This document provides information on gestational trophoblastic disease (GTD), which includes complete and partial hydatidiform moles, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It discusses the definitions, types, risk factors, pathogenesis, clinical presentation, diagnosis, treatment and management of GTD. Molar pregnancies are diagnosed using ultrasound imaging and quantitative beta-HCG levels. Treatment involves suction dilation and curettage followed by careful monitoring of beta-HCG levels to detect persistent trophoblastic disease. Chemotherapy may be used in high risk cases.

5. Gestational TrophoblasticGestational Trophoblastic
Disease (GTD)Disease (GTD)
Prof. Dr. Rafia Baloch
Head of Department
SZWH, CMC & SMBBMU
Larkana

6. It is a spectrum of trophoblastic diseases
that includes:
Complete molar pregnancy
Partial molar pregnancies
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Definitions
Gestational Trophoblastic Disease (GTD)
The last 2 may follow abortion, ectopic or normal pregnancy.

7. 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

8. • The termThe term Gestational TrophoblasticGestational Trophoblastic
TumorsTumors has been applied the latter threehas been applied the latter three
conditionsconditions
• 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)

9. Part I: Molar Pregnancy

10. Chorio
carcinoma
I-Pathologic
Classification
II-Clinical
Classification
βhCG based: WHO, FIGO,
ACOG 2004 & RCOG 2010
Benign
G.T.D.
G.T. Neoplasia
Malignant G.T.D.
Partial mole
Complete mole
Invasive
mole
Metastatic
Non metastatic
Low risk High risk
Gestational Trophoblastic Disease (GTD)
Placental site
trophoblastic
tumour
Persistent GTD
Classifications

11. Risk Factors
Incidence:USA 1/1000 South East 1/100 (Hospital)
Risk Factors:
Age: <20y (2fold) , > 40y(10 fold) & >50y (50% V.mole)
Prior Molar Pregnancy
Second molar: 1% - Third molar : 20%!
Diet:↑ in low fat Vit. A or carotene diet (complete mole)
Contraception :COC double the incidence
Previous spontaneous abortion: double the incidence
Repetitive H. moles in women with different partners

12. Partial moles have been linked to:
Higher educational levels
Smoking
Irregular menstrual cycles
Only male infants are among the
prior live births
Risk Factors

13. 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

14. Homozygous 90%
Pathogenesis of complete H. Mole

15. Pathogenesis of complete H. Mole
Heterozygous 10%

16. Pathogenesis of Partial H. Mole

17. 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 gametogenesisto abnormal gametogenesis
and fertilizationand fertilization
Hydatidiform Mole (molar pregnancy)Hydatidiform Mole (molar pregnancy)

18. Feature Partial mole Complete mole
Karyotype
Most commonly
69, XXX or - XXY
Most commonly
46, XX or -,XY
Pathology
Fetus Often present Absent
Amnion, fetal RBC Usually present Absent
Villous edema Variable, focal Diffuse
Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe
Features Of Partial And Complete Hydatidiform Moles

19. Complete Hydatiform Mole
Uterine wall

20. Pathology of
Molar
Pregnancy

21. 1-Trophoblastic proliferation
2-Hydropic Degeneration
Complete hydatidiform mole: Microscopically Enlarged,
edematous villi and abnormal trophoblastic proliferation that
diffusely involve the entire placenta

22. Complete hydatidiform mole: Macroscopically, these
microscopic changes transform the chorionic villi into clusters of
vesicles with variable dimensions the name hydatidiform mole
stems from this "bunch of grapes"

23. Partial H. Mole
Microscopically: The enlarged, edematous villi and
abnormal trophoblastic proliferation are slight and
focal and did not involve the entire villi.
There is a scalloping of chorionic villi
Fetal or embryonic or fetal RBCs
Macroscopically: The molar pattern did not involve
the entire placenta.
Uterine enlargement in excess of gestational age is
uncommon.
Theca-lutein cysts are rare
Fetal or embryonic tissue or amnion

