Document 5Lxmpa3rXkOaDDM6BnGb749GJ

tasm mmu* & \ : ; 1; V* i A ;i l` !i ' S' B ril. J . industr. M ed., 1964, 2 1, 20. P E R IT O N E A L T U M O U R S IN A S B E S T O S IS BY J. B. EN TIC K N A P an d W . J. SM ITH ER From East Ham Memorial Hospital and Dagenham, Essex, England (RECEIVED FOR PUBLICATION JANUARY 4 , 1963) 1 . .. Eleven cases erf diffuse abdom inal tum ours in aasoraediem w ith exposure let discovered in th e years 1958 to 1963. T here w ere eig h t m en an d th ree w d im m ^ w orked a t th e sam e factory. In seven o f th e m en th e age a t d eath ranged from lj one m an is still alive a t th e age o f 46. The w om en died a t 4 4 ,6 1 , an d 67. T h ei ` * first exposure varied from 20 to 46 years. T he sh o rtest period o f exposure * longest 32 years. A ll three o f th e m ain com m ercial types o f asbestos h ad been w orking operations. H istological confirm ation o f th e n atu re o f th e tu m o u r' necropsy in nine o f the 10 deceased and a t biopsy in six, including th e survivor, o f these cases is th e m inim al fibrosis found in th e lungs. In three m en an d one w as n o t diagnosed during life, and no p atien t w as com pletely disabled by pulm onary fibrosis. V on R okitansky in 1854 described prim ary tum ours o f th e peritoneum w hich he called `colloid cancer'. T he first case o f m alignant prim ary peri toneal tum our rep o rted in th is century w as described by M ilter an d W ynn (1908). Since then a consider able num ber o f such tum ours has been found. W inslow an d T aylor (1960) reviewed the literatu re and found 13 cases diagnosed as prim ary peritoneal m alignancies in w hich clinical and pathological d ata together w ith com plete necropsy reports were recorded. They added 12 m ore from th e files o f the U .S. A rm ed F orces In stitu te o f Pathology. In only one o f th eir cases w as evidence o f exposure to asbestos dem onstrated, although sections from the lungs w ere exam ined in each case (personal com m unication). A n association betw een asbestosis o f th e lungs and tum our form ation w as first reported by Lynch and Sm ith in 1935. G loyne (1951) reported a t necropsy a 141% incidence o f tum ours in asbestotics, all o f which w ere carcinom a o f th e lung. W agner, in a series o f recent publications (W agner, Sleggs, and M archand, 1960; Sleggs, M archand, and W agner, 1961), h as rep o rted a large series o f tum ours o f pleural m esothelium in association w ith exposure to asbestos. In 1954 Leicher reported an abdom inal tum our in a p atien t w ith pulm onary asbestosis and thought th a t asbestos w as also present in the tum our. B onser, F aukls, an d S tew art described in 1955 a series o f 72 necropsies on asbestotics in w hich fo u r cases o f abdom inal neoplasm s were found. In a co h o rt o f 1,495 asbestos w orkers M ancuso and C o u lter (1963) found five neoplasm s o f th e peri toneum am ong m em bers w ho died a t ages from 25 to 64 years, com pared w ith a n expected inddenoe o f 0 0 8 . Selikoff, C hurge, an d H am m ond (1963) rep o rted one case o f diffuse perito n ea! m eso theliom a in a group o f 632 asbestos w orkers w ho had been exposed fo r a t le a d 20 years in industry. A m ong 42 cases o f asbestosis a t necropsy R eal (1960) found I I cases o f abdom inal tum ours arising at various sites. O ne o f R eal's asbestotics w ith peri toneal tum our was know n to us. H eard and W illiam s (1961), review ing pathology an d lung function in asbestosis, described a subject w ith a peritoneal tum our w ho w as also know n to us. In th is paper w e refer to these tw o cases an d describe nine others n o t previously reported. Source o f M aterial C ertified cases o f asbestosis m ust be reported to H .M . C orm ier a t death u n d er th e B irths an d D eaths R egistration A ct 1953. N e c ro p ^ follow s a s a o tte r o f routtne. is j|W 'e # 8 ip o f the d eath benefit un d er th f; tio o s Of 194Sis p ay ab le if |IX iM M pil#4fiM plkffe'he th e cause o f death o r a m aterialcontrfbution thereto. F o r these reasons m any o th e r w orkers in th is section o f th e industry w ho die a t hom e o r in h o sp ital from w hatever c is usually i utely Infer cases desci surviving i of dyspepf previous e> There ar asbestos: c latter tw o a differ in g& tion, in ary other respe prim ary n a sure to cr< peritoneal t (personal c cuso and C tion) in woi have been n only to ante in a rep o rt his exporter solely to anr The cases same fa c to r No. and ' Sex If 2F 3M 4F 5M AM 7M KM M I0M Queei 26655 Not a Lond 19098 King 98753 Load 14116 Londi 40336 King 49534 Hand 35085 2U7A (lie 11M i Hanoi ! 2272S: i (He t. ii F Ilfra tw iF iiip p rM m m m * sto s JO . after the ths and the v d in . obtained a t Jable feature (, asbestosis am i fn s o f th e peri- _ from 25 to ed incidence o f m m ond (1963) m to n eal meso>s w orkers w ho in industry. >psy K eal (1960) p u rs arising a t otics w ith peri- H eard and d lung 1 -- wi t h a )ow n to us. In >es an d describe PERITONEAL TUMOURS IN ASBESTOSIS 21 |. * whatever cause are referred fo r necropsy. O ne o f us I t has proved im possible to ascertain th e degree o f l is usually present a t th e exam ination o r is im m edi- exposure to an y one type. I t can n o t be to o strongly uicly inform ed o f th e circum stances. T en o f th e em phasized th a t th e am ount o f exposure to asbestos cases described w ere discovered in th is w ay. T he w as o ften sm all. The exposures an d h is to ric m e I surviving p atien t is an asbestotic w hose com plaint outlined in T able 1. They upCrprifsoiiioii i0t oi-ctosr ? of dyspepsia led to investigation in th e lig h t o f th