Document ymEenpjyQwxypd2zqy9eGOOB2

V 'A PLAINTIFF'S EXHIBIT I0ct) 5/. /. industr. Med., I960, 17, 260.- 271 DIFFUSE PLEURAL MESOTHELIOMA AND ASBESTOS EXPOSURE IN THE NORTH WESTERN C.APE PROVINCE BY J. C. WAGNER, C. A. SLEGGS, and PAUL MARCHAND from the Pathology Division, Pneumoconiosis Research Unit of the Councilfor Scientific amt Imlustrial Research, Johannesburg, Wat End Hospital, Kimberley, ami the Department of Thoracic Surgery, University of the Witwatersrami anti Johannesburg General Hospital (MCHVCO KM PUIUCATTOIj AFK1L 24, I960) Primary malignant tumours of the pleura are uncommon. Thirty-three eases (22, males, 11 females, ages 31 to 68) of diffuse pleural mesothelioma are described; ail 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 the lungs of the first case (Case I), and secondly. uncommon tumour, in the last four yean we have 10 of the cases came from a hospital to which seen 33 tustologwaily proven cases: 2lpf these had suspected cases of tuberculosis were referred from a some association with the Cape asbestos held and large asbestos mining area. This hypothesis could /four cases had been exposed to asbestos in industry. not be supported at once from the original histories " The tumour is rarely encountered elsewhere in obtained from the patients, for they included house South Africa. During the past five yean, with the wives. domestic servants, cattle herders, farmers, a exception of the present series, no neoplasm of this water bailiff, an insurance agent, and an accountant, nature has bean diagnosed amongst 10,000 lungs none of whom were working on the asbestos mines examined at the Pneumoconiosis Bureau in at the time. We therefore undertook a detailed Johannesburg, or in the Pathology Department of investigation of their past occupation and place of the South African Institute for Medical Research. residence; and the association with asbestos ex Higginson and Oettle (1937) did not observe a single posure was discovered. The cases are summarized case in their survey of malignant tumours occurring in Table 3. Previous biopsy specimcss were re in the Bantu and Cape Coloured population of examined. and new cases diagnosed, including Johannesburg and the North Eastern Transvaal. asbestos miners. In only one case do the relatives Our lint nagopsy specimen of pleural meso deny that the patient either visited the asbestos thelioma with asbestosii was examined at the mines or was exposed to asbestos. Pneumoconiosis Research Unit in February, 1936 This is a preliminary publication and die problem (Case 1). During the early months of that year, is being intensively investigated. one of us (CJLS.) in the Northern Cape, treated six patients with gross pleural thickening. Pleural O biopsies from two of them showed the features of The Asbestos Area of the Na.-;u-V.';st Capa mesothelioma. In the ensuing two yean, eight According to Hall (1930) asbestos was discovered further cases were found from this region and five by Lichcnstein near Prieska during his travsis be from elsewhere in the Union. During this period tween 1803 and 1305. Siam tksa it 1ms been GA.S. had become perturbed at the number of established that the asbestos deposits i.;:a.-.d. from these unusual tumours occurring amongst his 20 miles south of Prieska, northwards through the patients, and stimulated an investigation. At this western part of the magisterial district of Hay, to stage there were two reasons to suggest that asbestos the eastern portion of the magisterial district of might be implicated. First, asbestos was found in Postmasburg and finally, to the western area of the 260 PLAINTIFFS EXHIBIT yjy-oreq-?? r DIFFUSE PLEURAL MESOTHEUOMA 261 moiapo ftu. I.--Mat r <lri<mli< MMM IUl ana of Kuruman (Fig. I). These deposits occur the slopes of 3 range of hills covering an area of pproximately 8.000 square mites. Known as the sbestns Mountains'*, these hills extend more or longitudinally between 22*30 and 23" E. The ole area is semi-arid, sparsely populated, and. from mining, cattle ranching is the only aponant occupation. In the Kuruman area several rge tracts of land in or abutting on these mountains been reserved for the aboriginal inhabitants here whites may only reside in the immediate unity of the mines. (The type .