86

U LYMPHO C TNH BNH HODGKINMc tiu hc tp 1. M t c c im i th ca bnh Hodgkin hch, lch, gan. 2. M t c c im ca t bo Reed - Sternberg, tnh a hnh thi t bo v cc c im vi th chnh ca 4 tp bnh Hodgkin.

I. I CNGNm 1832, Thomas Hodgkin (ngi Anh) ln u tin m t v lm sng 7 trng hp bnh ca hch v lch. Nm 1898, Karl Sternberg (ngi c) v Dorothy Reed (ngi M) m t cc c im ca t bo sau ny mang tn ca h - t bo Reed-Sternberg - v cng chnh l du hiu c trng chn on bnh Hodgkin. Bnh Hodgkin l mt trong hai nhm ln ca u lympho c tnh, trong c t bo ReedSternberg l t bo c trng ca bnh km theo nhiu loi t bo phn ng nh tng bo, m bo, i thc bo, bch cu a nhn a toan v lympho bo mc nhiu hay t ty thuc vo tp m hc ca bnh. M, nm 1988 t l mc bnh Hodgkin l 2,8/100.000 dn.

II. GII PHU BNH1. i th Bnh Hodgkin gp ch yu hch lympho nhng cng c th gp cc tng ca h to mu-lympho v xm nhp cc tng khc. Tn thng khng c hiu, thng l nhng khi khng c gii hn r rng hoc l cc nt ri rc. Din ct mu trng xm hay vng nht, thun nht hoc c hoi t hoc c cc chm chy mu. 1.1. Hch lympho Tn thng u tin thng thy hch lympho, him gp bnh Hodgkin ngoi hch. Lc u l mt hay nhiu hch to, kch thc thay i, khng dnh vo nhau. Sau , dnh thnh mt khi nhiu mi v lan sang cc nhm hch khc. Cc nhm hch ngoi bin nh hch c, nch, bn ... gp trong 90% cc trng hp, cc hch su nh hch trung tht, sau phc mc gp trong 50% cc trng hp.

Hnh 1. Hch lympho trong bnh Hodgkin th x nt

87 1.2. Lch Gp trong 25% cc trng hp. Lch to va, thng khng qu 400gam. Mt ngoi nhn, ng u hoc c cc nt li trn v lch. Din ct c cc nt mu trng xm, kch thc t vi mi-li-mt n vi cen-ti-mt ni r trn nn sm ca lch to nn hnh nh lch xc xch hay lch hoa cng. 1.3. Gan Khong 25% cc trng hp Hodgkin c gan to vi cc nt to nh khng u, c khi kh thy bng mt thng. 2. Vi th 2.1. T bo Reed-Sternberg L nhng t bo c tnh c trng ca bnh Hodgkin, c hiu chn on bnh Hodgkin. T bo Reed-Sternberg in hnh c kch thc ln 20-50m hoc hn. Bo tng rng, thun nht hoc dng ht, a toan nh. Nhn ln. Kch thc thay i, mng nhn dy, cht nhim sc th vn v tp trung st mng nhn. Ht nhn rt to, a toan, nm gia nhn v tch bit vi cht nhim sc to nn mt qung sng quanh ht nhn. i khi thy t bo hai nhn i xng vi nhau to nn hnh nh soi gng hay mt c. Nhng t bo ln, mt nhn nhng nhn khng c mi, ht nhn ni r gi l t bo Hodgkin hoc t bo dng Sternberg. Ngun gc ca t bo Reed-Sternberg v cc bin th ca n l nhng nguyn bo lympho pht trin t cc t bo Th.

Hnh 2. T bo Reed-Sternberg

2.2. Tnh a hnh thi t bo Xen ln vi cc t bo c tnh, m Hodgkin cn c s xm nhp a dng cc t bo khc vi t l thay i nh lympho bo nh, nguyn bo lympho, nguyn bo min dch, m bo dng bn lin, i thc bo, bch cu a nhn a toan v tng bo. Thng c x ha t hay nhiu thnh nhng di nh hoc m. 2.3. Cc tp m bnh hc ca bnh Hodgkin Theo phn loi Rye (1966), bnh Hodgkin c chia lm 4 tp m bnh hc. 2.3.1. Tp I: Bnh Hodgkin nhiu lympho bo (lymphocytic predominance type) Cu trc hch b xa do s tng sinh mnh ca lympho bo km hoc khng km m bo. S tng sinh c th lan ta hoc thnh nt khng u. Rt t t bo Reed-Sternberg in

88 hnh nhng xut hin cc bin th ca t bo Reed-Sternberg, l nhng t bo nh hn t bo Reed-Sternberg, nhn c np cun, nhiu thy, cht nhim sc c hc nh, ht nhn nh v khng r gi l t bo bp rang (popcorn cell). Ri rc c th thy tng bo, bch cu a nhn a toan. V hch t b xm ln. Hodgkin tp I gp trong 5% cc trng hp, 80% giai on lm sng I, II, thng gp nam gii trng thnh, tr tui. Thi gian sng thm di.

