Document 6wQQw65r9bQDJ6k0Nr0MEXw43

FILE NAME State of the Art Literature SAL DATE 1960 DOC SAL070 DOCUMENT DESCRIPTION Journal Article - Diffuse Pleural Mesothelioma and Asbestos Exposure in the North Western Cape Province aere,ne a Brit J. industr Med 1960. 17 260 DIFFUSE PLEURAL MESOTHELIOMA AND | ASBESTOS EXPOSURE IN THE NORTH WESTERN CAPE PROVINCE ar BY kymn J. C. WAGNER A. SLEGGS and PAUL MARCHAND . By From the Pathology Division Pneumoconiosis Research Unit of the Council for Sewatine Sewatine and Industrial Research Johannesburg West End Hospital komberley and the 3578 Department of Thoracic Surgery University of the Witwatersrand and Johannesburg General Hospital RECEIVED FOR PUBLICATION APRIL 24 1960 3578 Primary malignant tumours of the pleura are uncommon Thirty cases 22 males 13 females ages 31 to 68 of diffuse pleural mesothelioma are described all but one have a probable exposure to crocidolite asbestos Cape blu~ i In 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 Cuse ) and secondly ge uncommon tumour In the last four years we have 10 of the cases came from a hospital to which seen 33 histologically proven cases 28 of these had suspected cases of tuberculosis were referred from a e some association with the Cape asbestos field and four cases had been exposed to asbestos in industry The tumour is rarely encountered elsewhere in large asbestos mining area This hypothesis could not be supported at once from the original histories obtained from the patients for they included house- South Africa During the past five years 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 been 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 a 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 1957 did not observe a single posure was discovered The cases are summarized case in their survey of malignant tumours occurring in the Bantu and Cape Coloured population of Johannesburg and the North Eastern Transvaal in Table 3. Previous biopsy specimens were re- examined and new cases diagnosed including asbestos miners In only one case do the relatives Our first necropsy specimen of pleural mes deny that the patient either visited the asbestos thelioma with asbestosis was examined at the mines or was exposed to asbestos Pneumoconiosis Research Unit in February 1956 Case ) During the early months of that year one of us C.A.S. in the Northern Cape treated six This is a preliminary publication and the problem is being intensively investigated patients with gross pleural thickening Pleural biopsies from two of them showed the features of The Ashestos Area of the North ape mesothelioma In the ensuing two years eight According to Hail asbestos was discovered further cases were found from this region and five from elsewhere in the Union During this period by Lichenstein near Prieska during his travels be- tween 1503 and Ts^n Since then is has been C.A.S. had become perturbed at the number of estabushed estabushed that the asbestos deposits extend from these unusual tumours occurring amongst patients and stimulated an investigation At his this 20 miles south of Prieska nettfewards through the tern part of the imagisterial distret at Hay 10 stage there were two reasons to suggest tha asbestos the eastern portion of the in gisterial district of a might be implicated First asbestos was foxand in Postmasburg and finally to the western area of the te eame ied 24 7 Pa , er et. i aha Poy ed ited PA Ee iat e ee S , e al ur me ORANGE RIVER ASBESTOS HILLS UNON OF SOUTH AFRICA from . could stories houseners a untant . mines etailed lace of os ex- marized ere re- cluding latives bestos -oblem Tape overed els be been from gh the lay to e e eg FIG 1. Map of Griquake West asbestos fields Oe ene district of Kuruman Fig ) 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 22-30 and 23 E. The whole area is semi sparsely populated and apart from mining cattle ranching is the only In 1908 production had begun in the Kuruman district 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 Bechuanaland border Table 2 Initially the ore was quarried in numerous small open cast workings This was followed gradually important occupation In the Kuruman area several large tracts of land in or abutting on these mountains have been reserved for the aboriginal inhabitants and here whites may only reside in the immediate LXBEE CHEMICAL ANALYSES OF CROCIDOLITE AND from Vermaas 1952 AMOSITE vicinity of the mines The type of asbestos mined throughout this area is crocidolite 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 stages of transformation from a massive riebeckite rock through lamellar riebeckite to asbestiform crocidolite occur in this region Magnetite frequently associated with the crocidolite Vermaas 5,0 ALO Felvi tev Mg 0 No wR RJ thaw 0 Mex t Crocidolite 3194 0.20 1384 1384 1939 1939 1.37 uly 07 904 31 2 fa : .u.tollc .u.tollc 44 47 Joi 415 2563 057 057 Js? v9? lo 007 293 J wtd !! 