CHAPTER I CHAPTER I V
1. Hepatoce llular Tumours
A. CAHCL\O"'l.~ l h:l'A'l'OCELLUL.uu;.
Thie; tun wu r is en countered mo,-;t frequeu tly in bo Yi nes, all of 'l'rotie1·' 6 cases "11 d a Lo ( ho-;e tlP6criLed by Hooglarnl being of tl1 e liYer cell Yarieiy .(") H .is lrndoubleclly the c01m11011est maliguant internal tunwur of oxen. It i:; si 111iLnly (o liP regarcle<l a,; a common tumom· of slieep- (although 1elatiYel,1· fe11· c.ases of rn·opbsia in iliis
;mirn,tl Ju.n-e beeu seen, sorne 8 ce1·b1in l'<hes ho111 the litc1·ature are 111e11lion<«l b1· Hoogland). 'l'be tm110111· has not LeeJL recorded
\1·ith ce1tai11ty i11 <;tl1er <lomestic rnamrnaL (clog, (';Lt, l101sl') and :1lthongh pri111a1y liYer calf'inomas liaYe hee11 reconled in tlte pig liy Johne (JNDU) <lllcl l/aYP111L1 (J<Jl:i) it is not kno11·n to \1·l1id1 Y<UtP!y
!ltey heluuged, 11hile Fl'ldrn<111 (IDJ2) lllL'ni.iollS <I 1P,-;io11 in the lHg tliag11o:;ed as " liPp<d0111a, 11·itl1 P:11'1.1· cait·i110111<.dons l'iia11ges ··. I it fo11·b three casrs \\'P.te dc"nihe<l b1 ,Joes( a1Hl ErnPsti (IUJ(i). 111 Sou!lt Ahi.rn the irn·ille11t·e of ('<ll'c~11orn;1 hep<docelh1hre <llJlH'<ll'.'i to lie si1niLll' to il1at in othP1 cou11hies, <ll1d in !he On<lerslepo.,l't culledio11 th(•se gT011·tlb :11e f'ill'()lllliP1ecl rno.-;t h<·t1uP11i.ly in b0Yi1w-;
(G c:ises) and oYines (J <«lse.-;), \1·hile there is 01w exa111plt· from the tlollle.-;tic fo11·l <lild 111·0 from ,.;pet·ies noi .;Lite(l, <1ne of 11·l1id1 ""'"
consi<len)<l possihly io iie a (log.
l'.~TIJ OLO(:y.
(i) Cases in lJovines. Case 1 (Bo,uine, '2121).
This turnoul' 1vas c1e;.;nibec1 a . .; Lei11g situate<l in the right lobe of the liver, me<ISlning '2-1-x 18 cm. :incl bulging lirnenth i.he l'apsule. On examination of !.he tilices 1d1icl1 ctrnstit11te lite mu8<•m11 specim<•t1, the neoplastil' tis:me is se('il to be lighler in colour than the sunournl- ing liver tisrne, the fresh specirnPn having been rlescrihe<l as bgln hrm1 nish aml glossy in nppemarn e. Jt is irn perfectl,1- en('apirnlatetl, lhe1·e being many ouilying nodules (l to 2 toi11. in diarnder) in the sunounding tissue. Jt r-ontain,.; :1 Lnge eentral ca1it:-· 1-l:x (i c111.
linP<i b,v fih1ous iiss11e ;111d l1aYiJ1g· g·elatino11s <111<1 chec'.s.v 11ecrnt ir coniPnb. I11 other pal'ts <!lso !lie1e an) larg·e <tl'eas of softe11i1w.
app:1rentl.1· f'l1mpo:;e<l of fihri 11. ·111 p<n ts th0, i rn110\11· shnll's <l ish 11~t c·onnectiYe-tissue sepia <l<'ma1Tati11g iuPgularl.1 rn1111cl<'il a1rns :; m111.
i.o 0 l'.111. in tliarn<•lrr. 111 othr-•r par1s !lte i0xl11re i:; l!l1ifor111. P0ne- tration of an Lep;1hl' Yein 11-,b <le..;niht•tl lll<IC]'(1scopic·all.\'.
