Document J3qDr6JJLL3Vk0ygDDYyXELEZ

N" vr / Bril.J. Industr. Aled., 1964, 21, 20. < PERITONEAL TUMOURS IN ASBESTOSIS BY J. 0. ENTICKNAP and W. J. SMIT1IER From Cost Hum Memorial tlaxpitat mut Dagrntinm, tjsxex, Fuglaiul <m.ivtl) IIIK l>(MIUrATIIIN JASWAKY 4, 1963) : PLAINTIFF'S I EXHIBIT W" DOW-226 lilcsen eases ol didusc abdominal tumours in association with exposure to asliestns were discovered in the years 1953 to l%3. There were eight men and three women, all of whoa; had worked av the same factory. In seven of the iv.cn ilte age at death ranged front 3# to "lA years; one man is slili alive at the age of 46, The women died at 44. 61, and 67. The survival time after the li 'st exposure \aried from 20 to 46 years. The shortest period of exposure was 10 months ana the longest 32 years. All three of the main commercial types of asbestos had been involved irt their working operations. Histological confirmation of the nature of the tumour has been obtained at necropsy in nine of the 10 deceased and at biopsy in six, including the survivor. A remarkable feature of these eases is the minimal fibrosis found in the lungs. In three men and one woman, asbestosis was not diagnosed during life, and no patient was completely disabled by.pulmonary fibrosis. Von Rokitansky irt 1854 described primary tumours of the peritoneum which he called `colloid cancer". The first case of malignant printary peri toneal tumour reported in this century was de.seriived by Miller and Wynn (i')tlSl. Since then a consider able number of such tumours has been found. Winslow and Taylor (I960) reviewed the literature and found 13 cases diagnosed as primary peritoneal malignancies in which clinical and pathological data together with complete necropsy reports were recorded. They added 12 mere from the files of the U.S. Armed Forces Institute of Pathology. In only one of their caws was evidence of exposure to asbestos demonstrated, although sections from the lungs were examined in each case (personal com munication). An association between asbesiosis of the lungs and tumour formation wax lirst reported by Lynch and Smith in 1935. Cloync (1951) reported at necropsy a 141' incidence of tumours in asbestotics, all of which were carcinoma of the lung. Wagner, in a series of recent publications (Wagner. Slcggs. and Marchand, 1960; Sleggs, Marchand, and Wagner. 196)3. has reported a large series of tumours of pleural mcsothclium in association with exposure to asbcMos. In 1954 Leiehcr reported an abdominal tumour in a patient wi h pulmonary asbestosis anJ thou ;hi that asbestos w is also present in the tumour. Bonier, Faulds, and Stewart described in 1955 a scric of 72 necropsies sn asbestotics in which four eases of abdominal moplasms were frund. In a cohort of 1.495 asbestos workers M.incu-.o and Coulter (1963) found live- neoplasms of the peri toneum among members who died at ages from 25 to 64 years, compared will; an expected incidence of 0-08. SeiikofT, Churgc, and Hammond (1963) reported one case of diiaise peritoneal meso thelioma in a group of 632 asbestos workers who had been exposed for at least 20 years in industry." Among 42 cases of asbestosis at necropsy Keai (i960) found II cases of abdominal tumours arising ..; various sites. One of Real's asbestotics with peri toneal tumour was known to us. Heard and Williams (1961), reviewing pathology and iung function in asbestosis, described a subject with a peritoneal tumour w'ho was also known to us. In this paper wc refer to these two eases and describe nine others not previously reported. Source of Material Certified eases of asbestosis must bo reported to H.M. Coroner at death under the Births and Deaths Registration Act 1953. Necropsy follows .is a matter of routine. There is widespread knowledge of the hazard in the local working community. Industrial death benefit under the Industrial Diseases Regula tions of I94S is payable if asbestosis is shown ;o be the cause of death or a materia 1 contribution thereto. For these reasons many other workers in this section of the indw try who die at home or in hospital from </> CJ ro CX) cn op ; ! i 04994 DOW PERITONEAL TUMOURS IS ASRllSTOS/S wivatcwr cause arc referred for necropsy. One of ns is usually present at the examination or is immediaiely inforir.eJ of the circumstances. Ten of the eases described were discovered in this way. The surviving patient is an nsbcstoiic whose complaint of dyspepsia led to investigation in the light of previous experience. Type of Exposure There are three commercially important types of asbestos: cltrysotile, croeidoiite, and amosiic. The Litter two are grouped as amphibole asbestos. They ciiler in geological formation, in chemical composi tion. in crystalline form, in fibre xiVc, and in many other respects. Wagner ct aI. (1960) have reported primary mesotltelia! tumours associated with expo sure to croeidoiite. In North America primary peritoneal .umours have been reported by Cartier < (personal communication) and by Mancuso (Man* cuso and Coulter, 1963 and personal communica tion) in workers exposed to carysotile. So far there have been no eases reported where the exposure was only to amosiic. Cowing (personal communication), in a report not yet published, has found no cases in his