1952 Mining district in of asbestos first began in 1893 and gradually spread the Prieska northwards Teekay ued 500 46 oe, e Sa mer tm rary r pcm ot a Neer Le ee are te re Len r TET ETI E E S...O TE ENT EET ILE CAN, CA : ATR EPR ~~ kiutam kiutam a^ 61a = 61a 27560 27560 27555606 LIZMUKA 74014 74014 74014 74014 262 BRITISH JOURNAL OF INDUSTRIAL MEDICINE POPULATION OF . THE Taube 2 MAGISTERIAL DISTRICTS IN WHICH THE ASBESTOS ASBESTOS Itaken from Lutions Census 1921 and 19511 FIELDS ARE SITUATED District Priesku Kuruntin Hay Postmasburg ee ee ~ Whites Population 1921 nee ee ee 1921 whites eee Tolak 3,430 4,713 4,499 4.879 16698 16698 8,814 Included in the H. 8.309 21 411 13,313 Distoct a White J.301 4.313 7757 +587 Population 1951 meee Non alles ee seme 11305L 10.847 20.7 9 20.779 4421 21.014 14,12 4,208 08 i 23.547 12,338 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 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 overseers 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 fucrative clums 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 milis 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 in 1930 which was completely rebuilt in 1957 Griquatown 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 white prefers to live possible and the children play on the the mine and mill as close as Jumps from Case Histories The following eight case histories aspects of the disease and the different to asbestos dust illustrate various types of exposure Case -- B.P. a Bania male 36 years of age born 1920 was a mine labourer and was the first case diagnosed as i mesothelioma with evidence evidence of asbestosis He was born the Kurumau district but is not known whether he worked in the asbestos mines He was employed on the Witwatersrand Witwatersrand mines underground for two years and in the change rooms for a further 11 years A radiograph taken at mine hospital on August 18 1955 showed a massive sided pleural effusion and 3,000 inl of tluid was withdrawn He was admitted the Witwatersrand Native Labour Association Hospital on August 24 tion yielded 1,000 ml could be pulled out in 1955 and twee days of tluck gelatinous threads He was later aspirapus which 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 Dccupied 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 hit the right bronchial tree did not show any evidence of a primary bronchogenie carcinoma Histological sections of the pleural growth showed a papillary mesothelioma Fig ) There was evidence of asbestosis in both Jungs Fig 4 . Case 4. H. white female ^ nyears of age born 1898 was a social worker who could only have had a short exposure to asbestos as a child and probably a probably further slight exposure as a young woman have paid several shortshort visits to the mines mines She may with her husband at later period She was born in Griquatown where she lived unul she was 5 years of age Her family then moved to Kimberley where izam 1916 to clerk in an asbestoy warehouse asbestos mine from 1933-1940 1922 she worked as a Her husband owned an rT aa Shy ese AKT68k jeedaninsed DIFFUSE PLEURAL MESOTHELIOM^A t ct : * a 1 BS A ay fe i ' from , ae rw ob ps 4 ; irious } osure : rs ad ay an : ae , My 5 < | bornborn , case , losis nown ound 13 .sio j , .sio b: t | pira- : Thich . with bubutt J by justi { had { COM- : 7 Fig 7 } a. _ . "ys % no a ifd a5Ne%, a . A 4 (fae an ee - y M. og y} Fey Bo vis . eae 3 ee . re ke 6 a tb ; _ wey os a . 2 . + +e 8 al ew. es wFeA ew gg ct , a Pres %+4 * Pe % ogre * vs & ~ . ~ ' Le ee , te t sj res a few . ar ro .. ar a) o ft) a wy os SAL x . hs, ; hee ( the if 2 : Fig 2. Right lung of Case I showing a tumour compressing the f o fe, . a *, 3 a ~ e . Cra: . . - \ lung substance tions a=e" : oy PON - x e 2 7 i: a: 4 . . . Haematoxybu yey ya! both : Fr. 3 Cellular structure of tumour of Case 1. - 40 Haematoxybu - f 9A OA, % LY - pe ' and cusin sep, si,| . < y e : mays ag fo a oe & _ ; - . rn Lo .~. Torn d ly a may her FIG Sections of lung from Case 1 showing asbestos bodies + 40 Haematoxylin and eosin . : ~ ; 1 hee aN uM . 4 . al . d a Ny + er) . y . i \ 8 , lie * oy . ip Sey.05 oo . ~~! ry "og ~~ , . . > . . J . . + <ee . % . ~ te Ny 8 ^' \. a . F ee ya 7s . , e , 4 M untit Ito a Jan i . : SES awe. . a ee + a Weoteh oe 8 nn S 4 ee!of #4a oe ol Tu. 4 ef ae I cy See gs ve a - 4 : Cn pst Ms i ji Si Be reg Aa ny Es > py. {4 Fg fe yp GS aaa) FD . BS oss - $F dy as " nd ry * a i. ae a Y BAN F re) t is his iy 7 if ion 2 se ad (: V te: . 