NINTH Al'!>U.U. IliDliu'iA P:,TROLOOY SE!ffilAR

DISEASES OF mE LIVER

by

Bi:Jio/ARD :c. GiLL, M. D. Mary N, Emex~r Professor of Patholoey,

Cincinnati School of Medicine; Editor , iLl!leri co.n J ourrul of Pathology

l®ISTR~.TION 9: 30 - 10 :00 A,r1, C, D, T, , Nl.Y 19, 1957

Neeting t o s tar t promptly a t 10 :00 A. N,

FUCE:: VETERANS ADlffiliSTR'.TIC:1 HOSPIT.U. 1481 Wes t lOth Streot Indianapolis

Arr:mgements for 1\mch ,,<ill bo pro;·ided at thG Veterans Adm:i.nistrltl.on Hos!Jital,

(NOTE T!!E DATE !S NiLY 19, 1957 , THE TDIE IS Cli:liTJt,lL Oi~"LIG}IT TDiE)

AHNOI.INCEHENT

i:'.vltos you to a lcctlll'c to be given by

DOUGLAS A. !•hcFitDYEN, A. M. , N. D, Pr.:sbyterian l!ospi til of Chicago Professor of Biologic Chemi~ry, ~iveraity

of Illinois School of Ncdicine; Trus tee, :.merican Board. of Pat hology,

SUBJ.!;GT: BIOMETRIC CHEloliSTRY

Tll3: 10:00 ,\ , H, C.D, T,, f·lf..Y 18, 1957

F!:..'.C2: STUDF..tlT lfiiiOll BUILDilUl 1 Ind!IIJl3. University School of Hedicinc, IndianaFolis, Indi~~

(The first day of Ti:'lle Tt'ials fer t he InclianapoUs "500" •rill be

the "tfternoon of ~lay 18, 1957, for those who a re interested, )

SLIDE NO ,

1 , 2 , J , L.

s. 6. 7. 8. 9.

10 .

11 .

12 .

13 . 1u. 15. 16.

17. 18.

19.

NarES PREP!\RED BY DR. E. A. GALL

FOR Ti-lE

N I N'l'H ANNUAL IND JANA PATHOLOGY S lY.rnAR ( 19$7)

DISV.S.ES OF T:lE LIVER

GONTE;JTS

DIAGNOSIS PAGE NO.

His~oplasmosis 1 Acute con~rilobular necrosis 1 z.lassive hepatic necrosis , cause undetr.-mined 2 J-:assivo hepatic necrosis, herpes simplex infection 2 Subacute hepatic necrosis 3 Postnecrotic cirr hos is, progressive stage 3 Postnecrotic cirrhosi s , advanced L Pos t hoi;Otiti c ( trabeculax~ cirr hos is 4 Adva ncing Nutritional Cirrhosis Toxic hapatit i s S r:utrit iorwl cirrhosis , advanced 'Toxic hepatitis 6 Bili<lry (obstructive ) cirrhosis, moder ate ~evority 6 Cirrhosis (nutritional ~nd biliary) of fibrocystic disease cf t;,e pancreas (Huco-viscidosis) 6 Cardiac cir rhosis 7 Pi gmont.:.ry c i r rhosis of h<..mochx·omatosis /.l Subacute hupnt i t i s i n galactosemia 8 Bizarre vacuolar degener ation of hepatic par~.:nchyma in a case of amaurotic idiocy 8 Hepatoma in posr.necl'otic cirrhosis 9 Pr:L-.ary livar carcinOI'IB, prob'.:oly chol::ngi-ohepatoma 10 Dif fuse angiomatosis of the liver with malig-nant h .. mangi oma 10

Slide # l (2613)

A hepatitis chRracterized by irregular enlarge~ent of portal areas t·li t h an i 1;t ense i nfla nt-nator y e:,udate consisti ng of lymphocyt es, plasma cells and histioo,~es , He1·e, too, are non circumscl·ioed foci of necrosis in vhi ch pyknosis is a prominent feakrt~ , The pareocbyrnal cells a r e relativ.:~ly well presorved although here and 'ther e , particularly in centr ilobular regions, a s:ilnilar inflll!rl!11at ory oxudat.e Npl>lces the .. pi­t helium, Slllall cll'stors of l ropnocytcs are found :L"L scattered sinusoids , An incidental foatur e is t he postmortem overgrol\~ll of s mall colonies of coarse bacilli, If one searches car,.;iully in tho portal i nflammatory uxudat e , notably· in rel 3ti on to tho areas of necrosis, one will encounter occasional histiocyt~ and even giant ce1i s in which smr~l cl~r spherules may ot~ svon. Stainine; character, however , is of such nr.turo th!lt thosc ar e not cosily disti.lt{;Uishabl -> from v-ncuolos . Staining Kith tha PAS, Gridley or Gl' ocatt motho..-!s del:lonstra.tes the presence of lar ge numbt;r s of small sph~;rical spores usually intr.1cellular in location but al so f ound free i n the inter :.titi<ll tiss"..Los . Those oro t he s pores of Histcpl<lsma C::f>Sul<:tum.

Diagnosis : I!istoplasnosis

Slide #2 ( 8o87

Tho central half of each l obule shows uniform loss of parenchymal cell content, Cl ose scrutiny r eveals the presistence of sinusoids in ~rhich n.d colls are idunti:fiablo , Accompanying this process is a sprinkling of lymphccjtes a~d fairly largo n~~bers of histiccytes filled ·.~ith finel~ granular brown pigJ~~ent~ The ~urviving parunch;y-:na border ing the area of dicrupti on rvvcals ,r .. teatiun of r adinl structure although tho cel l cords (pl ates) e ru t hi ckened to 2 or mox:o cells in thicla1ess . At t he poil1t ~ediat~ly cont iguous with t he contrilobular '!one th~o: calls are st-rollon, multinucleated and often exhibit an acinar . pattern, Fatt y vacuoliz~tion in those r emaining pare:tc~T.llll ulements is notewort..lty. In tho portal arec there is a scant infla'11!1l:ltory exudate, sane ed~a, but no striking alteration . The .lesion is classified as cantrilobult:~r necrosis of toxic natu1·o a nd is cha.r act erist.ic though not diagnostic of carbon t otachlorido poi s oning . Identica l changes may bo :L~duccd by a l arge nlli~bor of hepatotoxic subst a nces , Complete ngeneration of tho lobules Without stigmata r.ay be antic.ipattd in t~ose cases recover ing f r om the acut~ episode,

Diagnosis : Acute centrilobular necrosis (carbon tetrachloride poisoning. )

Page 1

Slide /J3 (231.11)

This is an a:r.ample of .n<:ssi ve hepatic necrosis of undet er -mined etiology, In cc-ntrad!.stinction t o t he px·eceding slide there is no uniformity of the patter n of necrosis ;ll:Jich is ext ens i ve and in many areas r esults 1:1 cc.mpleto destruction of en tiro l obules . In a f e;r instanc<:s one nay still rccognizo3 r o:nnants cf thick.:.ned coli cords wi.thout any regular distribution. These r~prosant incipient foci of r<:g~neration. In ger.or ::.l, ho;mver, t hvre i s 1·rido loss cf paronchymal cslls, the r cmnin­ing t issue consisting oi col l apsed ond thickened reticulum fibrils and sinuscids !1llod ;;ith r od cells. Th•J re is only a spriitkl ing of l YJnphocytos and histicoytos, the l at ter containing pi gment of varied nature . At the pariphsry of l obules r eccgnizablo by persis tence of porval ~r~as, one ~y sao ccr d- lil:o stn:cturos simulating ductules but prcsun::bly r~.;pr<.sentiug regen-:.rating paronch~al cells. Those contras t very nicely with the apparently undisturbed interlcbul.lr ductul,,s soon in t he por tnl areas, Hith:i:n the psoudoductulos one rnay often r ecogni ze inspissat~;od bile plugs .

Diagnosis : :•:assive hepat i c necrosis , cause undet~mined.

Slido #4 (6978)

This is also an c:r.a;:tpl e cf ro.::.ss ive hepatic necrosis but of a scrne\vhat. more ful.minating nat ure tha:'l that seen in the pr~ceding e:r..amplo. Here cnu hCls the impression of hemorrhage, alt hough a mer e carr::ful in­specti on l'Ovoals tho f .1ct that t he l"i.ld calls a r c i n t !le main enclosed •Aithin d nusoids uhich have fallon together bocause of cor.~plote l oss of the interved.ng parenchymal cells . Thero is ro:narkably little E:vid<onco of infl~~~tory exudate . hesidual opitholial elymvnts have no rhyme or r eason in their distribution . Snell grcups of thum remain in r elation to por tal a r eas and othol's a r e f < urtd abcut t ho c<mtral ve i ns . Res i dual coli cords a r e thickunod and contain multinucleat ed cells and occasional mitot i c ficur Gs . L~terlcbular ductulos are unr~mnrkable, there is littl o or no inflor.matcor-.r e>..'\ldc.to in thoJ portal ar eas and pseudoductulo fol~:m­ticn is locking. The ir.portant feature in this l os i cn and cno 1-dl ich ~~y be easily overlodkud is demcnstrot od by close scrutiny of tl~ nuclei of r cmainine liver colls . Some of those appoar vesicuhr but others exhibit n pr<l e homogen<J c•us bas opltill ic appoarnnco. This ph.:lncmenon is indica t ive of basophilic inclusirP.S ~lhich, thouuh not pathcgn<mic, 1-1han Gbserved i..'l infants suggests infecticn with virus .