24. Scalloping of chorionic villi
Partial Hydatidiform Mole
Trophoblastic proliferation are slight and focal

25. MANAGEMENT OFMOLAR
PREGNENCY
HISTORY
INVESTIGATION
TREATMENT

26. What Is The Most Common Presenting
Symptom Of A Complete Molar Pregnancy?
A. Hyperemesis
B. Bilateral enlarged theca lutein cysts
C. Vaginal bleeding
D. Uterine enlargement> than expected for GA
E. Pregnancy-induced hypertension

27. What Is The Most Common Presenting
Symptom Of A Complete Molar Pregnancy?
A. Hyperemesis 10%
B. Bilateral enlarged theca lutein cysts 30%
C. Vaginal bleeding 85%
D. Uterine enlargement> than expected for GA 40%
E. Pregnancy-induced hypertension 1%

28. How Is Complete Mole Diagnosed?
Diagnosis of hydatidiform moleDiagnosis of hydatidiform mole
UltrasoundUltrasound is the standard criterion foris the standard criterion for
identifying both complete and partial molaridentifying both complete and partial molar
pregnancies. The classic image is of apregnancies. The classic image is of a
“snowstorm” pattern“snowstorm” pattern
QuantitativeQuantitative beta-HCGbeta-HCG

29. Complete hydatidiform mole. The classic "snowstorm"
appearance is created by the multiple placental vesicles.

30. Complete Molar Pregnancy

31. Complete H.Mole
(High-resolution) U/S
Complex intrauterine
mass containing many
small cysts.
Complete H.Mole
Associated theca-lutein
cysts. U/S Power Doppler

32. Signs and Symptoms of Partial Hydatidiform MoleSigns and Symptoms of Partial Hydatidiform Mole
• Vaginal bleedingVaginal bleeding
• Absence of fetal heart tonesAbsence of fetal heart tones
• Uterine enlargement and preeclampsiaUterine enlargement and preeclampsia
is reported in only 3% of patients.is reported in only 3% of patients.
• Theca lutein cysts, hyperemesis is rare.Theca lutein cysts, hyperemesis is rare.

33. In most patients with a partial mole,
the clinical and U/S diagnosis is
Usually missed or incomplete abortion.
This emphasizes the need for a
thorough histopathologic evaluation of
all missed or incomplete abortions
How Is Partial H .Mole Diagnosed?

34. Partial Molar Pregnancies

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. There are 2 important basic lines :
1-Evacuation of the mole
2-Regular follow-up to detect
persistent trophoblastic disease
If both basic lines are done
appropriately, mortality rates can be
reduced to zero.
What Is The Plan of Management?

38. TreatmentTreatment
Suction dilation and curettageSuction dilation and curettage :to remove:to remove
benign hydatidiform molesbenign 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

39. The Molar Content For Histopathological Examination

40. Chemotherapy with a single-Chemotherapy with a single-
agent drugagent 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

41. High-risk postmolar trophoblasticHigh-risk postmolar trophoblastic
tumortumor
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

42. 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 cyst regressionuterine involution, ovarian cyst regression
and cessation of bleedingand cessation of bleeding
Follow-upFollow-up

43. Quantitative serum hCG levels should beQuantitative serum hCG levels should be
obtained every 2 weeks until negative forobtained every 2 weeks until negative for
three consecutive determinations,three consecutive determinations,
Followed by every 3 months for 1 years.Followed by every 3 months for 1 years.
Contraception should be practiced duringContraception should be practiced during
this follow-up periodthis follow-up period
Follow-upFollow-up

44. Barrier methods until normal β hCG level.
Once βhCG level have normalized:Combined
oral contraceptive (COC ) pill may be used.
If oral COC was started before the diagnosis of
GTD ,COC can be continue as its potential to
increase risk of GTN is very low
IUCD should not be used until β hCG levels are
normal to reduce uterine perforation.
What Is Safe Contraception Following GTD?

45. When Anti-D Is Required?
It is required in partial due to the
presence of fetal RBCs
In complete mole: if diagnosis is not
confirmed histopathologically
Is Anti-D Prophylaxis Required For
This Case?

