;t ruetural f ind ings in

1||y uninvo |ved o ra|

|Sa of pat ients w ith HlV

|O n

38ford A , G elderblom H , R eichart P: U l trast ructural Endings invo lw d oral mucosa of patients w i th H IV infection . J O ral Pathol: 354 1.

es of clinically nor mal o ral mucosa taken f rom H IV seroposi t ivebeen invest igated by means of light - and electron mi crosÞ py .,rmal ities were found in all biopsies, regardless of the clinicalII V infect ion . I n par t icular sl it -l i ke vascular channels, spamenessr j uncti ons and swol len , protm ded endotheli a1 cel ls w i th mntity of w eibel -Palade bodies were noticed . T hese Endings werese described in lesions of eM ly stage k aposi 's u rÞ ma.

¹

' -

f 4

of severe v irus-induced

hosts immune system ,a var iety of iETEEnuno log-and clinical symptoms-

pma ( 1) is one of the dis-fil ls the CD C-surveil lance

he diagnosis of A ID S,Alt iEnate mani festation ofinfection . A bo ut 95% ofted k s £Á ur in malexual men, independent ofª ing of the Wal ter R eed:2, 3) - m ere has been anteady decl ine in the per -Mients w i th A I D S, pre-ES, decreasing from 21%, the current level of 14%

lt ho log ic pa t t em o f k S isby an i ncr ease i n Ø p i 1¤

ngio genesis i s m an i f esteddten den se ly p ac k ed v as-

t chan ne ls l ined b y en -

el i a l ce l ls . I n l at e r st ages

ssat io n and in t e r v ascu la r

1 cel ls beco m e m o re

, 6 ) . R ecen t ly . a t y p ica l

!e rat io n w i t h v esse ls l in ed

ido t he l ia l ce l l s p ro t r u d in g

m h Ø bee n d escr ib ed i ndu les o f cat -scr a t ch d i s-

B in t he Ø u r se o f H I V -

9 . Sim i la r En d ings hav e

X . Z h a n g t , A . L a n g f £ r d 2,

H . G e td e r b b m s a n d R R e i c h a r t 2

'D½á rm g pt d o aM Pa ð © Æy, Instih÷×, d

s tm zaØä y , B ý¢ æ æ I LKEWWWRV, Ö ç anWù Á × tNL M ¬ ¼, Á ô ± 'A U æ ' W É

ç Wæ æ W O WZÛ ô £ æ æ û â, - M M -Fõ ú, Ø ° , wØ t a w ² , e Ä ê k ØWTKÁ ¡ ¤

ô Æ Jt ¤ s a NM ± " ¢ NÄ " ô a naï B W° -Wù t Gô M FV .

k ey ww ds : A IDS ; H lV ; wmum - SUUÉ m ; a a

WÇ" £ " ; vað ¨ é r aM u m a© iee.

AÁ á " " fÁ mb k ¤Ó n Od d mr n . é " -

h wª" iM U û b ± , AM-MM mg ¤ zahnarz"MWChinRUem raM Wu g e - NØd - Fr¤-BU½m ØtatB´ n- m w r s tr. 15. D-t UMOBe ¤ Ò65. ÈÃ tGemmny.

b een rep o Ú ed t o occu r in c l i n ical l y no r -m al sk i n o f A I D S-p at ien ts ( 10 , 11) .

I t w as t h e p u r p ose o f t he p resen tst u d y t o ex am ine t he h i st o lo gy an d u l -

t r ast r uc tu r e o f c l i n ica l l y u n inv o lv ed

o r al m u co sa o f p at i en ts w i t h d m e r en tc l i n ical m an i festat io n s o f H I V i n f ec -

t to n -

Matedal and meth£ds

B io psi es w ere t ak en f ro m cl i nical l y no r -m al o r al m u co sa o f 10 H I V ¤" r o w si t i v e

m en and tw o w o m en (av erage age : 34 7% ho m o -/b isex u al m en : n = 7 ; i .v . d ru g

ab user s : n = 5) . Fo u r p at ien ts we re c l in -

ical l y asy m p to m at ic and t h ree pat ient s

v esse ls w i t h i n su bep i t he l ia l

¢

Fig . I . Swo llen , cuboidal and p rotm ded endothel ial cel ls of b loodconnectwe t issue. To luid ine blue x ø ô .

