Document 6w1xJ672b7ZnvBvymr756Mvv1

r^ . S] Ann. N.Y. Acad. S c i . . 132:674-679. 1965. j f I T MESOTHELIAL TUMORS AX'D EXPOSURE TO ASBESTOS DUST nos is of ground- i W. Glyn Owen were mu I Pathology Department, Broadgreen Hospital, Liverpool, England amount. ' I forward for hl-tr V4 The carcinogenic properties of asbestos have been recognized for several y e a r s ,b u t only recently has particular attention been given to the occur i post-mo r pleura! :! rence of mesothelia! tumors in workers exposed to asbestos dust.1'" In the present investigation evidence of asbestos exposure was sought in of un-pet l Dime-: 1 recorded examples of diffuse mesothelioma occurring in Liverpool and in mainly f neighbouring towns of the Merseyside area of North West England. This Detailed ?b is an industrial area with a population of over two million people. Ship building and ship repairing are prominent among the industries which use number . presence asbestos, and there are a number of factories in the area where processing of raw asbestos is carried out. i potential, i ponent o fibroblast M ethods this type Thirty cases were considered. All had malignant growths of the pleura f scopicalb or peritoneum and in all of them the diagnosis of diffuse mesothelioma had appearan been suggested at one time, though sometimes inaccurately or on inade quate grounds. A review of clinical histories and post-mortem records was \ differenu spindle c- followed by reassessment of all available histological material. In only one predomin instance was the diagnosis accepted without histological confirmation. In tures of r >*c *$ this case post-mortem findings typical of diffuse mesothelioma of the pleura had been recorded, but the sections and blocks of tumor tissue had been lost. With this exception the diagnosis of diffuse mesothelioma was only accepted if, in addition to all other evidence, the histological appear I The de. !f diffuse rr. blue and theliomai ances of the tumor were thought to be characteristic. Tumor tissue had i quantitie- i been preserved in 26 cases, the specimens being obtained at thoracotomy ii These co alone in 13 patients, at autopsy alone in eight patients, and from both treatment these sources in another five patients. behavior Evidence of exposure to asbestos was sought by microscopic examination was fain: of lung tissue for the presence of asbestos bodies and by obtaining detailed one of tht occupational histories from the patients or from their nearest relatives. by digest Histological Diagnosis Of the 30 cases considered 17 were finally selected as true examples of diffuse mesothelioma (.including one on post-mortem evidence alone':. Six teen were primary growths of the pleura and one was a primary peritoneal or within cant. Sin as hyalin tissue.10 mesothelioma. Of the remaining 13 tumors five were identified as secondary adenocarcinomas infiltrating the pileura. two as fibrosarcomas, and one as a bronchial oat cell carcinoma involving the pleura. Conclusive diag- Post-m fering fn 674 <r m SlPjPpppWII'f ^ l U J ^ R PiPPliPPiPiPPipiP^^ m s )S DUST Averpool, England ->recognized for several )een given to the occurasbestos dust.''~ exposure was sought in -.ng in Liverpool and in tn West England. 1 nis ,vo million people. Ship he industries which use e area where processing t growths of the pleura iffuse mesothelioma had accurately or on inadeiost-mortem records was al material. In only one logical confirmation. In ;e mesothelioma of the cks of tumor tissue had iffuse mesothelioma was the histological appearistic. Tumor tissue had obtained at thoracotomy patients, and from both microscopic examination nd by obtaining detailed heir nearest relatives. ;ted as true examples of ;m evidence alone!. Sixtvas a primary peritoneal re identified as secondary fibrosarcomas, and one pleura. Conclusive diag- : O w en: Mesotholial Tumors 675 1 nosis of the remaining five tumors could not be achieved. On histological 1 grounds two of these may have been mesotheliomas but the appearances were not entirely characteristic and the available material was small in i amount. In the other three cases the diagnosis of mesothelioma had been put ! forward on clinical grounds alone. So tumor tissue had ever been submitted i for histological examination, and neither exploratory thoracotomy nor I post-mortem examination had been carried out. Cytological examination of ] pleural fluid in two of these cases had shown the presence of malignant cells I of unspecified type. ; Difficulties in the histological diagnosis of diffuse mesothelioma arise ; mainly from similarity to secondary adenocarcinoma or to fibrosarcoma, i Detailed descriptions of the microscopic appearances have been given oy a number of