Revi

ew art
icl
e

PARANEOPLASTIC SYNDROMES

KetutSuega
Hemat
ologyM edi
calOncol
ogyDivisionUdayanaM edicalSchool/Sangl
ah Hospi
tal
DenpasarBali
Emai
l:ksuega@ yahoo.
com

ABSTRACTS

The t
erm Paraneoplastic Syndromes(PNS)refersto symptomsorsignsresulting from damage to organsort
issues
t
hatare remot
e from the site ofa malignantneoplasm ori
tsmetast
ases.W i
del
y known exampl
esincl
ude cancercachexia,
hypercal
cemi
a,Cushing’
ssyndrome,
andTrousseau’
ssyndrome.A parti
cularlydevastat
ingform ofparaneoplast
icsyndromesi
aa
groupofdi
sordersclassi
ÞedasParaneoplasticNeurologicalDisorders(PND).
TheincidenceofPNSvarieswi
ththeneurologi
cal
syndromeand with thetumor .PNS can occursin 7 to 10% ofal lpatientswith cancer.A paraneoplasticsyndromemay resul
t
from product
ion and release ofantibodiesand physiologically active substances,oritmay be idiopathic.However,notall
paraneopl
ast
ic syndromesare associated with these antibodies.Symptomscan be atypical,psychiatric,oreven ßuct
uati
ng,
and PNS shoul
d often be in the differentialdiagnosi
sofotherwi
se unexpl
ained neurol
ogicalsyndromes. An internat
ional
panelofneurol
ogistshasestablished di
agnosticcriteriathatdividepatientswith asuspected PNS into deÞniteand probable
cat
egori
es.Thesecriteriaarebasedonthepresenceorabsenceofcancer,thepresenceofwell-characterizedantibodies,andt
he
t
ypeofcl
ini
calsyndrome.Detection ofa“well
-characteri
zed”paraneopl
asti
cantibody i
sextremel
y hel
pfulbecausei
tproves
t
heparaneopl
asticetiologyoftheneurologicalsyndrome.Usual
ly,theparaneoplasticsyndromesaredividedintot
hefoll
owi
ng
cat
egori
es:(1)miscellaneous(nonspeci
Þc),(2)rheumatologic,(3)renal
,(4)gastrointestinal,(5)hematologic,(6)cutaneous,(7)
endocri
ne,and(8)neuromuscular
.Treatmentvarieswi
tht
het
ypeandl
ocati
onoftheparaneoplast
icdisorder,consi
stoft
reat
ment
oft
heunderl
yingtumor,aswellasthetreatmentofthepresumptiveimmune-mediateddisorderisbasedonimmunosuppression.
Becauseparaneoplasticsyndromesdifferwidelyfrom individualtoindividual,prognosismayvarygreatly.

Keywords:paraneoplasticsyndrome,paraneoplasticneurologicaldisorders,well-characterizedantibodies

INTRODUCTION neo (new),and pl asti

c(being formed orshaped),and
thusmeans“besi deanew format ion,orcancer .”These
The t erm PNS refers to sympt oms or signs syndromescanaffectanyorganorti ssue,i ncludingt he
resul
tingfrom damaget oorgansortissuesthatareremot e liver,skin,and muscles,butthenervoussystem i tself
2
from t
hesi teofamal ignantneoplasm ori tsmetast ases. isacommon site. In abroad sense,thesesyndromes
Paraneoplastic syndromes can affect most organs arecollectionsofsympt omsthatresul tfrom subst ances
and ti
ssues.W i del
y known exampl es i
ncl ude cancer produced by thetumor,and t hey occurremot el
y from
cachexia, hypercal cemi a,
Cushing’ s syndrome, and the tumor i tsel
f.The sympt oms may be endocri ne,
1
Trousseau’s syndrome. The t erm paraneoplasti c neuromuscul ar or muscul oskeletal, cardi ovascular,
comesfrom t heGreek rootspara(al ongsideornear), cutaneous, hemat ol
ogic, gastrointestinal, renal , or

Paraneoplasti
cSyndromes 61
Ketut Suega
 3
mi scel laneousi nnat ure. Amongt hebestcharact erized furthertherapy.Inpatientswi thmetast
aticdi sease,their
oft hePNS aret hoseproduci ngpol ypept i
dehormones syndromescanbedi sabling,andappropriat etreatment
such asAdrenocort icot ropi n (ACTH)orparat hyroid oftheparaneopl asiamaybethebestmeansofpal liati
ng
hormone t hataffectorgan funct i on atremot e sit es. patients.The hormones released by t umors may be
A part icul arly devast at ing form of paraneopl astic requiredfortumorgrowth(i. e.,t
hetumormayproduce
syndromesi a a group ofdi sorderscl assi Þed asPND itsown growth factorsand “autostimulat e”),and ap-
whi chaffectt hebrai nandcent ralnervoussyst em and propriateidentiÞcationofsuchhormonesmayal low a
4
theyaredegenerat i veprocessi nnat ure. new rat ionaltherapeuticapproach to thet reatmentof
4,
6
Thesesyndromesmayoccuri nupt o10–15% (2 theneoplasms.
–20% accordi ngt oseveralreport s)ofmal ignanci es,and
theymaybet heÞrstormostpromi nentmani fest ation. INCIDENCE
However,t hisi nci dencecoul dbeunderest imat ed.The
real i nci dence of deat hs and compl icat ions related Thei ncidenceofPNSvari eswiththeneurol ogi cal
to paraneopl ast i
c syndromes i s unknown. No race syndromeandwit hthet umor .PNS canoccursin7 to
7
predi lect ioni sreport ed.Nosexpredi l
ect i
oni sknown. 10% ofallpat ientswi th cancer . Approxi mat ely 10%
Peopl eofal lagesmaybeaffect edbycancersandt heir of patients wit h plasma celldi sorders accompanied
3
related paraneopl ast icsyndromes. Itisest i
mat ed that by malignantmonocl onalgammopat hiesare affect ed
7 – 10% ofal lpat ientswi t
h cancerwi llpresentwi th by a paraneoplasti c peri pheral neuropathy. M ore
signsand sympt omsofa paraneopl asti c condi tion at than halfofthe pati ents wit h the rare ost eoscleroti c
thet imeoft umordi agnosi s,althoughasmanyas50% form of myeloma devel op a severe predomi nant ly
oft hese i ndi vidual s may experi ence such a di sorder motorparaneopl astic peripheralneuropat hy.In ot her
atsome poi ntduri ng t hei ri ll
ness.The sympt omat ic hematologi calmal ignanci es,the i ncidence ofPNS i s
mani fest ations of paraneopl ast ic syndromes may very low,wit h the exception of Hodgkin’ s disease.
pose t he mostt roubl esome and t hreat eni ng cl inical However,the inci dence of PNS even i n Hodgkin’ s
probl emst hatpat i ent swi thcancerface.Di agnosisand disease iswel lbelow 1%.In solid tumors,t he more
treatmentofparaneopl ast ic condi ti onscan,t herefore, commonneurol ogicalsyndromesaremyastheni agravi s,
cont ribut et oani mprovedqual ifyofl i
fe,andi nsome whi choccursi n15% ofpatientswit hat hymoma,and
5
cases, prol ongl ife. LEM S,whi ch affects3% ofpat ient swi th SCLC.For
8
Thei mport anceoft heparaneopl ast icsyndromes othersolidt umors,thei nci denceofPNSi s< 1%.
(includi ng hormones det ect ed by i mmunoassay)and Nearl y 90% ofpati entshave associat ed cancer
theel uci dat ion oft hei rmechani smsarei mport antfor thatissmallcel llungcanceri nnearlyal lcases.Inour
many reasons.Thei rappearancemay bet heÞrstsign series,10 of11 pat ients had smallcelllung cancer .
ofamal ignancy,whi ch al lowsi tsearl y det ection i na Al t
hough theanti -Hu syndromehasararepreval ence
curabl e st ate.They may si mul ate met ast ati
c disease (probably<1 % ofpat ientswit hsmallcelllungcancer,
and prevent pat i ent s from havi ng curat ive t herapy. theknowledgeoft heexist enceofthisentit y and how
Conversel y, t reat abl e compl i
cat ions of mal ignancy itpresentsshoul d be rel evantt o radiologi stsbecause
(e.g., met astat icdi sease,i nfect i
on)maybeascri bedtoa such knowledge wi l
ldi rectt he i nvestigation t oward
paraneopl ast icsyndrome,l eadingt ot hewi thhol di ngof the search fora speci Þc cancer-namel y,lung cancer .
appropri atet herapy.Theycanbeusedast umormarkers Approximately 16% ofpat ientswi th smallcel ll ung
inprevi ousl yt reat edpat i ent st odet ectearl yrecurrence cancerandnoneurol ogicdysfunctionhaveadet ect abl e
ori n pat ient s undergoi ng adj uvantt herapy t o gui de level of ant i-Hu ant ibody in t heir sera. However,

