Document NeqVoGVkErzrNZxbZz4bKMwMQ

Original Contributions l MALIGNANT MESOTHELIOMA I WITH MINIMAL ASBESTOS ; EXPOSURE* Wei'jen Chen. M.IX,t and A'. Karle Motif(, M.D.$ JTAINTIKK'S KXII1H1T FJ1-3M Abstract TIu* association of malignant mesothelioma and ask-stos libers is well estab lished. The minimal ex|x>sure ibai may produce llie lumor is not known. The present re|Min documents the mininuil exposure by thorough examination of occupational history and |>crsonal hobbies, and counting of the number or asIn-stos lik-rs in the loons. The evidence lor the elemental coni|xisition of as k-sins lik-rs by uleriron prok- (El)AX) is also presented. The asMK'iation of an increased inci dence of malignant mesothelioma in in dustrial workers and others having exten sive cx|x>sure lo asi>csios is well esiablishccl cpidemiologically.'*4 The maximal sale exposure level remains a major problem because the presence of some ask-sios in the longs lias k-eu demonstrated in a large segment ol llie imputation.-'1 The great individual variation in rcs|>oiises to exo genous chemicals further complicates the problem. The rase til malignant mesothelioma rc|Kncd here is significant because we have established the presence of pulmo nary asbestos libers by means of electron prok analysis and we have obtained a complete and thorough history docu menting a most casual and minimal exposmr to asbestos in a iiimsmokcr. Estima tion of lltc number of ask-stns fillers in the lungs suggests the low level ex|K>sure and establishes lhai. for some individuals ai least, slight exposure to asbestos can result in malignanl mcsnlliclinma. CASE REPORT A 59 year old white male, a non smoker. was in relatively good health until Inly lii7.r, when he developed mild This investigation was supported in pstn by NIH grams KS 00077 ami (>M 001(H). I'rofrwiT. Department of Pathology. University of Washington School of Medicine. Seattle. VVsiwhiiiginii. . Jl'mlchsot. Deparimcol of l*iilliology. University ol Washington of Medicine. Sul!. Uni< vvrMiv tltivpimt. Vmvvaivi Atimiimuatmn Hospital, and Hurlmrview MckIkrI Unicr, Seattle. \V;i*hiiiguni. ' B001 0976 SC-ALL-21101 PRODUCED BY FORD SCF-FA-7285 i II > ' o. HUMAN PATHOLOGY- VOLUME >, NUMBER $ Mm /V7JY / ^/ Figure I. * host IiIim icu.iK mawm- right dilfd pleura) cIIiimom ami ihukriimg ol ilu' |ti*mi with mutit}>h' it*hih> I1m' ltii hum appeals m In- noiiiial. tiple cliemotliernpeiilir a^enis (cyioxan. iilei Inn resale. n-lliinrnnrueil. ailriainyein. and procurha/.ine) witlioni response. 11 is course had Iteen nne ol gradual deierinraliim niili marked shnnne.ss of hrealli and weijfhl loss, and lie expired Ml minnlis alter the tinsel of svinpimnx. An exlensive liislnrv of' more than :l(t years was ohiained In mi die wile oldie tieceased. Ai no lime in his life did lie smoke. He jpew li|) in I'eniisylvania and >>radualctl from a well known instiimc of tech nology as an engineer. Following a year ol' business management training liy a large building maierials linn, lie served in the Army Chemical Warfare Division (lining World War II. However, he had imspecific exposure 10 ashesios or oilier known res|irauiry toxins. following the war he reiurnetl as an executive in the linn where he worked until six years prior inexamina tion. He iranslerred to a lilterglass linn in a similar executive |x>silinn where he work ed until Ins death. At no time in his life chronic nuts'll and exertional ikspnea. Chesi x-rac examination showed lumor musses in tlit.