6. CrØ SÊ Ct ion of tubular structures w i th in cytoplÊ m o f endo thel ial cel l . E M X 46 .¢ Ú .

are character ized as k ,d-structures in the cytoplasm of-al cel ls (23) . T hei r Ø cur rence

eÊ ed in rapid ly pro li ferat ing cap.es during wound healing as wel l as

g tumor angiogenesis (24) . m ere-, the f requent fi nding of these cy-asmic organel les indicates a dra-

proli ferat ion of the endothel ials in the examined specimens- Sinceinnammatory infi lt rate was lacki ng

the examined specimens- i t is un-iy that the activat ion and pro li fer -

of endothelial Ê lls occurred dueAnnamznation , but may be mediated

Oral mucosa in H I V inf ection 39

t h e r et i cu 10 ¤end o t hel ial sy stem - T h e

et io lo gic r e lat io nsh i p o f H I V (27) and

late r o n o f C M V (28) to K S has been

d iscussed - I n v i t r o exp er i m en ts have

sho w n th e asso ci at io n o f t u m o r gro w th

facto r s w i t h t h e p ro l i f e r at i on o f aty p icalend o the l ia l ´ l s in K S (29 , 30 ) - m ere-

fo re i t h as been p r o posed , t ha t t he de -

v elOPIn en t o f lo cal ized o r d istan t f oc i o fend o t he l ia l hy p eµ l asi a m ay be t he re-

acu o n t o an angio ge nesis fac to r , o r to

th e p ro duct io n o f d iE e r en t cy to k inesand g r ow t h fac to rs ( 30 ) . T he sp m u m -o u s r egr essio n o f K S , r epo n ed in H I V -

ser o negat i v e p at ien ts d er d isco n t i nu a-

t io n o f i m m u n osu p p r essi ve t he rap y an d

o ccasio n al l y in H I V i n f ect ed p at ien ts(25) m ay i nd icate t h at k S is a p o ten -

t i al l y co n t r o l l ab le , r eact iv e h y peµ lasia( 3 0 . W h et he r t h e p ro l i f e rat io n o f en -

d o th el i a l Ê l ls seen in cl i n i cal l y u n in -

vo lv ed sk i n ( 11) and o r a l m uco sa , as

o b ser v ed i n t h is st ud y , m ay rep resent a

react iv e , pe rh ap s p ro tec t i ve p r Ø ess

and /o r w he t he r i t m ay p r em d e the laterdev e lo p m en t o f K S is un k no w n . T herep o r t t hat featu res o f C ast lem an 's d is-

ease , a no n-neo p l ast ic at y p iu l ly m p ho -

p r o l i f er at i v e d i so r de r asso ci ated w i t h

in t r af o l l ieu l ar cap i l lar y p r o l i fer at io nan d h yp erp last i c , h y al i n i zed endo th e-

l i u m J reÊ ed ed the late r Ø cu n e nÊ o f

k S in H I V i n f ec ted p at i en t s, m ay po in t

t o t h is po Ê ib i l i t y ( 32 ) .T E e u l t r ast r uct u r al En d in gs i n c l in -

ica l iy u n i n vo lv ed o r al m ucou o f p a¤

by H I V -specif ic or non-speciEc q to-

kines-D i f ferent etioh gic factors have been

discussed f or k aposi 's m rÞ ma (È ,

26) . T he relatively high i ncidence of k sin homo- or bisexual men , Þ mpared

wi th other high r isk groups (È , maypoint to the etiologic role of differentcofactors or sexually transmi tted sp -temic pathogens, capable of infect ing

Fig . 7. C i l ium-l ike struetum insen ing wi thin cytoplasm of endothelial cell - F inger-shapedproj ectmn extends outside of cel l ( arrow head ) . R B C , red blood Ê l1. E M x 28,Ã MB.

40 ZHANG Er AL.

mg. 8. E xt ravasated ew thrü " m w ithin Þ Hagen r ich Þ m eet ive tissue in clØ e asØ d at ion tophagocyte (PH CL E M X 6.Ä ô .

t ien t s w i t h H I V i n fec t io n w er e co m p a-

rab le w i t h t ho se al te ra t io ns in c l i n ica l l y

no r m a l sk in o f pat ien t s su f f e r ing f r o m

A I D S . T h e read i l y d e tec ta b le p rÊ m ceo f vascu la r ab no r m a l i t ies such as in -

cm ­ ed angio ge nesis- p ro t m d ed sw o l-

len end o the l i al cel ls , sl i t - l i k e v asc u l ar

chan ne ls, sp× se nes o f i n t er ce l lu l ar

Ju net to ns , InÁ ease m q u m t i t y o f W PBan d t ub u la r st r uc tu res as w el l as ex t r a-

vasated ew t h r© " Ê m ay b e m s ar d ed¡ an ind ica t io n t h at d u r in g H I V in -

fm t io n b l ´ d v essels un de r go ch a ngesw h ich p ro bab ly in vo l ve t h e en t i r e vas-

cu lar system - T her efo r e , a gener al p d n -

c ip le ei t he r rep resen ted b y spec i a cH I V - ind uced f ac t£ r s o r ad d i tm n al v i r a l

in fec t io ns m ay i nd uØ an d su pp o n the

d y sregu la t io n o f v ascu la r n eo gen esis-

Fu r th er h isto lo gic st ud ies and a c lo secl in ica l f o l low -u p o f t hese p a t ien ts ar e

nee ded to ev alu a te t h e p at ho ge ne t icre lev anu o f t h em p rese n t u l t r ast r uet u -

ra l f i nd ings.

