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FILE NAME State of the Art Literature SAL DATE 1953 Nov DOC SAL057 DOCUMENT DESCRIPTION Journal Article - Asbestosis and Bronchogenic Carcinoma at pinay Paced : Ta z C2oe at "td Peat Re A san. Re ee Se ry _; Eas 7, 4, " i tissunt chronic to the tosis in s with. causing iandiu- narynx narynx and is xgional xgional xgional : ulcerthe 1. The cerosis las~-na dition ase in sterio- heart : heart : clini I pain : find- te * : were- nated least Jungs conia s that s not ection n that a ene icha 1. in nchi copic 7024 Towi : by ...u . : Case Case Reports Asbestosis . . ih Asbestosis Asbestosis and Bronchogenic Carcinoma She eport 2, e eaport of One Autopsied Case and Review of the Available Literature | ta at ei KURT J. ISSELBACHER M.D. HANNA KLAUS M.D. and HARRIET L. HARDY M.D. . Br _ re Boston Massachusetts ie fe - clothing Fhe in Ly THERE are several reasons for presenting detail a case report and a review of the lationship available literature dealing with the between occupational exposure to lationship The apparent and respiratory tract malignancy apparent increase in bronchogenic carcinoma Specially in males reported in the past decade to as led scrutiny of respirable dusts as possible are Etiology Most English observers'- satisfied there : that is a statistically significant increase curtains and The chief operations are disintegration of the crude mineral carding the fiber separating the more useful long from the short fiber spinning plaiting and weaving the asbestos often with cotton Insulating material is produced by mixing magnesia diatomaceous earth and other materials with asbestos to make _ cements or fillings for insulating boilers engines and pipes Other textile asbestos products so made include asbestos cement sheets brake pulmonary electrodes workers malignancy among asbestos _ and clutch linings Some American writers consider that and switchboard Thecoenxtepnetrioinence contention to date does not support this " The work of Graham Doll and - Asbestos is a hydrated magnesium silicate Province the ITthaelicynhioRefhfosduepspilaies are in Canada Cape conchogenic particles Actual Hill and Ochsner.1h"as created much interest and Russia Asbestos dust given correlation of cigarette smoking with off manufacturing processes consists of frag- -* carcinoma E. R. whose case is ments fibers and small rounded or angular frein presented was exposed to harmful studies in industry show the size and mounts of asbestos dust and was a chain shape of the particles of asbestos to be moker This provides speculation as to the such as may gain entrance into the bronchioles ~ possible possible role of two etiologic agents - Experience has led to the acceptance of five Renan Few reported cases of lung cancer related to million particles of asbestos per cubic foot of air dustrial asbestos exposures provide data on of small enough size to be respirable to be the _ character He ae He and quantity of dust exposure safe working concentration + 7 | . Y correlation is a serious deficit in exact study of etiologic Some operations because of their dustiness correlation In the clinical report presented herein more hazardous than others in asbestos . herein State authorities have determined by manufacturing Bagging the asbestos separating this theasurement that the asbestos dust exposure the long from the short fibers carding spinning- | man of work was during his twelve years | and weaving show a greater statistical evidence aay ArLisS insiderably insiderably above the safe level which is con- : ofasbestosis than do other operations As might dered to be five million particles per cubic be the .. | * of expected longer the of oot air for an hour working day . the duratexipoosun re - the number of nny _ Itis pertinent to this presentation that there greater cases In the Mere- wether and Price series there was one case under re probably about 10,000 workers engaged in four years exposure and up to 53.6 per cent potentially hazardous asbestos manufacturing - with fifteen to nineteen years exposure operations in the United States Middleton Reports the number in Great Britain as between ' CASE REPORT fe000 to 5,000 Most of the industry is engaged asbestos textile manufacturing producing | oa sulating mattresses brake linings fire proof * R. MGH 735586 a forty year old asbestos mill worker entered the Massachusetts General Hospital in April 1951. The chief Hospital From the Departments of Medicine and Pathology and the Occupational Medical Clinic Massachusers General Hospital Hospital Boston Mass This work was supported in part by the National Institutes of Health Division of Research 721 is . te fae, ae) 2 afotee {een ae deo ah giet: (is gy 2 te Peevate aleee pts;Eee ae ideote . ot - 4 aE eee wre VA POE rie ls T ry y ene? ee ay Se Re 2 Bronchogenic Carcinoma et al -tions 30 and temperature 99 orally Hischa cha me reduced breath at i sounds 4 and Beem... both lung Bea - rales bases with sticky inspiratory cracking over the region of the left lower Reged. left of dullness was border cardiac lobe ; v3. cm 2 PULMONARY FUNCTION STUDIES * JEFORE AND AFTER A . . . : greater A oe vy there was some pulsus para- = was partially only In addition one + doxus Liver and spleen were not felt There -- spine over - * month before admission the patient noticed : *. was tenderness of the with spasm .: . increasing dyspnea on exertion a worsening of - of the lumbar musculature He had extreme of and patter . size lower lobes considerably chronic productive cough night sweats clubbfini gern s g toes Jet TR . anorexia feverishness and pound weight Laboratory data revealed a normal urinalysis loss He had worked in an asbestos mill for Hemoglobin was 14.0 gm per cent and the - , white count was 5,700 with a normal differen there for two years prior to this tial Chest ray revealed revealed the sion In the mill he had hospital admis- :: in and showing a reduced : picker room where spent one year in the _ honeycomb s+ crushing grinding and sorting of long asbestos fibers density in the lingula withbe a homogenous * . He also worked five was carried out . lymph enlargement of -:. . where the years in the carding room ts concentration of fibers had ~ been ll _ determined by authorities to be . QL lode giving the appearance of HD metastatic malignancy Electrocardiogram showed specific T wave LORE changes protein nitrogen was 27 mg per _ AA i about two years There had been no units Repeated examinations c^ hemoptysis Physical examination revealed a thesputum sputum were negative for acid . chronically ill and dyspneic man with evidence of isms asbestosis bodies and malignant cellosrTgwano- loss and cyanosis of the lips and nail weight . bronchoscopies revealed obstruction of beds The- lower lobe bronchus The the left a blood pressure was 110/75 pulse 96 respira- of ACTH 100 patient was given mg daily intramuscularly tee . AMERICAN JOURNAL OF MEDICINE catheterization performed ardiac studies were efore ardiacgnificant efore and after ACTHand likewise showed no gnificant changes Tables 1 and n Cardiac theterizaaet~ ion ddididreveal chronic cor pulmonale cor pulmonale pulmonale with congestive failure He was digitalized given mercurial diuretics anti- spasm| - Sxtreme ad the caltern Egenous 75 tent of zung a Filmns rete 1. Filmns i and . ertebra mincy Cardiac Catheterization studies performed FACTH 100 mg intramuscularly Friedlich J. R. O'Neill G. 15 30/10 - 1421 3.2 47 43/14lL 28 TOPE 5.55 38/15 ee 52/22 36 6.97a Unit of Scanel Massachusetts: General Hospital pulmonary tise the pulmonary hypertension hypertension penicillin streptomycin biotics : and and was increased an oxygen tent most of the time Chest rays d received adiation confused significant discharge d unsaturation |arterial oxygen d ppeared ppeared adiationppeared Before from the hospital he spine fourth with adiation 1,200 r to the lumbar :; now were suggestive of lymphatic spread of - became therapeutic measures tumor In spite of all : * dyspnea and cyanosis grew worse He fever Fo cw no :. and died on the hospital ye cemed necropsy patient the discharge patient wasemaciated For severalweeks after the 7 At the cemed somewhat better and returned to light thorax was lengthenedin the anteroposterior : ark However the cough increased markedly 7 the ~ ark diameterThere clubbing of fingers and the had severe dyspnea at so rest that after toes was rt opening thorax lungs months to be readmitted Physicalcollapse On the the did not amination entry revealed temperature completely * aminationamination on | a collapse- butremained inflated completely ts 100.4 rectally pulse of 120-144 respirations filling both pleural cavities The majority of ! 9. Pras | per minute He had marked : the pleural space was obliterated bilaterally by ~~ tachypnea moderate cyanosis and such dyspnea thatit was dense fibrous adhesions between the visceral moderate him speak There inspiratory difficult for to were many and parietal layers Both the visceral and - inspiratory andexpiratory wheezes throughout parietal pleurae were markedly thickened gray lung fields . abbling were ae At the right base mois moit st .. fibrous membranes measuring up to 0.3 cm 902055 " _ |. abbling thick There abbling rales together with dullness reduced . were 100 cc of clear colored Factile Factile fremitusand increased vocal fremitus ' . fluid loculatedin the left base The interiobar toe Theleft border of cardiac dullness now extended fissures were obliterated by fibrous tissue ~ - gut cm from the midsternal line P was . Scattered throughout the adherent layers of the a auch louder than A The liver was percussed diaphragmatic pleura especially on the right Own two and a half and there Own fingerbreadths plus ankle edema At this time white plaques were a number of whitish gray shiny 0.5 these resembled similar FasVEMBER plaques 2 the 0.5 cm long 1953 . a ST =. 3 q at 3): 4q 3 tle wee daly pert ry an ORT estekn punoeee Y Feran nad - 724 . : * - or Op yh oes no Asbestosis Bronchogenic Carcinoma et al Be ES wey. OTR, oF er s, i] 4 0 WaktieTE A pate 4 aahaehy vel id ima. reTe oP ae me *,* Fr. 3. Asbestboodsieis sin the lung The shaped 7. 