Gestational TrophoblasticGestational Trophoblastic
Disease (GTD)Disease (GTD)
Types of GTDTypes of GTD
BenignBenign
• Hydatidiform mole/molar pregnancyHydatidiform mole/molar pregnancy
(complete or incomplete)(complete or incomplete)
malignantmalignant
• Invasive moleInvasive mole
• Choriocarcinoma (chorioepithelioma)Choriocarcinoma (chorioepithelioma)
• Placental site trophoblastic tumorPlacental site trophoblastic tumor
 The termThe term Gestational TrophoblasticGestational Trophoblastic
TumorsTumors has been applied the latterhas been applied the latter
three conditionsthree conditions
 Arise from the trophoblastic elementsArise from the trophoblastic elements
 Retain the invasive tendencies of theRetain the invasive tendencies of the
normal placenta or metastasisnormal placenta or metastasis
 Keep secretion of the human chorionicKeep secretion of the human chorionic
gonadotropin (hCG)gonadotropin (hCG)
Types of GTDTypes of GTD
PATHOLOGICPATHOLOGIC
CLASSIFICATIONCLASSIFICATION
CLINICALCLINICAL
CLASSIFICATIONCLASSIFICATION
Hydatidiform moleHydatidiform mole
*complete*complete
*incomplete*incomplete
Benign gestationalBenign gestational
trophoblastic diseasetrophoblastic disease
Invasive moleInvasive mole
MalignantMalignant
trophoblastic diseasetrophoblastic disease
NonmetastaticNonmetastatic
Placental sitePlacental site
trophoblastictrophoblastic
tumortumor
MetastaticMetastatic
ChoriocarcinomaChoriocarcinoma High riskHigh risk Low riskLow risk
Pathologic and clinical classifications
for gestational trophoblastic disease
Hydatidiform MoleHydatidiform Mole
(molar pregnancy)(molar pregnancy)
Definition and EtiologyDefinition and Etiology
 Hydatidiform mole is a pregnancyHydatidiform mole is a pregnancy
characterized by vesicular swelling ofcharacterized by vesicular swelling of
placental villi and usually the absence ofplacental villi and usually the absence of
an intact fetus.an intact fetus.
 The etiology of hydatidiform moleThe etiology of hydatidiform mole
remains unclear, but it appears to be dueremains unclear, but it appears to be due
to abnormal gametogenesis andto abnormal gametogenesis and
fertilizationfertilization
 In aIn a ‘‘complete molecomplete mole’’ the mass ofthe mass of
tissue is completely made up oftissue is completely made up of
abnormal cellsabnormal cells
 There is no fetus and nothing canThere is no fetus and nothing can
be found at the time of the firstbe found at the time of the first
scan.scan.
Definition and EtiologyDefinition and Etiology
 In aIn a ‘‘partial molepartial mole’’, the mass may, the mass may
contain both these abnormal cellscontain both these abnormal cells
and often a fetus that has severeand often a fetus that has severe
defects.defects.
 In this case the fetus will beIn this case the fetus will be
consumed ( destroyed) by theconsumed ( destroyed) by the
growing abnormal mass verygrowing abnormal mass very
quickly.quickly. (shrink)(shrink)
Definition and EtiologyDefinition and Etiology
IncidenceIncidence
• 1 out of 1500-2000 pregnancies in the1 out of 1500-2000 pregnancies in the
U.S. and EuropeU.S. and Europe
• 1 out of 500-600 (another report 1%)1 out of 500-600 (another report 1%)
pregnancies in some Asian countries.pregnancies in some Asian countries.
• Complete > incompleteComplete > incomplete
 Repeat hydatidiform moles occure inRepeat hydatidiform moles occure in
0.5-2.6% of patients, and these0.5-2.6% of patients, and these
patiens have a subsequent greaterpatiens have a subsequent greater
risk of developing invasive mole orrisk of developing invasive mole or
choriocarcinomachoriocarcinoma
 There is an increased risk of molarThere is an increased risk of molar
pregnancy for women over the age 40pregnancy for women over the age 40
IncidenceIncidence
 Approximately 10-17% of hydatidiformApproximately 10-17% of hydatidiform
moles will result in invasive molemoles will result in invasive mole
 Approximately 2-3% of hydatidiformApproximately 2-3% of hydatidiform
moles progress to choriocarcinomamoles progress to choriocarcinoma
( most of them are curable)( most of them are curable)
IncidenceIncidence
Not definitely benign disease ,Not definitely benign disease ,
has a tight relationship with GTThas a tight relationship with GTT
Clinical risk factors for molarClinical risk factors for molar
pregnancypregnancy
Age (extremes of reproductive years)Age (extremes of reproductive years)
<15<15
>40>40
Reproductive historyReproductive history
prior hydatidiform moleprior hydatidiform mole
prior spontaneous abortionprior spontaneous abortion
DietDiet
Vitamin A deficiencyVitamin A deficiency
BirthplaceBirthplace
Outside North America( occasionally hasOutside North America( occasionally has
this disease)this disease)
CytogeneticsCytogenetics
Complete molar pregnancyComplete molar pregnancy
Chromosomes are paternal , diploidChromosomes are paternal , diploid
46,XX in 90% cases46,XX in 90% cases
46,XY in a small part46,XY in a small part
Partial molar pregnancyPartial molar pregnancy
Chromosomes are paternal and maternal, triploid.Chromosomes are paternal and maternal, triploid.
69,XXY 80%69,XXY 80%
69,XXX or 69,XYY 10-20%69,XXX or 69,XYY 10-20%
Wrong life message , so can not develop normally
Comparative Pathologic Features ofComparative Pathologic Features of
Complete and Partial HydatidiformComplete and Partial Hydatidiform
MoleMole
FeatureFeature Complete MoleComplete Mole Partial MolePartial Mole
KaryotypeKaryotype Usually diploid 46XXUsually diploid 46XX Usually triploidy 69XXX mostUsually triploidy 69XXX most
common.common.
VilliVilli All villi hydropin; noAll villi hydropin; no
normal adjacent villinormal adjacent villi
Normal adjacent villi may beNormal adjacent villi may be
presentpresent
vesselsvessels present they contain nopresent they contain no
fetal blood cellsfetal blood cells
blood cellsblood cells
Fetal tissueFetal tissue None presentNone present Usually presentUsually present
TrophoblastTrophoblast Hyperplasia usuallyHyperplasia usually
present to variablepresent to variable
degreesdegrees
Hyperplasia mild and focalHyperplasia mild and focal
Complete hydatidiform mole demonstrating
enlarged villi of various size
Hydatidiform mole: specimen from suction
curettage
A large amount of villi in the uterus.
