Document ba6baOYyBa8ODkyevGGajYz71

TSfft) S T 0 0 I1692 EKVIROXMKXT.U. M3WSCU 2, 30-16 (IOCS) t Pleura! Fibrocaldflc Plaques and Asbestos Exposure : - Laxhu 0. Meukxiax Department of Pathology, Central Hoepital of Kuopio, Kuopio S, Fiitland Received December JS, WT la a number of Krial investigations an ssocistion baa been demonstrated between the development of benign ealeific pleural plaques or malignant diffuse mesothelioma and slight inhalation of asbestos dust, often some 30 or 30 years previously. As the industrial use of asbestos has increased enormously during the last few decades, a rise in the frequency of mesothelioma-whieh has hitherto been rare--is anticipated in the near future (Thomson, 1903). From the standpoint of epidemiological research con cerning asbestos exposure, the demonstration of calcific plaques on roentgenograms has proved a useful criterion.* So far, only -an association has been disclosed, however, not an obvious causal relationship. Other pathogcaetie factors, still unknown, have to be taken into account either as a contributory or the sole cause. The occurrence of bilateral ealcifie plaques does not yet.imply the presence of asbestosis-pneumoconiosis. In the majority of subjects who have not been occupationally exposed to as bestos, pleural calcification is not combined with pulmonary changes or signs of pneumoconiosis. Occupational Expoture to Aibetlot and Pleural Plaque* In rocnlgenographically visible form, pleural calcification is relatively rare. The most common causes are hemothorax, pleurisy (usually tuberculous) and chronic empyema. Tn extensive roentgenological series the frequency of pleural calcification has been reported to be about (Floyd and Hepburn, 1939). It has been estimated that the lesions are bilateral in ever}* fifth or eighth ease (Claus, 1962). Bilateral pleural calcification attracted more gcuer&l interest when Sicgal et al., in 1943, reported that the)* had observed this condition in 6Zfo of talc miners in the northern areas of New York State (St, Lawrence County). The theory of a causal relationship with talc in this region, in the form of a fibrous, asbestifonn mineral, treraolite, was advanced. It was not until 12 years later, ' however, that bilateral pleural calcification was again described, this time by .. 'Jacob and Bohlig (1935) in of.asbestos workers in Dresden. Independently of these authors, the Danes, Frost cf al., in 1956 directed attention to the assoeia- . vluu u> tiftuciua exposure and pu.ur.-ii caiciticauon. in a scries 01 31 insulation ( workers they detected 11 cases of pleural calcification, S of which were bilateral, j In the insulation materials used, aslx-stos constituted an essential element. In ! many later investigations an association between pleural calcification and cx- posurc to asliestos has been demonstrated. The mo.-t important statistics ou j pleural plaques and asbestos exposure are listed in Table 1. It has been found that tlic more severe the degree of pucumocomoMs. ob-erved . among a.-beslos workers, the higher is the frequency of pleural calcification." DOW 06975 S T 0 0 I1693 ASHKiros ami ru.i'iui. i'Macni 31 Muller (1962) delected piniml calcification in 0% of a gioup of worker* who showed lli slijlitol ungraphic degree of a.-lw/stoais, while the currc>l>oud- ing figure was 3SJt in a group who had pulmonary changes of tire severest degree. Among 1117 members of the Heat atrl Frost Insulators and Ariostos Workers Union in Xew York, SclikofT (10<m) found J50 case* of pleural calcification. Of these, 143 were in a group of 303 workers with a history of jnorc than 30 years* exposure to asbestos. Among those who had been a shorter time on the job, only 5 exhibited pleural calcification. SclikulT observed, moreover, that calcification rarely occurred without fibrous of lira lung parenchyma--asbestosis--being pres ent as wdL The majority of investigators hold the view Uial rocntgcnograpliienlly dis cernible pleural calcification is a sign of asbestosis (1) if the lesion Is bilateral, and (2) if there b no previous history of hemothorax, tuberculous or other pleurisy, or empyema (Fru*t et of, 1330; Iturwrits, 1961; Antpacli, 1902; Lawson, 1003; Oostluiixcn et aL, 1901). Under the last-mentioned conditions SelikolT (1903) regards unilateral calci fication, as well, as strongly suggestive. The association with asbestos is brought out by the fact that not even in large groups of workers in gold, coal, copper, iron, chrome, and manganese mines was any typical case of pleural calcification discovered by Ilurwitz (1901), who investigated the chest roentgenograms of workers at diiTerrnt mines in South Africa. Those Hihjccls showing calcification were invariably asbestos workers. Gtnsswoot and rockwool, which arc commonly used as hiMiIatlon material in the building industry in addition to asbestos, also occur in disintegrated fonn as fibrous dust. However, such data as are available suggest that they do not seem to cause pleural