46. Invasive moleInvasive mole

47. DefinitionDefinition
This term is applied to a molarThis term is applied to a molar
pregnancy in which molar villi grow intopregnancy in which molar villi grow into
the myometrium or its blood vessels, andthe myometrium or its blood vessels, and
may extend into the broad ligament andmay extend into the broad ligament and
metastasize to the lungs, the vagina or themetastasize to the lungs, the vagina or the
vulva.vulva.

48. Invasive hydatidiform mole infiltrating the myometrium

49. 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.

50. 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

51. ChoriocarcinomaChoriocarcinoma

52. DefinitionDefinition
A malignant form of GTD which canA malignant form of GTD which can
develop from a hydatidiform mole or fromdevelop from a hydatidiform mole or from
placental trophoblast cells associated withplacental trophoblast cells associated with
a healthy fetus ,an abortion or an ectopica healthy fetus ,an abortion or an ectopic
pregnancy.pregnancy.

53. Characterized by abnormal trophoblasticCharacterized by abnormal trophoblastic
hyperplasia and anaplasia , absence ofhyperplasia and anaplasia , absence of
chorionic villichorionic villi
DefinitionDefinition

54. Gross specimen of choriocarcinoma

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

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

57. 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

58. FIGO Staging System for Gestational Trophoblastic TumorsFIGO Staging System for Gestational Trophoblastic 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

60. IIb
IIa

61. IIIa<3cm or locate in half lung
IIIb disease beyond IIIa

63. Diagnosis and evaluationDiagnosis and evaluation
Gestational trophoblastic tumor isGestational trophoblastic tumor is
diagnosed by rising hCG followingdiagnosed by rising hCG following
evacuation of a molar pregnancy or anyevacuation of a molar pregnancy or any
pregnancy eventpregnancy event
Once the diagnosis established the furtherOnce the diagnosis established the further
examinations should be done to determineexaminations should be done to determine
the extent of disease ( X-ray, CT, MRI)the extent of disease ( X-ray, CT, MRI)

64. TreatmentTreatment
Nonmetastatic GTDNonmetastatic GTD
Low-Risk Metastatic GTDLow-Risk Metastatic GTD
High-Risk Metastatic GTDHigh-Risk Metastatic GTD

65. Treatment of Nonmetastatic GTDTreatment of Nonmetastatic GTD
HysterectomyHysterectomy is advisable as initial treatment inis 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.

66. Single-agent chemotherapySingle-agent chemotherapy is the treatment ofis 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 Nonmetastatic GTDTreatment of Nonmetastatic GTD
To prevent relapse or metastasisTo prevent relapse or metastasis

67. 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-Risk Metastatic GTDTreatment of Low-Risk Metastatic GTD

68. Multiagent chemotherapyMultiagent chemotherapy with or withoutwith or without
adjuvant radiotherapy or surgery should be theadjuvant radiotherapy or surgery should be the
initial treatment for patients with high-ristinitial 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-Risk Metastatic GTDTreatment of High-Risk Metastatic GTD

69. EMA-CO Chemotherapy for poor Prognostic DiseaseEMA-CO Chemotherapy for poor Prognostic 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)

70. 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

71. Follow-up After SuccessfulFollow-up After Successful
TreatmentTreatment
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 forContraception should be maintained for
at least 1 year after the completion ofat least 1 year after the completion of
chemotherapy. Condom is the choice.chemotherapy. Condom is the choice.

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

73. 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 and growTumor cells infiltrate the myometrium and grow
between smooth-muscle cellsbetween smooth-muscle cells
DefinitionDefinition

75. Surum hCG levels are relatively low comparedSurum hCG levels are relatively low compared
to those seen with choriocarcinoma.to those seen with choriocarcinoma.
Several reports have noted a benign behavior ofSeveral reports have noted a benign behavior of
this disease. They are relatively chemotherapy-this disease. They are relatively chemotherapy-
resistant, and deaths from metastasis haveresistant, and deaths from metastasis have
occurred.occurred.
Surgery has been the mainstay of treatmentSurgery has been the mainstay of treatment
Dignosis and treatmentDignosis and treatment