The microscopic appearance of hydatidiform mole:
•Hyperplasia of trophobasitc cells
•Hydropic swelling of all villi
•Vessles are usually absent
A sonographic findings of a molar pregnancy. The
characteristic “snowstorm” pattern is evident.
Transvaginal sonogram demonstrating the “ snow storm” appearance.
Color Dopplor facilitates visualization of the enlarged spiral
arteriesclose proximity to the “ snow storm” appearance
Color Doppler image of a hydatidiform mole and surrounding
vessels. The uterine artery is easily identified from its anatomical
location.
Dopplor waveform analysis demonstrates low vascular resistance(RI=0.29) in
the spiral arteries, much lower than that obtained in normal early pregnancy
Partial hydartidiform mole
Microscopic image of partial molar pregnancy.
Here is a partial mole in a case of triploidy. Note the
scattered grape-like masses with intervening normal-
appearing placental tissue.
Large bilateral theca lutein cysts resembling ovarian germ cell
tumors. With resolution of the human chorionic gonadotropin(HCG)
stimulation, they return to normal-appearing ovaries.
Signs and Symptoms of CompleteSigns and Symptoms of Complete
Hydatidiform MoleHydatidiform Mole
• Vaginal bleedingVaginal bleeding
• Hyperemesis ( severe vomit)Hyperemesis ( severe vomit)
• Size inconsistent with gestationalSize inconsistent with gestational
age( with no fetal heart beating andage( with no fetal heart beating and
fetal movement)fetal movement)
• PreeclampsiaPreeclampsia
• Theca lutein ovarian cystsTheca lutein ovarian cysts
Signs and Symptoms of PartialSigns and Symptoms of Partial
Hydatidiform MoleHydatidiform Mole
• Vaginal bleedingVaginal bleeding
• Absence of fetal heart tonesAbsence of fetal heart tones
• Uterine enlargement andUterine enlargement and
preeclampsia is reported in only 3%preeclampsia is reported in only 3%
of patients.of patients.
• Theca lutein cysts, hyperemesis isTheca lutein cysts, hyperemesis is
rare.rare.
Diagnosis of hydatidiformDiagnosis of hydatidiform
molemole
Quantitative beta-HCGQuantitative beta-HCG
Ultrasound is the criterion standard forUltrasound is the criterion standard for
identifying both complete and partialidentifying both complete and partial
molar pregnancies. The classic imagemolar pregnancies. The classic image
is of ais of a ““snowstormsnowstorm”” patternpattern
 The most common symptom of a mole isThe most common symptom of a mole is
vaginal bleeding during the first trimestervaginal bleeding during the first trimester
 however very often no signs of a problemhowever very often no signs of a problem
appear and the mole can only be diagnosed byappear and the mole can only be diagnosed by
use of ultrasound scanning. (rutting check)use of ultrasound scanning. (rutting check)
 Occasionally, a uterus that is too large for theOccasionally, a uterus that is too large for the
stage of the pregnancy can be an indication.stage of the pregnancy can be an indication.
 NOTE: Vaginal bleeding does not alwaysNOTE: Vaginal bleeding does not always
indicate a problem!indicate a problem!
DiagnosisDiagnosis
Differential diagnosisDifferential diagnosis
• AbortionAbortion
• Multiple pregnancyMultiple pregnancy
• PolyhydramniosPolyhydramnios
TreatmentTreatment
Suction dilation and curettageSuction dilation and curettage :to:to
remove benign hydatidiform molesremove benign hydatidiform moles
When the diagnosis of hydatidiform mole isWhen the diagnosis of hydatidiform mole is
established, the molar pregnancy should beestablished, the molar pregnancy should be
evacuated.evacuated.
An oxytocic agent should be infusedAn oxytocic agent should be infused
intravenously after the start of evacuationintravenously after the start of evacuation
and continued for several hours to enhanceand continued for several hours to enhance
uterine contractilityuterine contractility
• Removal of the uterus (hysterectomy)Removal of the uterus (hysterectomy)
: used rarely to treat hydatidiform moles if: used rarely to treat hydatidiform moles if
future pregnancy is no longer desired.future pregnancy is no longer desired.
TreatmentTreatment
Chemotherapy with aChemotherapy with a
single-agent drugsingle-agent drug
Prophylactic (for prevention)Prophylactic (for prevention)
chemotherapy at the time ofchemotherapy at the time of
or immediately followingor immediately following
molar evacuation may bemolar evacuation may be
considered for the high-riskconsidered for the high-risk
patients( to prevent spread ofpatients( to prevent spread of
disease )disease )
TreatmentTreatment
High-risk postmolarHigh-risk postmolar
trophoblastic tumortrophoblastic tumor
1.1. Pre-evacuation uterine size larger than expectedPre-evacuation uterine size larger than expected
for gestational durationfor gestational duration
2.2. Bilateral ovarian enlargement (> 9 cm theca luteinBilateral ovarian enlargement (> 9 cm theca lutein
cysts)cysts)
3.3. Age greater than 40 yearsAge greater than 40 years
4.4. Very high hCG levels(>100,000 m IU/ml)Very high hCG levels(>100,000 m IU/ml)
5.5. Medical complications of molar pregnancy suchMedical complications of molar pregnancy such
as toxemia, hyperthyrodism and trophoblasticas toxemia, hyperthyrodism and trophoblastic
embolization (villi come out of placenta )embolization (villi come out of placenta )
6.6. repeat hydatidiform molerepeat hydatidiform mole
 Patients with hudatidiform mole arePatients with hudatidiform mole are
curative over 80% by treatment ofcurative over 80% by treatment of
evacuation.evacuation.
 The follow-up after evacuation is keyThe follow-up after evacuation is key
necessarynecessary
 uterine involution, ovarian cystuterine involution, ovarian cyst
regression and cessation of bleedingregression and cessation of bleeding
Follow-upFollow-up
 Quantitative serum hCG levels shouldQuantitative serum hCG levels should
be obtained every 1-2 weeks untilbe obtained every 1-2 weeks until
negative for three consecutivenegative for three consecutive
determinations,determinations,
 Followed by every 3 months for 1Followed by every 3 months for 1
years.years.
