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Gestationaltrophoblastic disease (GTD) encompasses a largegroup of neoplastic diseases arising fromtrophoblastic tissue. The most common diseases arethe following:
1 Hydatidiform mole-omplete and !ncomplete
mole" !n#asi#e mole (horioadenoma destruens)$ horiocarcinoma% &pithelioid trophoblastic tumor' lacental site trophoblastic tumor
!n addition there are some proliferations of
trophoblastic tissue which are benign but mayhistologically mimic disease.
*iscellaneous trophoblastic lesions:&+aggerated placental sitelacental site nodule or pla,ue
Patients with molar pregancy, the mostcommon form of GTD, may present withvaginal bleeding and excessive uterine
enlargement for gestational age, usuallybetween 11-2 wee!s of pregnancy" Pregnancy induced hypertension may occur in 1#$ of patients" %ther presenting signs includehyperthyroidism and hyperemesis gravidarum"&haracteristically, the serum '&G is elevated"
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(n ultrasound of the uterus reveals acharacteristic snowstorm pattern, representingthe hydropic chorionic villi which characteri)esthe disease" (fter evacuation of the uterus,
careful clinical followup with serialmeasurements of the serum '&G is necessaryto ensure there is no recurrence and all of thedisease has been removed"
The clinical presentations of the other forms of GTD are covered in the following discussionand tables"
OUTLINE
Epidemiology
Disease
Associations
Pathogenesis
Gross Appearanceand ClinicalVariants
Histopathologicaleat!res andVariants
La"oratory#$adiologic#OtherDiagnostic Testing
Di%erentialDiagnosis
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Prognosis andTreatment
Commonly Used
Terms
Internet Lin&s
EPIDE'IOLOG(
CHA$ACTE$I)ATION
INCIDENCE
Completemole
11 pregnancies*ost fre,uent form ofmolar pregnancy andGTD
Incompletemole
"'-/%0 of all molarpregnancies
Choriocarcinoma
1" pregnancies
The more abnormal thepregnancy the moreliely this will occur
112 normalgetstations11'$32 abortions1'$$$ ectopic
pregnancies1% molar pregnancies
Epithelioidtropho"lastic
t!mor4ery rare
Placental5arest form of GTD
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sitetropho"lastic
t!mor
AGE $ANGE*'EDIAN
6sually disorders ofreproducti#e age
!ncreased ris of molesat the e+tremes ofreproducti#e age
Completemole
11-"' wees ofpregnancy
Incompletemole7-$%th wees ofpregnancy
In+asi+emole
*ay occursimultaneously withintraca#itary molarpregnancy
GEOG$APH(*Hydatidi,orm
mole
5ate per 1
Indonesia7.7 pregnancies
Tai-an3.$ deli#eries
Philippines'. deli#eries
'e.ico%.2 pregnancies
Nigeria".2 deli#eries
/apan1.7 pregnancies
A!stralia1.% pregnancies
U0A1.1 pregnancies
Israel.3 li#e births
0-eeden.2 pregnancies
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Parag!ay." pregnancies
EPIDE'IOLOGIC
A00OCIATION0
Lo-socioeconomic conditions
Dietossible dietaryde8ciency of carotene
1lood gro!ps
A
horiocarcinoma morefre,uent
9tronger for women oftype and husbands oftype ; and con#erselyfor group ; women andtype husbands
1 or A1
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pregnancyand li+e"irths
!ncreases with anincreased number of li#ebirths
PATHOGENE0I0
CHA$ACTE$I)ATION
CO'PLETE'OLE
%2>> with both >chromosomes androgenicor paternal origin-5esultsfrom duplication of thehaploid sperm in anempty o#um
$-1$0 ha#e normal %2>?but both >?chromosomes arepaternal-5esults fromdispermy fertili@ation of
an empty o#um by twosperm
Hydatidiform moles arepregnanciescharacteri@ed byabnormal de#elopment of
both embryonic ande+traembryonic tissuesand are associated withthe mise+pression ofimprinted genes. The#ast maAority of complete
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hydatidiform moles arediploid and androgeneticwhereas partialhydatidiform moles aretriploid with an e+tra setof chromosomes ofpaternal origin.
INCO'PLETE'OLE
Triploidy (27chromosomes) withmaternal chromosomecomplement
*ost are 27>>? 27>>>and rarely 27>??5esults from fertili@ationof an egg with a haploidset of chromosomes by
either two sperms eachwith a haploid set ofchromosomes or by asingle sperm with adiploid genome of %2 >?(diandric-paternallyderi#ed triploidy)
PLACENTAL
0ITET$OPHO1LA0TIC TU'O$
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lacental sitetrophoblastic tumour(9TT) is a neoplasticproliferation of theimplantationintermediate trophoblast.lthoughclinicopathologicalstudies are notuncommon in casereports or small seriesmolecular and genetic
studies are ,uite limited.
LA1O$ATO$ (#$ADIOLOGIC#OTHE$
CHA$ACTE$I)ATION
I0H
Determination o, DNAploidy "y2!orescence in sit!hy"ridi3atio
!n the past " years thediagnosis of hydatidiformmoles has become morediBcult because of the
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n 4I0H5 inhydatidi,orm moles6E+al!ationo, I0H onisolatedn!clei7
widespread use of earlyuterine e#acuation.Di=erentiating hydropicdegeneration partial andcomplete moles isimportant because oftheir di=erent prognosis.Howe#er clinicaldiagnosis is less ob#iousand the pathologist has toseparate the di=erententities on the basis of
#ery subtle morphologiccriteria.
