Document RaKp4mpDpaYyn7n9Qz328yOeB

DOW 0 5 7 0 9 diffuse pleural mesothelioma and asbestos exposure IN THE NORTH WESTERN CAPT PROVINCE j. C. WAgner, C. A. Sleggs, and Paul Marchand BRITISH JOURNAL OF INDUSTRIAL MEDICINE 1960, 17, 260 06H *9SOJ.$ STC5CS491 Brit. J. industr. Med., I960. 17, 260. DIFFUSE PLEURAL MESOTHELIOMA AND ASBESTOS EXPOSURE IN THE NORTH WESTERN CAPE PROVENCE BY J. C. WAGNER. C. A. SLECGS. and PAUL MARCH AND From the Pathology Division. Pneumoconiosis Research Unit ofthe Council far Scientific and Industrial Research. Johannesburg, West End Hospital, Kimberley, anti the Department of Thoracic Surgery, University of the Witvatersrand and Johannesburg General Hospital 24, 1960)(riceived for publication april Primary malignant tumours of the pleura are uncommon. Thirty-three cases (22 males. 11 females, ages 31 to 68) of diffuse pleural mesothelioma are described; all but one have a probable exposure to crocidolite asbestos (Cape blue). In a majority this exposure was in the Asbestos Hills which lie to the west of Kimberley in the north west of Cape Province. The tumour is rarely seen elsewhere in South Africa. Mesothelioma of the pleura is regarded as an uncommon tumour. In the last four years we have seen 33 histologically proven cases; 28 of these had some association with the Cape asbestos field and four cases had been exposed to asbestos in industry. The tumour is rarely encountered elsewhere in South Africa. During the past five years, with the exception of the present series, no neoplasm of this nature has been diagnosed amongst 10,000 lungs examined at the Pneumoconiosis Bureau in Johannesburg, or in the Pathology Department of the South African Institute for Medical Research, Higginson and Oetxle (1957) did not observe a single case in their survey of malignant tumours occurring in the Bantu and Cape Coloured population of Johannesburg and the North Eastern Transvaal. Our first necropsy specimen of pleural meso thelioma with asbcstosis was examined at the Pneumoconiosis Research Unit in February, 1956 (Case 1). During the early months of that year, one of us (C.A.S.) in the Northern Cape, treated six patients with gross pleural thickening. Pleural biopsies from two of them showed the features of mesothelioma. In the ensuing two years, eight further cases were found from this region and five from elsewhere in the Union. During this period C.A.S. had become perturbed at the number of these unusual tumouri occurring amongst his patients, and stimulated an investigation. At this stage there were two reasons to suggest that asbestos might be implicated. First, asbestos was found in the lungs of the first case (Case 1), and secondly. 10 of the cases came from a hospital to which suspected cases of tuberculosis were referred from j large asbestos mining area. This hypothesis couid not be supported at once from the original histone* obtained from the patients, for they included house wives, domestic servants, cattle herders, farmers, j water bailiff, an insurance agent, and an accountant, one of whom were working on the asbestos mines at the time. We therefore undertook a detailed investigation of their past occupation and place of residence, and the association with asbestos -v posure was discovered. The cases are summanrsd in Table 3. Previous biopsy specimens were re examined, and new cases diagnosed, including asbestos miners. In only one case do the relatives deny that the patient either visited the asbestos mines or was exposed to asbestos. This is a preliminary publication and the problem is being intensively investigated. The Asbestos Area of the North-West Cape According to Hall (1930) asbestos was discovered by Lichenstein near Prieska during his travels be tween 1803 and 1806. Since then it has beet established that the asbestos deposits extend from 20 miles south of Prieska, northwards through the western part of the magisterial district of Hay. the eastern portion of the magisterial district of Postmasburg and finally, to the western area of the &OUJ OS7 10 DIFFUSE PLEURAL MESOTHELIO MA 26! b fr^ S O l? Fro. I---Map of Griqualand West asbestos nelds. district of Kuruman (Fig. I). These deposits occur in the slopes of a range of hills covering an area of approximately 8,000 square miles. Known as the "Asbestos Mountains'", these hills extend more or less longitudinally between 22*305 and 23s E. The whole area is semi-arid, sparsely populated, and, apart from mining, cattle ranching is the only important occupation. In the Kuruman area several large tracts of land in or abutting on these mountains have been reserved for the aboriginal inhabitants *nd here whites may only reside in the immediate vicinity of the mines. The type of asbestos mined throughout this area ctocidoiite. better known as Cape Blue Asbestos. The chemical analysis of the fibre is given in Table 1. Crocidolite is the fibrous form of riebeckite and all ^sges of transformation from a massive riebeckite hock through lamellar riebeckite to asbestiform ?