Document VGEzyNvm15Rbx1nL4MGBk0vR8

FILE NAME: Neighborhood Exposures (NE) DATE: 1960 DOC#: NE018 DOCUMENT DESCRIPTION: Medical Journal Article - Diffuse Pleural Mesothelioma and Asbestos Exposure in the North Western Cape Province s* I i 4 \* 1I* I? ** :i ( t n k j# % 41 4} tf DIFFUSE PLEURAL MESOTHELIOMA AND 1 ASBESTOS EXPOSURE IN THE NORTH WESTERN CAPE PROVINCE UY \ J. C. WAGNER, C. A. Sl.EGGS, and PAUL MARCHAND From till'Pathology Dnisnm, PneuntHoitiosis R.-seinili Unit of ilu Count il lor S ,i, mine am) . Industrial Research, Jolitmneshiiry. West F.nd Hospital. h.mberlev, and the i Department o f Thoracu Surgerv, University of ills' U'ii\\atersrund stud Johannesburg (leneiul Hospital IKH tIVtl) to: HI.IU.KMIOS sl'KIl M. IVoOl Primary malignant tumours of the pleura are uncommon. Thirty-three cases 22 males. , 11 females, ages 31 to 6S) of diliuse pleural mesothelioma are described; all hut one base a 1 probable exposure to crocidolite asbestos (Cape blue >. In a muiu'iiy 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 Afnca. 1 Mesothelioma of the pleura is regarded as an the lungs of the tirst case (Case II. and secondly, i uncommon tumour. In the last four years *c have 10 of the cases came front a hospital to which seen 33 histologically proven cases: 28 of these had suspected cases ol lubeteulosis were refetred from a some association with the Cape asbestos tield and large asbestos mining area. 1 his hypothesis could four cases had been exposed to asbestos m 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- l South Africa. During the past live years, with the wives, domestic servants, cattle herders, farmers, a exception of the present series, no neoplasm of this water baililf, an insurance agent, and an accountant. nature has been diagnosed amongst I0.0CK) 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 Oeitle (1957) did not obseive a single posure was discovered. The eases are summarized i case in their survey of malignant tumours occurring in Table 3. Previous biopsy specimens were re- | n the Bantu and Cape Coloured population of examined, and new. cases diagnosed, including i. Johannesburg and the North Eastern Tiansvaal. asbestos miners. In only one case do the relatives Our first necropsy specimen of pleural meso 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 Fcbru.uy. 1956 1his is a preliminary publication and the problem > (Case I). During the early months of that year, is being intensively investigated. one of us (C.A.S.) in the Northern Cape, Heated six I patients with gross pleural thtvkening Pleural biopsies from two of them showed the features of lite Xshestos Xu-a of the North-West Cape mesothelioma. In the ensuing two >c.n eight Curding i,< 11 ,il i to !0i ,i-r.e-iivs was discovered further cases were found from this region and live by l.ichensiem ne.u 1`ncska during his travels be- ' Irnm elsewhere in the Union. During this period tween IXOJ and lM)ts sin..,, trien it has been C.A.S. had become perturbed at me number of established th.n me asbesto-. deposits extend from these unusual tumours occuinng amongst his 20 miles south ol PneSka, lu-ithwards through the ^ patients, and stimulated an investigation Vt this we 'MU pan ,-i me magistcii.il district ol Ha,', to stage there were two reasons to suggest th.n ..shestus il..- c..stjn\ pvt imu ol the in. gistcrial divmei of might be implicated. First, asbestos was louud in Pnxtnuvhuig and tin.illy iti ihe western area of the I ai I DIFFUSE PLEURAL MESOTHELIOMA 261 a ic ar ( ) frti a could stories house* njnetrasn. ta, I . mines j leatcaeilcodf os exlarized ere re.iuding datives j ibestos } oblem 1 ; , ape osered vis be- j > been J from I ?h the 1 lay. to j ` 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 22-30' and 23 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 pf land in or abutting on these mountains have been reserved for the aboriginal inhabitants and here sshites may only reside in the immediate 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 t. Crocidolite is the fibrous form of riebeekue and all stages of transformation from a massive riebeekue rock through lamellar ricbeckite to asbcsiiform crocidolite occur in this region. Magnetite is frequeniU associated with the crocidolite (Vermaus. 1952). Mining of asbestos lirsi began in the 1'riesk.t district in IS93 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. #l his northward trend has continued and in about 1950 mining started at Pomfrci near the Bechuanaland border tTable 2). Initially the ore was quarried in numerous small open cast workings. This was followed gradually U it.M IC A L I Vili i I A N U S s r s O F ( K! 1C ID O L I 1E lirom \ e m u as, 1V52) ANO AMOSI fb b a i. wv. r<.u, l-u M i" C- N j ii k.O . H\1. 