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416 s4tla4 Occupational and &nvironmeniCtaatl O~Ubi&i *a&a6 Edited by David M. Sfain, MD Asbestosis and Pulmonary Carcinoma run X. DOTtA. MD. AND JOHN D. CAANgT. MD. CASTXO VALLZV. CALIF I Although asbestosis, a disabling industrial Report of Case disease, has been recognized for only some 30 A10404, Sam Frmeim VrUramt Aimmirtrtiieu years, the mechanism- by which the dust particles produce tissue alterations in this condition is better understood than for any of the other pneumoconioses. As^yjgs^j^ hvdratedmagnesiunyjljjj^jjvgke^iujajtensuc^MjfS^Sttt.A^b^JtfBafihL^nd Hotbtol.--The pabeat was a 70-year-old white mu who complained of the insidious progressive duraaness of the left upper extremity, first noted three weeks before admission The patient had bees di abetic for at least five years and was bcinf treated with insulin zinc snsprminn (Lease Iletia) (41 units per day). The only recorded occupational his bronauolesia3vealL-aasLBkut^&^J--i* of 10% to IS^o^ereon^rith asbestosis the changes progress to malignant neoplasms.1 tory is that he had been a pipe fitter; no details were given. He was an alert chronically ill man in no acute distress. Blood pressure was 1S5 systolic and SO diastolic, pulse, 82 per minute and irregular. Poe- Asbestosis usually affects persons from whom a history of industrial exposure to asbestos dusts is readily obtained, but in* stances of the disease occur with increasing frequency in which the circumstances of ex teroanterior diameter of the chat was iacrcaKd. there was diffuse hyperreaonance, and tattered inspiratory rales were bard over the bases. A gride II systolic apial murmur was noted and auricular fibrillation was present. The liver edge was palpable 2 cm below the ooetal margin. Strength was dimin posure are not known to the physicians or even to the patient. ished in the left upper extremity and flattening oi the left nasolabial fold was noted. Chest films (Fig 1 and 2) showed moderate pulmonary emphysema Submitted for publication Oct S, 1964. with some increase, in branchovascular markings. Accepted for publication Oct 28, 1964. Hematologic findings: Hgb, 174 gm/100 ml, \VBC Editorial Common by David M. Spain, MD, and 11,000/ cu mm, and normal differential. Blood ehen- Case Presentation by Frank R. Dutra. MD, Pathol istry analytical results: BUN, 16 mg and FBS SO ogist and Director oi Laboratoria. Eden Hospital, ing/100 ml. Urinalysis: 1+ albumin, l to 6 white astro Valley. Associate Clinical Professor of ,-ttood cells per high-power field. Pathology, University of California, San Francisco, ( He seemed to be improving in the hospital until and John D. Omey. MD. Pathologist, Edm Ho,- >1*11*hospital day whabesuddenly becLe weak p.tal, Castro Valley. Onieal Instructor in Pathology. University of aiifotnia Medial School, San Francisco. Reprint requests to Brookdale Hospital Center. Linden Blvd and Rodcaway Pkwy, Brooklyn, NY 11212 (Dr. Spain). sndNefnieomatose. He did not respond to intravenous glucose and died approximately 20 later. Autopsy: Doth had been "tH by thrombosis oi intracranial and coronary arteries with scute cerebral and myoardial infarction. The lungs Arch Environ Health--Vol 10, March, 1905 weighed 1.00 faces were sn were not pre the upper Id spherical mv was covered . Microscopi at well as th clusters of p asbesraeii U th: CO iai o .raj 1 n u| to- : ->J tec s CO pit iatnmtilar nuclei were : dvdy gigant chromatin ar The cytopla granular anc (Fig 3). P The cr; wedged if. bronchiole, ing-elonga: shortening respiratory the walls o irritation : first is r progresses throughou ment of ai' disease. L feres with stasis bec< posing fib: toward d tends to p: attendant the paric:.