calcification even after protracted exposure (Bjurc et of., 1004). On the other hand, it i* noteworthy that asbestosis and pleural calcification by no means invariably occur in conjunction. Of 30 patients with pleura! calcifica tion described by Hourihanc et of. (1900) from the London Hospital, only 7. exhibited nsbestosis-pulmonary fibrod*. Further, these authors found, only 8 cases of pleural calcification among 30 patients with asbestosis. Cartier (1903), also, mentions that lire majority of Canadian industrial asbestos worker* with pleural calcinosis showed no sign* of n>lc.toN, and thnt in most eases of as- bestosis, pleural calcification was not detected. Moreover, Cartier drew attention to the faet that of 130 Canadian arixstos workers exhibiting pleural calcifica tion, 00% had worked at one or the other of four smaller mines, while only lO^G `mm- from a larger mine with 16(10 workers, and no ca-e of calcification was oh* served among 1500 workers employed at the biggest mine. From this Cartier concluded that the factor enuring nbrtori* is not the same ns the factor thnt leads to pleural rnlrjfirntinn. Feline (Mfiller, 1038), too, stated that regional factors or contributory factors relating to the particular iudurity may l*> of importance to the development of pinna! calcification, since some investigators see these lesions in abundance while others observe none. He sugge-ti-d that different composition of the dust involved might a(Tird an t\p!an.I?im to the irregular occurrence of calcification. Xevcitlir|>.', i. may lie regarded as es- 06976 n k iiiiii i*1 * . II - 1* I* f i Lung (!bwr Aabwlot expowtv 16.9J 1.00IS. 9rmncs o Plbciul F u q m a A n v r o i Exroc* PUquc* x. kc -n || I*i*s - + + + + eo t J. | S ^M"I SP #. C3 I5 X. m" 9" 6+ SI +s i lE s fl 1 <S -1* U*5 *5 i* c E ts5 Cs KK I *l0 j 2 9 r >* V * i/. /' 3 %i * j ?/ *: f.e V** - j. f; ^ V f. ?.i - ?. it ?J :S ?i r.*. 5 ?. < r, DOW 06977 STOOIIbyb DOW 06978 I 34 LAVR! O. MKUKMAN* | ftabliftlKfl dial all tyi*> of n.-lolos may lx* associated with pleural calcification fincc it haa been detected in scnwntmc and ampliibolc aslicstos worker* and ^ in worker* cxjios'cd to tremolite talc dint. Calcification ha* been described in h worker* from the Camlian cliry?olile asbestos mines (Cartier, 1905), in workers g from the South African crocidolito mine* (Sttp d 1901), and in subjects ^ exposed to dust from the Finnish anthophyllitc asbestos minea (hiviluoto, 1900). -- In thia connection it eccma appropriate to emphasise die fact that except, Ci perhapa, under laboratory condition*, asbestos duct exposure 1* never "l>ure." The duat b always mixed in various degree* with other duata, aa other mineral dust*. . f? At preaent, we do not know wlictlicr amt to what extent there other mineral* cause.. a pleural calcification. Hut it should be recalled that pleural calcification waa 8nt '"9 described in talc worker* who had been exposed to duct compoced of trcmo5te~ ^t talc, asbestos, ami anthophyllitc. Furthermore, in tlie atudica performed bjf r*j Smith (1952), calcified pleural plaque* were found not only in trcmolite worker* but also in certain grou|* who had handled variou* other talc mixture*; - Nonoceujnttonal Pleural Catdficatinn ~ V ' ^ r- In-the population living in the limited area comprising the Finnish anthophyl- ^ lite asbestos deposit*, typical bilateral pleural calcification is common, without' I occupational exposure to the dust having occurred (Kiviluoto, 1900). ' In a commune (Tuu.nicini) in which an aslieato* mine and mill have-, been worked since 1919, calcification* were detected at roentgenological nuisr surveys in 0/c of the adult imputation. In the neighboring commune (KuusjSrvi) the cor* responding figure was G.5/? I the remainder of the Finnish imputation pteoraf calcification* arc a rare roentgenogrnphie fimting, the frequency being estimated at only OJj jhv thou.-nnd of population (llmiuio, 1900). : Kiviluoto discovend 120 cases of pleural calcification In a series ;fiNia^tbn- bestos area front which those who had worked at the ashcato* mine been omitted. The lesion was bilateral in 85% of cates. Hy analysing samples of snow, small amount* of asbestos dust havwl monstrated as far as 27 km from the anthophyllitc ashesto* mine mentioned earlier (Jatamnnen cl at., 1905). It haa thus been proved that the living in the surrounding* of tlie mine are exposed to asbestos dust, I I of exiiosure, however, need not necessarily be precisely tlie ai*bc*tos'm&e1 Oer> I tain observations seem to indicate that scattered asbestos rocks tnd dlwnsc* I. eurring in great numbers in this area may bo a source of asbestos dariZHre- wr,!-1:i!own fact tint thc-o ?ncomlu*libl* tnnc* liaw been used hy the local population ioi ciie cun*tiui'iioii oi iireplace* ouu iiovn, tutu cejiecuiuj* toe toe heated stone* in the Finnish hath (``fauna'*) on which water la throw*kotdcr to produce steam. It is aNo known that the children like plaving wfthwoch t stones, fascinated hy the way tiny split into fan-like piece* when cut. Cift*c- I quently, the ndic-lo. r.