0 u 1 u M i.O 1* C rocidolite M *>4 ii :u l M l* 34 37 u N o .)7 li 1*4 ) 31 : ? Vi.ioxite 44 -7 0 t>3 4 15 \* M 6 57 o <2 0 02 ) 20 :0 07 J3 o :< vi M 0 01 1u l tl ii.o ;j tOU 40 262 BRITISH J OURS 14L OF I.XDl S I lil.il. U tD I C l . X F T vui f 2 POPULATION OF THE VI AGIS 11 Kl XL n is i H1CIS IN VVillLlt lllli AVlthMUs I II t 1)3 ARt Mi.lMlfcl) " A c n (mm Lilu m Census 19)1. u iJ ItrSl O lM flw l W hite* P o p u la tio n N on-whiles Total Population m i * NS lin k * N o n -a lute la la l Pnokj Kurum in H jv l*u-atiu*burg JA JU 4 .7 1 ) 4.499 4 H.jlW 16 m u : i 4M tf.HM mn liiviutlv' t) 111 the tid y D istric t J.lh l 4 a li 275* 4 ii7 10 47 14.209 21.779 i 2 9 .5 9 7 9 .M l I2 .J4 9 1 21.1119 25.90ft 1 by a type of shallow mining; inclined shafting be today the non-white prefers to live as close as came more common after 1930. possible, and the children play on the dumps from \ According to Frood (1915), the quarrying was a family affair undertaken by the local inhabitants. The men quarried the rock, which was sorted and Case Histories \ then hand cobbed by the women and children. The following eight ease histories illustrate various ' Hand cobbing consists of separating the libre from aspects of the disease and tile different types ot exposure lv the handed ironstone by striking the rock cob with a 10 asbestos dust small hammer. As the market was selective, a l rotary sieve was sometimes used to grade the libre Case I. -ti. K, a it.oil a male. 3ft years ot age (born and eliminate the small particles of dust. After tv201, was a mine labourer, and was the nrsi ease J grading, it was bagged and weighed. The asbestos diagnosed as a mesothelioma with evidcncc of .isbestosis, \ was then transported by donkey wagon to the nearest lie was born m the Kuruman distiiei but it is not known rail-head. Before the establishment of the railway ewmhcptlloicyiedhoen wthoerkWedtiwi.niieUrstre.tuadsbgeosltdo-smimneinseusn. derHgerouwnads in this area between 1923 and 1930, such a journey for two years and m die change rooms lor a further could last as long as 10 days. This transport was 11 years generally undertaken by white youths (farmers' sons) A rudiogiaph taken .it a mine hospital.on August IS, under contract. The white inhabitants played very 1955 showed a mits.ixc right-sided pleural effusion, ' little part in actual recovery of the libre, being nearly and 3.000 ml. of thud was withdrawn. Ito was admitted ) always employed in the role of managers or over to the Wllvv.itcrsraiul Native Labour Association seers. issuing stores and supervising the grading and Hospital on August 24. IV55, and two days lutci aspira weighing of the libres. Farming activities were and tion yielded 1.000 ml. of thick gel.ittnvus pus 'which are still carried out round the mines. could bo pulled out in threads". He was treated wuh frequent aspirations and instillation ot v.iridasc but Since the 1939-1945 war, the demand for crocitlo- without improvement, and he died >m Febiuary 15, lite has enormously increased. The lucrative claims 1956 (Martmy. 195h. have been bought by registered companies, others At autopsy (lie right thoracic cavity was occupied by have been abandoned. As deeper and richer a large gelatinous tumour which displaced the mediasti 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 lirst crushing mill was established at Koeeas in the south. This was followed by a large mill at Kuruman num and compressed ihc left lung. The tumour hjd Iniiliinied the pericardium The right lung wa com pletely compressed by neoplastic tissue (Fig. C) hut the right bronchial tree oid not show .my evidence of a primary brunchogenic caicinoma. Histological sections of the pleural growth showed a papillary mesothelioma (Fig. 3). There was evidence of asbesiosis in both lungs IFig. 4). (operated between 1926 and 1931) where it was Case 4. - K II . a white female. 5n years of age Iborn situated within 300 yards of the main street, close lim, was a social Adiker. who could only have had a to which cobbing was also done for a lew years ( 1927-1930). This was followed by a mill at Piiesk.. in 1930, which was completely rebuilt in 1957. Griquatown had a small mill in I92S. The pi act ice 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 short exposure to asbestos as a child and piobably a lurihcr slight exposure as a young woman. She may have pant soer.il shoit \isps to the mines with hei husband at a later peiiod She was b um til (iriqu.itown wheie site lived unlit she w..s 5 years ot age Her l.iuniv then moved to Kimbeiley wluie t:.,ni loth m 1>2J -ne. worked as a .leak in an a-bcsti's vv.iiehotisc. tlei Im-band owned an isbesins mine Mom t-1 s i-1 mo sc as from irious osurc 'bom case lOSIS. nown was ound rther t IS. (SO' "X ) pira midi with but 15. J by :asii- had .um* I the of a lions urna both "om Jtl a ly a may her mtil -I to is a J an Z : ' * * # * & . "j V i f vAv ( 'V % * % r n r , , hi r ` tP -J' M i r * > ** *'* . ^ *T t> . ' J f , " \ ' x i i V ' , . .