- The"g: shadows . may in p. DOW 05985 -nui.tm e nun ' ihrce ,-ti dicaifd (-<5 Iiii were iCUItf ul SO ?o. t-ircii ;radc cjlnr -ahlc ct iFis CTU VBC iien- - 219 \ hue :nlii veak i:ra.uio* cute Ulg* ASBESTOSIS & CARCINOMA--DUTRA Sr CARNEY 417 v:#iicrt l.CilO pm topcilicr and their pleural sur,<i\ were noutii, eny, and cmpliysminUius. Blda were not |irc<eut. In Uw lateral inpcrior region ot tie upper k4* ot tlie lelt lung waa a subpleural .lierieal ma.* measuring lj cm in diameter. Thil covered l>y umbilieated pleural turface Microscopically, tlie pulmonary alveolar spaces well as the bronchial himina contained scattered clusters oi pipnent-ladot macrophages and a few ubestosis bodies. Emphysema was manifest by uretched, thinned, and broken alveolar septa crat ing smalt rustic spaces. There was perivascular, -mbronchinl, and nodular interstitial fibroaia. The i.hrotic areas contained a moderate amount of t.ulimeutle p)*mnt and numerous typiml aabastaala Lodia. Microscopically, the mass in the upper lobe of the left lung was a tumor which originated in an ectatic bronchus. It extended in a haphaard and stellate i*>!iion into tlie adjacent pulmonary parwsehyma. T.be architecture was comprised of immature and .1 typical squamous ceils among which keratin and intracellular bridges were not demonstrable. The nuclei were large and vesicular; some were of relalively gigantic proportions with irregularly dumped chromatin and distinct, wrinkled midear membranes. The cytoplasm ranged from colorless to finely panular and amphophilic Typial ssbestoais bodies were numerous both in and about the tumor maa* (Fig 3). Pathology of Asbestosis The, cryjailing asbestos fibers become wedged in the lumens oHKe respiratory bronchioles, and with the insniratnrv narrow. fibrosis and in pun to the pleural thickening; in advanced cases plcunil-pcrictrdial ad hesions and fibrosis may become so pronounced that a characteristic "porcupineheart shadow" results.* Concomitant with the development of fibrosis, distortion and epujufiflQitgus en largement of many alveoli become prominent. Bronchitis and bronchiolitis become chronic anj^jj^tg^Jgd^tobrgjjjygJjms. The de pendent portions of the lungs are usually more profoundly affected then the upper halves. This serves as a trees diagnostic point in diflerentiataur asbestosis from the mhre widespread and nodular alterations of scepsis. Asbestosis bodies are essential to the microscopic diagnosis of the condition. Some of these structures may lie free in alveoli, but most of them are embedded in fibrous tissues of the walls of alveoli or bronchioles. A few may be surrounded by giant cells of foreign body type. These bodies are comprised oi -SaSaSTTv^teiBHium ends are usually knobbed, while the central regions may be notched. The color is yellow to pinkish red in the usual histologic prepara tions. A few are as small as lp in length but the majority are 10>i to 60p long. -shortening p* MO. 'qnimory nrlr t1** ck~" * This mechanical irritatio^^Auju^^^^^saguaetihaaiMfc ^rs^i^jjjj^rogMioIar. As the disease nrnrrrettre. irry^lfr ililTo. fihrni rvm.rs i4(44e- Ultimately, the reactive tissue intertercs with Ivmnhatiedrainageoi tnelungand stasis becomes an additional factor predis posing fibroplasia. Increasing flow_pt lymph toward the subpleuraMymnhatir network tends to produce irritation of the pleura with attendant pleural thlckmia^afllLfidhcaioPd to the narietai picura. The "ground glass" appearance of the lung shadows in films of patients with asbestosis may in pan be due to diffuse parenchymal Clinical Findings Dyspnea is usually the first sign of disease, and it seldom occurs with an industrial ex posure to asbestos dusts of less than five years. Loss of weight is often marked. Dry cough is common, and more than hali of the patients expectorate small amounts of bloodstreaked sputum sometime during their ill ness. Asbestosis bodies may be' found in the sputum of most patients by microscopic ex amination. The chest becomes emphysematous, and fine cracklin^rales are present over the lower lobes. Cyano&and^dubbingof the naii ire frequently present-ta patients with moderate ly advanced disease, and cor pulmonale is often a late complication. Asbestosis does not predispose to tuberculosis, differing in this respect from silicosis.