\|n>iii'i< of (he ihluthunuls of this area tnnv ha\T conv- fneor^l in curly rliitdlmnil. In Caunio'n tiaiiT.i rucMuciiolojvc.il ctudy of plcwrat r.ilnfirafion. (lie li-tiil.;ilion of the entciflrMinn ea.--s from th! region indicate., that the a-li -to. cnjh,.,,,,. ,,( u,,. ,,|,|,.r n?.. in anv cYrntTmofT have l,Tim l.-fntr tin- exploitation of the n*lK>to. .I.jm. it*- \va.. fnrtcd. - '-.v Similar eiidtiuir pl.iiul calcification ha- remitty Ihtii drscrilfc-d in DOW 06979 S T 0 0 I1697 .V'ltUNro* AND M.M NU. M.Vp*- n.i wlicrc a high frtsptcitcy of |tl**ar:it calcification was nott-l in the jpn|.iii(.a (con* sitting mainly of farmer*) living nliout a fiiinll a*h'*tu* mine. lit thi- ea*c, loo, it was suggested that the a*lie.-ln content of the .-oil wa* a nunc likely -ourcc of exposure tlum 'tmoqdicric |Killutiou dcrivnl from the mine (Znlov 1/ /., 1907). Endemic plntral calcification in an nrlain population rc-iding near an a-bestos factory is de*eri!rd irt Ampach's (190?) rocntgcnnlo^iinl *tudy in the city of Dresden. Among 241 subjects with pleural calcification 177 had a history of ex posure to asbestos dti*t due either to working at tlsc a.lMlos factory or to living within a radius of 1S00 m from the factory. Endcinie pleural calcification witliout known exposure to niboto* dust hat also been described. In two arena in Czechoslovakia, i.c., in the district of Paeov (western section of lire former Jihlava region) (Hromek, 1902) and in the district of Pclhrimov in south Nohernia (Martova, 1901), hilatcral plaque-like pleural ealciOeations were found in relative ahundance during roentgenological mass survey* of the rural population. Neither fihrori* nor any other di.-cac of tlie lung w*as observed in tlicsc cases. Hromek was unable (o trace any asbestos exposure, and Manovfi succeeded in suggesting only uncertain exposure to tremo- lile tale. Tlie soil of the district of Pclhrimov being poor in calcium, fanners import, from the neighboring district of Chynov, a fertilizer called Kaleofen,'' which contains small amounts of tremolite talc. Marsova later studied the occur- ^___ _ . rencc of calcification in the district of Chynov; tlie frequency was only 0.3^e, while it was as high as 4.3'r in certain areas of tlvc district of Pclhrimov, At roentgenological mass surveys in the area of Ixipzig, Xeef (1933) detected 33 typical eases of bilateral plaque-like pleural calcification. Tlie whole series comprised 111,0C9 subjects. Calcified pleural plaques were more frequent in women than in men, a phenomenon which also was noted liy Mnr.*ovn in Czechoslovakia. No changes justifying a diagnosis of pneumoconiosis were observe1 in Xcefs eases, either, and only four subjects had a history of occupational ex]o>iira to Asbestos or tale. Xeef regarded bilateral pleural calcinosis as merely a change of old age. It may thu* lie considered cttublislied that although plairal calcification i* fre quently seen in workers expo-cd to aslicstiform dust the majority do not show this condition (M Oiler, 1902; Cartier, 1903; Hourilmiie, 1900). Furthermore, it may be stated that the longer the time tout has elapsed since the beginning of oc cupational dust cxjiosure, the higher is the frequency of pleural calcification (SclikofT, 1903). However, plaque-like hilatcral pleural calcification cannot be regarded as identical with nslieslosis, since in unselcetcd material from roctitegen- .'""|i':il oa-s <urvi V- the *" *' tt., inisth* nivobrd nutv the ptcuM. In the majority of cases tlie change* are not n*ociut<-< with lmui..-ii.t:iu- ni.ui-i* of tlie lung, nor do they cause any subjective or objective symptom- or signs of Asbestosi* (Kiviluoto, 1900; Raimio, 1900). In *omc setie/of tinro'-eupatioual, endetnie plaque-like phmr... calcification, exposure to a-hc*tos has K in uncer tain (Marsova, 1901), or even absent (TTromek, 1902). On the otlur hand, it should bo j oiiintl out that the role po-*ibly played by adw.-tn* eai.i.at !o de finitely < timitmted a* Jong a- the lungs have not hem ldtMto;d'v:flv i-vonmcd for nriiestus fdicrs or lsulics. . Comparative nutop-y studies on the relative frequency of pi. mat j ' a,,d DOW 06980 STOOI1698 3G Ml *1 o. Ml I l:M\x *ZfS3X- (lie content of n! ( du-l (; >!*.(> Ihh|--> in tlx- hing* have l*m p<ifoum-d only in Fiigland ilbim'ilnne ft at., UK'.lii and in Kinlaml (Mcuimau, 190G). Iti n autop-v iri* * fuun tin l.nnd<ui llo*pilal, jLirjii'-lil* pfenrnl thickening* wv.e cb*ei\ed in 4.2 tl.2%. Iii nil the-c m*i> email amount* of iiIk*(I' IkhIic- weie rceowred from the Inn;:. At con-rent ive autop*ic* pcrfmiui-d ill tin* .sum- ho*pitaI aOx slu* liodie* were detected in 21.3%. The Finui*h investigation wa* jierfonncd on a total of 435 consecutive autopsy ease* o( three central ho-pitnl* sildated far from each other in dilTcieut parts of tlie country (Memm.m, lOGti). One central hospital district incjinb'* antho- phyUite *l>estcH dcpo*iK The frequency of pleural plaques teas 39.3% in the whole material, the range living from 13 to .17%. The lungs were examined for asbestos bodies at tho-e two lin*pitals where plaque* were most frequently seen. This series comprisixl 229 ca*-s. Pleural plaques were observed in 124. In 79% of thc*e, asbestos lodir* wire found in the lung* in varying, mostly small amount*. Accordingly, asbc.