;\Iino,;copicall.1-, the turnour i:; in ln1).tP Jrnd of ib l'il'<'uE1for011('e situnied (lirel'il} lieJte<1il1 tliP glt"<ilh- tl1il'ke1w'1 l«!Jl.'illlt: of lhr live1,
\1hich lllOYi<lPs :m effeciiYe lirnilation. For the most p:irt, colh- g·en011s :;t1orna O<«~lll'S 0111.1· <JS th<-' acheniiiin of larg·<· hlnotl-vP,;sPls of lioih al'terial <incl Y011011s i~pe \1hirl1 co11rse !hrnngl1 the neoplnstic (ic:s110, aml in most pm·ts i11e1e i,.; littlP s11ggPstion of a lobular stn1('- ture. The IJarenchyrna consi.-;!.'i of l'O]'(ls oF cells (<111e 01 t11·0 el0me11L"
in thickness) \Yhir-11 somPtinws l1<11·e <in i11rlisiindl,- rnrlial anann·"'- ment in 10lation io the larger 11loocl-Y0.;seL. 'L'he:-0 .trahPr11lae app;ar
(3) Hoogland considered one of his ho1·ine cases as being <Jf mix0d type.
l:FITHELL~L 'l"U~101JltS OF Ll VER.
in trnnsection as ah eoli whicl1 uot infrequently but not usually shmv an insig11ifica11t cfmtral lurneu (u::;nally less t !tan 7 f in (li.ameter) arnuncl \Yhicli the C'elb i11ay he radially anangecl,
The cell:; ha,·e au outspoken resemblance to hepatic cells, being polyg011 al i 11 ,;hape, not ve1'y shaqily outlincecl, measnring some 12,u to 15,u in di a meter, 11·ith deu::;e, tiuely gi«l m1la r C,Y lo plasm \1·hich i:d:ains "·ith haemalmn-eo,;in .an 01Jaque pink-mauve, and single, central Jlndei "·l1id1 yary more in si;:e than clo those of the liYer cells. 'l'hese nucle>i <ne of short-onil sl1ape . . sometimes "·ith slightly angular outlines, aucl Y:ny from ca. G1..! to Ll/i. in long diameter, the la Lt.er size being e:x.ce>p1io11aL Like norrn nl Jwpat il' 1·e ll nuclei the typical ones ,ho11· a 1110clerntely prorninent chronrntin nei11·ork, but many are affectecl h~· p,vcn·osis, 'l'he nucleoli, of "·hich usually a siugle central one i,; Yisible iH Padi. nndeus, are> rather prnrniuent, the n : K ratio :1ppParing distinctly incrP:Ji'\ed: 11 : K ratios of 1 : D are encounterPd fre(1ue>ntly, although in the majoriLy of the irndei the rntio is in the neighhom·hood of 1 : 14. 'l'he cells sho\v neither fatty 1;banges nor pigmentation. l'lfnltinucleate cells are not seen.
'l'he tra beculae fonned by these cells are clen1arcated hy a slroma
"·hich is exclusiYel,v of capillary nat11re, no oollagPn hut only reti- culum fibrils occurring iu the in tertra becuLn areas. Areas of fresh haernonhage are frequent. There are also large necrotic tracls (co1n- posed of necrotie fibri11, en('upsul;ited by connective tissuP and some- times sh-o"·ing a p:irtial calcification) into which fresh li:iemorrhages have occurrecl at the peripher,\'. The bloocl cells in such areas are>
intimately mixed "·ith free ancl 'rnll-preserYed tumour cells. The tmnour cell stran<l;; ('an be seen to gTO\I" i11n1siYely into the wallR of the larger veins of the strorna, eYen ;ilrnthng 011 the intima, Actual sites of penti-ahon \Yere not discovered hy « ;;eareh of the sections, but clumps of free turn our ('f' lls mix eel "·i th the bloocl in such vessels could frequently he seen, aHesti11g that intranscular 1)entration had oc::;un ed.