>f asbestos mined throughout this area jcroctdolite. better known as Cape Blue Asbestos, s chemical analysis of the fibre is given in Table 1. olite is the fibrous form of riebeckite and all ;es of transformation from a massive riebeckite ek through lamellar riebeckite to asbeauform cidoliie occur in this region. Magnetite is quemiy associated with the erocidoiite (Vermaas, |J2). (Mining of asbestos first began in the Prieska anct in lsui and gradually spread northwards. In I MW production hud begun in the Kuruman dis trict. Between Idlf* and IMS a large number of claims were taken up. This northward trend has continued and in about I 50 mining started at Pomfret near the Bcchuanaiand border tTable 2). Initially the ore was quarried in numerous small open cast workings. This was followed gradually Twau i CHEMICAL ANALYSES OF CXOCiOOLITE AND AMOSITE (from Vgn ii, 1952a. 510, AI.0, ft4* M0 CtO w H.0H<0 * Tib, MM) F C/eoeolu* 51 94 o:o IS M l*J4 0l--J1T9 4*07 004 0)1 :ji " AmMlM 49*47 0*4) 4*15 35*45 4-37 0*52 002 >20 007 Ml >Zi 0*41 >41 Tout 1007) 100-44 0 f f ar c j r* 262 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Tails 2 POPULATION Or TNI MaCISTUIaL DISTRICTS IN WHICH THE aSOESTOS FIELDS ARE SITUATED (lakai from Uawa Cmwi 1911. uwt I9J11 OUwwi Wll Kmum H*y Hwmlwi 1 MyMwa 1921 > Whim 1 Non*wfcu Tout i J.4M i .w i 1.20* : on ' IfctfC i :mu i 1 *.* Mu i uju i IikJuM im tA Hr Oifttria ; White* J.J6I MU 2.7*? 4.M7 HopuiAUM 1*51 NfilMliUUI I0.M7 ZJ.TN MJJ 21.01* , ! Toil! 14.204 1S.S91 11242 15.90* by u typo of shallow mining: inclined shafting be came more common after 1930. According lo hrood (1912). the quarrying was a family atrair 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 panicles 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 the role of managers or over seers. issuing stores and supervising the grading and weighing of the fibres. Farming activities ware and are still carried out round the mines. Since the 1939*1943 war, the demand for erocido* lite has enormously increased. The lucrative claims have been bought by registered companies, others 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 still 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 lCuruman (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 yean (1927-1930). This was followed by a mill at Prisska in 1930, which was completely rebuilt in 1957. Griquatowu 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 dose us possible, and the children play on the dumps from the mine und null. Cum Histories The following eight cue histories illustrate various sspoets of the iliicaur and the diiferent types of exposure to asbestos dust. Case U--S.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 asheliosis. Hu was born in the Kuruman district but it is not known whether he worked in the asbestos mines. He was employed on the Witwatersnnd gold-mines underground for two years and in the change rooms for a further 11 years. A radiograph taken at a mine hospital on August IS. 1935 showed a massive right-sided pleural effusion, and 3,000 mL of fluid was withdrawn. He was admitted to the Witwatersrand Mauve Labour Association Hospital on August 24, 1935, and two days lster aspira tion yielded 1,000 mL of thick gelatinous pus "which could be pulled out ia threads'*. He was treated with frequent aspirations and instillation of veridsce 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 (rig. 2) but the right bronchial tree did not show any evidence of a primary bronehogeaic carcinoma. Hit:'!s~oal sootier.: of the pleural growth showed a papilla-/ .-uoiathaliams (Fig. 3). There was evidence of asacsiosis in both lungs (Fig. 4). Case "L--K.H., a white fentuia, 55 years of age (bom 1893), was a social worker, who could only have had a short exposure to asbestos ss a child asd probably a. further slight exposure as a young woman. She may have paid several short visits to the mines v.lut liar husband at a later period. Shs was born in G.-lquatov/a where she lived t: she was J years of age. Ilsr family titan may; _ KlT.borlsy where from 1516 to 1922 v.c.-lar.t aa a dark in aa asbestos warehouse, l-ls.