*to* wa* not demonstrated in the lungs in all cases showing . plaque*, amton the other hanJ.pbyflJM wr nd in tlie cases exhibiting asbestos bodic*. In tKenrhoIe material asbestos liodics were olwcrvcd in The series from London and Finland tlm* differ in eertain ie*pce(i. In the `Rtmish study the frequency fioth of ca*e showing plaques and cne* with as bestos in the lung* wa* higher. Moreover, in a piojiortion of the eases ttith plaque* (21% ), n*h- -to- wa* not demon Staled in the lungs, while in the I.ondon scries asliesto* wa* found in tin- lung* in nli ra*e* show ing plaques. In rc.-jKTt to anatomic .-trupture, tlie plaque* were identical in the two series. They a!*o usually ..bowed calcification varying in depnv in Isotli. In the majority of ca.-cs calcification wa* not heavy enough. however, to make the plaques visible on routine che*t roontgcimriam*. Another noteworthy difif-rciiee hetwceii the Finnish series and that from London i* that in the latter nlmo*t half the cases with plaques showed clinical, or in any event hbtnlugir.dly drmoutralde, asbestos!* (pulmonary fibred*). In the Finnish seric* pletttal plnqu<* were not associated with fibrosi* or any other chronic di*enc of the Inn;: fVm--queutly. although In the Finm*h *etie* can** showing loth pleural plaqm* and alsto* Imdic* wen* highly significantly more frequent than ea*e* in whieh thi* nl.it imi-hlp wa* not olrservcd, the courtudon cannot |e diawn that an uim-<mi,plicated causal nlationddp is iiivulvvd. The possibilily remains that pleural plaque* air due a!o to other, unknown factor*. The same i* suggesbil by sfati*tii s derived from autopsy material fnnn tlie two Inrge*l hnqdtal* in Mil.sii Adic-fo. I*di * wire found in .11% of ca*e*, plmra! Thf /.'/ <- .,,( /*/i wnit ChIo/oi/i'iim Tn inetit; im.: i;,*.:.. p?. ie.,| f :! ifle.ifaii,. :;p|N-nr a- patrlir* and Mi:i*i.. u.i*i: . >tna!.* m pl:.(*:-- fi-s: m. v. ii.-ix of diflV-r.-i.; (mM.-iii.. v.hi. h h..\c l* a dc-nil-d a* bi/,.u.. ! "y *. fact ||ii- iii. . m' r *< . i,.. ri.n-c, o: l.,rt-.|il.,- |*i-. |i. ;,rtii l i in. !. -*> .ij*tii",0. ., that in :-t 1 1 > *" iii"':i h tin* ~m in ii;. ri..ir frre : DOW 06981 G r i- ami im.m.w.i. HWi h 37 S T 00I1699 i Vie. 1. Ronitfrtiftsi.rn >f a TO-y. ir-nM f nin r flmwiim l-ilmi.il j'liunl Ifi> h<l nrvcr lifffl an Jvi i woiVtr, lull lir lia.l all hi* life livnl in A rjwn fniniiin tJirilM ilr|vi(<, at a iti-i.mrr uf 1 km fiuiu on<* .i*liciito* mine and 12 km from nwrthw. oilier calcific pleural chau-r> (Ilmwitz, I9fil; Rannio, I9GC). Bilateral, sym- metric involvement is very chained rUtio (Kivihmto, I9C0; 1001; MiknfT, 1903; Itaunin, 19001. Tlv left side is more lieavily aflortid, and in unilateral eases it is tlie side more oftm involved (Kiviluoto, 1900; Slikoff, 1905; R:.mi:o, I9G0>. The Intend ]<o>tim of tlie middle and lower field* ami the central |portion of tit- diaphragm am the .mas of predilection, hut in more advanrerl re*c cr.l*tfir-(rnn* an* n,--> found on the phsiral surfaen of tl peri- f i < Im *n .1 * *t nit' Irtwlr'o V h* fntllj streak.* ftillouin^ tin* 'Imttmii d tlie nh> in the lateial poiCon* ut (l:t -in>i (Kivitunto, 1900). Calcific ph.(|iie. are mo-lly found on th** parit tal plm-'a, a* In* !- Ik-cii erlahlidcd nnatnmicilly (Smith, ltV.2; IVtue, Kivihu.tn, I9C.0; Winkler, 1901; Mar.* ova, 1901). The phmal cavity i n-ual'y imfu- *. in any t \< lit in the area of pimple formatmn (K h 19*0; .Miilh-r, lt.VS; |<ni, ,,.n( l%0t M. uiiii.ni, I9f.fi). DOW 06982 WUtLA-OTnOUX STOOI1700 ' .-'w^sJsc r*- t . -^%' > a >'m. 9. Knnmiiil lh>**4* nri'j' tf TO ft# ill j<hlWT (Inn. TV- |inrl! plmni *Uiar ihMk !4l<waJ n hihf* yfc^iwi Urn tatwtfiu* iMHinlinMllj', lut Ik* tawfcSvntsltflT' ltirlt i >itiu'iil alartit wO Liu (r>n.i Ait aU wiws KfWi a lalir rn' |nntii|, ' DOW 06983 ASMIttIM AND 39 lomoois VutUoloqicnl Anatomy of Ftcnral ('aldficoh'ont Grotcly, the calcific plaque* seen in the imrictal pleura, ami sometime* in (tie viidYAl pleura m itII, nro jwirelniu-likc thickenings with n shiny surface. Tlujy re pearly white or ivory in rotor amt often project more or lew abruptly* tike a plateau, over (lie surrounding tissue (Fig*. 