62 JPenyDal
am, Vol
ume 12Nomor1Januari2011
thisl evel is signi Þcant
ly l ower t han i n pat ients these ant ibodies.In t he fut ure,physici ans who deal
who have smal lcel llung cancerand paraneopl astic with cancer-associ at ed syndromes shoul d be abl et o
neurologicdysfunct ion.Insomepat ientswi thanti -Hu different iate the paraneopl astic syndromes and the
“paraneoplastic” syndrome,no t umori s det
ected,as beni gndisorderst hatmimicparaneopl asti csyndromes.
wast hecaseforni ne(13%)of71 pat ientsi nthestudy Recentadvancedt houghtthatmostorallparaneopl astic
9
byDal mau,etal . andforonepat ientofourseri es. neurologic di sorders are i mmune-medi ated. The
The frequency of neurol ogi cal paraneopl astic mechanism ent ailsectopi cexpressi onbyat umorofan
syndromes i s somet hing less than 0. 5 per 100 000 ant igen t hatnormal ly isexpressed excl usively i nt he
population peryear .Overt hel ast10 years,therehas nervoussystem.Some oft hese so cal led onconeural
beenincreasingunderstandingof theirimmunological ant igensareal soexpressedi nthenormalt estis,anorgan
mechani smsand many new ant igens/ anti
bodi eshave thatis,li ke the brai n,an immunologi cal ly privi leged
beendescribed.Iti sli
kelyt hatthenextfew yearswil l site.Thet umorant igenisident icaltot heneuralant igen,
seethedescri pti
onofevenmoreandsot henumberof butforunknownreasonstheimmunesyst em i denti Þes
10
‘anti
bodynegat i
ve’caseswi llcontinuet oshrink. itasforei gnandmount sanimmuneat tack.Thei mmune
attack control sthegrowth oft hecancerand may i na
PATHOPHYSIOLOGY few inst ancesobli teratei t.However,t heanti bodi esand
cyt otoxicT cell sthatarespeci Þcfort het umoranti gen
The rel ationshi ps bet ween mal ignancies and arenotsufÞci enttocausetheneurol ogicdiseaseunl ess
otherdi seasesarecompl ex and i ntrigui ng.Asal ready theycrossthebloodbrai nbarrierandreactwithneurons
1
reported,a paraneopl ast i
c syndrome may resultfrom expressi ng theonconeuralantigen. Thisprocesst hen
product ionandrel easeofant ibodiesandphysi ologi cally setsup an inßammat ory responsei nt heneuralt issue.
activesubst ances,ori tmaybei diopat hi c.Infact,any Inmostcasestheact uali mmunopathogenicmechanism
tumormay produce hormones and prot ein hormone isuncertai n becausepassi vet ransferoftheant ibodi es
precursors,oravari et
yofenzymesandfetalprotei ns, toani mal sdoesnotreproducethecl inicalsyndrome,or
10
orcyt okines.M orerarel y,thet umormayi nterferewi th thepat hol ogy.
normal met abol i
c pat hways or st eroid met abolism. The discovery of paraneoplast ic ant ineuronal
Severalcancers al so produce fet alprot eins t hatare aut oant ibodiesresult edi nt hegeneralbel iefthatt hese
physi ologically expressed i n embryoni c cel ls during are i mmune-mediat ed di sorderstri ggered by aberrant
fetallifebutnotexpressedbynormaladul tcel ls.These expressi on of onconeural anti gens i n t he t umor .
substancesmay hel pl aborat oriesdet ectmal ignanci es Supportfort hishypothesi scomesfrom thefactthatt he
and usual ly are used as t umor markers (e. g., targetparaneoplast icant igensareexpressedbot hi nt he
Carci noembryoni c Ant igen [CEA],al pha-fet oprotein tumorandi nt heaffectedpartsofthenervoussyst em.
3
[AFP],cancerant igens[CA 19. 9]). Furthermore,t hetumorsareusual lysmallandheavi ly
Current ly,themechani smsofhow cancersaffect inÞl trated wit hi nßammat ory cel ls,and spont aneous
distantsitesarenotunderst oodpreci sely.W henat umor remissi onsatt het i
meofneurologi calpresentat ionhave
arises,thebody may produceant ibodi est o Þghtitby beendescri bed.TheseÞndi ngssuggestthatsomePNS
binding t o and dest royi ng tumorcel ls.Unfortunat ely, withoutani denti Þabl etumormayresultfrom i mmune-
in some cases, t hese ant ibodies cross-react wit h mediat ed eradicati on of t he t umor .In keepi ng wi th
normalt issuesanddest royt hem,whi chmaysti mul ate thishypothesis,onest udy found morel imit ed di sease
the onsetof paraneopl astic disorders.However,not distri bution and bett er oncologi c outcome in Small
all paraneopl astic syndromes are associ ated wit h Cel lLungCancer(SCLC)pati entswi thparaneopl astic
Paraneoplasti
cSyndromes 63
Ketut Suega
autoant ibodi es. Al thought heparaneopl ast i
cant i
bodi es and cytot oxic T-cel l responses are al so i nvol ved.
are synt hesi zed i ntrathecal ly,a pat hogeni c role coul d In t his pati ent, ident i
Þcat ion of any of the a
onl ybeprovedfort hoseparaneopl ast icaut oant i
bodi es known ant ibodi es would conÞrm t he di agnosi sofa
that are di rect ed agai nst easi l
y accessi bl e ant igens paraneoplasti c syndrome;depending on t he ant ibody
locat ed att hecel lsurface.Exampl esofsuch ant igens identi Þed, thi s Þndi ng would also directt hesearch
are t he acet yl chol i
ne recept or (ant i-AChR muscle fort he tumor .In approxi mat el y 40% ofpat ient s,no
12
type i n myast heni a gravi s and neuronal gangli onic anti bodi esareidenti Þed.
type i n aut onomi c neuropat hy), P/ Q-t ype volt age- At otal ly di fferentmechani sm seems atwork
gated cal ci um channel s (ant i-VGCC i n Lambert- in PCD i n Hodgki n’ s lymphoma because t he t arget
Eat on M yast heni c Syndrome [LEM S]),vol tagegated anti gens oft he associat ed anti -Trand ant imGluR1
pot assi um channel s (ant i-VGKC i n neuromyot onia), autoantibodi esare notexpressed in Hodgkin’ st umor
andt hemet abot ropi cglut amat erecept ormGl uR1 (anti - tissue. Dysregulat ion of the immune system i n
mGl uR1 i n paraneopl ast ic cerebel lar degenerat ion Hodgki n’slymphomaandanet iologicrol efor(vi ral?)
8
[PCD]).M ostparaneopl astic ant igens are l ocat ed i n infecti onshavebeenpost ulat edi nthisdi sorder .
the cyt oplasm (e. g. ,theYo ant igen)ornucl eus(e. g., A const ellati on of symptoms is deÞned as a
theHuandRiant igens),andapat hogeni crol efort he paraneopl ast icsyndromewheni tisassoci at edwi tht he
respect iveant ibodi eshasnotbedemonst rated Inthese presence ofactively growing t umort hatelaborat esa
disorders,i ndi rectl inesofevi dencesupportt heview factori nexcessintocirculation,whi ch,uponremoval
thatt hecel l ulari mmuneresponseagai nstt heseant igens byt umorresecti on,result si nt heal leviationofsyst emi c
isresponsi bl efort heneurol ogicaldamage.Therel ative sympt oms. By deÞni tion, such a fact or should be
cont ribut ion oft hecel lularand humorali mmuni ty to overexpressedint umorcel lsi nvi voandorproducedby
the cl i
ni caland pat hologi calmani festat ions has not tumorcel lsi nvi tro.M anyoft hesefact orsareprot eins
been resol ved Theparaneopl ast i
cant i
bodiesmay,in thatarenormallysecretedt oactlocal lyi naparacri ne
these cases,be surrogat e markers forT-l ymphocyt e fashion.However,when markedly overproduced by
8
activat ion. tumorcell s,theyent ert hecirculat ionandactonti ssue
5
The mechani sm by whi ch T cel ls recognize di stantfrom theproduct ionsi te.
antigens expressed i n neurons (whi ch i n normal Hemat ologic abnormal ities as PNS i nclude
circumst ances l ack expressi on of t he anti gen eryt hrocyt osis, anemia, neut rophili a, neutropeni a,
present ing mol ecul es of maj or hi stocompat ibi li
ty eosi nophili a, t hrombocyt osi s, t hrombocyt openi a,
compl ex cl assesIand II)i sunknown.Iti spossi ble venous thromboembol ism and Disseminat ed
thatt hesei nßammat ory inÞl tratesarenott hepri mary Intravascul arCoagul ation (DIC).Theseabnormal i t
ies
causesoft he neuronaldamage buta consequence of are,byandl arge,duet ot heproduct ionofbiol ogi cal ly
theant ineuralant ibodyt hatcausesneuraldysfunct ion. act ivegrowt hfactors,hormonesorasyetunidenti Þed
Becauseneuronaldysfunct ioncanresul ti nexpressi on “humors” by the tumor . As our understandi ng of
of maj or hi stocompat i
bi lity compl ex mol ecules,t he growthfact orscont roll i
nghematopoiesi shasi ncreased
T-cel li nÞl trates woul d be “second hi t“ resul t
ing i n inrecentyears,thebi ologi cbasi sofhemat ologicPNS
neuronal l oss.To dat e,however,an ani mal model are betterunderst ood.Forinstance,t umor-associat ed
isl acki ng. Immuni zati
on of ani mal s wi th puri Þed neut rophiliai s now known to be caused by t he
recombi nantHuD fusi on prot ei n has notreproduced production ofG-CSF by t he t umor .The mechani sm
10,
11
thedi sease. Ant i
bodi esappeart o benecessary but by whi ch t umorcauses thromboemboli sm have al so
notsufÞci ental one t o cause neurol ogi c dysfunction, been extensi vely invest igat ed. Cancer cells i nduce