Diacnc.sis : t1assive hepatic necrosis, heroes simplex in-f ecticn,

Page 2

Slide #5 (7337)

If one prasU!!Ws a noxious nc;ont with l oss iutensit~· or acting over o longar poricd cf til:1c t han tr.at Hbich affected the liver in the last two specime~, this is the r esult cne mi~ht anticipate . It is not ed t imt thero is total l ess cr l •bular architt.cture; ori mtat i on i s poss iblo only by the i dentificat ion of portal a reas . Those a r e r ecognized 'IIi th d:l.f'fi culty because in many there :l.s a psoud(.ductular pro­lii'erati on cf consirtorabl~ dor r oo. It is ncto•,;orthy that each portal area cont::ins a he<>.vy lymphocytic i nfiltrat j.o:t. This suggests without any degree of certainty the possibility that the underljing disease here is viral hepatitis. No singl e liver cell, and many .:tl'e pr esent, is comp1utel y normal . The ccrds a re disarmngod, th(,l cel ls are sHollen and irrogular and tho plat es a r c many colla thick . t·.ultinucluat:;d paNnchymal e l c.nonts show hyaline degeneration .:tnd necrosis . Fseudoductule for.1ation appo~rs not only at tbe periphery of tho l obules but throuehout tho lobular substance . Ther a is an irregul ar diffuse infloromator y exudate consisting mainly of round cells. Tho sinusoids in the zones of nec1·osis havo fallen together and show hemorrhagic extravasa·~ion and piJ;~~~ent containing histio­cytes. L:lrge granules of bile pigment ar .. notod within s~o~ollen liver cells .

Diagnosis : Subacute hepatic necr osis .

Slide lf6 (7680)

This secti on r eveals ;;ha t might be considered a contilmation of the process demonstrated in the l ast preparation, t he patient surv.Lvirig the insult for a longer period of t ime . Thooe arl)as in which paNnchymal cells wer ..: destroyed have nqw collapsed and reveal an appearance sug­gestive of organizing granulation t issue. In such areas ono may see true bilo ducts , mat•Y pseudcductules and i solated parenchymal cel ls sing]y and in stnall clus t ers . Those areas in which roganoration has continuud ar e manifest as nodules of parenchymal cells co:~lctel7 devoid of no~Al lobular pattern. ,\lthough central veins may bo soen ecc .. ntricdly located in some nodul es the)' are totally lacking. Cords of livor calls aro ona <til'

mor e cells t hick a nd she;; no r egular ori(mtat i on, In t he coarsened inter­nodular inflamed stroma many l ou!:ocytcs, notabl y lymphccrtus and histioC)I"tes are s aun . This is an ir.tcrmudiary eta~o between subacute hepatic necrosis and postn~crotic cirrhosis.

Diagnosis : Postnecrotic c i rrhosis, prQ~reGsive stago.

Slide #7 (7011)

Activity continues as characterized by inflammation and t'he. irx·e~ular swell.ing of some of t he parenchy.r.al cells , The process, hoHevar, is well beyond that sho•Nn in the preceding section . Of i mport arc broad strands of interlacing scar t5.ssuo i n tolhich one :nay se~ ductules and pseudodt:ctules gathered together indicating conde:-~sation of the com­ponent structUl·es of many lobules which have been co:r.;>letely destroyed, The broad character of the scarring is far more characteristic of this typo of l esion t han is the size and nature of t:1e parenchymal nodules. Tho roganerat;;d nodules shot~ a marked v:.~rill tion in size r anging from small nodules appr·oximately the size of norJ111ll lobules to nodules sev\lral c>3nti­meters in di.arl)et er . Within these nodules thoN is a suggest ion of ro\.ontion of no1~l architecture, but a closer scrutiny ~1dicatss t hat this is seriously distorted. Ono may find an occasional portal aroa saorningly in . norrn:1l stat e , Al so there a r e r ecognizable centr.:>.l veins which tw.vo very little relati onship to the center of tho nodules and ~~doubt~dly are obviously displaced,

Diagnosis : Postnecrotic cirrhosis, advanced,

Slide #8 (7698)

This is an obvious cirrhosis but it is recognizably different from r.ostnecrotic cirrhosis. IJ.tbough an occasional focus of broad scar­ring nay be encountered, of particular note is the relatively delicate trabecular pattern of the fibrosis. This surrounds nodules ranging in size from the cali ber of no1~l lobules to that of several lobules . Ih t ho fibrous trabecula may be seen a sprinkli:1g of i.nflam.'118torr colls and biliary ductulss . Occas i onally t he duc,;ules assumCJ a pseudo­adenomatous appearat~co ~lith inspissat~d bil e plur,s . I s usp.1ct that t his ductulor proliferation, wh.'Lch is quite limited in dist ribution, r epresents tho offects of focal ob::truct ion by scar. \olithin the nodules ono tnllY readily recognize portal area~ of unremarkable appearance and with no~al relations to central veins. It 7.0uld seem that ttds is the erA product of a slowly progressive fibrosis of deli~te nature st~~ing fror. portal areas in h5.t or miss fashion . In so.-ne instances the tracery surrounds single lobules (perilooular), in others it e~braces multiple lobules (multilobular) , It is suspected that this constitutes the result of chronic s:noldering inflal'IU!iat ion t~ith t he provocation of f ibrosis ; honea the designation "post hop:rt,itic cirrhosis" , For those who are squeamish about attributing t he l ooion t.o a specific e tiologic agent (although this is not the implication of the expression "post h<>patitic" ) p.;rhops trabecular or septo.l cirl'hosis mi ght be acceptable, The important point

Pago 4

Slide #8 {7698) {Continued)

i s that t his l es i on be dJ.stinguishcd from postnccrotic cirl'hosis on the one hand and nutr i t i onal cirrhosis on the othClr , The historJ of alcohol ­ism is no deterrent, alcoholics are entit l·2d to develop Uloro than one t ype of hupatic disease.

Diagnosis : Post hepatitic {trabecular) cirrhosis .

Slide #9 {6926)

I must apologize for the use of this specl.'l\en since in the original sections examined the lesion appeared to be r el atively early a:'ld I selected it f or contrast with the ne:~t case. In the sections which came through later the process was obviously a more advanced one than 1 had thO\!ght . Its contrast ~lith the preceding twc forme of cirrhosis, hcn~over , is quite striking. The proninent feature , of course, is the marked fatty "Vacuolization of parenchymal cells . This is of both coar se and fine variet y and scattered about one may f ind that t he shar;:>ened margins of the f a t vacuol es are quite fuzzy and contai n an abundance of formalin pj.grr.ent , This should be distinguished from bile and hemosiderin pi~ent W'l ich also appear in tMso ceEs t o a greater or l.;;ss degroe , In addition to the f~zzy appearance of the fat , o~~ ma~ also see necrosis of indiv~dual coils and an accoJT.panying fcca"- n.;;utrophilic reaction, Alt~ough tho nodular groups of parc.nchral Gl e--..,ents app...ar to be thv size of nomal lobules, it is apparent t~~t in no instance can one disti~guish a central vein. This cor,stitutcs th0 end stage of t ho process >IO have called creeping fibrosis , •,;hereby there extend from both portal areas and central veins delicate tongues of ccnnechve tissue which join to split th'3 l obules into pic- shaped segments . To t his is given the name pseudolobulo formation. He(lenoration and s1~olling of the cells 1·esults in the spherical or r ounded configuration of t ho nodules , The: peri.nodul'\r connective tissue in con­trast to that in postnocrotic <:::irrhosis is much nora delicate . In t his example there is an abundance of psuudoductule proliferation. ()lo should nate the presenca he re and there of intact interlobular ductules for contrast .

Diagnosis : Advancing nutrition~l cirrhosis. Toxic hupatitis ,

Pago 5

Slide /HJ.O (N- 54- 163)

I had hoped to have had t his as a contrast >fith the preceding slide but _ tno1·e is less difference in the degree of cirrhosis than I oxpoctud. Pseudolobulation, fatty vacuolization and delicate fibrosis are well shewn. T:lero3" is la~s ps<mdoductular p1·oliferation than in the preceding exa1~pJ.e . Her e , too, one may sec focal necrosis , tho par enchymal cells exhibit ing incr e<>.scd pigment deposit and focal l oss of staining \)Owor , Dlfla£llll1£'-tory r eaction to tho cellular degeneration is not a str lking featuro .

Diagnosis : Nutritional cirrhosis, advanc~d . Toxic hepatitis .