- iihIii upper and middle lnl>es and rijilti pleural elltistoii (! i^. I). HsploraItirv llioratonnm resealed minor nodules simUliiix dir riniir )i^'ln pnriela) and vis ceral |deni al- anil a pm'lion of I lie pericaidium. Hiopss examination of this lumor was reponeil iniiialls as "larj*i' cell tutdilIcieiitiatcd .11 iiinnm.'' A dmrnui'h meiaslalii win k-up including ii|i|ier Kasiroinleslinal series. Iiai inin enema, and liver and spleen scans vias negative. Suhsei|iienils die |ialieiil was Irealed wiili mul dnciion or lahricaiion. As an executive he 1 Htiisionallv inspecled major cmisirnciion siies Inn did 1101 personally handle. Imild- iinr maierials. Ilis avocaiional imeresis centered on s|xns. lie was 1101 a "dn-ii- yoiirseller" anti did mil liave a workshop al home or power looks. We were unable m uncover anv aciiviiv dial would simuesi more limit die casual exposure alluded 10. The aiilopst revealed mailed minor masses encasing die emire right lung with t XK usitin m ilu* miIh iiiimhmhis tissue ol llic ri^hi chcsi wall and jKTitardiimt 1M- Mieroscopicalk ilu* iiimnr consisii'd of !& 4 iVe- Figure 8. The aulop*y specimen olihe right lung is completely encased in a maiiecl. pletir.il tumor mass. The ummr alv* im-adrs by direct extension into die ficik'at'dmm. diaphragm. ami right 1 he*a wall. r>4 SO 01 0977 PRODUCED BY FORD MALIGNANT MESOTHELIOMA-Oilk. Mottit Figure 3. Sections or tumor from right plotnil shotting two riiilcrcnt* piiiicrii* trpiihdial unit inooohymiil) nf Hiiiioi i ells. (iiiitiK'U'iistk' or malig nant nu'viMlu'liimv.i. I. Sheets amt ag- <1 nuilijjMHiii epithelial cells. H. Spindle tells (s;ircoinau>us pattern) tvilli Jivpm)iromnik; nuclei. components resembling both epithelial and mesenchymal cells characteristic, of mesothelioma (I-ij*. :t)." 1'ive grams oh par enchyma) tissue was taken from each Iting and digested with sodium hv)>oehU>ride by ilie method or Smith and Naylor.' The extraction solutioit was filtered through it nuelcpore membrane (:>n). Figure ! shows one of the ttnstainetl asbestos bodies on a filter membrane under light micro scopy. The entire membrane will) retained fibers and crystals was coated with a thin Figure 4. Extracted asbestos ImkIv retained on nucle|>ore mem- hram* alio (iliraiinn. The center ;i>l>cMns IiIh') |iou*> unit twitted )m>t- iMMISiHC t ll'ill'lv (liuonil)lc. (>400.) RltOl 097R PRODUCED BY FORD HUMAN PATHOLOGY- VOLUME 9. NUMBER S Alov IV7K i Figure 5. Ik!\ owtefl will) i\ thin l;i\o <it |Mb(liuiti ml VK'wi'd bv K'uimin^ election iniiioMo|)\. The tcnicr (core) and htailrd urcilc;oh keen. .The Iwckgrourxi i;tc)c|<>:e i> .* n in iliiinieici. |/ Figure 7. X-ray <li%|cr*HHt Crum Itcuricrf |>iiiiiifi urmitiil lilicr (Fig. .V). This |Miruon contains a Luge Hiuniiiii nl Fe in nrifiiiion to Mg. Si. ami (In. Again lire |>ala<linnt )K`ak - On* coaling. ivxults liom Icivei o( paludiuin aul ilivu subjected to ik'dn)ii probe vi;i\ dispersion aiiiihsis. KDAX tenergy dispersive x-ray analv/.er) was used to aitalw.e ilit* x-ray dispersive spectrum ol dill'crcm elements." I'ijooc n depicts Dm' i>l tin- asbestos bodies seen under a low power Manning electron uiirrnscupe. 'I'lit.* lilicr core and beaded bod\ portions are readily discernible. By directing the electron lieam to e::!`.;:r a thin tore (Kij*. <>)or thick beaded portion (Fig. V) two distinct x-ray dis|K`ision patterns were discernible. `The tlilVevenve in unn|Kisiiion ol' these two areas is the presence of iron in thick beaded portion. Ollier EDAX patterns of some naked "asbestos" fibers exhibited the same elements as that from the thin portion of "asbestos" bodies. DISCUSSION Figure (i. N*i,i\ ili>|n/isi*n >peciruin (turn jvIh'x|i>n itliei M il: .V.