Gestational Trophoblastic
Disease (GTD)
Types of GTD
Benign
• Hydatidiform mole/molar pregnancy
(complete or incomplete)
malignant
• Invasive mole
• Choriocarcinoma (chorioepithelioma)
• Placental site trophoblastic tumor
Types of GTD




The term Gestational Trophoblastic
Tumors has been applied the latter
three conditions
Arise from the trophoblastic elements
Retain the invasive tendencies of the
normal placenta or metastasis
Keep secretion of the human chorionic
gonadotropin (hCG)
Pathologic and clinical classifications
for gestational trophoblastic disease
PATHOLOGIC
CLASSIFICATION
CLINICAL
CLASSIFICATION
Hydatidiform mole
*complete
*incomplete
Benign gestational
trophoblastic disease
Invasive mole
Placental site
trophoblastic
tumor
Choriocarcinoma
Malignant
trophoblastic disease
Nonmetastatic
Metastatic
High risk
Low risk
Hydatidiform Mole
(molar pregnancy)
Definition and Etiology
Hydatidiform mole is a pregnancy
characterized by vesicular swelling of
placental villi and usually the absence of
an intact fetus.
 The etiology of hydatidiform mole
remains unclear, but it appears to be due
to abnormal gametogenesis and
fertilization

Definition and Etiology


In a ‘complete mole’ the mass of
tissue is completely made up of
abnormal cells
There is no fetus and nothing can
be found at the time of the first
scan.
Definition and Etiology


In a ‘partial mole’, the mass may
contain both these abnormal cells
and often a fetus that has severe
defects.
In this case the fetus will be
consumed ( destroyed) by the
growing abnormal mass very
quickly. (shrink)
Incidence
• 1 out of 1500-2000 pregnancies in the
U.S. and Europe
• 1 out of 500-600 (another report 1%)
pregnancies in some Asian countries.
• Complete > incomplete
Incidence


Repeat hydatidiform moles occure in
0.5-2.6% of patients, and these
patiens have a subsequent greater risk
of developing invasive mole or
choriocarcinoma
There is an increased risk of molar
pregnancy for women over the age 40
Incidence


Approximately 10-17% of hydatidiform
moles will result in invasive mole
Approximately 2-3% of hydatidiform
moles progress to choriocarcinoma
( most of them are curable)
Not definitely benign disease ,
has a tight relationship with GTT
Clinical risk factors for molar pregnancy
Age (extremes of reproductive years)
<15
>40
Reproductive history
prior hydatidiform mole
prior spontaneous abortion
Diet
Vitamin A deficiency
Birthplace
Outside North America( occasionally has
this disease)
Cytogenetics
Complete molar pregnancy
Chromosomes are paternal , diploid
46,XX in 90% cases
46,XY in a small part
Partial molar pregnancy
Chromosomes are paternal and maternal, triploid.
69,XXY 80%
69,XXX or 69,XYY 10-20%
Wrong life message , so can not develop normally
Comparative Pathologic Features of
Complete and Partial Hydatidiform Mole
Feature
Complete Mole
Partial Mole
Karyotype
Usually diploid 46XX
Usually triploidy 69XXX most
common.
Villi
All villi hydropin; no
normal adjacent villi
Normal adjacent villi may be
present
vessels
present they contain no blood cells
fetal blood cells
Fetal tissue
None present
Usually present
Trophoblast
Hyperplasia usually
present to variable
degrees
Hyperplasia 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 Complete
Hydatidiform Mole
• Vaginal bleeding
• Hyperemesis ( severe vomit)
• Size inconsistent with gestational
age( with no fetal heart beating and
fetal movement)
• Preeclampsia
• Theca lutein ovarian cysts
Signs and Symptoms of Partial
Hydatidiform Mole
• Vaginal bleeding
• Absence of fetal heart tones
• Uterine enlargement and
preeclampsia is reported in only 3%
of patients.
• Theca lutein cysts, hyperemesis is
rare.
Diagnosis of hydatidiform mole
Quantitative beta-HCG
Ultrasound is the criterion standard for
identifying both complete and partial
molar pregnancies. The classic image
is of a “snowstorm” pattern
Diagnosis