 Contraception should be practicedContraception should be practiced
during this follow-up periodduring this follow-up period
Follow-upFollow-up
Invasive moleInvasive mole
DefinitionDefinition
This term is applied to a molarThis term is applied to a molar
pregnancy in which molar villi growpregnancy in which molar villi grow
into the myometrium or its bloodinto the myometrium or its blood
vessels, and may extend into thevessels, and may extend into the
broad ligament and metastasize to thebroad ligament and metastasize to the
lungs, the vagina or the vulva.lungs, the vagina or the vulva.
Invasive mole: the tissue invades into the myometrial layer.
No obvious borderline, with obvious bleeding.
Invasive hydatidiform mole infiltrating the myometrium
A case of invasive mole: inside the uterine cavity the typicalA case of invasive mole: inside the uterine cavity the typical
““snow stormsnow storm”” appearance can be detected, The location ofappearance can be detected, The location of
blood flow suggest an invasive mole.blood flow suggest an invasive mole.
The same patient owing to the myometrial invasion.The same patient owing to the myometrial invasion.
Reduced vascular resistance is detected in the uterine artery.Reduced vascular resistance is detected in the uterine artery.
Transvaginal color Doppler scan of a patient with invasive mole Following
uterine curettage, Persistent color signals within the myometeriun
Doppler image of invasive mole
Power Doppler easily detects a vascular echogenic
nodule within the myometrium, suggesting
invasive mole
Doppler image of invasive mole. Doppler waveform
analysis depicts low vascular resistance (RI= 0.35)
Common Sites for MetastaticCommon Sites for Metastatic
Gestational Trophoblastic TumorsGestational Trophoblastic Tumors
SiteSite Per centPer cent
LungLung 60-9560-95
VaginaVagina 40-5040-50
Vulva/cervixVulva/cervix 10-1510-15
BrainBrain 5-155-15
LiverLiver 5-155-15
KidneyKidney 0-50-5
SpleenSpleen 0-50-5
GastrointestinalGastrointestinal 0-50-5
ChoriocarcinomaChoriocarcinoma
DefinitionDefinition
A malignant form of GTD which canA malignant form of GTD which can
develop from a hydatidiform mole ordevelop from a hydatidiform mole or
from placental trophoblast cellsfrom placental trophoblast cells
associated with a healthy fetus ,anassociated with a healthy fetus ,an
abortion or an ectopic pregnancy.abortion or an ectopic pregnancy.
 Characterized by abnormalCharacterized by abnormal
trophoblastic hyperplasia andtrophoblastic hyperplasia and
anaplasia , absence of chorionic villianaplasia , absence of chorionic villi
DefinitionDefinition
Gross specimen of choriocarcinoma
Microscopic image of choriocarcinoma
absence of chorionic villiabsence of chorionic villi
Microscopic image of choriocarcinoma
Doppler image of choriocarcinoma
Doppler image of choriocarcinoma
Symptoms and signsSymptoms and signs
• BleedingBleeding
• InfectionInfection
• Abdominal swellingAbdominal swelling
• Vaginal massVaginal mass
• Lung symptomsLung symptoms
• Symptoms from other metastasesSymptoms from other metastases
WHO Prognostic Scoring SystemWHO Prognostic Scoring System
ScoreScore
Prognostic factorPrognostic factor 00 11 22 44
Age(years)Age(years) ≤≤3939 >39>39 —— ——
Pregnancy historyPregnancy history
HydatidiformHydatidiform
molemole
Abortion,Abortion,
ectopicectopic
TermTerm
pregnancypregnancy
——
Interval (months) ofInterval (months) of
treatmenttreatment
<4<4 4-64-6 7-127-12 >12>12
Initial hCG(mIU/ml)Initial hCG(mIU/ml) <10<1033
101033
-10-1044
101044
-10-1055
>10>1055
Largest tumor(cm)Largest tumor(cm) <3<3 3-53-5 >5>5 ——
Sites of metastasisSites of metastasis LungLung
Spleen,Spleen,
kidneykidney
GI tract, liverGI tract, liver BrainBrain
No. of metastasisNo. of metastasis —— 1-41-4 4-84-8 88
Previous (treatment)Previous (treatment) —— —— Single drugSingle drug 2 or more2 or more
0-4 low risk, 5-7 intermediate risk, >8 high risk for death
FIGO Staging System for GestationalFIGO Staging System for Gestational
Trophoblastic TumorsTrophoblastic Tumors
StageStage DescriptionDescription
ⅠⅠ Limited to uterine corpusLimited to uterine corpus
ⅡⅡ Extends to the adnexae, outside the uterus,Extends to the adnexae, outside the uterus,
but limited to the genital structuresbut limited to the genital structures
ⅢⅢ Extends to the lungs with or without genitalExtends to the lungs with or without genital
tracttract
ⅣⅣ All other metastatic sitesAll other metastatic sites
 Substages assigned for each stage asSubstages assigned for each stage as
follows:follows:
A: No risk factors presentA: No risk factors present
B: One risk factorB: One risk factor
C: Both risk factorsC: Both risk factors
 Risk factors used to assign substages:Risk factors used to assign substages:
1. Pretherapy serum hCG > 100,0001. Pretherapy serum hCG > 100,000
mlU/mlmlU/ml
2. Duration of disease >6 months2. Duration of disease >6 months
FIGO Staging System for GestationalFIGO Staging System for Gestational
Trophoblastic TumorsTrophoblastic Tumors
IIb
IIa
IIIa<3cm or locate in half lung
IIIb disease beyond IIIa
Diagnosis andDiagnosis and
evaluationevaluation
 Gestational trophoblastic tumor isGestational trophoblastic tumor is
diagnosed by rising hCG followingdiagnosed by rising hCG following
evacuation of a molar pregnancy orevacuation of a molar pregnancy or
any pregnancy eventany pregnancy event
 Once the diagnosis established theOnce the diagnosis established the
further examinations should be donefurther examinations should be done
to determine the extent of disease ( X-to determine the extent of disease ( X-
ray, CT, MRI)ray, CT, MRI)
TreatmentTreatment
 Nonmetastatic GTDNonmetastatic GTD
 Low-Risk Metastatic GTDLow-Risk Metastatic GTD
 High-Risk Metastatic GTDHigh-Risk Metastatic GTD
Treatment of NonmetastaticTreatment of Nonmetastatic
GTDGTD
 Hysterectomy is advisable as initial treatment inHysterectomy is advisable as initial treatment in
patients with nonmetastatic GTD who no longerpatients with nonmetastatic GTD who no longer
wish to preserve fertilitywish to preserve fertility
 This choice can reduce the number of courseThis choice can reduce the number of course
and shorter duration of chemotherapy.and shorter duration of chemotherapy.