Slide #11 (N-54-474)

In this specimen the presenting feature is an irregular stellate enlargement of all portal areas. These are fibrotic and the site of il''lflammation which appears to be ralatod to interlobular ductules. The l atter reveal slight dilatation and, ?>f stl•iking i..nport, periductular concentric arrangement of nvwly formed. connective tissue . In many of t ho ductules one llk'l.Y see smaE clumps of neutrophHs and often those appear to be invading the wall . Tho moderately scarr.:Jd portal areas also con­tain evidences of bile duct proliferatiat. This can be distinguished from pseudoductular proliferation ·~itb difficulty. It is obvious that tre stellate configuration and extension of fibrosis doas ~ot proceed from portal area to portal a r ea. Tho result ~o uld be i n most instances a gr anular r ather than a nodular livor. Of :iJnpOl•t is the f act that save for i:'l.tercellular bile stasis the parcnchYJna of this liver samplo shows relatively l ittle al ter ation from the normal ,

Diagnosis : Biliary (obstructive) cirrhosis, :nod·-r:tw severity,

Sl ide //'12 ( C-54-91)

At first glance one wuld consider this a:1othcr c.:xat:>plo of extreMe fatty degeneration of the liver ~ith progt~ssing nutritional cirrhosis . All parenchymal cells are the seat of profound v:tcuolization and there aro f eatures also suggestive of toxic hepntitis, Those are character ized by a fuzzy appotlrance of t ho fat vacuoles and oreas of necrosis 1olith neutrophil exudate of ndnor degree. '£he portal areas a re

P:l.ge 6

Slide /112 (C-5h-91) (Continu0d)

obviousl y enlarged, fibrotic a:'ld havG begun to show intruding creeping fibl osis . In additior:, h<r.-1over, "to the pst:udoductular pr olifera-tio:l so comnon in ordinar y nutritional c irrhosis t h•3r e is mark~>d dilatati on of the ducts as a result of i nspissated secret ion which has dist ondqd and obstruct ed the lurnons , Although many of t hese i nspissa t ed masr.os have tho appearance of dr ied bile , othnr s a r e h:;'<lline and eosino­philic and lack tho bile s t aining. The deposit is :1ot unl ike the type of secretion seen in the pancreas of th<.se cases. Thi s is a very ch'lractvristic lesion and is seen Hith increasing frequency in children with cystic fibrosis of the pancreas l>'ho have surviv"d oeyond infancy, To a certai:1 extent the l i vers are the bUJc.an countorparts of those seen i n depancreat i zed dogs . In addition to tho fat and nut ritional cirrhosis, hOivovor , t ho peculiar abnormal ities of s e.crotioli r esult i n i nt-r ahepatic obstructive phenomena as •t~ell. Tile combi.'1ati on of nut1•itiorull ci.J:•rhos i s and f ocal bili~ry cirrhosis is almost unique in cystic f ibr osis of t he pancreas, Hany cosm;, becaus~ cf i nc idental hepatot oxic insults, will also sh~tl p~tchy pcstnecrotic ~carri.'1g ,

Diagnosi s : Cirrhosis (nutrition~l and bilia17) of fibr ocyst i c di sease of tho pancreas (mucovisc i dosi.s) .

Slide 1/13 (i~-Sl-162)

This, too, i s a hi ghly char acteristic lesion. Thcrt. is h&patic fibr oci s ~<ihich is highlight ed by .:1 peculi ar Sl-lineing pattorn •lith s t r ands proceeding f r om the r egion of onv centra l vein to anot her, Although s~ll t ongues cf ccnn~ctive tissuG occasio~lly extend to include the por tal areas mc:<t of thesu are intact. This is the end picture of severe pr <:>­trP.cted and recurrent J>'!SSive congestion of the liver. The swinging fib­rosis shows collagoniz.ation ernboddcd i n lmich ore cor ds of atroohied li"er cells. So:ne of thes e resembl e pseudoductulcs but lie in the ccntr ilobular r egion and a re an:lto:ni cally unrnl ot ed to cholangi ol es . In r elation to some of t he central veins one may see hemor r hagic ex­trnv::.sation and scat t e r ed hemosider in laden pt1.:1gocytes , A similar lesion i s seen in hyper thyroidism of s<;ver e degree, \·inet her this relates to the cardiac complication or is t~.u Nsult of soroe form of metabolic ::.bnonn1.1lity i s not kno~m . TO.. for:nor nppears :nore lilwly,

Diognosis : Cardi<-c cirrhosis .

Page 7

Sl ide #1!1 (2368)

There is no difficul ty in recognizing this lesion. It is characteristic of the pigment ary cirrhosis in hemoclu'cmatosis , LY! this instance the f i br osis is relatively coarse and sholVS a distinct pez·i­lobulaT distribution 1~ith r.~aey central v&ins easily distineui:"habl e , The preso.Jti.r.g featur~, of course, is the heavy deposit of br ownish granul.:~r pigment 1-1hich is fC'Uild in the strocr.a, in tho epitl:elial cells of tho ductulos and also in too pare:nchynal cells thon,selvcs . Comparatively small amounts appear in Kupffer colls. An iron stain highlights dis­tr).bution of tho piemont. Jil addition stains with bas ic fuchsin reveal the i'ect tll:lt many of the granulos are not hor.tosid&rin but hvmofusc.i.n, Althot:gh th..; presence of this no!l iron- containing pig;;~ent is not patho­gnomonic of hemc>e~omatosis, it is highly sugg<:.stive. P.enofuscin is found r nr oly in the pigmentary cirr llcsis in cases Hith sc call ed "~xogenous hemochromatosis" (the post tr:.tnsfusional t ype of cirrhosis with pigmenta­tion) ,

Diagnosis : Pig"J·:mtary c:!.rrl:osis cf hc:ncchro::-.atosis,

Sl ide #15 (fl 11-51)

This is a severly alter~d liver with evidence of both acute and chronic 3Ctivity. All parenchYJlllll cells are distorted and the lobular pattern obscured. The coll co1·ds arc thickened and no longer exhibit tho radial patt<JI'Il although ce:1tral veins are distinguishable . Necrosis has occurred with some f ibrous replac0111ent and marked pseudoductular prolifer­ation, Within tho parenchyma there is much microvacuolar fatty chtmge, A pral'.ino:1t feature and one \ot) ich i!! Mid by s o.,o to be characteristic of this disease, is the c rran6ement of the parenchy:nd opithelium into an acinar pl'.ttorn. Jil addition thvre are droplets of bile ontrappod within thu aci no.r spaces .

Diagnosis : Subacute hep.~titis L> galactose~ .

Slide ;/16 (21~91 )

This is anoths r s&mplo I should not have selected. I expected t.o get dHferent histochemical rasults than thosu obtained, From t.he histor.1 nnd th~ findings at autop~y this appears to bo an instanco of

P<:ge 8

Slide ;116 (2491) (Continuod)

amaurotic idiocy r el ated t o s ane defect in lipid met abolistn , It probabl y falls ~~ithin the group of c<:'.ses among 1~ ich is listed Niemann- Pick •s di sease , The liver sect.!.on r eveals alteration in r !\Ildom fnshion of groups of parenchynal cells which are s~o1ollen , f inely vacuolat ed and ~>lith a foomy appear ance . I <!nticipated th:Jt they ~>rould contain a sk.in<:'.blc lipid in par affin scction1 a ch:lracteristic fo::ture of !:iomam1- Pick •s diseas ..: . P.o<lovcr, the Sudan and Oil red 0 stains failed to ent er those cells tll ­thougb s t oinable ~torial was found in l'_upffor c :>lls ( I rurni .. ·ld you tho:>sc a re pal'affin sections) . I'ioreover, PAS s t ain of the parenchymal lesion also •ras nozative. Althoug:~ t his is obviously :m inst ance of met abolic l ipid dis order of the ~raL~ , the losicn L~ t he liver cells is not so iden.,ifiable . I an unable to cla~<sify this procccs; ho•;evor, I have sent the sections to sov&r al pediatric pathologists a:'ld llope to have sOCle i nforl1l0tion for you at the t ime of t he meeting.

Diagnosis : Bi~arre vacuol~r dog~norntion of hepatic parenchyma in a case of amaurotic idiocy.

Slide #17 (7110)

Tho underlying les:.on h<.~rc is postnecrotic cilThosis in a st:~ee of continued activity as indicat.;d by t he r.1arlced pseudoductule prolifer ­at ion, };any of t he pseudoductulos are arranged in f r.ll1g:c like fashion about par.·enchymal nodules . Tho superimposed neopl'lsm is multi- centric, some of tho nodules r oplacing pa1•unchyma and others obviously insi nuating themselves into vanous cha.mels . The patwrn of the tumor is vari ed and forms both a :1osaic and a p."-pillary structure. The cords of tumor cells arc undiifer ontiate:d and cl~rly distinguishabla from the r egener ating livor calls, a situation ~rhich is not a l ways the case. JUtotic f i gur.:s of 'bizarre nat ure ar c manifest. l.i.fforts at acinus f ormat ion ar c det octed and careful scrutiny ;rill r ew al indication of bile pr oduction in r e­lation to sene of the t umor coils .

Diagnosi s : Hcpat~a in postnecr otic cirrhosi s .

Page 9

Slide #10 (6915)

This, too, is a multicc~tric neo?lasn. It occurs in a liver , h~~ever, ~mich is not the seat of significant cirrhosis ; tho alterations present May be attributed to tne pressure effucts of t ho t umor. The neoplasm is chnrncterized by a prominent acinar pattern although ther e is quit e n degree of vc.r iation. Sol i d shoot- like masses of C:lpithelial cells and narrot'' channel ed tt~ies on c!'oss suction shor,r a glnndular struc­tur6 . I am not too certain tvhot h.;..r t his should be cons idered n cholangiomn or a ccmb~ation of both t ypes of pr"~~ry liv~r t~~or, a cholanliohepat~ua . I :tm unable to detect cvidenca of bile formation j.n the neopl".stic cells.

Diagnosis : Primary live1· carcinoma, probably cholangiohepatoma .

Slide ffl9 (56-A-2)7)

I I{Ould classify tltis as a difft1so hemangio-endothelioma of the Iiver. Tlle les:.on varies quito strikin;;J.y fran one area to anoth0r. In some instanc~:Js ther e ar c simple cyst- like pools of blood similar to t hose seen in peliosis hl.lpatis. ln others t ho pattern is that o.l' cavomous and capillary homangioma, many ~Jith ovidcnoo of organi z:ltion. Fin<llly there is much :nor <J cellular c;,d pleomorphic ar ea oot1:.er sholffl in other secti~~ t han those w~ch you have . This has the appcar<lnco of Malignant neoplasm.