In limiie<l p:nb of the tumour a fairly regular :1nangernent of branched and highly eollageuisecl connPcti\'P-i is,;ue trnhP<'ulae rlemar- cate large lobules of H1e p.areu('byma, "·lii<'h has a more compact
appearance clne to the eapillary i'\troma being narrower arnl less con- spiruous, UerP also tlrn small lnrninn described previonsly arnl the radial anangemeut of the t11mour C'ells aroun<l them arp ·of regular occurrence, \\·hile the 11uclei are more i·eg'nl:n in si;:e an<l their nudroli less conspicuou6.
Mitotic figures were not see>11,
rrhe liver tissur shmn .a ('inhosis. ('l1ieAy of the perilo1rnlar t:qie, but in iiarts there is also intralobular penetration of 1hP connective tissue cutting up the liYer cells into small gToups, There is in parts consirlen1ble " rnunrl cell " infiltration.
RMnarl.'s,- 'l'his Yer:v large hm1011r ha::; :1 stnicture which is that
<'Ommonly associated \Yith adenoma: :maplastic changes are slight, mitoses are not seen and one is irnpressefl with the orclerly arrange- ment of the cells. Yet the evidence of intraYascular penetration, especially associaterl \1·ith the occurrence of secondar~· nodules in the immediate vicinity, necessitates a diagnosis of malignancy.
Diagnosis.- Carcinoma hepatocellnlare.
138
HEl' . .\.TOCELl.UL.-\R '1.'l'.~Wun,.;.
Case :2 (Bovine ;\224).
)fol·ro:;covicully, 1 he .'iJieci me11 rnnsi.-1.;; of a. vorlio11 of bln-i11e llrnr, nol olher11·i:;e• \·isibly alterell, lrni co111<1iuiug a soli1ary i·ou111ll'cl tumour me<1:mring 11 by 8.;i L:lll. At p<1rt of ii::; eircumference il bulges directly heueath thP capsuk of the lil'l'r \\·hil1• at other part:;. although. the1·e c11·e to the naked eye but faint indiL:atio11s of e11('apsula- 1 ion, it yet ap1wa1:; c:Jparl>- ofbet h orn tlH· sunou1Hiing liYPr ti,.;sm', 11·hi('h is 1larb-•r in colour. Ucc.asio11al thi11 sirancl,.; of c·nnned iYc t i;;sue coursP through 1 he 11e·opla~n1 <1nd 1 he:;p :;orne\\·hat imperfrctl,,- clenwrcate .•wli1l, i·o111Hle1l 111asscs pf h1mo11r parPnchyuw 1 to --J crn. 1n 1liarneter. In pla('e:; there :1re .;m:1ll lwemorrlrnges \-0 cm. diameter). Parl::; of the ('il'('111llfrre11l'e ;1re limited li.r the 1rnll,.; of hep:dic ,·ri11s, i11to \1·bi1·h lhen· i . .; no ,-i.;.ihle peuclr:llion. ('l•11irally I hen• is a l:irgP, dark, opaquP (111·c·rnti1·J :nea ca. 7 1·m. in dia111eier :111cl liaYi11g a ;leep re1l (lw1•111onhng·ic) margi11. 'l'his :1re:1 iR sPp:1r:1k d l'rom ilH-• tumour ti . .;:;up IJ.,. 1·on11e1·I i,-e 1i.;s11e. 'Jlil:rOsl'Oj>icall». a dis- 1 i llf't bu I Yery 1Iii11 co1111e!'! iYl'-t is,.;ue ('apsnlt• is seen io Pll!'lose th1· iumom· :1wl in ii· cH·c·ur m;111,-Yl·i11s of cmisiclera1JlP sizP. Tlit' h1rn0111· shmni ·01115· ,·ery 01 .. ·:1sio11:1t' suppu1·(i11g· slr:1nils of 1·11l1<1ge11ised ('Oll-