 Adjusted single-agent chemotherapy at the timeAdjusted single-agent chemotherapy at the time
of operation is indicated to eradicate any occultof operation is indicated to eradicate any occult
metastases and reduce tumor dissemination.metastases and reduce tumor dissemination.
 Single-agent chemotherapy is the treatment ofSingle-agent chemotherapy is the treatment of
choice for patients wishing to preserve theirchoice for patients wishing to preserve their
fertility.fertility.
 Methotrexate(MTX) and Actinomycin-D areMethotrexate(MTX) and Actinomycin-D are
generally chemotherapy agentsgenerally chemotherapy agents
 Treatment is continued until three consecutiveTreatment is continued until three consecutive
normal hCG levels have been obtained and twonormal hCG levels have been obtained and two
courses have been given after the first normalcourses have been given after the first normal
hCG level.hCG level.
Treatment of NonmetastaticTreatment of Nonmetastatic
GTDGTD
To prevent relapse or metastasisTo prevent relapse or metastasis
 Single-agent chemotherapy with MTX or actinomycin-Single-agent chemotherapy with MTX or actinomycin-
D is the treatment for patients in this categoryD is the treatment for patients in this category
 If resistance to sequential single-agent chemotherapyIf resistance to sequential single-agent chemotherapy
develops, combination chemotherapy would be takendevelops, combination chemotherapy would be taken
 Approximately 10-15% of patients treated with single-Approximately 10-15% of patients treated with single-
agent chemotherapy will require combinationagent chemotherapy will require combination
chemotherapy with or without surgery to achievechemotherapy with or without surgery to achieve
remissionremission
Treatment of Low-RiskTreatment of Low-Risk
Metastatic GTDMetastatic GTD
 Multiagent chemotherapy with or withoutMultiagent chemotherapy with or without
adjuvant radiotherapy or surgery should beadjuvant radiotherapy or surgery should be
the initial treatment for patients with high-ristthe initial treatment for patients with high-rist
metastatic GTDmetastatic GTD
 EMA-CO regimen formula is good choice forEMA-CO regimen formula is good choice for
high-rist metastatic GTDhigh-rist metastatic GTD
 Adjusted surgeries such as removing foci ofAdjusted surgeries such as removing foci of
chemotherapy-resistant disease, controllingchemotherapy-resistant disease, controlling
hemorrhage may be the one ofhemorrhage may be the one of treatmenttreatment
regimenregimen
Treatment of High-RiskTreatment of High-Risk
Metastatic GTDMetastatic GTD
EMA-CO Chemotherapy for poorEMA-CO Chemotherapy for poor
Prognostic DiseasePrognostic Disease
Etoposide(VP-16)Etoposide(VP-16) 100mg/M100mg/M22
IV daily×2 daysIV daily×2 days
(over 30-45(over 30-45
minutes)minutes)
MethotrexateMethotrexate 100mg/M100mg/M22
IV losding dose,IV losding dose,
then 200mg/M2 overthen 200mg/M2 over
12 hours day 112 hours day 1
Actinomycin DActinomycin D 0.5mg0.5mg IV daily×2 daysIV daily×2 days
Folinic acidFolinic acid 15mg IM or p.o. q 12 hours×4 starting 2415mg IM or p.o. q 12 hours×4 starting 24
hours after starting methotrexatehours after starting methotrexate
CyclophosphamideCyclophosphamide 600mg/M600mg/M22
IV on day8IV on day8
Oncovin (vincristine)Oncovin (vincristine) 1mg/M1mg/M22
IV on day8IV on day8
(Repeat every 15 days as toxicity permits)(Repeat every 15 days as toxicity permits)
PrognosisPrognosis
 Cure rates should approach 100% inCure rates should approach 100% in
nonmetastatic and low-risk metastaticnonmetastatic and low-risk metastatic
GTDGTD
 Intensive multimodality therapy hasIntensive multimodality therapy has
resulted in cure rates of 80-90% inresulted in cure rates of 80-90% in
patients with high-risk metastatic GTDpatients with high-risk metastatic GTD
Follow-up AfterFollow-up After
Successful TreatmentSuccessful Treatment
 Quantitative serum hCG levels should beQuantitative serum hCG levels should be
obtained monthly for 6 months, every twoobtained monthly for 6 months, every two
months for remainder of the first year,months for remainder of the first year,
every 3 months during the second yearevery 3 months during the second year
 Contraception should be maintained for atContraception should be maintained for at
least 1 year after the completion ofleast 1 year after the completion of
chemotherapy. Condom is the choice.chemotherapy. Condom is the choice.
Placenta Site TrophoblasticPlacenta Site Trophoblastic
Tumor (PSTT)Tumor (PSTT)
 Placenta Site Trophoblastic Tumor is anPlacenta Site Trophoblastic Tumor is an
extremely rare tumor that arised from theextremely rare tumor that arised from the
placental implantation siteplacental implantation site
 Tumor cells infiltrate the myometrium andTumor cells infiltrate the myometrium and
grow between smooth-muscle cellsgrow between smooth-muscle cells
DefinitionDefinition
 Surum hCG levels are relatively lowSurum hCG levels are relatively low
compared to those seen withcompared to those seen with
choriocarcinoma.choriocarcinoma.
 Several reports have noted a benignSeveral reports have noted a benign
behavior of this disease. They are relativelybehavior of this disease. They are relatively
chemotherapy-resistant, and deaths fromchemotherapy-resistant, and deaths from
metastasis have occurred.metastasis have occurred.
 Surgery has been the mainstay of treatmentSurgery has been the mainstay of treatment
Dignosis and treatmentDignosis and treatment

Hydatiform mole

  • 1.
  • 3.
    Types of GTDTypesof GTD BenignBenign • Hydatidiform mole/molar pregnancyHydatidiform mole/molar pregnancy (complete or incomplete)(complete or incomplete) malignantmalignant • Invasive moleInvasive mole • Choriocarcinoma (chorioepithelioma)Choriocarcinoma (chorioepithelioma) • Placental site trophoblastic tumorPlacental site trophoblastic tumor
  • 4.
