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FILE NAME Household Contact HC DATE 1971 DOC HC030 DOCUMENT DESCRIPTION Journal Article - Two Cases of Malignant Mesothelioma after Exposure to Asbestos Case Reports NOTICE THIS MATERIAL MAY BE PROTECTED BY COPYRIGHT LAW TITLE 17 U.S. CODE Two Cases of Malignant Mesothelioma after Exposure to Asbestos PAUL CHAMPION SUMMARY Malignant mesothelioma occurred in 2 young men after exposure to asbestos In one patient pleural plaques were of diagnostic importance The patient was incidentally exposed to asbestos from the clothing of his father who was an asbestos worker In the other patient chrysotile asbestos was probably the carcinogen The importance of clinical and radiographic observation of those in personal contact with workers in the asbestos industry and the important part played by all types of asbestos dust in the production of malignancy are stressed Introduction Asbestos is one of the most valuable and versatile materials extracted from the earths surface There are six varieties of asbestos all silicates which differ physically and chem- ically from one another crocidolite amosite amthophylite tremolite actinolite and chrysotile Crocidolite and amosite contain more iron than do the other forms Chrysotile commonly known as white asbestos is largely magnesium silicate and forms 90 per cent of the world's output of the mineral It is found principally in Canada and the Received for publication June 29 1970 From the Department of Medicine University of British Columbia and Vancouver General Hospital Vancouver British Columbia Canada U.S.S.R. No other type of asbestos is mined in Canada Repeated exposure to asbestos dust leads to a number of diseases Asbestosis is char- acterized by pulmonary fibrosis causing a restrictive defect with reduced vital capacity and defective gas transfer often leading to death from respiratory failure An increased incidence of carcinoma of the bronchus is as- sociated with asbestosis 1 An increased incidence of primary malignant tumors of the pleura and peritoneum is also associated with exposure to asbestos dust 1 The level of asbestos exposure necessary to produce such changes is not yet known Although it is generally recognized that exposure to asbestos is dangerous the potential of chrysotile as a carcinogen is not yet clear A fairly common radiographic abnormality in per- sons exposed to asbestos is the presence of AMERICAN REVIEW OF RESPIRATORY DISEASE VOLUME 103 1971 821 822 PAUL CHAMPION / / / / / Fig 1. Posteroanterior radiograph of chest in Case 1 showing the presence of a large pleural effusion on the right pleural plaques The degree of exposure necessary for plaque formation is not clear Before any serious attempt was made to protect workers from inhalation of asbestos fibers deaths from respiratory failure were commonplace in the asbestos industry and were mainly related to the pulmonary fibrosis resulting from heavy exposure The use of protective masks and ventilation might have resulted in decreased exposure to the dust and less severe asbestosis so that deaths from respiratory failure have decreased leaving workers alive long enough for the development of malignant tumors later in life It is not possible to say whether this suggestion will be verified or whether there is a definite increase in the occurrence of such tumors Two cases of malignant mesothelioma of the pleura are described that illustrate tain unusual features of their causes cer- CASE REPORTS Case : A year white man presented in March 1970 with a week history of breathlessness and a month history of general weakness and malaise after an influenza illness There had been no other change in his health no cough hemoptysis fever or weight loss The patient was born in Glasgow Scotland where he had lived for the first 28 years of his life he came to Canada in 1968. His previous employment had included work as a cable maker and die caster He had never been occupational-ly exposed to asbestos dust Occasionally he had worked with aluminum sprays and arsenic com- pounds He had smoked 20 cigarettes per day for 16 years The patient's year father had severe asbestosis for which he received compensation his ill health had followed employment as a pipe lagger in Scotland The patient's year mother had emphysema His only brother and two sisters were alive and well The patient's father usually brought his overalls home from work and had often worn them home from work No special precautions had been taken to pro- tect the children from contact with these over- alls The mother occasionally washed the over- alls Physical examination revealed a well nourished man with no clubbing of the fingers or lymphadenopathy