e length o f exposure. *" previous experience. V 2Vpe o f Exposure , C linical F eatures . A lt th e cases presented w ith abdom inal pain, t There are th ree com m ercially im p o rtan t types o f discom fort o r ascites (T able 2). T h e tim e from th e ; asbestos: chrysotile, crocidolite, and am osite. T he first exposure to th e onset o f sym ptom s w as alw ays : latter tw o are grouped as am phibole asbestos. T hey long, from 20 to 46 years. In th e m ajority o f cases differ in geological form ation, in chem ical com posi th e illness ra n a course o f less th a n six m onths. In tion, in crystalline form , in fibre size, an d in m any fo u r o f th e cases puim onary asbestosis h a d 'n o t been other respects. W agner e t at. (I960) have reported diagnosed o r certified previously; in one case toe prim ary m esothelial tum ours associated w ith expo diagnosis o f asbestosis w as n o t subm itted fo r certi sure to crocidolite. In N o rth A m erica prim ary fication in deference to th e p atien t's w ishes, an d in peritoaaal touaeum have been reported by C artier one case th e patient died before th e diagnosis o f (peraonatc0m tn u ateatto n > an d by M ancuso (M an- pulm onary asbestosis could be confirm ed and cuso and C o u lter, 1963* an d personal com m unica certified by th e Pneum oconiosis M edical B oard. tion) in w orkers exposed to chrysotile. So far th ere N one o f th e cases was severely affected by pulm onary , have been no cases reported w here th e exposure w as asbestosis. D isability is assessed by th e Pneum o only to am osite. C ow ing (personal com m unication), coniosis M edical B oard according to regulations in a report n o t yet published, has found no cases in m ade u nder th e N ational Insurance (In d u strial his experience o f w orkers exposed fo r m any years Injuries) A ct 1946 w hich cam e in to force in 1948. solely to am osite in South A frica. T his is o q p essed as a percentage except h t the cases The cases in th is series had all been exposed a t th e o f tw o fem ales w hose disability w as certffied as same factory' to d'dst from all th ree types o f asbestos. `to ta l'. Such `to ta l' disability is th e only alternative No. and Hospital Reference Sex ip g K Maty's 2F Not admitted to hospital 3M London 190984 4F T able 1 Age at Death YT Exposure Umph Exposure 44* 1933 10 months 67 1916-1919 3 years 32 1930-1934 4} years 61 1916-1924 8 years *Pdlnunuyf Asbestosis N ot diagnosed Year of Death 1961 Survival SX tr 23 Certified D isability N ot certified 1946 1962 46 T otal' 1963 1963 33 N ot certified 1936 1962 46 T otal' be reported to ths an d D eaths a s s m atter 'lecite o f th e Twfrretrial is show n to be button thereto. Jsin th issectlo n SM London 141164 6M London 40336/47 7M Kmg^Geotge's SM <rst IBM IIM 'Harold Wood 55085 London Clinic u irm London 27243/36 (Keal, i960) Hammenraith and-WiHiams, 1961) Alive 38 78 47 ST 1937-1940 194S-195S 1939-1942 1946-1960 1942-1962 1929-1954 1921-1948 H S! 13 yean 161 years 20 years 25 years 2 7 yean 31 yean 47 1927-1959 32 years 1933 1954 N ot diagnosed N ot diagnosed 1948 1934 (ABve) 26 1961 22 30% 20% 1962 20 N ot certified 1939 30 N ot certified 1961 40 N ot certified 1938 27 10% N ot diagnosed 1959 32 I tom itf ta is M to v - iri*inn 22 BRITISH JOURNAL OF INDUSTRIAL MEDICINE 23 Sex IF 3M 4F m 6M 7M 8M 9M IOM Survival after Onset o f 2 | months 19 months 6 months 3 months AB^tnonths 4 months 6 months 6 months Survival after Biopsy 2 months N o biopsy 21 months N o biopsy Alive after 10 months 3 months N o biopsy 7 days 1 month N o biopsy IIM Sm ooth. Wmisms,*IMl) T abue 2 Dyspnoea + + Ab dominal Pain + + + + + Ascites + + + +. + Ab dominal Vomiting Anorexia Distension Ita +* 0 > ft + 0 + .' +- * , + + + J ' + +- - -- \ 'toro. `to ro / r. Lon . , Cain +` + -- -+ ++ + + H+ + .+ + ++ - '- -, ft 0 Onte toro - + . ' .. + Lem + 0 . . 9 '' . 0 - 0 + 0 + 0 --+ + + 0 0 0 + Present; -- Absent; 0 N ot recorded. to `p artial' disability perm itted to th e assessors under th e special legislation introduced to cover those w orkers w hose disease w as (a) diagnosed after July 5, 1948, to o late fo r W orkm en's C om pensation, an d (ft) d u e to exposure w hich ceased before July 5,1948, to o early to benefit under the present scheme. T able 3 show s th e com ponents o f the histological picture and sets o u t th eir occurrence in th e different cases. In six o f them th e disease was seen a t tw o stages, e.g. in biopsy and necropsy specim ens, and in none o f these w as th e picture identical in both specim ens. * In th e biopsy m aterial fibrous tissue is relatively scanty an d m ore reg u lar, m ost o f th e specim ens con sisting o f pseudo-epithelial form ations. T he cells in it are alm ost spherical, and m ultilayers are com m on. In m o^t o f them no birfringent m aterial is seen, b u t in th e specim en from case 11M one particularly obvious piece 7 m icrons long is present. T he tum our m aterial recovered a t necropsy, on the o th er h and, consists m ostly o f irregular fibrous tissue in w hich a variable num ber o f clefts have form ed. L ining them and on th e surface o f th e tum ours are cu b o id al, polygonal o r colum nar cells. T his lining is usually form ed o f a single layer b u t occasionally is several cells thick. In som e places w ithin th e tum our th ere are solid cords and masses o f m ore th a n a hundred cells b ut these are n o t clearly differentiated from th e fibrocytic strom a and m erge im perceptibly w ith it. Stains fo r carbohydrate by th e periodic acid S chiff reagent are negative. H isto- chem ical tests fo r hyaluronic acid gave negative results in o u r hands, b