^>cidolite occur in this region. Magnetite is "Cduetuly associated with the crocidolite (Vermaas, <952). Mining of asbestos first began in the Prieska district in 1893 and gradually spread northwards. In 1908 production had begun in the Kuruman dis trict. Between 1916 and 1918 a large number of claims were taken up. This northward trend has continued and in about 1950 mining started at Pomfret near the Bechuanaiand border (Table 2). Initially the ore was quarried in numerous small open cast workings. This was followed gradually Table 1 CHEMICAL ANALYSES OF CROCIDOLITE AND AMOSITE (from Vrmaas, 1952). so. A.l,0| Fe,Q, Frt MgO Cat) N 4,0 K*0 H.0 -- H,QTiO, MnO F Crocidotiic 51 94 020 18-64 19-39 * 17 <H9 607 004 0-31 2-SB -- --- Amoiite 49-47 0*61 *-U 35*63 6-S7 0-52 002 0-20 007 2 33 0*25 0-61 0-01 local 100 TJ LOO 46 o> DOW 05711 262 BRITISH JOURSAL OF IS DL'STRIAL MEDICISE Table 2 POPULATION OF THE MAGISTERIAL DISTRICTS IN WHICH THE ASBESTOS FIELDS ARE SITUATED Itakcn frotrt Union Cemus I92l. and (951) District Kyeu.Ttdfl Hav pQtunasburj Population (921 Whites Von-^hires Total 3.4J0 wnj 4.499 4.3-9 i,309 16.693 21.411 3.814 IJ.3U Included in the Hay District Whicei 3,361 4.318 2.757 4.887 PopuUuon 1951 VonT-*fute$ 10.347 23.779 9.6JI 21.019 ] Tout W 208 28.59? 12.383 25.906 by a type of shallow mining: inclined shafting be came more common after 1930. According to Frood (1915), the quarrying was a family affair undertaken by the local inhabitants. The men quarried the rock, which was sorted and then hand cobbed by the women and children. Hand cobbing consists of separating the fibre from the banded ironstone by striking the rock cob with a small hammer. As the market was selective, a rotary sieve was sometimes used to grade the fibre and eliminate the small particles of dust. After grading, it was bagged and weighed. The asbestos was then transported by donkey wagon to the nearest rail-head. Before the establishment of the railway in this area between 1923 and 1930, such a journey could last as long as 10 days. This transport was generally undertaken by white youths (farmers' sons) under contract. The white inhabitants played very little part in actual recovery of the fibre, being nearly always employed! in Che role of managers or over seers. issuing stores and supervising the grading and weighing of the fibres. Farming activities were and are still carried out round the mines. Since the 1939*1945 war, the demand for crocidolite has enormously increased. The lucrative claims have been bought by registered companies, othere have been abandoned. As deeper and richer deposits have been found, vertical shafts are being sunk. However, the mines with large shallow deposits are still using the inclined shaft and tunnel, and quarrying is stilt used by the few remaining smaller producers. With the building of more mills, hand cobbing has diminished. In 1915 the first crushing mill was established at Koegas in the south. This was followed by a large mill at Kuruman (operated between 1926 and 1931) where it was situated within 300 yards of the main street, close to which cobbing was also done for a few years (1927-1930). This was followed by a mill at Prieska m 1930. which was completely rebuilt in 19J7, Criquaiown had a small mill in 1928. The practice today is for one mill to serve several mines in the immediate vicinity. In the early days the manager and labourers lived within a few yards of their place of work, and even today the non-white prefers to live as close as possible, and the children play on the dumps from the mine and mill. Case Histories The following eight case histories illustrate various aspects of the disease and the different types of exposure to asbestos dust. Case 1.--B.P., a Bantu male. 36 years of age (bom 1920), was a mine labourer, and was the first case diagnosed as a mesothelioma with evidence of asbestoses. He was bom in the Kuruman district but it is not known whether he worked in the asbestos mines. He was employed on the Witwatersrand gold-mines underground for two years and in the change rooms for a further II years. A radiograph taken at a mine hospital on August IS, 1955 showed a massive right-sided pleural effusion, and 3.000 ml. of fluid was withdrawn. He was admuiei to the Witwatersrand N'ative Labour Association Hospital on August 24, 1955. and two days later aspira tion yielded 1,000 ml, of thick gelatinous pus "which could be pulled out m threads" He was treated with frequent aspirations and instillation of varidase but without improvement, and he died on February 15. 1956 (Martiny, 1956). At autopsy the right thoracic cavity was occupied by a large gelatinous tumour which displaced the mediasti num and compressed the left lung. The tumour had infiltrated the pericardium. The right lung was com pletely compressed by neoplastic tissue (Fig. 2) but the right bronchial tree did not show any evidence of a primary bronchogenic carcinoma. Histological sections of the pleural growth showed a papillary mesothelioma (Fig. 3). There was evidence of asbestosis in both lungs (Fig. 4). Case 4.