-l. .-.bc .vi asba::os mhia from 19jj-i540. DIFFUSE 'PLEURAL MESOTHELIOMA 263 **b 264 BRITISH JOURSM. OF INDUSTRIAL .MEDICINF r C7 ' m/' PW.J.Il.l-'U V- r r OwJuiyT. IJJ. l i !l !: : ! vJ FtO. 7,--O* Much J,19H. Fic. I.--On July ). I6 Fig*. 5. i, 7. an4 1.--Hauu\urph *feowui| 4**lopjitA( oC tumaur ia Cam *. r^ jr^ s d jrrjtf! DIFFUSE PLEURAL MESOTHELIOMA \ laS i <4** vx iV..-v..*' * i!f y ' 'v>- / I V c,.-. t IT; . . >. !*: - x -A V V fm. lnifU Cam I*. hM) to. Hietitltntwdi sv;hm She wax referred u> (ha West lind I lospnal. Kimtwrrtoy, July II. 1154. because of dyspnoea and right chest liwumfort of acute onset. fhc chew radiograph unwed a loculuted pleural effusion .11 the riant base. jtraw<eoloorcd tlutd wax aspirated, which un cvamina* an was found to bit negative for M. luhrnulusi* but ntsined mcsothelial cells arranged in acini. At araeoseopy in Johannesburg on August 11. 1154 nour nodules were seen on the parietal pleura. I lisco- al examination of die biopsy specimen showed a olhelioma. Deep therapy and radio-active gold ..dilation in September. 1155 caused initial regression of ^th the pleural fluid and nodules hut did not arrest the pgress of the disease. She received a further course of ay therapv without improvement and died in nuary. HJ7. Tlte liver was enlarged and nodular fore death out no necropsy was done. <l;i|ts. 2, 4. 7. 3 show the radiological development ot the tumour atm case.) 14. S.S.. a Bantu male. 40 years of age (born Ml. was .in asbestos miner. He was born in the. man district and as a child often played on the vtos dump near an asbestos mine. He subsequently 'led with asbestos for several years, being employed an asbestos mine weighing fibre from 1138*41. In he worked on a Witwatenrand gold mine but returned to the Kuru/nan district in l*M.7 where he worked as .t farm labourer until his final illness. He ssas admitted to (he West !:.nd Hospital on March }. 1151. lie had been well until July, 1158 vsnert he hecantc aware of pains in the right side of his chest. In addition he had a slightly productive cough and short* nuis of breath on exertion. Chest radiograph on March 1. 1151 showed obliteration of the right lung held. Asbestos bodies were found in the sputum. Needle biopsy showed histological features consistent with a mesothelioma. Autopsy. Thu right Chest was occupied hy a huge whitish tumour which infiltrated the mediastinum, extending through the diaphragm onto the superior surface of the liver. A straw-coloured elfttsioa was present in (he left pleural sue hut the left lung -u. not elfected. The mediastinal, cervical, and para-anrue .ibtlommal lymph glands to the level of the renal arteries were infiltrated with tumour. In the right lung it was found (fiat the tumour mass had infiltrated along the interlobar fissures. The lobes of the lung svere compressed into three small segments (Fig. 11. On htst.m'gicil section a papillary type of pleural mesothelioma was seen (Tig. 10) which had infiltrated mu the lung parer.hyma in some areas. There wa. marked lymphatic spread throughout the 266 BRITISH JOURSAl. OF ISDUSTRlAL UEMCISE lung substance. Numerous uslsesto- bodies were present in the air spaces and occasional bodies end nhres were seen in the interstitial tissue. The lung itself was markedly atelectatic. Evidence of asbcstosis was observed in the left lung. Cose 15.--&S.V., a white female. *2 years of age (bom 1916), is a housewife, who lived on a mine near Johannesburg and was treated for tubereul...s pleurisy for six months. It was only after the histological diagnosis of a mesothelioma had been made tltut iter previous history was obtained. In addition, it was subseuuentty learnt that Iter father (Case 22) had Seen horn on the asbestos Held and had a long mining history. Tlw patient was horn in tlte tiri|ualown district and went to school at Kuniman. She spent most of her youth in the asbestos belt. She has lived near Johannes* hurg for 20 years. In March. I9SX this patient developed right cncM pain and rapidly increasing shortness of breath. Site was admitted to hospital and 2J00 ml. of slightly blood stained lluid wus removed front tlw right chest. A ihorucosenpie examination was earned nut 