u t only tw o o f th e tum ours were fixed as recom m ended by W agner, M unday, and H arrin g to n (1962), th e rem ainder being treaded w ith aqueous form alin. R eticulin w as ^dem onstrated in variable a m o u n tsin five ofth etu n & H irsex am in ed . ; V arious physical m ethods have ben p d to ; investigate th e tum ours. - E xam ination trad er , polarized fight reveals a few S m X S r i i i g e n t particles b u t does n o t show any H vtoi**colours. These are to o sm all, being less th a n 3 m icrons long, property to be called fibres, b u t th e ir extinction angle s is parallel to th eir long axis, as it is in asbestos fibres. P reparations o f fine d u st particles o f com parable : size, kindly provided by D r. A . A . H odgson o f the C ape A sbestos C om pany, show very sim ilar ap pearances, although a t th is rire m any o f th e fibtos are n o t birfringent. F urtherm ore, th e asbestos frag m ents seen in degenerating pulm onary bodies are usually o f sim ilar size and appearance. M aterial from three o f the tum ours has been calcined in an . attem pt to recover asbestos fibres, b u t none h as been dem onstrated. Owe Histories O ne typical m ate case an d one typical fem ale case are presented In som e deta|L sented is untisttal in th a t tw o are described. T he rem aining to o * . densed. T he clinical features a re sum m aritod ii T ables I an d 2 an d th e pathblogical findin{p in T able 3. In the tables th e cases a re a ^ a n g e d in order o f th e length o f exposure. ;/ t HISTOLOC No. in This Serie IF Biopsy Necropsy*! 2F Biopsy not it Necropsy*! jg Biopsy (not examined b) Necropsy*! 4F Biopsy not m Necropsy 5M Patient alive M Biopsy Necropsy! 7M Biopsy n o t mi N ecropsy 8M . Biopsy Necropsy! 9M Biopsy N ecropsy! IOM Biopsy no t ma N ecropsy IIM Biopsy N ecropsy Case No. 6 died at the aj "as heavily feeder for six he had a furt before his wa *" engineer'! Ashcsiosis w examination illness began death. Thre Hospital in 1 dragging abd "'iiting pair defaccation, a "me feeling <*'event weia 'w nchitis.M 'rlexant symp " 'niuincd not fiprororopiipaiiifi m m m IT WHfW iP gte i m PERITONEAL TUMOURS IN ASBESTOSIS 23 ' Tabu 3 HISTOLOGICAL FEATURES AND PRESENCE OF BIREFRINGENT MATERIAL IN AVAILABLE BIOPSY AND NECROPSY SPECIMENS FROM 10 CASES N o. In This Series IF Biopsy Necropsy*! Proportion Fibrous " T a n te 8 Arnuigemeot o f Cells Resembling EpiUielium Type o f Epithelial-like Cells & Alveo* Ur Clefts !u y Fronds Shrou Pave ment C uboii Co lumnar Poly gonal 0 0 0 0 0 0 0 0 4* + 4- 0 44** +4* +a a + Size o f 3J0*x!3t *is ifepsy ootm ade Nccropay*t 90% e 0 + 0 0 e + + a a 3x05 u gave negative. '''<rl _ . . with lemcMastrated in *' |mis examined, beco used to mation under birfringent wton's colours. 3 microns long, extinction angle of comparable odgson of the ap- . are >ncc. Material calcined in an It none has been l female case thin! case pte- crammed by us) Necropsy*!. w 4- 4" +0+ 00000 4F K opw not made 5 k + e + 0 0 0 4- 4- 5. Patient five 0% + + + 0 . 0 0 0 4- SM Necropsy! TM Biopsy not made Necropsy 2k 93% - 4 4 + 0 4- 4" a 4 + 0 4- 0 O 0 a 4* . 0 0 + 0 0 60 0 SM Necropsy! NotJivaHable 0+ ?+ Tr ! ? 50% DIfitaentiatioupoor 4* + + 0 0 0 0 + SM NffePcroypsy!. 9k + + + 0 0 6 0 f + + 0 0 0 e 0 4- IBM Biopsy not made Necropsy jo y . 0 + + 0 + 0 4* + IIM Biopsy Necropsy t. 20% 50% Tumnir in h u only 4 0 0 4- + + 0 0 + 4 00+ examtacd ' * Necrosis p rem i; t RetieoBn demonstrated; | Lyrapbocyiic infiltration. + 0 4- a a 0 i t + 4* 4- + N ot recorded + 1x0-3 p 4- 3 x 1 p Oa + 4- + tx e -3 is ? 4- 10x2 p. (yellow) 4 8 x 2 u + X frf a S x l is 4 10x2 is 4* N ot recorded i --VT XX Case No. (M (LondonH ospital 40336/47].--This died a t the age o f 38 w ith `carcinomatosis peritonei'. H e was heavily exposed to mixed asbestos dust as a hopper feeder for six m onths in 1939. After a break of five m onths he had a further two years' exposure as a `card' grinder before his w ar service. From 1946 to 196! he worked as as^ engineer's fitter with minimal exposure to dust. *'* " ` in 1954 on routine periodic ------ , -- before death. H is term inal i began w ith abdom inal pain four m onths before On examination he was a pale looking man. The fingers and toes showed mild clubbing. General examina tion was otherwise normal. The cardiovascular system was normal. The lungs showed poor expansion and scattered rhonchi. The abdomen was distended with ascites and the liver ballotted. Rectal examination was difficult because o f spasm and pain; a possible mass was felt. The central nervous system was normal. The ascites was confirmed by paracentesis, and a clear green fluid containing lymphocytes was obtained. The . T teee weeks before admission to the London Hospital in 1961 he complained o f the sudden onset o f dragging abdom inal pain whilst opening hisbow ela. A *" * worse on ..' fluid was not bloody and no neoplastic cells were seen. On June 7,1961, laparotomy confirmed the presence of fcard n areatoBis involving the Mver add peritoneum . A peritoneal biopsy (London H ospital 3312, June 1961) ' wes sepoH ed^s a `trabecularand mono-cellular, occa- 1 stone (6-35 kg.), mild < - f a t jj0 { tWlTHl i3w_h, " " apparently mucus secreting carcinoma, com patible wifl prim ary carcinoma o f the stomach' the patient developed a chest * which improved after a course o f chemo- perform ed on June 20, 1961, M itt m 24 BRITISH JOURNAL OF INDUSTRIAL MEDICINE f and mustine, 20 mg., was injected. On discharge he was not distressed by any abdom inal symptoms and was kept under supervision in the. out-patient department. He continued to attend periodically until bis death at home on September 17, 1961. Necropsy was performed on September 18, 1961 by D r. Enticknap. The body showed considerable wasting, and there was extensive pulmonary asbestosis with markedly increased black pigment markings. The entire peritoneal surface was replaced by continuous white growth in which all the organs were embedded. It par ticularly appeared to infiltrate the pancreas, but there were no discrete deposits there o r in any of the paren chymatous organs. There was a cuirass of growth 30 cm. x 20 cm. and 3 cm. thick on the deep surface of the abdominal wall. This was all thought to be due to a diameter) immediately below the capsule o f the liver (Figs. 3 and 4). Case No. 7M [King George's Hospital 49534}.