*! - ;><. ; ; i<t1 f i , l,V . > ".v5* Fu.. : l-x.. I. -Right lung ul Cue I honing i tumour tfi>iii|`.reii.g Ilia lung uhitjn.e Fio. 3 -- Cellular Mruciurc o tumour cl Cate I. and eo>m, 40 Hacmaiu\>l>i; Fui. 4 --Stunon .it lung iront ("jstt I honing aihcstu. htnlttii 40 H jtm ai.n tItn ano emit I : * ^ *A 1 ^V-- * `h r ^r - i t ? V 1S * 2> " "* w s * < ..S f,, : V . JV w, V - . . . V * h .it > JJ i**!. *. / . . . -, . . > ... L. ,J i o. i ' * 1 iv- r .* * :. /* J- v ' ' . , ' . * . : m r - mm 264 s ^ i ' " .fi BRITISH JOURS-AI. OF l.\ FLSTRIAl. MFDICIXL ? . : - * A W & r Fio. 5.-- On J.il>:< l>i<4 t -Wj, V e, o.- hini 7. ivi} *7. *# 4? - J- Jtittrta V-ntoiij rtStt d iffu se pleural m eso thelio m a 265 I t 1 f I Fio 9.-- Right tun*: of U > e 14 H o Hi -H itii'tAutc.il cction oi ftttr.o.tr Intu Ca** 14 24 II uuuto\>lm jiu She was referred to the West End Hospital, Kimbeiic), on July 19. 1954. because of dyspnoea and right chest discomfort of acute onset. The chest radiograph showed a loeulatcd pleural elfusion at the right huso. Straw-coloured fluid was aspirated, which on evainin.ition was found to be negative for M. luhemiloxh hut contained mcsothehal cells arranged in acini. At thoracoscope in Johannesburg on August II, 1954 tumour nodules were seen on the parietal pleura. Histo logical evamination of the biopsy specimen showed a mesothelioma. Deep therapy and radio-actisc gold instillation 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 t-rav therapy without improvement and died in January. 1957. The liver was enlarged and nodular before death but no necropsy was done. (Figs. 5, fi, 7, and 8 show the radiological development of the tumour in this case.) Case 14.--S S., a Bantu male. 40 years of age (born 1918), was an asbestos miner, He was born in the Kuruman district and as a child often played on the asbestos dump near an asbestos mine. He subsequently worked with asbestos for several years, being ernp'oyed at an asbestos mine weighing libre from 19)8-41 In 194^ he worked on a W'llwatersrand gold mine mu returned to the Kuitimnn district in 194) whets he worked as a larill labourer until Ills linal illness. lie was admitted to the West 1 nd Hospital on Match V 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 esertion. Chest radiograph on March 9, 1959 snowed obliteration of the right lung field. Asbestos boJies were found in the sputum. Needle biopsy showed histological Natures consistent with a mesothelioma. An runs*. -The light chest w,u occupied by a huge whitish tumour which innltrateJ me mediastinum, esteuding through the diaphragm onto the superior surface of the liver. A straw-coloured eiVnsiou was present in (he left pleiual sac but (he left lung was not allecled. The medi.i-un.d, eervic.il. nnu para-.uirtic abdominal lymph glands to the level of the renal arienes were infiltrated with tumour In the right lung it was found that the tumoiu mass had infiltrated .living the interlobar iissures. The lobes of the lung were compressed into tmee small segments (Fig 9). On histological section a papillary type of pleural mesothelioma was seen iFig. 10) which lud mliltr lied mivi the lung |..uenehym.t m some .uc.is There was nuiked lymphatic spread thuuighout the I i r v 266 BRITISH JOURNAL OF INDUSTRIAL MEDICINE lung substance. Numerous asbestos bodies were present haemoptysis He was relcired to the Johannesburg in the air spaces and occasional bodies and fibres were General Hospital I'm investigation, flic chest radio seen in the interstitial tissue. The lung itself was graph showed gross pleural thickening with a basal markedly atelectatic. Evidence of asbestosis was pleural cll'usion on the loll side. He was admitted to observed in the left lung. hospital and on June 10, 1957 a thoracoscopic pleural biopsy was taken. This showed the features ol a meso Case 15.--S.S.V., a white female, 42 years of age thelioma. On June 24. 1957 an attempt at dcconie.itam (born 1916), is a housewife, who lived on a mine near was made The left upper lobe was stripped .easily but Johannesburg and was treated for tuberculous pleurisy the grossly thickened pleura was so adherent to the fo.r six months. It was only after the histological lower lobe that the attempt was abandoned. Sections of diagnosis of a mesothelioma had been made that her the pleura continued the diagnosis of mesothelioma. previous history was obtained. In addition, it was He dic'd on December 13. 