AcknowtedsmeM f Supm rted by a grantfrom Bundesministerium ô r Fom hung undTechnotog-e (Nr . Im 71¢ ) .

Refeºences

1. CENTÄ s m R DESEASE CONTROL. Up× " : AÐ uimd immunodead em y sym-drome United States- MMWR 1986; 3S:17- 21.

2. R EDRH D R R , w mGô D C . I KAMOME C - T h Walter Ru d stag ng classtnca-t ion foe HT LV H UL A V in fect ion . NEnd J M ed 1õ 6 ; 3M : 131¤2.

3. RmCHA¢ PA , G ELDERBt OM H R .B ä RER J. K UNTZ A . T K H I V tnfec-tion : virob gy , et io logy . o r igin , imm u-n£ logy - preu ut ions and cl in ical OM er-

;4 h .È' ¤ .....

pam b in Hel- Ê lh . C¨ obiol - -1974 ; 8 : 33' 4 4 . . . .

3. G EIM AN EP. B" £EB S K am m-si - -

Þ m in the u tt ing d A I D S pand´ YI- -I n : B RODU S, ed . A I De : mÊ Sern cd - -cepu M Ä enw u k chat»t nF S. N4 ¤ ¤Y ork & B am l : M . D ekker . Inc ., 198, . .

4. N EWtA ND JR . L w m D R O Rmà 4 ­N G . IM moral K am i-s sarcoma; " 4 ¤ ¤

m lated light mô " Þ phc. ultm stm ctu s- - -and m m uzuú tstod Bem eal study. o l - -Surg 1988 ; 66 : 48- 58 . . . .

5. M cN UZT NS. FEn c--ER V . CONA½ MM- -Ear ly b ions d K am -i -s sarcoma in̈ ,ª ¤ ¤

mosexual men . A n ultmst ructural Þ ´ . . .m d son w ith ot k r w × ular pm lif Ø× . .t ions in sk in - A m J Pathol 1983; u t- - -62- 77 . . . .

6. M Am NEZ¤H ERNANDEZ A , A MENTAJ Ê ¤ ¤

T he basement membm e in patho logy. .t a b h ± , , 1ø Ê ; " : 6%»77 . . . .

7. B ECKm L Scm JWAN D . REICHART P. . .ÓTze ext rUEElltalar matr ix in oral k a× ma - - -u rØ ma (A I D S) : the immunohi sto- - -chemical distr ibution £f the co l lag e4 ¤ ¤type EV , V . v t of the pºÃ £MagenM YR - - EI and I I I - of laminin and of undU lin.- ¤ ¤ViFCho ws A Óh 19871 U : 1614 . . .

8. K RAMØ RH . R JH G M , H WANG Bc . CEF- - -NA½ M A , G REENS' AN JS Bau mem- -mem brane and Þ EBm ct ive tm ue pÙ . .teins in early lesions £ f k ap£Ä s aº¤. .

Þ ma as oeiated m th A I D S. J In vÄ . . .D ermatot 1985; " : 516- 20 . . . .

9. O NÄ " EEM RM . WANG NS. G tLMORE N. ¤ ¤ EJÒrmy S U ltmst rugtum l maºkem of ­lymph nodes .in pat ients with acq½red . .immune de×× ä y synd m m and in bo . .mosexual males w tt h unexptained per- 1¤ ¤

sistent lymphadem pathy - A m J CIM . . .PU M t l ÖM; « : 2 ­ 48. . . .

0. B EÒ1L.m N CM . EVERSOU L R O ral hairy . .leuk£plaU : ult rast rw tum l featum . J . .Od paÄ 04 1õ 6 ; 15: 49M . . .

1. Z HANG X , LANGFORD A , BECKER J, er 4 . .U lt rast ructural and imm un£histochem¤ . . .

ical f indings in oral hair y leukoplakia. . .Vi¡ £ ws A ± h m m i ´ : 53Ì 2. . .

2. G mMLEY PM . K ANG Y H . FREDERECK W . . . .et at. I nter feron related leuc´ yte in- . .

clushom in aÐ utzed m mum deh t m E Esyndrome: 1© aliu t im in T-cel ls. Am J ¬ ¬CIi n Pathot 1984; - 2: 147- 55. . . .

3. W EE- EL E R . PALADEG E New cytop lab E Emic comp£ nents in ar ter ial endothe- . . ôl turn- J Cett Bmt 19" ; 23: 101- 12. . . .