--This man died at the age o f 78, and death was certified as due to `carcinoma o f the tonsil'. He had been exposed to mixed asbestos dust for 20 years from 1942. Annual chest radiographs from 1948 onward* all show ede*#- sive calcified pleural thickening. T his w asbefieved to be due to old tuberculous infection, aKboMgh Ite stoutly denied any previous illness. T w o m onths before death he was adm itted to King George's H ospital w ith a strangu lated hernia which was reduced w ithout operation. Refusing any investigation, h o returned hom e M ere he rapidly went downhill and died from the effects o f a large growth in the pharynx. '' -- Necropsy on September 26,1962 by D r. D . Rushton shcwgd4>rowa atrophy o f the itg w e a M w ith modtaaiB ; \ 5 , . bodies and some birfringent spicules abdut 3 x 0-5 back o f the throat. There were secondary deposits to th e microns. The bulk o f the tum our material is loose upper left cervical nodes, and the growth extended into fibrous tissue composed o f spindle ceils among which are the cellular tissues o f the neck. The lungs showed con hyperchromatic polygonal cells in a proportion of about siderable fibrosis and pigmentation with a mass trf fibrous one in ten. Periodic acid Schiff staining does not reveal tissue 5 cm. across te the left upper lo b e M fc any mucus o r xymogen granules (Fig. 2.) central cavity. The pleurae were obliterated and the diaphragm was thickened and calcified. The upper Case No. IF [Queen Mary's Hospital 26655].--This surface o f the fiver was covered w ith firm w hite fibrous patient died a t the age o f 44 with `carcinomatosis peri tissue up to 1 cm, thick. There were numerous small tonei'. She had been exposed to mixed asbestos dust for nodules and plaques in the visceral and parietal peri a short period o f 10 m onths in 1935 in the carding depart ment. Asbestosis had not been diagnosed before death. The term inal illness presented with abdominal pain and distension after meats. On admission to Queen Mary's Hospital on January 15,1961 she complained of pain in toneum in the upper part o f the peritoneal cavity, but these did not clearly invade any o f the organs. The spleen was similarly encased in white thickening o f the capsule, but the bowel was unaffected. Histological examination of these tissues shows a the left groin; the abdomen was distended and a mass typical transitional-celled carcinoma of the tonsillar was felt. A t laparotom y on May 30 there was much free lymphadenoid tissue (Fig. 5) quite distinct from the t ^ e fluid in the abdomen, and widely scattered nodules were of growth seen in the peritoneum in th e other cases. On seen. A biopsy o f the peritoneum was taken. She died the other hand, the thickening o f the capsule o f the liver, in hospital on August 3, 1961. which does not invade thepareochym a, is o f th e same A t necropsy on August 4,1961, D r. M. S. Ross found tissue as that seen in the patients dying from the effects dense pleural adhesions, partiularly to the right dia o f abdominal growths. It is predominantly spindle-celled phragm, w ith m oderate pulmonary oedema and con w ith a smaller number of diffusely dfatributed^ hyper gestion. A little fibrosis was seen. The parietal peri chromatic polygonal cells, some o f which are forming toneum was studded w ith fleshy nodules up to the size of irregular clefts (Fig. 6). The lungs show relatively little a sixpence, as were the pelvic peritoneum and the surface fibrosis with a m oderate am ount of black pigment and a o f 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 (1 cm.). The ovaries were normal. Histological examination shows moderately advanced asbestosis o f the lungs with fragmentation of most of the few asbestos bodies. Birefringent spicules are present in the surface layers of the liver mass and are 1 x 0 - 5 microns in size. Case No. 2F (N o hospitalization).--This woman died at the age of 67 from coronary thrombosis and chronic bodies. Related to them are birfringent particles which bronchitis. She had been exposed to mixed asbestos dust are doubtless asbestos. There is advanced broncho under the bad conditions of 1916 to 1919 in the weaving pneumonia and long-standing changes of congestive department. She was diagnosed as a case o f moderate heart failure. Tb tum our from the peritoneum is pre asbestosis in 1946. She first complained of indigestion in dominantly irregular fibrous tissue, with uniformly 1960, 19 months before death. Gradually increasing distributed small birfringent particles. The spindle cells ascites developed- The term inal illness began three o f the m ain mass have fusiform nuclei of varying size, m onths before death with anorexia, flatulence, constipa but they are n o t hyperchromatic, nor do they look tion, and increasing ascites. D eath was caused by an particularly m alignant, and there is no pseudo-epithelial acute coronary occlusion. growth. Sections show, however, spherical secondary A necropsy by D r. D . Rushton confirmed the coronary deposits o f this peculiar fibrous tissue (up to 3 cm. in occlusion and patchy myocardial fibrosis. T h e r e was no I*,- -X-& ... ''XV- . ippim i*M .iiiiiiw j,ipi,ii... ,iuiun.uym||p|fi"1"I jiw inim puppp I, ' 1 o f the liver Spital 49534J.