3 a eS eae Oe, Se oe "2- " Fro 2. Cut surface of left lung after formalin fixationat was collapse of the intervening parenchyma pleurak Note diffuse fibrosis and marked thickening which oblitteherinatetrle obs ar fissure - . - ~ Lae, seen on the upper surface of the livetro be described The lungs weighed 2,710 gm were -* The veins and arteries appeared normal ~. -\There were adhesions between the visceral =a.nd parietal pericardium both at the apex and the base The apical adhesions were thin fibrous strands but those at the base were extensions c^fi voluminous and very firm throughout no dis- - the firm tissue described in the left lower lobe ' The heart crete nodules could be felt Fig 2. Multiple bronchus " weighed 360 gm There sections showed a uniform brownish gray surface was involvement of the left atrium and auricle - by thick pink throughout except in the left lower lobe where firm grayitsisshue for - an area there appeared to be a diffuse marked fibrosis ';, throughout the parenchyma The left lower was -, lobe bronchus completely occluded I cm.0.6 from its origin by pinkish gray firm tissue for 2. : measuring 2.3 by 0.7 cm The remaining myc- - cardium appeared uninvolved and measured cm.0.6 cm thick in the right ventricle 1.3 cm in the left endocardium and valves wers * distance of 1.4 cm here the bronchus measured ~ . 0.7 cm in diameter the firm pinkish gray tissue extended into the parenchyma for a distance of 1.7 cm Similar tissue extended from this point in the bronchus to the pleura and into The diaphragms contained firm grayish pink areas of plaque thickening which measured up to 0.5 cm in diameter These were seen on both the pleural and peritoneal surfaces were the wall of the left atrium which was adherent apposed and loosely adherent to similar con- to the pleura at this point the gross atrial in- . fluent areas in Glisson's capsule The remaining volvement measured 2.3 by 0.7 cm in extent . The upper lobe bronchi were rigid and nar- organs with the exception of the fourth lumbar vertebra were negative This vertebra appeared rowed by a thick white fibrous coat The right opalescent and resembled marble but its con- lower and to some extent the right middle and - sistency was softer than the adjacent vertebras left lower lobe bronchi were dilated and there _ The body appeared to have increased porosity AMERICAN JOURNAL OF MEDICINS row oe w whee e peter woe: V ay eq wr ry 1 wi e e aay ed dar Aaes EN to bl ve] the ducts asbestors ~~soe S.s us sin a, asl SquamousSquamous metaplasia alveolar BRB ZESSy %< sent Fide: 5. Adenocarcinoma invading the myocardium X 100 interstitialfibrosis 100 pCy Y #ait 2 lungs topographically Fal S Sections were sectioned i cleswere present in the macrophages The - ait oy Sections = Sections Aa the nd sus sof Sections ear from all segmental bronchi were taken- hilum the lobar and the periph basic patterns distribution was equal bilaterally being slight -".: me to moderate in the apical segments quite - marked in the remainder of the lung and oc- - *. * 8? > ral areas These ee histologic could be Reoeseen: | Fibrosis Throughout intensity hilar mid- lungs lobarand ome Fibrosis the there was - curring witpehriepqhueraalinltensity zones i n the = ne a bodies were seer cle proliferation proliferation offibrous tissue around the bronchi ~ While most of the asbestosis arteries ' - Tea pat alveolar ducts the interiobar septa the bronchioles and alveolar ducts a few fragments be seen 0 Being pleurae were also thickened There was could _ in the alveoli and were* nd 7 ribronchial and alveolar duct fibrosisin both found both in the macrophages andin the , ribronchial in an demonstrated asbestosis ame hices and slight alveolar wall thickening lymphatics Several aggregations of by connective tissue stains The . bodies were foundin the bronchi Fragmente.d- RO=< dhrosis increasedin the remaining portions of - asbestos fibers were found mostlyin the macro "2 ink ne vedi it | rc dschnrokoirseaid shubnugst ewxastehnedaevdiestto itnhtehepehriliaprhearndy lobar This con- firmed firmed the gross impression of diffuse fibrosis Asbestosis Asbestosis bodies Asbestosis bodies were present phages but occasional staining particles | were found free on the alveolar walls Much but by no means all of this materialin the ' macrophages took theiron stain - .- eo all inflammatory ae sections Fig 3. These were segmented _ Inflammatory response The chief a cells fs : averaging 50... long some straight and responding to the irritant were the macro- ae wt re 25 cf shaped Some others resembled dumb beils phages These cells were seen in abundancein stained dark brown on hematoxylin every section they lined up along the walls of . - s (which = and were preparations and blue on Prussian blue iron preparations Particles ofstaining dust and f^/rger f^/rger bE: f^/rger easily identifiable asbestosis bodyparti- the alveolar ducts filled the lumina of bron-- bron-- chioles and alveoli found throughout the septa and fibrous tissue Most of these con- it ae beogh coe rate es nae BF ae week a | gm formalized 65 sample of and ignited on ? washed with gentle heating The at 500 The ignited EE J. article by Hanawalt D. Rinn FL Anal EL vol 10 no 9 1938. This yl, ~- ee brown mee . eee Blood vessels - "2" bodies iron stain and of portions of asbestosis FriR ghs t middle The arteries and arterioolf tehse were also found in the macrophages =. and both moderate intimal lower lobes showed : thickening with hyalinization a +,tfhiobuerghctonsttoitluatyindgotwhne the iron on the asbestos near the hila but was found asbestosis body Anthra occasionally farther farther TphLages Multinucleated giant cells of = ) . body type were foundinabundance atlhelfoarreeiagsn 7. many ofthese contained birefringent asteroidal Tumor Adenocarcinoma was found originating in the inferior lingual segment of the left aaa probabldyilaactcaotuinotns lefrtAsabeystos granulomas The wcahrirtieed plaques ~ fibrin Someasbestosis bodies marked in Se " monia with polymorphonuclear infiltration 3present these had no : to -location particular any grouping of the relation or atrium showed direct extension + it and were left hilum into the through the - : dilated undoubtedly a terminal Throughout the lungs phenomenon = dium pericardium Fig 5. Metastatic and myocar .. 