--K.H., a white female, 56 years of age (bom 1898), was a social worker, who coutd only have had a short exposure to asbestos as a child and probably a further slight exposure as a young woman. She iruj have paid several short visits to the mines with her husband at a later period. She was born in Griquatowo where she lived until she was 5 years of age. Her family then moved to (Cimberiey where from 1916 to 1922 she worked as a clerk in an asbestos warehouse. Her husband owned an asbestos mine from 1933-1940. DOW 05732 <r> - -t -,y , C DIFFUSE PLEURAL MESOTHELIOMA 263 n6l99tiOXS Fsg. 2 ----Ri'iht fun of Calc I ihowing i tumour compresiing tit hint lufot&ncc- 5---Cellular structure of tumour of Cue 1. ttid conn. 40 HienniQayttrt ^ <--Section! of lun from C t chowm* aibeito! bo<)ie* *0 Htcmatoaylio an4 conn. oou 05713 264 BRITISH JOURSAL OF ISDUSTRIAL MEDICISE Fio. 7__On Mtrch J, 1956, Fi<i, 3 --On July X 1956 f u.j. S,, 6. 7. 4 --Radiograph* ihowmg development oi' tumour in C&ic 4. DOW 05714 DIFFUSE PLEURAL MESOTHELIOMA 265 CO (CD -jn cr 4-" V-C cr Fig. 9---Right lung of Case 14. Fig. 10.--Histological sections of tiimocr from Case 14. Haematoxylin and eojm. She was referred to the West End Hospital, Kimberley, July 19. 1954, because of dyspnoea and right chest discomfort of acute onset. The chest radiograph showed a locuiated pleural effusion at the right base. Straw-coloured fluid was aspirated, which on examina tion was found to be negative for .Vf, tuberculosis but contained mesotheh'al cells arranged in acini. At hnracoscopy in Johannesburg on August II, 1954 Ounour nodules were seen on the parietal pleura. Histo logical examination of the biopsy specimen showed a oewtheiioma. Deep therapy and radio-active gold sollation in September, 1955 caused initial regression of both the pleural fluid and nodules but did not arrest the Progress of the disease. She received a further course of my therapy without improvement and died in fcnuary, 1957. The liver was enlarged and nodular before death but no necropsy was done. (Figs. 5, S, 7, end 8 show the radiological development of the tumour this case.) Ctte 14.--S.S.. a Bantu male. 40 years of age (born 918), was an asbestos miner. He was bom in the Kfffuman district and as a child often played on the Hhettos dump near an asbestos mine. He subsequently orked with asbestos for several years, being employed * an asbestos mine weighing fibre from 1938-41. (n 19*1 he worked on a Witwutersrand gold mine but returned to the Kuruman district in 1943 where he worked as a farm labourer until his final illness. He was admitted to the West End Hospital on March 3. 1959. He had been well until July, 1958 when he became aware of pains in the right side of his chest. In addition he had a slightly productive cough and short ness of breath on exertion. Chest radiograph on March 9, 1959 showed obliteration of the right lung field. Asbestos bodies were found in the sputum. Needle biopsy showed histological features consistent with a mesothelioma. Autopsy,--The right chest was occupied by a huge whitish tumour which infiltrated the mediastinum, extending through the diaphragm onto the superior surface of the liver. A straw-cofoured effusion was present in the left pleural sac but the left lung was not affected. The mediastinal, cervical, and para-aortic abdominal lymph glands to the level of the renal arteries were infiltrated with tumour. In the right lung it was found that the tumour mass had infiltrated along the interlobar fissures. The lobes of the lung were compressed into three small segments (Fig. 9). On histological section a papillary type of pleural mesothelioma was seen (Fig. 10) which had infiltrated into the lung parenchyma in some areas. There was marked lymphatic spread throughout the DOW 05715 266 BRITISH JOURSAL OF 1SDVSTRIAL MEDICINE fung substance. Numerous asbestos bodies were present in the air spaces and occasional bodies and fibres were seen in the interstitial tissue. The lung itself was markedly atelectatic. Evidence of asbestosis was observed in the left lung. Case 15.--S.S.V.. a white female. 