--This 1was certified as due id been exposed to fom 1942. Annual js sit showed extenf was believed to be llthough he stoutly Mhs before death he |ita l with a strangu- ' ` operation, i hom e where he py O r, O . Rushton dtutn with moderate tonsil was replaced ulcerated, filling the ` tlary deposits in the berth extended into ` lungs showed con- )th a mass o f fibrous ] lobe which had a ibliterated and the , fled. The upper Jfirm white fibrous jre numerous milt | and parietal peri- ritoneal cavity, but iorgaas. th e spleen ihtg of the capsule, i tissues shows a l o f the tonsillar Jtinct from the type fie other cases. On ipsule o f the liver, i, is o f the same . from the effects itly spindlecelled distributed hyper* vhich are forming row relatively little ~ pigment and a :ules are present in and are 1 x 0-5 . - ;;;i-This woman died 'rf*ptosis and chronic nixed asbestos dust 19 in the weaving i case o f moderate jwas caused by an >, i frmed the coronary -kis. There was no , *<>!* i iii iflifttiini PERITONEAL TUMOURS IN ASBESTOSIS 25 FtO. t.--Biopsy section, x 130. Fkj. 2.--F.M. section, x 110. ... W * mM `'i/? * r* v i i 'i ; Fio. 3.--Biopsy Motion, K IM. im Fio. 4.--RM . ection, x 130. opp* m m fm 'i ywy(L"i|iwiP j jpMP I * mi ipwipiJiniijijip M R H mm BRITISH JOURNAL OF INDUSTRIAL MEDICINE cor pulmonale. Bilateral pleural plaques were presentand a 5 cm . calcified pleural plaque. The lungs showed a degree o f old fibrotic collapse, some carbon and shorty thickening consistent with patchy fibrosis. There was a chronic peptic ulcer. Widespread o f the peritoneum with and plaques was a confluent ftrm m ass S cm. across were seen in the pa and porta hepatis. The right lobe o f the [ a large yellowish-white rounded nodule but in contact with the serous o f the lungs confirms bowel shows greatly thickened but also contains Cells. A few from the _ . but the typical clefts and papillary O n e No. F {King George's H ospital 98753].--This woman died a t the age o f 61 with `ge m atosis o f the abdomen'. She had exposure to m ixedasbestos dust ftom I9 l ta the and m artres sputum in 1956a n d a radiographsb asbestosis. The ` " before death with loss o f weight, she was found to have liver, and ascites, She died within a few in 1962. At neoopsy Dr. I. in the liver shows extensive O m No. 3M {London Hospital 190984}.--This man died a t die age o f 52 w ith `peritoneal endothelioma arid asbestosis'. He had been exposed to mixed asbestos dust from 1930 to 1934 in the carding department. Pulmonary ***yrtnrit *** iik st2V at the London Hospital in 1963. This admission was for pain in the loins and under the right costal margin, anorexia, loss o f weight, general malaise, and pyrexia. A t laparotomy the liver was found to be slightly m ottled and granular with my adhesions between the lobes o f the liver and the diaphragm on the right. N o obvious masses were found in the liver, but in the porta hepatis there was a big irregular mass continuing into the liver, and there were also multiple para-aortic glands. Some o f the mass was excised for biopsy. The patient was followed up in the ,,pt-p"" department but died a t home two months after discharge front th e ward. The following is the biopsy report from the London H ospital: `M alignant papillary-tubular neoplasm, posibfy but not^ ^c^pe*KteicaHy renal in origin. Primary peritoneal endothelioma is suggested by the A t necropsy on July 29, 1963 D r. D . Rushton found extensive adhesions a t the base o f the right pleural cavity and the dorsal region o f the lung. The lungs were tough to feel, firm er than norm al, collapsed, and oedematous. There was old tuberculosis at the right apex, but the gross characteristics were n o t obviously asbestotic. Sections from the lung, however, showed fibrosis and asbestos The peritoneal cavity contained a large am ount of turbid yellow fluid. There were widespread numerous TMfft white nodules scattered over the whole surface o f the sm all bowel, (he large bowel, and the peritoneal surface generally. The diaphragm was extensively ad h e re n t thnupper surfece o f the liver. There was a large growth 4 in. (161-6 mm.) in diameter and white in colour near the liver hilum , which did not involve the stomach. The entire p a n c r e a t t e ^ ^ d u T to r a t^ M a o f the pancreas'. The necropsy sections is thickened byS m m . < there are some clefts lined by t5 x It O n e No. 5M [London Hospital 141164].--This man was Uncharged from the London H p ita l with an inoperable malignant growth in the peritoneum. A t the tim e o f writing 1 isidive and apparent^ weft 10 months after biopsy. H e had been exposed to mixed asbestos dust from 1937 to 1940 and again from 1945 to 1955, when asbestosis was diagnosed. The development o f a pleural effusion hi 1961, with its s in te r im plications, led to thoracotom y. There was no evidence o f malignancy, but a collapsed right lower lobe and 4 huge am ount o f clear straw-coloured fluid were removed. The removed lobe was clearly asbestotic. One year after lobectomy he was re-admitted for investigation o f dyspepsia with pain, vomiting, flatulence, and ascites. A t laparotomy there was m arked straw-coloured ascitic fluid and multiple small mtastass covering the peritoneum. The omentum was shrivelled and ipdurated, and on the upper surface of the left lobe o f the liver was a peritoneal plaque. No secondaries were seen