7 dilated and contained many air sacs were fourth lumbar vertebra tum wasoser en in the 7 J." . material probably a granular cosinophilic ~: were undergoing organization of these plugs mainly in ._ described in the diaphragm and Glisson's ne, olar dutc his t typesof fibrosis alve- -: sule were made up chiefly of hyalinized ca^ _ J fD os r small percentage ofthe total fibrosis - nective tissue No asbestosis bodies or cor- oo Bronchi The bronchi ofthe lower seen lobes showed /:" cells were seen These distinctive =: areas gian grossly marked bronchiectasis there war suggested granulomas . | ; Be ~ fibrosis of the muscular coat and peribronch-i..alsuggested were diffraction studies were out ca fibrosis While the latter was most sample of formalized lung tissue The the lower lobes it was seen in the hilar and . pattern indicated that the lung resirdeuseultwiansg zonal regions of almosatll segments mid- _ mostly asbestos Fig striking feature was Another asbestos 6. .. oo, " ", widespreadepithelium squamous Tes : metaplasia of the bronchial epithelium Fig 4. ~ This was most marked in the alveolar ducts it : ~ was found * in all areas and was not particularly wnt related ' topographically to the adenocarcinoma | fibrosis - fibers and leading to a progressive described later os 4 . Se rs ee been demaonndstsrcaatrreidngbywiGthairndtnheerlungs It has ; ; demonstrated and again by . _ AMERICAN JOURNAL OF MEDICINE ' ee aD elgg TS RY FS ae POSEN LALLREL ot Pt tee RAR SE TA) if A eh Dd A US OD) a . tS ton Go fete ~y pe Cat, yy ab & tae cer Ey Pa oath? SES be Pear 2 he Cone eS Oe iad cag at OTE - Asbestosis Bronchogenic Carcinoma et al 727 forwald is | forwald that usually the disease will not In general there a delay of five to seven with tup fibers less than 20...in length or a . years between the initial exposure to high con- concentration below million concentration concentration five particles per centrations of asbestos dusts and the onset of of air LR Gs - clinical asbestosis The average interval re- Tubhicefopoatthologic is processes resulting from the inhalation of asbestos particles are believed ported by Merewether eleven years While most patients with asbestosis have had an exposure of ten to sixteen years it is important ~ ' a terioles of the obes showed hyalinization most marked father the consequence of mechanical irritation from fibers lodged in the respiratory 18-10 The inhaled particles are in general too large pass beyond the respiratory bronchioles and they remain there to initiate a foreign body ' reaction which eventually leads to fibrosis considered pathologic sequence of events can be considered as occurring in three stages 1 and exudation 2 formation desquamation fafasbestosis bodies and 3 fibrosis and scarring long fibers traumatize the epithelial cells The the Sining smaller bronchioles and the constant Entation and friction cause the cells to desquamate a Macrophages pour forth in an effort to phagocytize phagocytize the fibers In our case fragmented to realize that the disease has occurred with as short an industrial exposure as 0.5 years.1.1 Usually no symptoms appear until a large | part of the respiratory reserve has been reduced by the fibrosis Merewether has frequently commented how markedly the lungs can be affected and yet the patient be fairly comfortable.17 However when symptoms once begin and significant dyspnea becomes apparent there is ' - usually a definite and rapid progression Then productive cough anorexia weight loss and fatigue are the common complaints Death eventually results from intercurrent infection cor pulmonale or carcinoma of the lung The case herein presented demonstrates many of the significant features in the pathogenesis nally farther tsbestos of phages nd 2 nat - and lymphatics A second reaction to the _ symptomatology and natural course asbestosis - fiber in the lung is the production of the . The patient had worked for twelve years in an -- atmosphere having a concentration of asbestos- - ; ; left . . particles known to be sufficient to produce --- . w present last year al posterior the entire of had been as the right which probably by sub- of murse a a pulmonary pathology However it was only "0 - ~~ during the of life that dyspnea cough | protein- matrix containing iron serves to reduce the chronic anorexia and weight loss manifested themselves Clubbing present for at least five Pc Ss which ition These bodies may be found in the years He had a very rapid downhill course due sad tions of the through the Their id myocar- seen in the Sindication Sindication te plaques cson's cap- nized con- | : or giant utum lung pleura lymph nodes and spleen.25 Se presence is held to be evidence of exposure fasbestos but by themselves are not necessarily - Sindication of asbestosis 17,27,28 3 The third and most significant tissue response the production of fibroblasts and the deposi- on of collagen about the distal bronchioles alveoli There ensues a diffuse fibrosis which . Compresses the alveoli and capillaries resulting - undoubtedly to the two associated factors