` I Im i lu inical lomjMincnts nl Mm*i iniii i mu Imlfs Mg si. amt (Iu. The itM. |k ..k icmiIk hum ilu *.mug in wimple piepava* !< in Ini mjiiiijiiu elnhnii mu i.iM.jn, Kcnnmin i. iionmi.il. There has Itecn an increase in interest in the biological elicit ol asbestos since liMid when Wagner el ill.' in South Alika reported the association ol' asbestos with malignant mesothelioma, ('.linical and pathological studies revealed no evident correlation Ixnwcen the occurrence of mesothelioma and severity ol asbestosis.2-'1 In some instances even indirect occupa tional exposure or community exposure may also he a factor comrilniiing to the development of malignant mesothelioma." This observation |>oscd the possibility that even a minimal exjiosttre to asbestos lor a short jKnjocJ may cause .the cancer decades litter. In our modern society, with broad ening usage of asbestos in consumer pro ducts. asbestos hits been becoming an en vironmental hazard.1'1 Tn a scries of necropsy studies Hhiiguvan and Koss't found it substantial increase in the number snoi 0979 PRODUCED BY FORD MALIGNANT MESOTHELIOMA-- Cun*. Morrr.T of asltt-slos Ixxlies per 5 >rin. of Iuiir after die IfHOs and also a gradual increase in lilt* number of asbestos lx xlics per ii urn. of limn will i increased a^c al drill It. 'Tin* case iiv have int'scnicd illusi rales dial minimal cx)Hixurc hi asltcsms can cause iiifMiilirliiiiiiii. We mole Tnidiiplc .*> nin. samples Ikiiii IkiiIi limns iind coiimed the aslant os libers. There was an avenire of IliH libers per .*> j*rain sample of limn. Tliis linnir is I I limes liinliei ilian ihcaj{einaulit'd mill ml ill? *t nm ) and alxmi six tinii's higher ill.ill die iiiran ol' ashcsltts (ilii'is CJK.li .* "iii.i ill a I'onirol (topiilalinn rc|xiricd In llli.inm.m mid Koss.:' II'one assimiedili.il Ixitlilimns weinlii'd liillll Kin., lhere would have been approximately fiO.-PMI filters (I (iS X ^') in I lie ItlllKS. If one assumes die nvernnces|x>sure lime for L'tl years, die yearly accumulation of filters in 'die limn would he U'tlJII per year f5(l.d(M)/L,ll). This limine is minuscule ii we consider die enormous niimltcrs of filters thal will la- inhaled in an envirnnineni old! libers )X'i ml. set hy tin- Omipaiionul Sal'eiy and lleahli Administration as die saleiv limit.11 Our ini'dioil ol i|iinmitnliou of litters differs markctlh I mm that of'l'onley.'1' Me exiraelcd die filters from Ii /mi. hisiolonic section siimples. whereas we used it n11'wei lissue samples. Our samples lliereforc are main thousands of limes larner than his. We believe dial die ease presented here would have I teen included in his eaii'n<i y <i (zero lilieis found |tcr grid). Ii is well I'sialtlislieil dial die Ittiniaii IxkIi can remove mosi of the filters in haled. The accumulation of ashcsios lilters in this patiem lo a level ahove die control levels resulted from cither cx|x>sure or diiiiiiiislicd clearance. Till' well ditcumcnied minimal exposure in this case suy;ni-sis tliai die latter maybe importani. The mainin ol' salti v Itel ween die averanc ex|xtsine and die level ai which some in dividuals develop malinnam nii'solhelionia ma\ he narrow indeed. Willi an awareness of die nimspciifuin of the so-called "ashestos" body.'11 wc established the identity of the filters and erisials In use ol electron probe analysis. As shown in l;ii>ures Ii and 7. the chemical eoiii|ioiieuls (Si. Mu. ('.a. Ve) are chararlerislit ol a^heslos.,'l:, One important ob servation is die relatively small amount of iron in die ore<lilKT). Yel a lai'Kcainmiut of iron is present on the beaded body poriinn. 