experience of workers exposed for many years solely to amositc in South Africa. The eases in this series had all been exposed at the same factory to dust from all three types of asbestos. It lias proved impossible to ascertain the degree of exposure to any one type. It cannot be too strongly emphasized that the amount of exposure to asbestos was often small. The exposures and histories are outlined in Table 1. They arc presented in order of the length of exposure. Clinical Features All the cases presented with abdominal p..in, discomfort or ascites (Table 2). The time from the first exposure to the onset of symptoms was always long, from 20 to s6 years. In the majority of cases the ilmcss ran a course of less than six mouths, in four of the crises pulmonary asbestosis had not been diagnosed or certified previously: in one ease the diagnosis of asbestosis was not submitted lor certi fication in deference to ibe patient's wishes, and in one case the patient died before tbc diagnosis of pulmonary asbestosis could be coniirmcu and certified by the Pneumoconiosis Medical Hoard. None of the cases was severely aiTectcd by pulmonary asbestosis. disability is assessed by the Pneumo coniosis Medical Hoard according to regulations made under the National Insurance (Industrial Injuries) Act 1946 which came into force in IWS. This is expressed as a percentage except'in the cases of two females whose disability was certified as 'total'. Such 'total' disability is the only alternative Taiile I i No. nU | So ! Hospital Reference 1 Af | Years I Uncih j at i 1 Death i or E&posure j Cr&p*O*kurc j t IF 1 0*>c( Mary'* . eotss i :f ; Not admitted to hmpital 1 i.M j l_onJ.n ivooa*; 4F 1 Kmc George** J 9475i | 5M ; l.pfulnn 1 HI 104 4M LonJtn i 40)26.47 2 ** i 1915 | |0 months 1 | | j i1 ; 1914*1919 j 3, years i 1 j * J2 ! 1930-1934 ( 4 J )n J j 1 ! 1916*1924 | 1 years Ati j 1937*1940 1 1 1943*1933 U 19)9*1942 I946-I90O 1) run 16) yen 7M KhtCMfcct : 4vjh 1942*1962 20 run *M j K.irnlJ Wood 1 35*IS 47 3929-1954 25 run 9M I0M 1 Cliaic 1 2117.61 1 J n< 1 .Kul, I960) IlM H immerwnith 4 (Heard and William*, SVil) - JO 1 I* 19) *1933 I93M9S4 27 run . 31 yean I92M959 32 yean of Pulmonary Ashestu&is 1 j Survifjil t | Year | alter [ of Y.t\i 1 { Death Eapo'orc } | 4>f-> 1 CeriiHd Oiwl>tnl]f Not diagnosed | 1961 ; 23 | Not ccrii**eU 1946 i} ; 1962 J . 46 ! -Tour 196) 1 1941 J 3) \ Not certified* ! 195* 1953 1954 1942 j 1| Binnsy 1962 1961 46 (Alive) 26 2 j 1 j `Total' )o :o:t Nei il.agnoMd ' Not diiKAoud 1942 1939 20 ! NeiciviilWd i 1 20 J Koiccrtilicii 1946 1954 * 5961 1951 40 j No* ctruSoI a| 10)2 Not 4u.-noi<4 1959 " 1 Not certified I v&SSSI GQiS- i i I I i` i' 1 I \ DOW 04995 22 BRITISH JOURNAL OF INDUSTRIAL MEDICINE N*. anj Sk'l IF JF 4F SSI M 7M SM M IOM IIM Sunm.il aAf Onw( of S> mpioms Snuivtl * attr Ul*sy l months 2 months * 19 months Nrt biopsy 4 months 21 months 2 months No biopsy Alis after 10 months Alive sftcr 10 months 4 months 2 months 2 mnnths No biopsy 4 months 7 ihn 4 months 4 months <KcjU I960) 1 month No biopsy 14 months 6 months (Heard sod Williams, 1961 > Table 2 D/t^nou 4+ +- Ab dominal Pain + 4- + + + 4* 4* -- 4- + ++ Ascites 4* + 4+ 4- Ab dominal Vomiting Distension Anemia Constipa tion Wv'l.ht ChriOfcC + 0 0w i Loss 1 + 0 + +0 i1 0 4* -- 4- Lou + + 4- 4- Loss 4- - - i Cain +++ 0 ! Gain + -- - 4- i Loss + -- + 0 + i Loss + + 0 0' 0 4- + 0 4-* o i e e* + + + o ! Cain i l + Present; -- Absent; 0 Not recorded. to `partial* disability permitted to the assessors under the special legislation introduced to cover those workers w hose disease was (a) diagnosed after July 5. 19-18. too late for Workmen's Compensation, and (6) due to exposure which ceased before July 5, 1943, loo early to benefit under the present scheme. Histological Appearances Table 3 shows the components of the histological picture and sets out their occurrence in the different eases. In six of them the disease was seen at two stages, e.f. in biopsy and necropsy specimens, and in none of these was the picture identical in both specimens. In the biopsy material fibrous tissue is relatively scanty and more regular, most of the specimens con sisting of pseudo-epithelial formations. The cells in it arc almost spherical, and multilayers arc common. In most of them no birefringent material is seen, but in the specimen from ease 11M one particularly obvious piece 7 microns long is present. The tumour material recovered at necropsy, on the Other hand, consists mostly of irregular fibrous tissue in which a variable number of clefts have formed. Lining them and on the surface of the tumours arc cuboidal, polygonal or columnar cells. This lining is usually formed of a single layer but occasionally is several cells thick. In some places within the tumour there arc solid cords and masses of more than a hundred cells but these are not clearly differentiated from the fibroeytic stroma and merge imperceptibly with it. Stains for carbohydrate by the periodic acid SchifT reagent are negative. Histo- chemical tests for hyaluronic acid gave negative results in our hands, but only two of the tumours were fixed as recommended by Wagner, Monday, and Harrington (1962), the remainder being treated with aqueous formalin. 