asbestosis and carcinoma of the lung The physical findings of clubbing cyanosis and dullness at the lung bases were all consistent with asbestosis as were the ray findings in the lungs apart from the evidence suggesting neoplasm The outstanding symptom the severe and progressive dyspnea was attributed to a combination of pulmonary fibrosis superim- led out on * resulting tidue was - ic occu- tation of ogressive 7 bas bas complete obliteration of the involved pulmonarytissue This process is more pronounced in thelower lobes of the lung for it is there that the are particles most abundant By ray one sees 1 fine ground glass or granular pattern in the lower lower lobes and frequently emphysema in the apper lobes The sequence of pathologic events described # occurs slowly In man the fibrosis previously Bo ends to progress even after the exposure has eased however in animals this does not seem ay the case It may be that intercurrent infec- on contributes to the progression in man NOVEMBER 1953 posed and spreading lung neoplasm pulmonary infection and finally congestive failure on the , basis of cor pulmonaic As indicated in the case history the day period of ACTH therapy was accompanied only by euphoria but objective measurements revealed no significant changes This was not surprising for two reasons ) the fibrosis had obviously been of long duration and therefore one would not expect it to change much at this time and 2 he had superimposed bronchogenic carcinoma It is of interest to compare these results to patients with chronic beryllium i ed at-d, 4j Bel sie thal pdbe rXen tbe han oR alel SBdle = a3 $A cae i Fwfacgse = al sab 7H si Pytes, au ths"? Ty fr thd hele 4 { a ax ane es FRESE nee paraee eee ab gas batters ae aa : aq: :TG 5 BEELER HITTER BIEEIEE 9493 4 PERE 313 4 He ; seed BS east (1dai4 3: 4439) 473 3, Asbestosis Bronchogenic Carcinoma al x 728 et . - poisoning who usually shoaw favorable re- - = sponse '_. to steroid therapy oa, eo Two further aspects of this case . number to be of significance others especially pe ey Vorwald and Karr have stated that inkaled more merit detailed consideration and ., dusts except those containing recognized anzei a analysis 1 pulmonary function and cardiac the , nogenic substances as radium and tar mo of studies and 2 catheterization the significance in general be considered as etiologic factor in _ posed bronchogenic carcinoma | e the se uperim- ".- te hee development of primn aro y pulmonary ensai eo oe wy oye PULMONARY FUNCTION AND CARDIAC a wot INCIDENCE OF ASBESTOSIS AND CARCINOMA OF T Merewether 235 LUNAN ips. | of { finding . CATHETERIZATION STUDIES-- we oo, a ' .. Table I indicates as one No. the patient had a reduction might expect that - _ * Author | Deaths with Cancer in vital and maxi- - 1. : / Asbestosis | - mum breathing capacities However the Lung f. (2) _ of an alveolar oxygen gradient of .. _ | 27 mm Hg demonstrates . of the dis- 235 fe LUNAN fu that one turbances in pulmonary i . function was a defect . in the diffusion of oxygen from the alveoli of the - . ' lungs to the capillaries This corresponds to the syndrome of capillary block de- " by and Total Baldw Balidwn in Cournand Richards1.32 and again by Austrian et al This diffusion ' Wyers .. Lynch | Cannon Gloyne wee eee f 115 LUNAN aed 40 efi LUNAN 121 LUNAN Pe 7.5- ral Total 603 Total neces i .. oo O 13.3 O 13.3 . , : 7 . > _ * defect is not surprising when one recalls the noma Our present fibrosis about the alveoli alveolar conclusion at is in favor laries and bronchioles that occurs idnucastbsesctaopsiils- of the concept that the association of breacion genic carcinoma with asbestosis is more ** In order for the patient to maintain a near coincidence That there is significant inciden normal arterial a alveolar oxygen saturation a high - of bronchogenic and this carcinoma in asbestosis oxygen was necessary is ap- .. apparent from Table -.- <= : parently was accomplished in part by hyper- . Merewether has cited the tae ventilation The patient had an * of respiratory rate of 40 minute average .- 235 casesasbestosis there were thirty with per cent.1 compensatory mechanism at restThis :. bronchogenic carcinoma or 13.2 per the apparently was not adequate during stress or exercise for average of the five analyses recorded in the per _ those conditions the arterial under literature is 13.8 cent is considera fell There was considerableodxeyggreene soaftpurualtimoon - ihnigrhoeurtitnhean the incidence of lung carcinoma nary hypertension and as in the cases of pulmo- necropsies which in a comparatis period 1935-1948 ranged from 0.8 to 2.4 per - associates a rise in the pressure occurred with pulmonary artery In contrast to asbestosis the incidence of exercise Table I. The :. bronchogenic carcinoma in silicosis as recorded of partial pressure carbon dioxide in the blood in the two largest series been similar mm to 36 Hg was low normal rather than cle- - what might be has vated Had there been a defect in alveolar . expected in the general popula- tion The data ventilation the pCO would probably have compiled by Merewether and the Miner's Phthisis : been higher As Arnot emphasized in discussing . Medical Bureau of South Africa are based on is not . this case,,carbon dioxide impaired in autopsied a total of 6,884 and 1,400 of and its transfer from the blood to the alveoli because disclose cases silicosis