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FILE NAME: Kaiser Gypsum (KG) DATE: 1967 Apr DOC#: KG096 DOCUMENT DESCRIPTION: Journal Article - Mesothelioma and Asbestos Exposure *Yv- . o *. *w- 'H ; \\ 559 Mesothelioma and Asbestos Exposure Jan Lichen, AID, and Harry Pistawka, AID, Harrisburg, Pa W i t h i n the past five years several arti cles have called attention to the association between mesotheliomas of the pleura and i,\.-ritoneum with asbestos exposure,1-* Wagner et ai- studied 33 cases of meso thelioma. All but one had probable exposure t o t h e blue asbestos. I^ ^ s to s has become a ubiquitous materi al in our civilization, Oauna et al5 reported that asbestos bodies were, found in the. lung smears of 11% of 100 consecutive autopsies at the Presbyterian University Hospital in Pittsburgh. Similar findings were reported !.v Thompson'7 in 500 consecutive lung 'moors from Capetown, South Africa, and . iaini. Via. Asbestos bodies were found in '/% of the men and 20% of the women. AsInutvs has been conclusively associated with increased incidence of lung cancer and other maim3ndess' and an increasing number of studies associate its presence with malig nant mesothelioma of the pleura and perito neum. Pathology Mesotheliomas of the pleura and peritoteum are rare neoplasms. Controversy in'olves histological typos, nomenclature, ori:n, and their very existence. Recently, mesotheliomas as an entity have become enerally accepted. Their morphologic varibilitv makes classification difficult and difrrentiation from other malignancies is often problem. Submitted for publication Ju n e 6, J966; accepted ipt 13. ----- From the Division of Occupational Health, De triment ot Health, Harrisburg, Pa. Dead before the N inlb International Cancer Con- ess, Tokyo, October 1966. hep rin i reriuesis to PO Box 90, ITnr. Xburg, P* 120 (Dr. l.ieben). Sacconi and Coblenz1give the incidence of pleural mesotheliomas as 1.1 cases per 1,000 autopsies. Campbell reported four cases of pleural mesotheliomas iti 3,533 con secutive autopsies.11 Mesothelioma occurs primarily in adults and is twice as common in males as in fe males.10-12 Pleural mesotheliomas occur equally on the right and loft though Weissman feels that pleural mesothelioma occurs on the right more frequently than on the left side.12 The criteria for diagnosis of pleural meso thelioma are presence of a firm pleural mass encasing the lung, histological structure compatible with mesothelioma, and absence of a demonstrable primary malignant neo plasm elsewhere. The histologic architecture may be mesenchymal, "epithelial," or mixed. A complete autopsy is necessary for une quivocal diagnosis, but for the purpose of this study, criteria were made less rigid in that unautopsied cases were accepted if a definite diagnosis of pleural mesothelioma had been made by biopsy, and malignancy elsewhere had been excluded clinically; chest x-ray examination, bronchoscopy, and cytologic studies of sputum or bronchial washing assisted in excluding the presence of bronchial carcinoma. Primary tumors of the peritoneum are among the rarest of tumors. Generally called mesotheliomas, they form large spreading masses over the peritoneum and histologi cally appear the same as pleural mesothe liomas. As with pleural mesotheliomas, ex clusion of a primary tumor is necessary. This study is an attempt to learn the ex tent of the relationship of asbestos exposure with mesothelioma diagnosed in southeast ern Pennsylvania. A rch nm'ron H ealth-- Voi 14, A p ril 1067 1967. Lieben {/Cdi^rC^r- t l O: v '---Vt- . O V.