* Arch Environ Health--Vol 10, March, 1965 iLL 11001S DOW 05986 til ASBEETOStS & CARCINOMA--DUTRA & CARNEY n r ! r v Pt-: \ . T V .> i y*r y*- T Fig 1 (left) and 2 (right).--Posteroanterior and lateral lias of chat at tine of admission. Evidences of enphysema with regions of increasing denity of branehovascular markings. There were no recognizable signs of fibrosis, and nodularity is absent. Roentgenologic Findings Attempts to correlate the roentgenographic changes with the physical findings oml degree of disability is hazardous in any given case of any of the dust diseases. This axiom is especially true in asbestosis.4 Pulmonary disability may occur in patients who have the most minimal alterations of the chest films, while others with films reflecting significant pulmonary changes may have little or no rec- STOOI n i 5 uiX". . 4* . Fig JA.--Squamous cell carcinoma invading tiasua of lung. Distorted alveoli containing phago cytes are in (he upper right comer, and several asbestosis bodies arc near the center of the field. Hematoxylin and eosin; X 192. - - * - r- - " h 7*:* * '*X ! ?/*' i a `-'I.:'-r'-.- i > .* i . ; . V ; -*! ^ iis : J Is * / * Arch Etmiron Hcaltlt--Vol 10. March, 1961 DOW 05987 ASiUTOSU 6 CACCIHOUA--DUTKA * CAAHCl STOOI1776 Arch Cnvirtm HttWt DOU 05988 . 1 i; -i ASBESTOSIS & CARCINOMA--DUTRA & CARNEY 421 double alteration or lung function. Gen* cr.tilv. the first rocntgenographic sign of .vbciio*ij is diffuse haziness over the lower third of the lung fields. Io more advanced cases tliis has progressed to a "ground glass" .ipi'camncc which obscures the broncho* vascular markings. Later, the upper portions of the lungs also become fibretic, but the up* per areas always remain more radiolucent than the lower. Asbestosia and Carcinoma of the Lung endocervidlis can lead to squamous carci noma of the uterine cervix through the same series of anatomical progression. Mcch|nic*l irnationo|j2ifcaibeatofcfcbeiwy<hoWyJeads ths hmnrhj 4Q^B^l2Mjtfuafihofaai*_niwaagHJiLaaUie same way. Sumnsiy Asbestosis is a chronic progressive pul monary disease which results from irritation of the lungs by crystalline asbestos fibers. In recent years it has become dear that '.here is a more than fortuitous relationship between asbestosis*and bronchogenic card* oorru. This belief is based on the following observations: (1) Appraximatdy 13.8% of because the occupational -f""* to dast containing asbestos fibers has not been eiidted, and because the chest films may not be diagnostic even in the presents of dis ;*tients with ashestosis develop squamous cell abling abnormality. carcinoma of '.he lung,1 an inddence con* In asbestosis, pulmonary and subpleural vderably greater than in persons the same .-.re without other lung diseases or who have Jier pneumoconioses.5 (2) The cancer is '.malty in one of the lower lobes where the v.vunber of asbestos fibers is greatest This cantrasts with the data from cases of bron chogenic carcinoma not associated with fibrosis distort the lungs sad lead to respira tory insufficiency. Squamous metaplasia of the bronchial epi thelium is induced by the irritating fibers, and in some cases there is progression to squamous edi carcinoma of the lung. Pleural isbestosis, in which the greater proportion mesothelioma is also reported, particularly in are in the upper lobes.