Gii phu bnh hc ung th biu m gan nguyn pht Muc tiu 1 Hiu bit c mt s nguyn nhn v yu t mguy c gy ung th gan. 2 Trnh by c cc hnh thi i th v vi th ung th gan. 3.Phn bit c ung th biu m gan v u nguyn bo gan Cc u c tnh nguyn pht ca gan c th pht sinh t thnh phn biu m hoc t thnh phn khng phi biu m, trong ung th biu m l loi hay gp nht v gi v tr quan trng nht trong bnh hc ung th gan. V phn loi, nm 1978 t chc y t th gii (WHO) a ra bng phn loi cc khi u gan v nm 2000 c sa chnh b sung. Bng phn loi ca t chc y t th1

gii c p dng rng ri nhiu nc trn th gii v Vit Nam. Theo phn loi ny, ung th biu m gan gm c: Ung th biu m t bo gan (Hepatocellular Carcinoma HCC). - Ung th biu m ng mt trong gan (Intrahepatic Cholangio Carcinoma ICC) - Th h hp t bo gan t bo ng mt (Combinet Hepatocellular and Cholangiocellular Carcinoma). - U nguyn bo gan (Heptoblastoma). 1. UNG TH BIU M T BO GAN 1.1. nh ngha: Ung th biu m t bo gan l u c tnh pht sinh t t bo gan, l loi hay gp nht chim khong 90% trong cc u biu m c tnh gan.2

Cc yu t nguyn nhn thng gp l virus vim gan B (HBV), rirus vim gan C (HCV), n thc phm mc c c t aflatoxin B1 v nghin ru mn tnh. 1.2. i th: Hnh nh i th ca u thay i tu theo kch thc, s lng u v c hay khng c x gan km theo. Nhn chung, hu ht ung th biu m t bo gan i km vi x gan c xu hng l mt u lan rng c bao x v vch si trong u. Trng hp khng km theo x gan thng l mt khi khng c v bao bc. Khi u nh gan thng khng to, trng lng khng tng. Khi u ln c th chim c thu gan hoc ton b gan, khi trng lng gan c th ti 2 n 3kg. S a3

dng v xm nhp, huyt khi u tnh mch ca v di cn trong gan thng gp ph bin cc u giai on mun s lm thay i hnh dng i th, mu sc v mt u. Trng hp nhiu nt u nh c phn b lan to, khp gan khi s c kh khn phn bit vi cc nt ti to x gan.V i th, ung th gan gm cc th sau: * Th nt (Nodular type) * Th khi ln (Massive type) * Th lan to (Diffuse type) Ngoi nhng th thng gp trn cn c mt th c bit l th x lt (fibrolamellar carcinoma).

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Ngy nay nh tin b ng k trong k thut chn on hnh nh kt hp vi sinh thit kim nh pht hin c nhng ung th gan sm khi kch thc u 2cm ng knh. 1.2.1. Ung th th nt Th nt c th l mt nt c nht 5cm ng knh hoc gm 2, 3 nt vi kch thc khc nhau. V tr u c th gan phi hoc gan tri hoc c hai, nhng gan phi gp nhiu hn. Nt c th vi su trong nhu m gan hoc li trn b mt gan. Qua mt ct, u c ranh gii tng i r rt vi m gan lnh. Khi nt pht trin trn x gan thng c v x bao bc kh r. U c mu vng nht trn nn nu ca gan. Trng5

hp c mt nt n c vi trong nhu m gan c gi l th hnh nhn. Khi nt c bao bc bi v x dy r c gi l th c v bc (Encapsulated type). Th c v bc kch thc nh thng l 2 3cm, pht trin chm, tin lng tt. 1.2.2. Ung th th khi U c kch thc > 5cm, u ln c th chim mt phn hay ton b thu gan. c im u l xm ln tnh mch ca, di cn trong gan lm thay i hnh dng khi u. Qua mt ct thng c tn thng phi hp nh mt c mu vng hoc chy mu c mu loang l tp sc. Trng hp m u km c nui dng hoi t nhn nh b

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u hoc lng nh m lm ta c th lm tng vi p xe gan. 1.2.3. Ung th th lan to: C nhiu nt u phn b lan to khp ton b gan phi, gan tri. Cc nt ny c th nh 1 2mm cho ti 1 2cm hoc ln hn. Cc nt nh rt kh phn bit vi x gan. Cc nt c ngn cch nhau bi gii x. Khi nhiu nt st nhp vi nhau s to thnh th gi khi, gan to. Qua mt ct nhn thy cc nt c bao quanh bi cc vnh x. Th gi khi cng c th b hoi t, chy mu, nhim mt nh trong ung th th khi. 1.3. M bnh hc

