obstetrical condition

1. Gestational TrophoblasticGestational Trophoblastic
Disease (GTD)Disease (GTD)

3. 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

4.  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

5. 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

6. Hydatidiform MoleHydatidiform Mole
(molar pregnancy)(molar pregnancy)

7. 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

8.  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

9.  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

10. 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

11.  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

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 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)

15. 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

16. 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

17. Complete hydatidiform mole demonstrating
enlarged villi of various size

18. Hydatidiform mole: specimen from suction
curettage

19. A large amount of villi in the uterus.

20. The microscopic appearance of hydatidiform mole:
•Hyperplasia of trophobasitc cells
•Hydropic swelling of all villi
•Vessles are usually absent

21. A sonographic findings of a molar pregnancy. The
characteristic “snowstorm” pattern is evident.

22. Transvaginal sonogram demonstrating the “ snow storm” appearance.

23. Color Dopplor facilitates visualization of the enlarged spiral
arteriesclose proximity to the “ snow storm” appearance

24. Color Doppler image of a hydatidiform mole and surrounding
vessels. The uterine artery is easily identified from its anatomical
location.

26. Dopplor waveform analysis demonstrates low vascular resistance(RI=0.29) in
the spiral arteries, much lower than that obtained in normal early pregnancy

28. Partial hydartidiform mole

29. Microscopic image of partial molar pregnancy.

30. Here is a partial mole in a case of triploidy. Note the
scattered grape-like masses with intervening normal-
appearing placental tissue.

31. 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.

32. 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

33. 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.

34. 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

35.  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

36. Differential diagnosisDifferential diagnosis
• AbortionAbortion
• Multiple pregnancyMultiple pregnancy
• PolyhydramniosPolyhydramnios

37. 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

38. • 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

39. 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

40. 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

41.  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

42.  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

43. Invasive moleInvasive mole

44. 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.

45. Invasive mole: the tissue invades into the myometrial layer.
No obvious borderline, with obvious bleeding.

46. Invasive hydatidiform mole infiltrating the myometrium

47. 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.

48. 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.

49. Transvaginal color Doppler scan of a patient with invasive mole Following
uterine curettage, Persistent color signals within the myometeriun

50. Doppler image of invasive mole

51. Power Doppler easily detects a vascular echogenic
nodule within the myometrium, suggesting
invasive mole

52. Doppler image of invasive mole. Doppler waveform
analysis depicts low vascular resistance (RI= 0.35)

53. 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

54. ChoriocarcinomaChoriocarcinoma

55. 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.

56.  Characterized by abnormalCharacterized by abnormal
trophoblastic hyperplasia andtrophoblastic hyperplasia and
anaplasia , absence of chorionic villianaplasia , absence of chorionic villi
DefinitionDefinition

57. Gross specimen of choriocarcinoma

58. Microscopic image of choriocarcinoma
absence of chorionic villiabsence of chorionic villi

59. Microscopic image of choriocarcinoma

60. Doppler image of choriocarcinoma

61. Doppler image of choriocarcinoma

62. Symptoms and signsSymptoms and signs
• BleedingBleeding
• InfectionInfection
• Abdominal swellingAbdominal swelling
• Vaginal massVaginal mass
• Lung symptomsLung symptoms
• Symptoms from other metastasesSymptoms from other metastases

63. 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

64. 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

65.  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

67. IIb
IIa

68. IIIa<3cm or locate in 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 GTDNonmetastatic GTD
 Low-Risk Metastatic GTDLow-Risk Metastatic GTD
 High-Risk Metastatic GTDHigh-Risk Metastatic GTD

72. 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.

73.  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

74.  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

75.  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

76. 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)

77. 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

78. 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.

79. Placenta Site TrophoblasticPlacenta Site Trophoblastic
Tumor (PSTT)Tumor (PSTT)

80.  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

82.  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