Diagnosis : Diffuse angiomatosis of the liver with malignant hem.'lng ioma .

Page 10

List of Diagnoses to be sent to: Dr , E, A, Gall Department of Pathology University of Cincinnati Cincinnati , Ohio

l.

2,

3 ,

4 .

5,

G,

'1 ,

8,

9 ,

10,

11.

12 ,

14 ,

15 ,

16,

11 ,

18.

19 ,

NINTH ANNUAL INDIANA PATHOLOGY SE~!lliAR

DISEASES OF THE LIVER

presented by;

Edward A. Gall, M, D, !.'ary Ll . 12nery Professor of Pathology

Univeraity oi' Cincinnati Coll ege of Medici.ne

Director oi' t he Department of Pathology Cincinnati General Hospita l

Cincinnati , Ohio

Dat e: May 19 , 1957 Tirr.e: 10: 00 A. M. (C . D.T . ) Place : Veterans Adm . Hospital

1481 West lOth Street Indianapolis, Indiana

Sponsored jointly by: Indiana ASs ' n . oi' Pathologists Indiana Cancer Soci ety u. s . Veterans Adm. Hospital Indiana Univ . School of Medicine

1.

2 .

3 .

4.

5 .

6 .

7 .

s.

9 .

10.

11 .

12.

13 .

14 .

15 .

16 .

17 .

18.

19 .

LIST OF DIAGNOSIS FOR YOUR FILE

Case 1 . I.U.Id . C. L 2613

The pati ent was o. 38 year old white rn.an vrho vras admitted to the hospita l on three diffore1~t occasions . His chief those of no so bleeds , weaknes s and o!l.SY fatigability . symptoms for several months. Ho noticed "bbck to rry several occasions .

compls ints were He h~d ha.d these

stools" on

Physical examination wns essentially negative except for moderate oplenomegoly.

Laboratory exemination revea l ed a.n extromo degr ee of anomie. . The patient ht<d a constant modor o to l eukocytosis nnd c.;>pr oxi.ma.to l y 75 to 90 por oont of the cells were lymphocytes . Mnny of theso lymphocytes were considered to be ntypionl. Thora was a. constant throbooytoponia in tho ronge of 55, 000 plntolots. The prothrombin· time varied from 15 . 8 to 19 . 0 seconds with o. oepho.lin flocculation r eaction of 3 plus •. Tho serum proteins , serum o.ll~lino and ncid phosphntaso, and serum co lciumo Wil ro a.ll within nornnl limits . Ropoa.tod bone marrow biopsies vroro oonsidorod abnormal but the type of aberrant oha.nge could not bo identified; Tho spleen enlo.rgod dur i ng the hospito.liza.tion. It wna thought at tho timo that ho had leukemi a. duo to tho presence of o.typioo.l lymphocytes on the poriphoro.l smoar .

1

Tho pa.t i ent was readmitted to tho hospital approximately 3 ~r.onths lc.tor with osscntio.lly tho same cornploints .

Physical oxo.mina.tion at this timo revoaled splenomegaly o.nd dofinito hopRtomegnly.

Ropoatod oxamino.tions of the bono m.'lrrow lood to n diagnosis of ostoosolorcsis of undetermined etiology togothor with mi nimal myelofibros i s ond apl asio of tho mye loid ond erythroid e l ements . Ho wns discharged f rom tho hospita l only to be readmitted o.pproxirr~toly tvro wooks later with ossontio.lly tho so.me oomplo.ints but in n moro dobilito.ted condition tha.n had been previously noted . Duri ng tho wock prior to this admission ho had daily temper&ture olevntions to 102 degroos •

. Physical ex&mination revealed extrema splenomegaly and hepatomogaly, There wero masses in the mid- epigastrium, whioh waro thought to be independent of the liver and spleen . During this ad­mission ho ran a constantly elovated tempero.tw·o,

Laboratory examination revea l ed o. profound anemia , His hemoglobin ranged between 6 , 5 and 7, 5 grams per cent inspito of ropoatod whole blood transfusions , During this admission the poriphornl white ootmt WnB definitely grsnulooytopenio 1000 1;o 2000 WBC, but tho predominate ooll wtts still o. lymphocyte whioh rcn oonsist~ntly 70 t • 90 por oont or tho total whito blood count . F!o a lso ha.d a thrombo­cytopenia .

C0 so I - continued

The patient •s course wns pr ogressively wors e a nd he died cpproxima.tely t1vo wooks ai'ter his final edmission.

The live r weighed 4, 700 grams , It was firm and cut with increased resistance , Tho out surfo.oe had a "nutmeg" appearanoo . -Ce.so 2 . I . U. M.C. 8087

The pntiont wo.s a 40 yoo.r old '~hi to woman who vra.s odmi ttod to the hospital on 9- 22- 56 ond die d i n the admitting room. Sho htld suffered f r om chronic headaches for many years . In recent ye o.ra sho developed pnranoid symptoms . Roo ontly she ho.d boon drinking much o.loohol, Approximately one wook ago she drnnk s omo o leaning fluid , Shortly aft er tho in~ostion of tho f l uid, sha dovolop~d abdomino.l distention and hfl l" hoadaohe o.nd mon·~a l symptoms booame much more sovoro , Within o duy or two sho becomo ataxic ond fell i'r equt)nt ly, Her urina ry output progressively dooreased in omount . Sbo wos hosp i talizod in a looo. l hospi tnl a nd wns noticed to bo jo.undice for tha first time , Her NPN was 132 mgm. per cent . The bilirubin ~ms 3 , 7 mgm. per coot diroot ond 4,65 mgm. per oont indirect . Tho sorologioo.l t est for syphilis v~s nogsti vo , Tho homogr om was not rornnr knblo. Tho a4 hour urine output on tho day pr ior to admission was 200 oo . On the day of admiss i on to Long Hospi tal s he h!ld o. ]:>l ood prossuro of 70/0 . Tho honrt rato was 40. She wns c omntoso ond responded only to painful stimuli , Thoro was obvious icterus . Ro.los woro board in both lung fields , Thoro wos a 2 plus podol odarr~ . Tho electrocardiogro~ reveale d cvidonoo of hyporknlema . The hemoglobin was 11. 9 grams% rod blood count of 3, 559, 000 end a ·.~hi te blood count of 9 , 250 por cu, ml. with a normD. l difforontio.l. Exeminotion of tne ser um electr olytes rovoa l od chlorides of 65 mEq , per lite r , aodi um of 108 mEq . par l i t e r , sorum potassium of 7 . 5 mEq . per lit e r, The NPN wes 175 mgm. per cant·,

Tho live r woighod 1150 grams . The oopsulo was smooth . Thoro wes marked aooontuo.tion of tho lobulo.r pattern on section. Tho oontrnl lobular zones v:or e dark red-brcii'O ond depr essed , ~·he intervening pa r enohyma was yo llow,

Case 5 . I.U.M.C. R 2341

The patient was a 7 year old white boy who was brought to the hospital on 10- 4 -51 in e comatose state . The child bed been en . epileptic s ince the sge of 3 1/2 years end had been mentally retarded, He Walt well until 5 days prior to his admi ssion when he developed a. , low grade fever sod pains in the ohest. Three days prior to admission he had s eve·ra l convuls ions after whioh he l a psed i nto ~ semi-oomatoso state , On the day of e.dmission he was icter ic . He had a constant low grade fever ran!,l;ing between 100 end 101 degr ees F . since the onset of his present illness . There was no history of ingestion of poisons except that th9 child had a habit of collecting match covers and ~~s soon chewing match covers a few days before the onsot of biB present illness.

P.hysioo.l oxo.mination revec l ed a woll deve loped, wall nourished, white boy who w&.s severely icteric end in a oomo.tos o s tate . He had u.odorate anterior and posterior oorvioal lymphadenopathy. Thoro wns a smo.ll ecnhymosis ovor ~~e left oyo . Tha abdominal examination was ossontially negative ,

Tho lo.boro.tory exomi not ion revealed on onsantially normn l ur itlalys is . A homogrom reveal e d ll hemoglobin of' 13 grams por oont . Rod blood count vros 4 , 830, 000 ond tho white blood count was 12 , 750 por ou . ml, with e differential count of 5 per c ent bands, SO por oont polys , 13 por cent lymphooyt? s and 2 per c ent monocytos . A serum bilirubin we.s 18. 5 tr,gm. diruot and 11, 5 mgm. per 100 ml. indirect. Prothrombin time ~~a 15. 9 seconds, The serum alkaline phosphatase wos 35 . 5 K &: A unit s . The cephalin flocculation reaction was 4 plus , The total nonprotein nit rogen was 4·5 mgrn . por 100 ml , The totnl cholosterol wes 180 mgm. wi th the cholester ol ester s 30 mgni. par 100 ml.. The t otel arJrum proteins woro 6 , 4 gm. per cent ond the serum albumin was 4.4 gm. por cent end tho serum globulins wera 2 . 02 grams per cont. Blood cultures wore negative end tho olootrolytos woro within nor~l limits .

Tho p1tiont 1 s course in thu hospital wcs pr ograssivl)ly vror se ~nspi to of g0norol supportive thoro.py and antibiotics . He diod four days oftor his admission to tho hospit~ l .

Tho li vc r we ighed 540 gm. The surface was finely granular end wos mottled irroguler with snell rod areas intorape r sod with aroas of light ~llorr. Tho liver cut \'fith increased roaistanco end tho out aurfaco was spooklod diffusely with small red spots .