There were classic signs of right pleural effusion A chest film figure ) confirmed the presence of a large right pleural effusion on the left hemidiaphragm was a small MALIGNANT MESOTHELIOMA AFTER ASBESTOS EXPOSURE 823 rte Serie a ye e w ani Seal eal eases eat rer taba Tole psig, Fig 2. Enlarged view of a portion of figure 1 showing a small calcified pleural plaque on the left hemidiaphragm calcified pleural plaque 2 cm in length figure 2 No other abnormality was noted The hemo- globin was 15.7 g per 100 ml erythrocyte sedi- mentation rate . modified West 11 mm per hour leukocyte count 7,800 per mmwith 40 per cent lymphocytes 50 per cent neutrophils 2 per cent segmented forms and 8 per cent monocytes Serum proteins and hepatic function tests were normal Bronchoscopy revealed no ab- normality Aspirated pleural fluid was initially colored but after repeated thoracenteses it became slightly stained No fluid sam- ples demonstrated acid bacilli on microscopy -- -- culture Cytologic examination revealed clumps of malignant mesothelial cells Three pleural biopsies with an Abrams needle revealed normal pleura and connective tissue only At open pleural biopsy performed by Dr. Ian Munroe 2 liters of serosanguinous fluid were removed from the right side of the chest and it was seen that the visceral and parietal pleura were studded with pale nodules 8 mm to 2 cm in diameter Histologic examination of these nodules revealed malignant mesothelioma On the right side of the diaphragm was a calcified pleural plaque 8 cm in length At the time of the open picural biopsy kaolin powder was insufflated into the right pleural cavity to effect pleurodesis Because there was a small recurrence of pleural fluid after this procedure 20 mg of nitrogen mustard were instilled into the cavity The effusion did not recur subsequently The patient remained free from symptoms during the month follow pe- riod lost no weight and was not anemic After discharge from the hospital however slight clubbing of the fingers developed The patient's mother and sister were examined radiographically Emphysematous changes were seen in the mother's chest film In the sister's chest film a calcified pleural plaque was seen on the dome of the left diaphragm The sister had also had no contact with asbestos oth- er than from contact with her father Case 2 A year white Canadian man presented with a history of discomfort in the right chest of six wecks duration The pain was pleuritic and occasionally severe Dyspnea was not marked and was absent at the onset of ill ness There was cough with minimal mucoid sputum The patient had lost 5 pounds in weight The patient had been born in Fulford Que bec At the age of three years he moved to the town of Asbestos Quebec where he lived for the next 23 years Asbestos is a mining town and the patient's wife remembered it as being continually in a haze of dust from the asbestos mines and workshops After leaving school the patient worked for mine prospector in ten years as an asbestos Quebec and elsewhere in Canada For short periods he also worked in the open pit but never performed any deep mining duties In 1961 he moved to Vancouver where he became a salesman at a local department store He had been a moderately heavy smoker 20 to 30 cigarettes per day for 14 years As a teenager in Asbestos he had had two pneumonic Lowean 824 PAUL CHAMPION e ee oe mites ee illnesses from which recovery was uneventful and swift In 1963 he was believed to have had a myocardial infarction On physical examination he was slim but did not appear wasted His pulse rate was 116 beats per min and regular his blood pressure was 120/70 mm Hg The classic signs of a large right pleural effusion were present A chest film confirmed the presence of an ef fusion on the right side No pleural plaques were seen Hemoglobin was 15.6 per 100 ml leukocyte count 10,400 per mmwith a normal differen- tial count erythrocyte sedimentation rate modified West 25 mm per hour serum proteins were normal Aspirated pleural fluid was initially colored and contained many lympho- cytes and some polymorphonuclear leukocytes Clumps of large monocytic cells were present and believed to be atypical pleural mesothelial cells The sputum contained no malignant cells Bronchoscopy was normal At diagnostic thoracotomy performed by Dr. Elliot Harrison colored fluid was again withdrawn The right lung was found to be partially collapsed The parietal pleura and the lung surface particularly in the upper thorax were covered with fibrin and sized nodules On the chest wall and mediastinum and extending down onto the diaphragm were yellowish round tumor nodules 1 cm to 3 cm in diameter Histologic examination of samples of these nodules showed