1957. subsequently learnt that her father (Case 22j had been born on the asbestos field and had a long mining history Case 16. - A.N.V., a white male, 50 years of age morn The patient was born in the Griquatown district and 1906), was a farmer, who was born at Griquatown and went to school at Kuruman. She spent most of her went to a village school near an asbestos nunc. From youth in the asbestos belt. She has lived near Johannes 1914-16 he transported asbestos in donkey waggons front burg for 20 years. Hay to Pricska. During these journeys he often slept on In March, 1958 this patient developed right chest pair asbestos bags. In 1914 he worked in an asbestos mine, and rapidly increasing shortness of breath. She was for a month. admitted to hospital and 2,500 ml. of slightly blood The patient hcc.m.e ill m December, lv>55 with vague stained fluid was removed from the right chest. A Mihsicrnal pain and dyspnoea. A left-sided pleural thoracoscopic examination was carried out on July 2?. illusion was diagnosed and he was referred to Mr. J. K. when a small biopsy was taken but this consisted ol Hrcmmer in Pretoria. Thoie was no d deuce of malig fibrous tissue. Bronchoscopy was normal and no nancy in bronchial and scalene biopsies. Some apical neoplastic cells were observed in the bronchial washings. pleural thickening and a dense homogeneous opa.it) at X W. nihmiilous was not cultured from numerous speci the base ol the left lung was seen in the radiograph on mwaesnhsincgfs. spSuhtea,wpasleaudramlittlleudidtonaorJofhraonmnesthbeurghionnucrshiin.igl FAeubgruusatry3,. 19I9557ti.reve1anleodracaottohtincyken(eMdr. noHdrueltanimeptlieurina I, home on October 16, 1958. wiih a large mass on the left diaphragm Amesothelioma Radiographs then showed massive thickening ol tnc was seen on histological section. right pleura with fluid in the right chest. At thoracotomy In Apiil. tv 59 lie was examined l-y Xti J l>. Nissei in t.Mr. Dennis Fuller) the parietal pleura was 2 on thick, Kimberley who found small nodules m die subcutaneous frorr "hard as rock" and stripped with great difficulty front rhe tissue swci the neck and chest. \ large umi mass was shov chest wall. The visceral peel stripped fairly easily limn found m the thoracotomy wound and a mass was present shaC the upper lobe but separation became more dulicull o-.ci in the left hypoelieindnum. Thcic was generalised the the lower lobe where the peel was thicker During the lyntph.idcnop.nlvy and numerous nodules were present on t decortication a necrotic mass was found in the pnic-n- on the tongue. Chest i.uliogreplis showed the tell pleuial Ucvt ehymu of the left lower lobe. At the base, conllucnt witlt cavity to he obliterated. He was one of ihe few .a-cs to the diaphragm and perhaps the mediastinum, was a h.nd develop widespread metastases. bioj craggy mass which could not be removed. Histological A btopsy of one of the subcutaneous chest nudities maSI stuecbtuiolanrs, mofestohteheslpioecmima.en Sruebvseeaqleudenatlny atdherneoeidspfeocrimmenosf sshpoecwimedena sfriommilatrh.eipppleeautraar.ieeTthoethpoatsieensteednieidn omne Moraiygin2a2l. the of sputum were examined for asbestos bodies but none 1959. No necropsy was pci formed. the! were found. not The patient is.still alive (April, I960, but her condition is deteriorating. Case 22.--D.A.B.. a white male. 68 yeais ot ago, and a farmer, was the lather of the prev ious patient Although a diagnosis of pleural mesothelioma was made in January. |9y7 it was not until July. 1959 that details ol his exposuie to asbestos was obtained He was born in Griquatown and went to selniol tlicie He worked in Kutuman. Rostmasburg and (.fiqu.iiown until the age of 62. Between I9IS and Ivj2 ne winked as an asbestos miner underground and was mostly m charge of blasting. Between 1932 and 1944 he fanned in the district but returned to asbestos mining iron-. I`>45 to 1952. In January. IS):" ihe- patient consulted las doeior be cause of lelt-sided ehe-l pain wuh cough and slight Case 24. -D.G., a white male, 32 seats ol age tborn I922i, by profession art accountant, was born in England but came to South Aftiea as an infant. He spent Ins early childhood tli Kurnman and left at the age of 7 lie later qualified as a chartered accoum.int in KimOctlcy. In 1944. at the age ol 22. he had been discharged medically unlit ir.nii the nuny hve.i.'c of a left pleural clfusiou. Neitlici then nor un in.my subsequent oes.i-ious were aciil-l.t-l bacilli louilil. Cllhci III sptiluin Ol pleuial fluid. His uni; sitb-i, picul .iinia.l wuh isbcstus was the1 auditing of the N-oks of an .mii-Mlc nunc in tire Tr.msva.il. In Sepienu-ei. I ' . ' f 1 complained o l kll-u.lcd cliosl p.mis .md shoiuu^s ol b i.a th \ i.n lio g i.ip h m the chest showed ilaticning oi me iliaphiugin on me left side wuh o b l ile r .i lio n o l in ..io,*hfen.e .m e te .uni ihnkcmng of llle- o b liq u e - l l s s . u e lie n k ,, , , n n .l l l l . l l H i S O.C.lMOnS ( 19C I c\t Fie l the lac VO' tin rci PM co I av Cd cc I cc l fJd Hr, | | On September II, 1956. *1 and 12.