Hydatiform mole

obstetrical condition

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

3. Types of GTDTypes of GTD
BenignBenign
•Hydatidiform mole/molar pregnancy Hydatidiform mole/molar pregnancy
(complete or incomplete)(complete or incomplete)
malignantmalignant
•Invasive mole Invasive mole
•Choriocarcinoma (chorioepithelioma)Choriocarcinoma (chorioepithelioma)
•Placental site trophoblastic tumorPlacental site trophoblastic tumor

4. The term The term Gestational Trophoblastic Gestational Trophoblastic
Tumors Tumors has been applied the latter has been applied the latter
three conditionsthree conditions
Arise from the trophoblastic elementsArise from the trophoblastic elements
Retain the invasive tendencies of the Retain the invasive tendencies of the
normal placenta or metastasisnormal placenta or metastasis
Keep secretion of the human chorionic Keep secretion of the human chorionic
gonadotropin (hCG)gonadotropin (hCG)
Types of GTDTypes of GTD

5. PATHOLOGIC PATHOLOGIC
CLASSIFICATIONCLASSIFICATION
CLINICAL CLINICAL
CLASSIFICATIONCLASSIFICATION
Hydatidiform moleHydatidiform mole
*complete*complete
*incomplete*incomplete
Benign gestational Benign gestational
trophoblastic diseasetrophoblastic disease
Invasive moleInvasive mole
Malignant Malignant
trophoblastic diseasetrophoblastic disease
Nonmetastatic Nonmetastatic
Placental site Placental site
trophoblastic trophoblastic
tumortumor
Metastatic Metastatic
Choriocarcinoma Choriocarcinoma High risk High risk Low riskLow risk
Pathologic and clinical classifications
for gestational trophoblastic disease

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

7. Definition and Etiology Definition and Etiology
 Hydatidiform mole is a pregnancy Hydatidiform mole is a pregnancy
characterized by vesicular swelling of characterized by vesicular swelling of
placental villi and usually the absence of placental villi and usually the absence of
an intact fetus.an intact fetus.
 The etiology of hydatidiform mole The etiology of hydatidiform mole
remains unclear, but it appears to be due remains unclear, but it appears to be due
to abnormal gametogenesis and to abnormal gametogenesis and
fertilization fertilization

8. In a In a ‘‘complete molecomplete mole’’ the mass of the mass of
tissue is completely made up of tissue is completely made up of
abnormal cells abnormal cells
There is no fetus and nothing can There is no fetus and nothing can
be found at the time of the first be found at the time of the first
scan. scan.
Definition and Etiology Definition and Etiology

9. In a In a ‘‘partial molepartial mole’’, the mass may , the mass may
contain both these abnormal cells contain both these abnormal cells
and often a fetus that has severe and often a fetus that has severe
defects. defects.
In this case the fetus will be In this case the fetus will be
consumed ( destroyed) by the consumed ( destroyed) by the
growing abnormal mass very growing abnormal mass very
quickly.quickly. (shrink)(shrink)
Definition and Etiology Definition and Etiology

10. Incidence Incidence
•1 out of 1500-2000 pregnancies in the 1 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 in Repeat hydatidiform moles occure in
0.5-2.6% of patients, and these 0.5-2.6% of patients, and these
patiens have a subsequent greater patiens have a subsequent greater
risk of developing invasive mole or risk of developing invasive mole or
choriocarcinomachoriocarcinoma
There is an increased risk of molar There is an increased risk of molar
pregnancy for women over the age 40pregnancy for women over the age 40
Incidence Incidence

12. Approximately 10-17% of hydatidiform Approximately 10-17% of hydatidiform
moles will result in invasive molemoles will result in invasive mole
Approximately 2-3% of hydatidiform Approximately 2-3% of hydatidiform
moles progress to choriocarcinoma moles progress to choriocarcinoma
( most of them are curable) ( most of them are curable)
Incidence Incidence
Not definitely benign disease , Not definitely benign disease ,
has a tight relationship with GTThas a tight relationship with GTT