64 JPenyDal
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plateletaggregat ion bot hin vi tro and in vivo.Plat elet DIAGNOSISAND UNDERLYING CAUSES
aggregat ing mat erialhas been i solated and part ially
charact erized from t umorcel ls.The i nvol vementof The causes of t he paraneoplasti c syndromes
platelet gl ycoprot ein II b/ IIIa int he tumor-pl atel et associatedwit hunderlyi ngcancersarenotwel lknown.
interact ionhasal sobeenshown.M al i
gnantcel l
scontai n Onlyafew casesclearl ydemonst rateanet iologi cand
a uni que procoagul ant ,cancer procoagul antA,t hat a pathogeneti c factor.Currentevidence suggest sthat
directlyact ivatesfactorX.Toget herwi thtissuefactor, mostparaneoplast ic syndromes are t he resultoft he
thisprocoagul antappearst ohavebeencont ributetoa way in whi ch ouri mmunesyst emsrespond to cancer .
highi nci denceoft hromboembol ism i ncancerpat ient s. According to thi shypot hesis,the processst artswi th
Bet terunderst andingofhemat ologicPNS i simport ant proteins normal ly presentonly in nerve cel ls.These
13,14
forcl inicalcareoft hepat ient swi thcancer . proteins are also found, for unknown reasons, i n
Increased comprehensi on of t he molecul ar somecancers.Innervecell st heprotei nsareprobabl y
mechani smsofparaneopl astic syndromeswi llpermit essenti alforgrowthandmai ntenance,sot heymayal so
earlier di agnoses of cancer and al so be useful for beessenti alforthosecancers’growth.W henaperson’ s
followi ngt heresponset oant i
neopl astictherapy,usi ng immunesystem sensesatumorgrowingi nthebody,i t
cancerproduct sast umormarkersoft he progressi on can respond by ident ifying those cancerouscell sand
orremi ssion ofdi sease.Ason Þgurebel ow proposed thecruci alprotein orprotei nswithi n them asforei gn,
pathogenesi s of paraneopl ast ic neurol ogic di sorders or“nonsel f.”Thei mmunesystem t husrespondswi th
isdepi cted.A t umornoti nvol vingt henervoussyst em anat tackoneachprotei nandallthecel lsthatcontai n
expresses a neuronal prot ei nt hat i mmune system it.The i mmune at tack,ifi tisvi gorousenough,can
recogni zed as nonsel f.In t he illustrat
ion,ant ibodi es slow the growt h ofthe t umor,butital so at tacksthe
arereact ing wi th volat e-gated cal cium channel satthe nerve cel lsthatnormall y cont ain the protein(s).Asa
neuromuscul arjunct i
on,causi ng the Lambert -Eatern result,a person can devel op severe nervous syst em
6
myast heni csyndrome. probl ems,such asmemory l oss,lack ofcoordi nat i
on,
and weakness.M eanwhi le,t he growt h oft he cancer
may beslowed so successfully thatitbecomessmall
2
anddi fÞcul ttodetectbyconventi onalmeans.
Cl inicalsyndromesareneverpathognomonicfor
aparaneopl asticetiology,and ahigh index ofcl inical
suspici on is i mportant .Symptoms can be at ypical ,
psychi atric,orevenßuct uati ng,andPNS shoul doften
beint hedifferenti aldiagnosi sofot herwiseunexpl ained
8
neurologicalsyndromes.
Even if i ts causes are not known, fever i s
consi dered to resultfrom t he release ofendogenous
pyrogens (ie, l ymphoki nes or tissue pyrogenes).
Fever al so may be rel ated t o necrot ic-inßammat ory
phenomenaofthetumorand/orto alterat ionsi n li
ver
gure1.ProposedpathogenesisofPNS6
Fi function and consequentdisordersofsteroidogenesi s.
Dysgeusia seems to be related to al terations i nt he

