Document 4JNxMom3B76zdbe5KGXkk4Vve

Case Reports Two Cases of Malignant Mesothelioma after Exposure to Asbestos' PAUL CHAMPION SUMMARY________________________ Malignant moothclioma occurri-t! in 2 young men after exposure to asbestos. In one patient, pleural plaques vrre of diagnostic importance. The patient was incidentally exposed to asbestos fmm the clothing of his father > ho was an asbestos worker. In the oilier patient, chrysolite j-Ik.io. ujs prohablv the caret".ten. The importance of clinical cr..i radiographic observation of those in personal contact with workci.t in the asbestos indtisirs ar.d the important part played by all types of asbestos dust in the ptoiluuioti of malignancy are sttesstd. Introduction Asbestos is one of the most valuable and ver satile materials exracted from the earths' surface. There are six varieties of asbestos, all silicates, which differ physically and chem ically from one another crocidolite. amosite, amihophylite. tremolite, actinolite, and chrysotile. Crocidolite and amosite contain more iron than do the other forms. Chryscv tile, commonly known as white asbestos, is largely magnesium silicate and forms 90 per cent of the world's output of the mineral. ]t is found principally in Canada and the (Received for publication June 29.1910) 1 From the Department of Medicine, Univer sity of British Columbia, and Vancouver Gen eral Hospital. Vancouver, BritUlt Columbia, Canada. U.S.S.R. No other type of asbestos is mined in Canada. Repeated et posure to asbestos dust leads to a number of diseases. Asbestosis is char acterized by pulmonary fibrosis causing a re strictive 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 as bestos is dangerous, the potential of chryso tile 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 10J, 1971 821 822 PALL CHAMPION Fig. I. Posteroanterior radiograph of chest in Case l showing the presence of a large pleural effusion on the right. pleural plaques. The degree of exposure nec essary for plaque formation is not dear. 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 develop ment 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 cer tain unusual features of their causes. CASE REPORTS Case I: A 51-ycar old white man presented in March 1070 with a six-week hi-toiy of breath lessness and a seven month hi-tory of general weakness and malaise after an inPuen/a-like ill ness. There had been no oih.r change in hi' health, no cough, hemoptysis, fever, or weight loss. The patient was bom in Glasgow, Scotland, where he had lived for the first 28 years of his life; he came to Canada in 1963. 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. TUc patient's 69-year-old father had severe as bestosis for which he received compaction; his ill health had followed employment as a pipe logger in Scotland. The patient s 53-ycar old mother had emphysema. His only brother and two sisters were alive and well. The patient's fa ther 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 tho-c over alls. The mother occasionally washed the over alls. Physical examination revealed a well nour ished man with no clubbing of the lingers or lymphadeiiopathy. Tfiere were classic signs of right pleural effusion. A che-t him uig-.iic I) confirmed the pre-eticc of a brgi right plmi.il effusion; on the left lictnidiaplu.-.gm w..s a small DOUI 05736 -4^25?.' - - . -.j-..-i^l>i Fig. 2. Enlarged view of a portion of figure 1 showing a small, calcified pleural plaque on the left hemidiaphragm. calcified, pleural plaque 2 on in length (figure 2). No other abnormality was noted. The hemo globin was 15.7 g per 100 ml; cn'.i-.rocyte sedi mentation rate (modified West 11 mm per' hour; hukeicytc lumit, 7 ?00 :>-.t :nm3 with -iO per cent lymphocytes. 50 per err.: neutrophils. 2 per cent segmented forms, ar.i 8 per cent monocytes. Scrum proteins and hepatic function tests were normal. Bronchoscopy re'.ealcd no ab normality. Aspirated pleural fluid was initially straw colored, but after repeated thoracenteses, it became slightly blood-<uincd. No fluid sam ples demonstrated acid-fast bacilli or. microscopy or culture. Cytologic examination revealed clumps of malignant mcsothclial cells. Three pleural biopsies with an Abrams needle revealed normal pleura and connective tissue only. At open pleural biopsy (performed by Dr. Ian Munroc). 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 nod ules 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 pleural biopsy, kaolin powder was insufflated into the right pleural cav ity to effect plcurodcsis. Because there was a 'null recurrence of pleural fluid after this pro cedure. 