11ecliYe tissue, rnusl of lhe l'olL1g·e11 heing 1·unfi11ed lo lhe larg'l•1· hlood- ,-E'Ssf-'ls. A,; in lhe 1n·e,·ious C':1~e the neoplastic· ti,;snP is cornposl'll ol·
1ra1wL:ube (t1~11:1ll:y l\YO l'ells i11 thil'kiwss) \\·lrnse 1·P,lb ltaYe ::111 m1mi~-- 1akaLle resem1Jlauce to liYer L:ells: thPy are i1ol>·g011al l'lerne111~ some11·hat Yari:i11le in size (101,( to OYer 201,( in lli<1mPler), moderntel.\
lli:>tinctl.\- outli11!-'cl. \\-iih .-;ingle. ('Pntral 11udei similar io (hose of hepatic 1~elb, li11t 11101·p rn1·iahle in ,;izP an<l 1rnn:ill,,- l'01rniclerabl.'- l;irger. Tlw uud ei 111p;1,;111·e 1·01-'- 111 lO<i,u in cliame1er, \\·hile largp1· and obYiously dPµ'f-'11ernte ones m :lY n•ach a 1lia111eter of 15,i;. 'Jhesl' degenerating n11dei arp foirl» cornmon a111l sho"- a 1listi11c1 dnom:i- t-.ol~-;;is, the l'en1rnl porl ion of 1he nucleus being 1mstai1wd (i.e. ('OlTl-
]iletely dis:;oh·e1l 0111) or :;ho11·ing a little cloudy gr:inular 1lehri:>, whil1•
the chrnmaiin is ;;egn•gatecl at the 11eriphPry c:i11sinµ; a m:irkeil thicken i 11g ( 11p to l · :)1,() of i he nuC']ear membrane. Such nuclei {)ftp11 appE':lr like largP Y;1cuoles within ihe 1·elL. ThP n11!'leoli ::irP 11rarl.1·
;11'ntys prominent, 11: ~ rntios of I:!) bei11g 1·ommo11J.,- PnrountNed, :1lthougli 1: 1--t n'p1Pse11is :1 lllO!'E' ;i\·eragf' figurE'.
Heg·anl ing the c:dopbsm of i he tumour cells, a fe:iture is thP Y;nia1io11 i11 sfoini11g i·e:1clio11, 1101 onl,,- from one parl of ibe t.urnour to anotliPr :incl from 0111' (·ell to 1lw next, hut :1C'ti1allv witl1in onr and 1 he :-;:imn cell. 'l'lrns tliP cytoplas111 lll:J,\- lil-' <listi111'tl,,-eosinophili<· 01· 1listinctlv ha-;ophilil'. l t is not· ];1111\\'ll wheil1Pr this ma\· 1101 lw cill artefoc( llm• to lhe long pn•spn·:di.i111 (1:{ :-·pars) in K:1ist'rling. How- p,·er, ill sorne sedi.nns 1 his rnri;1hilih- i-; not ;;een :111il of I hl'se it c:in he sai(l 1lefinitel>" ihat- the cYlopl.is;H is less t'osinophilil' 1han 1.hai of tlw liYer cells. 'J'hr rylopl:isrnic gra1111ln1i011:; ;11·p fow anrl i11c011- spic11011s. J,nmi11a are selclorn sePn anrl \\·hen tlw.\· orru1· :ire small :incl ill-rlt'finecl, no 1listind rnrlial :Hrang·ernen1 of lhe l'ells lwing ,;een :ll"Olln(l them. 'rhP ('ell trnlwr11lne arr separntell h,,- a strorn:1 P-xch1siv0l5· of rnpillar~- n:iture :ind onl:v 111oclf•ratt' in prnmi.nenf'e.