--Radiograph fom 195' u* 195"'. A radiograph taken early in 195b showed ihe development of a left superior modiastin.il shadow which onlarood progressively (Fig. II) and later the do elopment of diffuse nodular pleural thickening on the 'oft. During 1957 similar but loss marked changes doveI.'pod on the right side (Fig. 12). He consented to bi.<ps> in June. 1957. and. at operation, a diffuse pleural malign.inet was present. Sections of the parietal pleura onl> were removed and the liistoloeie.il appearances were those of a meso thelioma He died on October 6. 1957. A necropsy was not performed. Case 30.--G.F., a white male. 50 years of age (boin 19091. 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 age of 21. From the age of 21 to 26 he worked in a factory in the Cape as a boiler-maker and litter. He volunteered the inlornution 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 lie would cough a lot at such work. Between 2b and 32 years of jge ne worked in a factory in Jonanncsburg in a similar Capacity nut was not exposed to such heavy dust con centrations. For the p.isl 20 years he lud not been in contact with asbestos. Enquiries were made from me factory in the Cape av to tne nature ol the asbestos toed 3 ami thc'C have revealed that during the relevant periods Cape croiidvitilc was exclusively in use He was lirst seen on March 14. 1959 complaining oi cough, pain in the right sliest .old iccciu onset ol bietithlessnevv Three pints of lluid had been aspirated limn the pleura and eytolo.gic.il csanimntion showed li e peseme of malignant cells. The r.idiogiaph show.d marked pleural thickening and hydro-pneumothoi.iv. On Match 17, 1959, a thor.ieoM.op> vas done. I he pleura felt thickened anti the lung v-..ts 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 liiUa-pIcuralty and his condition temporarily improved. When last vsummed he com plained ol increased breathlessness. Discussion In 1924 Robertson denied the existence id primal y malignant tumours of ihe pleura and con sidered them to be secundar, in ungm. Since then, on the one hand. Willis U94S. lua) and bmuu uiul Hinson (1957) have supported Robertson's views, while on the oilier hand, pinn.iir neoplasms ol this naitire have been described by many uulhois in ICcCllt yCJIS. These include 1 i.hiavsen t I`35h1 ill Sweden Helium and Rovo ilu5?i in It.dy, (iodwm 11v571 in ihe I'lined Males and McLuuuliov il'5M ?*!! V : c U 4 i s r > a lJ l W S H n i M l i ' S <A k V a > , - 268 BRITISH JOURNAL OF INDUSTRIAL M EDICI\E in Britain. Evidence in support of the mosoihelial The amount of meiachiomaiic substance 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 1 19-421 and partly due to the fact that until recently we had not Sano. 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 10^ formol-saline. Further, Lison remarked on by Klemperer and Rabin (1031). Such (1953) states that the metuchromasta of hyaluronic a variation is appreciated when the multipotentiality acid is optimal at a concentration of 1,10.000 and of the cells lining coclomic cavities ate eonsideied. gradually decreases at higher levels. When the high Maximovv first demonstrated this feature in 1927. concentrations that Meyer and Chalice (1939. 1940) Novak (1931) stated that the nuicosa of all parts of found in their tumours are considered, this variation the Mullerian canal and the germinal epithelium in mctachromatic properties seems to have been were derived from these' cells. Keusbey (1947) partially explained. In addition, with the great showed that in the embryo, the mesonephros, differences in the histology of the various lesions, it nietancphros, 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 non-glandular structure. Campbell (1950) considered the presence of botn Three of the five autopsies performed showed epithelial and mesenchymal elements a major evidence of peritoneal metastases. In the other two, diagnostic feature. In describing the histology of iniru-ihorueic spread was observed, in one case to the 11 of these tumours McCaughcyl 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 metastases has been obiumed 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 nodule in the Using McCaughcy's classification on our series thoracotomy scat which showed a similar appearance of tumours, the majority are. as in Campbell's scries, 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 pupillary 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. .recording to Doll, a anaplastic type. One case had the appearances of a total of 61 eases had been reported. Included in " tumour of mesenchymal type" but even in this case these eases was one mesothelioma, Carrier 11952) primitive tubular structures were seen. mentioned two cases of dittos.: mesothelioma from a Apart from the original