1 i fy L py oa SAE ge be TER t . v YY FT A eReNts amanRio aaceh pweeectans ne Seye eweek Se Fa ux he ha ee n h Droy earyeah < veins i, Ce, fee A gata: Aen a Fol Ritat ere ms) Salads EatIAs pee NMaei) oa ite oie 4 ny core were EAEERR WT Cie Peal et Pr eh oy ey WS eK ie ae NS ROLE TS Ms. Ree a ane mye tinea we { Fig On July 21 1954 1954 Fig 6. On Jids 7 19955 . ad ae Aiea - t | 4 3 a , , 4! i 4 . . 1 + on * * La f : ae we Fig On March , 1990 Ch 8 - An Jul S. ly n ty Fres 2 0 : add R. Jagtap s wing decoroghnight decoroghnight or 14 of bukase bukase k - oS a at ^' Fy SRC RG $4 IEna yee hy pk rp SIP nes age wee Aad Va eo 7 v Cae a 4 y ewe Y $3 peck ray ran 7 FAH: ai utt : " - i mh +. aX,Ye<~<te Sft e 7 . 7 ; (-) FIG Right lung of Case 14 Meo? *. ? c- ~ of red "Si. SF > rs tat o a4 " EL Estological sections sections of tumoar from Case 14 Haematoxylin Haematoxylin HaematoxyHlaemaitoxylnin and eosin oh M, % oa 24 She was referred to the West End Hospital Kimberley returned to the Kuruman district in 1943 where he on July 19 1954 because of dyspnoea and right chest worked as farm labourer until his final illness 0 discomfort of acute onset The chest radiograph He was admitted to the West End Hospital March 3 + showed a loculated pleural effusion at the right base 1959. He had been well until July 1958 when he i coloured fluid was aspirated which on examina- became aware of pains in the right side of his chest In tion was found to be negative for M. tuberculosis hut addition he had a slightly productive cough and short- j contained mesothelial cells arranged in acini AL , thoracoscopy in Johannesburg on August 11 1954 tumour nodules were seen on the parietal pleura Histo- logical examination of the biopsy specimen showed a ness of breath on exertion Chest radiograph on 0 March 9 1959 showed obliteration of the right lung field Asbestos bodies were found in the sputum Needle biopsy showed histological features consistent mesothelioma Deep therapy and active gold with a mesothelioma mesothelioma death 5 instillation in September 1955 caused initial regression of Autopsy --The right chest was occupied by a huge ' both the pleural fluid and nodules but did not arrest the whitish tumour which infiltrated the mediastinumn progress of the disease She received a further course of extending through the diaphragm onto the superior : ray therapy without improvement and died in of surface of the liver liver eilusion straw A coloureit eilusion was January 1957. The liver was enlarged and nodular in the left pleural she but the left lung was not before but no necropsy was done Figs 5 6 7 present and 8 show the radiological development of the tumour affected The mediastinal cervical and aortic abdominal lymph glands to the level of the renal arteries in this case case were indiltrated with tumour Case 14.-S.S. a Bantu male 40 years of age born In the right lung was found dat the tum^ta mass 1919 was an asbestos miner He was born in the had infiltrated along the intertobar fissures The lobes 9 i Kuruman district and as a child often played on the of the lung were compressed into three small segnients asbestos dump near an asbestos mine He subsequently Fig 9 On histological section a papillary type of worked with asbestos for several years being employed pleural mesothelioma was seen Fig 10 which had at an asbestos mine weighing tibre from 1938-41 ... infiltrated into the hang parenchyma in some areils 1942 he worked on a Witwatersrand gold mine but There was marked i,,mphaniespread throughout the F a +B f.. bea . Der ey, 2 a kb aaa E he, b. Ny call Pas A af =e B) ard at 266 BRITISH JOURNAL OF INDUSTRIAL MEDICINE lung 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 SEM 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 haemoptysis He was referred to the Johannesburg General Hospital for investigation The chest radio- graph showed gross pieural thickening with a basal pleural effusion on the left side He was admitted to hospital and on June 10 1957 a thoracoscopie pleural biopsy was taken This showed the features of a mesothelioma On June 24 1957 an attempt at decorneation 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 subsequently 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 Johannesburg for 20 years In March 1958 this patient developed right chest pain Case 16. - A.N.X. a white niale 50 years of age bom 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 Priuska During these journeys he often slept on asbestos bags In 1914 he worked in an asbestos mine revaled ye and rapidly increasing shortness of breath She was for a month admitted to hospital and 2,500 ml of slightly blood- The patient became all in December 1955 with vague stained fluid was removed from the right chest A substernal pain and dyspnoea A sided pleural thoracoscopic examination was carried out on July 27 effusion was diagnosed and he was referred to Mr. J. K. when a small biopsy was taken but this consisted of Bremmer in Pretoria There was no evidence of malig- fibrous tissue Bronchoscopy was normal and na ncy in bronchial and scalene biopsies Some apical neoplastic cells were observed in the bronchial washings pleural thickening and a dense homogeneous opacity at M. tuberculosis was not cultured from numerous speci- the base the left lung was seen the radiograph on mens of sputa pleural fluid nor from the bronchial August 3. 