* Squamous metaplasia cases of asbestosis in South Africa. II 'Y- uie^the bronchi and" bronchioles is often observed in asbestosis. REFERENCES and the metaplastic cells frequently are atypical with appcaraaces_sugg5tin^jritBt* tion toward rarrinnma It has also been suggested that asbestosis may predispose to mesothelioma of the -leura. Thirty-three cases of this tumor were observed over a period of four years among couth African workers in asbestos mining operations, and one case of asbestosis com* 1 Telischi, M., and Rubenstone A. I.: Pulmo nary Asbestosis, Arch Path 72 -234-243, 1961. 2. Gardner. L. U.: Pneumoconioses, Med din N Amer 1239-1260 (July) 1942. 3. Asbestosis: Report of The Section an Nature and Prevalence Committee on Occupational Diseases of the Chest, American College of Qiat Physi cians, Dis Clicst 45:107-111,1964. 4. Wright, C. W.: Functional Abnormalities of Industrial Pulmonary Fibrosis, AKA Arch r.iicated by pleural mesothelioma has been Health 11:196-203, 1955. iescribed in this country.7 At the proent time, the mechanism by vitich asbestosis predisposes to neoplasm of :he lung or pleura is unlsown. Squamous metaplasia of bronchial columnar epithelial ciis, predisposing to carcinoma, is known to xcur as a result of chronic inflammation 'rom the smoking of cigarettes as chronic 5. Gloyne, S. R-: Pneumoconiosis: Histologic Survey of Necropsy. Material in 1,205- Cases, Lancet 1:810414,1M1. A Isselbacher, ICJk Kl^oa, K.; and Hardy. H. L.: Asbestosis and Bronchogenic Carcinoma. Amer J Med 15:721-732 1953. 7. Case Records of Massachusetts General Hos pital, Benjamin Cattleman; ed. Case 62-1963. New Eng J Med 269:747-754. 1962 Arch Environ Health--Vol 10, March, 1965 tr? t >T LLLII001S DOW 05989 * ** - m ASBESTOSIS (r CARCINOMA--DUTRA 6r CARNEY Editorial Comment This case presentation excellently illustrates many aspects of the relationship of asbestosis to pulmonary carcinoma. An especially pertinent statement is made in reference to clinical history of previous exposure to asbestos, and well worth re peating "but instances of the occur with increasing frequency in which the circumstances of exposure are not known to die physicians or even the patients." Perhaps a positive history of exposure would be obtained more often if the ques tioner, who is trying to obtain a previous history of exposure to asbestos, was more fully aware of the various industrial processes or products in which a worker might be exposed to asbestos fibers. Asbestos fibers consist of silicate minerals often re ferred to as amphiboles. Ten percent of the mined rock consists of t^ese mineral fibers which contain complex silicates. The best known sourooi located in Canada (about three fourths of the world supply), Rhodesia, SoaA &Hka, and the USSR. The complex mineral fibers are removed from tho^owder tMUim the long fibers are separated from the short ones. It U during these processes that the most dangerous exposure occurs. The long fibers are used for the manufacture of asbestos doth and gaskets, while the short ones are used for paper, heat resistant boards, filter pads, and brake blocks and linings, and are increasingly found in plastics. Each year new uses for these fibers are constantly being developed. In the currently reported case, the only occupational history is that the individual had been a pipe fitter. It is conceivable that part of his work was concerned with the use of asbestos-containing coverings for these pipes. This might have been the possible source of exposure in that it may have been necessary for him to saw through this asbestos material and thus produce a certain amount of asbestosis-containing dust In this case, the carcinoma was of the squamous type. There seem to be a difference of opinion as to the most prevalent histologic type of carcinoma that is found in association with asbestosis. In this report, it is stated that squamous cell carcinoma is the usual form, whereas Spencer1 states that adenocarcinoma is the most frequent form. It has become increasingly