42 years of age (born 1916), is a housewife, who lived on a mine near Johannesburg and was treated for tuberculous pleurisy for six months. It was only after the histological diagnosis of a mesothelioma had been made that her previous history was obtained. In addition, it was subveauently learnt that her father (Case 22) had been born on the asbestos field and had a long mining history. The patient was born in the Griquatown district and went to school at Kuruman. She spent most of her youth in the asbestos belt. She has lived near Johannes burg for 20 years. In March, 1958 this patient developed right chest pain and rapidly increasing shortness of breath. She was admitted to hospital and 2.500 ml. of slightly blood stained fluid was removed from the right chest, A thoracoscopic examination was carried out on July 27, when a small biopsy was taken but this consisted of fibrous tissue. Bronchoscopy was normal and no neoplastic cells were observed in the bronchial washings. \f. tuberculosis was not cultured from numerous speci mens cf sputa, pleural fluid nor from the bronchial washings. She was admitted to a Johannesburg nursing home on October 16. 1958. Radiographs then showed massive thickening of the right pleura with fluid in the right chest. At thoracotomy ( Mr. Dennis Fuller) the parietal pleura was 2 cm. thick, "hard as rock" and stripped with great difficulty from the chest wall. The visceral peel stripped fairly easily from the upper lobe but separation became more difficult over the lower lobe where the peel was thicker. During the decortication a necrotic mass was found in the paren chyma of the left lower lobe. At the base, confluent with the diaphragm and perhaps the mediastinum, was a hard craggy mass which could not be removed. Histological sections of the specimen revealed an adenoid form of tubular mesothelioma. Subsequently three specimens of sputum were examined for asbestos bodies but none were found. The patient is still alive (April, I960), but her condition is deteriorating. Case 22.--D.A.B., a white male, 68 years of age, and a farmer, was the father of the previous patient. Although a diagnosis of pleural mesothelioma was made in January. 1957 it was not until July, 1959 (hat details of his exposure to asbestos was obtained. He was born in Gnquatown and went to school there. He worked in Kuruman, Postmasburg and Griquatown until the age of 62, Between 1918 and 1932 he worked as an asbestos miner underground and was mostly in charge of blasting. Between 1932 and 1944 he farmed in the district but returned to asbestos mining from (94J to 1952. In January. I957 the patient consulted his doctor be cause of left-sided chest pam with cough and slight haemoptysis. He was referred Co the Johannesburg General Hospital for investigation. The chest radio graph showed gross pleural thickening with a basal pleural effusion on the left side. He was admitted to hospital and on June 10, 1957 a thoracoscopic pleural biopsy was taken. This showed the features of a mesothelioma. On June 24. 1957 an attempt at decortication was made. The left upper lobe was stripped easily but the grossly thickened pleura was so adherent to the lower lobe that the attempt was abandoned. Sections of the pleura confirmed the diagnosis of mesothelioma. He died on December 13. 1957. Case 16.--A.N.V., a white male. 50 years of age (born 1906), was a farmer, who was born at Griquatown and went to a village school near an asbestos mine. From 1914-16 he transported asbestos in donkey waggons from Hay to Prieska, During these journeys he often slept on asbestos bags. In 1914 he worked in an asbestos mine for a month. The patient became ill in December, 1955 with vague substernal pain and dyspnoea. A left-sided pleura! effusion was diagnosed and he was referred to Mr. J. K. Bremmer in Pretoria. There was no evidence of malig nancy in bronchial and scalene biopsies. Some apical pleurat thickening and a dense homogeneous opacity at the base of the left lung was seen in the radiograph on August 3, 1956. Thoracotomy (Mr. Bremmer) in February, 1957 revealed a thickened nodular pleura with a large mass on the left diaphragm. A mesothelioma was seen on histological section. In April. 1959 he was examined by Mr. J. D. Yisser m Kimberley who found small nodules in the subcutaneous tissue over the neck and chest. A large firm mass was found in the thoracotomy wound and a mass was present in the left hypochondrium. There was generalised lymphadenopathy and numerous nodules were present on the tongue. Chest radiographs showed the left pleural cavity to be obliterated. He was one of the few cases to develop widespread metastases. A biopsy of one of the subcutaneous chest nodules showed a similar appearance to those seen in the original specimen from the pleura. The patient died on May 22. 1959. No necropsy was performed. Case 24,--D.G., a white male, 32 years of age ib*Tn 1922). by profession an accountant, was born in England but came to South Africa as an infant. He spent ho early childhood in Kuruman and left at the age of ~ He later qualified as a chartered accountant in Kimberley In 1944. at the age of 22, he had been discharged medically unfit from the army because of a left pleural effusion. Neither then nor on many subsequent occasions were acid-fast bacilli found, either in sputum or pleural fluid. His only subsequent contact with asbestos was the auditing of the books of an amosite mine in the Transvaal. In September. 