1956. Thoracotomy Mr. Bremmeri in washings She was admitted to a Johannesburg nursing February 19957 revealed a thickened nodular pleura . home on October 16 1958 with a large mass on the left diaphragm A mesothelioma mesothelioma 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 hum 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 paten- was seen on histological section In April 1959 he was examined by Mr. D. Visser in Kimberley who touad shall nodules in the subcutaneous Issue over the neck and chest A large nem mass was found the thoracotomy wound and a mass was present in the left hypochondri^"m hypochondri^"m There was generalized yniphadenopathy and numerous nodules were present the tongue Chest radiographs showed the left pleural e e from 19 ew showed shadow + the de -! ag on the . develop e chyma ofthe left lower lobe At the base confluent withi cavity to he obliterated He was one of the few cases to . biopsy an the diaphragm and perhaps the mediastinum was a hard develop widespread metastases malign ee craggy mass which could not be removed Histological A biopsy of one of the subcutaneous chest nadules Secti sections of the specimen revealed an adenoid form of showed a similar appearance to those seen in the original the histo tubular mesothelioma Subsequently three specimens specimen from the pleura The patient died on May 22 thelion of sputum were examined for asbestos bodies but none 1959. No necropsy was performed not perh were found ; The patient still alive April 1960 but her condition is deteriorating Case D.G. a white male 32 years of age burn 1922 by profession an accountant was born in England but came to South Africa as an infant He spent his Case 1909 exposul Case 22.-D.A.B. a white male 68 years age and a farmer was the father of the previous patient a diagnosis of pleural mesothelioma was January 1957 it was not until July 1959 that Although made in details of his exposure to asbestos was obtained He was born in Griquatown and went to school there He worked in Kuruman Postmasburg and Griquatown until the age of 62. Hetween 1918 and 1932 he worked 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 froin 1945 to 1952 In January 1957 cause of sided the patient consulted f^"s doctor bechest pain with cough and slight early childhood in Kuruman and left at the age of 7 Ho later qualified as 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 bacith found either in sputum or pleural fund His oni subsequent contact with asbestos was the andauing of the books of an amosite ming m the Transvaal Transvaal 11 September 1553 1e complained of sisted chest pains and shortitesy of beath A radiograph of the chest showed showed flattening of the diaphrag~-non the left side with obliteration of the cordophrenie cordophrenie angle and thicthickkering ethricikenringg of the oblique oblique lissure He was seech on naingTous naingTous D^'casions D^'casions Fields He The g factory volunt tinuous reman pipes cough age h capaci central cont factor + more NYH TRYC HED PHT SAS BA NL ART LI A A Ag TRree mf rat <Her, MI Oety, ts fi Sy ea <. i Fr. 11. On September 11. 1956 Fu 12. --On August 23 1957 Fius 21 and Radiographs shaving development of tumour in Case 24 fom . ~~ . 1983 to 1957. A radiograph taken early in 1956 showed the development of a left superior mediastinal shadow which enlarged progressively Fig 11 and later e the de elopment of diffuse nodular pleural thickening the left During 1957 similar but less marked changes 4i developed on the right side Fig 12 He consented to a biopsy in June 1957 and at operation a diffuse pleural 4 , ! re 4 t malignancy was present Sections of the parietal pleura only were the histological appearances were those thelioma He died on October 6. 1957. A removed and of a meso- necropsy was 4 not performed 1 Case 30. G.Fa. white male 50 years of age thorn 1 4 . 