14. Clinical risk factors for molar Clinical 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
Birthplace Birthplace
Outside North America( occasionally has Outside 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 of Comparative Pathologic Features of
Complete and Partial Hydatidiform Complete and Partial Hydatidiform
MoleMole
FeatureFeatureComplete MoleComplete Mole Partial MolePartial Mole
KaryotypeKaryotype Usually diploid 46XXUsually diploid 46XXUsually triploidy 69XXX most Usually triploidy 69XXX most
common. common.
VilliVilli All villi hydropin; no All villi hydropin; no
normal adjacent villinormal adjacent villi
Normal adjacent villi may be Normal adjacent villi may be
present present
vesselsvessels present they contain no present they contain no
fetal blood cellsfetal blood cells
blood cellsblood cells
Fetal tissueFetal tissueNone presentNone present Usually presentUsually present
TrophoblastTrophoblastHyperplasia usually Hyperplasia usually
present to variable present 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 Complete Signs and Symptoms of Complete
Hydatidiform MoleHydatidiform Mole
•Vaginal bleedingVaginal bleeding
•Hyperemesis ( severe vomit)Hyperemesis ( severe vomit)
•Size inconsistent with gestational Size inconsistent with gestational
age( with no fetal heart beating and age( with no fetal heart beating and
fetal movement)fetal movement)
•PreeclampsiaPreeclampsia
•Theca lutein ovarian cystsTheca lutein ovarian cysts

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

34. Diagnosis of hydatidiform Diagnosis of hydatidiform
molemole
Quantitative beta-HCGQuantitative beta-HCG
Ultrasound is the criterion standard for Ultrasound is the criterion standard for
identifying both complete and partial identifying both complete and partial
molar pregnancies. The classic image molar pregnancies. The classic image
is of a is of a ““snowstormsnowstorm”” pattern pattern

35. The most common symptom of a mole is The most common symptom of a mole is
vaginal bleeding during the first trimester vaginal bleeding during the first trimester
however very often no signs of a problem however very often no signs of a problem
appear and the mole can only be diagnosed by appear 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 the Occasionally, 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 always NOTE: Vaginal bleeding does not always
indicate a problem!indicate a problem!
DiagnosisDiagnosis

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

37. Treatment Treatment
Suction dilation and curettageSuction dilation and curettage :to :to
remove benign hydatidiform molesremove benign hydatidiform moles
When the diagnosis of hydatidiform mole is When the diagnosis of hydatidiform mole is
established, the molar pregnancy should be established, the molar pregnancy should be
evacuated. evacuated.
An oxytocic agent should be infused An oxytocic agent should be infused
intravenously after the start of evacuation intravenously after the start of evacuation
and continued for several hours to enhance and 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.
Treatment Treatment

39. Chemotherapy with a Chemotherapy with a
single-agent drugsingle-agent drug
Prophylactic (for prevention) Prophylactic (for prevention)
chemotherapy at the time of chemotherapy at the time of
or immediately following or immediately following
molar evacuation may be molar evacuation may be
considered for the high-risk considered for the high-risk
patients( to prevent spread of patients( to prevent spread of
disease )disease )
Treatment Treatment

40. High-risk postmolar High-risk postmolar
trophoblastic tumortrophoblastic tumor
1.1.Pre-evacuation uterine size larger than expected Pre-evacuation uterine size larger than expected
for gestational durationfor gestational duration
2.2.Bilateral ovarian enlargement (> 9 cm theca lutein Bilateral 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 such Medical complications of molar pregnancy such
as toxemia, hyperthyrodism and trophoblastic as toxemia, hyperthyrodism and trophoblastic
embolization (villi come out of placenta )embolization (villi come out of placenta )
6.6. repeat hydatidiform mole repeat hydatidiform mole

41. Patients with hudatidiform mole are Patients with hudatidiform mole are
curative over 80% by treatment of curative over 80% by treatment of
evacuation. evacuation.
The follow-up after evacuation is key The follow-up after evacuation is key
necessary necessary
uterine involution, ovarian cyst uterine involution, ovarian cyst
regression and cessation of bleedingregression and cessation of bleeding
Follow-upFollow-up

42. Quantitative serum hCG levels should Quantitative serum hCG levels should
be obtained every 1-2 weeks until be obtained every 1-2 weeks until
negative for three consecutive negative for three consecutive
determinations, determinations,
Followed by every 3 months for 1 Followed by every 3 months for 1
years. years.
Contraception should be practiced Contraception should be practiced
during this follow-up periodduring this follow-up period
Follow-upFollow-up