Hnh 3. Bnh Hodgkin nhiu lympho bo

2.3.2. Tp II: Bnh Hodgkin th x nt (nodular sclerosis type) M hch b xm ln bi nhng nt trn hay a dng, bao quanh cc nt l nhng b x. Cc nt gm nhng tng bo, lympho bo, bch cu a nhn a toan, cc t bo Hodgkin v c bit l cc t bo khuyt (lacunar cell) - l mt bin th ca t bo ReedSternberg, c kch thc rt ln 40-50m, nhn c nhiu mi, mng nhn mng, trong nhn c nhiu ht nhn, bo tng rng v sng nhng thng co li to nn mt khong trng gia t bo v m dng lympho xung quanh, to nn hnh t bo nm trong hc. Qu trnh x ha tng dn, lc u khu tr quanh cc nt c nhiu t bo, sau c th xa hon ton cu trc hch lympho. C th c cc hoi t. Tp ny hay gp n gii v c th gp trong tt c cc giai on lm sng ca bnh, trong 60% giai on lm sng I, II v khong 35% giai on lm sng III.

Hnh 4. Bnh Hodgkin th x nt

89 2.3.3. Tp III: Bnh Hodgkin th hn hp t bo (mixed cellularity type) Hch lympho c s xm nhp a hnh thi, bao gm lympho bo, m bo, tng bo, bch cu a nhn a toan v trung tnh. Nhiu t bo Reed-Sternberg in hnh v cc t bo Hodgkin n nhn. Thng thy cc hoi t v x ha. Tt c to nn hnh nh hn hp t bo. y l tp hay gp nht, nam gii mc bnh nhiu hn n gii v gp trong mi giai on lm sng ca bnh Hodgkin, gn 50% giai on lm sng III, IV. Thi gian sng thm ca bnh nhn tng i ngn. Tin lng xu hn tp I v tp II.

Hnh 5. Bnh Hodgkin th hn hp t bo

2.3.4. Tp IV: Bnh Hodgkin th t lympho bo (lymphocytic depletion type) Tp ny gm hai loi nh: - Loi x ha lan ta: Ngho t bo c bit l lympho bo. X ha lan rng thnh khi v cu trc, c, t t bo, t si to keo. T bo Reed-Sternberg nhiu v thng b co ko, toan tnh mnh. Loi ny gp giai on cui ca bnh Hodgkin khng c iu tr hoc sau iu tr tia. - Loi lin vng: c trng bi rt nhiu t bo Reed-Sternberg c hnh dng k qui. Tp ny t gp, khong 1-5% cc trng hp, thng gp nam gii, tui trung bnh khong 50 tui, tui tr hn gp bnh nhn AIDS, thng tng ng vi giai on lm sng III v IV, thi gian sng thm ngn.

Hnh 6. Bnh Hodgkin t lympho bo

90

III. LM SNG- Hch to, khng au, thng mt bn. Hay gp hch c, nch, bn, trung tht. - Triu chng: St, ra m hi, st cn, thiu mu, gan lch to. Cc giai on lm sng Bnh Hodgkin biu hin 4 giai on lm sng (theo phn loi TNM cc u c tnh ca Hip hi Quc t chng ung th, Genve 1979)Giai on I II nh ngha Xm nhp mt vng hch duy nht (I) Hoc xm nhp khu tr mt tng hay mt v tr ngoi hch (IE) Xm nhp 2 vng hch tr ln cng mt pha c honh (II) Hoc xm nhp khu tr mt tng hay mt v tr ngoi hch kt hp vi mt hay nhiu vng hch, mt pha c honh (IIE) Xm nhp nhng vng hch hai pha c honh (III) Hoc km theo: Xm nhp khu tr mt tng hay mt v tr ngoi hch (IIIE) Xm nhp vo lch (IIIS) Xm nhp ngoi lch (IIIES) Xm nhp lan ta ri rc vo mt hay nhiu tng hay v tr ngoi hch, km theo hoc khng theo xm nhp hch

III

IV

E: ngoi hch (extra lymphatic) S: lch (spleen) Trong bng phn giai on lm sng c ghi thm ch B nu bnh nhn c mt trong cc triu chng sau: - Gim 10% trng lng - St trn 38oC - Ra m hi m Ghi ch A nu bnh nhn khng c cc triu chng . Ngy nay vi nhiu phng php chn on sm c bit l xc nh tp m bnh hc v c phc iu tr phi hp x tr v ha tr, ngi ta c th ko di thi gian sng thm ca mt s bnh nhn tp I v tp II n 10 - 15 nm.

91

U LYMPHO C TNH KHNG HODGKINMc tiu hc tp 1. M t c cc c im i th, vi th v mt s phn loi m bnh hc chnh ca u lympho c tnh khng Hodgkin.

I. I CNGU lympho c tnh khng Hodgkin chim t l cao hn so vi bnh Hodgkin, M nm 1988 t l l 13,8/100.000 dn, gp khong 5 ln bnh Hodgkin. Bnh hay gp nam nhiu hn n, c xu hng tng theo tui nhng mc khc nhau mi tp bnh. tr em thng gp cc tp c c tnh cao nh u lympho nguyn bo lympho v u lympho t bo nh nhn khng kha.