'This finilinn is in afpi'cMiciil with die niilinn dim die cnaiinR aroimil die litter is die iiKKt'i'K'ation of .ferritin or lerri- lin-like |tariirles ilcposiictl on ihc liber surfaci'."' We re|Hrt this ease to emphasize ajpiin die association of nialiy>naui mesothclioina with a very limited ex|>osurc to asltcsios. and the validity of (relatively) ipiiek ideiitilicalinu of "aslK'slos" Ixidies by eleciron probe x-ray dispersion analysis. This icclniiipic can serve lo ideuiil'y oilier crystals or meials preseni in lissue. Acknowledgment The am hors wish In thank l)r. Arnold Schmidt for pi'rl'orniinK die clccmin probe analy sis. REFERENCES I. tint;Hi'). I. I... Sli'iX". < A., null M.ttiTuiuil. I'.; ) till use- jtlriirnl im'Miilii'lioinn nail .islK-Mm cx* |mixuu. in itu- Ninth MVslrm lln|X' I'mvinrc. III. |. lull. Mill.. /?."fil>. I mill. " Syliknll. |. ).. Clime. J.. mill llmiunnnil. K. C.: AsIk'Xiux i'k|mkiiii* mill ni'u|)lnxin. |.A.M.A.. /iViV:'.1". I `.Mil. ' .X. .KeliSufr. I. |.. Clmi't;..).. mill llnmmnml. K. kiiniinn Ix'ini'i'ii cs|tn<nMr in nxlx'xinx mul liirsnilivlinmit. Snv I.nt*. 1- Mi'll.. J7J:.Mill. l'.ni:V ' I. Xi'wlnmxi'. M. I..: A sluilv nl' ilu- II >< 111 .ill I v nf trails in mi nsls'slns liirinn. Hr. |. lull. Mcil.. 2A:"!I.|. I tlli'.l. n. IllMKmmi. II. S.. aiul Ktiw. < .: Si'iul;n lirmls ill previtlcure mill iiiiiri'inrniinii nl |tiilmimmy aslx'slns ImhIus.-- t'.tlll in l'.'7". /Siill. I'ntli. Imli. Mill.. IIHiM'.t. I!l7li. Ii. S|tenrer. II.: l`iilliolKy of llie I.iiiik- Ed. riuislnill. New Vnri. I'cTKnmnil I'ipw. Inc. I'.HiK. |i. !l"7. 7. Sinilli. M. |.. mill N'iiylnr. H.: A iiiciIiikI for cx- Ivurlint; leiTiit-ilinnK Inriici I'rinti |inlnni mill |iiiliuiiiimi liximi'. Anii'i. ). Clin, 1`mli.. VtiLTill. ltd" K. KIIAX 7117A Mmmul. HOAX Inniiiminnnl. 107:1. II. AiiiIitmiii. II. A.. I .ills. R,. Itmiin. S. M.. Kixli- iK-in. A. X.. mill Sclilutll. I. Ilnmi'lmli). inmnti nxlx*xlnx imi|i];isliif risk. Ann. \.V. Aiml. Sri..'7/:SHI. I1I7H. III. Selikiitl'. I- VirlnilMin. \V. ).. mill Lintel. A. M.: AxlKtinx air |mlluiinn. Ai rh. Km ii . I li-nlili. :l. .|t>7'J. 11. -Vjliiitlxnn. tV. (.: AvIkX/k-.llir 'I'l.V (iliroxlmlil limit vnlni'l n|i|nnmli. Ann. N.V. Acini. Sii.. '7/:ln". I!7lt. 8001 OVt-D PRODUCED BY FORD HUMAN PATHOLOGY-VOLUME 9. NUMBER S May IV7H IV. Poole} . F. D.: MivilMiunia in relation in expo sure. hi hogovski, 1).. ct al. (Editors!: Bio logical t'.llccis of Asbestos. Lyon. International Agency lor Research on Cttimi . HI7.S. p. 2S2. 13. <irmt, I'.. Cruller. and de Tivcille. B.T.J'.: "Alc*itis" Ixxlict: ilieir iinmiKtiliciiv. Am. Ind. Iltg. AkH..|..^A':r>4l. l`Hi7. M. iumger. A. M.. Rubin.'I. b.. and Seliknff. J.. .}: Chemical rharacieriealitm of asbestos bixly cotes by electron inicrnpmbe analysis. J. HisKK'liein. Cytnchcni., V;7v3. l!i7S. I *>. Robin. I. H.. itml Magginrc. C, J.: Elemental analysis of iisIk'sIiis liltcr* Ity means of electron probe Itvhnitpics. Knviron. Ilcitllh Pcrsp.. V;K|. MI7-I. Hi. Davis. J. Nl. (.: FieriVI iii-iiiiiTii%i-ii|>c studies III aslx-simi* in man and animals. Aim. N.V, Atad..Sti.JJ':m. IIHirt. Department of Pathology University of Washington Selimil or Medicine Seattle. Washington ttHlttr> (Dr. Chen) t i SO 01 6961 c> PRODUCED BY FORD