case all the histological Canadian chrysolite mine. A further three cases diagnoses were made on biopsy material. Three of were described by van du School (1958). Un- these biopsy findings were confirmed at necropsy, fortunately no indication is given m the literature In the remainder, we have hud to rely on clinical regarding the l,pe of asbestos to which the majority and radiological examination to exclude oilier of recorded cases of carcinoma were exposed, primary sites of malignancy. However, discussion with management and medical Following the work of Meyer and Chalice U939, officers of two of the factories, in which the'majority 1940), the possibility of demonstrating hyaluronic of the cases reported in Britain were employed, acid in these tumours both chemically and histo- suggests that most of these workers were handling chemically has been eonsideied as a diugnosiic aid. chrysotile asbestos (Wagner, 1958). The possibility Both these investigations are still in an early stage that some of these people may also have been iHarington, 1959). exposed to crocidolitc dust cannot be excluded. Preliminary results of the liisiochenucal expert- Attempts to produce tumours in experimental ments show that there is meiacliroimuic substance animals by exposing them to asbestos dust have been in both the stroma and glandular structures of the made. Voivv.dd and Kan (I9JX) were unsuccessful, tumours. This mctachronlasia can bo reversed by Lynch. Mclvcr. and Cam (1957) succeeded in prt> incubation with testicular hyaluronidase. This ducing tumours in mice, hut lung neoplasms in his material stains strongly with Hale's (1946) colloidal control animals were far too numerous for the iron method. The periodic acid Schilf technique result*io be considered significant. On the other has given variable reactions. These results are not handSchuuhl (1958) working m Druckrey's specific for hyaluronic acid but are strongly laboratory has been able to produce sarcomas in suggestive of its presence. rats. This has occurred after subcutaneous and DIFFUSE PLEURAL MESOTHELIOMA 26lJ intrapcritoneal inoculation of both asbestos fibres (Table 3). Eighteen of these 25 eases were born in and dust. 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 18 people II admit In our series of mesotheliomata, histological definite childhood exposure to the dust and two evidence of asbestosis has been observed in eight others were exposed industrially in later life. In of 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 was 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. In 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 arc significant. Two numerous asbestos bodies, fragments of fibre, and of the patients were lagging locomotive boilers and dust immediately below the pleural clastic 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 (ire-proof clothing from 1939-1945. As far as can more probable that this distribution is a result of the be ascertained these people were never in the marked atelectasis. Similar features have been Griqualand district. These findings tend to add observed in atelectatic lungs of asbestos miners in stipportto asbestos being the common factor in the which no mesotheliomas have been observed. development of these tumours, and to counter the Pleural fibrosis has been a common finding in suggestion that there may be some other environ cases of asbestosis and in some cases large pleural mental cause in (he region of Griqualand West. plaques measuring up to 10 cm. in thickness have If asbestos dust is a factor in the occurrence of '>nseen. These plaques, which were first described these tumours, similar cases might have been ex ployne (19331. have been observed following pected from the neighbourhood of the Transvaal y/stire to both amosite and crocidolite asbestos asbestos mines in the Pietersburg and Lydenburg ousts. In these cases of benign pleural thickening districts, where crocidolite and amosite asbestos is no evidence of stromal metachromasia has been mined. According to Vermaas (1952), crocidolite observed. and amosite occur in the same seams in the Pietcrs- In all the histological sections of pleura examined burg district. As can be seen from Table I, amosite in the cases of these mesotheliomas and in more is similar in composition to crocidolite. In (he past than 100 cases of asbestosis, no asbestos bodies, four years the lungs of 24 cases of asbestosis from fragments of fibres,, or dust have been observed the Lydenburg distiict have been examined. In beyond the pleural elastic laminae. this nuiteii.il two cases of adcno-carcinoma have Three patients from the Kuruman district, with been observed. The one was in a white miner with l . clinical and radiological features consistent with 19 years' service, who had an adcno-carcinoma