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 w_shmgs. W. iuherrulu.ii* was not cultured from numerous .speci mens of sputa, pleural fluid mu from the bronchial washings. She was admitted to a Juiunnvsbitrg nursing home on October 16, 1958. Radiogrjphs 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 ruck** and stripped with great difficulty from the chest wall. The visceral peel stripped fairly easily from the upper lobe but separation became more dirtied: 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 couid not be removed. Histological lections 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.8., 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, IV57 it was not until July, 1959 that details of his exposure to asbestos was obtained. He was bom in Griquatown and went to school there. He worked in Kurumxn, Posimasburg 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 19J2 and 1944 he farmed in the-district but returned to asbestos mining from 1945 to 1952. In January, 1957 the patient consulted his doctor be cause of left-sided chest pain with cough and slight hacnvpi)M. lie wa icfsr.cd to the General Hospital foi imcsiigaiinn. The chest r.'.i.ojraph showed gross pleural thickening wun a Local pleural effusion on the left sale. He was admitted to hospital and on Jane 10. 1457 a thoracoscopic pleural biopsy was taker.. This showed the features of a meso thelioma. On June 24, 195" 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 tlte attempt was abandoned. Sections of the pleura continued the diagnosis of mewittvelioina. He died on December 13. 1957. Case 16. A.N.V.. a white male, 50 years of age .horn l'M6). was a farmer, who was horn at (iriuuatown at:.! went to a village school near an ads.-dnx mine. From 1914-16 he transported ashvsto* tti donkey wapgons from Hay to Prieska. During titesu journeys he often slept on asbestos batpc In 1914 he worked in an asbestos mine for a month. The p.nwni became ill in December, 1955 with vag-ac substemul pain and dyspnoea. A left-sided pleural clfusion was diagtu>seU and he was referred to Mr. J. K. tlrcmmcr in Pretoria. There was no evidence of malig nancy in bronchial and scalene biopsies, borne apical pleural :hi*k*ni: t and a dense homogeneous opacity at the base of the left Umg was -uen in the radiograph on August J. 1956. Thoracotomy (Mr. llremmef) in February. 1957 revealed a thickened nodular pleura with aCirge muss on the left diaphragm. A mesothelioma was seen on histological section. In April. 1959 he was examined by Mr. J. D. Visser in 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 hypochondrtum. There was generalised lymphadcnopathy and numerous nodules were present on the tongue. Chest radiographs showed die left pleural cavity to be obliterated. He was one of .he few eases to develop widespread metaxtase*. A biopsy of one of the suoeutancu... 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.--O.G- a white male. 32 years of age (bom 1922), by profession an accountant, was bom in England but came to South Africa as an infant. He spent h-.s early childhood in Kuruman and left at the age of 7. He later qualified as a eharu.ee aecnumaat in Kimberley. In 1944, at the age of 22, he had been discharged rr.edicaiiy unfit from the army because of a left pieurai effusion. Neither then nor on many subsequent occasions were acid-fast bacilli found, cither in sputum or ;::.u.-al f.uid. His only subsequent contact with asbestos was the auditing of :..c cooks of an amositc mine in ate Transvaal. In September. 1953 he complained of left-,.Led cheat pains and short.- of breath. A radiograph of ths cats; showed flattesting ::.i t v ...... m on the left side with obliteration of the .. -..e.-iic angle and thickening of the oblique fissure. Hu was seen on numerous occat.cr.s DIFFUSE PLEURAL MESOT11EL!0/. i o:.-- i i t i i; *k i no. II.--Oa >!>>> II. 19M. Fto. 11.^On Ausuh 11. II>1. from 1953 to 1937. A radiograph taken early in 1956 showed tho development of a left superior mediastinal shadow which enlarged progressively (Pig. II) and later the development of diffuse nodular pleural thickening on the left. During 1937 similar but lets marked changes developed on the right side (Fig. 12). He consented to biopsy in June, 1937, and, at operation, a diffuse pleural malignancy was present. Sections of the pariesal pleura only were removed and the histological appearances were those of a meso thelioma. He died on October 6, 1937. A necropsy was not performed. Case 30.