     The termTheterm Gestational TrophoblasticGestational Trophoblastic TumorsTumors has been applied the latterhas been applied the latter three conditionsthree conditions  Arise from the trophoblastic elementsArise from the trophoblastic elements  Retain the invasive tendencies of theRetain the invasive tendencies of the normal placenta or metastasisnormal placenta or metastasis  Keep secretion of the human chorionicKeep secretion of the human chorionic gonadotropin (hCG)gonadotropin (hCG) Types of GTDTypes of GTD
  • 5.
    PATHOLOGICPATHOLOGIC CLASSIFICATIONCLASSIFICATION CLINICALCLINICAL CLASSIFICATIONCLASSIFICATION Hydatidiform moleHydatidiform mole *complete*complete *incomplete*incomplete BenigngestationalBenign gestational trophoblastic diseasetrophoblastic disease Invasive moleInvasive mole MalignantMalignant trophoblastic diseasetrophoblastic disease NonmetastaticNonmetastatic Placental sitePlacental site trophoblastictrophoblastic tumortumor MetastaticMetastatic ChoriocarcinomaChoriocarcinoma High riskHigh risk Low riskLow risk Pathologic and clinical classifications for gestational trophoblastic disease
  • 6.
    Hydatidiform MoleHydatidiform Mole (molarpregnancy)(molar pregnancy)
  • 7.
    Definition and EtiologyDefinitionand Etiology  Hydatidiform mole is a pregnancyHydatidiform mole is a pregnancy characterized by vesicular swelling ofcharacterized by vesicular swelling of placental villi and usually the absence ofplacental villi and usually the absence of an intact fetus.an intact fetus.  The etiology of hydatidiform moleThe etiology of hydatidiform mole remains unclear, but it appears to be dueremains unclear, but it appears to be due to abnormal gametogenesis andto abnormal gametogenesis and fertilizationfertilization
  • 8.
     In aIna ‘‘complete molecomplete mole’’ the mass ofthe mass of tissue is completely made up oftissue is completely made up of abnormal cellsabnormal cells  There is no fetus and nothing canThere is no fetus and nothing can be found at the time of the firstbe found at the time of the first scan.scan. Definition and EtiologyDefinition and Etiology
  • 9.
     In aIna ‘‘partial molepartial mole’’, the mass may, the mass may contain both these abnormal cellscontain both these abnormal cells and often a fetus that has severeand often a fetus that has severe defects.defects.  In this case the fetus will beIn this case the fetus will be consumed ( destroyed) by theconsumed ( destroyed) by the growing abnormal mass verygrowing abnormal mass very quickly.quickly. (shrink)(shrink) Definition and EtiologyDefinition and Etiology
  • 10.
    IncidenceIncidence • 1 outof 1500-2000 pregnancies in the1 out of 1500-2000 pregnancies in the U.S. and EuropeU.S. and Europe • 1 out of 500-600 (another report 1%)1 out of 500-600 (another report 1%) pregnancies in some Asian countries.pregnancies in some Asian countries. • Complete > incompleteComplete > incomplete
  • 11.
     Repeat hydatidiformmoles occure inRepeat hydatidiform moles occure in 0.5-2.6% of patients, and these0.5-2.6% of patients, and these patiens have a subsequent greaterpatiens have a subsequent greater risk of developing invasive mole orrisk of developing invasive mole or choriocarcinomachoriocarcinoma  There is an increased risk of molarThere is an increased risk of molar pregnancy for women over the age 40pregnancy for women over the age 40 IncidenceIncidence
  • 12.
     Approximately 10-17%of hydatidiformApproximately 10-17% of hydatidiform moles will result in invasive molemoles will result in invasive mole  Approximately 2-3% of hydatidiformApproximately 2-3% of hydatidiform moles progress to choriocarcinomamoles progress to choriocarcinoma ( most of them are curable)( most of them are curable) IncidenceIncidence Not definitely benign disease ,Not definitely benign disease , has a tight relationship with GTThas a tight relationship with GTT
  • 14.
    Clinical risk factorsfor molarClinical risk factors for molar pregnancypregnancy Age (extremes of reproductive years)Age (extremes of reproductive years) <15<15 >40>40 Reproductive historyReproductive history prior hydatidiform moleprior hydatidiform mole prior spontaneous abortionprior spontaneous abortion DietDiet Vitamin A deficiencyVitamin A deficiency BirthplaceBirthplace Outside North America( occasionally hasOutside North America( occasionally has this disease)this disease)
  • 15.
    CytogeneticsCytogenetics Complete molar pregnancyCompletemolar pregnancy Chromosomes are paternal , diploidChromosomes are paternal , diploid 46,XX in 90% cases46,XX in 90% cases 46,XY in a small part46,XY in a small part Partial molar pregnancyPartial molar pregnancy Chromosomes are paternal and maternal, triploid.Chromosomes are paternal and maternal, triploid. 69,XXY 80%69,XXY 80% 69,XXX or 69,XYY 10-20%69,XXX or 69,XYY 10-20% Wrong life message , so can not develop normally
  • 16.
    Comparative Pathologic FeaturesofComparative Pathologic Features of Complete and Partial HydatidiformComplete and Partial Hydatidiform MoleMole FeatureFeature Complete MoleComplete Mole Partial MolePartial Mole KaryotypeKaryotype Usually diploid 46XXUsually diploid 46XX Usually triploidy 69XXX mostUsually triploidy 69XXX most common.common. VilliVilli All villi hydropin; noAll villi hydropin; no normal adjacent villinormal adjacent villi Normal adjacent villi may beNormal adjacent villi may be presentpresent vesselsvessels present they contain nopresent they contain no fetal blood cellsfetal blood cells blood cellsblood cells Fetal tissueFetal tissue None presentNone present Usually presentUsually present TrophoblastTrophoblast Hyperplasia usuallyHyperplasia usually present to variablepresent to variable degreesdegrees Hyperplasia mild and focalHyperplasia mild and focal
  • 17.
    Complete hydatidiform moledemonstrating enlarged villi of various size
  • 18.
    Hydatidiform mole: specimenfrom suction curettage
  • 19.
    A large amountof villi in the uterus.
  • 20.
    The microscopic appearanceof hydatidiform mole: •Hyperplasia of trophobasitc cells •Hydropic swelling of all villi •Vessles are usually absent
  • 21.
    A sonographic findingsof a molar pregnancy. The characteristic “snowstorm” pattern is evident.
  • 22.