!n diBcult cases ploidymay be determined by#arious methodsincluding Cuorescence insitu hybridi@ation (!9H)
on routine histologicalsections from paraBn-embedded specimens.Howe#er !9H analysis isoften diBcult because ofthe presence of numeroustruncated nuclei. !n thisconte+t we ha#e tested
the ad#antages of !9H onisolated nuclei a well-nown #ariant of thetechni,ue that might bemore sensiti#e.
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G$O00APPEA$ANCE#CLINICAL
VA$IANT0
CHA$ACTE$I)ATION
Completemole
Hydropic chorionic #illiEarge for dates uterus
Incompletemole
;ften small for datesuterus resembling amissed abortion
4olume of tissue usually
F" ml
4illi are grossly enlargedbut smaller than seen in acomplete moleragments of normalplacenta and a fetus maybe found
In+asi+emole
5e,uires demonstrationof molar #illi in#ading intothe myometrium ordeported to e+trauterinesites
Choriocarcin 6sually presents with
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oma
abnormal uterinebleeding but symptoms of metastases may be the8rst symptom
Dar red hemorrhagicmass with a shaggyirregular surface
Epithelioidtropho"lastic t!mor
9imilar presentation aschoriocarcinoma andin#ades the myometriumin an e+pansile rather
than permeati#e growth
ot associated withcentral necrosis orhemorrhage
&le#ated serum HG
Placentalsitetropho"lastic t!mor
4ariable in si@e but may
present with di=usenodular enlargement ofthe myometrium-occasionally polypoidproAecting into the uterineca#ity
!n#asi#e tumor fre,uentlye+tends into the uterine
serosa and adne+alstructures
0ITE0
1$OADLIGA'ENT
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EpithelioidTropho"lastic n7
TE0TI0
Placentalsitetropho"lasti
c t!mor in alaterec!rrenceo, anonseminomato!sgerm cellt!mor o, thetestis7
lacental sitetrophoblastic tumor(9TT) is a well-de8nedentity in the femalegenital tract. !n the malegenital tract a singlecase of 9TT in the testisof a young boy has beenreported. Despite its #eryrare occurrence 9TT ofthe testis has beenincorporated in the latest
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circumferentialtrophoblastic proliferationaround the #illus
Incomplete
mole
*olar change is focal witha mi+ture of edematous#illi and small relati#elynormal si@ed #illi
entral cisterns are lessconspicuous
9maller #illi with stromal
8brosis
!n#aginations oftrophoblast into the#illous stroma gi#ing ascalloped appearanceappearing as inclusionswithin the stroma
In+asi+emole
*olar #illi withtrophoblast within themyometrium or at ane+trauterine stie
4illi are usually %-' mm indiameter but hydropicchanges are not asmared as in complete
moles
Choriocarcinoma
*asses and sheets oftrophoblastic cells without#illi in#ading thesurrounding tissue and
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permeating #ascularspaces
entral hemorrhage and
necrosis with a rim of#iable tumor
dmi+ture ofintermediate cyto- andsyncytio-trophoblasticcells with considerablenuclear atypia
Epithelioidtropho"lastic t!mor
EpithelioidTropho"lasti
c7A7
Placentalsitetropho"lastic t!mor
bundant e+tracellular
eosinophilic 8brinoid ispresent within the tumor
lood #essel walls aree+tensi#ely replaced bytrophoblastic cells and8brinoid material
&+tensi#e necrosis may
be present
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P$OGNO0I0ANDT$EAT'ENT
CHA$ACTE$I)ATION
Prognosticactors
Completemole
!n more than 20 ofpatients who re,uiredchemotherapy therewere large for dates uteriand o#arian enlargmentsecondary to theca-lutein
cysts
120 de#elop into in#asi#emoles and ".'0 de#elopinto choriocarcinoma
.2-1.'0 of patients areat ris of ha#ing recurrentmolar pregnancies
Incompletemole
'0 will ha#e persistent ormetastatic GTD re,uiringchemotherapy
horiocarcinoma is rare
In+asi+emole
horiocarcinoma occurs2-1+ more fre,uentlythan following a
hydatidiform mole
*etastases may occur in"-%0 of cases
Choriocarcinoma
*etastases especially tobrain and li#er can occur
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in "-20 of patients
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I1on8ned to uterus with 1ris factor
ICon8ned to uterus with "
ris factors
II
Tumor e+tending outsideuterus but limited togenital structures(adne+a #agina broadligament)
IIAo ris factors
II11 ris factor
IIC" ris factors
III Tumor e+tending to lungswith or without nowngenital tract in#ol#ement
IIIAo ris factors
III11 ris factor
IIIC" ris factors
IV ll other metastatic sites
IVAo ris factors
IV11 ris factor
IVC" ris factors
8 (ear0!r+i+al
!n diseases treated withsurgery and combinationchemotherapy:
Disease con8ned touterus-10*etastatic disease-3$0
'etastasis Eungs brain li#er
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Treatment
ombination surgery withchemotherapy*-methotre+ateactinomycin D andchlorambucil
.