--G.F.. a white male, 30 years of age (bom 1909), is a storekeeper, with a history of industrial exposure. He has never been near the Cape Asbestos Fields. He was bom in South West Africa and lived there until the ags of 21. From the age of 21 to 26 ht worked in a factory in the Cape as a boiler-maker and fitter. He voluotcercd the information that he had worked con tinuously with asbestos, lagging pipes and boilers. He remarked that the removal of asbestos lagging from old pipes created a very dusty atmosphere and that he would cough a lot at such work. Between 26 and 32 years of a3i he worked in a factory in Johannesburg in a similar capacity but was not exposed to such heavy dust con centrations. For the past 20 years he had not been in contact with asbestos. Enquiries were made from the factory in the Cape as is the nature of the asbestos used ) and those have revealed that during the relevant periods Cape croddolix was exclusively in use. He was first seen on March 14. 1939 complaining of cough, puin in the right chest and recent onset of breath lessness. Three pints of fluid had been aspirated from the pleura and cytologies! examination showed the presence of malignant cells. The radiograph showed marked pleural thickening and hydro-pneumothora.v. On March 17, 1939, a thoracoscopy was done. Thu pleura felt thickened and the lung was collapsed and immobile. Several biopsies wen taken. These showed the presence of a mesothelioma. Toe underlying lung showed the presence of asbestosis. He was treated with nitrogen mustard intra-pieurally 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. Wiiiis (1943, 1933) and Smart and Hinson (1937) have supported Robcitson'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, Bcilor.i and 3ovo 09571 in Italy. Godwin (1957) in the United States, and McCsughcy $ ** V y. wVv \ .\> , '^ \ \ :&t> BRITISH JOURNAL OF INDUSTRIAL '.IF.DICINU in Britain. Evidence in support of the moothslial The amount of mcuchromatic substanuc in these origin of these tumours can be found in the tissue tumours has varied considerably. This we think is culture experiments of Stout and Murray (1942) ana partly due to the fact that until recently hud not Suno, Weiss, and Gault (1950). appreciated the solubility of hyaluronic acid in The variegated histological pattern of tumours aqueous media and the majority of these tumours / arising from the mesothelium of the pleura was were fixed in 10i formol-salir.e. Further. Lison remarked on by Klemperer and Rabin (1931). Such (1953) states that the metachromasia of hyaluronic a variation is appreciated when the multipotcntiality acid is optimal at a concentration of I/IO.CCO and of the cells lining cociomic cavities are considered. gradually decreases at higher levels. When the high Maximow first demonstrated this feature in 1927. concentrations that Meyer and Chaffee (1939, 1940) Novak (1931) stated that the mucosa of all parts of found in their tumours arc considered, this variation the MOllcrian canal and the germinal epithelium in metachromatic properties seems to have been were derived from these cells. Kcasbey (1947) partially explained. In addition, with the great showed that in the embryo, the mesonephros, diiferenecs in the histology of the various lesions, it metanephros, Wolffian body, genital ridge, and all would be logical to expect certain tumours with a dependent urogenital structures are derived from marked adenoid appearance to secrete more than the mesothelium. those with an essentially aon-glandular structure. Campbell (1950) considered the presence of both Three of the live autopsies performed showed epithelial and mesenchymal elements a major evidence of peritoneal metastasis. In the other two. diagnostic feature. In describing the histology of intra-thoracic spread was observed, in one case to the 11 of these tumours McCaughcy (1958) demonstrated other lung and chest wall, and in the