Case 4 . I.U .M. C. 6978

The pltiont was the first born of an apporontly normal mother , Tho pregnancy and delivery were norrno.l . The patient was circumcised o.t tho age of 3 do.ys . The mother bogon to spi ko o. favor on the third post ~rtum day to lOS dogr aas . This continued until tho tenth post por tum day. No diagnos is wes mcda . She ho.d hlld sevore l blood cult ur es o.nd ohos t f ilms all of which woro negat ive . Four days followi ng tho circumcisi on tho inrant began to have favor gro.dua lly rising to 102 , Chest X-ro.ys and blood cultures vmro n~gativo . Tho infant began to blood during tho tooth day of lifo, from the eirc~ision wound cud from the various n~odlo wounds , Thoro was ana episode of bleeding from tho mouth . A hemogram on th~ tenth do.y of lifo rovoalod a he~oglobin or 15 groms , rod blood count of 4 , 011, 000, whi to blood cou:1t or 9 , 550 with tho n orma.l di!'foranti n l , Tho plllt0 l ot count vras 129 ,170 , Dlood W!l s dr llvm i nto ll ololln tube a nd allowed to clot. Only f ragment s woro olottod o.r t e r 75 minutes . A trona fusion was ~;i von tho e l eventh dDy of lifo . Tho mothor ' a infection finally rQSpondod to torrnmycin . Tho ini'o.nt wns given ilotyoin, terramycin end vito.::dn K which did not ch~ ngo tho cliniool picture , Ha died 12 days foll~7ing birth .

Tho li vor weighed 132 gr n.ms . U >'ltl.B soft smoot h end blotchy yollow o.nd N d, with p.roos or hcnnorrho.go •

Co. so 5 . I.U.M. C • . 7337

Tho po. tiont wns a 59 yea r old whi to womAn who was admitt ed to tho hospi tal on 12-2~54 a.nd diod on 12- 9- 54 . Tho compl aints upon nd!Tdsaion "oro those of jaundice of ton days durntion, chills llnd rovor of 6 cbyo durntion, !>nd vomiting 11 ooffoo ground" l!l!lterial . Tho potiont hc.d boon hospitnlizod he ro from 10- 7- 54 to 11- 22- 54 who re sho hod undergone a subtoto.l go.str eotomy for upper g~strointostinal blood­ing . She ha.d ohronio esophagi tis vri th constr i ction or t he oo.r dio. , Sho roooivod por iodio dilatations of the esopho.gus . A s ubtoto. l p;o.stroct orcy was done t o r eliovo hor hyporllcidity. She wos discho.r god from tho hospital ten days post oper atively.

C~so 5 , continued

Physica l examination of this admiss ion rovca l cd an under­nourished, mtlrkodly jaundiced , "<;hi to fomo lc who wos in a semioomtose stato . Tho sclerae were icteric , Tho abdo~sn was flat end tho livor wos palpable 4 oontimotors bolow tho right costal margin. The sploon was not palpable . Tho liver wos non-tondor. :

Laboratory examin~tion revealed a serum bilirubin of 4.1 mgm. dir!J'et and 4 . 2 per 100 m1 . indirect . The thymol turbidity was 13 uni ts . Tho tote 1 serum proteins was 7 ,4 grams per cent with the serum albumin 6 , 49 grams per oont end the globulins 3 . 91 grau~ per cont . Tho serum alknline phosph~t~se was 12 ,.6 K &: A units . Tha prothroobin time was 53 per cent of normnl. The red and whito blood counts WGr e within normtll limits and tho differential sme~r rovoalod 29 pe r cent polys , 23 por oent lymphocytes , and 16 par cent monooytos • Tho pla.telct count wns 111,000.

Tho patient improved during tho first four days of hor hospital ization but begon to vomit a1torod blood on tho s i xth hospital doy. On the following dny she went into shook cmd vomited "coffee ground" mo.tarial. She expired on tho seventh hospi tc.l day, which vro.s fi!'too11 days aftor tho first noticeo.blo jaundioo and betv;een 60 and 27 days boforo tho transfusion of 17 units of blood which oocurrod on he r previous hospitalization.

Tho liver woighod 1540 gro.ms , Tho S\tr!'o.oo wns s mooth 11nd light brown. On section tho livor OVfl s mottled yo llow-b r own,

Case 6 , I.U .M. C, 7660

The patient \Vas o. 25 year old vrhite man who was admitted to the hospital on 10-6-55 and died on 10-7-55, The patient had been admitted to tho hospital on four previous nocasions . His first admission wus in October of 1953 at which time he complained of intermittent jaundice, 'l'roakness , and ::al.llise of t?to years duration. He had a pparently been feeling well until December of 1951 when ha had attacks of "a sick fooling in tho uppo r abdomen on tho l of't side" , Ho ''ias noted to bo jaundiced in 1951. His urine at that time was dark and his stools were a light to.n . ln tho spring of 1952 ho had a similar episode, Ho

Caso 6 . conti nued

had other attacks in t he summer ond fall of 1952 , The l at ter attack was o.ocompanied by chi lls e nd rover, At tho.t t i me he had a gall bladder series whi ch s howed that t he gall b l adde r di d not concent r ate dye . In July of 1953 he vraa admitted to a loc:>.l hos pi tal where t he gall bladder vro.s "dilated end was found to bo obstructed" , Tho gnll bladder wus anastomosed to tho jejunum. In Ootober of 1953 a bone marrow nspiro.tion wns done wniob wos reported to bo oompntiblo with Bnnti •s syndromo . In May 4 1955 the thymol t urb i dity wuo 15 . 5 units , The cephalin floccula­tion reaction vro.a 4 plus , The prothrombin t ime vma 35 per cent of ' normc 1. The totn 1 proto ins waa 7 ,4 grams par cent with the s er um albumin 2 .68 grnma por cent and tho serum globulins 4 . 72 grams per cont . Tho serum bilirubins vrero 2 , 6 lll{lm• direct , 3 mgm. indirect, o.nd a total of 5 ,6 mgm. pe r 100 ml . Si nce &~y of 1955 he ho.d boon doing fo.ir1y ·:;ell oxoopt for tho rapid £tccumulntion of o.bdominnl fluid . Pbysicnl exomination upon his torminel admission revealed a blood pr essure of 120/50, pulse 76, respirations 18, He wa s mar kedly jaundiced and the abdomen vras pr otuberant . Spider nevi were on the ches t , Ther e vma abdominal flui d wave . Tho liver and spleen vrero palpa bl e . Shortly ~ftor admiss ion he vomited lar ge quent i ties of blood and became hypoten­sive , Ho died shortly ther eafter inspite of' blood transfusions . On this e~~ission his prothrombin timo was 11 per oont of normal , Tho se rum bilirubin wea 1 , 9 w~. direct , 2 , 9 mgm. indirect with a total of 4. 8 mgm. p<lr 100 ml.

Tho livor woighed Tho nodu l es varied in s i ze , betwoo n tho nodules •

Caso 7 , I .U , lo\ , C. 7011

1400 grams . Tho surfo.oo was nodula r, On uoction, ·there was fibr ous tissuo bands

Tho patient v:ss a 41 yoo.r old white ~r.~:n who was admitted to the hospitel on 2- 18- 54 end died on 2-24- 54 , The history of the pr esent illness dates to November of 1953 when he had an onset of abdomino.l distention. In the oarly par t of Dooomber 1953 ho developed swelling of the l ower extremities , Six wooks pri or to hio admission he was a.dmi ttod to his loco 1 hos pi t e l because of woalmosa , chills, fevar 1

n•usea, abdominal distention, and edema of the l ogs , He was treatod vnth diuretics , dieita lis , multiple paracentesis , and a low sodium

Case 7, continued

diet ~ Three weeks prior to admission to this hospit al he had the onset of irritability, insomnia , and purposeleasness movements of the upper extremities .

Physical examination !"evealed a poorly developed white man who was unresponsive. There was s l i ght icterus of t ho sclerae . The.tre ~~re reles i n both lun~ bases, Examination of the heart vms notre" mar~ble , The abdomen wao distended, and there wns evidence of o. fluid wuvo . Thoro wore no masses or organs palpable . Tho patient's scrotum wus cden:atoue ,

Laboratory examination r evealed a negative urinal ysis except for a faint traoo of albumin . Tho hemogram wos essentially negative , Ser ological toot for syphilis was negative , Tho sorum bilirubin was 1. 8 mgm. direct nnd 2 .4 mgm. per 100 ml. indiroot . Tho total sorum proto ins were 6 gro.ms por cent with 2 . 8 graru; per cent albumin end 5 . 1 gr ams per oont globulins . The nonprotein nitrogen vms 37 mgm. po r 100 11\l.

Tho patient wo s plo.oed on a low sodium diet . He improved until the day of his domiso when ha bocamo e.outely end critioo.lly ill Gnd wns in shook. He begcn to vomit lo.rgo quantities of dark blood. It wns thought that he vms bleedi ng from e. ruptured osophagoo. l vo.rix, In spite of blood trcnsfusions ond gonoro.l su~ortivo measures tho po.tiont diod,

Tho liver vreighod 1120 grcms . Tho surfo.oo was nodulo.r 1

and the nodules varied in size .

C!ISO 8 , I.U .M.C. 7698

The pntient was e. 49 year old white man who was admitted to the hospital on 10~-55 o.nd died on 10- 28- 55. The potient \'IllS admitted t o the hospital for surgery of esopho.geal varices which had been pre" sent for several years , He hod eonsumed lar ge quantities of o.loohol throughout his life . In tho eo.rly 1930' s he oonsurnod one" fifth" or liquol' o. day . In 1935 ho ho.d on opisodo or jaundice which requi r ed bed roat . In July of 1953 he noted blo.ok to.rry stools ond vomited some

Case 8. continued,

bl ood, X-ray examination at that time r evealed esophageal varices , From that timo until the timo of his admission he r equir ed numerous blood transfuaions because of the esophageal hemorrhage . He was a~~itted to tho hospital for elective surgery.