Paraneoplasti
cSyndromes 65
Ketut Suega
body’ sl evelofcopperandzi ncort oamorphofuncti onal Di agnosi ng a neurological syndrome as
variat ion oft het ast ing bodi es(i e,gust at
ivepapi llae). paraneopl ast icrequi restheexcl usi onofotherpossi bl e
Cachexi ai sthoughtt obecausedbybi oactivemol ecules causesby areasonabl y compl eteworkup.Becauseof
produced by t he t umor,such as al pha-l ymphotoxi n the difÞcul tiesi n di agnosi s,an i nternationalpanelof
(TumorNecrosi sFact or[TNF]al pha),pept ides,and neurol ogi st s has establ ished di agnost ic cri teri at hat
nucl eot ides, whi ch are abl et o affect met aboli sm. divide pat ient s wi th a suspect ed PNS into deÞnit e
Such modi Þcat ions i ncl ude i ncrease i n the serum and probabl e categories.These cri teria are based on
level s offat ty aci ds;decrease ofurea,al anine,and the presence or absence of cancer,the presence of
carbondi oxide;andal t
erat ionsofgl ucosemetabol ism. well-characterized anti bodies,and t hetypeofcl inical
8, 15
Cyt oki nes,growt hfact ors,i mmunecompl exsandot her syndrome.
8
activesubst ancesmayormaynotpl ayapart si nother Patientswit hadeÞni tePNSincl udethosewit h:
paraneopl asticsyndromessuchasrenal ,hemat ological (a) A classi cal syndrome (i .
e. , encephalomyel itis,
3,
4
andgast roint est inal . limbi c encephal itis,subacute cerebell ardegenerat ion,
Thebl oodofmany,butnotal l,peopl esufferi ng opsocl onus-myocl onus,subacutesensoryneuronopat hy,
from neurol ogi calparaneopl astic syndromescont ains chroni c gastroint estinal pseudo-obstructi on, LEM S,
antibodi es t hat t he i mmune syst em has produced ordermat omyosi t is)and cancert hatdevel opswi thin
in response t o speci Þc prot eins. The presence of 5 yearsoft he diagnosi softhe neurologi caldi sorder,
such ant ibodi es can t el l physi cians t hat a person’ s regardlessofthepresenceof
neurol ogi cal di sorder i s paraneopl astic; it can also paraneopl ast icanti bodi es.
indicat et he probabl e site oft he cancert hati satthe (b)A noncl assicalsyndromethatobject i
vel yi mproves
2
rootoft het roubl e. orresolves aft ercancertreat ment ,provi ded t hatthe
Al though paraneopl astic syndromes affect i ng syndromeisnotsuscepti bletospontaneousremi ssion
thenervoussyst em cancauseabewi lderingvari etyof (c) A noncl assical syndrome wi th paraneoplast ic
sympt oms,t hey t end t o share cert ai n charact eristics antibodi es (wel l charact eri
zed or not) and cancer
thathel pdoct orsi dent i
fyt hem: thatdevelops wit hin 5 years oft he diagnosi s ofthe
1.The neurol ogi cal si gns and sympt oms usual ly neurol ogi -caldi sorder .
appearrapi dl y-wi thinamat terofdays,weeks,ora (d)A neurol ogicalsyndrome (classi calornot )wi th
few mont hs.Incont rast ,degenerat ivedi seasesl ike well-characterizedparaneopl asticant ibodies(i .
e. ,anti -
Parki nson and Al zhei merdevel op graduall y,over Hu,ant i-Yo,ant i-Ri,anti amphi physin,ant i-CV2,or
years. anti-M a2).
2.Theneurol ogi calsi gnsusual lyprecedet hoseoft he Patientswit hapossibl ePNSincl udet hosewi th:
cancer,whi chi soft enext remel ysmal landdi fÞcul t (a) A cl assical syndrome wi thout paraneoplast i c
todet ect. anti-bodiesand no cancerbutathigh ri sk to havean
3.The neurol ogi cal di sorder usual ly causes severe underl yi ngtumor(e. g. ,smokinghabit).
di sabi l
ity.M anypeopl ewi thcerebel l
ardegenerat ion (b)A neurologicalsyndrome(cl assi calornot)wi t
hout
becomeunabl et o wal k.M any peopl ewit h limbi c cancerbutwit h part i
al ly haract erized paraneoplast i c
encephal i
t i
s cannotfunct ion because t hey cannot antibodi es.
rememberongoi ng event s.W hi let he cancermay (c)A noncl assicalneurol ogicalsyndrome,noparaneo-
st i
llbe rest rict ed t o one corneroft he body,the plastic ant ibodi es,and cancert hatpresents wi thin2
immune response t ot hatcanceri sthorough and yearsoft heneurologi calsyndrome.
syst emat i
c.