'Rcticulin was demonstrated in variable amounts in five of the tumours examined. Various physical methods have been used to investigate the tumours. Examination under polarized light reveals a few small birefringeitt particles but docs not show any Newton's colours. These arc too small, being less than 3 microns long, properly to be called fibres, but their extinction angle is parallel to their long axis, as it is in asbestos fibres. Preparations of fine dust particles of comparable size, kindly provided by Dr. A. A. Hodgson of site Cape Asbestos Company, show very similar ap pearances, although at this size many of the fibres arc not birefringent. Furthermore, the asbestos frag ments seen in degenerating pulmonary bodies are usually of similar size and appearance. Material from three of the tumours has been calcined in an attempt to recover asbestos fibres, but none has been demonstrated. Case Histories One typical male case and one typical female ease are presented in some detail. The third case pre sented is unusual in that two primary tumours are described. The remaining case histories arc con densed. The clinical features are summarized in Tables I and 2 and the pathological findings in Table 3. In the tables the eases arc arranged in order of the length of exposure. DOW 04996 I* * |9'S2TEUTS PERITONEAL TUMOURS IN ASDESTOSIS 1J Taiu.i: 3 III.MOl.OCiCAL FEaTURCS AND PRLM-NCT: Or niKITUINfil NT MATI.KIAL IN AVAILAIW.C IIIOCXY ANf> MTkOftV M'LCIMI.NS I KOM 10 t'A.Vi.S No. in Tiu> .VfK*4 1 | | ii* ; I :r 1 N*r* mi*%n>ot;nude 5M iiiot : ; hy h) < N%\aro|H)*| | ar MtOpt) fUt nude ! Necropsy jxi ll*H** NiK-ni dim ; , Pt'0|SrtHM R<">vmMtng >ti'roui Ti^ue - Small 70 V. ay. ov. !Alr; i I+ I + 0 +0+ +++ l St/c u` Ilirclr. :vni ov\ ! I ft j I +* .L t i +! JQnJ :* 2*0* j * Not reconlcJ I *0-* ;a I S.i f\i U*,pw Nccropt) ; J| 7M 1 Rt.'psv not made 1 100 v. - _ ay. IM Bi.w Nccropsjrf ; Net atjibhle j SO*. Oiilercmui* i lien poor. 0 T| i T + + f! 4 4/1 *4 o +i I 6 t IxOJti i ?i .I*/ (iyod*U:m?*) li.*p\v Nccropsyt | JvO>Vy., toxt ' R*'PM* not AutU * NVcrop> ! 10*4 * 11M Btopsv Necropsy $0*1 Tumour in ! looC only 1 ' cimmcd | :t I i- rI 2 > 0 5 : Mu 10 : :* Not recorded * Ntfcrokis present; t Reticulin dcmonitratcd; Lymphocjrt* ieftttratiorv. Case No. 6.\1 [London Hospital 40336/47).--Tin's man died ai the age of 33 with 'carcinomatosis peritonei', hie was heaxiiy exposed to mixed asbestos dust as a hopper feeder for six months in 1939. After a break of live months he had a further two years' exposure as a 'card' grinder before his war service. From 1946 to 1961 lie worked as as engineer's fitter with minimal exposure to dust. Asbevtoxis was diagnoscJ in 1934 on routine periodic examination seven years before death. His terminal illness began with alvlomin.il pain four months before death. Three weeks before admission to the London Hospital in 1961 he complained of the sudden onset of dragging abdominal pain whi!,l opening his bowels. A nagging pain continued, worse on micturition and delaee.ition, although evacuation was normal. There was tome feeling of abdonrnal distension, possibly related to a recent wc.ght gain of I stone (6 35 kg.), mild chronic bronchitis, and some exertional dyspnoea but no other relevant symptoms. The family history and social history contained nothing relevant. On examination he was a pate looking man. The fingers and iocs showed mild clubbing. General examina tion xvas otherwise normal. The cardiovascular system was normal. The lungs showed poor expansion and scattered rhonehi. The abdomen was distended with ascites and the liver balloited. Rectal examination^xxus difficult because of spasm and pain; a possible mass xxax felt. The central nervous system was normal. The ascites was confirmed by paracentesis, anil a clear green fluid containing lymphocytes xxas obtained. The Ihiiil was not blivvly and no neoplastic cells were wen. On June 7, 1961. laparotomy conlirmexl the presence of carcinomatosis involving the liver anil peritoneum. A peritoneal biopsy (London Hospital 3313. June 1961) was reported as a- 'trabecular and mono-eelluiar. occa sionally cystic, apparently mucus secreting carcinoma*, compatible with primary carcinoma of the stomach' (Fig. J). Post-operatively the patient developed a chest infection which improved after a course of chemo therapy. Paracentesis was performed on June 20, 1961, i r DOW 04997 24 RRITISII JOURNAL 01' INDUSTRIAL MEDICINE amt .uustinc. 20 wt. was iniccicvl. On discharge lie was no: uivaIn any afvd.unaul s\mptnnv, ami was kept under s,t;vrv ision in I fie out-patient dcpanuictu. liecontinued to attend periodically until lii.s death at home on September 17. I'K.I. Necropsy was performed on September IS. 1961 by Dr. I nucknap. "1 lie tvjv showed considerable wasting, and llKec was extensive pulmonary aslvcstnsis ss it is markedly increased black,pigment markings, The entire peritoneal surface was replaced by continuous wnitc frowlit in wiiielt all the organs were embedded. It par. tiailnrl) appeared to imiltrate the pancreas, hut there were no discrete deposits there or in any of the parenCh> matous organs. There was a cuirass of grow tit 30 cm. v 20 cm. and 3 cm. thick on the deep surface of the alxlonuu.il wall. This was all thought to he due to a carcinoma of the pancreas. 