respectively of its great diffusion capacity This speed of 1.32 and an incidence of lung carcinoma found per cent Karr found diffusion plus the increased alveolar 0.70 Vorwald and ventilation no doubt accounted for the lowered pCO value two lung carcinomas in 136 silicotics 1.47 per oe cent Klotz noted an incidence of 8 his fifty does ^ SBESTOSIS OF THE but series of per cent cases not seem large CARCINOMA LUNG 1 The association of and enough to be statistically significant Howe = asbestosis of the lung has been carcinoma Gloyne in reviewing necropsy material from mentioned frequently in the literature Heretofore 1929 to 1949 796 cases also described the some cases have believed that the authors were too few in surprisingly high incidence of lung carcinema in silicosis of 6.9 , per cent and 7.7 per cent in AMERICAN JOURNAL OF MEDICINE . , statedthatespecially pneumoconioses In same bronchogenic a inhaled- Series jum and tar cannot 7 Gloyne's cases were analyzed as in factors in Seeries oi period as whole this * carcinoma was about eigh 8.3 Similarly per cent of cases withoutany pneumo-*. years Merewether found that caric had canceorf the lung Merewetahnedr'~. dying of carcinoma of the lung had a lo comparable i" over a mean exposure to asbestos 16.5 years han of time so that it seems unreasonable-? those dying with no evidence of malignancy rryyetgiuollmoogincary carci- carci- CARCINOMA LONG population OF = Ginterpret the figure of6.9 percentreffecting : 13.4 years Finally a short but adequzur increase of lung carcinoma in the general exposure may be followed by - pulmen se The discrepancyin the data proba- many years later In Merew Se population Gloyne's malignancy ? No. Due to material 7 Cancer material which Lung . * Loci- dence _ % figure | lower lobe 15 16.3 Callicosis pertinent 17 +] 14.1 Nis explained by the fact that : serieiss the case of a woman who was an nib qatn was selected from the pneumoconioses ' - workerfor only six months yet later devain < and rays - the histories unusual | lung carcinoma Gloyne reported the =<22 Gloyne = noted that 14.1 per cent of patients \a woman with an exposure of nineteen mentio with asbestosis had lung carcinoma This - who died fifteen years later at the age of ser farallels .. squamouscell carcinoma the ie fe rv the inform ~. ; nse farallels the observations of previous workers**. one with a : is significantly above that recorded for - re | of ve P ERNE As has been mentioned the asbestos Table summarizes probably acts as a mechanical irritant *tion of the twenty cases of asbestosis with particle 11 the pulmonary changes in silicosis are | carcinoma that have been autopsied and > while considered due to the chemical properties of File aut so corded in the available literature Four sm < have been added to the list compiled by E1- present < isin favor ociation of broncho- ztosis is more than sigri^-cantincidence were thirty with -..: 13.2 cent An es recorded in the This is considerably of lung carcinoma a in a comparable from 0.8 to 2.4 per - 8 1 the incidence of recoasrredcoe rdd ed - as been similar to the general popula| ' Merewether and a Bureau of South af 6.384 and 1,438 respectively and- HAZ carcinoma of and and Karr found t^"lzotics1.47 per ence of 3 per cent s not seem large mitant However | ~ by material from o described the if lung , ta C, carcinomacent in MEDICINE Carcinoma the ; lung appears Carcinoma of to be promi- burger 1943. Itis noted thatin about 227~ in oo femaflemealess with asbestosis Of Merewether's < one cases nine were females or 29 per cent ay andin Gloyne's series of seventeen cases . fifths of the cases in which the primary site ~ the origin - indicated of the neoplawsasmsin th : : lower lobes Thisis in contrast to the g incidence published autopsy seth was per cent In the _ carcinoma sams autopsy reports population where bronchogenic autopsy data as to the sex of the patient2to be more frequent in the upper lobesIn incidents available in twenty ofwhichfive series there an o ree the Lindskog's person contrast 57 per cent were females In : per cent in the upper lobes26 com ls lower lobes drawn Lindskog noted an incidence of 4.0 per a No conclusions should be in Hill" in un Graham5.4 per cent Doll and 8.4 per the small number of cases listed .. Centand Ochsner10 10.3 per cent The higher Nevertheless since asbestos Tabis : sbestos theory particles lodge tVILAo asbestosis 7: in supports the that greater extent in the lower respiratory " a where the changes of asbestosis are also more neoplasms a*. a higher incidence of carcinom pronounced ~ in this location should be expected an etiologic relationship exists In our case the asbestosis _* was widespread and and the turner severe Gees lingual which originated in theinferior seg- ment of the left upper lobe was in- an a eS ound metaplasia lungs fibrosis ee thelium The squamous of significantly involved by the and frequentlyin asbestosisis presumably a.: flammation of asbestosis - of prolongedirritation in the lower=: It also notedin Table ry that twelve nu FE consequencetract Some pathologists consider nineteen previously recorded cases had Infin respiratory in precede quamous efx metaplasia as an alteration in the of the squamous cell type The incidence cellular structure that may or be the _squamous cell carcinoma is said to be high step towards the of male mokers withpulmonary mitial development