66 JPenyDal
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Differenti aldiagnosi s4 ofblood,urine,andCSF.CBC countsmaydemonst rate
Thei mport anceandfrequencyofparaneopl astic anemi a.Thi sanemiamaybetheresul tofanyofseveral
syndromes make i ti mperat
ive t o est ablish the differentt ypes ofcancer,ori tmay be the resultof
appropri atediagnosi s.Ift hecauseoft heparaneoplasti c differentbeni gn conditi ons.A pl ateletcountmustbe
syndrome i s unknown,t his may mean excludi ng all performedinanypat i
entwi thsympt omsofDIC.
other known causes of t he syndrome. In general , Bloodenzymesmaybealt ered,eveninheal t
hy
paraneopl asticsyndromesmustbedi fferent
i at
edfrom: individual sorthosewhohavebenignconditi ons.Tumor
1.Di rect i nvasi on by t he primary t umor or it s markersare very usefulfordiagnosisofcancerst hat
met astases arecli nical ly si
lent ,butmostmarkersarenotspeci Þc
3
2.Obst ructioncausedbyt umorort umorproducts fordetermi ningtheoriginoft hecancer .
3.Vascul arabnormal ities M any pat ient s wit h paraneopl astic di sorders
4.Infect i
ons mayhaveautoant ibodi esagainstseveralt issuesoft he
5.Fl uidandel ectrolyteabnormal i
ties body.Demonst rat ion ofthese autoant ibodi es is very
6.Toxi city of cancer t herapy, incl uding cytotoxic import anttoconÞrm thedi agnosisofaparaneopl astic
chemot herapy,radi at i
on therapy,i mmunotherapy, syndrome and dist ingui sh it from non neopl astic
orant ibiotictherapy. forms.M ostknownaut oanti bodiesaredirect edagai nst
nervous system structures. Detect i
on of a “wel l
-
Laboratori um findi ngs characterized” paraneoplast ic antibody is extremely
Once a paraneopl asti
c di agnosi s has been helpfulbecause i tprovesthe paraneoplasti c etiology
established ori ssuspect ed,rapi d dent iÞcat ion ofthe of the neurologi cal syndrome. The paraneoplast i
c
tumorbecomesessent ialbutmay bedi fÞcul tbecause antibodi esaregenerally divided i nto threecat egori es.
most PNS devel op i nt he earl y st ages of cancer . The wel l-charact erized antibodi es are react ive wi th
The workup general ly st arts with a det ailed hi story, molecularly deÞned onconeural ant igens. These
including smoki ng habi t
s,wei ghtl oss,ni ghtsweat s, antibodi esarest ronglyassociatedwi thcancerandhave
and fever .A t horough physi calexami nat ion should been detect ed unambiguously by severallaborat ories
includepal pat i
onforpat hologicall ymphnodes,rectal in a reasonable numberofpati entswith well -deÞned
and pel vi c exami nati
on,and pal pat i
on ofbreast sand neurological syndromes.The part ially characteri zed
testis.Oft en,t het umori sdet ected by hi gh-resol ution antibodies are those wi th an uni denti Þed target
Comput ed Tomography (CT)oft he chest ,abdomen, antigen and t hose t hathave eit herbeen descri bed by
andpel vis.IftheCTscanremai nsnegat ive,whol e-body asi nglegroup ofi nvestigatorsorhavebeen report ed
Fluorodeoxygl ucose Posi tron Emi ssion Tomography in onl y a few pati ents. The thi rd group consi sts of
(FDG-PET)orPET/ CT i srecommended t o det ectan antibodiest hatare associat ed with speci Þc disorders
occul ttumorori tsmet ast ases.Inaddi t
ion,t het ypeof butdo notdifferenti ate between paraneoplast ic and
8
antibody and PNS may suggesta speci Þc underl ying nonparaneopl asticcases.
tumor and i ndicate furt her diagnost ict ests,such as
mammography(mayberepl acedbyM RI)orul t
rasound Imagi ngstudies
oft het estesorpel vi
s.W henal ltestsremai nnegative, Any possibl
e imaging study may be usefulto
repeateval uat i
on at3 t o 6 mont hi nterval sfor2 – 3 detecttheprimarytumorinpat ientswithparaneopl
asti
c
8
yearsi srecommended. disorders. CT scanning and magnet i
c resonance
Pat i
ent swi t
hasuspect edparaneopl asti cdisorder imagi ng ofthewhol ebody allow detect
ion ofthesit
e
shoul d recei veacompl etepanelofl aborat ory studies andtheext ensionoft heunderlyingprimaryt umorand
Paraneoplasti
cSyndromes 67
Ketut Suega
Tabel1.Ant
ibodies,clinicalsyndromes,associatedtumors8

itsmet astases,ifpresent .Sci nt

igraphymaybeusefuli n Pathologicalfeatures
patientswi t
h endocri nedi sordersrelated t
o ahormone- Anotherfactorcompli cati
ng ourunderst anding
produci ngt umor .Posi tronEmi ssionTomography(PET) of t he neuronal degenerati on i n paraneopl astic
and Si ngle Phot on Emi ssion Comput ed Tomography neurol ogi
c disordersisthe factt hatthe pathological
(SPECT)scanni ngmaybeperformedt oeval uatepat ient s featuresoft hesedisordersvary widely.Forexampl e,
wi th neurol ogic di sorders.These exami nat i
ons al l ow inparaneopl asticcerebellardegenerati
on,therei stotal
differentiat
ion ofparaneopl ast
ic and nonparaneopl ast ic lossoft hePurkinjecellsofthecerebellum,wi t
hl i
ttl
eor
3,
8,16,17
neurol ogicdi sorder . Endoscopy i susefult o det ect nopathol ogicalchangeelsewherei nthenervoussyst em
tumorsoft herespi ratoryt reeandoft hedigestivetract,and and no i dentiÞable inßammat ory inÞlt
rates wi thi
n
3
italsoal lowst heexami nert oobt ainbiopsysampl es. the cerebellum itself.By cont rast,in paraneoplastic