1909 is a storekeeper with a history of industrial > exposure He has never been near the Cape Asbestos ; Fields . He was born in South West Africa and lived there until the age of 21. From the age of 21 to 26 he worked in ' factory in the Cape as a maker and fitter He volunteered 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 j cough a lot at such work Between 26 and 32 years of } 4 age he worked in factory in Jonannesburg in a similar i capacity but was not exposed to such heavy dust con- centrations For the past 20 years he had not been in r . contact with asbestos Enquiries were made from the factory the Cape as to the nature of the asbest^,yused t 3 and these have revealed that during the relevant relevant periods Cape crocidolite was exclusively use He was first seen on March 14 1959 complaining of cough pain the right chest and recent onset of breathlessness Three pints of fluid had been aspirated from the pleura and cytological presence of malignant cells examination showed the The radiograph showed marked pleural thickening and pneumothorax On March 17 1959 a thoracoscopy was done The pleura felt immobile thickened and the lung was Several biopsies were taken collapsed and These showed the presence of a mesotheli ma showed the presence of asbestosis The underlying lung He was treated with nitrogen mustard pleurally and 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 considered them to be secondary in origin Since then on the one hand Willis 1948 1953 and Smart and Elinson 1957 have supported Robertson's Views while on the other hand primary neoplasts of this nature have been described by many authors in recent years These include Tubassen 1195115955 in Sweden Belloni and Bovo 1957 1957 in Italy Godwin 1957 in the United States and McCaughey 1958 ae REDE LL RE or ae AP ots ts od EY LEONE T f wee /^' Ghd ST on. Lae . Rea teat hay 2 'e RT Ae Tete iat se PT cote PTY 4 et. Bis o oe e'sM20 Bel a A BRITISH JOURNAL OF INDUSTRIAL MEDICINE in Britain Evidence in support of the mesothelial origin of these tumours can be found in the tissue culture experiments of Stout and Murray 1942 and Sano Weiss and Gault 1950 The variegated histological pattern of tumours arising from the mesothelium of the pleura was remarked on by Klemperer and Rabin 1931 Such a variation is appreciated when the multipotentiality of the cells lining coelomic cavities are considered Maximow first demonstrated this feature in 1927 Novak 1931 stated that the mucosa of all parts of the M^...llerian 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 mesothelium Campbell 1950 considered the presence of both epithelial and mesenchymal elements a major diagnostic feature In describing the histology of 11 of these tumours McCaughey 1958 demonstrated that either the epithelial or the mesenchymmesaenchlymal element might predominate He classified his cuses into the following four groups Tumours of epithelial character tumours of mesenchymal type tumours of mixed type and tumours of anaplastic type Using McCaughey'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 Ch^tlee1939 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 stilt 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 hyaluronidase This material stains strongly with Hale's 1946 colloida iron method The periodic acid Schiff technique has given variable reactions These results are not specific for hyaluronic acid but are 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 tumours were fixed in 10 formol 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 1940 found in their tumours are considered this variation in metachromatic properties seems to have been partially explained In addition with the great 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 glandular structure Three of the five autopsies performed showed evidence of peritoneal metastases In the other two 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 Biopsy evidence of metastases has been obtained in two cases one from the omentum and the other from the subcutaneous tissue of the chest wall while a third patient developed an implantation nodule in the appearance thoracotomy scar which showed a similar to that of the previous biopsy specimen The first recorded case of carcinonta the lung associated with asbestos was described by Lynch and Smith 1935 By 1955 according to Doll a total of 61 cases had been reported Included in these cases was one mesothelioma Cartier 1952 mentioned two cases of diffuse mesothelioma from Canadian chrysotile mine were described by van der A further three School 1958 cases Un- fortunately no indication is given in the literature regarding the type of asbestos to which the majority of recorded cases of carcinoma were exposed However discussion with management and medical officers of two of the factories in which themajority of the cases reported in Britain were employed suggests that most of these workers were handling possibility chrysotile asbestos Wagner 1958 The that some of these people may also have been exposed to crucidolite dust cannot be excluded Attempts to produce tumours in