second to the that either the epithelial or the mesenchymal element mediastinal lymph glands and pericardium. Biopsy might predominate. He classified his cases into the evidence of mciaM.nw.s has been obtained in two following four groups; Tumours of epithelial cases, one from the omentum and the other from the character: tumours of mesenchymal type: tumours subcutaneous tissue of the chest wall: while a third of mixed type: and tumours of anaplastic type. patient developed an implantation nudu.c m the Using McCaughey's dassiiication on our scries thoracotomy scar which showed a similar appearance of tumours, the majority are. as in Cumpocil's series, to that of the previous biopsy specimen. of the mixed type. Of the remainder, a few showed The first recorded case of carcinoma of the lung the papillary, tubular structure of the "tumours of associated with asbestos was described by Lynch epithelial character", and there were several of the and Smith (1935). By 1955, according to Doll, a anaplastic type. One case had the appearances of a total of 61 cases had been reported. Included in "tumour of mesenchymal type" but even in this case these cases was one mesothelioma. Cartier (1952.3 primitive tubular structures were seer.. mentioned two cases of diffuse mesothelioma from a Apart from the original case all the histological Canadian chr rf.ie mine. A further three cases diagnoses were made on biopsy material. Throe of were describe., by van dar School (!9Ja). Un these biopsy findings were confirmed at necropsy. fortunately ::j indication is given m the literature In the remainder, we have had to rely on clinical regarding the type of asbestos to which the .aajority and radiological examination to exclude other of recorded esses 'of carcinoma were exposed. primary sites of malignancy. ,However, discussion -it' management and medical Following the work of V.cycr and Chaffee (i 959,, officers of two of the ries, in which the majority 1940). the possibility of demonstrating hyaluronic' of the cases report;.. Britain were employed, acid in these tumours both chemically'and histo- suggests that most of these workers were handling chemically has been considered as a diagnostic aid. vchrysotiic_a*bestos (Wagner. 1958;. The possibility Both these investigations are still in an early stage tnaT--SSm: .ese people may also have teen (Harington. 1959). exposed tn c. ...doiitu dust cannot be excluded. Preliminary results of the histochemicai experi Attempts to pruutu- tumours in experimental ments -.how that there is metachromatic substance animals by exposing the..; to asbestos dust have been in both the stroma and glandular structures of the made. Vorv.-uiu an- i-ierr (193.S', ware unsuccessful. tumours. This metachromasia can be reversed by Lynch, Mcivcr, and Cuir. (!9a7; ...acceded tr. pro incubation with testicular hyaluronidase. This ducing tumours in mice, but lung r.eopLs.r.s m his material stains strongly"wiiTTHjQe's (794$) colloidal control animals were far too numerous .'a.- the iron method. The periodic acid Schiflf technique results to be considered significant. On the o.r.er has given variable reactions. These results arc not hand Schmihl (19:':., v.orkinj m Dr.::\ ray's specific for hyaluronic acid but are strongly laboratory' has been able to produce saracr.._s ,r. suggestive of its presence. rata. 71.B has occurred after subcutaneous and DIFFUSE PLEURAL MESOTHELIOMA 269 i .peritoneal inoculation of both asbestos fibres .1 bust. Me states that "mineral asbestos'' was .,ed but dues not name the variety. In our series of mesothcliomata. histological evidence of asbcsiosis has been observed in eight of the 10. cases in which lung parenchyma was in* eluded in the specimen examined. No lung tissue was present in the biopsies from the remaining 23 cases. It was only in the four cases that came to necropsy that large sections of the lung tissue were available for examination. In all of these specimens evidence of asbe*to*is was found. At first it was thought that the presence of numerous asbestos bodies, fragments of fibre, and dust immediately below the pleural elastic laminae in these sontimeiu. might have been significant in the pathogenous of the