Physical examination. Tho blood pressure wae 100/65 , pulse was 76 , respirations ware 20, There were several spider nevi on the rig+rt and left shoulders . No jsundioe was noted, Tho liver edge wns pslpable three centimeters below the right costal margin, There wus some tenderne ss on palpation of the liver , The inferior pole of the spleen was pal pated just below the left costal margin.

Lnboratory examination. The hornograms woro within normal limits . The toto.l ser um proteins wero 7 . 1 gr ams por cent with a serum albumin of 4 , 54 gr~_s per cent ond the sorum globulins 2 , 56 grou~ pe r oent , 'f·he prothrombin time was 79 ,5 per cent of nonnc.l. The total serum bilirubin was 1 , 1 mgm. per 100 ml . vnth tho direct fraction 0 , 2 mgrn . en~ the indirect f r notion 0,9 mgm. per 100 ml, Tho serum olknline phospho:taso was 3 ,8 K & A units, ThO totol ser um oholestor ols vroro 114 mgm. per 100 ml. The serum cephalin floooul:ltion reo.otion wo.s 3 plus ,

, Tho po.tiont vro.s taken to surilery where c. splonoctomy and a po.rtial tJsopho.go-gastrootorny with removal of tho lower third or tho esophagua was perfonned , Following surgery ho developed e.n osophago- ploural fistula with empyema in th9 l eft ohost , His post­operative oourso wets extremely complioe.torl tmd his condition pro­gressively dotor ioro.t ed . Ho died on 10-28 - 56 whioh was 20 days after his initio.l surgery,

Tho liver weighed 1230 grams, Tho sur f ace was nodulo.r and yellowish- brown . The liver out w·ith increased rosiste.nce . On sootion, the nodules vnriud from 0. 1 oon~imoter to one oentimetor in diamet er , Tho portal end splenic veins oonte ined a rooont thrombus ,

Case 9 . I .U.M.C. 6926

The patient wee a 48 yea r old whi·te malo who wee admitted t o the hos pital in o semi- comatose c ondit i on on 12-9- 53 a nd died on 12 - 10- 53 , The hi story was gi von by his wi fe . He apparent ly had boon bl~ding f r om the mouth and rectum approximately 12 h 8urS pr ior to his admission. A history of alcoholi sm dating back about 15 years with a ~rked increase in the quantity oonsurr.ed over the past 6 years was given by his wife , During the past 6 years the dietary intake had beon poor . Six months prior to his admission he had an episode of vomiting of b l ood end passing of dar k tar ry stool s , At that tima he became jaundi ced f or tho first t i me , Dur ing t he subs equent six mont hs ho had had int e r mittent jaundic e .

Physical oxsmination revea l ed a blood pressure of 70/40, pulse v~s 110 t>nd the respirations were 34 , Tho patient wss obviously icteric . A hop:~tio fetor wo.e noted. Tho liver was enlar ged two finger breadths below tho right ooste.l m:u-gin . There oms free fluid within the abdomina l cavity a.nd tho soroturr. was odomatous .

Laboratory oxaminotion: The thymol turbidity c•as 5 units , Tho· cephalin flodculation rooction wa s 4 pluh Tho total so rum proteins woro S , B grams pe r cent wi t h a s e r um albumi n 2 , 68 gr11rns par cent end tho serum globulins 1 . 12 gr ams por cont . Tho se r um alko.lino phosphatase wns 12 , 6 K & A units . The tote 1 s o rum bilir ubin wos 12 , 6 mgm . with tho dir ect f r eotion 5 , 6 ~~. end tho indirect fraction 7 mgm, pe r coat . A benogr am rovoclod a r.ll r lood onornia with a hemoglobin of 6 . 2 grams per coat . 'Ibo white blood oountwllS 27 , 600 per cu. ml , v.i.th a IIXlrkod shift to t.'lo l oft ,

,\ftor his admission a Sengsta kon tube wns anohered, but he diod shortly thereafter.

Tho l iver weighed 2575 grams . nodular , the nodules 4 mm. in diameter , yellow.

Tho surfo.oo Wlls uniformly On sootion it was firm llnd

An erosion of tho osopho.geo.l muooao. with ho,..or rhago from c. vc.rix , just above tho cardia , was found.

Case 10. Submitted by Dr . Gal l N- 54-163 Admit ted Cincinnati General Hospital 3-30-54; died 4-7-54

A 43 year old white female complained of progressive abdominal enl~trgement and anorexia . She had boon well until about thr ee weeks oo.• Uer; the illness bege.!l. during an upper respi ratory i nfection for which sho r eceived penicilli n, Icter us appeared severa l days bo.t'orG entry , Tho po.tiont wo.s a known ha~tvy eloohol io for 19 yao.rs, I n r ooont ye~trs hor woie;ht he.d remained stat io a t a. bout 200 lbs ,

Physico.l oxamin~tion showed a l ethargic , icter ic , obese w~men with many ocohymosos of tho skin, Temperature 99° , Tho liver vma 0nlarged but its edge not fs l t , There wo.s ascites end periphornl odoma.

Tho po.t iont l o.psed into oomn on the third hospi t o 1 do.y o.nd iotor uo doopenod, Bloody oozing was noted from o. Levine tube . Sho dovoloped evidence of pneumonia end died on the eighth hospital day,

Autopsy showed the liver to weigh 3013 gms , nnd t o extend 7 to 12 em, bonae. th the o~sto 1 mnrgin. I t s surface ''ms yellowish gr o'on and uniformaly f i nely nodular , thG nodules moe. suring 1 t o 3 mm. Tho ap l oon vro i ghod 350 gms , Tho oaophagus rovoo.lod superfi oio.l erosions but no vnr i oos wor o soon,

other pertinent autopsy findings ware confluent lobular pneumonia, rnnr kod pulmonory edomn ond chronic activo pyelonephritis ,

Case 11 .• Submi tted by Dr . Gall N- 54- 474 Ad~ittod October 5, 1954; died October 4, 1954

An 82 year old white male wo.s admitted from o. r ooming house unabl e to gi 'Te a c l ocr hi s t ory, Ho had been i noroaaingly woo.k for a.bout two woe Jr.s a nd in failing hae.lth for two yoo.r s . Friends who had visited him at hoJTB ha.d not noticed jaundice ,

Case 11 . continued

Physical examinat ion s howed tamp<:J r ature 103 . 8° . Ho wo.s well dovolopod 1 poorly nouri shed, semicomatos e and ma rkedly i oter io·. Coars e r alos wore audibl e thr oughout the ohost . Tho liver oxtendod two finger­breadths bonoe.th tho cos tal r.JArgin end was questionably tondor ,

LAboratory: WBC 18, 000 to 32, 000. Stool, guaiac posi•ive , _ BUN 28 mgm,%,

' oollo.pso . Tho patient showed dooponing stupor, anuria a nd vasomotor Re diod the dt<y following entry,

At autopsy the livor woi!!;hOd 1505 grns , Its surfllco wo.a smooth o.nd shi.ny and on section rovoo l ud a do.rk tan appec.ro.nco , l::!trnhopatio bilo duots were mo.rkcdly dila•od ond i'illed vrith dark greon, viscid bile , A numb9r of contiguous , fo.oetod calculi woro observed in 1lhe larger hilo.r intro.hapati o duota . The common bilo duot wo.s dilatod o.nd sov·arnl stonos wore impaotod in the ampu lla. , Tho go. l l b l adder wns thick wo.llcd, contracted nnd oonto. ined l oo , of wntor oloar, sticky flui d ,

Tho sploon woighod 295 gms . Tho esophagus was negative,

Othor pertinent findings: Lobular pneumonia and mild ohronio pe.ncroo.titia ,

Case 12 , Submitted by Dr, Gall . C-54-91

A 7 yee.r old white girl had had n-Anifestotions of cystic fibrosis of ~~e pancreas since infancy. Theso consisted of frequent eopious, foul smelling stools , repeated upper r espiratory infection end roent gen ~vidonoe of br onohiootasis , Thoro was malnutrition and, more r ecently, ascites . Distended abdominal veins snd " liver palms" were noted . X-ray studios revealed esophageal va.rioos . Family history indicated that throo younger siblings a ls o exhibited ovidonce of fibrocystio disease ,

Ce.se 12, continued

There we re many entr i e s but on the f inal one the pat ient succumbed to a stubborn overv•lle lming respiratory infection. At no time had there been evidence of icterus .

At autopsy the live r weighed 10Z5 gms . (normal , 680 gms . ) , It waG firm and diffusely nodular . The capsule transmitted a yellowish color with small e;reons ih flecks . On section nodules range from 1 t o 8 1""1• and thoro wero ooarsfl bands of' fibrous tissue f r om an irregular ne~work , The ga ll bladde r was small end contained grayish viscid materia l. The cystic duct W!lS apparently occluded ,

Other pertinent findings: Chronic pneumonitis end bronohiootasis with organizing pneumonia one obstructive emphysema.

