Langerhans cell histiocytosis

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M a ria d e L o u rd e s L . ~ C h a u ffa ille , R o s a n a M .V a le rio , C y b e lle M a ria C o s ta D in iz , M ilv ia M a ria S im o e s , S ilv a E n o k ih a ra , N y lc e o M ic h a la n y , K a rin V e n tu ra F e rre ira , J o s e A n to n io B a d d in i M a rtin e z , K a rin e M a rq u e s H a s s u n , A lv a ro N a g ib A ta lla h , J o s e K e rb a u y

L angerhans cell histiocytosis

D i s c i p l i n a d e H e m a t o l o g i a e H e m o t e r a p i a , D i s c i p l i n a d e C l i n i c a M e d i c a , D i s c i p l i n a d e A n a t o m i a P a t o l o g i c a , D i s c i p l i n a d e D e r m a t o l o g i a , D i s c i p l i n a d e P n e u m o l o g i a - E s c o l a P a u l i s t a d e M e d i c i n a ,

U n i v e r s i d a d e F e d e r a l d e S i i o P a u l o - S i i o P a u l o , B r a z i l .

T h e a u th o rs p re se n t a ra re ca se o f L a n g e rh a n s ce ll h istio cyto sis in a 3 1 ye a r o ld fe m a le p a tie n t w ith vu lva r, p e ri-a n a l a n d o ra l le sio n s, d ia b e te s in sip id u s, p u lm o n a ry skin a n d b o n e in filtra tio n s. S kin b io p sy im m u n o h isto ch e m istry p re se n te d p o sitive S 1 0 0 p ro te in a n d vim e n tin e , b u t th e d ia g n o sis w a s d o n e w ith th e d e m o n stra tio n o f B irb e ck g ra n u le s w ith e le tro n ic m u cro sco p y. T h e tre a tm e n t w a s b a se d o n syste m ica l ch e m o th e ra p y a lth o u g h vu lva r le sio n h a s a b a d re sp o n se to ch e m o th e ra p y.

U N IT E R M S : H istio cyto sis X , L a n g e rh a n s ce ll. D ia b e te s in sip id u s.

IN T R O D U C T IO N

T

h eh is tio c y to s isa u th o rs p re s e n t(L C H )a ra re c a s e o f L a n g e rh a n sw ith v u lv a r, p e ria n a l a n d o ra lc e ll le s io n s , p u lm o n a ry a n d d ia b e te s in s ip id u s (D I), s k in a n d b o n e in filtra tio n s .

C A S E R E P O R T

A 3 1 -y e a r o ld w h ite w o m a n w a s a d m itte d to th e H o s p ita l S . P a u lo in A p ril, 1 9 9 6 , d u e to a n u lc e ra te d le s io n

A d d re s s fo r c o rre s p o n d e n c e : M a ria d e L o u rd e s L . F . C h a u ffa ille R u a B o tu c a tu , 7 4 0 -3Q

a n d a r

S a o P a u lo /S P - B ra s il - C E P 0 4 0 2 3 -9 0 0

in th e v u l v a th a t h a d a p p e a re d 1 y e a r p re v io u s ly . S h e a ls o c o m p la in e d o f c u ta n e o u s n o d e s in th e rig h t s h o u ld e r a n d fo re a rm , g e n g iv itis , lo o s e n in g o f th e te e th , h a lito s is , o to rrh e a , p o ly d ip s ia , a m e n o rrh e a , g a la c to rrh e a a n d a w e ig h t g a in o f 2 4 k g in th e th re e p re v io u s y e a rs , a s w e ll a s a s p o n ta n e o u s p n e u m o th o ra x 1 0 y e a rs e a rlie r. S h e w a s o b e s e , w ith a 3 c m b ro w n is h -re d p a p u la r le s io n o n th e rig h t s h o u ld e r a n d a n o th e r o f 1 c m o n th e fo re a rm ; e ry th e m a to u s p la q u e in th e ro o f o f th e m o u th , w ith s u p e rio r te e th e x tru s io n a n d lo o s e n in g . T h e liv e r w a s 5 c m fro m th e L C M a n d th e re w a s e d e m a o f th e la b ia m a jo ris a n d u lc e ra te d v u lv a r le s io n w ith a g ra n u lo m a to u s a s p e c t; a n d a p e ria n a l le s io n w ith th e s a m e c h a ra c te ris tic s . L a b o ra to ry e x a m s : H b = 1 3 .7 g /d l; W B C = 6 .7 0 0 /m m 3 (s ta b 1 % , s e g m e n te d 5 6 0 / 0 , e o s in o p h ils 5 % , b a s o p h ils 10 / 0 ,