* ' *v: 550 M ESO TH ELIO M A--LJEBEN & PI S T AW K A Method One hundred and sixty-two hospitals servin'; a population of 6Vi million people were re quested to report all mesotheliomas diagnosed between 1958 and 1963. Replies were received from 152 hospitals. Hospital records of 62 re ported cases were reviewed and only mesothe liomas confirmed by operation, biopsy, or au topsy were included in the study. Forty-two cases satisfied our critera. There were 34 meso theliomas of the pleura and eight of the perito neum. Among the pleural mesotheliomas there was a definite preponderance for occurrence on the right side of the chest. Of 34 pleural meso theliomas only seven occurred on the left side, 25 on the right side, and two were not stated. Sections of as many of the tumors and lungs as possible were borrowed and reviewed by a single consultant pathologist familiar with mes otheliomas. In the 15 instances in which lung sections were available, they were examined for the presence of asbestos bodies. All slides were reviewed without the benefit of the complete history and autopsy protocol available to the pathologists who made the original diagnosis. Results of the 33 cases reviewed (Table) by our pathologist agreed with those of the outside pathologists in 17 cases; he rejected seven cases as unacceptable histologically, had serious doubts in nine cases (of these one slide was read as metastasis and one slide as anaplastic malignancy). Of the 15 cases in which lung tis sue was available, asbestos bodies were iden tified in seven. The discrepancies between the original pathological diagnosis and that of our patholo gist are reported to illustrate the difficulties and disagreements which are so frequent in the diagnosis of this tumor. For inclusion in this study the diagnoses of the originally reporting pathologists have been accepted and cases re ported by them were investigated. Efforts were made to obtain a complete em ployment and residence history for each pa tient. Inquiry was also made into the employ ment history of family contacts. Data were obtained from the individual if alive, from fam ily members, or employers. Of the 42 patients, ter, had definite occupa tional exposure to asbestos during lifetime, three were family contacts of asbestos workers, eight either lived in the immediate neighbor hood of asbestos plants or had been employed next to an asbestos plant. Ten patients had a questionable asbestos exposure and, in the oth er 11 patients, either no asbestos exposure could be elicited on direct questioning or no survivor could be located. Tahle 1.--Readings ol Consultant Pathologist Case No. Meso> heliom a A sbestos B o d ie s 10 3 -0 4 0 5 -0 6 0 9 -0 1 0 -0 2 -N 3 -N 4 -N 6 -N 1 -F 2 F 3 F 1 -Q 2 -Q 4 -Q 5 -Q 6 -Q 7-Q S -Q 9 -0 1 0 -Q 1 -X 2 -X 3 -X 4 X 5 -X 6 X 7 X 8 -X 9 -X 10 X Yes N ot a cce pta ble P ro b a b ly not Yes P ro b a b ly not P ro b a b ly not Yes Yes P rob a bly not N ot a ccepta ble Yes Yes Yes Yes P ro b a b ly not Yes Yes P ro b a b ly yes N ot a ccepta ble Yes Yes P rob a b ly not M ay be M etast Yes Yes N ot a cce pta ble N ot a ccepta ble A n a p la s tic m a lig n a n cy P rob a bly not N o e p ith e lia l cells M e so th e lio m a m u st be P ro b a b ly not Yes Yes p roven N o lu n g tissu Yes N o f ll . ig t! SLU Yes Yes N o lu n g tissu Yes N o lu n g I i $si.< N o 'u n g t*$su N o lu n g tissu . N o lu n g tissu . N o lu n g tissu . N o lu n g tissu N o lu n ^ tissu N o lu n g tis iu Yes No No No N o lu n g tissu No No No Yes N o lu n g tissu* N o lu n g tissu* N o lu n g tir.su No No N o lu n g tiis '. N o lu n g tissu* N o lu n g 1*7'v ." Yes Exposure of Ten Mesothelioma Patients Wb Worked With Asbestos.--Patient 1-0 worked 3 years in the textile department ot a largo a: bestos plant. Patients 2-0, 3-0, and 4-0 worked more Finn 20 years in asbestos insulation plants and pa tient 5-0 worked in ar. insulation plant for onb one year. Patient 6-0 worked 15 years in a plant rnanu facturing acoustic tile and linoleum, Patient 7-0 was a boiler maker in a railroa; yard where, for 25 years, he worked on insole tion of steam engines. Patient 8-0 built bakery, ovens in which larg< amounts of asbestos insulation were used. Patient 9-0 was a certified accountant wlu worked more than 30 yeais in the office of ai asbestos textile plant. Patient 10-0 was a plasterer who came ir contact with a large amount'of asbestos in hi woi k. Of these ten men, patients 1-0, ci-O, and 10-i had mesotheliomas of the peritoneum; the oil, cr seven men had pleural mesotheliomas. Neighborhood Cases.