    Transvaginal sonogram demonstratingthe “ snow storm” appearance.
  • 23.
    Color Dopplor facilitatesvisualization of the enlarged spiral arteriesclose proximity to the “ snow storm” appearance
  • 24.
    Color Doppler imageof a hydatidiform mole and surrounding vessels. The uterine artery is easily identified from its anatomical location.
  • 26.
    Dopplor waveform analysisdemonstrates low vascular resistance(RI=0.29) in the spiral arteries, much lower than that obtained in normal early pregnancy
  • 28.
  • 29.
    Microscopic image ofpartial molar pregnancy.
  • 30.
    Here is apartial mole in a case of triploidy. Note the scattered grape-like masses with intervening normal- appearing placental tissue.
  • 31.
    Large bilateral thecalutein cysts resembling ovarian germ cell tumors. With resolution of the human chorionic gonadotropin(HCG) stimulation, they return to normal-appearing ovaries.
  • 32.
    Signs and Symptomsof CompleteSigns and Symptoms of Complete Hydatidiform MoleHydatidiform Mole • Vaginal bleedingVaginal bleeding • Hyperemesis ( severe vomit)Hyperemesis ( severe vomit) • Size inconsistent with gestationalSize inconsistent with gestational age( with no fetal heart beating andage( with no fetal heart beating and fetal movement)fetal movement) • PreeclampsiaPreeclampsia • Theca lutein ovarian cystsTheca lutein ovarian cysts
  • 33.
    Signs and Symptomsof PartialSigns and Symptoms of Partial Hydatidiform MoleHydatidiform Mole • Vaginal bleedingVaginal bleeding • Absence of fetal heart tonesAbsence of fetal heart tones • Uterine enlargement andUterine enlargement and preeclampsia is reported in only 3%preeclampsia is reported in only 3% of patients.of patients. • Theca lutein cysts, hyperemesis isTheca lutein cysts, hyperemesis is rare.rare.
  • 34.
    Diagnosis of hydatidiformDiagnosisof hydatidiform molemole Quantitative beta-HCGQuantitative beta-HCG Ultrasound is the criterion standard forUltrasound is the criterion standard for identifying both complete and partialidentifying both complete and partial molar pregnancies. The classic imagemolar pregnancies. The classic image is of ais of a ““snowstormsnowstorm”” patternpattern
  • 35.
     The mostcommon symptom of a mole isThe most common symptom of a mole is vaginal bleeding during the first trimestervaginal bleeding during the first trimester  however very often no signs of a problemhowever very often no signs of a problem appear and the mole can only be diagnosed byappear and the mole can only be diagnosed by use of ultrasound scanning. (rutting check)use of ultrasound scanning. (rutting check)  Occasionally, a uterus that is too large for theOccasionally, a uterus that is too large for the stage of the pregnancy can be an indication.stage of the pregnancy can be an indication.  NOTE: Vaginal bleeding does not alwaysNOTE: Vaginal bleeding does not always indicate a problem!indicate a problem! DiagnosisDiagnosis
  • 36.
    Differential diagnosisDifferential diagnosis •AbortionAbortion • Multiple pregnancyMultiple pregnancy • PolyhydramniosPolyhydramnios
  • 37.
    TreatmentTreatment Suction dilation andcurettageSuction dilation and curettage :to:to remove benign hydatidiform molesremove benign hydatidiform moles When the diagnosis of hydatidiform mole isWhen the diagnosis of hydatidiform mole is established, the molar pregnancy should beestablished, the molar pregnancy should be evacuated.evacuated. An oxytocic agent should be infusedAn oxytocic agent should be infused intravenously after the start of evacuationintravenously after the start of evacuation and continued for several hours to enhanceand continued for several hours to enhance uterine contractilityuterine contractility
  • 38.
    • Removal ofthe uterus (hysterectomy)Removal of the uterus (hysterectomy) : used rarely to treat hydatidiform moles if: used rarely to treat hydatidiform moles if future pregnancy is no longer desired.future pregnancy is no longer desired. TreatmentTreatment
  • 39.
    Chemotherapy with aChemotherapywith a single-agent drugsingle-agent drug Prophylactic (for prevention)Prophylactic (for prevention) chemotherapy at the time ofchemotherapy at the time of or immediately followingor immediately following molar evacuation may bemolar evacuation may be considered for the high-riskconsidered for the high-risk patients( to prevent spread ofpatients( to prevent spread of disease )disease ) TreatmentTreatment
  • 40.
    High-risk postmolarHigh-risk postmolar trophoblastictumortrophoblastic tumor 1.1. Pre-evacuation uterine size larger than expectedPre-evacuation uterine size larger than expected for gestational durationfor gestational duration 2.2. Bilateral ovarian enlargement (> 9 cm theca luteinBilateral ovarian enlargement (> 9 cm theca lutein cysts)cysts) 3.3. Age greater than 40 yearsAge greater than 40 years 4.4. Very high hCG levels(>100,000 m IU/ml)Very high hCG levels(>100,000 m IU/ml) 5.5. Medical complications of molar pregnancy suchMedical complications of molar pregnancy such as toxemia, hyperthyrodism and trophoblasticas toxemia, hyperthyrodism and trophoblastic embolization (villi come out of placenta )embolization (villi come out of placenta ) 6.6. repeat hydatidiform molerepeat hydatidiform mole
  • 41.
     Patients withhudatidiform mole arePatients with hudatidiform mole are curative over 80% by treatment ofcurative over 80% by treatment of evacuation.evacuation.  The follow-up after evacuation is keyThe follow-up after evacuation is key necessarynecessary  uterine involution, ovarian cystuterine involution, ovarian cyst regression and cessation of bleedingregression and cessation of bleeding Follow-upFollow-up
  • 42.
     Quantitative serumhCG levels shouldQuantitative serum hCG levels should be obtained every 1-2 weeks untilbe obtained every 1-2 weeks until negative for three consecutivenegative for three consecutive determinations,determinations,  Followed by every 3 months for 1Followed by every 3 months for 1 years.years.  Contraception should be practicedContraception should be practiced during this follow-up periodduring this follow-up period Follow-upFollow-up
  • 43.
  • 44.
    DefinitionDefinition This term isapplied to a molarThis term is applied to a molar pregnancy in which molar villi growpregnancy in which molar villi grow into the myometrium or its bloodinto the myometrium or its blood vessels, and may extend into thevessels, and may extend into the broad ligament and metastasize to thebroad ligament and metastasize to the lungs, the vagina or the vulva.lungs, the vagina or the vulva.