apparent that pulmonary cancers arising in scars are more frequent than was formerly believed. These are generally adenocarcinomas. Whether or not some substance or substances, as for instance the iron in the asbestosis body, is spedfically carcinogenic or whether carcinoma arises because of the nonspedfic alterations produced by the asbestos remains to be de termined. With the squamous cell carcinoma, it is conceivable that the squamous metaplasia, the bronchiectasis, and the fibrosis caused by the asbestos fibers might impair the lung's ability to effectively rid itsdf of other carcinogens, and by this process enhance the development of carcinoma. In particular, it would be important to note what proportion of individuals with asbestosis and pulmonary carcinoma were cigarette smokers. At any rate, the inddence of pulmonary carcinoma in in dividuals with asbestosis in various reports has ranged from 13%-20%. Statistically, this is a highly significant relationship. Of more immediate interest are the cases of mesothelioma of the pleura that occur in individuals with asbestosis. Inxmost recent report3 from Liverpool, England, evidence of exposure to asbestos rwret^d in 14 of 16 consecutive cases of pleural mesothelioma. Asbestosis bodies were present in lung tissue in ten of these cases. In another study on two patients with mesothelioma, one individual had not been in contact with asbestos for 20 years and in the other case the exposure had been only intermittent and slight In all individuals with mesothelioma careful search should now be made for asbestosis bodies and fibers in the lung and tumor'tissue. It Arch Environ Health--Voi 10, March, J96S ' I IS SU: miss> turei perij peril # asso< a fic: to th the a gasti supp 1. 1 1 f o( PI CO --< o o CO / *%. -%*r - V DOU 05990 I * . . < * in t rc- :> ihe '.V.A." uosinre .i^ht .1 revra! i in : the -fng liOit i 01 -tnnt .J in the L-een of -iible \ this -- i '!i ; | ; , j ' I i be a is ell .e ::cer ; rally ;e the .rises c de vious .ijht thir rtant lor.'.a n ir.caliw that -c of :n oi .1 had ^ ,utc earch te. It ASBESTOStS & CARCINOMA--DUTRA * CARNEY OX is suggested that thick frozen sections be used bodies may easily be missed in thin sections.* Fibrosis of the pleura with adhesions to surrounding struc tures is oomxnoapUce in asbestosis. The asbestosis bodies produce alterations in the periphery of the lung whereby these bodies gain entrance to the pleural tissues via the peripheral lymphatics in the lung. Because of the occurrence of mesothelioma in asswnarion with asbestosis, it is likely dut substances in asbestos fibers are spe cifically carcinogenic. It is unlikely that other inhaled carcinogens would gain access to the pleura and produce carcinoma in tissue previously rendered less resistant by the asbestos. A case of asbestosis in which the individual ^ bth bronchogenic and gastric carcinomas and in which the latter tumor contained retractile granules leads supfwrt to this concept of the specific carcinogenicity of the asbestos fibers., R17ZUNCU 1. Spower, H.: Pathology of Lung, New York: The Msrmillan Co, 1962, ft 61*419. 2. Owm, W. G.: Diffuse Mesothelioma and Asbestos Exposure m UmereA Beit lied J 2:214, 1964. 2. Fowler, P. B. S.; Slower, J. S.; and Warner, F. C: Exposure to Asbestos sad Mesothelioma *i Pleura, Brit Med J 2:211,1964. Arch Environ Health--Vol 10. March. 1965 6 U I I001S LI 566^ BLWk PHOTOCOPY MOUIST TO* JOUtNAL AKTICll* BIT PLEASE LIST ONLY ONI ARTICLE MR SHUT PImm Km Oil *aat a* Ma m Rim RM I* liaf1 '* 1 Q THIS JOURNAL IS AT RMOCRT. PLEASE REORDER M_ jtm G CHECK HERE IP YOU RANT ARTICLE ORDERED FROM ANOTHER LIBRARY--ALLOW U WEEKS DELIVERY. 3------ 1' Fat imediata copy (NO FORM NECESSARY) OR* Mfcrial Mnctty la PRINTING |5fPT. ia teMaant ef SK SMs. Haw ID0A.M. ll:A.IL. UPP.M. C4S.M0N0AY FRIOAY. TO: 00 --1 o --J 00 DOW 0*992