experimental animals by exposing them to asbestos dust have been made Vorw^/ldand Kart 1938 were unsuccessful Lynch Melver and Cain 1957 succeeded in pro- ducing tumours in mice but lung neoplasms in his control animals were far too numerous for the results to be considered significant On the other hand Schmahl 1958 working in Druckrey's laboratory has been able to produce sarcomas in Tuts This has occurred after subcutaneous and 1 wee . Aginne: n jms gine mele glee Mme , Minty A og ! geht aE SOG tre game pow wren pe otnew ee mee ep vy LA ye Y * 8 ra Bes ty ARS, th feats rie eg be 7 ; oe 7 . DIFFUSE PLEURAL MESOTHELIOMA 269 269 oe intraperitoneal inoculation of both asbestos fibres De and dust He states that mineral asbestos was used but does not name the variety fe In our series of mesotheliomata histological evidence of asbestosis has been observed in eight wm of the 10 cases in which lung parenchyma was in- we cluded in the specimen examined No lung tissue was present in the biopsies from the remaining pe 23 cases It was only in the four cases that came necropsy that large sections of the lung tissue were pore available for examination In all of these specimens evidence of asbestosis was found gm 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 specimens might have been significant in fe the pathogenesis of the tumours However it is - more probable that this distribution is a result of the pom marked atelectasis Similar features have been ee observed in atelectatic lungs of asbestos miners in which no mesotheliomas have been observed Pleural fibrosis has been a common finding in oe : cases of asbestosis and in some cases large pleural plaques measuring up to 1-0 cm in thickness have . - seen These plaques which were first described (oa, Gloyne 1933 have been observed following Asure to both amosite and crocidolite asbestos justs In these cases of benign pleural thickening no evidence of stromal metachromasia has been , observed In all the histological sections of pleura examined in the cases of these mesotheliomas and in more than 100 cases of asbestosis no asbestos bodies fragments of fibres or dust have been observed beyond the pleural elastic laminae Three patients from the Kuruman district with clinical and radiological features consistent with those of diffuse pleural mesothelioma had markedly abnormal cells in the pleural fluid These cells showed no specific features to distinguish them from cells originating in secondary malignant pleural deposits nor from the grossly atypical cells some- times seen in malignant pleural effusions As 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 six had a definite mining history and one had been exposed to asbestos while lagging steam pipes The ! other case was born in the Kuruman district and nothing else is known of him until his arrival at a Witwatersrand mine at the age of 23. In the ' remaining 25 cases we can only present circum- ntial evidence of exposure to asbestos dust Table 3 Eighteen of these 25 cases were born in the vicinity of the mines and two arrived in the district as infants Of these 18 people 11 admit delinite childhood exposure to the dust and two others were exposed industrially in later life In addition two patients with childhood exposure later worked in the asbestos mines Three cases arrived inthe region at an older age but were employed either on the mines or in transporting asbestos A further three of these 25 cases have had industrial exposure and in only one case do the relatives deny any exposure to asbestos dust The four industrial cases are significant Two of the patients were lagging locomotive boilers and one was lagging steam pipes A man who was an upholsterer by trade was employed in making proof clothing from 1939-1945 be ascertained these people were As far as can never in the Griqualand district These findings tend to add to support 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 of Griqualand West If asbestos dust is a factor in the occurrence of these tumours similar cases might have been ex- pected from the neighbourhood of the Transvaal asbestos mines in the Pietersburg and Lydenburg districts where crocidolite and amosite asbestos is mined According to Vermaas 1952 erocidolite and amosite occur in the same seams in the Pieters- burg district As can be seen from Table 1 amosite is similar in composition to crocidolite In the past four years the lungs of 24 cases of asbestosis from the Lydenburg district have been examined In this material two cases of carcinomia have been observed The one was in a white miner with 19 years service who had an 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 one case of asbestosis has been received from the Pietersburg 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 20 to 40 years or more after exposure to dust Until com- paratively recently the mining in the Transvaal has been on a small scale and there were no settle- ments in the vicinity of the mines The lungs of 20 asbestos miners from the Cape Asbestos Field have been examined in whom no mesotheli mawas observed One autopsy specimen consisting of three fragments of lung showed asbestosis and an carcinoma Radiological features of asbestosis have been observed in many miners from this region without any suggestion of or rN herd sca ore] ~~ ae a s .. ip ee ov 4 eet a Ay fy FO ab TTR VATE SO ^'BT 270 BRITISH JOURNAL OF INDUSTRIAL MEDICINE thor 1 Case No. i 4 3 3 4 $ 4 ? 