  • 45.
    Invasive mole: thetissue invades into the myometrial layer. No obvious borderline, with obvious bleeding.
  • 46.
    Invasive hydatidiform moleinfiltrating the myometrium
  • 47.
    A case ofinvasive mole: inside the uterine cavity the typicalA case of invasive mole: inside the uterine cavity the typical ““snow stormsnow storm”” appearance can be detected, The location ofappearance can be detected, The location of blood flow suggest an invasive mole.blood flow suggest an invasive mole.
  • 48.
    The same patientowing to the myometrial invasion.The same patient owing to the myometrial invasion. Reduced vascular resistance is detected in the uterine artery.Reduced vascular resistance is detected in the uterine artery.
  • 49.
    Transvaginal color Dopplerscan of a patient with invasive mole Following uterine curettage, Persistent color signals within the myometeriun
  • 50.
    Doppler image ofinvasive mole
  • 51.
    Power Doppler easilydetects a vascular echogenic nodule within the myometrium, suggesting invasive mole
  • 52.
    Doppler image ofinvasive mole. Doppler waveform analysis depicts low vascular resistance (RI= 0.35)
  • 53.
    Common Sites forMetastaticCommon Sites for Metastatic Gestational Trophoblastic TumorsGestational Trophoblastic Tumors SiteSite Per centPer cent LungLung 60-9560-95 VaginaVagina 40-5040-50 Vulva/cervixVulva/cervix 10-1510-15 BrainBrain 5-155-15 LiverLiver 5-155-15 KidneyKidney 0-50-5 SpleenSpleen 0-50-5 GastrointestinalGastrointestinal 0-50-5
  • 54.
  • 55.
    DefinitionDefinition A malignant formof GTD which canA malignant form of GTD which can develop from a hydatidiform mole ordevelop from a hydatidiform mole or from placental trophoblast cellsfrom placental trophoblast cells associated with a healthy fetus ,anassociated with a healthy fetus ,an abortion or an ectopic pregnancy.abortion or an ectopic pregnancy.
  • 56.
     Characterized byabnormalCharacterized by abnormal trophoblastic hyperplasia andtrophoblastic hyperplasia and anaplasia , absence of chorionic villianaplasia , absence of chorionic villi DefinitionDefinition
  • 57.
    Gross specimen ofchoriocarcinoma
  • 58.
    Microscopic image ofchoriocarcinoma absence of chorionic villiabsence of chorionic villi
  • 59.
    Microscopic image ofchoriocarcinoma
  • 60.
    Doppler image ofchoriocarcinoma
  • 61.
    Doppler image ofchoriocarcinoma
  • 62.
    Symptoms and signsSymptomsand signs • BleedingBleeding • InfectionInfection • Abdominal swellingAbdominal swelling • Vaginal massVaginal mass • Lung symptomsLung symptoms • Symptoms from other metastasesSymptoms from other metastases
  • 63.
    WHO Prognostic ScoringSystemWHO Prognostic Scoring System ScoreScore Prognostic factorPrognostic factor 00 11 22 44 Age(years)Age(years) ≤≤3939 >39>39 —— —— Pregnancy historyPregnancy history HydatidiformHydatidiform molemole Abortion,Abortion, ectopicectopic TermTerm pregnancypregnancy —— Interval (months) ofInterval (months) of treatmenttreatment <4<4 4-64-6 7-127-12 >12>12 Initial hCG(mIU/ml)Initial hCG(mIU/ml) <10<1033 101033 -10-1044 101044 -10-1055 >10>1055 Largest tumor(cm)Largest tumor(cm) <3<3 3-53-5 >5>5 —— Sites of metastasisSites of metastasis LungLung Spleen,Spleen, kidneykidney GI tract, liverGI tract, liver BrainBrain No. of metastasisNo. of metastasis —— 1-41-4 4-84-8 88 Previous (treatment)Previous (treatment) —— —— Single drugSingle drug 2 or more2 or more 0-4 low risk, 5-7 intermediate risk, >8 high risk for death
  • 64.
    FIGO Staging Systemfor GestationalFIGO Staging System for Gestational Trophoblastic TumorsTrophoblastic Tumors StageStage DescriptionDescription ⅠⅠ Limited to uterine corpusLimited to uterine corpus ⅡⅡ Extends to the adnexae, outside the uterus,Extends to the adnexae, outside the uterus, but limited to the genital structuresbut limited to the genital structures ⅢⅢ Extends to the lungs with or without genitalExtends to the lungs with or without genital tracttract ⅣⅣ All other metastatic sitesAll other metastatic sites
  • 65.
     Substages assignedfor each stage asSubstages assigned for each stage as follows:follows: A: No risk factors presentA: No risk factors present B: One risk factorB: One risk factor C: Both risk factorsC: Both risk factors  Risk factors used to assign substages:Risk factors used to assign substages: 1. Pretherapy serum hCG > 100,0001. Pretherapy serum hCG > 100,000 mlU/mlmlU/ml 2. Duration of disease >6 months2. Duration of disease >6 months FIGO Staging System for GestationalFIGO Staging System for Gestational Trophoblastic TumorsTrophoblastic Tumors
  • 67.
  • 68.
    IIIa<3cm or locatein half lung IIIb disease beyond IIIa
  • 70.
    Diagnosis andDiagnosis and evaluationevaluation Gestational trophoblastic tumor isGestational trophoblastic tumor is diagnosed by rising hCG followingdiagnosed by rising hCG following evacuation of a molar pregnancy orevacuation of a molar pregnancy or any pregnancy eventany pregnancy event  Once the diagnosis established theOnce the diagnosis established the further examinations should be donefurther examinations should be done to determine the extent of disease ( X-to determine the extent of disease ( X- ray, CT, MRI)ray, CT, MRI)
  • 71.
    TreatmentTreatment  Nonmetastatic GTDNonmetastaticGTD  Low-Risk Metastatic GTDLow-Risk Metastatic GTD  High-Risk Metastatic GTDHigh-Risk Metastatic GTD
  • 72.