authors.0"- All agree that the main diagnostic feature is the presence of a mixed structural pattern which they attribute to the dual potentiality of the mesothelium. Characteristically, an endothelial com ponent of papillary or tubulo-papillary structure is mixed with areas of fibroblastic activity often of sarcomatous appearance. A mixed pattern of this type was clearly visible in 11 of the 16 mesotheliomas examined micro scopically in this series. Two others were predominantly sarcomatous in appearance, one was mainly papillary in structure, and two were poorly differentiated growths composed of sheets of malignant cells including spindle cells and several tumor giant cells. But even in these tumors of predominantly one-cell-pattern there were some areas in which other fea tures of mesothelioma could be distinguished. The demonstration of hyaluronic acid production assists the diagnosis of diffuse mesothelioma.1' A substance giving positive reactions with alcian blue and with Hale's colloidal iron stain was demonstrated in all the meso theliomas in this series, but in the majority it was present in very small quantities, being confined in some instances to a few isolated tumor cells. These color reactions were abolished or markedly reduced by previous treatment of the tissues with testicular hyaluronidase, in contrast to the behavior of mucin in secreting adenocarcinomas. On the other hand there was failure of the tissues to stain with Southgate's mueicarmine in all but one of the examples. This tumor gave a faint reaction which was abolished by digestion with hyaluronidase. Only material present within tumor cells or within spaces lined by cells of endothelial type was considered signifi cant. Similar reactions in stromal elements were regarded as nonspecific as hyaluronic acid may be produced by any actively growing connective tissue.10 Post-m ortem Appca ra nces Post-mortem examinations had been performed on 12 of the patients suf fering from mesothelioma including the one where no histological material WUPIWIW1 MW.' ,-;' 676 Annals New York Academy of Sciences had been preserved. In all cases tumor was present which was confined to the lining'layers of serous cavities. There was one primary peritoneal meso thelioma. In this subject the growth had spread widely over the surface of the bowel and over both surfaces of the liver but no primary tumor could be detected in these or in any other organ. The remaining examples were considered to be primary growths of the pleura though extensive peritoneal involvement had occurred in two of them. In nearly all instances the lung on the affected side was shrunken and encased in thick tumor tissue which obliterated the pleural space and which extended deeply into the inter lobar fissures. Only one blood-borne metastasis was encountered. This was an isolated nodule of tumor situated deeply within the substance of the liver. Lym phatic spread was recorded more frequently, axillary or mediastinal lymph node deposits being present in half the cases. No bronchial or other intrapulmonary neoplasm was detected at any of the post-mortem examinations and no primary tumors were found in any other organs. Evidence of Asbestos Exposure Evidence of exposure to asbestos was obtained in 14, or 82 per cent, of the group of 17 cases selected as examples of diffuse mesothelioma. Each of the other three patients in this group had worked in places where they may have handled asbestos but no detailed information could be obtained about the nature of their duties. None of the patients in the second group was known to have worked with asbestos and in none were asbestos bodies found in the lungs. Two men in this group had spent several years at sea, one as a ship's stoker, and both could possibly have been exposed to asbes tos though there was no direct evidence to suggest this. The tumor in the first case was one of the two which were difficult to classify histologically and wnich may have been mesotheliomas. The tumor in the second case had never been submitted for histological examination. In neither case had lung tissue been preserved. \ ery little lung tissue had been preserved for examination, most of the thoracotomy specimens and much of the post-mortem material consisting only of blocks of tumor tissue. Asbestos bodies were never seen within tumor tissue. Sections containing lung were available in 10 of the con firmed mesothelioma cases, and asbestos bodies were identified in seven of these. They were scanty in most specimens so that prolonged search was neces-ary to find them. In the three negative cases only small fragments of lung attached to tumor tissue were available for examination. In con trast, asbestos bodies were found in only 18, or 9 per cent, of 200 consecu tive pneumonectomy and post-mortem specimens of lung seen during the same period. In this group routine histological method.