Document OJRjY1d6jbga5zYLJ1JRmObvj

FILE NAME: Texaco (TEX) DATE: 1960 Nov DOC#: TEX021 DOCUMENT DESCRIPTION: Journal Article - Primary Malignant Mesothelioma of the Pleura > P rim a ry A-aliguaiiL M e so th e lio m a o die Ideara' i PLA IN TIFF'S EXHIBIT I 60/11/00 H. JJ. KJSKN.STADT. M.D., and F. W. WILSON, M.D. ' ^ Port Arthur, Texas . T HE imacno.sis ok primary maiigiiaiicv of the* pleura continues to l>c quite a difficult prohlent in spite of all modern clinical skills ami siblc for chest pain and discomfort before being visible on roentgenograms. Later, thev 'make themselves known by pleural effusions, idio advanced laboratory and x-ray facilities. Un pathic pneumothorax, *or dense massive shadows fortunately, (his disease is quite uncommon; and covering a large portion of the hemithorax. fov investigators have been able to accumulate Microscopically, the benign mesotheliomas a broad knowledge of its characteristic features. form fibrous masses, while those that re inaTig-' Nevertheless, mesothelioma is perhaps not as nnnt consist either o f solid conglomerations or rare as the literature reports and probably ni:iv glandular and follicular arrangements of epi Ik* seen but not recognized properly. thelial cells or, more rarely,.of fibrusnrcomntmis This tumor is most frequently confuseli with tissue. The localized tumors can be eradicated itenign Jesions of the pleura or the mediastinum, surgically; the diffuse types, however, have been with primary malignancy of the underlying lung considered inoperable until recently when Harris tissue as well ns of the enclosing rib cage, and. nnd associates4 reported a cure, or at least a ! finally, with metastatic disease from a distant long-tenn survival, after radical pleuropneumo- j tumor. Many diagnostic difficulties arc created necloinv during the a irly stage of the develop tlur great variety of clinical roentgenologic ment. Jn addition, Richert and Sherman' report il pathologic manifestations of (his tumor that a i a long-term arrest after early administration t W i y puzzle clinicians, chest surgeons, roentgen- of radioactive gold. I ologists, and pathologists. Tins peculiar behavior I f the experience o f these investigators can be . I was explained at first hy Marimow1ami later by confirmed by others, it seems mandatory for all .Siout and ^Murray1 with the aid of ccH culture physicians who may encounter mesotheliomas ` methods. in their practice to acquaint themselves with The growtli originat*s from msothlial (ce the symptomatology* and natural history o f this llunie) cells that arc inultipotcutial and am form growtli. It is obvious that a tumor of such greari . a great variety of msothlial as well as mesciiT . variability will produce a different picture iiu t-hvmnl tissues in manifold combinations.3 Thus, each individual case. However, the experience nu-sothdiomas not only differ from each other gained from the observation of 2 patients xvith _ V hut also may sJkjw amazing differences in mi- malignant mesothelioma showed a diarseteris- CToscopic sections of the same growth.3 tic similarity that malces it worthwhile to review - Clinically; 2 types cnii be distinguished:' a th an . The first case was previously reported in localized and a diffuse mesothelioma! The local- detail/ while the second is a new case. zed form is usually benign, fibrous, and asymp tomatic until late and is often discovered during routine chest x-ray examinations. It forms a globular density .attached to the chest wall or CASE BETORXS C c 1. A_ diffuse p a in ______________________________ iviiicti u j i u i l y in crrm w l in in lr n iily . tin* d_iaph_ ragm. There are all kinds of tnmsitiuns In-tween thTs tu m o r an d the m a lig n a n t .tv p cs very insidious, and his initial discomfort was at first not v,<f r,J' separated from a previously prrscnt anfiin jxx-- `1which___g__r_o__w_ mdnififiullsvelyn,minl vdaidmesr- apidly, and sliow , varly symptomatology. The latter,may be respon- P4" 8 lhat ^ P*1" had in character and persistence and no longer responded to vasodilating remedies. Initially, an x-ray film (. (lie d m t was normal. W j . . etsEN*STAOT anttr. w . w ilson* \re with the St. is Ilosjiitai atid Park Place Hospital. Fort Ar* soon tills natient experienced a "spontaneous** pneumn- lltorax vvitliowt a history o f traum a o r pliysical exertion. A roentgenogram taken at (Ids time showed a partly coh `Texas. ' lapsed lung without abnorm al shadows In tlds organ, in l NOVEMBER iSOO *. *A - --------- ------ *> ' r ? \ t. ^ t o <r "I ? ' <> * ? o -, <> <; - * r o w * *>. o .. * -* 9 0 .. * , :rrt * v*m ''' V**.\ * '> O .' 7 ;p 0 f - ' o. *fll ^ il** jiliu cil ip.ii t*. m in tin- UntV fili (;*; , *. ,, ;i i i i **i i i <( i t i M fin t% f f i u d M*aA ;i^ p tr .il * < l I m <| ,m t * n . . i , t * Itti lumi'f ii*ll*. 'I I* cli-*l p ii per.*i\lfil all*.r il , h;,l Imi in .,!**,Im iI. ;iml a ilm *c [ilnoll*m;i\ J (In rl' p 'il will, .vliiiiilm" (if lite r-iil itt- lii*iiiiili'*i.,* j ,. ji<w:ii<l irliiiilim i itf |ln* hllctfl c ilic i **:ill. Thoracic exphiruliim was pcrforiiinl l,i*.in*<- uf <n hcarnhlc pniii. Imi llii< revealed only a dense Munii.,, will massivi; aiUir-siim*. Decori Seal ion gasi- u-h. Amnesia nml weight loss became nmrked ami Ini i sC 'ctc caci,evia. Neither large doses of narcotics n* murosurgrcnl prpvuliitrj reduced flic pain. An esplm tors- laparotomy followed, but only sim ilar adite*!,,* *. i * encountered. No diagnosis was made tmlil a rtmii, slot,ms I, x-rav film nnrvpeclcdlv revealed tl,al w sri tilts eri; destroy***!. Riopsy of this region revealed pic* *. lai incsotlirlioma. p ' O'- - c W .v * - *& ,; - , -.-Mr, %_ : :*.-?-_ *a ;.* * * - ;v. - 4 jL i-Js Kip. 1. Large mesothcluil cells noted in the hloody pleu ral effusion. Fig. 2- Upper seaHoped Ixwdcr of tlie pleural walls. Core 2. A .Sf,'-,*car-<i|J..oil rcfiiicry..fprcan_ hy li. worked with asbestos insulating material for quit* . sviu'ie noticed, Mircess..and_a..rnttling noise in the li___ hrmil horns. Cheat examination In January 1959 rr,<-ali n Ititvidy pleural *li,isio. This fluid was bacteriological negative but contained large mesothclial cells. which e* patliologlst suspected were malignant f figure I ) . Ilo* ever, his suspicion was not shared b y a nnmlier of n'ti pathologists wlw were consulted. T h e p u lim tY p .u i, m tinned to increase and radiated over the w hole felt hen tl,rax. Tle pler;l fluid rcaccunutluled itt spile of , '|H*ated thorough paracenteses. ..Som e dyspnea hut l,tc cough was notnl. ~......... ..... ....... Ksploratorv thoracotomy in s large m edical center i waled multiple hard plaques covering tint entire pirn* space and extensive pleural adhesions. A portion of t' pleura was removed lor microscopic studies. T h e path* ogist reported " grauulnmata o f unknown origin." A In biopsy periorined at the same tin ,c revealed shot bodies in the hronelu'oles. In spite o P n eg ativ e skin bneteriologie tests, the patient w as placed on an an tuberculous regime after the operation. T h e fluid did , return, but a dense fibrothorax d e v e lo p ! w ith shrinli of the entire hemithorax. Tle pleural dehsitv increas on successive x-ray films and finally revealed an upr scalloped border (figure 2 ). T h e pain w as constant e- and night anti did not respond to large doses <*f n colics. In November 1959, iiiterrostal blocks w ere perform followed by nerve sections. These procedures were wit out benefit, and. in December 1059. a clmrdotomy also done. Shortly after ibis operation, x-ray cxsmuwt,' revealed that several ribs were destroyed. Similar roc genograins bad been previously m ade almost at mooli inter, sis, but no bony defect liad ever been jidted. I cisional biopsy