    Treatment of NonmetastaticTreatmentof Nonmetastatic GTDGTD  Hysterectomy is advisable as initial treatment inHysterectomy is advisable as initial treatment in patients with nonmetastatic GTD who no longerpatients with nonmetastatic GTD who no longer wish to preserve fertilitywish to preserve fertility  This choice can reduce the number of courseThis choice can reduce the number of course and shorter duration of chemotherapy.and shorter duration of chemotherapy.  Adjusted single-agent chemotherapy at the timeAdjusted single-agent chemotherapy at the time of operation is indicated to eradicate any occultof operation is indicated to eradicate any occult metastases and reduce tumor dissemination.metastases and reduce tumor dissemination.
  • 73.
     Single-agent chemotherapyis the treatment ofSingle-agent chemotherapy is the treatment of choice for patients wishing to preserve theirchoice for patients wishing to preserve their fertility.fertility.  Methotrexate(MTX) and Actinomycin-D areMethotrexate(MTX) and Actinomycin-D are generally chemotherapy agentsgenerally chemotherapy agents  Treatment is continued until three consecutiveTreatment is continued until three consecutive normal hCG levels have been obtained and twonormal hCG levels have been obtained and two courses have been given after the first normalcourses have been given after the first normal hCG level.hCG level. Treatment of NonmetastaticTreatment of Nonmetastatic GTDGTD To prevent relapse or metastasisTo prevent relapse or metastasis
  • 74.
     Single-agent chemotherapywith MTX or actinomycin-Single-agent chemotherapy with MTX or actinomycin- D is the treatment for patients in this categoryD is the treatment for patients in this category  If resistance to sequential single-agent chemotherapyIf resistance to sequential single-agent chemotherapy develops, combination chemotherapy would be takendevelops, combination chemotherapy would be taken  Approximately 10-15% of patients treated with single-Approximately 10-15% of patients treated with single- agent chemotherapy will require combinationagent chemotherapy will require combination chemotherapy with or without surgery to achievechemotherapy with or without surgery to achieve remissionremission Treatment of Low-RiskTreatment of Low-Risk Metastatic GTDMetastatic GTD
  • 75.
     Multiagent chemotherapywith or withoutMultiagent chemotherapy with or without adjuvant radiotherapy or surgery should beadjuvant radiotherapy or surgery should be the initial treatment for patients with high-ristthe initial treatment for patients with high-rist metastatic GTDmetastatic GTD  EMA-CO regimen formula is good choice forEMA-CO regimen formula is good choice for high-rist metastatic GTDhigh-rist metastatic GTD  Adjusted surgeries such as removing foci ofAdjusted surgeries such as removing foci of chemotherapy-resistant disease, controllingchemotherapy-resistant disease, controlling hemorrhage may be the one ofhemorrhage may be the one of treatmenttreatment regimenregimen Treatment of High-RiskTreatment of High-Risk Metastatic GTDMetastatic GTD
  • 76.
    EMA-CO Chemotherapy forpoorEMA-CO Chemotherapy for poor Prognostic DiseasePrognostic Disease Etoposide(VP-16)Etoposide(VP-16) 100mg/M100mg/M22 IV daily×2 daysIV daily×2 days (over 30-45(over 30-45 minutes)minutes) MethotrexateMethotrexate 100mg/M100mg/M22 IV losding dose,IV losding dose, then 200mg/M2 overthen 200mg/M2 over 12 hours day 112 hours day 1 Actinomycin DActinomycin D 0.5mg0.5mg IV daily×2 daysIV daily×2 days Folinic acidFolinic acid 15mg IM or p.o. q 12 hours×4 starting 2415mg IM or p.o. q 12 hours×4 starting 24 hours after starting methotrexatehours after starting methotrexate CyclophosphamideCyclophosphamide 600mg/M600mg/M22 IV on day8IV on day8 Oncovin (vincristine)Oncovin (vincristine) 1mg/M1mg/M22 IV on day8IV on day8 (Repeat every 15 days as toxicity permits)(Repeat every 15 days as toxicity permits)
  • 77.
    PrognosisPrognosis  Cure ratesshould approach 100% inCure rates should approach 100% in nonmetastatic and low-risk metastaticnonmetastatic and low-risk metastatic GTDGTD  Intensive multimodality therapy hasIntensive multimodality therapy has resulted in cure rates of 80-90% inresulted in cure rates of 80-90% in patients with high-risk metastatic GTDpatients with high-risk metastatic GTD
  • 78.
    Follow-up AfterFollow-up After SuccessfulTreatmentSuccessful Treatment  Quantitative serum hCG levels should beQuantitative serum hCG levels should be obtained monthly for 6 months, every twoobtained monthly for 6 months, every two months for remainder of the first year,months for remainder of the first year, every 3 months during the second yearevery 3 months during the second year  Contraception should be maintained for atContraception should be maintained for at least 1 year after the completion ofleast 1 year after the completion of chemotherapy. Condom is the choice.chemotherapy. Condom is the choice.
  • 79.
    Placenta Site TrophoblasticPlacentaSite Trophoblastic Tumor (PSTT)Tumor (PSTT)
  • 80.
     Placenta SiteTrophoblastic Tumor is anPlacenta Site Trophoblastic Tumor is an extremely rare tumor that arised from theextremely rare tumor that arised from the placental implantation siteplacental implantation site  Tumor cells infiltrate the myometrium andTumor cells infiltrate the myometrium and grow between smooth-muscle cellsgrow between smooth-muscle cells DefinitionDefinition
  • 82.
     Surum hCGlevels are relatively lowSurum hCG levels are relatively low compared to those seen withcompared to those seen with choriocarcinoma.choriocarcinoma.  Several reports have noted a benignSeveral reports have noted a benign behavior of this disease. They are relativelybehavior of this disease. They are relatively chemotherapy-resistant, and deaths fromchemotherapy-resistant, and deaths from metastasis have occurred.metastasis have occurred.  Surgery has been the mainstay of treatmentSurgery has been the mainstay of treatment Dignosis and treatmentDignosis and treatment

Editor's Notes

  • #3 Platlete bone marrow
  • #5 because the diagnosis and decision to institute treatment are often undertaken without knowledge of the history
  • #16 Triploid : has three set of chromsomes
  • #23 This method does not answer the question of whether the mole is invasive ,or its potential malignancy
  • #31 Scattered: some parts of them are
  • #37 Polyhy’dramnios
  • #40 Prophylactic (for prevention)
  • #41 trophoblastic embolization (villi come out of placenta and locate in brain or lungs to block blood flow)
  • #71 CT Conouted tomography
  • #74 additional two courses should be given To make disease stable
  • #79 Oral contraceptives may interfere with the accurate measurement of hCG