1953 he complained of left-sided chest pains and shortness of breath. A radiograph of (he chcd showed flattening of the diaphragm on the left side with obliteration of the costophrenic angle and thickening -jf the oblique fissure. He was seen on numerous occasions GO --! G=> CP CP 4T QOld 05716 DIFFUSE PLEURAL MESOTHELIOMA 267 Fic. f(.--On September il, (456. (mg, 12.--On August 23. 1957. Figs, II jnU 12,---RtPiogrtpki shoeing development of tumour in Cjtse 24. n,m 1953 to 1957. A radiograph taken early in 1956 Plotted the development of a left superior mediastinal dtadow which enlarged progressively (Fig. tl) and later 'N: Je clopment of diffuse nodular pleural thickening Jn the left. During 1957 similar but less marked changes *xebped on the right side (Fig. 12). He consented to ^tipsy tn June. 1957, and. at operation, a diffuse pleural Talignancy was present. Sections of the parietal pleura only were removed and "*** histological appearances were those of a mesohelioma. He died on October 6. 1957. A necropsy was ** performed. Case 30.--O F., a white male, 50 years of age (born q99), is a storekeeper, with a history of industrial ^Posure, He has never been near the Cape Asbestos ftridl. He was born in South West Africa and lived there until Tfcage of 21, From the age of 21 to 26 he worked in a '*aory in the Cape as a boiler-maker and fitter. He "*liu!6eered the information that he had worked conhhoously with asbestos, lagging pipes and boilers. He fcftarited that the removal of asbestos lugging from old *ce$ created a very dusty atmosphere and that he would a lot at such work. Between 26 and 32 years of "fc he worked in a factory in Johannesburg in a similar ogaenv but was not exposed to such heavy dust conantsuians. For the past 20 years he had not been in "htact with asbestos. Enquiries were made from the Sfcajr. m the CaPe JS 10 the nature of the asbestos used and these have revealed that during the relevant periods Cape crocidolite was exclusively in use. He was first seen on March 14, 1959 complaining of cough, pain in the right chest and recent onset of breath lessness. Three pints of fluid had been aspirated from the pleura and cytological examination showed the presence of malignant cells. The radiograph showed marked pleural thickening and hydro-pneumothorax. On March 17, 1959, a thoracoscopy was done. The pleura felt thickened and the lung was collapsed and immobile. Several biopsies were taken. These showed the presence of a mesothelioma. The underlying lung showed the presence of asbestosis. He was treated with nitrogen mustard intra-pleurally and his condition temporarily improved. When last examined he com plained of increased breathlessness. Discussion In 1924 Robertson denied the existence of primary malignant tumours of the pleura and con sidered them to be secondary in origin. Since then, on the one hand. Willis (1948, 1953) and Smart and Hinson (1957) have supported Robertson's views, while on the other hand, primary neoplasms of this nature have been described by many authors in recent years. These include Tobiassen (1955) in Sweden. Belloni and Bovo (1957) in Italy, Godwin (1957) in the United States, and McCaughey (1958) DOW 05717 ST0565499 268 BRITISH JOL'RS'AL OF lSDL STRIAL SfEDfClSE in Britain. Evidence in support of the mesothelial origin of these tumours can be found in the tissue culture experiments of Stout and Murray 11942) and Sano. Weiss, and Gault (1950). The variegated histotogica! pattern of tumours arising from tfte mesotheiiuni of the pleura was remarked on b) Klemperer and Rabin (1931). Such a variation is appreciated when the mullipotentiality of the cells lining codomic cavities are considered. Maximow first demonstrated this feature in 1927, Novak (1931) stated that the mucosa of ail parts of the Mullerian canal and the germinal epithelium were derived from these cells. Keasbey (1947) showed that in the embryo, the mesonephros, metanephros, Wolffian body, genital ridge, and all dependent urogenital structures are derived from the mesotheiium. Campbell 11950) considered the presence of both epithelial and mesenchymal elements a major diagnostic feature. In describing the histology of 11 of these tumours McCaughey (19 58) demonstrated that either the epithelial or the mesenchymal element might predominate. He classified his cases into the following four groups: Tumours of epithelial character: tumours of mesenchymal type: tumours of mixed type: and tumours of anaplastic type. Using McCiughey's classification on our series of tumours, the majority are. as in Campbell's series, of the mixed type. Of the remainder, a few' showed the papillary tubular structure of the "tumours of epithelial character", and there were several of the anaplastic type. One case had the appearances of a "tumour of mesenchymal type" but even in this case primitive tubular structures were seen. Apart from the original case all the histological diagnoses were made