ly m p h o c y te s 3 0 % , m o n o c y te s 7 % ); P la te le ts = 2 3 0 .0 0 0 / m m3_; _{S G O T = 5 4 (1 3 ),} _{S G P T = 6 0 (1 4 ),} _{a lk a lin e} _{p h o s p h a ta s e}

= 3 4 0 (2 5 0 ), L D H = 4 2 4 (4 5 0 ), u ric a c id = 7 .8 (6 .0 ); th e p u lm o n a ry fu n c tio n h a d a m ix e d v e n tila to ry a b n o rm a lity a n d p re d o m in a n c e o f a lig h t re s tric tiv e p a tte rn ; tra n s b ro n c h ia l b io p s y p re s e n te d u n s p e c ific in filtra te ; w a te r d e p riv a tio n te s t c o n s is te n t w ith D I a n d m e g a te s t c o n s is te n t

C H A U F F A IL L E , M .L .L .F .; V A L E R IO , R .M .; D IN IZ , C .M .C .; S IM O E S , M .M .; E N O K IH A R A , S .; M IC H A L A N Y , N .; F E R R E IR A , K .V .; M A R T IN E Z , J.A .B .; H A S S U N , . 1 • • a _ a • • • • • • • • • • . • • • • • • • • • • • • •

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F ig u re 1 - Im m u n o h is to c h e m is try s h o w in g p o s itiv e 8 1 0 0 p ro te in .

w ith panhypopituitarism ; chest radiography show ed

bilateral interstitial infiltrate w ith m ediastinum

enlargem ent; bone scintillography had anom alous

hyperconcentration of radioindicator in the distal third of the bilateral fem ur, in the focal left paranasal area and in the jaw ; com puterized tom ography (C T ) w ith interstitial

m icronodular infiltration, cystic areas in pulm onar

parenchym a and interlobular fissure in the rosary; skull

m agnetic nuclear resonance w ith a tum or in the

infundibulo-hypothalam ic area; abdom inal scan w it~

hepatom egaly and signs of m oderate hepatic steatosis.

Skin and vulvar lesion biopsies show ed L angerhans cell histiocytosis w ith positive S 100 protein, vim entine and H A M 56, and negative L C A , H M B 45, Pan B and Pan T antigens. E lectron m icroscopy show ed the presence of B irbeck granules.

D IS C U S S IO N

H istiocytoses are disorders characterized by the

proliferation of cells from the m onocyte-phagocytic series.

T here is a great biological diversity from a benign and indolent pattern to a m alignant and fulm inant one. It is m ore frequent in children w ith an average age of 2 or 3

years old (1 ). Its incidence is estim ated as 0.2 to 0.5 cases

per 100,000 children per year in the U SA . In adults, the incidence is unknow n.

Its etiology is unknow n but it is thought it could be a proliferative disorder in response to an antigenic stim ulus of infectious, genetic abnorm ality, deregulated im m une response, or even clonal origin.

H and-SchU ller-C hristian, L etterer-Siw e and.

eosinophilic granulom a w ere the first clinical

descriptions. L ater on, they w ere nam ed H istiocytosis

X , w here X stood for etiology unknow n. In 1985 the

International G roup of Pathologists and C linicians

recom m ended a new classification that w as published

by the W riting G roup of the H istiocyte Society (W G H S)

dividing them into: L angerhans cell histiocytosis

(L C H ), non-L angerhans cell histiocytosis (N L C H ) and

m alignant histiocytosis. T his classification has the

advantage of recognizing the pathognom onic cell.

C linical presentation m ay be localized or system atic, invading skin, lungs and bones in adults, and bone m arrow and lym phonodes in children.