20 mg of nitrogen mustard were instilled into the cavity. The effusion did not recur subsstpivntls. The patient remained free from symptoms during the four-month follow-up pe riod, lost no "eight, and was not anemic. After discharge from the hospital, however, slight dubbing of the fingers developed. The patient's mother and sister weie examined radiographically. Emphysematous changes were seen in the mothers ches* film. In the sister's chest film a calcified pleural plaque w as seen on the dome of the left diaphragm. The sister had also had no contact with asbestos oth er tlian from contact with her father. Case 2: A 52-ycar-otd white Canadian man pre sented with a history of discomfort in the right chest of six weeks' 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 lo-^ 5 pounds in weight. The patient had been bom 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 con tinually in a haze of dust from the asbestos mines and workshops." AftcT leaving school, the patient worked for ten years as an asbestos mine prospector in Quebec and elsewhere in Canada. For short periods, he also worked in the open pit but never performed any deep mining duties. In K'Gl, 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 U years. As a teenager in Asbestos, he had had two pneumonic 824 PAUL CHAMPION illnesjes, from which recovery was uneventful and swift. In 1943, 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'TO 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 mm3 with a normal diilerential count; erythrocyte sedimentation rate (mod ified West), 25 mm per hour; serum proteins were normal Aspirated pleural fluid was initial ly straw-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 thor acotomy (performed by Dr. Elliot Harrison), straw-colored fluid was again withdrawn. The rich: lum was found to he partially mHapscd. The parietal pleura and the iunj surface, par ticularly in the upper thoiax, were covered with fibrin and pea-sired 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 ex amination of samples of these nodules showed malignant mesothelioma. The patient was treated with irradiation to the right chest in April 1908. 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 hyalinired and calcified plaques in persons exposed to asbestos dust is common. The plaques may be found on the visceral, parietal, or dia phragmatic 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 read) the pleura and peritoneum and came a charac teristic fibrous reaction is incompletely un derstood. Anton (-1) believed that although pleural plaques might he cau-cd by inhalants such as talc am! by specific inf.cttons, milltip .- pleural plaque- seen on cht-t film- are characteristic of asbestos exposure. The de gree of exposure that might induce plaque formation appean to be somewhat less than -that necessary to produce asbestosis. The plaques can be found anywhere on the pleu ral surface but are particularly common on the diaphragmatic pleura. Although they can be seen in routine posteroanierior and lateral chest roentgenograms, oblique views are oc casionally 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 Haiti remaining in the diest 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 C/> --1 those exposed to some lonit of asbestos dust. D Titus the sister of the first patient, having ol .been found to have a pleural plaque, must CT be considered to be at risk. Hottrihanc mid vTl crico-workers (3. 3). recently described 29 pa rotients who had been exposed to asbestos and roin whom pleural plaques were the sole radio graphic evidence of disease. In 5 of these patients, malignant mesotheliomas of die pleura or peritoneum subsequently devel oped; in addition, one patient died of car cinoma of the bronchus. A comprehensive study by Newbouse <<3> and Nets house and Thompson (7) illus trated the importance of nonoccupational exposure to asbestos in subsequent develop ment 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 loggers, for example, to re turn home from work with a large amount of asbestos ott their clothing, resulting in steady exposure of other member' of the house.hohl to asbestos. Cuse l illustrates the danger to which relatives of asbestos workers oc 09 rs if! O arc exposed. This is probably pjitio.d .r 1 y true of the children of an ashr-tus w.jdtr who might come into com.vet v-itli their 3 C c MALIGNANT MESOTHELIOMA AFTER ASBESTOS ENrOSVRE 825 father's o'oralis, and the worker's wife, who might wash these garments. Two close rela mes of the first patient were examined radio graphically, and one was shown to have pleu ral plaques. The average time between the onset of ex posure and the development of a mesothelial tumor is approximately 30 years to S3 years (6), but there are examples of induction times of 13 years or less (5). It is of interest that in die 2 patients described herein, the tumors developed at 32 years and 31 years of age. after exposure to the dust from early childhood. It is obviously important to in stitute regular radiographic examination of the chest not only in asbestos workers but also in their relatives. The patient in Case 2 had w-orked for m:ny yean in the Canadian mining indus try and had lived in a mining town. He had been exposed only to chrysotile. As in Case I, a primary malignant pleural tumor devel oped in the fourth decade of his life. Chryso tile is believed by some to be free of carcinogenic ellect. Wagner (s. 9j has stated that one difficulty in assessing .!.