malignant mesothelioma The patient was treated with irradiation to the right chest in April 1968. He died in autumn of that year Discussion In Case 1 the diagnosis of malignant mesothelioma was initially suspected because a pleural plaque was seen on the dome of the left hemidiaphragm The presence of hyalinized and calcified plaques in persons exposed to asbestos dust is common The plaques may be found on the visceral parietal or diaphragmatic pleura Fibers of asbestos have been found in the pleura and peritoneum of persons exposed to asbestos dust 1-3 The mechanisms whereby these fibers reach the pleura and peritoneum and cause a characteristic fibrous reaction is incompletely un- derstood Anton 4 believed that although pleural plaques might be caused by inhalants such as talc and by specific infections multiple pleural plaques seen on chest films are characteristic of asbestos exposure The de- gree of exposure that might induce plaque formation appears to be somewhat less than that necessary to produce asbestosis The plaques can be found anywhere on the pleural surface but are particularly common on the diaphragmatic pleura Although they can be seen in routine posteroanterior and lateral chest roentgenograms oblique views are occasionally necessary to detect them In Case 1 in addition to the small plaque on the left diaphragm a large pleural plaque was found at thoracotomy on the right diaphragm this plaque had not been seen on chest films that had included oblique views It is likely that even the small amount of fluid remaining in the chest after aspiration had served to conceal this plaque There is a close relationship between the presence of pleural plaques and subsequent development of malignant mesotheliomas in those exposed to some form of asbestos dust Thus the sister of the first patient having been found to have a pleural plaque must be considered to be at risk Hourihane and workers 3 5 recently described 29 patients who had been exposed to asbestos and in whom pleural plaques were the sole radiographic evidence of disease In 5 of these patients malignant mesotheliomas of the pleura or peritoneum subsequently developed in addition one patient died of car- cinoma of the bronchus A comprehensive study by Newhouse 6 and Newhouse and Thompson 7 illus trated the importance of nonoccupational exposure to asbestos in subsequent development of malignant tumors Among patients with mesotheliomas in the area of London England were 9 whose only contact with asbestos was through closely related persons who worked with the mineral It is not un- common for pipe laggers for example to return home from work with a large amount of asbestos on their clothing resulting in steady exposure of other members of the household to asbestos Case 1 illustrates the danger to which relatives of asbestos workers are exposed This is probably particularly true of the children of an asbestos worker who might come into contact with their MALIGNANT MESOTHELIOMA AFTER ASBESTOS EXPOSURE 825 definite father's overalls and the worker's wife who ers in the asbestos industry Although some might wash these garments Two close rela- investigators believe that the only were examined radio- increase in carcinoma of the bronchus occur- tives of the first patient with as- and one was shown to have pleu- ring in the industry is in patients graphically bestosis cigarette smokers exposed to asbes- ral plaques seven times the risk of development The average time between the onset of ex- tos are at of a of malignant tumors as workers who do not mesothelial posure and the development , tumor is approximately 30 years to 35 years handle asbestos 13 6 but there are examples of induction There is probably no really safe level of asbestos exposure The minor exposure ex- times of 15 years or less 5 It is of interest before of the dis- that in the 2 patients described herein the perienced by relatives signs Na RRtS tumors developed at 32 years and 31 years of ease process develop makes pronouncements to the dust from early of safe or comparatively safe industrial ex- ana age after exposure in- levels for asbestos workers unrealistic oar childhood It is obviously important to posure piaie n examination of and misguided It is clear that only minor stitute regular radiographic of nara the chest not only in asbestos workers but exposure is required for the development also in their relatives malignant tumors and this fact serves to prtaeg The patient in Case 2 had worked for stress the importance of regular screening by examination of the chest of in the Canadian mining indus- radiographic many years and had lived in a mining town He had workers and their relatives The screening of try been exposed