In one section eYidPnf'e of i1n«1Sio11 of :1 raps11lar YE'i11 is seen an<l 1 his i~ confirmecl ll\- tl1e presp11c·e of l"irc·11lati11g 1 nmour cells i11 fop 11ortal rarlif'lPs of thP s111T011111ling· li.YE'r tisR1lP. - .\pnd from i:hiR thP liYer sho\1·s i10 si~·nificant cliang·e~. anrl no fatty changes or pigmc•nta-. tion ::ire seeu either in 1he liYer 01· i.n the tumour parenchyrnu.
El'ITllFl.1.11. 'IT .\IOUC.; 01:' LIV.EJL
Nc1111u.f>s.- 'L'hi.; llllllOllr i11 j(.; g('lle1·al 11atlll(' i . .; .;imilar (o ca~e 1, Yi;r,., it JHb.;l'.;.;e.; a lll(lrp .. adl·llu111;11ou . .; .. l.1·_pe 111' . .;(n1('t1ln' ::11111 .;ho11·,; littlt• :rnapla.;ia. Yet it .;!1011·.; i11tra1·a.;l'nbr in1·a.;io11, all hough
rneb,;L1.;l'~ :1re JJ()t .;p\ up. It i . .; lP hl' n•111:nked tlrnl thP 1'ieriJity of Pmboli i.-; 110 nitPriu11 ut a lie11i>.:·11 11:tl111·p: 011 ihP 111nlr::n·y, the uec;unern·e 11f Yasc1ilnr i111·:i.;ic111, 11-'li;lf,.1·er iL 1·p:'1dts. rnu1d· he l~eld as lite Ji11al al'l1iler of rnalig11:1111'_1· in li1·(·1· (t1111011rs.
1 Jiu !J 110.1·1s.- C..'<t1Ti 11om :1 h P[l::t t CIC'P 11 uLt re.
F1i:. (il.- C.:ar<·ino111a l1q>at<1c·c·ll11lar<' of thl' ox. p1i1J8; nat. ,izv).
('0.,1' :; (/Jor/111'. :)(iOSl.
Th,• .;ul:_jed 11·:1s a11 '1ged (lfi YP<'i"'I Fril' . .;la1111 1·011· i11 good c·1111- dition 11·!ii1·li 11·:1..; i:;l:n1ghtPred 011 :1<·(·011111 of .;teriliiy. It \\'as sl:tl1·11 to l1an• h·e11 of . .;eni1e :1ppc•arn111'd'l. TlH' 'JIPCirnen (Fig. fil) 1·onsi.;1:;
of a podio11 of the livt>I' in 11·hich i.; 11rr.;p1J( :i rn1111c1ecl grnwt h 4·· 5 t·111.
in dia1iwte1·, for the rnosl part e11do.'l'cl 11·ithin a cli.,lin('t c·o1111Pc·t1Ye- 1issup C'apsuk hut at one part of ih cirn1111fPl'Plll'P protru1li11g into the liYCl' tissm., frorn \Yhil'h ho11·pypr it :1J11J<'<ll'=" fairly clistinc·tl>·
demarl':il·ecl. The l'nnsiste11c·e re.;t>1llblPs that of thP li1·er iissup hut the colour is tll11('h lighter, ex<·Ppl iu t•x1<'11si1·p haernorrhagic· arPas 11·hi('h are present P:<JIPCiall>· iO\\·arcls i11e 1·PnirP :rn<l 11hi('h :ne :1..;:<111·iatNl
( ') 'l'l1ese det:1ils are tak<'" from tile 1101 k of Qnmlan (19:20, liith Heport.
D.\'.S. at p. 027) 11]10 1rnest1gated the call'(' ol stenlib in this anilllal hnt 11·as not concerned with the othe1· pathological frai.urPs.
140
11·ith stran<ls of com1ectirn tissue. 111 parts a finely lolmlated pattern is seen- vaguely clemarcate<l areas l to 2 mm. in dinrne(el'. The remainder of the liYel is not Yisi bl.\· :1llere<l.