* dangers ol chry-otiic is that most workers a:e exposed to a mixture of asbestos fii.en and other chemical agents. Data reported by Wright (10) referring to work by MacDonald and associates- suggest dial the incidence of primary malignant tumors of the pleura is not increasing in Canada, where chrysotile is mined! Wright (10) suggested that chryso tile is associated less with malignant mesothe lial tumors than other types of asbestos. Smith and co-workers (11) showed experi mentally that chrysotile alone was not car cinogenic to hamsters unless combined with the hydrocarbon 3-4 benzpyrene. Benzpyrene alone was not carcinogenic in these experi ments. Although it has been suggested that the incidence of malignant tumors is not in creased in those exposed to asbestos who do not smoke, no clear-cut studies are available (12). Smoking is a common habit through out the general population, including work- - MacDonald, A. D., Harper, A., El Attar, O. A., and McDonald, J. C.: Unpublished data, 1969. ers in the asbestos industry. Although some investigators believe ila.it the only definite increase in carcinoma of the bronchus occur ring in the industry is in patients with asbestosis, cigarette smokers exposed to asbes tos are at seven times the risk of development of malignant tumors as workers who do not handle asbestos (13). There is probably no really safe level of asbestos exposure. The minor exposure ex perienced by relatives before signs of die dis ease process develop makes pronouncements of safe or comparatively safe industrial ex posure levels (or asbestos workers unrealistic and misguided. It is dear that only minor exposure is required for the development of malignant tumors, and this fact serves to stress the importance of regular screening by radiographic examination of the chest of workers and their relatives. The screening of relatives must be routine if full understand ing of the dangers of asbestos to the com munity is to be gained. Furthermore, at present it must be assumed that all forms of asbestos, including chrysotile, remain a se rious health hazard because they cause pulmoiijiy fibrosis and induce malignant tu mors. Acknowledgments The writer wishes to thank Dr. S. Crzybowski. Associate Professor, Department of Medicine, for his advice and kind permission to discuss Case l; and Dr. Elliot Harrison, fot his kind permis sion to discuss Case 2. RESUMES'. ... Dos casos de mesotelioma maligno despues de exposicion al asbesto Sc cnconnd un mesotelioma maligno en dos jdvencs despues de estar expuestos al asbesto. En uno de los pacicntcs las placas plcurales fueron de importancia para cl diagnOstico. El paciente estuvo accidcritalmcntc expuesto al as besto a travis de la ropa dc su padre, quien era un obrero dc asbestos. En el otro paciente. el as besto crisdtilo fue probablcmcntc cl carcindgenn. Sc rccalca la importancia de la observacidn dinica y radiognifica en aqucllos individuos que cstAn en contacto personal con obreros de la industria dc asbestos, y cl papcl tan importantc que desempeiia cl polvo dc asbestos cn la produccidn malignidad. iSf .:-vS ( `! IV i DOU 05739 826 FALX CHAMPION RESUME Deux cas de mdsothdlioine malin suivant 1'exposition k l'amiante Du mdsothdliome malin a <t< consult chez deux jeunes hommes aprts 1'exposition k l'amiante. Chez l'un des malades des plaques pleuraies dtaient de 1'imporunce diagnostique. Ce malade avait ttt expost fortuitement i l'amiante dans les vftements de son ptre, qui travaillait dans 1'industrie de l'amiante. Chez l'auire malade 1'asbeste chrysotile paraissait itre Ie carcinogine. On insiste sur l'importance de l'observation Clinique et ndiographique des personnes qui sont en contact avec ceux qui travaillcnt dans 1'industrie de 1'asbeste, et le rile important que jouent tous les genres de poussiire d'asbeste dans la production des malignites. Rafarenees 1. Leading Article: The dangers of asbestos. Lancet, 1968,1,32 2. Levine, H.: Asbestos bodies in the perito neum, New Eng. J. Med., 1903, 273,630. 3. Hourihanc, D. O. B.: A biopsy series of mesotheliomata and attempts to identify as bestos within some of the tumors, Ann. N. V. Acad. Sci., 1963,132, 647. 4. Anton, H. C.: Multiple pleural plaques: II.. Brit. J. Radiol., 1968, H, 341. 3. Hourihane, D. O. B., Lcssof. L., and Rich ardson, P. C.: Hyaline and calcified pleural plaques as an index of exposure to asbestos: A study of radiological and pathological fea tures of 100 cases with a consideration of epidemiology, Brit. Med. J., 1966, 1, 1069. 6. Newhouse, M. L.: The medical risks of ex posure to asbestos. Practitioner. 1967, 199, 283. 7. Newhouse. M. I_ and Thompson. H.: Meso thelioma of pleura and peritoneum follow ing exposure to asbestos in the London area, Brit. J. Industr. Med., 1965.22, Gl. 8. Wagner, j, C: Epidemiology of diffuse -'cso- thclial tumours: Evidence of and ass> ...<:iou from studies in South Africa and the United Kingdom, Ann. N. Y. Acad. Sci., 1963. 132, 573. 9. Wagner, j. C., Sleggs, C. A., and Marchand. P.: Diffuse plural mesothelioma and asbes tos exposure in the North Western Cape Province, Brit. J. Industr. Med., I960. IT, 260. 10. Wright, C. W.: Asbestos anil health in t'.'tiO. Amcr. Rev. Rexp. Dis., 19ii9. tint, 4. 11. Smith, W. E., Miller, I.. .hr! K. L.: Tests for carcinogenicity of jiIic-ur. \mi. N. Y. Acad. Sci.. IW3,132, 1jo. 12. Hardy, H. L., and Leahy, J. E.: Rcioziminu of occupational lung disease, Clin. Notes Rcsp. Dis.. I%8, if, 3. 13. Sclikolf, I. j., Churg, J., and Hammond, E. C.: Asbestos exposure and iitopl.iM.i. J.A.M.A., 1961,22. DOW 05740