2 am) 3). Tticir surface may he eitlier smooth or nodular, as if parked with split Ttic plaques sliow wide variation* in thickness, (lie range being from aliout 0.3 nun to 10 mm or larger. The variation in extent I* nl*o considerable, from small apevk* about 0.3 cm in diameter to alroot continuous pla|uee rovering the parietal ami visceral pleurae. It i* noteworthy, however, that the plaques rrem to "avoid** the comer* of the chest, since lesions are not found in the phrenieocmdal sinus or in the area op posite the apices of the lungs (Menrman, 1006). Histologically, it has Item established that the calcified plaques consist of collagrnous, hyaline, sclerotic connective tissue poor In cells, in which calcium has secondarily accumulated in varying amounts (Figs. 4 and 5) (Smith, 1032; Fehre, 1930; Mfiflcr, I03S; Meurman, 1900). The calcium concentration sliowt wide variation in different plaques in (fie same ease and also in different parts of the same lesion. The rafciuin content, fait not (Ik* thickness of the plaques, is decisive for their visibility on routine roentgenograms. A heavily calcified plaque ' apj>ears yellowish gray and transparent, am! if it ft peeled off from tlic inner surface of the thorax, which is readily done, it feels lime-hard and fractures wlien bent. Ptaques with a lower calcium content feel like cartilage and hend like leatlicr. Hatho-anatomically the plaques eorresiiond to the changes that have long licen known by pathologists under the name of "sugar icing" or "frosting" (German: Zuckcrgu**) (Meurman, 1900). These lesions, the etiology of which has remained obscure, have mostly l>ccn encountered on the peritoneal surface of the liver and # . spleen, Ittil also on (fie pleura and pericardium, ami occasionally on the intestinal scroa (Uorrmann, 1927). Pleural plaques of the type described above, as well as "sugar icing," seem to develop as primarily chronic lesions, be., without any inflammatory, acute fibrinous stage followed ly a granulation-tissue stage (Meurman, 1900). In no ease of plaques so far inve-tignted has an acute p-iinaty stage been observed. Also the thinnest plaques have been found to consist of collagenous hyaline sclerotic connective tissue. Tlie accumulation of calcium in the plaques Is obviously a late, sceondaiy . ............ . *' ..... * '-* t :. i<i'ranhh ;dlv motidr.thV calcific plaques have so far not Iicen foutul in ouhjcrts younger than 30 years (Kiviluoto, 1900), while wvll-dvvciopcd, weakly calcifies! pleural plaques have l*vn observed at autopsy in an IS-year-old subject (Meurman, I960). It is a well-known fact Fit X TtH.r;.n> cavity of nn St-jrar-oM ns.k-iitliir.al norkrr wtiv .liVU of rosiui *,,K` to liver i-irrlio-i*. TVrr .arc lypi.al. Ihirk liil.lrml jlmra! plupu-. with low r.al.iin ran- crim.'ikm, vl.il.lc on mci>*urn.n*nm-. Tt.N I,ml lur,| llt * ,t|.|nn<r ,,f nl,,ut X Lin from .any .artir.(,v. nunc, ont.-iif,* of tfie am mnt.ainins n.J.-fo- rkim-il. ffo |ih| not No I.-lira. ai.ro rr,,vc,,1 fr,,m a |,,nff in lm-k iums i-timi- I wo t>|.ir;t! vI-.Iih I.mIm. re fmin.1. |M4l DOW 06984 S T 0 0 I1702 . 40 1AVKI 0. MEUKMAN L* ,* * j* , i?*1 f *' 1 * '- - .*. ' * .: v. * . '.'t* v v .. * . >:* *v .. v-r.* "r> v"2&: '<3 ,, ; ^ ' *' *m Til1'" . - * - ** *.'..* ^v-. '* . / *.**' - ._ . * ;* t .f>/ . *' '*>- > .. ' * *i* * I. # ~ * f . I ' ; . * f Vtetfi* : ..:____________j vj Fib. 4. riHiinrnhTOj-r.ij-l. t>{ .i ^ton from the mania of t; |Li*l*i* *!*ins fr.rn onlinny .ivy cultipii dNti*f<hT li**w I" < rVitilir, lo*Ui-t a r. !',. !.!. v.in fit- ^-ti rtiininr. Xli. V 4. Ilm'KiiiM.tvf.ii'li #.f ji l !*tn|ivi'.il fmoi llr* iMdin of .i |>hml ilia .-.( to il.f |. ft ..iMcnt !;* JIT *rr( i. |> nvty |nrli<><l Mwl* <f* *o Ilf <|.f< not i-wi*a ftWwn. ,\li/<irtn foil training. X 00U 06*85 S T 0 0 I1703 All>'Kt AMI I'l.t.l IIM. VI.MJI '-H ' U (lull hyaline ewmectiveli-MU- lib? nmu-i', ofT. r- \ny f.-ivniahh* conditions for the accumulation of calcium djm.-ils (Huyd, 19t). Ctitiiful Ftahteet in fn*i of f*f ral Cnlnftotlion III general, It A|i|K'.iri> Unit the pre. enec of calcific plaques Ml the phmar 'lorn not m nidi 01150 nny subjective or objective symptoms or signs. Since in (he iftajorHy of ease* the lesion* arc not asoeinted with nny pathological rhanciin (lie limp or any other orpiu>, diuical disease prn|cr line's not seem to be involved (Kiviluoto, I960; Markova, 1001; Meunuan, 1900; Haunio, 19<*G). Pulmonary fibrosis i a relatively common accompaniment, however, in particular when the p!n(|thi nrc so heavily calcified as to lie visible on roentgcnogvauis. In tins 126 cases descrilictl hy Kiviluoto, slight jiuhnonnry fibrosis was detertet! in J2 and marked fibro-is in a further 12%. All Mibjcrt* who bad lievii orenna tionally exposed to aslicsto# dust at asliestos mines or mills were omitted from this series. Of the A3 subjects with pleural calcifications more thoroughly studied by Raimio, only two showed roeiitgemigraphicnlly discernible fibros'is of the lung, and these subjects had !