:Thficros('()pi('nll.\· (Figs. G2, (j;) <lllll li4) there is l l l pai·b a tlic;tinct rnnnective-tis,;ne encapsulation (:Fig. (;2) rich in both arterial and Yeuo11s hlootl-Ye~sels. In other iiarts this c.apsule is absent ancl the tmno11r cell.-; make direct contact 1Yith the hepatic lHtreuch_vma (Fig.
G3). The shndure variefi sorne11·hat. 1ll general there are elongated colmnns of cells (usually two cPlls thick, sometimes more) 1d1ich haYe a dist.iuct resemblance to liver eel b, being pol_vherlral and lrnving an opaqne granul:n cytoplasm and sorne1Yhal ('hromatin-poor, ronndecl to oval nuclei 11·hirh shm1· a <tistinct coarse-llleshecl chrornnt i11 Jtetwork.
The follmYi ng <lifferences 11et.1Yeen the h1rnom· cell.-; aml liner cells are noted: (a) they are more yari.aLle in si;:e than normal liver cells, measuring between Fl/'· and 00/A in tlimne(m·; (/1) the cytoplas- mic gmnulations are on tlie whole a little more <listiuct, but the li1·er cells in this material are thernseh-es exhemph· val'iabh~ in this respect so thai the clifference is not coustaut
l;r
striking. The grauules are, however, less eosiuophilic: in tbe tmnour cells than in the liver eell~: (c) the nuclei are fairl.' regularly larger, mN1s1uing lO·G to 12/'· in long diarneter as t·omp<nerl 11·ith 7·5 to 91' for the li.Y(~1· cell nuclei; (d) the aYenige 11udeoli of the tumour cells hear an areal ratio to the 1rnele11s of 1 : 14 to 1 : 2ri. (ln the liver cells, this ratio is usually gTeater than l : 2Ci.) \Ylien it is also l'emem- benecl that the tm110111· Clell nuclei are enlarged, it will be seen that thi8 implie.-; a nrnrke<l absolute enlargement of the nucleoli of the 11eoplasti \' c:ells and they are i 11 cou se(1 ue11 ce con sitlera b ly more prnminent than in the liYer cells; (e) sheaYes of needle-like ('J'ystals are fre(]uent iu and among the tumour cells. The>- s1'1 in ,-ery\\ eakly with Smlan III.
'l'he tumour ('Pll !'olumns ai·e sepal'aterl by a strnrna \Yhich <·011s1sts
e:\.clusivel,1- of capillaries 1vith associated fihrillar 1·eticulnrn, 110
c:ollagen being seen. This is a promineut fer.hll'e. ln sorne parts, hmYever, there are also prescent lraheculae of loose and O]'Pll
collagenous tissue carr.ving larger Lloocl-ves,els aiul these rnay <'Oll1-
plet.ely or incompletely rlemarc:ate lobules of tumour parenchyma of Ye1·y inconstant size. The5e lobules 0ppear to eonesponrl roughly with liver lolmles, but central veins, hile-rluds, anrl a rarli::il arrange- ment of cell trabeeulae are absent. This druchue occurs onh· i11
limited parts of the tumour. .
Small lumina, ,;ome D/A (o('casionall.\- as rnu<'h as l:\u) in rliameter (Figs. 62 an(l G3) occur fairly hequentl,1- awl in transedion the cells of the corcls are seen to be l'arlially anaiigted around them. 11he larger lurnina are irregularly honlerce<l li,1· tlrn tnmonr cell:-; which do not at any time assume an outspoken colunrnai· form. A fair number of shrunkeu cells with strongl,1· eosiuophilic ('ytoplasrn and pycnotic nuclei ::ire seen. ~fitosec; are absent.
Occasionally, indications of Yascular peuetratiou rnay he seell, and tumour cells occur rarely within the veins of the cap~ule. In one section it is .seen that there has heen i1wasion of n medimn-si;:ed
EPITHELIAL TU::IIOURS OF LIVER.
vein of .a connective-tissue trabecula immediately bene.ath the cap:rnle:
the vessel is lined by tumour cells which assume a more cuhoiclal form and grow into the n1scular lumen as papilliform elevations (Fig. 64).