-, were supplemented ( by the examination of from lung tissue, a mi bestos bodies. Because of the limit to assess the degree of from mesothelioma but a slight to moderate deg with the clinical histori had complained of resp nant tumor within the pi Twelve of the mesoth asbestos dust during th. coverers, who had been . had been engaged main! had worked in ship repa Two patients were boik mainly sheet metal work for fireproofing and hea engaged in preparing ai and both had frequently other men who were har asbestos factories. A mi factory had started wor years before the introdui asbestos worker. The oth had worked at an asbesti 1919, and had then marr health for forty years a which she died two years patients had been emplo had worked in departmen ing of old sacks. Sacks su ous contents and were gej asbestos sack.- were noto handling. Close environmi working in the offices of a ies of cement were made entire area became extren into the factory yard. On i with a layer of fine white every day. Five patients gave nega ' rif vfgvw `t-v-spumr* of Sciences resent which was confined to one primary peritoneal mesox-ad widely over the surface "but no primary tumor could he remaining examples were i though extensive peritonea! nearly all instances the lung in thick tumor tissue which nded deeply into the inter- ltered. This was an isolated ubstance of the liver.' L>mxillary or mediastinal lymph lasm was detected at any of y tumors were found in any oosure ned in 14. or 82 per cent, of diffuse mesothelioma. Each worked in places where they formation could be obtained patients in the second group in none were asbestos bodies d spent several years at sea, have been exposed to asbes:gest this. The tumor in the ult to classify histologically le tumor in the second case tamination. In neither case or examination, most of the mortem material consisting ies were never seen within available in 10 of the con5 were identified in seven of >that prolonged search was cases only small fragments le for examination. In conr 9 per cent, of 200 consecu:ns of lung seen during the methods were supplemented Owen: Mesothelial Tumors 677 by tr.c- examination of smears made from spun deposit; of fluid expressed from jung tissue. a much more sensitive method for the detection of as bestos bodies. Because of the limited amount of lung tissue available it was difficult to assess the degree of pulmonary fibrosis present in the patients suffering from mesothelioma but none of the specimens examined showed more than a .-lignt to moderate degree of fibrous reaction. This finding correlates well witr: the clinical histories. All patients had enjoyed good health and none had complained of respiratory symptoms until the development of malig nant tumor within the pleural cavity. Occupational H istories Twelve of the mesothelioma patients are known to have been exposed to asbestos dust during the course of their work. Five were aggers, or pipe coherers, who had been employed by firms of insulation engineers and who had been engaged mainly in the insulation of steam pipes. Three of these had worked in ship repairers' yards and all had handled asbestos regularly. Two patients were boiler makers in the ship building industry. Though mainly sheet metal workers, both gave clear accounts of the use of asbestos for fireproofing and heat insulation in ship construction. Both had been engaged in preparing and fitting asbestos sheets in ships' compartments and both had frequently worked in confined spaces in close proximity to other men who were handling asbestos. Only two patients had worked in asbestos factories. A man employed for forty-three years at one asbestos factory had started work at fifteen years of age in 1915. nearly twenty years before the introduction in Great -Britain-of legislation.to protect the asbestos worker. The other patient was a female card room operative. She had worked at an asbestos factory for a period of five years from 1914 to 1919, and had then married and left the industry. She remained in good health for forty years and then developed a pleural mesothelioma from which she died two years after the onset of the first symptoms. Two female patients had been employed by firms of sackware manufacturers. Both had worked in departments dealing with the sorting, cleaning, and repair ing of old sacks. Sacks submitted for repair contained traces of their previ ous contents and were generally extremely dusty. At each of the factories asbestos sacks were notorious for the fine dust which they produced on handling. Close environmental exposure had occurred in the case of a typist working in the offices of a firm of concrete manufacturers. Regular deliver ies of cement were made from a nearby asbestos cement works and the entire area became extremely dusty when the loads of cement were tipped into the factory yard. Or. these occasions the office furniture became coated with a layer of fine white powder which had to be removed at least once every day. Five patients gave negative or inconclusive occupational histories but in 3?l P M8WP fW i.