those of diffuse pleural mesothelioma had markedly arising from a bronchus. The other case was a abnormat cells in the pleural fluid. These cells Bantu miner who had a peripheral tumour. No showed no specific features to distinguish them from service record was obtainable in this case. Only cells originating in secondary malignant pleural one case of asbestosis has been received from the deposits nor from the grossly atypical cells some Pietersburg area.. All of these men were actually times seen in non-malignant pleural effusions. As employed on the mines at the time of death, the no biopsy or autopsy examinations were obtained in majority having'had a relatively short service. Our these cases they have been excluded from the series. findings suggest that mesothelioma occurs 20 to 40 The pathological evidence for associating these years or more after exposure to dust. Until com tumours with asbestos exposure is not conclusive. paratively recently the mining in the Transvaal As previously stated, only in eight of the 33 cases has has been on a small scale, and there were no settle evidence of asbestos been demonstrated. Of these, ments in the vicinity of the mines. six had a definite mining history and one had been The lungs of 20 asbestos miners from the Cape exposed to asbestos while lagging steam pipes. The Asbestos Field have been examined, in .shorn no other case was born in the kuruman district and mesothelioma was observed One autopsy specimen nothing else is known of him, until his arrival at a consisting of three Ijagmcnis of lung showed Witwatersrand gold-mine at the age of 23. In the asbestosis .old an adeno-careiiuiinj Radiological remaining cases vvc can only present circum- I'cuturcs vi iut>s-ioii> have been observed m many \itia l evidence of exposure to asbestos dust miners Irom (his region, without any suggestion of c CN t 1 4* IC I II i: u 14 IJ !* Il U . IV ?< Jl: JJ4! J? >U K h 4 41 4? 270 BRITISH JOUR,Sa l o f i n d u s t r i a l m e d i c i n e the T able 3 Prt D IFFU SE PLEU RA L M ESOTHELIO M A : ASSOCIATION V -H H ASBESTOS (1) C i m No. t:> (31 (41 151 Year Age of at Race Sex Birth | Diagnosis (6) Born ou Ashesios Fluids 17) Asbestos exposure ( 8) (9) 110). pu iiTiK ! DugllOsCd Mmotugicat j baa, on Ntwropsy fc'videiice of ( U t4 Biopsy Asbestosts iSya I i 1920 : 36 B M : il9 l3 -42 MXD M j 1902 53 B F 4 1896 58 wF w 5 1925 31 B M 6 190J 53 F 7 1920 36 W M i 1894 63 MXD F 9 1905 j; MXD M 10 1909 49 W M 11 12 IT 14 _____ 15 16 17 IS 19 :o :t ns 23 24 25 26 2* 28 29 30 31 3: 33 1898 1910 1909 1918 1916 . 1896 1911 1920 1922 1906 1912 1889 1895 1922 1899 1895 1904 1899 1913 1909 1913 1908 1890 60 MXD M 48 B M 50 W F 40 B M 42 W F 60 W M 48 MXD F 38 B M 37 MXD M 53 w F 44 wM 68 w M 63 wF 35 wM 50 wF 49 wM 52 wM 60 wM 44 wM 50 w M 44 \v M 49 wM 59 wF r - % i t ,, 0 Other hiatur; unknown until cjiiic tu the Wit- watersrand at the age ol 23 I Mined asbestos from 1930-3J; leu area Mt the | age of 27 Lived hole life in u location near an asbestos mill Lived on asbestos fields until the a*c of S. j worked in asbestos warehouse 1916-20 Spent all his working iife in the vicinity of mines Lived all her life in the vicinity of mines > Lived all his life in the vicinity of mines; worked i as a miner From the age ol 24 lived in a village serving local , mines; otien visited m ires; watched cobbing outside houses Whole life tpcm near minus, digging wells ( Lived at the mine from age 7-17 years: played ; on dumps and in mine as a boy, returned to assist from age 2125 Whole life spent near mutes, miner 1931 ` 3 ; Lived near mines until the age of 17: miner 1927 Lived near mine uii.nl the age of 21. played with , fibre as a child Whole Itie spent neat mine, miner 19)6-41, played on dumps as a child Daughter ol Case 22: lived at mine until age ol 2U. went to school near cobbing hedi 1 Went to school near mines: transported asbestos 1914-16 Lived on major wagon route till age ol 15; . several subsequent visits Whole hie in (he vicinity of the mines; miner 1945-5 Family lived at mine, mtner 1936-1959 Spent whole hie in village on wagon toote to Kimberley Lived in the vicinity of minus until the age of 16; otto, on dumps as a child Whole life in the \u.mu> ol the mines; inner 1913 32. and 1945-52 Lived m the vuinity of the mines until the age .I Id Lived m the vicinity of a null from the age of 1*7; played un the dumps as a child Lived m a mining urea from the uge of 10 to 1 years: after 1916 spent whole life in same tiVwii a> Case 24 Mined and transput ted asbestos iron: 1929*33 as overseer Born in North West Cape; iraii|ijrw*d asbestos from 1920*24 Lived whole hie on larnt in mining area Irani the age of 12: transported abeM<-> 1916*21 Maintaining locomotivi bailers 1931-4? Maintaining steam pipes m explosive factories 1930-40 Worked as filter on railways maintaining locomotive boiler, dates unknown Making asbestos blankets for the Air Force 1939-45 N o h isto ry o f c v p o su ie to abe*Os Kb'S: Column 4-- Race: W M \D B \\ hue Mixed Coloured 1 Bantu Column 6 - Born on asbestos itetJv Nut b.