The liver shmYs no other pathological alterations and there is no pigmentation either of the liver or of the tumour cells.
Fm. 62.-Structurc of the hepatocellular carcinoma of the ox shown in fig. 61 : Limited anaplasia and strict encapsulation at this portion of the circumference. (5608;
250 x).
Re marks .- 'l'his tumour had previously been diagnosed as
" liver-cell adenoma ", which is readily understandable when the regular arrangement of the cells, the (at least partial) encapsulation, and the limited anaplasia are considered. The closer analysis under- taken here, especially of parts of the tumour (which had not previously been sectioned) where aggressive growth occurs, renders the
142
Fro. 63.- Another portion of the margin of the hepatocellular carcinoma shown in fig. 61 : Failure of encapsulation and direct encroachment on the hepatic tissue at the right side of the field. (5608; 125 X ).
I 1
1;.
f J.~ ''~l:t
' ' "
Fro. 64.--Penetration into the lumen of a vein by hepatocellular carcinoma of the ox (same case as figs. 62 and 63) : Assumption of a cystic papilliform type of growth as the tumour cells line-out the intima of the vessel. (5608; 125 x ).
El'ITHEl.IAL Tl'.\lOl.lt~ OF 1.LYEH.
ahove (liag11rn;i,; u11te1iahle according- to the criteria >rn are using;
and in spite of tlif' absence of es1<1blishme11t or mdasbses, their possibility remai11s ;111d the grn1dh 111ust lw considered malignant.
Dia,r;nosis .- Ca J'(· i110111a h Ppa tot·e 11 uLire.
C([se 4 (Bovinf', GOT.').
This ::iJH'!'imen lta-' pteYiou.-dy i)('ell dP;;crihed h1· de Kock ;rnd Fonrie (19~8) 1d10 kindly ga1·e me jJPrmission to tm(l~J'fake a criti(-;d l'e-exalllination of theil' 111~dl'l't;1l. l·'rnrn tl1eil' (le-;niplio11 "e learn that thP spr!'imPn (·011sis1s of .. a piel·P of' ho1·i11e liH•J' . . . sh(rn·i11g·
thP pn•sence of' a (·il'cu111s(·ri1H•r1 iu111our . . . thl~ iu111onr is lJl'(•sent i11 thr .-wbsta1J(f' ol· t·hf' li1·PI', hut at 01w plan' it is asso('iatecl "·ith ihP l«lp,;ule and (-;111 n(·tually lie ,;pt•11 011 tl1e .-;urf;1c·<• of tl1e o!'g;111.
'L'lte l.«l[J,;ule of' lite liYCI', O\'l'l' lhe lll'OJllasrn. sLnuls out ;is a p;ilf'
gre~·ish->1·hit1' a1·f'a-!- <·111. in 1li<1lllPIC'J'. (hc•r th1· 1m11t1111· lhP rapsnlP is ilTPg·nlarl.1· ihi1·l;PnPd ;111d l'<1i.-;ed ;1h0Yc' !lw sul'LH'<' of the JiY<'l'.