cigarette t squamous & f nancy At autopsy our patient showed t eil carcinoma.5 the exposure period A lag between to : squamous metaplasia and adenocarcinema c Possible ris carcinogen and the onset of malignancy the lingula It may of significance that he wo vox. characteristic Nordmann noted in his cases a chain smoker for over twenty years in vize : that the average duration between the initial the observation by Wynder and Grahari te See Exposure to asbestos and the development of = LOVEMBER 1953 males with adenocarcinoma of the lung pd 730 ee Carcinoma EY: frequently Asbestosis Bronchogenic Isselbacher al chain 13.8 awe eA chain smokers However it is our per be belief that the of * carcinoma in cent of the cases cited in adenocarcinoma presence an ~ the literature In silicosis the incidence is -. one of be rather than the squamous cell type may by - - be explained the fact that is not unusual con- siderably less than this The asbestos particle a may servaes a carcinogen because of the to of > ftihned several cellular types in various sections chronic mechanical irritation it produces ... . a of approximately same tumor fs 5. Since .. there are 10,000-10,0 0- ad ~. -, Rap ae wet me ee Duratiom Occupations . of Exposure from Exposure Nature Aga | _ YPJ M. Weaver sr... 35 | Spinner Po ge 1,71 Mattress and open- 1K 15.yTor 15.yTor - Tumor Primary Se Oe Lenser, epeeiP oe le dice Pact t 4a . at lab APM ' . a Wa d q 4 a4 4 % Ee Sm 1) aga e e als he Bite! Kes aids tet a be on ~ ene lower ive- pray woBaar 7. Homburger : oo. pececes .* : Homburgerene So edn cee ee eereecs - Homburgerinn Homburgerinn ed. at. on . Caress, . os areal .scances. 00s differences in cell arrangements may not really Jie... represent different etiologic varieties of cancer me ify SUMMARY AND CONCLUSIONS '. * ale 7 1. A case of asbestosis with superimposed' +> ./, adenocarcinoma of the lung with metastases - oS following documented harmful industrial ex- workers potentially hazardous 7 engaged in asbestos operations in this country it is reason- able to assume that there are many unrecognized cases of asbestosis From the evidence presented ' a higher incidence of bronchogenic carcinoma should be expected in this group os - Addendum Since the submission of this manu- a - 2. ACTH adrenocorticotrophic hormone MGH 778205 patient was forty +. was given with no objective changes in the year old contractor's helper whose work since patient's clinical course | a age seventeen consisted of cutting and sawing -, > . 3. Pulmonary function and cardiac catheter- asbestos board to insulate pipes boilers and after ization studies were performed before and _ refrigerators For years he had smoked one diffusion ACTH They revealed an alveolar . defect and pulmonary hypertension bronchogenic 4. Asbestos is associated with bronchogenic package of cigarettes daily He died after year illness during of the last four months of which he received 5,000 r of deep ray to the left chest AMERICAN JOURNAL OF MEDICINE RE?x Ne1 shy BSF rere PRC mee thi < crearec lh pata oan AAaEr Bemis b i osr 5 TOvy : Se ae Banaes ofys -9 ag, i o eee i AT te ugh ts mes ee LENSE MUERO es Pena Sat fetta s faite, sAt RS ERR eo bai E egines e pro. Bats, tact r ee (ee 2 iscon- firm weighed lungs the andweighed As autopsy were 350 gm There was a poorly differentiated > -with reference tto o 1930 pulmonary asbestosis Tubercle 11 particle * 7 Gardner Etiology of pneumoconi ris of the ' 21. ee left 10,000 -... i diaphragm right . . A >, alveolar wall found in pulmonary asbestosis and Brit curious bodies __. 20. L. denocarcinoma arising from the left lower lobe Bronchus U. almost completely replacing the left slower Fe lobe The tumor had spread to the te lobe # upper hilum pericardiumspread pleura and diaphragm metastasized J. fungdiaphragm andand had metastasized to the % and adrenal The remaining lung - tissue pulmonary Thowepderibronchial fibrosis focal pneumoconiris GARDNER L. U. and Commancs D. E. Studies on _. experimental pneumoconiosis vt Inhalation o"" * asbestos dust its effect upon primary tuberculous- _ infection Indust Hyg 13 65 97 1931 = 22 Cooxz W. E. _ ~ 2s 1929 asbestosis Brit M.J578 of asbestbair ZataZata Cody particles lufnorgesignnotnot completelcyeilnlvsoTlvehd e Demonstration vlules in _ thickening Histology pulmonary : Brit J. 1025 _ tumor the giant the peculJ.iar bodies of pulmonary asbestosis- oO Fall foreign the sputum . and numerous asbestosis bodies sur- 23. McDonald S. rounded by macrophages filled with asbestosis ogg, M. 2 1927 ree . ~ Cody and sbestosis bodies were * parts of st by + a bodybody giant The seen in equal distribution not ; 7 24. Stewart M. and Haddow A. of in J. - +asbestosis bodies in material obtained by lung *puncture Path S Bart 32 T.. 172 1929 aa . . * 25. GLOYNE S. asbestos presence of asbestos fibre in the nd picurs soeys " MEREWETHER R. Annual Report the 1931_ Asbestosis two cases Arch Path of A. MEREWETHER Inspector of Factories ' Stationery London of 1947. Chief26. Chief 26. Stewart H. L. BUTCHER C. and Colzman H. M. 12 909 + ' 1931_ a WYERS SLOYNE Pulmonary Asbestosis nedim aS nedim WYERS Office H. + ee t 1949 Post Grad M. J. 25 631 27. Woon W. B. and S. R. ' asbestosis Lancet : 1383 1934 9. codes al nodes kidney a, F . F ny) ~ ; fh. enal niur m iver wares, row. peris m peris IDine - rccus : 350n GLOYNE asbestosis M. A Vorwald necropsy