*cen working at an adiestn* mine, llaunio stales, however, that in case* in which extensive pleural calcification* arc present on the roent genogram, fibrosis of the lung way fie difficult to distinguish because it may 1)0 masked by the ealcifieation. On the other hand, in SclikofT* (I9G3) extensive side* comprising insulation workers in New York, pleura! cnleification was almost invariably associated with pulmonary fibrosis varying in d< grc-e. The discrepancies may thus obviously be due to difference* in coui|io*iUon of (lie series, i.c.t whether they consist of oc cupationally or environmentally exposed subjects. Calci/ie Plenenl Plaque* atv! Dijjuxe }fesotheliowa It i* striking that nu association between nsliestos cxjHismr on the otic band and on the other ttvo different kinds of pleural lesion, i.e., Ix-nign calcific dis seminated plaques in one study am! malignant diffuse mesothelioma in another, was observed at roughly the same time by investigator* working independently of each other in different parts of the world (Jaeob and Hoidig, j 9.V>; Wagner, 19A9). Hoth these lesions are often associated with nono< eupational, obviously very slight asbestos exposure. Another feature in common seems to Ik* Unit the conditions only became manifest after several decades have chipped since the first ex|sure to a.-le-to dust (Kiviluoto, 19(50; Wagner et at., I960). Moreover, bid, !. 1,iti. have . n 'jb'i rvcd *?? em* n?! fb- -nine case fWcWs. I0.*3: W.-nmcr, I960; I.iwson, 1963; Kuticknap ct al., 196-1; .'jteel et a/., liMi-i; Jtourmam? n at., I960; Cathinnn, 19671. From the histological standpoint attention may, in addition, lie drawn to the structural resemblance Utween the stroma of benign hyaline- sclerotic pleural plaques and diffuse mesothelioma of the second main group, the fibrutie type (Tfouribatic, I960). Numerous studies published in different parts of the world argue in favor of a sigiiifie.uU cuirel.iti'm Iwtiwcn (Fie development of nn-M.tli.fionia ;iM,j \|Miure. In Fo.ilb Africa, Wagner rt at. (I960) wen* the first to .haw :,M, ..C,on to this rel.-i1ion.bip, and somewhat later similar re-ult: \V iv it purled lv Tli-un--fon DOW 06986 S T 0 0 I1704 42 l.WKt <. Ml.I'll>1 IN (IOf.2). Comiiirin;' i-vidi,. I*,- uni: rover l*ctN produced 1y Owen (19GI#; Ilourihain* (1!M*.|), :ui<! NrliM.!'C and *1 l,om*oa (ICfo) ill Kiiflmidj I'.lmes et ot, (HiC.*i in Nmlli lul.ni-!; .SIM et ot. (U'0.*) in V-S.A.; Ivfinij; (I9C.0) mid J(oilt*i h in Germany; and MOCu|ty (190?| in Australia. On tin* Otlirr Ji.uk!, riiif-jt r-tivt study of n 10-ycnr autopsy series from the Mahno Hospital, |n rform, at by tltv pnsent out hot ill eo-0|K'ration with Swedish patholgi*t (H;.r*tiand tt nt., 19G^, Raw no defmiti proof of on association between cx|Kiure tn *!k(<i- iIm*i muI tin* *vvlo^itiietil of <li(Tuc incrothelinmn. Thin ncoplam was h*ti**tc*I in 31 ca*.In |S of these, niliMliw tiodici* were found in tin* Iiiiij'-*, in 6 ca*e* in relative abundance. However, in n control eerie* from the mine iio|iif.il with the Mine eonijKi-itinit ft? it^arih ape mul lex, hsbestos iKxtie? were foutwl in the lungs in 12 can**, in 1 in large amount*. Since tmall iiumtirr* of ashodo* lavlii-.. in the lung* ure a fnqueiit fimliiig according to available >tnti*tirs from different part* of the world, lh<ic result? caittioi be -r.Ji regarded a? clear evhhnee of an a*ociation between a*1cstos exposure nud iur#o* tiielioma. Tlie ?aim* tmdertal wn* later roi-ntgenolngicnlly examined by Kivituoto wV (jicrsoaat eoinmunieation 1907*. Among the case* with mesothelioma, two showed ohviou# flint Otic utuvif.iiii piti;r:,I cahif.r.-itKin. The remits cunr n.in;-. tin- tel.-.t ion-hip 1.*t\it-en adjcstos cxjKi-ure and diffue inesottieiiiiiiia are tint* niir'diM eonttadielorv. and the same applies to n-bcsUw exposure and pleural plaques. It seem. obvious that a?lieto? play? an essential part in the development of loth tin si ti .-ions, hut it also apjiear* that other, as yrl lmkimu n fart nr., po--i!!y environmental, may be involved. Those factors may, moveover, Ik* reqKueib!" for the development of henigtt (polystrosili* fi!iroa, CoAVrj^, cited by llotvman, 19271 or malignant change? of the pleura or |>eritoiKum, |crltap* even without ^xjio.itrc* to ndn-sto*. Cartier's (1903) stale- metit that the factor tint catw a! -tod- is not identical with the factor caus ing calcific pleural plaques thoufore seem* to hold good. Hut till? unknown factor very frequently apjiear-i to lc n.-sorinlid with e\|*n.-urc to asbestos dust. Theories Concerning the !>uth>-jei,(Jii.* of Ph nrnt Cinque* The cnleifirntion of plrui.il phiqu* i* readily accounted for by tlieir hislo- logical structure. Hyaline sclerotic collagenous connective tissue is precisely the kiiiil of tissue with low vitality that favors the piccipitation of calcium ions as phosphates. With iiirrcad'e/ age the fluid concentration in the tissues is lowered, with the result that calcium salt precipitate* in the sclerotic tissue gradually itinriMe. It i much mure difficult tei mulct ^tand why and how hyaline .... !y }m nme im*culsir!y shaped areas of tile p:u it a I taint -<iiu< tint. - y ;.i \ i ai i pa-m On tin* a--umptinu that :-*bt-- dut j. tin* only cau-e of plaque formation, it might !- M".:'.f.tr<! tfri* f I * e.iU:;?ivi* tn* -11; r:i.iji rnii.|.t. of direct mechanical fiietioii (>i val / a1. 191.1; Kr.i!:*-**.i, 1P,',h. *J`|ii* tlnOty prcnpjiw> that the yd* fi! ;. p ti.f*. \ i*i*.:! ji!. :r;, niLI .rr;itr!i the .tuf^c. of tin* |.:.ii. t:d pb lit:, a- .1 i.