11 Ls|.slogleal csaniiuulino confirms extensive pulmonary axlx'stosiswiih numerous fragmenting ami intact asbestos bodies and some hirefiingent spicules about 3 -< 0*3 microns. The hulk of tire tumour material is. loose lihrous tissue composed of spindle cells among which arc hy perch roma lie poly gonal eeils in a proportion ofahoul oik in ten. Periodic acid Schiff xfaining does not reveal any mucus or xyniogcn grannies (Tig. 2.) Case No. IF [Queen Mary's Hospital 26655].--This patient died at the age of 44 with `carcinomatosis peritonci'. Site had heen exposed to mixed asbestos dust for a short period of 10 months m 1933 in the carding depart* men;. Ashcstosis had not been diagnosed before death. The terminal illness presented with abdominal pain and distension after meals. On admission to Queen Mary's Hospital on January 13, 1961 site complained cf pain in the left grom; the abdomen was distended and a mass was felt. At laparotomy ott May 30 there was much free fluid in the abdomen, and widely scattered nodules were seen. A biopsy of the peritoneum was taken. She died in hospital on August 3, 1961. At necropsy on August 4, 1961. Dr. M. S. Ross found dense pleural adhesions, particularly to the right dia phragm, with moderate pulmonary oedema and con gestion. A little libtosis was seen. "The parietal peri toneum was studded with fleshy nodules up to the size of a sixpence, as were the pelvic peritoneum and the surface of the bowel. The omentum was a mass of growth, and there was a large mass (6 cm.) in the right lobe of the liver, with numerous satellite nodules (I cm.). The ovaries were normal. Histological examination shows moderately advanced ashcstosis of the lungs with fragmentation of most of the bodies. Related to them are birefringent particles which are doubtless asbestos. Tlvcrc is advanced broncho pneumonia and long-standing changes of congestive heart failure. The tumour from the peritoneum is pre dominantly irregular liirous tissue, w-ith uniformly distributed small birefring.nt particles. The spindle cells of the main mass have fusiform nuclei of varying size, but tl cy arc not hypcrc iromatic, nor do tlwy It ok panic ilarly malignant, and there is no pscudn-cpilhc.ial growth. Sections show, lowcvcr, spherical secondary deposits of this peculiar l brous tissue (up to 3 cm. in diameter) immediately below the c-pwile of ;.tc liver (l ips. 3 ami 4|. fuse No. 7M |Kin;: (icorpe's Hospital 49\V;|. This rain died at the age of 7K. and death was cert.-ticd as due to `c.'.icinoma of the lunsii'. lie haul been espiued to mised asbestos dull for 2<> years from 1912. Annual chest radiographs from I94N onwards all showed cs;.sive calcified pleural thickening. 'Ihis was behaved :o ivj due to old tuberculous infection, although he Mo..by denied any previous illness. Two months before death r.e was admitted to King Cieorge's Hospital with a strangu lated hernia which was reduced without ojvrunui:. Refusing any investigation, he returned home where oc rapidly went dnwnniil and died from ttw effects of a large growth in the pharynx. Necropsy on September 26. 1962 by Dr. D. iti.s'unn showed hrown atrophy of llte myocardium w..l. moderate generalised atlveroselerosis. Tite left ioi.m! was replaced by a large fungating growth centrally okci.de,I. Man;; ;'..e back of the throat. Tbere were secondary vfeposite in the upper left cervical nodes, and Uk growth cxierated ir.:u IIk celiular tissues of the neck. The lungs showed eonxiderahle lihrosisand pigmental ion with a mass of'lihions tissue 3 cm. across in the left upper lobe unieh lud a central cavity. The pleurae were obliterated and the diaphragm was thickened and calcined. The upper surface of the liver was covered w.;h lirni wnite lihrous tissue up to I cm. thick. There were numerous small nodules and piattues in the visceral and parietal peri toneum in the upper part of the peritoneal cavity, but these did not clearly invade any of the organs. The spleen Was similarly encased in white thickening of live Capsule, but the (vowel was unatfccied. Histological examination of these tissue* show* a typical fransitional-eelled carcinoma of the tonsiif.tr lymphadenoid tissue (Fig. 3) spiitc distinct from the tv pc of grow tit seen in tiie peritoneum in the oilier cases. On the other hand, the thickening of the eapsuie of die liver, which docs not invade the parenchyma, is of the same tissue as that seen in the patients dying from the effects of abdominal growths. It is predominantly spindle-celled wiirt a smaller number of did'uscly distr.buted hyperchromatic polygonal cells, some of which are forming irregtdar clefts <Fig. 6). The lungs show relative;)- little fibrosis with a moderate amount of black p.gmeiit and a few asbestos bodies. Birefringent spicules are present in the surface layers of the liver mass and arc i 0-3 microns in size. Case .No. IF (No hospitalization).--This woman died at the age of 67 from coronary thromix'sis ami chronic bronchitis. She had been exposcu to mived ashostevs dust under the had conditions of 1916 to 1919 in the weaving department. She was diagnosed as a ease of moilerafe ashcstosis in 1946. She lirsi complained of indigestion in I960. 