Caso 13 . Submitted by Dr . Gall l!- 51-162 Admitted 3 -20-51; died 3/23/57

A 67 year old white malo had been i n tho hospita l in July, 1950, bocnuse of dooomponsatod hyp<~rtons ive onrdiovasoulnr disoaso , H•J returned i n August booo.uso of o. pulmonory inf'nrot., I n November , 1950, a miQ thigh nmputation \vas onrriad out beoo.uao of a r te r ial embolism o.nd gangrone. He was discharged early in February, 1951, for homo cc.-re with digitalis r.nd morcuhydrin but roturned bocause of' pr ogressive e.nast<roo ~tnd disor icmtot i on .

Thoro \'tO s alight i cte rus . The nook voino wore distondod ~tnd thoro wns extensive nnnse.rca. Dullness was olioitod in both bt~ses . Thoro \7ere both fino and coarse r s los . Blood pressuro 86/50, Tho heart did not npoon r enlarged but sounds wore distnnt . A fluid vro.vo vro.s noted in tho abdomen end tho liver extended throe fingerbroadths bolov• tho right coste 1 margin .

Laborlltory: RBC 5 . 3 million with 14 , 5 ~ms . hemoglobin, VIBC 11, 40'0 , Urine nogativo . BlJl! 38 to 82 w.gms .% EKG r evealed ovidonoo of old enterior and poster i or myooordio.l infarcts ,

C~ae 13 , continued

Course : 350 co , of oleer fluid was removed f r om tho r ight ohost end 5500 oo . of sirnilcr t r cnsudato from tho nbdomen . Co~ superven~d and he died on tho third bospit~l dny.

At a11topsy the liver wei ghed 1475 gms . Its capsule was thick­ened, opaque end finely nodulDr. On So)ction tho surfa.oo wc.s f inely gro.nula.r, nutmeg in appea runoe with a. mot ·t led pale reddish brown and yn~lovdsh hue , Cons i stency wes s l ightly increased . The gnRl bladder en& bile ducts \VSre negative ,

The hecu•t weighed 400 gms . ond was dilated . D"le r i ght ventr i cle meo.sured 5 mm. Tho left vent r i cle wa.s particul arly dilated ond thin walled, mef.\sur ing 5 t o 12 mr.~ . There was o. large r.pico.l mur o. l thrombus in tho left ventrio lo . Tho vnlvos "170ro not ronArknblo . t!oat of the left vontriolo wns r oploood by soo.r and w::s r.Arlrodly thin, There wvre sovoro. l old coronary occlusions .

Tho lungs contained e large organized thrombus in o. major vessel of tho right lol'tor lobo . Mioroaoopi oally mnny small organizi ng emboli wer e prosont i n th~J minor pulnonery vo.soulor channel s .

other porti::lcnt findings: Beni!';n prosta tio hyper trophy ond oh,onio pyelonephritis .

Co.oe 14. I . U . M.C. L 2368

H. A,, a 59 year old whi te man was admitted to the hospi tal with the chief complaints of pai n in the hips ond legs , end weakness on exertion. Thir teen days pr i or to his admission tho pat i ent collapsed while working, He experienced a smothering sensation on exertion during thet episode . Ho has lost about 20 pounds during the past year . He had noticod swelling of his feet and snkles for approximately ~7o yea r s prior to his admission. He ala~ had nocturia f r om two to eight times per night for sever·a.l years,

fhysioa l exn~nation st tho time of admission r evea.lod a

Case 14 . continued .

poorly nourished white man . His skin was deep ton . The jugular veins were distended. No lymphadenopathy was noted. Thora \'illS a very slight diotontion r-f the abdomen , which wos tympanitic , The liver wos plllpnblo 5 om. be l ow the right oosto l mD.r gin. A slight tenderness to pc lpt\tion was prasent. The skin of the logs a nd o.nklos o.ppeo r od t hickened ond dnrk brown in color, Thoro was a~ pl us pitting odenn bilnt or o.lly ovor the pretibial region .

' During tho petiont •s hospitel sto.y, ho experienced sovero.l petit malseizuros . On 12 -7-48 his o.bdo~en booo.me distended, ond ho bogan t" vomit . The vomitus vms e. dark brown color . Tho potiont Y/ll.S

found dood in bed on tho evening of 12 -7-48, approximately throo wooks after his odmi ssion ,

Laboratory oxomin~tions r oveolod o. t r o.oe of albuminur io. in sovoro.l ur ino s pecimens , Thora we re also hynlino and grcnulnr C'-Sts VIi th 10 to 55 pus calls p'Jr high power field , Severa 1 hemograms revo,alod a homo.globin of 11 . 5 grems por lOO ml . The r ed blood count was 5, 200, 000 ond tba white blo~d count 5, 000 per ou , ml , Tho differential counts wero ncr~~l. Tho fastinG blood sugars on various ocoosions woro 175, 148, ond 154 "~· por 100 rnl . The nonprotein nitrogen varied from 58 to G7 mgm. p~r 100 ml . A glucose tolerance tost rovoaled a prolonged olovation of the ourvo . The chest X- r ay showed tho heart to be enlarged in the trO.nS -a'(>iCO 1 dinmetor with straightening of i ts ltift borde r , Tha.ra was a lso a pl eura l effusion on tho right side.,

Tho liver weighed 1200 grams , Its surfo.oo was finely nodule r . It was ooppcr-bro1•m ,

Case 15 , St. Joseph Memorial Bos~itol Kokomo, Indi&na A- ll-51

The pat i ent vms born en Ma rch 16, 1951 and died on l.tay 6 , 1951 . The infant vms full torm, Throe dnys after birth ' slight jaundice was noted end diarrhea developed ;•hich continued until tima ~f ~dmission on Apri l 13 , 1951 . Prior to his admission sever~l comple t e blood counts hnd bee n done ond were found to bo within normal limi ts on sovora.l occasi ons . At the time of admission, tho temperoturo vms 99 . 5 . Tho liver wos palpable and its r.targin wos shorp. A mild icterus wgs present . The psticnt wes moderate l y ma l nourished and weighed 6 lbs . ll o z . During hos!l'i to lizntion many dil'foront for mulas we r e given . Protein milk end laotie oeid milk wos toloratod bettor thon oll tho othor fornulo.s . ilia jnundioo did not progress very fo st . Thor o '110.3

me r kod di stention of the sbdcmen. On April 25, 1951 an abdomi nal paracentesis yielded epproxi~tely 800 ml . of serous fluid . The abdomen gradually became distended again ond \'r.! S rna rkadly distended at the time of death . During his hospitalization ho had temper ature el,evo,tion with as high os 102 , 5 end untibiotics wore gi ven . Chest X-r oys o.nd repeated physical examinntions fe<ilod to help the cli nicians in explaining his temperature elevations ,

FQmily history: A younge r sibling di ed e<t the o.go of 1 month from cirrhos is , otiolegy of which was undetermined . An o lder sibling bas boen proven to ho.vo golnotos omio . Tho MOther ho.d o. positive Rh antibody titer during t his pre&nanoy. An older sibling is a mongol, The>roiS one child l i ving ond \Vall vdth appar ently no oonsenitcl abno~lities ,

lAbora t ory studi es : The hemogl obin was ll. B grams pe r oont. The red blood count wos 3 , 910, 000 end t he white count was 12 , 850 per cu. ml . Tho differ entia l count reve&led 51 per cent polys, 35 percent lymphocytes , end 14 pe r cent monocytos . Urinalysis revealed a traoo of olbuminuria with sovo r-ol coarsely granular casta . The r e was a t hree ·plus reacti on for sugor in the urine, which wos thought to be due to tho ad~inistro.tion of intravenous fluids . Stools ~~re soft, end yellow with no incroue in fe.t content. Tryps it\ was present in t ho stools os determined by a ge latin fi lm s·trip. The study of the osiotio f l uid vms negative for baoterill and tumor cells. On April 27, 1951, t ho serum bilirub in •nos 1 , 5 mgm. direct end 2 ,9 t:~p . per 100 ml indirect , Tho oephnlin flocculati on reaction was 4 plus . The thymol turb i dity was 5 , 6 units s nd the prothrombin was 100 por cent of normo. l .

At autopsy t he body mot>aured 53 em. in length ond 1•re i ghed 2900 gra ms . The abdomen vros distended end conta in ad 250 ml . of s a rous f l uid . Tho liver morgin vms 4 em. bol~w tho right costal margin. The liver woighod 200 grams !'nd wcs e. pale greonish- bro'm end yellow in

Case 15 , Cont inued

color. The liver was firm in consis t ency. The ga 11 bladder contained 5 ml . of dark b lack bile . There were no anomalins of the extra hepatic bi liary system. 'l'ha1·e was bile stain ing of the feces in the small bowel , Tho fooos in t he colon wore flrayish-white , The pancreas showed no gross abnormalities . Blood tokon at a utopsy r evoalod a serum bilirubin of 1 . 35 mgm . direct and 3 , 6 mgm. per 100 ml , indirect . The se rological test for syphilis was negative. Cister nal spina 1 fluid examinetion rovoo.lod n creatinine of 8 msm. per oent ond protein of 51 ~·· per cent . Tho ~onprotein nitrogen of tho spinel fluid wos 210 mgm. per cent,

Case 16, 'r.U.M.C, R 2491

Tho patient wee a ten ye!l r old wni to girl who was first seen in the out- patient clinic at the oge of a, Her parents stated thct tho child was mentally retarded snd hod convulsions . The early dove lopmcnt~. 1 history w3 a normal. Ts lking was sl•w and ot the a ge of throo yonr s he r spoooh \'Ill S limited to o fow words . From t hat timo on hor mental processes woro greatl y rotardod . At the ago of six her IQ was 60 , She bogo n t.o havo epileptic soizut·os et tho n;;;o of o>ight , Tho so vro re oharo.ctorizod by ralling o£ tho oyos , salivation, and generalized cortvulsions . Family history and the! po.st roodioal history .vero non-contribut ory. Physica l examination e.t thCl ago of 8 revealed a wo 11 nourished, whi to fennlo with dull i'acios . Tho opt.io nerves \VOro pnlo end atrophic . Tho liv' r ~nd spleen woro polpnblo tvto fi3ger breadths bol~ tho costa l rn&rgins , Tho neurologic ox~mination \VO.B

negative , An EEG showod tho "poti to =1 typo vorio.nt" . She vms troo.tod with o.nti - oonvulsivos and did fo.ir ly woll exoopt f a he r progressive mental retardation. In August of 1950 her seizures becarr~ mo re frequent . Physical examinat ion at this time revea l ed e.ssentially the s ame l'indings with t he exception that the neuro l ogical examino.tion revealed hyporreflexio. , Pncumoencephalograms wero negati ve . Ono ycor later she vros admitted to tho Indiana Epileptic Vi llage , Ro r c ourse in that institution is n·ot knovtn , Sbo diod nine months aftor sho was admitted, and tho b ody was brought to this institution for o.utopay.