-t:!! of -iMy i,,(lV. a,tJ,,,. r:,,,.ii,- a filuinniH lMid.Ui.-i, in Ihr P "KiK jl:til til.- fd.t 1'.* .!. v ..l-..,,l i, f}. i'y di i. | .j. i::,u h\*;i!iu.- .rhintir <-n:i. | DOW 06987 ST00II705 ambtob axo pusvral plaques 43 19G4; * rt at. *0) and neethr tissue in tle manner typical of scar formation. This hypothesis U com patible with tin* predominant location of tin* pliujuc*. in those areas of the parietal pleura where the rcspirotoiy movements are strongest (Kiviluoto, 19C0). from tfie Swedish oriation hcfioma. -iv found io from ndiedoa cr email tiling (o tinot f|C m| IIKfO* livilooto- ** Although asbestos dust is found tinder the visceral pleura in only relatively small amounts in advanced eases of asbestos?*, penetration of Uio pleura by asbestos dust is by no means imjosiblc, since asbestos bodies protruding into the pleural eavtiy have been recovered from the surface of the lungs (Meurman, 1906). Likewise, asliestos fillers, though no asliestoa bodies, have tiecn found in parietal pleural plaques (Houriliane, 1906). On the oilier hand, the presence of asliestos fibers in the parietal pleura docs not necessarily, mean that these fibers have migrated from tlie lungs through the pleural cavity. Asbestos dust has been recovered from many organs, e*, tlic kidneys, bone marrow, liver, adrenals, spleen, and gastrointestinal tract (Sellkoff t of., llNVi). Hence it seems possible that asliestos filters arc transported to the parietal pleura with the blood stream or via the lymphatics. Another argilT y ~cnt-agsrnsC tfwF;ai~ii 1 TitfilfjUWRJWI9otrtKQpryiIfthftlHhc latter presupposes a- fw4i?Wi.prelimhuiry stage of.fihrfc6ttt%x*udnt?on, and according to patho-anatomical .. j,. 1 experience fibrinous exudation as a rule leads to oblHeration of tlic pleural cavity. I aiffoaov^^ t-lmrtot 3 ^ v So far, no evidence has been jmslucid of cither fibrinous exudation or any other preliminary stage of plaque formation preceding the hyaline sclerotic connective- -s-intlal 1 tissue stage. In addition, plaque oenir admittedly when the pleural cavity is r, a* unfused or, if it is obliterated, a* a rule at those sites where it has remained oja-n. ; .'(ora Of purely chcmic.d theories regarding the pathogenesis of plaques, that offered resit is by Lawson t1063) seems to lie the most precise. Lawson suggests that the cura or state* magnesium contained in asliestos nnd tale may lie responsible for calcification hy activating alkaline pho*dintnse. r raus- A combined effect of physical and chemical factors is prcsup|>oscd hy the i factor theory advanced by tlic present author (Meurman, 1966), according to which the sites of predilection of the plaques arc those areas of the parietal pleura where . the greatest amount of stretching is caused hy the respiratory movement*. The hi*lo civ the in ions -uo is tissue ivaliitc anas effort of nslotos ns a contributor)* factor would consist of altering tlic com position of the final pn--ing from the lungs to the pleural cavity. This ehnngc would lie <100 to iutrnpuhiiouury damage caused hy the asliesto* Alters, com parable with inirrolienairrhnges. And hemothorax is known to lie the most com mon cause of pleural calcification. So far no conclusive evidence has licen advanced in sup|iort of any theory concvniing the pathogenesis of plaque formation. wn. il 11 at the i I lo rn* n *M|- rMM\l!V I his p;i|vr i- a review of r*ccnl literature concerning calcific pleural plaques. Il I' e-taldi-licd t!irt niultiplc calcific pleural plaques are a ran* m-ntgenogi.upltic finding in all |>opulatinn groups except miners and industrial wnrkci*"I"' handle a-lwsto- m- talc. A noteworthy concent rat ion of ca-e* -bowing plaque* ha- a! Is-en oil..., vef in imputation- living in the vicinity of a-l<r.*fn- mini. I lower er. iii e,a tain area* a fiirrli fn-quciiey of pleural ralrifieatiiui let- Ims-ii noinl v. ii l<"i* any a-l e\po..ne l-.iic/ ,|, loon-tial.le. I'buial plaque- area common DOW 06.988 S T 0 0 I1706 44 UU'kl O. MCl'MMAX aulofMjr finding, and a eirtnin rvsulflril)* ha# been observed in llicir lQMWv. Anatomically and hulolo-hulty, the plaques correspond to fibrotto Wdtfc|. although in liKhl cam (T*c!r calcium content I# #o low that I visible on roaitfci'iKjyrmiv*. In Industrial woikerr occupationally expos'd to asbestos due (ion is often associated nidi jiufiiionaty fibrosis. J5y contrast which slight cxpourc to edicstos dust results from living in tn asbestos deposits, or In the neighborhood of asbestos factor] not as n rale associated with pulmonary fibrosis. If this cowl is to mild that it cannot be demonstrated rocntgcnographlc manifest itself as respiratory insufficiency. In addition to asbci some unknown endogenous or exogenous contributory factor sc< ble for pleural plnque formation. Tlie presence or abseneo of vfously decisive in respeet to tlte development of plaques. In sc certain areas this hypothetical factor appears to' be capable of pleural plaques even without exposure to asbestos dust. Th 1 plaques is as yet obscure. KKKF.P.KXCE* Axr.cu, M. (19G2). Sind IVinavrrkiiftmigru plofnorr.onuh fQr cii Arrk.CnrrTbcj>atfitft. 