19 months before death. Gradually increasing ascites - developed. The terminal illness Ivg-in th ec months before death with a norex.a, flatulence, constipa tion. and inc casing ascites. Death was caused by an acute coronary occlusion. A necropsy by Dr. D. Rusliton confirmed the coronary occlusion and patchy myocardial librosis. There was no a I i t I i i< ST03I2562 v DOW 04998 E9S2IC01S 2S BRITISH JOURNAL OF INDUSTRIAL MHD/CINK rn cor pulmonale. Uil.ilcr.it pleural plaques were present an.! a 5 cm. Calcified pleural plaque. I he limits slnmcd a moderate degree ol old tihioiic collapse. some carNm from Iltc mavx arc predominantly neurotic lihrous tixxuc but the typical clefts and papillary lot nviiinitx .i.c seen. pigment, and sliouy thickening eoustsieui with patchy lilvosis. Tlterc was a tlironic peptic ulcer. Widespread and generalized thickening of ilic pcnioncum with numerous irregular ll.illened noduiex and plaques was present, and there was a continent (inn mass 5 cm. across in lire omenlum. Discrete nodular depos.ts were seen in tl;c pancreas and porta liepatis. The right lobe of ihe Ever contained a large yellowish-white rounded nodule nviinly in its substance but in contact with the serous surface anteriorly. Histological examination of iltc lungs confirms asbesiosis. The small bowel shows g-catfy titickcncd serosa, which is mainly spindle-celled, hut also contains spaces lined by cuhoidal and ilancned cells. ' A few lymphocytes and some fibrinoid necrosis are unusual features, and similar tissue in the liver shows extensive necrosis. ____ Case No. 4I-* (King (Icorgc'x iloxpit.il 9.X753). Tiiiv wom.ig died at the age of 61 with `geiicrah/cil Carcino matosis of the abdomen". .She had had eight years* exposure to mixed asbestos dust from 1916 in the jnmi.r.e and mattress department in the days before luc huA.nl was appreciated. Asbestos bodies were found m the sputum in 1956 and a radiograph showed some degree of asliestO'is. The terminal illness begun three months before death with abdominal vwvlliit;:, J.seomfort, .mu loss of weight. When admitted to Kutgfieorgc's llospi;..: she was found to have abdominal masses, ,.n enlarged liver, and ascites. She died within a few daw of admistion in 1962. At necropsy Dr. J. Spencer found pienral adhesions and thickening w ith little pulmonary fibrosis. The entire peritoneum, including the diaphragm, was studded with firm creamy new growth, which was also present on the Case No. 3M (London Hospital 1909N-1).--This man died at the age of 52 with `peritoneal endothelioma and asbesiosis*. He had been exposed to mixed asbestos dust from 1930 to I93-4 in the carding department. Pulmonary asbesiosis was diagnoscJ during his stay at the London Hospital in 1963. This admission was for pain in the loins and under the right costal margin, anoiexia, toss of surfaces of the liver and spleen. The ovaries and uterus were embedded ir. a mass of tumour. Histological examination of the necropsy material confirms extensive pulmonary axhcxtosis. 1 he bowel wail is thickened by 8 mm. of reactive fibrous tissue in which there arc some clefts lined by p<cud.>-cpiihc!iiim. Bircfringcni spicules 5 x 1 microns can be found. weight, general malaise, and pyrexia. At laparotomy the liver was found to be slightly mottled and granular with many adhesions between the lobes of the liver and (he diaphragm on the tight. No obvious masses were found in the liver, bui in the porta liepatis there was a big irregular mass comii.uir.g into the liver, and there were also multiple par.vaoriie glands. Some of the mass was excised for biopsy. The patient was followed up in the oui-p.uient department but died at home two months after discharge from die ward. The following is the biopsy report from the London Hospital: `Malignant papillary-tubular neoplasm, possibly but not characteristically renal in origin. Primary peritoneal cn'dothclioma is suggested by the persistent cleft formation and the large dark ceils'. At necropsy on July 29, 1963 Dr. D. Ruxluort found extensive adhesions at the base of the right pleural cavity and the dorsal region of the lung. The lungs were lough to feel, firmer than normal, collapsed, and oedematous. There was old tuberculosis a; the right apex, but the gross dtaractcristics were rot obviously asbcstoiic. Sections front the lung, however, showed fibrosis and asbestos Case No. 5M (London Hospital 141164'. -This man was discharged from the London Hospital with an inoperable malignant growth in the peritoneum. At the time of writing lie is alive and apparently wed 10 months after biopsy. He had been exposed to mixed asivsios dust from 1937 to 19-10 and again from iV45 to i\>5.