Gestational Trophoblastic

Disease (GTD)
Dr. Swati Singh

Department of Obs and Gyn

UDUTH

Molar Pregnancy

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

Classifications
Gestational Trophoblastic Disease (GTD)
Invasive Chorio
I-Pathologic Partial mole
mole
Complete
mole
Classification
carcinoma

II-Clinical
Classification
hCG based:
WHO, FIGO,
ACOG 2004 &
RCOG 2010

Pe
rsi
st

Benign
G.T.D.

en
tG

TD

Placental site
trophoblastic
tumour

G.T. Neoplasia
Malignant G.T.D.
Metastatic

Non metastatic
Low risk

High risk

Hydatidiform Mole

(H. MOLE)
=
Vesicular Mole

Hydatidiform Moles (H.M.)

Hydatidiform moles are abnormal pregnancies
characterized histologically by :

Trophoblastic proliferation (Both

syncitiotrophoblast & cytotrophoblast)

Edema of the villous stroma (Hydropic) .

Based on the degree and extent of these tissue
changes, hydatidiform moles are categorized as
either
Complete hydatidiform mole.
Partial hydatidiform mole.

Features Of Partial And Complete Hydatidiform Moles

Feature

Partial mole

Complete mole

Most commonly
69, XXX or - XXY

Most commonly
46, XX or -,XY

Fetus

Often present

Absent

Amnion, fetal RBC

Usually present

Absent

Villous edema

Variable, focal

Diffuse

Karyotype
Pathology

Trophoblastic proliferation Focal, slight-moderate

Diffuse, slight-severe

Clinical presentation
Diagnosis

Missed abortion

Molar gestation

Uterine size

Small for dates

50% large for dates

Theca lutein cysts

Rare

25-30%

Medical complications

Rare

10-25%

Postmolar CTN

2.5-7.5%

6.8-20%

Epidemiology& Risk Factors

Incidence:USA 1/1000 South East 1/500 (Hospital) and in
Nigeria 1/379.

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

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

Karyotype

Homozygous 90%

Pathogenesis of complete H. Mole

Karyotype

Heterozygous 10%

Pathogenesis of complete H. Mole

Karyotype

Pathogenesis of Partial H. Mole

Complete H. Mole
Microscopically Enlarged, edematous villi and abnormal
trophoblastic proliferation that diffusely involve the
entire villi
No fetal tissue, RBCs or amnion are produced
Macroscopically, these microscopic changes transform the
chorionic villi into clusters of vesicles with variable
dimensions like bunch of grapes"
No fetal or embryonic tissue are produced
Uterine enlargement in excess of gestational age .
Theca-lutein cyst associated in 30%

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"

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

Vesicles

Maternal side
Partial Hydatiform Mole

Partial H. mole.

Presentation
The classic features are
Irregular vaginal bleeding
Hyperemesis
Excessive uterine enlargement &
Early failed pregnancy.
Breathlessness due to anaemia
Abdominal pain
Some women will present early with passage of molar tissue

Rarer presentations include:

Hyperthyroidism
Early onset pre-eclampsia
Abdominal distension due to theca lutein cysts

Very rarely
Acute respiratory failure
Neurological symptoms such as seizures (?
metastatic disease).

Clinical Findings
Anemia
Breathlessness
Pseudo- Toxemia which consist of
Systolic hypertension edema and
proteinuria

The Uterus is doughy in consistence

Absence of fetal part
Enlarged Cystic Ovaries

Complete Molar Pregnancy

Complete hydatidiform mole. The classic "snowstorm"

appearance is created by the multiple placental vesicles.

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

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

Classically: A thickened, hydropic placenta with fetal

or embryonic tissue
Multiple soft markers, including:

Cystic spaces in the placenta and

Transverse to AP dimension a ratio of the gestation
sac of > 1.5, is required for the reliable diagnosis of
a partial molar pregnancy

Differential diagnosis
Multiple pregnancy.
Hydatidiform mole.
Threatened abortion.
Ectopic pregnancy.

Partial Molar Pregnancies

Management
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.

Is That The Same For Partial Mole?

For Partial mole: It depends on the fetal parts
Small fetal parts :Suction curettage
Large fetal parts: Medical (oxytocics)
In partial mole the oxytocics is safe ,as the
hazard to embolise and disseminate
trophoblastic tissue is very low
Also, the needing for chemotherapy is 0.10.5%.

Post-evacuation Surveillance

Why?
To determine when pregnancy
can be allowed

To detect persistent
trophoblastic disease (i.e. GTN)

The Post-evacuation Surveillance. How?

A baseline serum -hCG level is obtained within
48 hours after evacuation.
Levels are monitored every 1 to 2 weeks
while still elevated to detect persistent
trophoblastic disease (GTN).
These levels should progressively fall to an
undetectable level (<5 mu/ml).
If symptoms are persistent, more frequent hCG
estimation and U/S examination D&C are
advised

What Is The Optimum Follow-up

Period Following Normalization of
hCG?

A. For 6 months from the date of uterine

evacuation.

B. For 6 months from normalization of the

hCG level.

C. For 12 months from the date of uterine

evacuation. (For Nigeria)

What Is Safe Contraception Following GTD?