68 JPenyDal
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encephal omyel i
tis, there i s not onl ywidespread Rheumat ologic18
destructionofneurons,i ncl udingPurkinj
ecells,butal so o Paraneopl astic arthropathies ari se as rheumat ic
ßoridi nßammat i
on wi thi nthecentralnervoussyst em polyarthri tisorpolymyalgi a,part i
cul arl
yinpati ents
and i ntraneuronal deposi t
s of antibodies. In some with myel omas; lymphomas; acute l eukemi a;
pati
ent s wi t
h paraneopl asti
c syndromes,part icularly malignanthist iocytosis;and tumors ofthe colon,
opsocl onus–myocl onus,aut opsy may demonstrate an pancreas,prost ate,andCNS.
enti
relynormalbrai 1,
n. 16 o W ith lung cancers,pleuralmesothelioma,phreni c
neurilemmoma,and hypert rophicosteoart hropat hy
CLINICAL SYNDROM ES maybeobservedinasmanyas95% ofcases.
o In some cases, t he t umor can be preceded
Because of t heir compl exity and variety, by scleroderma, wi th i ts pecul i
ar cl inical
the cl ini cal pi ctures of t hese syndromes may vary manifest ati ons.
greatly. Paraneopl ast ic syndromes may or may o The wi despread form i s typicalof mali gnanci es
notbe charact eristi c of a speci Þc syst em.Usuall y, ofthe breast,ut erus,and lung (both alveol arand
bronchialforms).
the paraneopl astic syndromes are di vided int o the
o Ontheotherhand,thelocal izedform i scharact eristic
followi ng cat egori es:(1)mi scellaneous(nonspeci Þc),
ofcarcinoi dsand oflung t umors(bronchoal veol ar
(2)rheumat ol ogi c,(3)renal ,(4)gast rointest inal,(5)
forms).
hemat ol ogic,(6) cut aneous,(7) endocri ne,and (8)
o Pati ents wi th lymphomas orcancers oft he l ung,
neuromuscul ar .
breast, or gonads may have syst emic lupus
A compl ete hi story and physi calexaminat ion
erythemat osus(SLE).
can suggestneopl asi a.Personswi th a fami ly history
o Pati ents with myel oma, renal carcinoma, and
ofmal i gnanci es(eg,breast ,colon)maybeati ncreased
lymphomas may present , although rarel y, wi th
risk and shoul d be screened forcancer .Nonspeci Þc
secondary amyl oidosi s of the connective t issues
syndromescan precede t he clinicalmani festationsof Hypert rophicosteoart hropat hypresentswi thdi gital
thet umor,andt hisoccurrencei sanegat i
veprognost ic clubbingandpainfulswell ingofthehi p,wri st ,and
3
factor. knee,accompani edbyanart i culareffusion.
Mi scel laneous(nonspeci Þc)3 o Somet imes,the long bones also are i nvol ved.In
o Fever, dysgeusi a, anorexi a, and cachexi a are suchcases,pati entscompl ai nofpainandpresenta
incl udedi nt hiscat egory. typi calel evati on(t hickeninganddet achment )oft he
o Fever frequent lyi s associated wi thl ymphomas, periost eum onX-ray.
acut el eukemi as,sarcomas,renalcel lcarcinomas o For pat ient s wi t
h scl eroderma or systemi cl upus
(Grawi tz t umors), and di gestive mal ignanci es erythemat osus (SLE), the clini cal pict ure is
(incl udingt hel iver). charact eri sticofnonparaneoplast i
cconditi ons.
o General ly,feveroccursi nt heeveni ng and isofa Renal19,
20

cont inual -remi ttentt ype. o Pati entswit htumorst hatsecret eAdrenocort icot ropic
o Dysgeusi a mani festsi n a vari ety of ways,from Hormone (ACTH) or ACTH-l ike subst ances
ageusi at o aversi on t o protein (in part i
cular,meat may have hypokalemic nephropathy, whi ch i s
prot eins). charact eri zedbyuri narypot assium l eakageofmore
o Anorexi ai sacommondi sorderamongpat ientswit h than 20 mEq per24 hours.Thisoccursi n 50% of
neopl ast
icsyndromesandi sresponsi ble,al ongwi th indi vidual s wit h ACTH-secret ing t umors of t he
dysgeusi a,forwei ghtl ossandevencachexi a. lung(i e,smal lcelll ungcancer).
Paraneoplasti
cSyndromes 69
Ketut Suega
o Ot her t ypes of t umors t hatcan produce ACTH, ofphenomena:(1)mi grat ingt hrombophlebi tist hat
ant idi uret ichormone(ADH),andguthormonesmay is resistantto standard ant icoagulanttherapy and
causehypokal emi a,hyponat remi aorhypernatremi a, involvesthearm vei ns,thei nferiorvenacava,andt he
hyperphosphoremi a,andal kal osisoraci dosi s jugularveinsandusuallyappearsasovalformat ions
o Nephrot icsyndromei sobserved,al t houghseldom, along thel ittleand mi ddl eveins,accompani ed by
in pat ient s who have Hodgki nl ymphoma (HL); cutaneousnecrosi sand (2)marantic(nonbact erial)
non-Hodgki n l ymphoma (NHL); l eukemi as; endocardi tis charact erized by growt hs devel opi ng
mel anomas;ormal ignanci esofl ung,t hyroid,colon, on theheartval vest hatmay break and form clot s
breast ,ovary,orpancreat ichead. andemboli.
o Pat ient s wi th myel oma, renal carci noma, or o In some cases,symptoms resul tfrom migrat ing
lymphomas present rarel y wi th secondary vascular t hrombosis (i e, Trousseau syndrome)
amyl oidosi s of t he kidneys,heart ,or CNS.The occurringi natl east2 sites.
cl i
ni calpi ctureofsecondaryamyl oidosi si srel ated o Leukemoi dreacti ons,characterizedbyt hepresence
torenalandcardi acinjuries. ofimmat ureW BCsi nt hebloodstream,usual lyare
o Co-exi st enceofsubacut et hyroi dit i
sand renalcel l accompanied by hypereosinophi lia and i tchi ng.
carci nomaasaPNS. These react ionst ypical ly are observed i n pat ient s
20
Gastroint est inal wi th lymphomas or cancers of the lung,breast,
o Wat ery di arrhea accompani ed by an el ectrolyte orstomach.Pat ient s wi th lung cancerorpl eural
imbal ance l eads t o ast heni a, confusi on, and mesothel iomamayhavecryogl obul inemia.
exhaust ion. Cutaneous23
o These probl ems are t ypical of pat ients wi th o Itchingi sthemostfrequentcutaneousmani fest ation
proct osi gmoi dt umors(bot hbeni gnandmal ignant) inpatientswi thcancer .
and ofmedul l
ary thyroi d carci nomas(M TCs)that o Herpes zoster, icht hyosi s, ßushes, al opeci a, or
produce several prost agl andi ns (PGs; especial ly hypert richosisalsomaybeobserved.Herpeszost er
PG E2 and F2) t hatl ead t o mal absorpti on and, and alopeci apresent ing aspartofaparaneopl astic
consequent l
y,unavai labilityofnut rient s. syndrome are si mi lar t o their equi valentbenign
o These al terat ionsal so can be observed i n pat ient s forms.
wi thmel anomas,myel omas,ovari ant umors,pi neal o Acant hosis ni gricans and dermic mel anosi s are
bodyt umors,andl ungmet astases. characterized by a blacki sh pi gment ati on of t he
Hemat ol ogi c21 skin and usuall y occurin pat i
entswi th met ast atic
o Sympt oms rel ated t o eryt hrocyt osi s or anemia, mel anomas or pancreati c tumors. Acant hosi s
thrombocyt osis, di ssemi nated intravascul ar nigricans and dermic melanosi s oft en are
coagul at ion (DIC),and l eukemoi d react i
ons may pathognomoni c fort he presence ofa mal ignancy.
resul t from many t ypes of cancers. The most They are si milar butdiffer by l ocat ion.Dermi c
promi nentcl inicalpictureofparaneopl asticdi sorders mel anosi si s diffuse;acant hosis nigri cans usual ly
affect ing t he hemat opoi etic syst em i ssi mi lart oa isaccompani edbyconßuentpapil l
omasandaffect s
cl i
ni calpi cturet hati snotrel atedt ot umors. the oral,umbili cal,axi llary,and inguinal areas.
o Thrombocyt osi s (> 500, 000 pl atelet s per dl) can Three typesofacant hosi snigri cansare descri bed
be observed i n pat ients wi th canceroft he l ung, benign, pseudoacanthosis, and mal ignant . The
breast ,di gest ive organs,or reproduct i
ve organs. mal ignantform i scharacterizedbyrapi dgrowthof
Thi st hrombocyt osisleadst ot hefol lowi ng2 t ypes hyperkerat oticwart s(Leser-Trél atsign).