II. PHN LOIKhc vi bnh Hodgkin, hin nay c nhiu bng phn loi u lympho c tnh khng Hodgkin. Phn loi u tin ca Rappaport (1966) da vo cu trc u (to thnh nt hay lan ta) v loi t bo (lympho bo, m bo v hn hp t bo) vi cc mc bit ha ca t bo. Vo nhng nm 70, xut hin phn loi ca Lukes v Collins (1974) phn chia cc Tp nh theo 2 dng t bo T v B. Sau l phn loi ca Kiel (1975) sp xp cc u lympho c tnh khng Hodgkin thnh 2 nhm ln: c tnh thp v c tnh cao. Ngoi ra, cn c phn loi ca Dofman, ca T chc Y t Th gii, ca Anh ... Nm 1982, Vin Ung th quc gia M a ra bng Cng thc thc hnh (Working Formulation, WF) dnh cho lm sng. Bng ny chia u lympho c tnh khng Hodgkin thnh 3 nhm ln c gi tr tin lng bnh l c tnh thp, c tnh trung gian v c tnh cao bao gm 10 tp m bnh hc. Gn y, mt nhm Quc t nghin cu u lympho c tnh khng Hodgkin bao gm cc nh khoa hc ca nhiu nc a ra bng phn loi REAL (1995) da trn hnh thi hc, min dch di truyn t bo v sinh hc phn t xc nh cc tp u. Nh vy, phn loi u lympho c tnh khng Hodgkin c nhiu i mi trong nhng thp k v nhng nm gn y nhng rt phc tp v cho n nay vn cn nhiu im cha thng nht. Vic s dng phn loi no l ty thuc theo tng khu vc, tng nc v trng phi. M v cc nc ni ting Anh khc s dng bng Cng thc thc hnh (WF) v phn loi ca Rappaport, Chu u dng bng phn loi Kiel. Trong phm vi bi hc ny, chng ti ch cp n bng Cng thc thc hnh dnh cho lm sng v y l phn loi tng i n gin, d p dng v c gi tr trong theo di tin lng bnh. CNG THC THC HNH c tnh thp - WF1: u lympho c tnh (ULPA), lympho bo nh - WF2: ULPA, nang, u th t bo nh nhn kha - WF3: ULPA, nang, hn hp t bo ln v t bo nh nhn kha c tnh trung gian - WF4: ULPA, nang, u th t bo ln - WF5: ULPA, lan ta, t bo nh nhn kha

92 - WF6: ULPA, lan ta, hn hp t bo ln v nh - WF7: ULPA, lan ta, t bo ln c tnh cao - WF8: ULPA, t bo ln, nguyn bo min dch - WF9: ULPA, nguyn bo lympho - WF10: ULPA, t bo nh nhn khng kha Cc loi khc - Loi m bo thc s - U lympho da, t bo T - Cc loi khc

Hnh 1. ULPA, nang, u th t bo nh nhn kha (WF2) (x 50)

Hnh 2. ULPA, nang, u th t bo nh nhn kha (WF2) (x 400)

93

Hnh 3. ULPA, lan to, hn hp t bo ln v t bo nh (WF6)

Hnh 4. ULPA, lan to, t bo ln (WF7)

Hnh 5. ULPA, t bo ln,nguyn bo min dch (WF8)

94

Hnh 6. ULPA, nguyn

bo lympho (WF9)

III. GII PHU BNH1. i th Hch lympho bao gm cc nhm hch ngoi bin v cc nhm hch su thng l ni khi pht ca u lympho c tnh khng Hodgkin. Hch to, c th to thnh khi ln c nhiu thy, di ng hoc dnh vo da v m quanh hch. Din ct thun nht, mu trng xm, i khi c hoi t v chy mu mt s tp. 2. Vi th Da vo: - Cu trc ni tri ca m hch b ung th: dng nang hay dng lan ta. - Loi t bo chim u th: t bo nh (nhn kha hay khng kha), t bo ln, hn hp t bo ln v t bo nh, nguyn bo min dch, nguyn bo lympho ... Phn chia cc tp m bnh hc theo phn loi ca bng Cng thc thc hnh. V vi th ni chung, khc vi bnh Hodgkin, trong u lympho c tnh khng Hodgkin thng khng thy c im a hnh thi t bo.

IV. LM SNGTriu chng c trng ca u lympho c tnh khng Hodgkin l cc hch ngoi bin to, khng au. C th ng ring l hoc dnh vo nhau thnh mt khi c nh. V tr thng gp l hch c (40%), hch nch (20%) v hch bn. C th gp hch trung tht, hch sau phc mc. U lympho c tnh khng Hodgkin ngoi hch thng gp hn so vi bnh Hodgkin nh u lympho nim mc ng tiu ha, a-mi-dan, ty xng, tuyn v, lch, gan, da ... V tin lng t l sng 10 nm tng ng ca 3 nhm c tnh thp, trung gian v cao l 45%, 26% v 23%.