8 ag 10 120 120 13 I ... 16 17 18 287 287 287 287 2 aan aan aan XA XA 28 29 30 = 23 23 KEYS Preto 2 31 . Year Age or. , Birth Diagnosis DIFFUSE PLEural 141 Race Sex 6 Born on Asbestos Freids TABLE 3 mesothelioma assOCIATION 7 : Asbestos Exposure : WITH ASBESTOS 8 : Diagnosed 01 Biopsy ! a a 4 Necropsy rs | 10 + Sunset + Histological fram, of : Evidence | Asbestosis 5 t jun ere We publi Belle Cann Carlins ve . t 1920 .1913 1902 ee ee: ee 36 B M ' . 42 MXD M 3 F 1896 58 W 4 1925 1925 31 *** 242 1903 33 *** 242 1920 36 *** M : 1694 63 . MXD F -. Other history unknown until came to the Wit- - . watersrand at the age of 23 : f : Mined asbestos from 1930-33 left area at the . Lived whole age of 27 life in a location near an asbestos Limvielld on asbestos fields until the age ul 5 v worked in asbestos warehouse 1916-20 - Spent all his working life in the vicinity of miles ' - Lived all her life in the vicinity of mines Lived all his life in the vicinity of mines worked ! - = as miner From the age of 24 lived in a village serving local , mines often visted mures watched calibing * ' : . : - - rfi ~ : . - ' ' | - 1 Doll Ftunci if ': ~ \ Giy Gon _- | ad - & , Hale Halt - EL j { r , 3 Heres Hur - : , 24 : 1905 1909 : 513 MXD M 513 %% M 1898 60 MXD NZX 1910 628 H NZX 1909 628 W NZX ' 1918 * M 1916 * > F , 1896 1911 8 > U * MXD F 1920 38 B M 1922 1906 1912 37 MXD M 53 W F . 7 W 1889 1889 8 * 1895 63 * F 1922 29 * M 1699 50 * F wells outside houses Whole life spent near mines diggnig ) Lived at the mine froin age 1-17 years played | and in mine as a boy returned to on dumps assist from age 21-25 : Whole life spent near mines miner 1931-13 : until the age of 17 miner 1927 Lived near mines of 21. played with Lived near mine until the age : fibre as a child Whole tile spent near mines miner 1935-41 ' played on dumps as a child of of Case 22 lived at niine until age ' Daughter school near cobbing sheus We2n0 t towesncthotool neat inines transported asbestos 1914-16 Lived un major wagen route till age of 15 Whole life several subsequent visits in the vicinity of the mines numer 1945-58 Family lived at mine miner 1938-1959 Spent whole life in village on wagon luute t Kimberley Lived in the vicinity of mines ofter an dumps as a child Whale life in the vicinity of until the age . the mines of 16 winer 1913-32 and 1945-32 Lived the vicinity of the mares umil the age 139 139 v mill from the age 1-7 Layed in the vidinn^ a as a cluld Livpleadyiend aun mitnhiengd^a"rienagsfrom the age of 10 18 years after 1918 spent whole life in same ' Klan i ta-> 1 L suid 4 5 . L, : ' s - | . Sod ah o | 1 c - si . = j Sua : - a ( - - ; i} - " j' - . au : . Sul 1895 1904 1694 1913 1909 1913 1908 1890 908 908 908 # 50 1 $ 3 2 ZZZZZ 2 ZZZZZ ZZZ W ZZZZZ ... ZZZZZ 22 M 2 ZZ W M < F 1991941 Csase 24 from 1929-33 Mined and transported asbestos . us Otersect Born in North West Cape transported asbestos from 1924-24 area fr nt Liveu whole life un farm in mining of 12 transported asbesti 1916-21 the age 1931-45 1931-45 Maintaining locomotive boilers in explosive factories Maintaining strani pipes ?) 1930-40 Worked as fitter on railways maintaining locomotive boilers dates unknown Malong asbestos blankets for the Air maintaining Force 1939-45 No history of exposure to asbestos asbestos } = Q as . - i Su Ase : - - ar ; . Sul . - @e . : - , - 74 at Column 4Race W MXD B - White Mixed Coloured Hantu Columu 10 histologicalen Column 6 Culam~-n.. Positive histologicalen Both en asbestos Neids ce Necrops dae of asbestosis . Not born on asbestos Necropsy not done No tissue subminer ' Only sinai gments of lung of 1. nelds parietal pleura submitted at QO Small tagments " evidenat ^ inkrawie ^ inkrawie tissue but 110 sulupas Joc histological . usbestosis KNampen KNampen medical pleural involvement involvement of individual susceptibility must also be con- { tumour formation However these cases Hurwitz sidered has been a common finding in not been a We wish to record the great assistance that we have 1959 It is possible possible that there has for umuur received in this investigation from the medical prac sufficient lapse lapse of time after exposure Further Further the factor titioners of the Griqualand West District and the development in these cases RRCPrarie Ratt geetay oy yang Bi Satie TT ERS T bates mat ADR he MONA my! 5 Fos n Ob yey see oatRiye Ati eie eee at ca oe q oe x PRS SEE rer SS pueaotn a ASG daetetts ORAN - oa Le ite AEF are ees 3.4 ae ds .