\ when nshcxlosis was diagnosed. The dcvctopnieni of a pleural elusion in 1961. with its sinister implications, led to thoracotomy. Thcic was no evidence of malignancy, hut a collapsed right lower lobe and a large amount of clear straw-coloured fluid were removed. Tbc removed lobe was clearly asbcstoiic. One year after lolvetomy iic was re-admitted for investigation of dyspepsia with pain, vomiting, flatulence, and ascites. At laparotomy t.'tete was marked straw-coloured ascitic fluid and multiple small mctasiases covering the peritoneum. The omentum was shrivelled and indurated, and on the upper surface of the left lobe of the liver was a peritonea! plaque. No secondaries were seen in the liver. The condition was considered to be inoperable, and a biopsy was taken from the omentum. bodies. The peritoneal cavity contained a large amount of Specimens from both operations were kindly supplied turbid yellow fluid. There were widespread numerous by Dr. D. Kourihancof the Bernard Baron Institute. Tne small white noddies scattered over the whole surface of lobectomy specimen confirms iltc presence of auvaneeJ the small bowel, the Urge bowel, and the peritoneal asbextotie fibrosis, but there is no tumour. The ab surface generally. The diaphragm was extensively ad dominal biopsy shows cuboidal and columnar cells form it rent to the, upper sir face of the liver. There wax a large ing clefts, solid masses, anc alveoli. The histological g pwtlt 4 in.*(101-6 mi s.) in diameter and white ir. colour . appearan cs in this case are more reminiscent of adeno ivar the liver hilum, v -hich did not involve the stomach, carcinoma than in any of the other cases deseribsd, but. T te entire pancreatic tc-d was replaced by growth. Dr. in view of the characteristics -cen in the whole seties and R tsluon registered the cause of death as `carcinomatosis the absence of any mucus secretions, this diagnosis is di-c to carcinoma of th: pancreas'. The necropsy sections discarded and the case U included. I ! r ' t }' i. I fc t I t . DOW 04999 W S Z IC 0 F S TLRITONI.AI. tumours in asiirstosis 29 OW No. S\; (lUoid Wood II.KjMi.ii <<os51. This IW'* si#s'l >t the ;v:c o' 47 w i;r, \\1ivmo.1',11 ,iv;. ^ibvlomin r. lie *l.n! -Veil cspo-cd to mixed .ivivvtn.s Ci.siv !\ir 25 scars Jroiv. 1929 io 1954. I or litc greater purl o:` that l.mc lie was most r.K; ic.i !.u;s in i!:c 'scaring ssfa iVvpi1 ,tI.ir in h.s position .is fo.-cmuii. l:or the next live years lie was lore, man o; tr.c c.rd.'iii.ig Pulr-ion.i;y a>ix:vti>vis u.o never diagnoses! uitlioi:gh lie ssa.s radiogi.ipbcd annually. Hi* icnr.in.il illness 5vj.ui when lie presented to one of u* six in.ir.ili* iv'.ve Jer.ili complaining .H' burning ab dominal iV.in. I ic was admitted In hospital for insesliga- lion. Ai Inp.uotomv the mm gcon repo, ted mucoid looking c.iicinomr.wnis tlcposi;* in ilic peritoneum, liver, and abdominal organs. There were several pint* of \i*eou* free lluid. A biopsy wav taken, on which Dr. II. Ilcnnivoii rei.'ricd mainly anaplastic grouih with Occasional capillary and luhtilar forms. A primary pancreatic growth was thought likely. The patient thc.l two tlayv later. At necropsy Dr. Ilennivon found that tire coils of the hostel 'sere licit! together by numerous soft notluies of gross ;h. wliieli sveie also pi went on the pailei.il peritoneum. on the liver Ctirf.isV, in the abdominal nodes, anti in the pancreas. Histoiojic.il examination of necropsy r.ialeria! con firms pulmonary .lslicstosis. The hostel is invaded by grosstli from outside. This shows the same instolojical structure of clefts in a solid, predominantly fibrous tumour ssith the cap.llary and alveolar pseutio-cpiilielial formation seen in the other cases. There are occasional bircftingcnt part.cles. Although the tumour docs not appear to he highly malignant, it is clearly invading the muscle of the bowel. Case No. 9M (London Clinic 1961 ].--This patient died at the age of 57 with ' eaiciiuimtitosis peritonei', lie had hectvcxposed to mixed asbestos dust for about 27 years. His exposure was minimal at any one time because his stork had always been clerical, supervisory, and technical. Ashcsiosis was diagnosed in 194.S. but lie did not svisli to apply for certification. Tlie terminal illness began about six months before his linal admission to liic London Clinic in 1961 because of abdominal pain which radiated to the left llanlt. A peritonea I biopsy (2117/61) was reported to show 'an extensile fibrous reaction amongst which there arc clefts and acmus-like formations lined by cells with serosal characters'. At necropsy Dr. F. E. Camps showed a pulmonary embolus, pneumonia, minimal pulmonary asbestosis, a hiatus hernia, and ditVusc infiltration of the peritoneum by hard white tissue. The histological appearances of the necropsy I ssue arc very similar to those of the f.rst case describeJ. case 6M. (London 403)6/47), showing both stroma and aiveolar foimationi. The lungs show a moderate dsgicc o' asbestosis. Cave Nii. 10.M (London Hovpital J7243/3< |.--This Case svj! fully described h; Kcal (Iv60) as us case number 14, He had been cx[ ssed in the same ft dory as the previous eases in tins schc. to mixed asbestos dust for four years from 5931, and Ic s heavily for 17 years from 19)7. Pulmonary asbestosis was dingn.ivcil or. periodic ex.iminuiion in 1954. lliviulogic.it evam;n..tioi. of material from the London Hospital necropsy, kindly, provided by Dr. J. lutnJeils, contimiv pulmonary ..sIvvioMs and bronchopneumonia. One seciinn slu-w* iieum entirely surroiauled by tumour. This tv p.c- dominaniiy tdveo!.ir witli a mono-layer of euisu.dal in.mg cells winch are regular in we. Some typical 'ndeuocarcinomatous* formations are seen, and some lill.ited alveoli contain papillary processes. There are however some epiliieli.il lined ciefts quite unii*e carc.nom.i in liscir irregular siil-l.kc configuration. Case Nu. IIM (Hammersmith Hospital 22''252:. This case was fully dev.