4. K UMAR P, ERROE A . SAÐ AR A , k tJMAR . .S. WeiM -Pal¤de k Mm u a marker tm ¤ ¤

m ovau ulam tton indua d by tuzm . .and rheumat£id anBiogenesis factors. . . .Cancer Ra 1õ 5; 45: 43394 8 . E ¤ ¤

5. L ANGm RD A . R tJF B . k tJNZE R . POHU . . .H ¤D . RÕ´ A¢ R Reg ± " £ " £fO ral . . .

b m h m m m a: m pon of a ¥ , e .B FJ j. .D ermatoIJ in pre" - . . .

6. SM M B . IS WENTMAt D A . K OZENER B a ¤ ¤M alignant neOPIu m- as Å iau d wi th . . .t he HT I Í HUL A V M ´ ion- A nti bm ­c hemother l õ 7; 3¤: g L 97. . . .

7. BOLU mM L B ® " E . H tJANG E-S KY AL¤ . . .WAn SK . G EM LÞ G . K am i -s sar- . .

cells- Cytt

13.

14.

" -

17.

18.

va" om in 110 paUenu . IM J OFad M U M-

toÂr Sw g 1987; 26: 12 È 53.4 . L UMERMAN H , FREEDMAN PD . K ERPEL

SM , PHBEA N 3A O ral k aw gi -- U F

Þ ma: a cl in iÞ patho losiC Study of nh£mØ exuai and bisexual men fm m tbeNew York metm poUtan am - - O m t su rg1988; " : 7114 .

5 . L SEJ H J , O DÄ " AÐ B M ult iÊ nt r ie an¤st£" rcoma (K am i -s sam ma) : l ight

u M elm u ï z mhu Å UÒ È ± Ed izEEZEBunohistoh g a l azzd inp of tdtopathic u min E urope and A fr ica and of cau s au o-

d ated w it h A I D S. v tk ho ws A rch 1õ 5;" " : 29 4 1.

6 . k u wrz A A . G BZD ER¤Ø M H R . W ENU LT , RB O U ® PA U l trastructural a nd-inss m or± k aF ç 's u rÞ ma (A ID S) . J

O d p althou õ 7; " : 3Ç - 9 .7 . A NGMÐ R B UR SM , M ACHER A M . et

d . EPit t-eb jd anS omatØ is in H I V in-fed ion : nØ pl" m or cat-m atch dis-

ease? L ancet 1988 ; Ë " 6 (O nly) .8 . G X Kó ELL CL W m EZES W M A , W E- -

¢ Ø G R Epitheloid angiomatogig a d ts-

t inct vau MM dUOM er in pat ients withô aÖ utrd immunodes d enq syn-drome or A ID S-related complex . L an-

ü , 1987i M: " £ 6 .9 . L E BOET P, B ERGER T , E Gm ® B A typ-

teal Ø tam oØ vag ulu p ro ti fe rat ion inm theats w ith A ED S am ­ u miated w it hthe cat ñ r ateh d iseau baci llus- La b I n -

m zt 1ÖÜ : SS i 53 A K A bstr . 314.

´ .

n .

n .

24.

25.

10 . & m WAEn L M um AMW ER J , STEm± GÒR . Pm-k aF M ¤- m zumna. J A m A Ø d

D ermatot 1ü " ; EE: 3774 " -11. D E D o- - EU U G D . G£ £m ENE S,

A NDRE J. L EÞ ux M . M AU- EEJGE JD .C1inia l ly ½m W Ived sk in m A ID S: evi -

dem e o f aw pm l dermal vem ls similarto ear ly lesions obsew ed in k am si -s

" rm ma. J CØ paÅ £t l õ 7; " : 154- 7.

12. G ELDERBLOM H . O GEJM H . BAEJER H .O n the © cur renm of £ " Þ m avirus-l tke

26.

27.

O ral m ucosa m H I V inf ectêon 4 1

ible hypem lm a (H yp£thesis) . L ancet1986 ; " : 1309- 11.

I A OU WT N A , SUN N CL L EONG L A ,OSEAS R S, PRINCE H E . M ult icentr ic an-

gi fo luq du lp µ h node hypem lasia(Cast leman's disease) fo l lowed by K a-

posh Ê rÞ ma in two homosexual malesw i th the acquired immunodenciencysyndrome- J Cttn Pashol 1985; 83:27- 33.

posi 'S SM Þ ma D N A enÁ d es a grow th

facto r that is a member of É e PG F fam-i ly . Celt 1987; " : ?29- 37 .

30 . E NSOLE B , B EBEM ELD R N AKAMURA S,SALAm JDDEN ¥ , w £" £.STAAL R G AU D

RC PØ sible role of grow th factors andq tOMnes in t he pathogenm is of k apÕsi -s sarÞ ma. I V . I nt. Conf . on A I D S.

Stock holm 1988 , A bst r . No . 2647 .

n .

31. BRÞ ¡ 11 k aposi's mzÞ ma: a revers-