in the liver. The condition was considered to be inoperable, and a biopsy was taken from the omentum. Specimens from both operations were kindly supplied by D r. D. H ourihane o f the Bernard Baron Institute. The lobectomy specimen confirms the presence o f advanced asbestotic fibrosis, but tbw e is no tum our. The ab- ing cteftv so W masses, and ,alveoli. ^ 1lire histologiesI ` fecasearem orerem inisoentofi' i any o f the other < in visw o f the haraetertstics seen in the whole series and ~ " " secretions, this diagnosis is Case No. g] man died a t th He had been e from 1929 to was m ost met) position as for man o f the m M sterm taaH l six months b dominai pain, tion. A t lag looking carcin and abdomin. viscous free fli Bennison rej occasional ca pancreatic gro The patient Bennison foui together by nu also present < surface,,in the Histological firms pulmon; growth from structure o f . tumour with t formation seei birfringent p appear to be 1 muscle o f the Case No. 9A at the age o f 5 been exposed His exposure ork had alws Asbestosis wa: apply for certi six months bef >n 1961 becate eft flank. A peritonea extensive fibre and 'acinus-Iik characters'. At necropsj embolus, pnei hiatus hernia,; hard white tiss The histolo( ' cr>' similar tc 'fondcm 4033 ''rm ations. asbestosis. C'a No. j sas was full amber 24. K ! e previous ct .'ears froi . T3 S ,:i .' *; ' ii,1'l"ii|J L iiu p g fW P f  |o tic fibrous tissue -'nations are seen. 987531.--This neralized carcino? ' ; eight years' H 6 in the jointing :fore the hazard found in the I some degree of an three months discomfort, and C'a Hospital an enlarged ys o f admission pleural adhesions The entire udded with >present on the i and uterus m aterial The bowel wall i in which do-epithelium. She found. il64J,--This man [ospital w ith an t'fto n e w n . A t the y well 10 months * mixed asbestos in 1945 to 1955, development o f a implications, led S, Je of malignancy, "% arge am ount o f The removed w ith pain, m m there | multiple ! om entum m Instistnutrefa. cTehoef ;y;!;f, .1pe oo faaqduvea.ncNedo condiTtiohne waba-s . * $yn5wnraasr tcaekilesnfofrrmom* ofadeno- described, but, m : rhole series and m* is PERITONEAL TUMOURS IN ASBESTOSIS 29 Case No. 8M [Harold Wood Hospital 55085].--This 1937. Pulmonary asbestosis was diagnosed on periodic un died at the age of 47 with `carcinomatosis abdom ini'. examination in 1954. Histological exam ination o f le had been exposed to mixed asbestos dusts for 25 years m aterial from the London H ospital necropsy, kindly !fi>m 1929 to 1954. For the greater part o f that time he provided by D r. J. Landells, confirms pulmonary as a* most meticulous in the wearing of a respirator in his bestosis and bronchopneumonia. O ne section ^Kmt p,-smon as foreman. For the next five years he was fore ileum entirely surrounded by tum our. H its is p re man of the gardening staff. Pulmonary asbestos was dominantly alveolar with a mono-layer o f cuboidat lining never diagnosed although he was radiographed annually. ceils which are regular in sire. Some typical `adeno- 11is terminal illness began when he presented to one o f us carcinomatous' formations are seen, and some dilated m\ months before death complaining of burning ab alveoli contain papillary processes. There are however dominal pain. H e was adm itted to hospital for investiga some epithelial lined clefts quite unlike carcinom a in tion. At laparotom y the surgeon reported mucoid their irregular slit-tike configuration. looking carcinomatous deposits in the peritoneum, liver, and abdominal organs. There were several pints of Case No, JIM [Hammersmith H ospital 227252].-- wscous free fluid. A biopsy was taken, on which D r. H. This case was folly described by Heard and Williams Dennison reported mainly anaplastic growth with (1961) as their case number 6, He originally presented occasional capillary and tubular forms. A prim ary to tme o f us (W JS .) became be was concerned over bis pancreatic growth was thought likely. ICp fogrt hyd The patient died two days later. A t necropsy D r. and distension foreiglttnsontixs/D r. B H eard has kindly Dennison found th at the coils o f the bowel were held provided sections from the lynpuy 18, together by numerous soft nodules o f growth, which were 1959) and necropsy (December, 1959). Histological also present on the parietal peritoneum, on the liver examination o f the biopsy specimen shows a nodule about surface, in the abdom inal nodes, and in the pancreas. 1 cm. aero with fronds o f very vaaentar tissue and some Histological examination o f necropsy m aterial con small alveolar and solid masses. One nodule contains firms pulmonary asbestosis. The bowel is invaded by birefringent needles 5 x 1 microns. growth from outside. This shows the same histological structure o f clefts in a solid, predominantly fibrous tumour with the capillary and alveolar pseudo-epithelial D iscu ssio n formation seen in the other cases. There are occasional birfringent particles. ' Although the tumour does not In th e p ast five an d a h a lf years w e have seen 52 appear to be highly m alignant, it is clearly invading the c a se so f asbestosis a t necropsy. N ineteen (36 % >had muscle o f the. bowel. carcinom a o f th e lung, none o f w hich w as pleural in Case No. 9M [London Clinic 1961].