-rihed by Heard :>r.,l \Viih..m\ tl96l) as their case nunilier 6. lie origmaity pi evented t.i one of us (VV'J.S.) because he svn* concerned over his 'nitjdlc-agcd spread'. I Ic had had ahslom.ii.il disco:nf,.rt and distension for eight months. Dr. II. I lear.l has kindly provided histological sections from the biopsy (June iS. 1959) and necropsy (Pc-vm'.s.T, IM59). I listoiov.ical extimination of ihe biopsy specimen shows a nodule abo;.-. I cm. across with fronds of very vascular tissue and some . small alveolar and solid masses. One noduic contains bircfringcnt needles 5 x I microns. Discussion in the past five and a half years c have seen 52 cases of asbestosis at necropsy. Nineteen (.'6".,l li.iJ " carcinoma of the lung, none of which sstis jsleur.il in origin. Fourteen (27"') had jtibdommn'i tumours.) nine (17"A) of which ttppcnrcsl 50 Originate tn die'' peritoneum. There was a single etise of careinonta of the breast (2".i). A possible total of 9.550 people have been occupationally exposed to asbestos at this one factory since 1913. Including two cases, the necropsies of which neither of us attensled, this gives an incidence of peritoneal tumour of about I in l.dCO of those exposed. It should be noted, however, that as many as 46 years may pass before the onset of the syndrofne, and in none of our cases was the interval less than 20 years. A number of cases may nave stied elsewhere since no special ciVort has been made to .follow up all the people occupationally exposed and the eventual incidence may be higher. It seems ele.tr that this is another clinical condition that must be recognized as part of the asbestosis syndrome, just as carcinoma of the bronchus is now rccogni/cd. Furthermore, the condition is associated with in dustrial exposure though there m.iy not be enough pulmonary libroxis to qualify forceriilieaiion. In previous series (Ke.il. I9MI; Homer i7 /.. 19551 of somewhat rniil.tr cases, the majority of patients were women. .ndccJ Kcal cone.tided that most ot his cases were ovarian carcinoma, as did the p.al'.ologists in two of the three female eases reported here, but eight of our ] 1 cases were men, and we have also ; DOW 05000 S9S2IG01S 30 BRITISH 'JOURNAL OF INDUSTRIAL MEDICINE been able i< examine material from a white South Alt ie.m man aged 44 by (he courtesy of Dr. J. C. Wagner. This man (i:N>..5253) lived near asbestos dumps in his youth hut was not occupationally ex poseJ. A single section sliows a cellular reaction in iihro-talty tissue ol the peritoneum anil demonstrates a transitional form between columnar pseudoepithelium and irregular tibrous tissue. There are no asbestos bodies nor any birefringent material. . A hyaluronidase test with toluidme blue was negative on this section but the lorm of fixation is unknown. Histologically it is similar to and is probably pathogenciic.illy identical with the London cases. There can be no doubt that the predominant abnormal material in the histological sections is of tibrous tissue origin, and such cells as resemble serosal epithelium appear to be derived from them. In the early stages, seen in peritoneal-hiopsy, the lesions arc more cellular, and later they become more tibrous. Progressive massive fibrosis in the related industrial conditions of silicosis is considered by the authors to be somewhat analogous, and silicotic granuloma due to talc is another comparable condi tion. Since much inhaled foreign material passes into the gut (IHiding. )063) it is probable that some at least will enter the abdominal lymphatics. We have suggestive evidence of its presence in these peri toneal tumours, and further searches by electron microscopy and by .v-ray diffraction methods at present being carried out may confirm this. How ever, in these patients with peritoneal tumours the pulmonary changes due to asbestos arc below average in severity (disability has been commonly assessed at 10 to 30%). It may well be that the shorter life span of the severely aflcctcd worker is the reason why the syndrome is not more common. Another cause of confusion is the frequent diagnosis 'oT'Sonie other form of neoplasm of which we have examples in carcinoma of the stomach, ovary, pancreas, and tonsil, as wcil as the unclassified cases of carcinoma of the peritoneum. Wagner, in a series of publications (Wagner cl ah, 1960; Slcggs, Marchand and Wagner, 1961) has claimed that tumours of the mesoi helium arc peculiarly liable to occur in asbestosis. In one African community he has claimed a very high incidence indeed (personal communication) despite often minor exposure, in some cases confined to childhood. Wc do not exclude the possibility that the masses which occur in the abdomen in the syn drome we describe arc mesotheliomas and therefore true neoplasms, but wc do not believe that our evidence, or any other of which wc arc aware, just.tics such a confide t assumption. Tnc earliest reference to similar masses which we have encountered is von Rokitansky's' (1854) description of primary 'colloid cancers' of the peri toneum. Neither he nor any subsequent author Oilers any convincing proof of their ma!igr..i;u character, and there docs not appear to have keen any great advance on the opinion of l.ubarseU (I H95j that `There is scarcely another variety of tumour which is so ill defined and which admits of so much doubt as to its precise nature'. I Hstologicn! studies, such as that of Stumpf (1954), merely demonstrate what is clear from this material, that serosa! cells may assume many weird shapes as well as several distinct organized patterns under ahnorm.il circum stances. The tissue cultures of Stout and Murray (1942), while clearly demonstrating the ability of mcsothclial cells to assume an epithelial appearance, arc at least as consistent with the masses being due to reactive processes as to their being neoplastic. To quote further, while Ackerman (I954j states that 'it is the majority opinion that although primary peri toneal tumours arc rare they do exist', Willis (1952) considers that `It will be well to preserve an open mind regarding (their) exact histogenesis', and Drown and Johnson (1951) frankly consider them the `end result of a low graJc inflammatory process with organization of the exudate'. It is abundantly clear that speculation is more readily available than fact concerning these tumours, and we consider it more helpful to add to the lat'.er than to the former. We arc impressed by the lack of occupational data in nearly all of the clime.:! histories with the exception of the most recent. It is our opinion that these masses do not in fact closely 'resemble neoplasms, and. apart from these contro versial eases, we have not encountered a meso thelioma in several thousand necropsies (see Enlieknap, 1952). In the uniform presence of a history of exposure to an industrial irritant that has not yet been shown to be oncogcr.ic. we think it unwise to give the name of a speeilic neoplasm to this syndrome and prefer, with Miller and Wynn, who recorded the first British case in 1903. to say 'We shall not attempt to give an explanation . . . wc merely record the faci(s)*. The exact nature of the tumours may only lie elucidated by their experimental production in animals, and details of Wagner's (1962) experiments are awaited with interest. Wc have in this scries had an opportunity to examine by conventional methods a large amount of hitman tissue showing these changes and feel it is unlikely that such studies wili permit more than an informed opinion. As wc !u\c been unable in the course of studying these cases to form a definite opinion as to the nature of the abdominal masses, wc prefer to evade the issue by referring to the predominant tissue in them as `wild fibrous tissue', and wc believe it may be a direct i tl I jk r*' I' : I1 I* !f i; i v lt k . * * DOW 500j PERITONEAL TUMOURS IN ASBESTOSIS 31 react ion to the presence of foreign material in the serosal cells. We propose that the condition be callcsl the peritoneal tumour of axbcxtosis until its exact nature becomes dear. In the fifth century a.ii. air^rrmurrif was first used to denote plastering or stuccoing. In our view the term asbestos!* was most aptly chosen for the patho* logic.il eifect of asbestos. Asbestos may 'plaster' the lung, the pleura, or the peritoneum! We would like to express our thanks to the many people who have helped us to colicet tltc imonnation on which this report is based. They are too numerous to list individually. but without their generous help it could not ha\e been written. H.M. Coroner for West Esses lias kindly given us permission to report the cases which canto within his jurisdiction. Mr. D. K. Halt, laboratory photographer, was responsible for the photographs. ' ROT-WIncm AeSimijn. I. V. (1VS4>. All'll Titinrmr AifWncv, Sett. 6. Him:. 2) end 24* j*. 1UU, AfuwJ K^a takutute el' l'thelogjr, VVdttiing* IliNtH'f. O. M.. 2.S,, ami Sicwdrt, At. J. (IV))], Amrr. / Ww, r.ih.. 25, 2. Ilrpiitt, NV. J.. diul ln f. (1951). 10*), 4(5* r.nhslndtS I. II. Jt'JSI) (irn't /fm/t, Xy., 101 * 273. (,i.unc. S. lUI'lMl fjfNti', , KiO. II, II., amt William*. 11.(0611. Mi, *M, iliUUiV. A, t'. An h. HUM, 4,67. KimI. I;. I.. 4IW4U. Im-h.i, h, t:i|. LviClicr. ,Uth. Cevrrbehtt., I.V llij. LuharnH, V. A. ClK`IJl. w h'(Islettuf htgr^His** Urr f*mtk. M, A+hi., ltd. ii, I*. 265, Wicxhailcn. l.vftkh. K. M,, and Smith, W. A. ( O.ljl. A*urt.J. Crntrer, 24. 5ft, T. K,, ami Omiter, r j. A**4. rnnriMiN. HUh. 4. 2 Ml. Miller, J,, amlV/ynn.W. ll.tl'M*). J. f,,tk. itort.. 12. 267. Rtikiuii^U. (*, v*n (UM). AIuimhiI / futiu Aaut.. p. 2t>. Sydvnham Ir*m,, (.iMitkitii. ScliWtifl* 11`Will, Ptinmui (*m\mttni<4iion. ScliUlT, t. 2.. ( lu.nv. J.. ami llanimmisl, I:. C\ I'divr ttigKiihil at * Jon.i Mewling VviiiKH on UailMWtu'.jr 4ttil Misvd^o nf ih CiuM i.t the Amk'iU.'.-iii SIciIiw^I Akmki.humi atd the AincfK'jn College of ClWxt l*1t>M<urtN tit iu<K 17, 1965 at Aibntic Ct>, VJ. SkYjh,.C'5*., A2.*.. MdftihdAt), IV, and NVatmrf, J. C, (1V6I). A. Air. mrd. Smut. A. I*. and Murray, M. K. (1942). Anh. >4. VS1. S'lumpf, It. M. C**r<'f. 7, 142. Wagner. J. C. (I*l62l. A'uUtre |/,rN/.K 194, 110. --. Murray, o. and Hamr;ioft, i. S. (1962). J. fat*. Bmr/^ ----Slecck, C A., and Marchand, ?. 0960). Brit. /. imlutir, M'Jn. :iQ. Willi*, R. A.. 0952). TJti Spread rtf Tmettattfi In the Human Bade, 2nd cd,, p. 57. Buturworth. London. Wirulew, 0.2m and Taylor, li. &. (I960). Caattr. U, 127* i rt 1 i i it k t I' i S M J J iM i N \ 5 l i t i; . DOW 05002