111 tlw subsL11J('e of the li,·er it (thl' lH·opla.-;m) i.' 1'01111d lo ]ip (·in·u111- snibed and .-;lrnl'ply J11;11·kf'cl oh frn111 th1· app<1rvn(l.1· 11ornwl Ji,·er tissue ln· :1 ,,·Pll-tlefi1wd fi.hnius (·apsule ,,·hil'li ''<ll'i("' i11 thi!'k1Jt•ss frnm
1
1·1u. to '2 (·111. I 11 tlw latlrr tbi.('J, ]Jortion tlJt•J'e arl' l'f'\Nal fnl'i ,,-Jiich 1·ary ill .-;ize l'rllm l mm. to ± 111m. i11 (Ji;1rn1·ter, thPsl' i'ol'i vary in colour frn111 pal(• g1·p.1·ish ,n'llo\\· to a pale gn·eu. The sub- stance of ihe neo11L1sm slw>1·s a lohulated ap11e:11·a11!'t'. ThP lohulP~Yary i11 size frorn those '2 n1111. in di;1rnPtC'1· to dong-;11<'<1 011es 1 1·nL
long. Ln hPt 1\'ee11 t l1e lolrnlrs are rPd(li,;l1 spots (ltaP111onl1;1ges) JwrP a11ll there. .Lu plat·es these as.-rnlllP a li11Par appearnn(·P ;uu1 oc-cm·
rngulal'ly thrnnghout the- snbsLrnl'e of tl1P neoplasm. The colour i.-;
for the mos! part green. but ligh t<•1· .-;hades of ;,!'l'P\·ish and <',·ell yello"·ish gn'en can be i1lentifil'd . HP(l spots a11d sornPtimes l'Pcl li11es 0<·<·1u in an inegular manner lhroug·hout 1he .-;uhstal!l'e of ibr (11mo11r ". 'l'o tl1is c1esniplio11 it slioul<1 IJP addPcl th<li the 11eopb srn is irregulai·l.1· rounded in outline. that it lllf'a-;1nP.-; ca. -!- cm. in c1inmeLPr and that l1rsi1lPs lhc -;malln nodules i1resr11i in il1c' tm11om·
l'apsulP then' ouur sen•ral e11tirPl,1· outside tiiP f'a11s11le hut in the i111me1liate 11Pig·hhom·l10od of 11iP rnai11 mass. Tht>se arP fail'ly shal'ril>- 1·in·urnsn ibed lrni to thP uakPd e.111 sho\\· 110 sign of ('11P:q1.-;ulat,io11.
There <ll'P ftll'ther 11111l!iple fo!'i 1111111. to.-, rn111. in di;1metl'I'. distin- guish<'d ho111 the> ]i,·Pr ti.-;su1• 11.1· ;\ ligh1PI' colnu1· 11ut not olhp1·1,·isP sharply <lPrn<1l'<'atPd thPrdrom. }'nrther. tlw («lpsul<' appt«HS ,·e1'.1·
tlPfil'iPnl if 11ot ('11tirel.1 i!1!'ki11g i11 pLH·('S arnl inpg·ular 111a"S('H of nropla,;iie ti.-;,;up appral' h(•J'e to hnd of'I' fro111 tlw main 111;1.-;s ;IJl(l to liP in im111l'di<lil' 1·011tad "·it Ii the· lit'pat i1· parP11ch.1·ma.
)li<Tc,;<·opi(-;111.1·. n1 !lw .'iPCfio11s ;1,«1ilalil<> thPrl' is a (k11se
<·ollag(·'llOlb l';1psuJ(, "·hi!'h co111pletel.1· ('11clo'ie,; thP gTe<ilt'r Jl<1rt. of' tliP cil'cumfe!'ell('t' of lh<' rn;1in t11111onr 111;1.-;.-; f'rnm the snnomHliug· Ji,·p1·
tissue, a.lthough it rnriPs greatly i11 thi!'knes,;. Fnrn1 thi.-; capsule occasio11al (rnl:eC'ulaP of (·ollagPnous tiss11<' ino:·ppd 1l1rn11gh the i:;uh- siance of tlw neopbsnt. ,\pari from thrse nnd O(·l'asion;tl hlorn]-Yp.';seh a<·r·m11p:11tie<l h1· a l it-tlP l'olbµ:enons I iss1ie, tlw strom;1 i~ P111irel.1· of capillan· natnrP a11cl dP111<1rcatP,., onP from another flw parc'nchymal n11its 1() lw cle'inihPrl. 111 g'ellPral i hi~ rnpillan· ~fro111;1 j, smne"·hat more prn1i1inp11t 111;111 1l1e co1TPS]l011<ling- (intralobular) capillarif's of
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