S a o P a u lo M e d ic a l J o u rn a l/R P M 1 1 6 (1 ): 1 6 2 5 -1 6 2 8 , 1 9 9 8 C H A U F F A IL L E , M .L .L .F .; V A L I~ R IO , R .M .; D IN IZ , C .M .C .; S IM O E S , M .M .;

E N O K IH A R A , S .; M IC H A L A N Y , N .; F E R R E IR A , K .V .; M A R T IN E Z , J .A .B .; H A S S U N ,

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1 6 2 7

F ig u re 2 - E le c tro n m ic ro s c o p y (4 0 0 x ): a rro w s h o w in g th e B irb e c k g ra n u le .

S k in a tta c k m a y b e th e o n ly m a n ife sta tio n o f th e d ise a se a n d m a y p re se n t sp o n ta n e o u s re m issio n , o r it m a y fo rm p a rt o f th e in v o lv e m e n t o f o th e r o rg a n s w ith a w o rse p ro g n o sis. T h e se le sio n s m a y p re c e d e sy ste m a tic m a n ife sta tio n s b y o n e y e a r o r m o re . T h e y o c c u r in 3 0 % to 4 0 % o f th e c a se s a n d a re v e ry h e te ro g e n e o u s. In th e a x illa e , in g u in a l, p e ria n a l, n e c k a n d re tro a u ric u la r a re a s, p a p u le s a n d su b c u ta n e o u s n o d e s m a y u lc e ra te le a d in g to le sio n s th a t a re d iffic u lt to h e a l d e sp ite tre a tm e n t. G e n ita l u lc e rs a re m o re fre q u e n t in a d u lts. L o c a liz e d o r d isse m in a te d le sio n s o c c u r in o ra l m u c o sa w ith p la q u e s th a t te n d to u lc e ra te le a d in g to lo ss o f te e th . T h e se e v id e n t d e rm a l-m u c o sa l p re se n ta tio n s w e re w e ll d o c u m e n te ~ in th is c a se .

L u n g in v o lv e m e n t in L C H m a y b e se e n iso la te d o r n o t (2 ). In a lm o st 2 0 % o f c a se s, sp o n ta n e o u s

p n e u m o th o ra x is th e first m a n ife sta tio n o f th e d ise a se . R a d io lo g ic a lly , th e re a re d iffu se , re tic u lo -n o d u la r o p a c itie s, o v e r m u ltip le c y stic im a g e s m a in ly in th e u p p e r a n d m id -lu n g z o n e s. T h e c h e st c o m p u te riz e d to m o g ra p h y sc a n is su p e rio r to X -ra y in d e te c tin g th e se a b n o rm a litie s a s w a s d e m o n stra te d h e re ; sin c e th e

"h o n e y c o m b " a b n o rm a litie s c o u ld b e se e n . P u lm o n a ry fu n c tio n te sts g e n e ra lly sh o w a m ix e d p a tte rn w ith lo w e r d iffu sio n c a p a c ity a n d h y p o x e m ia th a t g e t w o rse w ith e x e rc ise (2 ).

B o n e le sio n , fo c a l o r d isse m in a te d , is ly tic a n d m a y b e c u ra b le w ith c u re tta g e , a lth o u g h it c a n re a p p e a r. G in g iv a l in filtra tio n w ith b o n e a b so rp tio n le a d in g to to o th flo a tin g is a n a d u lt fe a tu re o f th e d ise a se .

V u l v a r p re se n ta tio n s a re ra re , b u t in a d u lts it is m o re fre q u e n t w ith a ro u n d 4 0 c a se s re la te d in th e lite ra tu re . C o n sid e rin g th e tim e o f e v o lu tio n fo r v u lv a r le sio n p re se n ta tio n , th e p a tie n ts c a n b e c la ssifie d in to 4 g ro u p s: g e n ita l tra c t o n ly ; le sio n s su b se q u e n tly in v o lv in g m u ltip le o rg a n s; o ra l o r sk in le sio n s fo llo w e d b y in v o lv e m e n t o f th e g e n ita l tra c t; a n d D I fo llo w e d b y in v o lv e m e n t o f m u ltip le o rg a n s a n d g e n ita l le sio n s. T h e th ird c a se is a p p a re n tly th e m o st fre q u e n t (3 ).