43. Invasive moleInvasive mole

44. Definition Definition
This term is applied to a molar This term is applied to a molar
pregnancy in which molar villi grow pregnancy in which molar villi grow
into the myometrium or its blood into the myometrium or its blood
vessels, and may extend into the vessels, and may extend into the
broad ligament and metastasize to the broad 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 typical A case of invasive mole: inside the uterine cavity the typical
““snow stormsnow storm”” appearance can be detected, The location of appearance 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 Metastatic Common Sites for Metastatic
Gestational Trophoblastic TumorsGestational Trophoblastic Tumors
Site Site Per centPer cent
Lung Lung 60-9560-95
Vagina Vagina 40-5040-50
Vulva/cervixVulva/cervix 10-1510-15
Brain Brain 5-155-15
Liver Liver 5-155-15
Kidney Kidney 0-50-5
Spleen Spleen 0-50-5
Gastrointestinal Gastrointestinal 0-50-5

54. Choriocarcinoma Choriocarcinoma

55. Definition Definition
A malignant form of GTD which can A malignant form of GTD which can
develop from a hydatidiform mole or develop from a hydatidiform mole or
from placental trophoblast cells from placental trophoblast cells
associated with a healthy fetus ,an associated with a healthy fetus ,an
abortion or an ectopic pregnancy.abortion or an ectopic pregnancy.

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

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 signs Symptoms 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
Hydatidiform Hydatidiform
molemole
Abortion,Abortion,
ectopicectopic
Term Term
pregnancypregnancy
——
Interval (months) of Interval (months) of
treatment treatment
<4<4 4-64-6 7-127-12 >12>12
Initial hCG(mIU/ml)Initial hCG(mIU/ml)<10<10
33
1010
33
-10-10
44
1010
44
-10-10
55
>10>10
55
Largest tumor(cm)Largest tumor(cm) <3<3 3-53-5 >5>5 ——
Sites of metastasisSites of metastasisLung Lung
Spleen,Spleen,
kidneykidney
GI tract, liverGI tract, liverBrainBrain
No. of metastasisNo. of metastasis —— 1-41-4 4-84-8 88
Previous (treatment)Previous (treatment)—— —— Single drugSingle drug2 or more2 or more
0-4 low risk, 5-7 intermediate risk, >8 high risk for death

64. FIGO Staging System for Gestational FIGO Staging System for Gestational
Trophoblastic TumorsTrophoblastic Tumors
StageStage Description Description
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 genital Extends to the lungs with or without genital
tracttract
ⅣⅣ All other metastatic sitesAll other metastatic sites

65. Substages assigned for each stage as Substages 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 > 100,000 1. Pretherapy serum hCG > 100,000
mlU/mlmlU/ml
2. Duration of disease >6 months2. Duration of disease >6 months
FIGO Staging System for Gestational FIGO Staging System for Gestational
Trophoblastic TumorsTrophoblastic Tumors

67. IIb
IIa

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

70. Diagnosis and Diagnosis and
evaluationevaluation
Gestational trophoblastic tumor is Gestational trophoblastic tumor is
diagnosed by rising hCG following diagnosed by rising hCG following
evacuation of a molar pregnancy or evacuation of a molar pregnancy or
any pregnancy eventany pregnancy event
Once the diagnosis established the Once the diagnosis established the
further examinations should be done further 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. Treatment Treatment
Nonmetastatic GTDNonmetastatic GTD
Low-Risk Metastatic GTDLow-Risk Metastatic GTD
High-Risk Metastatic GTDHigh-Risk Metastatic GTD

72. Treatment of Nonmetastatic Treatment of Nonmetastatic
GTDGTD
Hysterectomy is advisable as initial treatment in Hysterectomy is advisable as initial treatment in
patients with nonmetastatic GTD who no longer patients with nonmetastatic GTD who no longer
wish to preserve fertility wish to preserve fertility
This choice can reduce the number of course This choice can reduce the number of course
and shorter duration of chemotherapy.and shorter duration of chemotherapy.
Adjusted single-agent chemotherapy at the time Adjusted single-agent chemotherapy at the time
of operation is indicated to eradicate any occult of operation is indicated to eradicate any occult
metastases and reduce tumor dissemination.metastases and reduce tumor dissemination.