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Ung th biu m t bo gan gm cc t bo ging t bo gan. M m bao gm cc khe mch dng xoang c lp bi lp t bo ni m. Cc t bo ni m ny khng ging vi t bo ni m trong gan bnh thng, chng dng tnh vi CD34 v cc khng nguyn lin quan ti yu t VIII. Quan st trn siu cu trc cho thy mt cu trc dng mng y gia cc t bo ni m v t o u. Cu trc ny (+) vi lamidin v collagen typ IV. Do vy cc khong mch dng xoang ging nh cc mao mch v c gi l mao mch ho. Trong cc xoang mch ny c mt s lng i thc bo a dng (+) vi

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lysozym, CD68 v ging nh t bo Kupffer cc u bit ho r. Ung th t bao gan thng a dng v cu trc v t bo. Nhng kiu cu trc khc nhau v nhng bin th v t bo thng xuyn cng xy ra. 1.3.1. Cc th cu trc 1.3.1.1. Th b y l th ph bin nht v thng gp ung th bit ho r v va. Cc t bo u xp xp thnh dy, thnh b, c dy khc nhau t hai ti nhiu hng t bo. Cc b c tch bit bi cc xoang mch ph bi t bo ni m thp dt. Cc t bo Kuffer khng c hoc c vi s lng t. Cc si collagen tng sinh trong cc khong Disse9

bao quanh cc xoang v mng y v chng tr thnh mao mch ho. M m x t hoc khng c, tr khi t bo u xm nhp vo vch x gan. 1.3.1.2 Th gi tuyn v tuyn nang Cc t bo u sp xp to thnh cu trc gi tuyn, thng l mt lp t bo u. Mt s tuyn hoc cu trc nang c to thnh do gin cc knh mt gia cc t bo u. Cc knh ny cha mt, thng khng c m m. Cc tuyn gi thng cha cht dch protein c mnh vn t bo, i thc bo. Cht dch ny nhum dng tnh vi PAS nhng khng bt mu vi mucicarmin v xanh alcian. i khi cc tuyn gi gin thnh nang. Cc tuyn b gin ny c th10

c to nn do s thoi ho ca cc b t bo dy. Ni chung trong u bit ho r cu trc tuyn thng nh hn trong cc u bit ho va. 1.3.1.3 Th o. Cc t bo u hp thnh m to nh khng u nhau ng tch bit nhau. Mi m c t bo ni b bao quanh chng t chng cch bit nhau bi cc xoang mch dn rng khin ngi ta c cm gic nh nhng hn o khi quan st di vt knh nh ca knh hin vi quang hc. C l y l cc b ung th b ct ngang. 1.3.1.4. Th nh

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Cc t bo u bm quanh trc lin kt. Cc nh ny thng hnh thp, chn nh nhiu hng t bo, phn nh nh thng ch c mt hai hng t bo. hnh thi nh c th thy cc t bo nhn ln, nhiu nhn khng u nhau nh cc hp bo. 1.3.1.5. Th c Cu trc c bn vn l b, nhng cc t bo u qu sn lm cho cc xoang hp li do b chn p nn kh nhn bit to cho m u c hnh nh c. 1.3.6. Th t bo sng Cc t bo c bo tng sng chim u th thng vn xp thnh cc b, m v tch bit bi cc xoang mch. S sng ca bo tng hu ht l do cha lng ln12

glycogen, nhum PAS dng tnh, nhng c th do nc v m. 1.3.1.7. Th x Th ny t gp, hnh nh c trng l s x ho ni bt dc theo cc khe mch dng xoang vi cc mc teo khc nhau ca cc t bo u. Th ny c th thy cc u nh, nhng thng thy trong cc trng hp sau ho tr, x tr v gy tc mch. 1.3.1.8. Th t bo a hnh thi Cc t bo u thiu s kt dnh, do vy khng thy kiu b r rng, chng thng tch ri nhau, phn tch lan to. C s thay i r rt v kch thc, hnh thi v tnh cht bt mu ca t bo v nhn. Tng ch s nhn chia. Thng thy cc t bo khng13

l n nhn hoc a nhn k qui. Th a hnh thi t bo thng gp trong cc u bit ho km. 1.3.1.9. Th dng sarcom Ung th biu m t bo gan i khi c hnh nh dng sarcom, c trng bi tng sinh t bo hnh thoi v cc t bo khng l k qui. Khi u ch ton thnh phn t bo dng sarcom s kh phn bit sarcom tht nh sarcom x, sarcom c. Tuy nhin s thay i ny ch mt phn u. Ho m min dch s gip cho chn on xc nh (bng 1) Bng 1. Cc market sau y c dng chn on ung th biu m t bo gan.14

Khng nguyn

Kt qu dng trong chn on)

Hepatocyte (Dako) Dng tnh (thng s Polyclonal carcinoembryoni antigen Alpha fetoprotein Fibrinogen Dng tnh hoc m tnh Dng tnh hoc m tnh Cytokeratins 8 and Thng dng tnh 18 Cytokeratins 7 and Thng dng tnh 19 Cytokeratin 20 Epithelial Thng dng tnh m tnh15