T h e d ia g n o sis w a s m a d e b y le sio n b io p sy . H isto c h e m istry w a s p o sitiv e fo r S 1 0 0 , C D 1a , H L A -D r a n d v im e n tin e , w h ic h a re g e n e ra lly n e g a tiv e in N L C H . T h e W G H S c o n sid e rs th e p re se n c e o f B irb e c k g ra n u le s o r C D la p o sitiv ity a s fu n d a m e n ta l c rite ria fo r

C H A U F F A IL L E , M .L .L .F .; V A L E R IO , R .M .; D IN IZ , C .M .C .; S IM O E S , M .M .;

I( U •flT fll 1 fll-l flt\.1. I(~ Q R flIIV _I _ I !:IIn n o rh !:lln ~1 "0 1 1h i~ tin l"\Itn d ~

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th e d ia g n o sis. In th e p re se n t c a se , th e d e fin itiv e

d ia g n o sis w a s m a d e b y d e m o n stra tin g B irb e c k g ra n u le s

w ith e le c tro n m ic ro sc o p y . U su a lly , h isto lo g ic a l a sp e c ts

d o n o t re la te to th e e x te n sio n a n d a g re ssi v e n e ss o f th e

d ise a se a n d in th e in itia l p h a se th e L a n g e rh a n s c e lls

a n d h istio c y te s m a y b e se e n in g re a te r n u m b e rs.

It is im p o rta n t to k n o w if th e d ise a se is lo c a liz e d o r

d isse m in a te d , sin c e th e in v o lv e m e n t o f m o re th a n o n e

o rg a n re q u ire s sy ste m a tic th e ra p y . T h e tre a tm e n t in a d u lts

is b a se d in p o ly c h e m o th e ra p y w ith e to p o sid e , v in c a

a lk a lo id s a n d g lu c o c o rtic o id . P o o r p ro g n o sis fa c to rs a re

a d v a n c e d a g e , d ise a se e x te n t a n d fu n c tio n a l o rg a n

a b n o rm a litie s (4 ). R e la p se s a re c o m m o n . V u lv a r le sio n s

d o n o t im p ro v e w ith sy ste m a tic c h e m o th e ra p y n e e d in g

lo c a l in te rv e n tio n . R a d io th e ra p y , P U V A a n d in tra le sio n

g lu c o c o rtic o id a re a lso u se d . T h is p a tie n t re c e iv e d tw o

c y c le s o f e to p o sid e (1 0 0 m g /m2_{/d a y /3} _{d a y s) a n d v in c ristin e}

(2 m g /d a y ) e v e ry 3 0 d a y s, w ith o u t im p ro v e m e n t. S h e w a s

su b m itte d to p a rtia l v u lv e c to m y a n d is a t p re se n t re c e iv in g

v in b la stin e 1 0 m g /w e e k /4 m o n th s .

REFERENCES

1 . T ro c h te n b e rg D S , D e ssy p ris E N . C a se R e p o rt: re v e rsib le

h e p a to m e g a ly a n d d ia b e te s m e llitu s in a n a d u lt w ith

d isse m in a te d h istio c y to sis X . A m J M e d S c i 1 9 9 0 ;

2 9 9 (3 ): 1 7 9 -1 8 4 .

. 2 . S o le r P , K a m b o u c h n e r M , V a ly e re D , H a n c e A J. P u lm o n a ry

L a n g e rh a n s c e ll g ra n u lo m a to sis (h istio c y to sis X ). A n n u R e v

M e d 1 9 9 2 ;4 3 :1 0 5 -1 1 5 .

3 . A x io tis C A , M e rin o M J, D u ra y P H . L a n g e rh a n s c e ll

h istio c y to sis o f th e fe m a le g e n ita l tra c t. C a n c e r 1 9 9 1 ;

6 7 : 1 6 5 0 -6 0 .

4 . K o m p D M , P e rry M e . In tro d u c tio n : th e h istio c y tic

sy n d ro m e s. S e m in O n c o l 1 9 9 1 ; 1 8 ( 1 ): 1 - 2 .

S a o P a u lo M e d ic a l J o u rn a l/R P M 1 1 6 (1 ): 1 6 2 5 -1 6 2 8 , 1 9 9 8 C H A U F F A IL L E , M .L .L .F .; V A L E R IO , R .M .; D IN IZ , C .M .C .; S IM O E S , M .M .;