcaatAut Lwvurt*i Nv--ow w--mr D**crosrr or Asnesro* Bwns axo G*.vxvu* Matxxuu - ex Lutes Ptueocvm. X 33 . * :X , 1 ; t ' 4.U. yM( ew( this wss examined, the carcinomatous proces^ '.-mph cfcinreU widely. :r.::krates penbroachsa. Itrscas shout the re*p:r.*.ory tubes and gred invaded rhu malU o: :hc htrge veins within th` i to. the lmis. ' ; . pleural cxtt-niion* -a: :r. :hc large medastitc. ieoaoid in form he. Tubular, with a lining tj of the bronchiole*. Thv-e tubular structures ar' In many of the air sacs, especially those of the more fibrous areas, there is a scattering of asbestos bodies, singly or in groups, of various shapes and sizes. These are usually en gulfed by large multmucleated cells or associated with mononuclear phagocytic collection.*. Asbestos bodies arc also to be found, singly or in small groups, within the fibrosed areas of alveolar walls or peribronchial and perivascular lymph courses. H** rfc~------ " within the fibrous tis** *w----- * 372 KENXETK M. LYNCH AND W. ATMAS SMITH In jummarv, the limited necropsy showed: carcinoma of tungs, pleura, and mediastinum, mixed squamous-ccll and glandular in form but squamous b the main, judged to be of bronchia! origin: pulmonary asbestosis with fibrosis, bronchiectasis, purulent bronchitis and acute bronchopneumonia: dilatation of the right heart. * The exposure to asbestos dust in this case was of about twelve to thirteen years' duration, more or les3 continuous, beginning about fifteen years before death, which occurred at fifty years. There is no means of estimating accu rately the duration of the carcinoma, but it was probably making itself felt with the aggravation of symptoms, particularly pain, about two years before death. It is worthy of note that, although the fibrosis was advanced, it was of the diffuse form generally reported in asbestosis and showed no evidence of the nodular type seen in true silicosis which we have encountered in other ad vanced cases of asbestosis. The only hyaline nodules found were in the lymph nodes, and these may have been fibrous tubercles. Epithelial Metaplasia * It has been interesting to note that in several coses of advanced asbestosis squamous metaplasia of bronchial epithelium has occurred. The following case is summarized in order to record this observation: A Negro man (No. 2:145-35-23). who suffered Aft illness diagnosed as asthma and ap parently died from right heart failure, was found at necropsy to have hypertrophy and dilata tion of the right heart, minor atherosclerosis of the pulmonary artery, pulmonary asbestosis. chronic bronchitis and bronchiectasis, and acute lobular pneumonia. His lungs were quite voluminous. They did not show the grossly exaggerated fibrous state seen in other cases of advasced asbestosis but in sections fibrosis was observed along the course of interlobular lymphatic distribution. This was mainly an old condition and throughout the fibrous areas were numerous asbestos bodies. In part the fibrosis was dis posed in hyaline laminated nodules, such as occur in silicosis, with asbestos bodies embedded within them. , To this silicosisdikc nodular fibrosis in asbestosb we have previously applied the term asbesto-sitfeosis. At the present time we have not determined the significance of this com bination type of fibrosis, whether from asbestos dust Inhalation entirely or from exposure to other silica dust in addition to asbestos. It has. however, been a conspicuous finding in our material from a number of necropsied asbestosb eases, as previously mentioned. Asbestos bodies were ajso fouad In open alveoli, free and engulfed by macrophages, and in peribronchial lymph nodes. While black granular particles were present in the same areas as the asbestos bodies, they did not appear as the material of tree silicosis. Broachi and bronchioles throughout showed dilatation, vascular engorgement, mono nuclear leukocytosis, denuded lining surface and foci of transformation of undenuded epi thelium into stratified squamous form. The ex|x>sure of tins man to asbestos dust was not known, but he had told a friend that he had worked in an asbestos plan: as a young man and bad developed a cough there. Comment = During the past twelve years in 2343 consecutive necropsies we have en countered 7 cases of primary lung carcinoma, including one instance of early occurrence discovered only on histologic examination and the two asbestosis cases. Among these necropsies are 33 showing some degree of asbestosis. In tha* or' is* r ? 'r' ? .(.wi:.*\Snun <l :* be of r.vhius' and as of sbou: ;v.v;ve to thirteen dag about nr:cv.*J years before so means o: estimating accu- a3 probably making itself felt * pain, abou: r.v.> year? before sis was advanced. i; was of the ad showed no evidence of the have encountered in other adocules found were in the lymph 3. I'CXMONAaV ASESTOSIS. V o/^ the majority this is a minor rinding and not the cause of illness or death; in a few the condition is advanced. Including all necropsies and all lung cancer cases, the incidence of primary pulmonary carcinoma in ur necropsy service over this period is 0.3 per cent. Omitting the 35 cases showing asbestos deposits and the 2 cases of lung cancer in asbestosis, the incidence rate is 0.21 per cent. Among the asbestosis cases f35) the incidence of lung carcinoma (2 cases) is approximately 6 per cent. Whether this is to be taken as of significance, especially in comparison to the general rate, is questionable. The series of asbestosis cases is small and the possible statistical error great. It has seemed desirable, in addition, to record the observation that ad vanced asbestosis may lead to bronchial epithelial metaplasia of a type en countered in other locations where cylindrical epithelium may give rise to squamous-cell carcinoma. * cal cases of advanced asbestosis t has occurred. The following *ervaaoa: s. 21aess wigr.oied is asthma and ap- iropsy to have hypertrophy and diku&soa.iry orrery. pulmonary asbestosis, .x pneumoma. . show the grossly exaggerated fibrous .a 3KGQS* fiiror:* a* observed along Ibis was .tcainly za old condition and bodies. Is par; the fibrosis was dis- ilzcosisr arch asbestos bodies embedded i vs have previously applied the teem acemucec the ricrir.cance o: this comia: inhalation entirely or from exposure however, been a cunstikuous finding in leases, as previously mentioned. tree and engulfed V.y macrophages. and ir partidee were present in the same the material o: true silicosis. slamcSea. vascular cncoigcmeot, mono-' d of asssfotmatioa of unuenuded epi- lot 5ovm. hut ho h;<t told a friend that a and had deve-V/C*; a coui-h there. : .oosecuriv* necropsies we have en- tta, indudfn? c.*v instance of early xamination ur.r; the two asbestosis ring some degree of asbestosis. In \ i j j i j j * j \ t& < f : : j Lvxch, a.vd Ssurx. IV. A.: Am. J. Cancer 24: 56, 1935. G&ov.vz, $.: Tubercle If: s, 1935. Ciovxz, S.: Tubercle 13: 100, 1936. . Ecwxr, >. 5., and ZtiGtz. A. J.: Am. Rev. Tuberc. 34: 143, 1936. Xoaoiuxx, M.; Zucbr.Krobsforscb. 47: 233, 1933. Asostaox, C. S., and Dislt. J. H.; J. Hygiene 3S: 135. 1953. VoawAtD. A J., and Kak. J. W.: Am. J. Path. 14: 49, 1933. Slot*. M. 0.: Am. J. Cancer 35: 33, 1939.