The most common symptom of a mole is
vaginal bleeding during the first trimester
however very often no signs of a problem
appear and the mole can only be diagnosed by
use of ultrasound scanning. (rutting check)
Occasionally, a uterus that is too large for the
stage of the pregnancy can be an indication.
NOTE: Vaginal bleeding does not always
indicate a problem!
Differential diagnosis
• Abortion
• Multiple pregnancy
• Polyhydramnios
Treatment
Suction dilation and curettage :to remove
benign hydatidiform moles
When the diagnosis of hydatidiform mole is
established, the molar pregnancy should be
evacuated.
An oxytocic agent should be infused
intravenously after the start of evacuation
and continued for several hours to enhance
uterine contractility
Treatment
• Removal of the uterus (hysterectomy) :
used rarely to treat hydatidiform moles if
future pregnancy is no longer desired.
Treatment
Chemotherapy with a
single-agent drug
Prophylactic (for prevention)
chemotherapy at the time of
or immediately following
molar evacuation may be
considered for the high-risk
patients( to prevent spread
of disease )
High-risk postmolar
trophoblastic tumor
1.
2.
3.
4.
5.
6.
Pre-evacuation uterine size larger than expected
for gestational duration
Bilateral ovarian enlargement (> 9 cm theca
lutein cysts)
Age greater than 40 years
Very high hCG levels(>100,000 m IU/ml)
Medical complications of molar pregnancy such as
toxemia, hyperthyrodism and trophoblastic
embolization (villi come out of placenta )
repeat hydatidiform mole
Follow-up



Patients with hudatidiform mole are
curative over 80% by treatment of
evacuation.
The follow-up after evacuation is key
necessary
uterine involution, ovarian cyst
regression and cessation of bleeding
Follow-up



Quantitative serum hCG levels should
be obtained every 1-2 weeks until
negative for three consecutive
determinations,
Followed by every 3 months for 1
years.
Contraception should be practiced
during this follow-up period
Invasive mole
Definition
This term is applied to a molar
pregnancy in which molar villi grow
into the myometrium or its blood
vessels, and may extend into the
broad ligament and metastasize to the
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 typical
“snow storm” appearance can be detected, The location of
blood flow suggest an invasive mole.
The same patient owing to the myometrial invasion.
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 Metastatic
Gestational Trophoblastic Tumors
Site
Lung
Vagina
Vulva/cervix
Brain
Liver
Kidney
Spleen
Gastrointestinal
Per cent
60-95
40-50
10-15
5-15
5-15
0-5
0-5
0-5
Choriocarcinoma
Definition
A malignant form of GTD which
can develop from a hydatidiform mole
or from placental trophoblast cells
associated with a healthy fetus ,an
abortion or an ectopic pregnancy.
Definition

Characterized by abnormal
trophoblastic hyperplasia and
anaplasia , absence of chorionic villi
Gross specimen of choriocarcinoma
Microscopic image of choriocarcinoma
absence of chorionic villi
Microscopic image of choriocarcinoma
Doppler image of choriocarcinoma
Doppler image of choriocarcinoma
Symptoms and signs
•
•
•
•
•
•
Bleeding
Infection
Abdominal swelling
Vaginal mass
Lung symptoms
Symptoms from other metastases
WHO Prognostic Scoring System
Score
Prognostic factor
0
1
2
4
Age(years)
≤39
>39
—
—
Pregnancy history
Hydatidiform Abortion,
mole
ectopic
Term
pregnancy
—
Interval (months) of
treatment
<4
4-6
7-12
>12
Initial hCG(mIU/ml)
<103
103-104
104-105
>105
Largest tumor(cm)
<3
3-5
>5
—
Sites of metastasis
Lung
Spleen,
kidney
GI tract, liver
Brain
No. of metastasis
—
1-4
4-8
8
Previous (treatment)
—
—
Single drug
2 or more
0-4 low risk, 5-7 intermediate risk, >8 high risk for death
FIGO Staging System for Gestational
Trophoblastic Tumors
Stage
Ⅰ
Ⅱ
Ⅲ
Ⅳ
Description
Limited to uterine corpus
Extends to the adnexae, outside the uterus,
but limited to the genital structures
Extends to the lungs with or without genital
tract
All other metastatic sites
FIGO Staging System for Gestational
Trophoblastic Tumors