--This patient died at the age o f 57 with ' carcinomatosis peritonei'. H e had been exposed to mixed asbestos dust for about 27 years. His exposure was minimal a t any one time because his work had always been clerical, supervisory, and technical. Asbestosis was diagnosed in 1948, but he did not wish to apply for certification. The term inai illness began about origin. F ourteen (27% ) had abdom inal tum ours, nine (17% ) o f w hich appeared to o rig in ate in th e peritoneum . T here w as a single case o f carcinom a o f th e b reast (2% ). A possible to ta l o f 9,550 people have been occupationally exposed to asbestos a t tibia one facto ry ..since 1913. Including tw o cases, th e necropsies o f w hich n eith er o f u s atten d ed , th is gives six months before h& final admission to the London Clinic an incidence o f p eritoneal tu m o u r o f ab o u t 1 in 1,000 in 1961 because o f abdom inal pain which radiated to the left Bank. A peritoneal biopsy (2117/61) was reported to show `an extensive fibrous reaction amongst which there are clefts and acinus-like form ations lined by cells with serosal characters'. At necropsy D r. F . E. Camps showed a pulmonary embolus, pneum onia, minimal pulmonary asbestosis, a hiatus hernia,and diffuse infiltration of the peritoneum by hard white tissue. o f those exposed. It should be n o ted , how ever. th at as m any as 46 years m ay pass before the onset o f the syndrom e, an d in none o f o u r cases w as th e interval less th an 20 years. A num ber o f cases m ay have died elsew here since n o special effort h as been m ade to follow u p all th e people occupationally exposed and th e eventual incidence m ay oe higher. I t seem s clear th a t this is another clinical condition th a t m ust be recognized as p a rt o f th e asbestosis syndrom e, ju st The histological appearances o f the necropsy tissue are a s carcinom a o f th e bronchus is now recognized. rcry similar to those o f the first case described, case 6M London 40336/47), showing both strom a and alveolar formations. The lungs show a moderate degree o f asbestosis. F urtherm ore, the condition is associated w ith in d u strial exposure though th ere m ay n o t b e enough pulm onary fibrosis to qualify fo r codification. In previous series (R eal, 1960; B onser ttm l., I95S) Case No. 10M [London H ospital 27245/56].--This o f som ew hat sim ilar cases, th e m ajo rity o f p atien ts casc as fully described by Real (1960) as his case w ere w om en. Indeed K eal concluded th a t m ost o f number 24. He had been exposed in the same factory as h is cases w ere ovarian carcinom a, a s d id th e p a th o - the previous caw s in this series to mixed asbestos dust for logists in tw o o f th e th ree fem atecases rep o rted here, four years from 1931, and less heavily for 17 years from b u t eig h t o f o u r 11 cases w ere m en, an d w e have also ; >' i -i WWtWJt' s i* oMMfii niai-tiU m tm tm N- 30 BRITISH JOURNAL OF INDUSTRIAL MEDICINE been ab le to exam ine m aterial from a w hite South A frican m an aged 44 by th e courtesy o f D r. J. C. W agner. T h is m an (EN7Q5253) lived near asbestos dum ps in his youth b u t w as n o t occupationally ex posed. A single section show s a cellular reaction in fibro-fatty tissue o f th e peritoneum and dem onstrates a tran sitio n al form betw een colum nar pseudo- epithelium an d irreg u lar fibrous tissue. T here are no asbestos bodies n o r an y birefiringent m aterial. A hyaluronidase test w ith toluidine blue w as negative on t l sectio n b u t th e form o f fixation is unknow n. HistolQ$pa% it is sim itar to a n d is probably p atto * genetically identical w ith th e L ondon cases. . T here can b e no do u b t th a t th e predom inant abnorm al m aterial in th e sections is o f fibrous tissue o rig in , an d such cd fe as resem ble serosal epithelium ap p ear to b e derived from them . In th e m o # stages, see In peritonea! biopsy, fhe lesions are m ore cellular, an d later they becom e m ore fibrous. Progressive m assive fibrosis in th e related description o f prim ary `colloid canoers' o f th e peri* toneum . N either h e n o r to y su b se q u e n t au th o r offers any convincing p ro o f o f th eir m alignant character, and there does not ap pear to have been th a t T h e re is scam tiy w hich is so ill doubt as to its such as th at < w hat is clear fto ra may assum e m an y 1 , d istin ct o r g ^ r e d '|4 M M s m ip |^ stances. The (1942), w hile d ea rly au th o rs to be som ew hat analogous, and silicotic granulom a due to talc is an o th er com parable condi tio n . Since m uch inhaled foreign m aterial passes in to th e gut (H ilding, 1963) it is probable th a t som e a t least w ill en ter th e abdom inal lym phatics. W e have suggestive evidence o f its presence in these peri toneal tum ours, and fu rth er searches by electron m icroscopy an d by x-ray diffraction m ethods a t present being carried o u t m ay confirm this. How ever, in these patien ts w ith peritoneal tum ours the pulm onary changes due to asbestos are below average in severity (disability has been com m only assessed a t 10 to 30% ). I t m ay well be th a t th e sh o rter life sp an o f th e severely affected w orker is the reason why the syndrom e is n o t m ore com m on. A n o th er cause o f confusion is th e frequent diagnosis o f som e o th e r form o f neoplasm o f w hich we have exam ples in carcinom a o f th e stom ach, ovary, pancreas, an d to n sil, a s w ell as th e unclassified cases o f carcinom a o f th e peritoneum . W agner, in a series o f publications (W agner et al., 1960; Steggs, M archand and W agner, 1961) has claim ed th a t tum ours o f th e m esothelium are peculiarly liable to occur in asbestosis. In one A frican com m unity h e h as claim ed a very high incidence indeed (personal com m unication) despite often m inor exposure, in som e cases confined to childhood. W e d o n o t exclude th e possibility th a t th e m asses w hich occur in the abdom en in the syn drom e w e describe a re m esotheliom