of these bones revealed - a "nuligor growth interpret! os-"fibrous sarcoma** ly tlie patbo girt (figures 3 and 4). In the following weeks, various other p a rts of the Is* tlmrack* cage were destroyed, particularly th e lowrr A sal vertebrae nod the upper sternum . T h is led to compression nml transection as well as to obstruction tlie trachea nml esophagus. The patient suflcfcd uuhe aide pain until bis dntse in M ay '1060. ....... T he essential findings 1 autopsy w ere " hlrsmlrfbo ifillic left pieu rt {nkSdiog mctliirfiniwn. rih*^vfH*r h \* r. spleen, And JUhgs, Hypostatic pnetinmnitlffejulritwuy tumor^ a n d ' j k fiSft' Is ............................................ SI2 THE JOURNAL-LANCET ' -- - V ' irwa a f g .H m I U U & M H j a m 014833 Fig. 3 (left) and F ig . < (ri^hl). Filiraircnnn (imijiiKnl n( ii lar blindici nf ipindlc cells willi liyjH-icliriiintic Im/jiii- umici. DISCUSSION ccntesis or aspiiation of the piieumatlmnix. A no rexia. weight lews, and cachexia grjicuallv tie- vcloj). Acliiiiui.str:itioii of itnrcofics ' ami euro- o -ijii' - -- ........................ -- ,0 'y surgical procedure's ore without benefit or only 3%*,)lnfek qf ` familiarity with this entity cun *- slightly useful to the patient. Percussion density oi the medical centers cnri<" anti shrinking of the lionlithorax, witli or with lur these, patients failed to make an "early diag out scoliosis, mav be observed. Clubbing of fin nosis, in tlit:,fact that the referrhig phy- gers, artictilar rheumatism, and ostcoarthropa- W ! tlienj to the pcssibilitv of s u c k ii tliv have been reported in some cases but liave patients were observed for months not been observed in our patients. The}' are ap .% sjK'CiaJtsts who failed to recognize parently more often seen with the localized be- 4i}fcfe^ti|ity* hftUI bone destniction, which Was oign mesotheliomas. Chills, fever, cough, dysp nea. and cyanosis arc usually mild or absent. The roentgenologist should be aware: o f the fact that the chost'x-ray may be entirely negative *wsmut%3ii >tirW OjrsjiCCCS5iu, ........................ 0 ^ I 4 iit Si thbVotigli iibwledgo th i?iv for some time. Pleural -effusion, fihrothorax or pneumothorax are nonspecific. However, the in J^ijSIbiKlriy o' this tuinor. The dnicfen creasing density'of the Sbrothorax, particularly | ^ ( 'b itfegfi io 'diffuse unilateral chest pain after surgical exploration and the shrinking and w %nt origin gradually increasing in infeii- narrowing of the entire hernitborax may be sig- iifiddlc-agcd or eldcrjv person. I in iiificttiiC. Either the mediastinum is polled toward ` iiHititm riwy be negative, or there the lateral chest wall or vice versa. Scalloped i Unexplained pleural cflitimm ,df margins of the pleural walls or o f th fibro- a S|>ont.iiicous pnemiintJiorav The, tlioRix (figure 2) arc late manifestations. Done >Ic examination I tin* pleural titjid' destruction should be constantly looked for with rejx'atcd Bucky exposures. If present, this an-__ ^ ,i n J^is fluidxnn .V recognized uounccs the final, probably incurable stage. - - Thoracic exploration Is always necessary to , The pain isjnot markedly relieved by (Kira* confirm the'diagnosis. Therefore, the chest sur- " NOVEMBER I960 513* . ' I JAM 014834 ^i-p A / \ r---' ,r A t / IV * * . > <* . . . \ I I*I-*M*d it '"(I*.. IJIllil e|\*- lll.ll tl.> j, .t > vr tin- tiMiH-i i old !>* re la te d I* . t|,.- . viuee (lux' xxi-u- located in (In- In- ,, .and nut h i the p lr m .i." Iluxvevei. a\ln-%|..-. ,,, lenal could have icached llie |il<-<ii.iI i, .,. uillnuil brine deiimnxlialile iiiienivciipr la addition, along flic diaphragm atic m o !.i. . . the pleural space there was n " thick gie i,,. which was partially calcified" at aulupxv. 