on biopsy material. Three of these biopsy findings were confirmed at necropsy. In the remainder, we have had to rely on clinical and radiological examination to exclude other primary sites of malignancy. Following the work of Meyer and Chaffee (1939, 1940), the possibility of demonstrating hyaluronic acid in these tumours both chemically and histochemically has been considered as a diagnostic aid. Both these investigations are still in an early stage (Harington, 1959). Preliminary results of the histochemical experi ments show that there is metachromatic substance in both the stroma and glandular structures of the tumours. This metachromasia can be reversed by incubation with testicular hyaturonidase. This material stains strongly with Hale's (1946) colloidal iron method. The periodic acid SchifT technique has given variable reactions. These results are not specific for hyaluronic acid but ate strongly suggestive of its presence. The amount of metachromatic substance in these tumours has varied considerably. This we think is partly due to the fact that until recently we had not appreciated the solubility of hyaluronic acid in aqueous media and the majority of these turnout were fixed in l0i formol-saline. Further, Lison (1953) states that the metachromasia of hyaluronic acid is optimal at a concentration of 1 10,000 and gradually decreases at higher levels. When the high concentrations that Meyer and Chaffee (1939. 1940i found in their tumours are considered, this variation in metachromatic properties seems to have been partially explained. In addition, with the greai differences in the histology of the various lesions, it would be logical to expect certain tumours with a marked adenoid appearance to secrete more than those with an essentially non-glandular structure. Three of the five autopsies performed showed evidence of peritoneal metastases. In the other two. intra-thoracic spread was observed, in one case to the other lung and chest wall, and in the second to the mediastinal lymph glands and pericardium. Biop>> evidence of metastases has been obtained in two cases, one from the omentum and the other from the subcutaneous tissue of the chest wail; while a (bird patient developed an implantation nodute in the thoracotomy scar which showed a similar appearance to that of the previous biopsy specimen. The first recorded case of carcinoma of the lung associated with asbestos was described by Lynch and Smith (1935). By 1955, according to Doll, 4 total of 61 cases had been reported. Included m these cases was one mesothelioma. Cartier (1953' mentioned two cases of diffuse mesothelioma from a Canadian chrysotile mine. A further three cases were described by van der Schoot (1958). Un fortunately no indication is given in the literature regarding the type of asbestos to which (he majoruy of recorded cases of carcinoma were exposed. However, discussion with management and medical officers of two of the factories, in which the majority of the cases reported in Britain were employed, suggests that most of these workers were handling chrysotile asbestos (Wagner. 1958). The possible that some of these people may also have been exposed to crocidolite dust cannot be excluded. Attempts to produce tumours In experimental animals by exposing them to asbestos dust have be9 made. Vorwald and Karr (1938) were unsuccessful Lynch. Mclvcr, and Cain (1957) succeeded in pro ducing tumours in mice, but lung neoplasms m to control animals were far too numerous for the results to be considered significant. On the othet hand Schmahl (1958) working in Druckre' * laboratory has been able to produce sarcomas t* rats. This has occurred after subcutaneous and *?.:* vV* ULl DIFFUSE PLEURAL MESOTHELIOMA 269 .ntraperitoneal inoculation of both asbestos fibres (Table 3). Eighteen of these 25 cases were born in ir.J Just. He states that "mineral asbestos" was the vicinity of the mines and two arrived in the used but does not name the variety. district as infants. Of these IS people U admit In our series of mesocheliomata, histological definite childhood exposure to the dust and two I evidence of asbestosis has been observed in eight others were exposed industrially in later life. In jf the 10 cases in which lung parenchyma was in addition two patients with childhood exposure later cluded in the specimen examined. No lung tissue worked in the asbestos mines. Three cases arrived as present in the biopsies from the remaining in the region at an older age but were employed either 23 cases. It was only in the four cases that came to on the mines or in transporting asbestos. A further necropsy that large sections of the lung tissue were three of these 25 cases have had industrial exposure, available for examination, (n all of these specimens and in only one case do the relatives deny any evidence of asbestosis was found. exposure to asbestos dust. At first it was thought that the presence of The