Tho liv-:> r woighod 650 gr ams, It wns bluish-brown . Tho out surfo.oo was sHghtly yellow ond tinely mottled,

Case 17. I.U.M, C, 7 110

The patient was o 57 yoe.r old oolflred mo.n who entered the hos pital CID 4 - 19- 54 end di ed on 6- 3- 54 . 'fhe patient had had severe alcoholism of mar.y years duration sssooi~ted with poor dietary intake for pr., longed p3riods . Ho had hac e wei!lht loss of 30 to 40 pounds

\.i n the pnst year . l!~ had had about 12 episodes of hematomas is in the 1JOSt yoer , He had o lso he.d c onstant r oo·t;c 1 blo,.ding f or t ho t wo weeks prior to his admi ssion . 'l'J-o pationt notod grudua l enlargement of tho o.bdonen for ono yeor, ond one we.::k prior to edmi ssion o. ~racontosis •una dono . Abcut 20~0 nl . of fluid wus removed ,

Physioo.l oxamins t ion rcvc~ lod a ohronio11lly ill, omo.o i c.t od, oolor <3d malo with multiple spid.: r .nevi on th<~ nook r nd chest . The oonjunctivo.e wart> ictorio, Thoro I'Tvro S."lvcral sp:~ll shotty lymph nodes movable in tho ~xil)A ~f tho suporclc.vioulnr rogion. The liver ~s on:lo.rgod six centimotors bolow tre right ooato.l m:.rgin und ·;ms f i rm ll!'ld non-tender. :i'h!>L'G ">9.~ 11bdomino.l distontio;1 with def'ini to .Cluid \VD.Ve ond ahifting dullMss .

Laboratory examin~tion revealed a thyr.~l turbidity ?f 16 units , The totn l se:-um bilirutin was 1.6 ngm. with the di1·ect i'rr.o'Cion o. s mgm, a nd the indil•ect I.'roction 0,8 mtl;m. per 100 ml . Tho BSP t ed' showed 70 pe r cent dye retention i n 45 minutes, The serum olkali no phosphatase vtns 7,7 K & A units . The totol serum proteir2s in the early port of the di~oaso ','Jero nor:-.!ll snd let or •;ere slightly lo•7cl'od, i<-t"l so rum oholeste rols were 2!5 ~gm. per 100 ml, ·.nth the estel's being 94· mgm. pe r 100 '111. Hemogralllll ::-eveeolad pe::siatent a.nemill. with th e. h~moglohin ranginr; below leH>lA of 10 r;r~>ms , lJ~.tJOt gastroi.nte.-.t ~nal scdes s howed ~;.sophageal ve rires, Sev;,ral o.bdom::.nal ;>!lr:loontes cs l'roro per­formed and the fluid ~s negotive for c~noer colls,

During his oourso in the h,.spitol his j111mdice inor onaod i n seve rity , The patient diod o.ft<lr ~ m:-.saivo hemorrhtq;e from tho upper gastrointestinal tro.ct ,

Tho live r woighad 1920 grcma . Tho suri'o.oo was polo br own, i'ir:n, ~nd nodulo.r tho noduloa mcc suring up t o 1 om. On ~eotion , in t ho coutor of t he right lobo 'i:horo wna o. soft, i'riabl o, gro.y mass 12 em, in dio.mot~r . So.tellito nod~los wore oluatorod around the mo.in IW.SS .

Case 18, I.U. I!.C. 6915

The patient was a 51 year old whl.to wom~n who was admitted t~ the hospi t a l on 11- 7- 53 and died on 11-30-53 . She compl ained ot nauoea of one 'Neek duration, diarrhea of three l'teeks durati on, a 45 pound weight loss ovllr a period of four months , a sharp dull pnin above the s ymphysis pubis of thr oe years duration, f ovor of 100 to 103 'a.ogr oes of two .-reeks duration and en epigastric pnin of two weeks duration . She he.d had tuoorculosis ~:enty years o.go . .She ho.d had " rr,,la ria" on t wo different oooesions during hor youth , Approxirr.ately throe ye ars ego s ho notiood a lump ebout 1 inoh i n dbmetar in tho opigo at r ium which grow u :rtil it now axt <mdocl 6 inches be l ow tho right c os to 1 rnllrgin , It was hard and nodula r. About ·bhroo or f our months a go sh~ bL~an to loso woight , became nauseated ond ooo~sionally vomited,

P~~sical cxna.i~ation revealed o blood p ressure of 185/55, tom­perature of 98 end ~~ght 1~6 pQunds, The liver wus F~lpable 6 inches below tho ri&ht costa 1 maqpn ~>r.d wss very firm with irregular sized nodulos on the surfaoo . The fluid wave was present end there was shifting dullness ,

Lnboratory <lxo.mination revc;>a l 9d a hQmcgram of 11.6 grams pa r oon":; of hemoglobin Vlith a rod blood ce ll oow1t of' 4 , 000,000 ond o. vrloito blood count of 24, SoO p< r cu, rnl, with !7 pvr cent tanda , 76 polys , 5 por cent lymprooytoo . Srr. a rs of blood v::.ro ne&ativo for pQro.sitos . Th~ s erum c.llalline phosphatase VIliS 14.2 K & J, units, 'Iho thyl:lol turbidity was 2 ut.i ts , Tho oep'tt.lin floccul!ltion reaction was 2 plus . 'Iho RSP to at rovoo led 15% of the dye rote:.ned c.ftor 30 minutes . 'l'ho total se rum pl·ot?ins w.:>r o 6,1 gre;rns pe r cent , X-ray ex,mination of tho ontiro g!latroiutostinal tro.ot wcs negetive . A paro.oontesis yioldod 6,200 ml , of cloudy buff color ed rluid,

The p~tiout • s condition detoriorntad ortd she died ou 11- 50-53 .

Tho live r ~roighod 3200 gr~rns , Tho capsule was thick, ond nwtorous ::.odt•l!>s up to 4 en , studded tho sur!'coo . On section ona l:!.rgo areo. in the right lobo wns oornposod of tumor , 10 om, in dicu:otor ,

Case 19 . Reid Memorial Hospital Richmond, Ind:l.e.1l8. 56 A 237

Blanche Blatt i s a 70 year old white woman who was ad.>nitted to the hospital on 6-26 - 56 end died on 7-14- 56 . Her chief complaint upon admis-sion was severe pain i n t he r ight upper quadr ant of the

\abdomen which radiated through to t he back end up into the right shoulde r region. The pe,in wes cons t ant a nd wu.s exegge·ra.ted by move.­.ment and b ree.thing . She experienc·~;;d a s·imUar pain 2 weeks prior to admission ,

A ravi(!w of her pe·s:t medi ca 1 hist ory l"evua.1.ed that she had an illnes s in the oerly 1940 ' !1 .chare cter i ze d by enor~xia , bloating , and intoler-an·oe t-o fatty f oods . A-fte r a medicQl work up , she was told thot sho had oir~hosis.

Physionl e-xaminntion upon her t <J r mi rial admission revealed a chr<>ni oally ill, palo, whi te fems.la . The tip af the spl een was palpable on deep inspirotion, and tho mar(;in of the liver was pa lpable <t centimeters be l ow tho -ri ght costa l ~rgin. Tho liv0r was not

• tender . X- r ny oxnmi not.ions oJ.' tbc chest, gall b la.dder, s nnll bowel, colon , and p<.lvis rqvonl~d no significant feat ures othe r than di vert icula of tho dosoonding ansi s igmoid colon. Lnborator :;r oxamino.tion rav<;lal o-d .a bomcglobin of" 9 to 11 grMns per cont . Tho BSP test rovee l ed 19 . 8% of the dye reto.im:d o.ft.or 30 minut-es at\d 12% of the dye retained in 45 minutes . Tha r o was n marked p ro l onged, e l ovetoci cu.rv.a in the glucose tolera.nco t ost , Tho ce pho.lin floooul::ct i on, thy)nO l turbidity, s erum a lkaline phosphatase, serum b ilirub:in, s e rum amylase , a nd s e rum lipas·o t ests wo re all within norma l limits , Routine ur ina.Mlys es and. -tho ~ examination of the stoo l s for ova &md parasites v:ero also negative .

During her stay in the hospi tal t he abdomi rir> l pain persis t ed and vras accompanied 'by nauaea. and anorexia . !I'ermina lly ·she suddenly pre,sented the SYlJlPtoms of shock and dieod 1 1/2 hours later ,