histologic 7 Abe.ryllium- 29. Symposium ia Lynch 810 et S. R. Pneumoconiosis A survey 28. M. J. in of survey 109 1974 ore, a material in 1205 cases Lancet 1 on the treatment of chronic 1951 . - ; 24. with | : Vorwald A. Pneumoconiosis ACTH and cortisone Arch Indust Hyg 543 J. eas W. and Kark J. ut 3 1951 and and wetieee? J. E. Path carcinoma 49 Am 14 + 1938 30. Baldwin Cournand insuficeny RiCHARDS J. J. D. W. Pulmonary insufficiency L. Physiologi- . Personal communication with 1957 Vorwald A. A. Graham E. Primary cancer of the lung clamification clinical methods of analysis standard sg, subjects Medicins normal in special consideration of its etiology Bull Naw s valuesin : 27 York Acad nt. Med 27 261 1951 - a 243 1948 Cournand and RicHARDS 37. Baldwin woo? 37. D. DzF A> ts: WYNDER WYNDER E. and Graham A. E. Tobacco smok- Jr. Pulmonary insufficiency mudy =: Ring as a possible etiologic factorin W IL A of thirty fibrosis pulmonary cases of Medicine ees. carcinoma J. A. M. d 143 329 1950 Te 28 ; 1949 : R. paseo DOLL and Hmi A. B. Smoking and carcinoma Baldwin 32. Cournand A.and Richards DIF pas: of the lung Preliminary oe of 122 ce. .1950 Report Brit M. J. :. . W. Jr. insufficiency IL A study - 9 cases of chronic OCHINER A. and DeBakey 1941 E. Carcinoma the emphysema pulmonary 22 of .Medicine 28 201 1949 > 33. MCCLEMENT Arch Surg tlung 42 209 1941 33. Austrian R. J. H. Renzetti M. D. OCHINEAR.DeBakey E. DrCamp P..T Donald K. Razy R. L. and AL : is RaCy . J. J. A. M. Clinical and Cournand * Bronchogenic carcinoma physiologic features of some types of A. Lanza 148 691 1952 mh a pulmonary diseases with impairment of . ees A. alveolar hh Personal communication 1952 ) ) nniizzeded ented 10:11 : , 338- a vi vi 1200 ving 0 and . oe 2835 cn A. (. capillary diffusion Am J. Med 11 667 1951 6. Silicosis and Asbestosis p 386. New abemos A. Pulmonary E LaYnozark M. and SMITH J. wees:! 1938. Oxford W. - p Univ in Press REIS Ide3m 27 oo ob abemos ff Carcinoma of lung Sik unkt axbesto- Am J. W. B. and R. silicosCaincser 24 56 1935 axbesto- | Feeay WOOD Gloyne Pulmonary 35. R. cases of squamous lf: of Gloyne S. carcinoma the lung ns es asbestosis Lancet 1 445 1930 - '_ _ - in asbestosis Tubercle 17 5 1935 Report 36. eae MEREWETHER W. , E. R. and PRICE C. S. R. A case oat cell ~ Glovne cso carcinoma lung of on the Effects of Asbestos Dust on the Lungs and of geass in 37. * Dust Suppression in the Asbestos Industry occurring asbestosis Tuberds 18 100 1936 37 D. S. and Gerora A. J. Egbert Pulmonary asbest- peascc London 1930. H. M. Stationery Office mags 16s: Case Records of the Massachusetts General Hospital . *, - tosis and carcinoma Report of a case with Decropsy findings Am Rev. Tubere 34 143 1936 Sas case 38221 New England J. Med 246 867 1952 *.> 38. , M. Der Berufskrebs der Asbestosarbei-- asbes- R. A. A memorandum on Ses& Merewether 39.NLoYrNdCmHann eet 15 ter Zischr Asbetosarbei- 152 - tosis Tubercle 15 69 109 1933 Tubercle f Krebsforsch 47 288 1938 K. M. and Suth W. A. Pulmonary 1934 oa a ye J. Durkan T. and Pratt C an Vorwald aasnbdestosis M. D. 3 Experimental studies on asticatonia Arch Industo + v A report of bronchial carcinoma epithelial metaplasia Am I. Cancer 36 1939 - oe, ot wo Tang "s ot oe oye Ee = oe us : no C. 3 Hyg 1 1951 GLAOYNE fe, GLOYNE S. R. Reaction of tissues to asbestos fibre eeVEMBER 1953 32 - 40. Kozisch F. Lungenkrebs und Beruf Zmtra^>blf Gewerbehyg Gewerbehyg 27 1940 =. = wey i id ri ie i t'4 i 4 i a q prey + 1 4 | 5 |. Carcinoma NLoirndzbmaacnhn AmiaAnstboesseteotsicsanBcerrsonpcuhlomogneaniirecs lung cancerCompens ate A. Krebsforsch inPansebuesmtoocsioasbestosni ioofstihse alsubnesgtosis the 44 Bronchogenic Stoll R. and Angrist A. Asbestosis H. im f SMrIiTnHg of a case carcinoma a Asbestos Int Med 41. and Winter W. unde th Lungenkrebach path Anat 307 387 194t ( M. and Soncz A. Lungenkrebs durch 249 19482 re 2.= .. Asbeststaub Tierversuch Zuschr f 2 50 L.L. and 19412 168 51 43. a " . Mad 3 1949 St ... Rousseau Giroux 51 M. and Owen K. Carcinoma and Smom A. : :. Report Brit J Cancer 52 . * Laval m^'d6 1941 R Bass Holles Tote and ANGENT A. carci+ associated with bronchogenic 88 831 19512 * J. lung Environmental noma with pulmonary asbestosisAm cancer 18:53 Path efrte, .1942 rr 18:53 Hoepen W. C. : wat of lunge 5 1951 A. | Arch Wedlar EnIgnldaunsdt Lungenakbsrterbascted Bureau Union 1943 carDceiuntosmcahe London 45. Wedlar ' Registrar Asbestos 20 49 Statistical Review 1950 South Africa und an H. W. Medi 1951 >. Lo deeapem Toon. mak Wehruchr 69 575 54, of . 7 Bull Hyg 19 363 1944 in i and Wales . for the Year 1948. 46+ . Homburger F. Coincidence of primary .M. Stationery Office.. 55. 4 7 + of lungs and pulmonary asbestosis Report Miners Phthisis Medical Analysis of '. 1" Pretoria 1936 - as 2. literature and report of three cases Am J. 19 797 1943 Path O. of tee of vet Klotz Association silicosis and carcinoma 56 LYNCH and of lung Am J. eeS 47. M K. . W. i. 2 rs Cancer 38 1939 ~ and Cannon M. Asbestosis 57. LINDSKOG oa VT {1 7 Analysis of and Bloomea Bronchogenic forty necropsied Chest Dir 4 874 1948 cases 14 G. F.F. W. D. carcinoma Cancer 1 234 1948 A. - . Wurm Pathology of Tumors St. Louis Health Lindezoo Pub 1948 cancer Supp 209 1948 a 59. .- C. Mosby Co. 49. CURETON Squamous cell carcinoma occur- G. Bronchogenic An Surg 49. J. R_ 3. 124 667 1946 . = fantsemesisep omen mong ere) Le Oe ty. adie) BREAPS