Dng tnh (canlicular pattern)

membrane antigen BER EP4 m tnh

Mt s c im c t bo u - Tit mt: C th thy mt s trng hp, y l tnh c hiu ca ung th t bo gan. Mt c th di dng nhng git mt trong bo tng ca t bo, nhng hay gp hn c l trong cc tiu qun mt, i khi c c trong lng tuyn gi. - Cc th vi: + Th vi hyalin hnh cu: nm trong bo tng t bo v thng nm cnh nhn, hnh trn nh. Khng ng nht, c qung sng bao quanh, a toan mnh, PAS (+), bt mu da cam ti khi nhum 316

mu Masson v dng tnh vi

1

anti

trysin. Loi th vi ny thng thy trong ung th biu m t bo gan, him gp trong cc u khc. + Th vi hyalin mallory: thy trong bo tng, hnh dng khng u, mt s trng hp c trung tm nht mu v vin ngoi thm mu, a toan, PAS (-), nht mu vi nhum 3 mu Masson. N c to nn do s tp trung cc si trung gian v (+) vi cc antiubiquitin. Loi ny thng thy trong ung th biu m t bo gan. + Th vi nht mu: trong bo tng t bo, hnh trn hay bu dc, khng bt mu hay a toan nh. Chng hin din nh s tch t ca cc cht v nh hnh trong li17

ni bo b gin rng, nhum (+) vi antifibrinogen. Th ny thng thy trong ung th th x lt, nhng cng c th thy trong cc typ thng thng ca ung th biu m t bo gan, c bit trong typ x (scirrhous HCC). + Th vi knh m: gp bnh nhn HBs Ag (+).Th ny bt mu vi Orcein, xanh Victoria hay aldehyde fuchsin v ho m min dch (+) vi khng th khng HBs Ag. Th ny khng thy u xm nhp tnh mch ca hoc di gan v hu nh c ngh l do cc t bo gan c HBs Ag (+) b mc kt trong m u. - Glycogen: cc t bo u cha mt lng glycogen khc nhau biu hin di nhng18

ht nh phn tn. Trong ung th gan t bo sng, t bo u cha lng ln glycogen. - Thay i m: trong t bo u c th thy nhng ht nh hoc di dng hnh cu kch thc khc nhau. Thay i m dng lan to thng gp nht trong cc u nh giai on sm. T l ny gim xung vi s gia tng kch thc ca u v tng i t gp u giai on mun. Ri lon chuyn ho lin quan ti to u v cung cp mu khng trong giai on sm ca u. C ch ca s hnh thnh cc ht m trong cc t bo nht l ung th giai on sm c th l do ri lon chuyn ho ca t bo v s cung cp mu khng to nn. Tuy

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nhin c ch ny vn cha c xc nh r. 1.4 Phn m hc u (WHO 2000) Theo m hc, ung th biu m t bo gan c chia thnh bit h r, va, km v khng bit ho. 1.4.1 Bit ho r Loi bit ho r thng thy nht trong cc u nh, giai on sm, u 2cm, him khi gp cc u giai on mun. M u v t bo u gn ging vi t bo gan bnh thng. Tng nh cc t bo khng in hnh ti thiu, t l nhn trn bo tng tng nh, b t bo mng thng c cu trc gi tuyn hay tuyn nang v thng c thay i m

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(nhim m). Hu ht cc u > 3cm bit ho r nm vng ngoi vi u. 1.4.2. Bit ho va Thng gp nhng u c ng knh > 3cm. M u v t bo u c s khc bit tng i r rt so vi m v t bo gan bnh thng. Cc t bo u sp xp thnh b thng c 3 hng t bo hoc hn. T bo u c bo thng rng a toan, nhn trn v ht nhn r. T l nhn trn bo tng tng ng nh t bo gan bnh thng hoc hn va phi. M u c th thy kiu gi tuyn v cc tuyn ny thng cha mt hay dch protein. 1.4.3. Bit ho km

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M u v t bo u c s khc bit r rt so vi bnh thng. T bo u pht trin dy c khng th phn bit c cc mch mu dng xoang v ch thy cc mch dng khe trong cc u ln. Cc t bo u c t l nhn trn bo tng tng r, a hnh thi t bo v c c cc t bo khng l k qui. Loi bit ha km cc k him trong cc u giai on sm. 1.4.4. Th khng bit ho Cc t bo u khng bit ho c bo tng t, nhn trn hoc hnh thoi ngn, tng sinh trong vng c hoc vng tu. Chn on ung th th ny rt kh khn nu ch da vo hnh thi m hc, cn s dng ho m min dch chn on xc nh. y l th22

him gp, t l < 2% cc ung th biu m t bo gan. Tin lng xu. c im lm sng, v tr, triu chng v du hiu, quy trnh chn on khng khc bt vi ung th biu m t bo gan ni chung. Nhn chung ung th biu m t bo gan rt thay i v mt m hc ngay c trong mt nt n c. Nhn t s phn m hc hu ht cc nt