--Patient I N' was a 55 year-old woman who never had anv ociupa Arch Environ Health--Vo! 14. April 7.967 `^._tjiiifcau*Sii.vj5i .c`h \ a u MHSOTHFJJOAlA--LIEBEN & PIW AW A'A 561 iinu-i! asbestos exposure. H er work was always^ Patients 1-F and 3-1' bad peritoneal and pa fLLretarial; she was bom and lived until the age tient 2-F pleural mesotheliomas. of o, m flic immediate neighborhood of u as- Mesothelioma Patients With Questionable I'.-sios textile and friction material plant where t Asbestos Exposure.---A study of these ten men patient 1-0 had worked (or 35 years. From the elicited either a relatively minor or question f age of IS she lived for 30 y ears across the street able exposure to asbestos. from the plant where patient 6-0 had worked Patient 1-Q was a welder for 35 years. Ac for 15 years. cording to a common reference,13 eight out of ii . Patient 2-N, a clergyman from 1935 until his 12 welding electrodes contain asbestos, which is death in 1961. never had any occupational as used as a filler. bestos exposure. Prior to becoming a minister Patient 2-Q was a self-employed Swiss-born he lived for 19 years witliin one half of a mile Swiss ebecsemaker. A thorough study of the of the insulrrion plant where patients 3-0, 4-0, processes of Swiss cheese manufacture revealed and 5-0 had worked as insulation m anufactur no use of asbestos. During the study of the ing workers. manufacturing process a 500-gal boiler was no Patient 3-N never had any occupational as ticed. This boiler was covered with a friable as bestos exposure except that, 20 years prior to bestos insulation which flaked off on contact. his death, he had woiked for one year across Patient 3-Q, a 14-year-old boy v-itb mesothe (he street from the insulation plant mentioned lioma, had no occupational contact with asbes in the history ot patient 2-N. tos nor did any of his family. On questioning, P aten t 4-N worked for 26 years across the the boy's father told the authors that his boy the insulation plant mentioned in had lived with him and had helped him while oniflBIcm with patients 2-N and 3-N. lie had replaced most of the plaster hoard dur Patients o-N, a nurse, and 6-N, a m eat dis- ing extensive remodeling of his house. Plaster ributor, had no occupational exposure nor hoard contains a high percentage of asbestos. .roily contac t with asbestos. They both lived Patient 4-Q is employed in industrial sales lithin three fourths of a mile of two asbestos and never had any occupational asbestos expo >lauis in a town with the greatest incidence of sure. Extensive questioning revealed that, on nesothchomaa in this study. two occasions sovoial years before, he applied v'dtii-nts 7-N and S-N were both foremen in a asbestos insulation to boilers in his homo, mix Image battery plant. A careful check of the ing asbestos cement himself. His total exposure )];-.nt and their employment records revealed during these applications was only a matter of iO asbestos exposure, past nor present. The hours. ilant is located less than l 1/ ' miles from an as- Patient. 5-Q was a brewery worker for 20 edos textile plant. The exposure of these two ns'-s is questionable. years. The brewery was no longer in business Patients 1-N and 4-N had peritoneal and pa- when the rase was investigated. Reviewing . .is 2-N, 3-N. 5-N, S-N, 7-N, and 8-N had the literature of beer production the following lout a! m esotheliom as. paragraph was discovered: Mesothelioma Patients W ith Family Con- "When ready for packaging the beer is fil ictj^^^nsed to Asbestos.