% OE 4 wt Ab etse tte nit, * ~tne PW -# 271 DIFFUSE PLEURAL MESOTHELIOMA Martiny D. 19561. Prin Transv Mine owed Ogn Art 35. 63 pathologists thoracic surgeons and in Johannesburg Maximow A. 1927 Arch exp Zellforsch 4 . Pretoria and Durban : McCaughey W. F. 1958 1 Path Buct 76 517 K. and Challee E. 1939 Proc Sin exp Had NF NF permission We thank the Secretary of Health for to Meyer 42 797 publish this paper E. 19401. <biol Chem 133 83 22 826 Novak E. 1931 Amer J. Obst~ rKrynen Roberison E. 1924 J. Camer Res B. 317 Sano M. E. and Gault 5 1950 / thorac Surga REFERENCES Weiss 19 783 Bellant G. and Bovo 1957 Aeta me~ patav 17 367 Schmall D. 1958 Z. Krebsforsch , 62 561 51.319 51.319 19421 ee] Campbell W. 1950 Amer J. Path 2b 473 Sirait J. and Hinson K. 1957 Bru J. Fich Path 16 kisugun kisugun Cartier P. 1952 Arch imlustr Hyg 5 262. Contribution to the Stout A. P. and Murray M. 19421 Arch 1 34.951 - discussion nairobijal nairobijal wun.d. wun.d. Suppl 195 4 Doll R. 1955 Brit J. industr Med 12 81 Tobiassen A. 1955 1955 deta jath Ly Frood G. E. 1915 Memorandum on the Asbestos Indierte no the School of the Government Mining Engineer van der H. M. 1958 Neid 7. Genersk E102 1124 Soc S. Afr 55 199 Cape Province Report + Union of South Africa pp 76-82 Vermaas F. S. 1952 Trans geol J. Path 14. 49 = - Glayne S. R. 1933 Tubercle Lond 14 493 Vorwald 4. J. and Karr J. W. 1938 Amer Pneumocomotis Research in Godwin M. 1957 Cancer Philad 10 298 Wagner J. C. 1958 Memoramition Memoramition on Pneumocomotis 1953 - x Hale C. W. 1946 Nature Lond 157 802 Europe Submitted to the C.S ER Pathology a finments Hall A. L. 1930 Asbestos in the Union of South Africa Memo- Willis R. A. 1948. 1st ed and nl =o randum no 12. Geological Survey of South Africa Butterworth London - oo : 1 communication Harington J. S. 1959 Personal Higginson J. and Oettle A. G. 1957 Hurwitz M. 1959 Proceedings of Experts on Pneumoconiosis Acta Un int Caner 13 944 International Conference or Johannesburg Feb 1959 1959 Addendum By Churchill London In the press - 4, Keasbey L. E. 1947 Amer J. Puch 23 871 the end of June 1960. a total of 47 cases of and Rabin C. B. 1931 Arch Puth Ch.cugin . mesothelioma had been identified In 45 of these Klemperer 11. 385 Aline Lison L. 1953 Histochimie et Cytochimie Animules pp 332-337 a possible association with exposure to crocidolite ON - LynchGKa . u M. th ani d e SmritPharWi.s A. 1935 Amer J. Camer 24. Sn has been established In one case a mesothelioma Stat -_ peritoneum Melver H. A. and Cain J. R. 1957 A.MA. Areit iu^ instr awe. of the was present : Hith 15. 20 ae ls at e a v Sera THE JULY 1960 ISSUE agen -~ The July 1960 issue contains the following papers are pew Decompression Sickness during Construction of the Dartford Tunnel By F. Campbell G ldingP. Griffiths H. V. Hempleman W. D. M. Paton and D. N. Walder " " A Comparison of the " altitude and pressure Syndromes of Decompression Sickness By ee - ry a M. de G. Gribble - & 1 Poisoning Caused by the Use of Chemical Paint Removers Containing Methylene Chloride in F Phosgene Stoves By W. B. Gerritsen and C. H. Buschmann ventilated Rooms Heated by Kerosene - ad A Study on the Acute Toxicity of the aryl Phosphates Used as Plasticizers By H. F. Bondy E. J. Field ad A. N. Worden and J. P. W. Hughes 0 Si15t| Aerosol Inhalation of E.D.T.A Mosatil by Workers Constantly Exposed to Lead Poisoning By LJ Petrovi~ M. Stankovi~ M. Savi~ evi~and D. Poleti - + Still A Biochemical Study of the Urinary Protein of Men Exposed to Metallic Mercury By J. C. Smith and ~- ! : = a! ee A Agnes R. Wells A Simplified Method for the Estimation of Nickel in Urine By J. Gwynne Morgan Clinical Bronchographic Radiological and Physiological Observations in Ten Cases of Asbestosis By histological evides bestosis ~ ig tissue submintza Tragments of la ul DU evidence 1 be con- G. L. Leathart The Measurement of Occupational Mortality F. D. K. Liddell Observations on the Occupational Life History of the Coal Face Worker at Two Collieries By O. P. Lidmonds and D. S. Kerr The Assessment of Electroencephalographic Changes and Memory Disturbances in Industrial Poisons By B. Chalupa J. Synkov^and M. ev~ ^>k Acute Intoxications with I we have ical prac and the Book Reviews A number of copies are still available and may be obtained from the Publishing Manager Butish Medical Association Tavistock Square W.C. price 17s 6d