70 JPenyDal
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o Flushesappeart hatare si mi lart ot hose rel ated to o Hyponat remia and hypercal cemia may occur i n
beni gncondi ti
onssuchasst ress. patientswi t
h tumorsthatare produci ng hormones
o Hypert richosi sisnotdi fferentfrom t heform i tt akes thataffectwaterand el ectrol yticbal ance(i e,ADH
when rel ated t o an endocri ne i mbal ance (usual ly andParat hyroidHormone[PTH]-l ikemol ecules).
related t o adrenal dysfunct ion). Paraneoplast ic o Hypogl ycemi a seems relat ed t o producti on of
hypert richosi s i s charact eri zed by a sudden Insulinl ikeGrowthFactor(IGF)-1 andIGF-2.
appearanceofwool y hai ron t hefaceand earsthat o Product ion of bet a HCG by spermat ic cord
suddenl ydi sappearsaft ert het umori sremoved. leiomyosarcomaasaPNS.
o Ichthyosi s,whi chi nt heearl yst agescoul dmi mi ca Neuromuscul ar(paraneopl asticneurol ogicdi sorders)25
beni gndermat osis,ischaract eri zedbydesquamati on o Oneormoreneurologicalparaneopl asti csyndromes
oft he ext ensory surface oft he l imbs (resembl es may be presenti n pat ientswi th cancer,especial ly
thescalesofaÞsh,i n anci entGreek i chtusmeans thosesufferi ng from l ung cancer .Each partoft he
Þsh)22 nervoussyst em canbeaffected,withsensory,mot or,
o Pat i
ent s wi th glucagonoma may have necrot izi ng ormi xedneuropat hies.
mi grat ing eryt hema (NM E) resul ti
ng from o Sensory neuropat hy,usual l
y relat ed to l ung cancer
erythemat ous and exfol iative i njuries t hat di ffer only,ori ginatesfrom gangli oni cdegenerat ion,and
from exfol iat
ive eryt hrodermi a.Thi si st ypi calof itsonseti scharact eri zedbyparest hesiasandt abetic-
leukemi asand l ymphomasand resul tsi n bl ushing like pain,acut e hyporeßexi a wi th a reduct ion of
anddi ffuseski ndesquamat iont hataffect scut aneous propriocept ive sensi tivit
y and at axia (bot h static
adnexa,whi chsubsequent l
yresul tsi nal opeci aand and dynamic), vibratory anesthesi a, deafness,
nailfragi lity butwhi ch rarel yi saccompanied by cutaneous hypoest hesia or anest hesia,dysgeusi a,
fever,chi lls,andi tching. anddysosmi a.
o Pat i
ent wi th CLL present ing pemphi gus o M ixedneuropat hyappearswi thseveralmal ignancies
paraneopl ast i
cast hei ni t
ialpresent ati
on. and has an ext remely variable present ation,wi th
Endocrine24 motororsensory symptoms eitherprecedi ng the
o Endocri ne sympt oms rel at ed t o paraneoplast ic clinicalonsetoft umordiseaseoraccompanyi ngi t
.
syndromes usual ly resembl et he more common Thespi nalcord can beaffected by eit hersubacut e
endocri ne di sorders (eg, Cushi ng syndrome). necrotic myelit i
s or subacut e myel i
tis. These
Cushi ng syndrome,accompani ed by hypokal emi a, condit ionsl ead to aprogressiveßacci d parapl egi a
very hi gh pl asma ACTH l evel s, and i ncreased with areßexi a, l ack of sphinct eric cont rol, and
serum anduri necort isolconcent rations,i sthemost anest hesiaoft helowerlimbs.ALateralAmyot rophi c
commonexampl eofanendocri nedi sorderl inkedt o Syndrome (LAS)may occur,present ing wit h the
amal i
gnancy.Thi si srelat edt ot heect opicproduct ion typicalmuscul arastheniaandat rophy,hyperreßexi a
of ACTH or ACTH-l ike mol ecul es from many with pyrami dal fasciculat ions, and degenerat ion
tumors(eg,smal lcel lcanceroft hel ung).Pati ents of the second motor neuron.Thi s form of LAS
wi thCushi ngsyndromeaspartofaparaneopl asti c differsfrom t henonparaneoplast icform becausei t
syndrome appearsi mi l
art o pat ient swi th Cushi ng includessensory i nvolvement(i .e.,propri oception
disease,wi tht het ypi calmoonfaci esandobesit yof andpall esthesia).
the trunk.Sympt oms caused by human chorioni c o Thecerebellum maybethesit eofsubacut eneuronal
gonadot ropi nanduri narygonadot ropi npept ideare degenerat ion i n patientswi th smal lcellcarcinoma
absent .Gynecomast i
amayoccuri nmal es. orbreastorgynecol ogictumors.Suchdegenerat ion
Paraneoplasti
cSyndromes 71
Ketut Suega
 present scl inicallywi t
hcerebel larat axi a,dysart hria, 4.Cancermaytakeweeksto5 yearst obecomeevi dent
and nyst agmus. Dysphagi a, pal pebral ptosi s, insomepati entswi thposit
iveserum paraneoplastic
deafness,and a posi tive Babi nskisi gn al so may ant ibodies.
occur.Thecerebel lum ofpat i ent swi t
hl ungcancer 5.Di sabilit
yissevereinmostcases.
alsomaybeaffect edbyencephal it
is.Insuchcases, 6.Neurologi calsymptomsandsignsareoccasi onally
thecl ini calpi cturei scharact eri zedbyconvulsions, partially responsivet oimmunul ogical t
reat
ment s,
deliri
um,andal ackofl ong-t erm memory.Inother ort reatmentoft heunderlyingtumour .
patient s, t he pat hol ogi cal process i nvol ves the 7.Earl y i dentiÞcati
on of cancer and subsequent
medul la(i .e.,encephal omyel itis). treat mentmayi mprovesurvi val.
o In some pat i
ent s wi t
hl eukemi as,l ymphomas,or
Table2.Paraneoplasticneurologicalsyndromes8
epithel ial cancers, a rare degenerat ive process
involvi ng t he semi ovalcent er may be observed. Centralnervoussystem
Thi s degenerat ive process i s charact erized by Encephalomyelitis
Limbicencephalitis
convul sions, cerebel l
ar at axi a, progressive
Brainstem encephalitis
dement ia,aphasi a,hemi paresi s,hemi hypoesthesi a,
Subacute cerebellardegeneration
dysphagi a,and nyst agmus.The process develops
Opsoclonus-myoclonus
rapidly,l eadi ngt odeat hwi thi n6 mont hsofonset.
Stiff-personsyndrome
o ELM S may occur i n pat ient s wi thl ymphomas;
Paraneoplasticvisualsyndromes
thymomas; or cancers of t he pancreas, rect um,
Cancer-associatedretinopathy
kidney, breast , prost ate, or ut erus. ELM S may
M elanoma-associatedretinopathy
resolveaft ersurgi calresect ionoft hepri marytumor
Paraneoplasticopticneuropathy
butnotaft erradi otherapyorchemot herapy.Patients M otorneuronsyndromes
wi t
hl ymphomasorcancersoft he l ung,st omach, Subacutemotorneuronopathy
breast,orut erusmay have cl inicalmani festations Othermotorneuronsyndromes
of pol ymyosi t
is and dermat omyosi t i
st hat are Peripheralnervoussystem
charact eri zed by ast heni a,pai n,and progressi ve Subacute sensoryneuronopathy
hypert rophy of proxi malmuscl es affect ing,then Acutesensorimotorneuropath
involvi ng,t he dermi s and t he ski n.Thi sl eads to Chronicsensorimotorneuropathy
violet-col oredrashesoft hefaceandhands. AssociationwithM -proteins
Subacuteautonomicneuropathy
Despi tet heirclinicalvari ety,there are a numberof Paraneoplasticperipheralnervevasculitis
10
general i
zationsaroundt heparaneopl ast
icsyndromes: Neuromuscularjunctionandmuscle
1.Theypresentacut elyorsubacut elywi thprogressi
on Lambert-Eatonmyasthenicsyndrome
overdayst oweeks. M yastheniagravis
2.M ostpat ients are notknown t o have cancer at Neuromyotonia
present ati
on but ,ift hey are,the cancerisusual ly Dermatomyositis
ratherl imitedinext ent. Acutenecrotizingmyopathy
3.The cl inicalpresent ation and the ident
iÞcation of Cachecticmyopathy
serum ant ibodieshel ppredi ctthelikelytumoursit e
*Classical paraneoplastic neurological syndromes are i
n
int hemaj ori
tyofcases. italics.