-W U ^ uiiu,UHpiaii .n|ii. iLuij m . 4 678 Annals New York Academy of Sciences two of these asbestos bodies were detected in the lungs. One was a lorry driver for a firm of ship repairers and fitters. Though he denied asbestos exposure it was later learned that he did carry loads of asbestos on several occasions. The second patient was a woman who had done several different types of work, none of which involved the use of asbestos. The time and place of exposure in this case remain unknown. Of the remaining three patients one had been a boiler maker in the ship building industry, one was apprenticed to a firm of ship repairers and fitters for a period of seven years, and the other was a general laborer on the dock railway system. All may have handled asbestos but there was no direct evidence that they had done so. General Information No attempt was made in this investigation to ascertain the type of asbes tos fibers to which patients had been exposed, and no information was sought from factories or other industrial concerns where patients had been employed. The series covers a period of ten years from 1953 onwards. In the meso thelioma group there were 12 male and five female patients. All but one have died. Their average age was 58 years, the youngest being 42 and the oldest 82 years of age at death. Duration of exposure to asbestos ranged from five to 45 years. The short est interval recorded between the first known exposure to asbestos and the development of tumor was 13 years, and in all but two cases this interval exceeded 20 years. There were latent intervals of up to 40 years between the end of exposure and the development of tumor. Co n c l u s io n A close association between exposure to asbestos dust and the develop ment of diffuse mesothelioma is confirmed, and it is concluded that asbestos exposure is a major factor in the causation of this tumor. R eferences 1. Gloyne, S. R. 1951. P neum oconiosis. L an cet 1: 810. 2. Doll, R. 1955. M o rtality from lung cancer in asbestos w orkers. B rit. J . In d u st. Med. 12: 81. 3. W agnep., J . C., C. A. Sr.egos & P . Marc ha nd. I960. D iffuse p le u ra l m eso theliom a and asbestos exposure in the N orth W estern Cape Province. B rit. J. In dust. Med. 17: 260. 4. Sexjkoff, I. J., J . Chcrg & E. C. H ammond. 1964. A sbestos ex p osure an d neoplasia. J.A .M .A . 188: 22. 5. H o c r ih a n e D. O 'B. 1964. T h e p ath o lo g y o f m esotheliorr.ata an d an an alysis o f th e ir asso ciatio n w ith asb esto s ex p o su re. T h o ra x 19 : 268. 6. Klem perer, P. & C. B. Ra b in . 1931. P rim a ry neo p lasm s o f th e p le u ra . Arch. P a th . 11 : 385. 7. Go d w in, M. C. 1957. D iffuse m esotheliom as. C a n c e r 10: 298. 8. McCacghey, W. T. E. 1953. P rim a ry tu m o u rs of the pleu ra. J . P ath . B act. 76: 517. I m r n m mgfe 9. W ag.ver, J. C., T demonstration o S4: 73. 10. T aylor, H. E. & ground substam J. Path. 33: 525 f Sciences ;e longs. One -was a lorry ."hough he denied asbestos .ads of asbestos on several had done several different A asbestos. The time and ;. Of the remaining three tip building industr>', one liters for a period of seven .e dock railway system. Ail ect evidence that they had i j ; j \ ; Ov.-en: Msothlial Tumors 679 9. " ag.v e e, J . C., 1). E . Mu .voay & J . S. H arington. 1962. H .'stochem ical ;lfJ dem onstration U : 73. of hyaluronic acid in pleural ir.esothei '" Jo rnas. J. P a th . B act. T aylor, H . E . & A . M. S avxijers 1957. T he asso c,at: or. o f m e ta c h ro m a tic grour.d substar.ee w ith fibroblastic activity in g ram ilation tissue. Anier. J . P ath . 33: 525. * ascertain the type of asbes, and no information was tcerns where patients had [953 onwards. In the meso male patients. All but one youngest being 42 and the five to 45 years. The shortxposure to asbestos and the but two cases this interval ; of up to 40 years between <r. estos dust and the developit is concluded that asbestos this tumor. 810. in asbestos workers. Brit. J. 1. 1960. D iffuse pleural meso orth W estern Cape Province. 1964. Asbestos exposure and aesotheliomata and an analysis e. Thorax 19: 26S. ,ary neoplasm s of the pleura. Cancer 10: 29S. rs of the pleura. J. Path. Bact. np.jpM uui u'u-j^impiuiP fm m m m m m m m m