four industrial cases are significant. Two j numerous asbestos bodies, fragments of fibre, and of the patients were lagging locomotive boilers and ^ dust immediately below the pleural elastic laminae one was lagging steam pipes. A man. who was an in these specimens, might have been significant in upholsterer by trade, was employed in making (the pathogenesis of the tumours. However, it is more probable that this distribution is a result of the fire-proof clothing from 1939-1945. As far as can be ascertained these people were never in the , marked atelectasis. Similar features have beenGriqualand district. These findings tend to add observed in atelectatic lungs of asbestos miners in support to asbestos being the common factor in the . *hich no mesotheliomas have been observed. development of these tumours, and to counter the I Pleural fibrosis has been a common finding in suggestion that there may be some other environ | -ases of asbestosis and in some cases large pleural mental cause in the region of Griqualand West. plaques measuring up to 10 cm. in thickness have If asbestos dust is a factor in the occurrence of been seen. These plaques, which were first described these tumours, similar cases might have been ex py Gloyne (1933). have been observed following pected from the neighbourhood of the Transvaal posure to both amosite and crocidolite asbestos asbestos mines in the Petersburg and Lydenburg dtots. In these cases of benign pleural thickening districts, where crocidolite and amosite asbestos is 30 evidence of stromal metachromasia has been mined. According to Vermaas (1952), crocidolite * fcserved. and amosite occur in the same seams in the Peters t a!! the histological sections of pleura examined burg district. As can be seen from Table I. amosite * the cases of these mesotheliomas and in more is similar in composition to crocidolite. In the past 100 cases of asbestosis. no asbestos bodies. four years the lungs of 24 cases of asbestosis from /*prcna of fibres, or dust have been observed the Lydenburg district have been examined. In f pleural elastic laminae. this material two cases of adeno-carcinoma have \ **)re* patients from the Kuruman district, with been observed. The one was in a white miner with Tjj43* and radiological features consistent with Ia7*e of diffuse pleural mesothelioma had markedly "formal cells in the pleural fluid. These cells no specific features to distinguish them from 19 years' service, who had an adeno-carcinoma arising from a bronchus. The other case was a Bantu miner who had a peripheral tumour. No service record was obtainable in this case. Only f originating in secondary malignant pleural one case of asbestosis. has been received from the i ,*j**its oor from the grossly atypical cells some- Petersburg area. All, of these men were actually f ***> In non-malignant pleural effusions. As employed on the mines at the time of death, the :jfapsy or autopsy examinations were obtained in majority having had a relatively short service. Our cases they have been excluded from the series. findings suggest that mesothelioma occurs 20 to 40 Pathological evidence for associating these years or more after exposure to dust. Until com un with asbestos exposure is not conclusive. paratively recently the mining in the Transvaal ^PJ^viously stated, only in eight of the 33 cases has has been on a small scale, and there were no settle ^*~nce of asbestos been demonstrated. Of these. ments in the vicinity of the mines. adefinite mining history and one had been The lungs of 20 asbestos miners from the Cape to asbestos while lagging steam pipes. The Asbestos Field have been examined, in whom no , 0416 born in the Kuruman district and mesothelioma was observed. One autopsy specimen else is known of him. until his arrival at a consisting of three fragments of lung showed atersrand gold-mine at the age of 23. fn the asbestosis and an adeno-carcinoma. Radiological Totting 25 cases we can only present circum* features of asbestosis have been observed in many nUal evidence of exposure to asbestos dust miners from this region, without any suggestion of / DOU 05719 BRITISH JOURSAL OF INDUSTRIAL MEDICINE Table 3 DIFFUSE PLEURAL MESOTHELIOMA: ASSOCIATION 1 -ITH ASBESTOS C/5 -- 1 0 :n CT'l CA 01 o - Dc.