tumours. However, it is more probable that this distribution is a result of the marked atelectasis. Similar features have been observed in atelectatic lungs of asbestos miners in which no mesotheliomas have been observed. Pleural fibrosis has been a common finding in cases of asbcsiosis and in some cases large pleural plauucs measuring up to 1-0 cm. in thickness have been seen. These plaques, which were ftist described by Gloync (1933). have been observed following exposure to both amesite and crocidoiite asbestos dusts. In these cases of benign pleural thickening no evidence of stromal metaehromaiua has been observed. in all the histological sections of pleura examined in the eases of these mesotheliomas ami m more than 100 eases of asbcstoxix. no asbestos bodies, fragments of fibres, or Oust have been observed beyond the pieurni elastic laminae. Three patients from the Kuruman district, with clinical and radiological features consistent with those of diffuse pleural mesothelioma bad markedly abnormal cells in the pleural fluid. These ceils showed no specific features to distinguish them front ceils originating in secondary malignant pleural deposits nor from the grossly atypical cells some* times seen in non-malignant pleural effusions. "'A* no biopsy or autopsy examinations were obtained in these cases they have been excluded from the series. The pathological evidence for associating these tumours with asbestos exposure is not conclusive. As previously stated, only in eight of the 33 cases has evidence of asbestos been demonstrated. Of these, si* had a definite mining history and one had been exposed to asbestos while lagging steam pipes. The other case was born in'the "ICuruman-district and nothing else is known nf him. until his arrival at a Witwatersrand gold-mine at the age of 23. In the remaining 23 eases we can only present circum stantial evidence of exposure to asbestos dust (Table 3i. Eighteen of these 25 cases were born in the vicinity of the mines and two arrived in the district as infants. Of these IS people II admit definite childhood exposure to the oast and two others were exposed industrially in iuicr life. In addition two patients with childhood exposure later worked in the asbestos mines. Three cases arrived in the region at an older age but were employed either on the mines or in transporting asbestos. \ further three of these 23 cases have had industrial exposure, and in oniy one case do the relatives deny any exposure to asbestos dust. The. four industrial cases are significant. Two of the patients were lagging iQcaBiauuc-huilers and one was lagging steam pipes. A man. who was an upholsterer by trade, was employed in making 'fire-proof clothing from 1939*1945. As far as can be ascertained these people were never in the Griqualand district. These findings tend to add support to asbestos being the common factor in the development of these tumours, and to counter the suggestion that there may be some other environ mental cause in the region iff GnuuaUud West. If asbestos dust is a factor in the intcurrciiee of these tumours, similar cases might have been ex pected fr.nt the neighbourhood of the Transv:,... asbestos mines in thifPietcrsbu.-g and Lydeuburg districts, where crocidoiite and amosite asbestos is mined. According to Vcrmaas i!932). crocidol.te and amosite occur in the same seams in the 1`icictsburg district. As can be seen from Tabic .. ..nmsiie is similar u; composition to crocidoiite. in the pusi four years the lungs of 24 cases of axbestosis from the Lydenhurg district have beer, examined. In this material two eases of auer.o-eimtmoma have been observed. The or.e was in a white miner with 19 years' service, who had an adeno-curciininta arising from a bronchus. The other tai.se was a Bantu miner who had a peripheral tumour. No service record was obtainable in this case. Only one case of asbestos* has been received from the Pictcrsburg area. All of these men were actually employed on the mines at the time of death, the majority having had a relatively short service. Our findings suggest that mesothelioma occurs 23 to at) years or more after exposure n> dust. Until com paratively recently the mining m the Transvaal has been on a small scale, and there were no sedi ments in the vicinity of the mines. The lungs of 20 asbestos -e.