as and therefore tru e neoplasm s, b u t w e d o n o t believe th a t o u r evidence, o r any o th er o f w hich we are aw are, justifies such a confident assum ption. T h e earliest reference to sim ilar m asses w hich we have encountered is von R okitansky's (1854) m ind regarding (th eir) exact h rito g taeritf, an d B row n a n d Johnson (1931) fran ld y cem g th e th e `en d resu lt o f a low grade iefiam n tatrey process w ith organization o f th e exudate*. I t is abundantly clear th a t speculation is m ore readily avaU able th an fact concerning these tum ours, an d we consider it m ore helpful to ad d to th e latter th a n to th e frem er. W e are im pressed by ti lade o f occupational d ate- in- nearly a f t of. tto c B p ic a l histories w ith th e exception o f th e m ost recent. f t is o u r opinion th a t these m asses d no* in fact closely resem ble neoplasm s, an d , a p a rt from these contro versial cases, we have n o t encountered a m eso theliom a in several thousand necropsies (see E nticknap, 1952). tit th e uniform presence o f a history o f exposure to an industrial irrita n t * iiat has n o t yet been show n to be oncogenic, we th in k it unw ise to give t t e nam e a f a specific neoptatsm totiiB syndrom e an d prefer, w ith M ilter and W ynn, who recorded th e first B ritish case in 1908, to say `We shall n o t attem p t to give an explanation . . . we m erely reco rd th e faet(s)\ T he exact n atu re o f th e tum ours m ay only be elucidated by th eir experim ental p roduction in anim als, and details o f W agner's (1962) experim ents are aw aited w ith interest. W e have in th is series had an o p p o rtu n ity to exam ine by conventional m ethods a large am ount o f hum an tissue sto w in g these changes an d te d it is u n lftely th a t such studies will perm it m ore th an an inforihed. opinion. A s w e have been n a to te la -h e course o f studying f|igpe cases to form a definite opinion a s to th e n ato re o f the abdom inal m asses, we p refer to e v a d e th e issue by referring to th e predom inant tls s u e in them a s 'wild fibrous tissue', to d w e believe it m ay b e a direct j Iy . reaction to the ; serosal cells, called the peril exact nature be In the fifth ce to denote plast term asbestosis logical effect of lung, th e pleur; We would IS people who havt which thisrepor individually, but have been writt kindly given us came within his photographer, w AvWerman^L, V. (I and 24, p. 10 ton. mm-1 SHWWWp ip ? ! 5 1 o f th e periv f??o p isB t author .^.hetr,! r to h aw been Lubarsch (1895) ? |p y o f tum our flits o f so much blogicat studies, u t an d M urray th e ability of due V'-3 To >th a t `It -,,>h. f t p tf a s ty peri* f , W illis (1952) .reserve a n open ` ' and PERITONEAL TVMOURS IN ASBESTOSIS n reaction to th e presence o f foreign m aterial in the serosal cells. W e propose th a t th e condition be called the peritoneal tum our o f asbestosis u n til its evict nature becom es clear. In the fifth century a .d . o ta r^ eo rcix n f w as first used to denote plastering o r stuccoing, in o u r view th e term asbestosis w as m ost a p tly chosen fo r th e p ath o logical effect o f asbestos. A sbestos m ay `p laster' th e lung, the p leu ra, o r th e peritoneum . - We would like to express our thanks to the many people who have helped us to collect the inform ation on which this report is based. They are too numerous to list individually, b u t w ithout their generous help it could not have been w ritten. H.M . Coroner fo r West Essex has kindly give us permission to report the cases which came within his jurisdiction. M r. 0 , R. H all, laboratory Photographer, was responsible for the photographs. AckermavL. V .(t9S4). A ttn o f Tumour Pathology, Sect. 6, fase. 23 and 24, p. 100. Armed Forces Institute o f Pathology, Washing ton. Bonier, O. M .Fauids, 1. S,, and Stewart, M. J. (I9SS). Amer. J. elio. Path., 25, 2. " ................................. ,2 0 9 ,4 1 5 . r'BTeTimd W W .^ 'R .(lW t'). Thorax, g A. C. <1963k Arch, rnrironm. Hlth, 6 , 67. E. B. (I960). Lancet, fi, I2M. sr,F,<1954). Arch. Cewerbepath. Gewerbehyg., 13,382. tubarsele V A. (1*95). Lubarsch-Ostertax Ergebntae tier Path. u. /bu tt., Bd. it p. 265. Wiesbaden. Lynch, K. M,, and Smith, W. AVISOS), e r .Z Cancer, 24,56. M ancuso.T. F ., and Coulter, E. }, (1963). Arch, antranm. Hlth, 6219k < '- . R ^S ik y rC ^^S M )1 Soe. Trans.. London. Selikoff (1963). Personal Communication. Sctikoff, f. J., Churge, J., andHamrnond, E. C. Paper presented a t a Joint Meeting o f Sections on Radiology and Diseases o f the O iest o f the American Medical Association and the American College of Chest Phyjicisnson June 7 1963 at AttanticCity, N J. Steggs, C. A .. Marchand, P,, and Wagner, J. C .(i9 6 l). S.Afr.m ed.J., -- .Stumpf, H. H. (1954). CornerR, 7^(,1l.4%22.)- **.**., * 1 * . Wagner, J. C. (1962). NatarelxmdX 196,180. D . E., and Harrington, J. S. (1962). Z Path. Bart., 4 ,7 3 . --_ 7*2o!' C and Marchand, P. (1960). Brit. Z Imhatr. Med., W lfils,'r . A ., (1952). The Spread o f Tumonn In the Human Body, 2rtded., p. 57. Butterworth, London. Winslow, D . J., and Taylor, H. B. (i960). Cancer, 13,127. |ilation' is m ore ? these tum ours, tdd to th e latter Wed by th e lack , o f th e clinical iost recent. I t is it in fee t closely in these controntered a m esohecropsies (see "a irritan t th at has w e think it nd W ynn, who to say `We ion . . . we fs m ay only be j pro d u ctio n in ^62) experim ents f, th is series had tionalm ethods shourfng m e su ch stu d ies will jo n . ' m a m hg these cases to M&MlM'"wt f e ,, to e issue by im to w ssa^ S sK i . ty be a direct f Ilfl wrap " m m m.