Substages assigned for each stage as
follows:
A: No risk factors present
B: One risk factor
C: Both risk factors
Risk factors used to assign substages:
1.
Pretherapy serum hCG > 100,000
mlU/ml
2. Duration of disease >6 months
IIa
IIb
IIIa<3cm or locate in half lung
IIIb disease beyond IIIa
Diagnosis and evaluation


Gestational trophoblastic tumor is
diagnosed by rising hCG following
evacuation of a molar pregnancy or
any pregnancy event
Once the diagnosis established the
further examinations should be done
to determine the extent of disease ( Xray, CT, MRI)
Treatment



Nonmetastatic GTD
Low-Risk Metastatic GTD
High-Risk Metastatic GTD
Treatment of Nonmetastatic GTD



Hysterectomy is advisable as initial treatment in
patients with nonmetastatic GTD who no longer
wish to preserve fertility
This choice can reduce the number of course
and shorter duration of chemotherapy.
Adjusted single-agent chemotherapy at the time
of operation is indicated to eradicate any occult
metastases and reduce tumor dissemination.
Treatment of Nonmetastatic GTD



Single-agent chemotherapy is the treatment of
choice for patients wishing to preserve their
fertility.
Methotrexate(MTX) and Actinomycin-D are
generally chemotherapy agents
Treatment is continued until three consecutive
normal hCG levels have been obtained and two
courses have been given after the first normal
hCG level.
To prevent relapse or metastasis
Treatment of Low-Risk
Metastatic GTD



Single-agent chemotherapy with MTX or actinomycinD is the treatment for patients in this category
If resistance to sequential single-agent chemotherapy
develops, combination chemotherapy would be taken
Approximately 10-15% of patients treated with singleagent chemotherapy will require combination
chemotherapy with or without surgery to achieve
remission
Treatment of High-Risk
Metastatic GTD



Multiagent chemotherapy with or without
adjuvant radiotherapy or surgery should be
the initial treatment for patients with highrist metastatic GTD
EMA-CO regimen formula is good choice for
high-rist metastatic GTD
Adjusted surgeries such as removing foci of
chemotherapy-resistant disease, controlling
hemorrhage may be the one of treatment
regimen
EMA-CO Chemotherapy for poor
Prognostic Disease
100mg/M2
IV daily×2 days
(over 30-45 minutes)
Methotrexate
100mg/M2
IV losding dose,
then 200mg/M2
over 12 hours day 1
Actinomycin D
0.5mg
IV daily×2 days
Folinic acid
15mg IM or p.o. q 12 hours×4 starting 24
hours after starting methotrexate
Cyclophosphamide
600mg/M2
Etoposide(VP-16)
Oncovin (vincristine) 1mg/M2
(Repeat every 15 days as toxicity permits)
IV on day8
IV on day8
Prognosis


Cure rates should approach 100% in
nonmetastatic and low-risk metastatic
GTD
Intensive multimodality therapy has
resulted in cure rates of 80-90% in
patients with high-risk metastatic GTD
Follow-up After Successful
Treatment


Quantitative serum hCG levels should be
obtained monthly for 6 months, every two
months for remainder of the first year,
every 3 months during the second year
Contraception should be maintained for at
least 1 year after the completion of
chemotherapy. Condom is the choice.
Placenta Site Trophoblastic
Tumor (PSTT)
Definition


Placenta Site Trophoblastic Tumor is an
extremely rare tumor that arised from the
placental implantation site
Tumor cells infiltrate the myometrium and
grow between smooth-muscle cells
Dignosis and treatment



Surum hCG levels are relatively low
compared to those seen with
choriocarcinoma.
Several reports have noted a benign
behavior of this disease. They are relatively
chemotherapy-resistant, and deaths from
metastasis have occurred.
Surgery has been the mainstay of treatment