72 JPenyDal
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 TREATM ENT associated PCD and anti
amphi physin-associated stiff-
person syndrome. Immunot herapy modal iti
es t hat
Treat mentvari eswi tht he type and l ocation of are recommended fort hese disordersi ncl
ude plasma
the paraneopl ast i
c di sorder . Two t reat ment opt ions exchange, immunoadsorpt ion (extraction of pat ient
1,
8
exist. The Þrst t herapeut ic opt ion i st reat ment of IgG overaprot ei
nA column),st eroids,andi vIg.
the underl ying t umor, based on t he usual surgery,
radiat ion,orchemot herapy(si ngl yori ncombi nati on). PROGNOSIS
Thet herapeut icprot ocol saret hoset hatgeneral ly are
appl i
ed t o neopl ast ic di sorders wi t
houtt he presence Becauseparaneopl asticsyndromesdi fferwidel y
ofparaneopl ast i c syndrome. The second opti on i sthe from i ndividual to indivi dual, prognosi s may vary
treatmentoft hepresumpt iveimmune-medi ateddisorder greatly.Forexample,DIC i ndi catesapoorprognosis,
is based on i mmunosuppressi on (by int ravenous whi lehypertrophi cost eoart hropat hy isoneoft hefew
immunogl obul ins,st eroi ds,orot herimmunosuppressive paraneopl asticsyndromesthatmayimproveapat i
ent ’
s
drugsorbypl asmaexchange). Thi st reat mentshoul dbe prognosi s.Somedi sorders,suchast heLambert –Eaton
reservedforpat i ent swi thclearlyi dent iÞabl eanti bodies myast henicsyndromeand myastheniagravi s,respond
int hei rserum. Thesurgi calprocedurest hatusual lyare wel l to i mmunosuppression and subsequent ly t o
appl i
edt oneopl ast i
cdi sordersal soareappl iedtothose treat mentoftheunderl yingtumor 3
.
wi thparaneopl ast icsyndrome.Ont heot herhand,some The peri pheral neuropat hy associ ated wi th
paraneopl ast i
cdi sordersmaydi sappearrapi dlywit hout osteosclerotic myel oma general l
y resol ves when t he
surgery on t he pri mary t umor(e. g.,i n pat ients wi th tumori streatedwit hradi otherapy.A few di sorders,such
hypert rophi c ost eoart hropat hy,resect ion oft he tumor as opsocl onus-myocl onus i n adul ts,may respond t o
ort hei psi lateralvagusnervel eadst o rapi d remi ssion treatmentoft heunderlyingt umor,i mmunosuppressi on,
1,3
ofsympt oms).
orbot h,ort hey may resol ve spont aneousl y.In many
Unfort unat ely,mostparaneopl ast ic syndromes
inst ances,itis notclear whether t he paraneopl astic
do notrespond t ot reat mentofei thert het umororthe
syndrome resolves spont aneousl y or i n response t o
immunesyst em.A person wi th such acondi tion may
treatment. Disorders i nvolving the cent ral nervous
remai n subst ant i
al l
y di sabled even when t he tumor
syst em, such as encephalomyeli tis associat ed wit h
thatcreat ed t he probl em hasbeen t reat ed effect ivel y.
cancer or paraneoplast ic cerebell ar degenerat ion,
The paraneopl ast ic syndrome may have brought
usual ly respond poorl yt o treat ment ,alt hough t hey
thatcancert ol ightand al l
owed earl yt reatmentofi t,
may stabi lize when t he underl ying tumori streated.
butt he neurol ogi calprobl em i t
sel fremai ns,and t he
Pat ientswi thparaneopl asticsyndromesappeart ohave
person mustusual lyl earn t o dealwi thi tasachronic
condi t ion.2 a bet terprognosi swit h respectto t he tumorthan do
Despi tet he i mmunol ogi cal et iology of most pati entswit ht hesametypeoft umorwhodonothave
oft he PNS,t he resul tsofmmunot herapy have been paraneopl asticsyndromes.Thereasonforthedi fferent
disappoi nt ing. Except ions are t he neurol ogi cal prognoses probabl y has to do wit h the underl ying
syndromes associ ated wi th paraneopl ast i
c ant ibodi es pathol ogi cfeatures.
thataredi rect edagai nstant i
genst hatarel ocat edatthe The Lambert-Eat on myastheni c syndrome and
surfaceoft hecel l(i .
e. ,ant i
genst hatareaccessibl et o myastheni a gravisare diseasesofthe neuromuscul ar
circul atingant i bodi es).Thesei ncl udenotonl ydi sorders junct ion,whichcanrecoveri tsfunctiononcet hecausal
oft heperi pheralnervoussyst em (LEM S,myast henia insul thasresol ved,becauset hereisnol ossoftheparent
gravi s, and neuromyot onia) but al so ant i-mGl uR1- neuron.Di sorders such as paraneopl astic cerebellar

Paraneoplasti
cSyndromes 73
Ketut Suega
degenerat ionareusual l
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