only to chrysotile As in Case relatives must be routine if full understandof asbestos to the com- a primary malignant pleural tumor devel- ing of the dangers at in the fourth decade of his life Chryso- munity is to be gained Furthermore oped believed some to be free of it must be assumed that all forms of present tile is by remain a se- carcinogenic effect Wagner 8 9 has stated asbestos including chrysotile that one difficulty in assessing the dangers rious health hazard because they cause pul- fibrosis and induce malignant tu- of chrysotile is that most workers are exposed monary to a mixture of asbestos fibers and other mors chemical agents Data reported by Wright 10 referring to work by MacDonald and associates suggest that the incidence of primary malignant tumors of the pleura is not increasing in Canada where chrysotile Acknowledgments The writer wishes to thank Dr. S. Grzybowski Associate Professor Department of Medicine for his advice and kind permission to discuss Case 1 and Dr. Elliot Harrison for his kind permis sion to discuss Case 2 is mined Wright 10 suggested that chryso- tile is associated less with malignant mesothe- RESUMEN _- wees lial tumors than other types of asbestos Smith and workers 11 showed experi- mentally that chrysotile alone was not carcinogenic to hamsters unless combined with the hydrocarbon 3-4 benzpyrene Benzpyrene alone was not carcinogenic in these experiments Although it has been suggested that the incidence of malignant tumors is not increased in those exposed to asbestos who do not smoke no clear studies are available 12 Smoking is a common habit through- out the general population including work- Dos casos de mesotelioma maligno despu^'s de exposici^nal asbesto Se encontr^ un mesotelioma maligno en dos j^venes despu^'s de estar expuestos al asbesto En uno de los pacientes las placas pleurales fueron de importancia para el diagn^stico El paciente estuvo accidentalmente expuesto al asbesto a trav^'s de la ropa de su padre quien era un obrero de asbestos En el otro paciente el as- besto cris^tilo fue probablemente el carcin^geno Se recalca la importancia de la observaci^n cl^>nica y radiogr^fica en aquellos individuos que est^n en contacto personal con obreros de la in- 2 MacDonald A. D. Harper A. El Attar O. A. and McDonald J. .: Unpublished data dustria de asbestos y el papel tan importante que desempe^-a el polvo de asbestos en la pro ducci^nmalignidad 1969 1 1 826 PAUL CHAMPION RESUME plaques as an index of exposure to asbestos an Deux cas de m^'soth^'liomemalin suivant A study of radiological and pathological fea- tures of 100 cases with a consideration of l'exposition ^ l'amiante OF epidemiology Brit Med J. 1966 , 1069 Du m^'soth^'liommealin a ^'t^'constat^'chez deux Newhouse M. L The medical risks of ex- aint jeunes hommes apr^s l'exposition ^ l'amiante posure to asbestos Practitioner 1967 199 Chez l'un des malades des plaques pleurales ^'taientde l'importance diagnostique Ce malade avait ^'t^'expos^' fortuitement ^ l'amiante dans les v^"tements de son p^re qui travaillait dans 285 Newhouse M. L. and Thompson H Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area l'industrie de l'amiante Chez l'autre malade Brit J. Industr Med 1965 22 61 l'asbeste chrysotile paraissait ^"tre le carcinog^ne On insiste sur l'importance de l'observation clinique et radiographique des personnes qui sont en contact avec ceux qui travaillent dans Wagner J. C Epidemiology of diffuse meso thelial tumours Evidence of and association from studies in South Africa and the United Kingdom Ann N. Y. Acad Sci 1965 132 l'industrie de l'asbeste et le r^le important que jouent tous les genres de poussi^re d'asbeste dans la production des malignit^'s 575 Wagner J. C. Sleggs C. A. and Marchand P Diffuse plural mesothelioma and asbestos exposure in the North Western Cape References Province Brit J. Industr Med 1960 17 1. Leading Article The dangers of asbestos Lancet 1968 1 32 2. Levine H Asbestos bodies in the peritoneum New Eng J. Med 1968 278,630 278,630 3. Hourihane D. O. B A biopsy series of mesotheliomata and attempts to identify as- bestos within some of the tumors Ann N. Y. Acad Sci 1965 132 647 4. Anton H. C Multiple pleural plaques II Brit J. Radiol 1968 41 341 5. Hourihane D. O. B. Lessof L. and Rich- ardson P. C Hyaline and calcified pleural 260 10. Wright G. W Asbestos and health in 1969 Amer Rev. Resp Dis 1969 100 4 11. Smith W. E. Miller L. and Elsasser R. E Tests for carcinogenicity of asbestos Ann N. Y. Acad Sci 1965 132 456 12. Hardy H. L. and Leahy J. .: Recognition of occupational lung disease Clin Notes Resp Dis 1968 6 3 13. Selikoff I. J. Churg J. and Hammond E. C Asbestos exposure and neoplasia J.A.M.A. 1964 22