-j from site Cape Asbestos Field have been examined, in whom no mesothelioma was observed. One autopsy specimen consisting of three fragments of lung showed asbestos* and an aJcr.o-carctnoma. ivadiologtcal features of asbestosts have been observed i.t many mine.-' from this region, without any suggestion of 270 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Tabu 3 tumour formation. However, pleural involvement hat been a common finding in these caeca (Hurwitz, 1939). It ia poenble that them has not been a raAcicnt' lapse at time altar exposure Tor tumour development in these cases. Further, the factor of individual susceptibility must also be coo* ndcred. We wish to record the neat saaiaunes that we have received ia this investigation from the medical pne> dtionen of the Onquaiand West Diaries and the  1 DIFFUSE PLEURAL MESOTHELIOMA 271 ad pashoiogjsii ia J< Malaria, and Durban. Ws ibaak the Saemai7 of HaaMi for this ca Rsnaavas __._LaW, m..__mN_.i_(_I_f_M. lO. . (IMTV Amur. 7. MMtfM.ff.W. M, IS, 47X w.f. (IfW, Arr*. MMM*. Aft, i. Si ( M V (7*Vj). '. J. MM, U. II. Ma.*, a (Ifl5l> Muwi>ai Cm* Miiiaw, ton M Ik* On IMm T M AM. p*. 7Ml. Otom. S. a. (Iflit. TMmir <L*M>. 14.4fJ. OdM. M. C (Iflh. Cam* (/MM), l.a HI Hlh. C W. (If**. j........................ -- Had. A. L. (IfMl. j A i dm Ummm V Iii* 4A4*m. HmUmm+T'sHTi"" . HMM1.M4 - k a. a (inn. am u*. ** c*m*. tasn. Hma. M. (Ifffi *' - ^ Jfi"Tna Ma.i.&.<iaan. TT)ar "* * lUtiftn. BS bf8Mlf. A. (Iftn. Ian J. C--r. 14. 34. .La. item. a.x-4. m. mm. Manmy. O. (115*1. M*r. n*. MM mM Qffrt Am, IS, tt. Mum. A. (Im. ArtA m ZrU/tmtA, 4. I. McCmmMt. w. T. <lf). /. Amu, IS, 1IT. M*n*. cwm a iifm. n*. m m m <m. r.v --. -- (1440V /. MM. CSma. US. u. notm. a (inn. am*, j. ohm. a**, sa ns. hMlm. H. a (Ifl**. J. cmmr Art, $, JI7. im, m. a. w*M, a. im cm. a a (ifiov. j. <m **t. If. 711. iisaiw. p. (tfisv agMiif--ii .sam. Smart. J h4 Haaaa. K. T. w. (inn. Bur. j. Mm. 51. Ilf. Saa. A. f, M Mmr, M. a. (1**H am m. (C*Mn> is. m. Tain*, a (inn. am mm. .mm na. i**n in. 4. If*. M, Am MM. H. C M. (inti. MM T. Gumrtk, If*. IIS*. Vwim. r. H. a (Ifm :m rum. Smr. S. Afr., Si. If*. Vara*14. A. J, tm4 Km*. J. W. (IflSV Mm J. J>M, 14. 4f. ar. i. C (inn. iraam--Sin m MamM Armmrt m A****. SataManCUa a a (If**, IM M. aa4 lfV AMArlrrr a/ Turn mm. By the end of Juno I960, a total of@easof mesothelioma had beat identified. In 43 of these a possible association with espoaura to croddoiita haa bean established. Io oaa caaa a maaotheiioma of the | THE JULY (I960) ISSUE The July (1960) isaue contains the following papen:-- Dacornprenden Skkaaos daring Constmctloa of the Dnrtford Tunesi. By F. Campbell Golding, P. Griffiths, H. V. Hampieman, W. D. M. Paton, and D. N. Wilder. A Cnapartiaa of the - Hl^iltflwla " and "High gramai Syndronae of Pscaapwisa Slrkwsm By M. da G. GribWe. Phosgene Poisoning Camed by the Use of Chsasiral Paint Resown Connieleg Methylene Chloride la IM TentHatad Roaan Heated by Kersesns Staves. By W. B. Gemtsen and C H. Buschmann. A Study on the Acate Toxicity of the Trt-aryi Pboaphataa Used aa Pbtsddien. By H. F. Boody, E. J. Field, A. N. Worden, and J. P. W. Hughes. Aeoiil Inbetstine of CaNatEJXT.A. (Moeatfl) by Workers Constantly Exposed to Lead Poisoning. By D. Petrovit. M. Stankovid, M. Savidovid, and D. Poled. A Dloehenital Stndy of the Urinary Protein of Men Exposed to Metallic Msrory. By J. C Smith and Agnes R. Weils. A SliapiHM Method for the Ejtknedan of Nkfcai in Urine. By J. Gwyme Morgan. QMcai, Brenehogmphk, RadMagkni, sad Physleleglcnl Obeanadana la Tea Caasn of Asbnstoata. By G. L. Leathart the Meaeaemant of Oeeapedonai Mortality. F. D. K. Liddell. Obearraduae oe the Occapetieaai Lab Hhsory of the Cflai Face Worker at Two Cofihrtea By O. P. Edmonds and D. S. Kerr. Tbs AsaasaoMK of Docmeneepkaiovapkic Changes and Msmory Distarhancaa in Acate Iatoxicadoaa with Indamrial Puloons. By B. Chaiupa, J. Synkovi, and M. Serittk. Book Reviews. A number of copies are still available and may be obtained from the Publishing Manager, British Medical Association, Tavistock Square, W.C.1, price 17j. 6d. T ?i K- .*. W*i