73. Single-agent chemotherapy is the treatment of Single-agent chemotherapy is the treatment of
choice for patients wishing to preserve their choice for patients wishing to preserve their
fertility.fertility.
Methotrexate(MTX) and Actinomycin-D are Methotrexate(MTX) and Actinomycin-D are
generally chemotherapy agentsgenerally chemotherapy agents
Treatment is continued until three consecutive Treatment is continued until three consecutive
normal hCG levels have been obtained and two normal hCG levels have been obtained and two
courses have been given after the first normal courses have been given after the first normal
hCG level. hCG level.
Treatment of Nonmetastatic Treatment 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 chemotherapy If resistance to sequential single-agent chemotherapy
develops, combination chemotherapy would be taken develops, 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 combination agent chemotherapy will require combination
chemotherapy with or without surgery to achieve chemotherapy with or without surgery to achieve
remissionremission
Treatment of Low-Risk Treatment of Low-Risk
Metastatic GTDMetastatic GTD

75. Multiagent chemotherapy with or without Multiagent chemotherapy with or without
adjuvant radiotherapy or surgery should be adjuvant radiotherapy or surgery should be
the initial treatment for patients with high-rist the initial treatment for patients with high-rist
metastatic GTDmetastatic GTD
EMA-CO regimen formula is good choice for EMA-CO regimen formula is good choice for
high-rist metastatic GTDhigh-rist metastatic GTD
Adjusted surgeries such as removing foci of Adjusted surgeries such as removing foci of
chemotherapy-resistant disease, controlling chemotherapy-resistant disease, controlling
hemorrhage may be the one ofhemorrhage may be the one of treatment treatment
regimenregimen
Treatment of High-Risk Treatment of High-Risk
Metastatic GTDMetastatic GTD

76. EMA-CO Chemotherapy for poor EMA-CO Chemotherapy for poor
Prognostic DiseasePrognostic Disease
Etoposide(VP-16)Etoposide(VP-16)100mg/M100mg/M
22
IV daily×2 days IV daily×2 days
(over 30-45 (over 30-45
minutes)minutes)
MethotrexateMethotrexate 100mg/M100mg/M
22
IV losding dose, IV losding dose,
then 200mg/M2 over then 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 24 15mg IM or p.o. q 12 hours×4 starting 24
hours after starting methotrexatehours after starting methotrexate
Cyclophosphamide Cyclophosphamide 600mg/M600mg/M
22
IV on day8IV on day8
Oncovin (vincristine)Oncovin (vincristine)1mg/M1mg/M
22
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% in Cure rates should approach 100% in
nonmetastatic and low-risk metastatic nonmetastatic and low-risk metastatic
GTDGTD
Intensive multimodality therapy has Intensive multimodality therapy has
resulted in cure rates of 80-90% in resulted in cure rates of 80-90% in
patients with high-risk metastatic GTDpatients with high-risk metastatic GTD

78. Follow-up After Follow-up After
Successful TreatmentSuccessful Treatment
Quantitative serum hCG levels should be Quantitative serum hCG levels should be
obtained monthly for 6 months, every two obtained 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 at Contraception should be maintained for at
least 1 year after the completion of least 1 year after the completion of
chemotherapy. Condom is the choice.chemotherapy. Condom is the choice.

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

80. Placenta Site Trophoblastic Tumor is an Placenta Site Trophoblastic Tumor is an
extremely rare tumor that arised from the extremely rare tumor that arised from the
placental implantation siteplacental implantation site
Tumor cells infiltrate the myometrium and Tumor cells infiltrate the myometrium and
grow between smooth-muscle cellsgrow between smooth-muscle cells
Definition Definition

82. Surum hCG levels are relatively low Surum hCG levels are relatively low
compared to those seen with compared to those seen with
choriocarcinoma. choriocarcinoma.
Several reports have noted a benign Several reports have noted a benign
behavior of this disease. They are relatively behavior of this disease. They are relatively
chemotherapy-resistant, and deaths from chemotherapy-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 treatment Dignosis and treatment