-Pan. -,.r\ Seerc i9:o X 19! J 1898 1910 1909 1918 1916 1896 1911 1920 i9:: 1906 1895 1904 1899 190 1909 (90 1908 1890 KEYS: Column 4-- Race: W - White MXD - Mixed (Coloured! B - 8amu Other history unknown until came t< wjtersrand at the age of 23 Mined asbestos from 1930-33; left a Lived whole life in a location near att asbestos mill ____ ..i asbestos fields until the age of 3: worked in asbestos warehouse 1916-20 Spent all his working life m the vicinity of mines Lived all her life in the vicinity of mines Lived all bis life in the vicinity of mines: worked From the age of 24 lived in a village serving local mines: often visited mines: watched cobbing outside houses Whole life spent near mines, digging wells Lived at the mine from age 7-17 years: clayed on dumps and in mine as a boy: returned to assist from age :t-25 Whole life spent near mines: miner 1931-33 Lived near mines until the age of 17: miner 1927 Lived near mine until the age of 21: played with fibre as a child Whole life spent near mines: miner 1938-41; played on dumps as a child Daughter of Case 22: lived at mine until age of 20: went to school near cobbing sheds Went to school near mines: transported asbestos 1914-16 Lived on maior wagon route till age of IS; several subsequent visits Whole life in the vicinity of the mines; miner 1945-58 Family lived at mine; miner 1938-1959 Spent whole life in village on wagon route to Kimberley Lived m the vicinity of mines until the age of 16; often on dumps as a child Whole life in the vicinity of the mines; miner 1913-32. and 1945-52 Lived in the vicimiv of the mines until the age of 30 Lived in the vicinity of a mill from the age of 1-7; plaved on the dumps as a child Lived in a mining area from the age of 10 to 18 vears: after 1918 spent whole life in same town as Case 24 Mined 4nd transported asbestos from 1929-33 Born m North West Cape; transported asbestos from 1920-24 Lived whole life on farm in mining area from the age of 12: transported asbestos 1916-21 Maintaining locomotive boilers 1931-45 Maintaining steam pipes in explosive factories 1930-40 Worked as fitter on railways, maintaining locomotive boilers, dates unknown Making asbestos blankets for the Air Force 1939-4} No history of exposure to asbestos Column 6 - - Born on asbestos fields - - Not born on asbestos fields 0 w Unknown Column 9-- - -- Necropsy done -- -- Necropsy not done - Only small fragment* of parietal pleura submitted at autopsy for histological . 12 Ge. - V - ; -V IV`V| pe 'w . 1 iru Oenle. A --K pm. i x Pneum v .> 1 .1. Lonuon. | rv jui> (i9 Lision Si * H. V. Hempl V 1 **risoo of *1 ^-^G-Gr ` . ^euihted .> ***** the Ac 1 N. wordc kkalariof Petrov ic. . . *hsucaj Sr ` ft. wc ' J^WdMeth Broncho, , i Uatha 'jL S****ement tumour formation. However, pleural involvement has been a common finding in these cases (Hurwitz, 1959). It is possible that there has not been a sufficient lapse of time after exposure for tumour development in these cases. Further, the factor of individual susceptibility must also sidered. We wish to record the great assistance tha^ received in this investigation from the ^ mioners of the Griquaiand West Distr.v DOW 05720 DIFFUSE PLEURAL MESOTHELIOMA 271 Tirade surgeons ami pathologists in Johannesburg, Pretoria, and Durban. We thank the Secretary of Health for permission to Referestfs V.loni. G.. and Bovo. G. (1957). Acta med. potav . 17. 367. , .mpbcll. W N. (19!0). Amtr. J. Pam.. 26. 47J. ' artier. 9 (1952). Arch. indusir. 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Path.. t4. 49. Wagner. J. C. (1958). Memorandum on Pneumoconiosis Research ii Europe. Submitted 10 the C.S l.R. Willis. R. A. (1948. 1st ed. and 1953). Pathology of Tumours Butteruorth. London. Addendum By the end of June I960, a total of 47 cases of mesothelioma had been identified. In 45 of these a possible association with exposure to crocidolite has been established. In one case a mesothelioma of the peritoneum was present. THE JULY (1960) ISSUE The July (I960) issue contains the following papers:-- Dw*npression Sickness during Construction of the Dartford Tunnel. By F. Campbell Golding, P. Griffiths, H. V. Hempieman, W. D. M. Paton, and D. N. Walder. ' Gaoparison of the ** High-altitude " and " High-pressure " Syndromes of Decompression Sickness. By M. de G. Gribble. Poisoning Caused by the Use of Chemical Paint Removers Containing Methylene Chloride in HI-ventilated Rooms Heated by Kerosene Stoves. By W. B. Gerrilsen and C. H. Buschmann. ' $**dy on the Acute Toxicity of the Tri-aryl Phosphates Used as Plasticizers. By H. F. Bondy, E. J. Field, A. N. Worden, and J. P. W. Hughes. Inhalation of CaNa2E.D.T.A. (Mosatil) by Workers Constantly Exposed to Lead Poisoning. By Li- Petrovic, M. Stankovid. M. Saviievii, and D. Poleti. ' *0cbemical Study of the Urinary Protein of Men Exposed to Metallic Mercury. By J. C. Smith and Agnes R. Wells. ' "**pUfied Method for the Estimation of Nickel in Urine. By J. Gwynne Morgan. ^**1* Bronchographic, Radiological, and Physiological Observations in Ten Cases of Asbestosis. By . L. Leathart. Measurement of Occupational Mortality. F. D. K. Liddell. %UTV*t*ons on the Occupational Life History of the Coal Face Worker at Two Collieries. By O. P. Edmonds ^^D.S. Kerr. ,'**Mmnt of Electroenccphalographic Changes and Memory Disturbances in Acute intoxications with `duMrial Poisons. By B. Chalupa. J. Synkova, and M. Seviik. 7* **riews. number of copies are still available and may be obtained from the Publishing Manager. British `^Association. Tavistock Square. W.C.I, price I7r. 6J. DOW 2 0 S J 'J i;0 1 S c