-rn on ashestn* fluids u L nkr.ov u Col jinn 9 -- * Nvxnij's, dilue Newrops r u t Oi-nc * Only somiI haginents ol parietal pleura Mibuviiled at autiipsy tur hiMoIogtwjl svam itia.ion Column 10 >- Positive histological of asbestosiS - No lung tissue subaM * 0 >- Small fragments of tissue, but no evi4eoa abesUMs 4 I tumour formation. However, iileur.il mv.ilvemeiu ol individual siiswcpubilit> must also be eon- j hns been a common finding in these cases tH urw iu. side-red 1959). It is possible that there has not been a sufficient lapse of lime alter exposure fur imiwur development in these cases, further, the factor wish to ih o i .1 it-.c great assistance that we have iVwwlVw' 111 thli li1vgTllStfh>n n*m he mcdi-al practitionv.lv o| th,, (ii ivjudl.tnd . 1 Out riel. and (he 7 Tt.1. IIO O ~)l DIFFUSE PLEURAL MESOTHELIOMA 271 thoracic surgeons and pathologists in Johannesburg, Pretoria, and Durban. Wc thank the Secretary of Health for permission to to (III publish this paper. to**cl ' hem IK* o f ' U u t m oti .S rra * il>m m * J II ! Ill . SGU>,1 REFERENCES BcIUiiii. l i . anti lliivti, G , (1*457). At tu **./. putav . 17, Ih1 Campbell. W . N ( *#301. Anur. J. ruth., 26. 473 Cartier. I*. (1952) A rth .w d u \tr. / ( if ,, 5, 262. (Coitlrtlui(iui the IWUVMOII Doll, R. 11955). lint. J. tnJuur. J M , 12. HI. Froosi, G . E. B. (1915). Memorandum on the Asbestos /m/ii.f. to the Cape Pro finer. Report ot' the Government Mining Engineer, Union o f South A ir tea, pp. 76*82. Glo>ne. S. R . (1933). Tuben le (Com/.). 14. 493. < GovUm. M. C . (19571. Corner {Philud.), 10, 29S. Hale. C . W. (1946). \a tu re {LondA, 157. 002. Hall. A L . (1930). Asben o t in the Union oj South A lm a . Memo randum no. 12. Geological Survey of South Africa. Hanngton. J. S. (1959). Personal communication. Higginvon. J.. and Oettle, A. G . (1957). Acta L'n. int. Cunt r., 15.9-1*#. Hurt*nr. M. (1959). Proceedings ot International Conh rente ot L tp en s on PftennitH onions. Johannesburg. K b 1959. Churchill. London. (In the press.) Keusbev. L. E. (1947). 4m-r. J. Path.. 23. 87. Klemperer. P . and Rabin. C . B. (1931). A nh. Path. (CA.cuvm), I I . 385. Livon. L. )1953) Htstothmue el Cylochtnne Animolet, pp. 532*337. Gauthier A illar, Pan. L>rwh. K . M .. and Smith. W. A. (19351. 4mer. J. Comer, 24. 5*> -- . Mclver. F A. and Cam, J. R. (1957). a.M.A. Anh. iwlmir. Hhh. is. : r Murliny, O. 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(1948, Ivt ed. and 1953). Pathology . / f Uuneruonh, London. Addendum By the end of June 1960. a total of 47 eases of mesothelioma hud been identified. In 45 of these a possible association with exposure to crocidolue h.is been established. In one ease a mesothelioma of the peritoneum was present. Sud . ! nM U t _ I li I !j SiU 1 >. SuS^f imoto,inJcieru no iiu ubtnkvu ' ran n en o i j *H> n i d n t , con- 'c have d pracnd the THE JULY (1960) ISSUE The July (I960) issue contains the following papers:-- Decompression Sickness during Construction of (lie Hartford Tunnel. Uy F. Campbell Golding, P. Grillitlis. H. V. Hempleman, W. D. M. Paton, and D. N. Walde-r. A Comparison of the High-altitudc " and * High-pressure " Syndromes of Decompression Sickness. Uy M. de G. Gribble. Phosgene Poisoning Caused by the Use of Chemical Paint Removers Containing Methylene ( hiuridc in Ill-ventilated Rooms Heated by Kerosene Stoves. Uy W. B. Gerritscn and C. H. Buschmann. A Study on the Acute Toxicity of the Tri-aryl Phosphates Used as Plasticisers. Uy H. F. Bondy. E J. Field. A. N. Worden, and J. P. W. Hughes. Aerosol Inhalation of CaNajE.D.T.A. (Mosalil) by Workers Constantly Exposed to l ead Poisoning. Uy Lj. Petrovic, M. Stankovic, M. Savtcevie, and D. Poleti. A Biochemical Study of the Urinao- Protein of Men Exposed to Metallic Mercury. Uy J. C. Smith and Agnes R. Wells. A Simplified Method for the Estimation of Nickel in Urine. By J. Cwynne Morgan. Clinical. Bronchographic, Radiological, and-Physiological Observations in Tefi Cases of Asbe-tosis. Uy G. L. Leathart. The Measurement of Occupational Mortality. K D. K. Liddell. Observations on the Occupational Life History of the Coal Face Worker at I'wu C ollieries. By O. P Edmond and D. S. Kerr. The Assessment of Electroenccphalograpliic Changes and Memory Disturbances in \eute Intoxications with Industrial Poisons. By B. Chalupa. J. Synko\;i. and M. Sevcik. Book Reviews. A number of copies are still available and may be om.uued lion, ihe Publi-ihiug M . m . l i i m d i Medical Association. Tavistock Square. W C I. priee 1.7,. 6,/. ) T siso m n r ''n i l