'll, calcium deposit could he dem onstrated <m (. initial x-ray pictures (figure 5. double airn , indicating some pleural scarring prior to llir'rfi vrlopmcnt of the iMalignant grow th. SUM M ARY l'ijj. 5. (iati tini i|i'|i'ii almi;; llie diaphragmatic sorfoco ni II' pleural spate. genu .must ! familiar with th various macro scopic /ratines ni tlu- growth which forms fine nodules. large plaques. massive adhesions. ami a dense fibroilmrax. * O f utmost importance is. ni course, tlie cor rect pathologic interpretation of tlie pleumi Iiojjsv on which the decision fo t radical treatment depends. I the majority o f. cases, the speci mens have been misinterpreted as fibrous pleural thickening, pleural adhesions, granulomatous tis sues. or metastatic malignancy. The careful pa thologist am only slate (hat the lesions arc com patible with malignant mesothelioma, because this diagnosis actually requires a complete au topsy excluding any other primary neoplasm. However, in practice, one should proceed with surgical therapy if a thorough clinical invest inatiou lias eliminated auv distant ninliguancv. O nr second case is particularly interesting mfunsbrstrfs tffthltlitniani mesothriioiha lias The symptomatology and natural course ol pi uiaiy malignant .mesothelioma has hern ill.,, (rated by .2 ease reports. In spite o f early clu. ical suspicion, early thoracic exploration. ` ` various specialists. these p.i advanced hopeless stag: bony thorax .before (I,- iblished. T h e early t-lin patlio logii^charnetei <\ tics of tins neoplasm must he kept in mind e order to bring these patients in tim e to ratlu.i surgical procedures or effective irradiation tlu-i.i pv that mav he curative o r a l least prolong lit* Tlic authors x\-ijli lu express their nppretiat ion lo Hi John H. Childers. Department of 'I'nlhnlngv. .MnU.. |lr.iuch. tlniversile of Texas, Calx-cston; mid i)r. h:.n.l Crawford. Department of Siirgorv. Baylor Medical Set-- * Houston. for tticir lielp in the preparation of this p>p U K VEJU CK CES ^ -----------^ --------------" (, A* A .: O ln f )m MrNKhel ( IV c W llf (I.t s (men Hntilr ) . mihI tlif Z^Uftt dr* s<rleti C u u tis lr . et|trr, Zrltlnodw 4 :1 . 19!!7, 2. S tovt. A . P -. fid M . 9U LoiHrtp<l ( * W J tlwUnma. of (it cKaiiKtrritio iy| hr m r iM d oriturr. Arch. Talli. 3 4 :9 5 1 . I!M.< 3. C tr hforH of III M f'trtfh tttrlli CVrral K. 4 N-w KgUm l J . Mod. 2CO: 491. 1939. . . 4. lU im is M . S- II v m a x . 31. M . od K n w i , D` If.* ^ * t)tectaldr fori* o f m**ll2|lc tm tn lM iwwn . J3 ft. Che*! 3 " .I . 1939. 5 . SlmMAHT. od Sw raM tif, C . D .. P fo U tttil ***' in illltiM f plrvinl m ttnlhHiom tiratoi with 799. 1959. * - "' Gw Kiicjcivaut. 11 M.: M aKgiwX w>a ohr l >oma o f ili* |^ * * U fa. d ir t i 30:349. 193. . 7 W tN x u n , M* S tM tcii, W , A .W A u n tr . M . IV * U > . E . D .i X frtd lirlNiNMW of the |4 m M . P h * Chr*l -** 119. 1959. 8* C tfT fx o , J . T mi o f thr p tn tn i. Am 1* M* ^ 228:030. 1934. 0 . F o m c . M . A. hI H a i . W . A .: DM u*r m (HHiovna o f Ilo pVrtua. Am . H e*. T d * m . 7 A :lG il, 1913. 10. M iu c k , H . P - U u r tip in . M . L . k d b cK xe rt XV. ' MKI?_ca_*m__m_ari**y|ci_r-cIim^momn*riUtfMoLH^o*w.rd. a llr f AnK 2S8o--r-yte?. a*r.h1ajr p.HtotttM*V'f'r- . * * lljd R r. ------------------------------ a.`J finestIg.itors agree Unit exposure to at- l i F .i x o i , A ,, .m l Mm a u c a , C .: A r in w i r erri"** r 1- B .|ij,cdi>puscs tu^uaiignanc}* of the pini- mnn jr r . M W rna f it . 47:103, 1934 13. l i o n , C W ,, m 4 llu x w c u . Ila A ilm lw M t IdwcvtT. such tystoiv alerted tlie susjicifni of Ihr-'authors in the second case. " On the basis uf his autopsy, our pathologist SH THE JOUKNAL-LANCET . Aned. W .chr. I4 :3 ti|. 19S9. "v " , . . 14. StN. K . W .rrl"~ "W U v a jH litjr io h o M i W * . * * * Im lu X . ItraUb 12:19. I9 S S . --. . . 15. fc K iw M a in X E . P .: The Piin i .i nwmio.8 P to U o . S r ^ * - - . C ria , tu .! CharlM C T h e ~ M . 1IISSL . . . .. JAM 014835