19, 109*120. Raw, J, PCgasiio.M, H,, j\i Win:M*kt, J. (1061). Catdlopulmoiut] worker* dealing with .in-l Tkamx J9,77- 77. KornManx. A. (1927). t'l^r PutyMiodiU chronica fihtoia und \rrwa eAor* Arrh. /%*Ar<f. A fit. /'/.**.?. A7*`rt. .Vrd. 261, 700 729. Hot*. tV. (1931). "A Te\t*|V>l; of I'ail.olofy," mtli edition, Ktm|<ti Claim, P. (l'Ctt). i<. Sevtioa VI. "Clinical .ttwlin of pu Ann. AM*. A<W.So. 132, 397 3SS. Catut.m in. Jl, a.no Ki.n*citi.a, V. (I. (IPS'). Caw record* of (he M Jl(M|wtnl. Caw .V *r F> 'j'. /. .Vc<f. 47C, 230-2J7. ClAfi*, II. C. (11*12). Kiii*' unsiwi'l.iilktic dojiprl^llitr PJeurave Koinltrmtr. 07, M2 SIS. KkMM, P. C, MiCmmim, tV. T. K, jino tV-w:, O. I* COM). JHfft (he |h ura and alw<. tint. M'-t. /. 1,3.7Q-133. KkTirKx.tr, 3. II, ani Smii iii.it, (V. J. (1901). IVriloneal tumours ft M. AJeii. at, 20-31. Fmim, TV. (1936). ft** iloj'p Jiitigr IVuravt-ffcaKumgcti infolge b wirlunp n. Fort'rhr. Ft* i. j. < S3, lfi-23. '`mi*. C,, AMI !! i n. It )| r.f.r.f til.* |Aura. Pntmonnrg I>r*< . 40, 213 224. 1 ao^r. 3n Ciaws, J, ano Miinu, P. K. (IMC). A*Vilp*i* with plruml iiinl.iti*n worl< i*. /><*.'/. Mfl. ft ,11. 3, 202*201. Otatrtu.iA, C. (I9i3). !.* Ml'ifi-.niniii |-l< ttri*-1<* in It* hk umynnlu'i 279 C.IH//I, I. M**o.m. hiltil m* Mi! !. I, ini. Pi* i.in. V. (l-*.Ts. A-I-.i,.. i II I. N,. | . \|f | awl In. -ih-t:..:...t. Ilm mi \ni., Jl r |: a**i*i,!i<n i*l. n-l.-. DOW 06989 S T 0 0 I1707 JUNTUB AN* flAUtb fWJVM * 46 a.\ flint waaox, f. C. (IMVK llyaliw aml al*ifV>J % _____ ;rfrt|wiiif la iJinln*. Brit. J//. J. It Ml# 1071. .H(Tulay i,Mt raiMtrriMht.frh pkunllnWt fim'n a ul>yv.irt4r inf Wuft. s; wkiii. I: Itortlptwlnik gS, MM, of Rndiam (1904). Die rCotri*ilngi*el>t Kwoij.tikationm d*T J.unrtMuWwe. 83^ IIMOb - Plroral ralriftnHim m a ft>nl*rook>*ie ig o( "on-oempntionAl IjctlWM. Actm R<*thL S*ppL 1M, 1-47. , J, ax SitAmo, J. (1006). CBnical, radkriogtcal and pkytiologieal th. hfrml Med. 117, 416411. die .libMoM. /ffl. Gararixpalhal. CmiMif. 1* 1S9-J0I. } a*n Hawaii V. (WO. Ot>*efrallon on atmtMphcrk air pollution .Am*. S.Y. Aomi. Sri 132, 316-24*. Uvnjr, J. FT fl08). PVwml nlrifotkm aa nafei otvbnlom*. CK. Radiol 14, 111-917. Mntri O. (1000. Beilrag nr .\liolo(K drr PkoraccTWlningnn. Jf. 7V*rfc. 121, 339431. McravAX, L. (1900). AAcrtoa bodice awl pMral platan In a Finnish anira of nutopajr tin Aft* PaOmL Microbiol. Send. Sappt. 131tfjtlW McNutt, J. C. (1002). Malignant plrtml naBithrfiwn In an athcaloa worker. Med. J. Amtralia 2, 903-061. 4Jffrrr- MCuxa, H. (1090). Obtr Khnerc Forme* JW^iUtotnan. i* mDta StsaMungeucrkrank-- mgr*" (K. XC. JStten awl W. KfatcrkOUcr, cdO^ToiJ^pp. 401401. SteinkojJT, D.irovlatU. Mfurn, II. (1902). PVunmfailkinini bfi Jri.tjbc<Crtanblungp. f)iag*. 3, 33-33. Nor, W, (1903). Ikidtiilifr Plruravrk: Hwpa Im Altec. Forltehr. Rocmlgeatlr. 99, 632-' vH*** Xrwnovr% >f. ?, am Thomcmox, II. (1904). Mcndhelionvi of pktirn him]. p.-rilovt-iun following esporar* of a-tx-Moa in Itic I/>mlnn area. Bril. /. /*</. .Ifrrf. 22, 201-3(3. OMTitrcex, S. F, Thtjion, C. P. am Strio-Car.Men, 0. K. (1901). Cak-ific-d flrunl ptaqcr* in ubHow. Pme. Mint .Vrrf. Ofieere A--. 10; 190401. Oats, tV. (3. (1901). Dilfiw nvnottirTioma and ciponn to uftmtoo du<t in Ike Mer- icytitk* im. Brit. JW. /. 2, 211-3IS. Riimo, V. (1906). Omirrrnrv of imttrual pkunt eaktSealion in Finland, .(an. J/rrf. Inter*. r, 5/*/d. 47,141. ;'rr Ronjactt, A. G. (1003). (t die Koinsbtrni vatAdagw inwi Mcaothclimii. Xhl. AIlf. Pathol. .1**1. 108, 1. SctiKorr, I. 3, Oman, J. axi* Ifitoioxa, K. C. (1000). Relation between rspooun to abc*tw ami mrAithrlinnii Xenr Kft. J. Med. 272, 400404. ScuKorr, I. J. (1903). IT* eminence of plrttml calcification among adwtoc intiLi(ion worker*, .tan. .Y.J*. .Imd. Set. 132; 331-307.. Iwm. V, Sana, A. R. axi* Cimmcm, J. (1913). The dual hatanl In ItctnolHo tale mining. .la*. /. Rotate nut. Radium Therapy. Xaft. Med. 40,11-39. Straw, C. A, MAaciMX*. P,, as* W.iunra, J. C. (1901). DiflTiuc pleura! mm>thc!ioma in Suvtk Aftira. S. Africa* Med. /. 3S, 2540. Smith, A. R. (I0S3). Flniral cniriOratlon mofling fraaa wpomw to* certain dual*. Am. J. Roentyenol. Radium Thempg .Yarf. Med. 67, 374-332. ?. r, aaw <>. <! (I30J). I*J* U...J lA iw^liiiu .<! io' .-o`o. fit.t.i.i to litvito*. Bril. J. Difiuri Cheat 59,130-132. jjre Tnoam, /. G. (1003). McmUirKnma of ptmim or iwrltomum and Hmllrd Ka*nl a*bcjtw*. S. Africa* Meit. J. 36, ,39.700. S W.wxra. J. C. (1900). Some pathologica! n-pcrl* of asbntOH* in the Union of Swwlli Afncn. im `Piorrrdinei of the rnenmoconra*!* Conknnet- (A. J. Onii-I.in, ed.) i.ilunmiJiurg IX. n*. 373-2<?. Oimrliilt, l/>mlon. \\'.cva, J. C, .r.w, C. A, va Mon-inxn, p. (!>. Diffu-e i* <im! nw-n.d,. nml A>U,tu* *iiire ill I1.C Nnilli \V. ,t Cape Pratiiier. Rrit. J. f*.l. Me l. 17, 371. DOU 06990 STOOI1708 DOW 06991