--Patient 1-F, a 3- tered through pulp filters consisting essentially eat^^ P child, was the daughter of a ccram icl of cotton fibers and asbestos. After each filtra lgineer who worked in an insulation plant*' tion this `F1LTERMASS' is removed, mangled, at utilizes 400 tons of Canadian chrysotile and washed in clear, warm water, then bleach nd 1,500 tons of South African amesite annu- ed and sterilized at 160 to 180 F with chlorine. dy. -v The washed pulp then goes directly to a pad Patient 2-F, a 40-year-old nurse, never had\ forming machine where it is compressed at 89 j.v occupational asbestos exposure, but her fa- \ to 90 pounds per square inch to form new filter ier had worked for 35 years in the insulation ] pads.11" ant where patients 3-0, 4-0, and 5-0 had I Asbestos-containing pipe insulation is used in orked and which was also credited with three breweries. ighborhood cases. The-nurse's brother also Patients 6-Q,- 7-Q, and 8-Q were all steel id worked in this plant for one year. workers. Patient 6-Q was a crane operator; 7-Q Patient 3-F, a 67-year-old woman, never h a d \ a forger; and 8-Q a foreman and supervisor. In iv asbestos exposure nor had she lived near all cases the companies did not recall any as 1 asbestos plant. She had two sons who bestos exposure for these men. Pipe insulation >rked as insulators in o shipyard for six containing asbestos is extensively utilized by ars. These sons lived at homo until 15 years steel companies. ior to their mother's death. / Patient 9-Q was a spinner in a silk company Arch Em-iron Health-- Vat 14, April 19G7 562 M E S O T H E L I O M A --.L I E U E S & P I S T A WK A from 1925 to 193S, and later in a plastic fabri cation plant which utilized fiber glass; he also had been a welder for 25 years. He thinks he has used asbestos but could not recall when and where. Patient 10-Q, a 63-year-old man, was a core-maker all his life. He worked-in two foun dries in one of which asbestos cement is used in small quantities but, according to the plant manager, the core-maker did not have any coa-_ tact.with this material. The son stated that his father had used asbestos pipe insulation for pipes in the basement of their home several years prior to the onset of his illness and that he had done some sawing of this pipe insula tion material. All cases in this group had pleural mesothe liomas. Mesothelioma Patients Without Asbestos Exposure.--In the other 11 patients (1-X to 11X) no occupational, familial or neighborhood asbestos exposure evidence could be elicited. Ten of these patients had mesothelioma of the pleura and one peritoneal mesothelioma. Comment This study presents a good deal of uroim stantlal evidence and many unanswere questions. Asbestos is a ubiquitous material usemuch more frequently than is generally tse ized. Some uses, such as in the brewer} were not previously known to the writer T?here_ sire undoubtedly m any others. If we assume that asbestos may be th causative, or trigger agent for malignan mesothelioma in some of the cases dosenbof above, we must admit that the minima ,,dose-effect relationship and duration of ; latent period are unknown. The occupation al exposure of the; insulation workers or as bestos textile workers were certainly mam thousand times higher than those of tin neighborhood cases or family contacts. Simi lar findings have recently been reported from England.1 The attack rate for mesotheliomas k ex Aiclt Environ Health-- Vol Id, April 1907 Mn SOT i {EAOMA-- TJEf EN & PISTAWKA 503 tremely low. N ot all mesotheliomas were re tients no history of asbestos exposure could ported to us by the hospitals, but, even if wc bo obtained. double the incidence, only a minute fraction of the exposed population was affected. References There are precedents for this with beryllium 1. Ntwhmi.se, MX., and Thompson. H.: Mesothe Ii disease which acts in a somewhat similar lioma ot (he Pleura and Peritoneum Following Ex it pattern; occupational diseases, familial con posure to Asbestos in (ho London Area, Brit J In- II tacts. neighborhood cases plus a very low ditslr Med 22:261-269, 1965. attack rate, and a long latent period be 2. Hourihane, P.O.: The Pathology of Mesothe- i tween exposure and onset of disease. liomata and an Analysis of Their Association With Asbestos Exposure, Thorax 19:i.6S-277, 1964. ii Another question which arises is why 3. Sclikoff. I.J.; Churgh. J.; and Hammond, C.