Barrier methods until normal hCG level.
Once hCG 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 hCG levels are
normal to reduce uterine perforation.

Part II: Gestational Trophoblastic

Neoplasia (GTN)

Nonmetastatic disease
Locally invasive GTT develops in about
15%

Patient usually present with

Irregular vaginal bleeding
Theca lutein cysts
Uterine subinvolution or asymptomatic
enlargement
Persistently elevated serum hCG level

Persistent GTT
After hydatiaiform mole

Invasive Mole
Villus formation preserved
Trophoblast cells invade myometrium and blood vessels

Villus

Myometrium
Myometrium invaded

Myometrial invasion

Vesicles

Invasive H. Mole

Sometimes involving the peritoneum, parametrium, or

vaginal vault. Originate almost always from H. mole

Placental-site trophoblastic
tumor
Uncommon but important variant
of choriocarcinoma

Characteristic
Produce small amount of hCG and
hPL
Remain confined to the uterus
Metastasizing late in their course

Relatively insensitive to
chemotherapy

Gestational Choriocarcinoma
Aneuploidy (not multiplication of 23 )
1 in 30,000 pregnancies in western world
1 in 300 to 1000 in Nigeria
40% after molar pregnancy: Easily Diagnosed
60% non-molar pregnancy: Difficult Diagnosis
The main presentations are often nongynecologic including hemoptysis or pulmonary
embolism, cerebral hemorrhage, gastrointestinal

Gestational Choriocarcinoma
Sheets of anaplastic cytotrophoblast and
syncytiotrophoblast cells with hemorrhage &
necrosis.
Myometrial & B. vessels invasion and early metastases
No Villus formation
Syncytiotrophoblast

Cytotrophoblast

Metastatic disease
Metastatic GTT occur in about 4%
after complete mole

Symptom of metastases may result

from spontaneous bleeding at
metastatic foci

The common site of metastases are

Lung(80%)
vagina(30%)
pelvis(20%)
liver(10%)
brain(10%)

GTN Vaginal
Metastasis

Cranial MRI scan:

Large metastasis on the
left (black arrows)

Brain MRI of a patient

with a solitary brain
metastasis in remission

Autopsy specimen
Multiple
hemorrhagic
hepatic metastasis

CT Scan: Liver
metastsis

FIGO Anatomic Staging Of GTN

Stage I Disease confined to the uterus
Stage II GTN extends outside of the uterus
but is limited to the genital
structures (adnexa, vagina, broad
ligament)
Stage III GTN extends to the lungs, with or
without known genital tract
involvement
Stage
IV

All other metastatic sites (brain,

liver)

Staging : FIGO
Risk factor affecting staging
hCG level > 100,000 mIU/ml
Duration of disease longer than 6
months from termination of
pregnancy

Stage 1-4
Without risk factors a
1 risk factor
b
With 2 risk factors c

FIGO Prognostic Scoring For GTN (2000(

FIGO SCORING

Age (years)

<40

>40

Antecedent pregnancy

Mole

Abortion

Term

--

Pregnancy to treatment
Interval (months)

<4

4to <7

7to <13

13

Pretreatment serum
hCG (iu/l)

<1000

1000-10,000

10,000-100,000

> 100,000

Largest tumour size,

including uterus (cm)

<3

3 to<5

--

Site of metastases

Lung

Spleen &
Kidney

Gastrointestinal

Liver &
brain

Number of metastases

--

1-4

5-8

>8

Previous failed
chemotherapy

--

--

Single drug

2 Drugs

Total Score Survival : 6 = Low risk (100%) 7 = High risk. (95%)

What Is The Optimum Treatment For GTN?

GTN
Non metastatic GTD

Metastatic

Low Risk ( 6)
Single agent
Chemotherapy
Methotrexate or
Actinomycen D

High Risk (7)

Multi-agent
Chemotherapy

What is the best methotrexate regimen?

MTX:1mg/kg IM D:1, 3 ,5 ,7 alternating with
Folinic acid 0.1mg/kg IM D 2 , 4 , 6 , 8
followed by 6 rest days
Treatment is continued, until the hCG level
has returned to normal and then for a further
6 consecutive weeks.
As any chemotherapy treatment is reevaluated if FBC,
liver or kidney FT are affected or at drug resistance

Chemotherapy
Combination chemotherapy
Triple therapy : MTX, Act-D,
cyclophosphamide
EMA-CO : etoposide, MTX, Act-D,
cyclophosphamide, vincristine
EMA-EP : etoposide and cisplatin on day 8

Duration of therapy Until 3 normal hCG level

After that, at least 2 additional course are

administered

Follow Up
Stage 1-3 receive follow-up with
Weekly hCG level until normal for 3 wks
Monthly hCG level until normal for 12
months

Effective contraception during the entire

interval of hormonal follow-up

Stage 4 receive follow-up with

Weekly hCG level until normal for 3 wks
Monthly hCG level until normal for 24
months

What Is The Survival of GTN By

FIGO Stage?
Stage

Survival

Percent %

424/424

100

II

27/27

100

III

130/131

99

IV

14/18

78

Disaia &Creasman Clinical Gynecological Oncology 2007