`. pleural mesotheliomas are so much more Exposure to Asbestos and Mesothelioma, Neu* Eng frequent, than peritoneal mesotheliomas. J M ed 272:560-563 (March) 1965. The most striking finding of this study was that of the 42 mesotheliomas which cam ^ ro m a geographical area of approxi- 30,000 sq mi, six were clustered in 4. Wagner, J.C.; Sleggs, C-A ; and Marchand, P.: Diffuse Pleural Mesothelioma and Aslrestos Expo sure in N.W. Cape Province, Brit J Induslr M ed J7;200-27J, I960. 5. Canna, D,;-Totten, R.; and Gross, P.: Asbestos ancraround an insulation plant (Figure). These included two insulation manufactur ing workers (Cases 2-0 and 3-0), three neighborhood cases (Cases 2-N, 3-N, and 4- Bodies in Human Lungs a t Autopsies. JA M A 192:371-373 (M ay 3) 1963. 6. Thompson, J.G.; Kaschuln, R.O ; and MacDon ald, R.R.: Asbestos as a Modem Urban Hazard, S A /r M ed J 37:77-31 (.Jan) 1963. N) and one family contact (Case 2-F)--the 7. Thompson, ,T.G.: Asbestos and Urban Dweller, daughter of an insulation worker. read before the Conference on Biological Effects of Asbestos, New York, Oct J9, 1964. Summary 8. Doll, 13.: Mentality From Lung Cancer in As bestos Workers, n t J Induslr M ed 12:81, 1955. Forty-two cases of mesotheliomas report 9. Lieben, J.: Asbestos and Malignancy, Arch. E n ed from 352 hospitals over a five-year peri viron Health 13:619-621 (Ncv) 1966. od, were studied with regard to exposure to asbestos. Survivors or employers, or both, were questioned regarding lire possibility of 10. Sacconi, A., and Coblenz, A.: Endothelioma of the Pleura, W ith Report of Two Cases, Am er J Clin Tath 13:186-207, 1913. 11. Campbell, W.: Pleural Mesothelioma, A.ncr J asbestos exposure. Ten patients actually Path 26:473-487, 1950. worked in asbestos plants; eight lived or 12. Weissman, H.t Primary Endothlia of the worked Cose to an asbestos industry; three Pleura, Die Chest 12:562-570. 1946. p a U fl^ were family members of asbestos^ ert1i3e.s LanydmSanel,ecTt,ion(edof):MMetaetlas,lsedH8a,nAdbmoeorki:caJn- SPorcoipe wcS^Pb. In ten patients a history of as ty of Metals, 1961, p 5. sumed exposure to asbestos was obtained 14. Modern Chemical Processes, New York: Rein after prolonged questioning. In 11 other pa- hold Publishing Co., 1952, vol 2, p 167. DISCOVERY OF QUININE Many of the drug sources known in ancient times were apparently discovered by acci dent. For example, according to an bid South American Indian legend, the curative power of cinchona bark (containing quinine) for malaria was discovered by a sick, fe verish Indian lost in the jungle. He quenched his thirst by drinking from a pool of water. From the bitter taste of the water, he recognized that it was tainted with the poison from the quina-quina tree. Although he shared this fictitious belief, he drank deeply so as vo bring about a quick death. To his great surprise, ho recovered completely. When he returned to his village, he told the store of his cure and thereafter cinchona hark was used as a medicine for the fever prevalent in that region. The Incas later taught tire Spanish conquistadors that malaria could be cured with cinchona extract..-- Rossman, R.E.: The History and Significance of Serendipity in Medical Discovery, Trans Coll Physicians Phila 33:101-120 (Oct) 1965. A rch Environ Health--Vol 14, April 1967