Gestational Trophoblastic

Disease (GTD)
Dr Jyotsna Yadav
Associate Professor
Dept of OBS and GYNAE
Overview
Gestational trophoblastic disease (GTD)
comprises a group of disorders spanning the
premalignant conditions of complete and
partial molar pregnancies (also known as
hydatidiform moles) through to the malignant
conditions of invasive mole, choriocarcinoma
and the very rare placental site trophoblastic
tumour (PSTT) and epithelioidtrophoblastic
tumour (ETT).
If there is any evidence of persistence of GTD
after primary treatment, most commonly
defined as a persistent elevation of human
chorionic gonadotrophin (hCG), the condition
is referred to as gestational trophoblastic
neoplasia (GTN).
 The diagnosis of GTN does not require
histological confirmation.
The diagnosis of complete mole, partial mole,
atypical PSN and PSTT/ETT does require
histological confirmation.
GTD Overview
Heterogeneous group of related lesions
Arise from abnormal proliferation of trophoblast of the
placenta
Unique because the maternal lesions arise from fetal
(not maternal) tissue
Most GTD lesions produce the beta subunit of human
chorionic gonadotropin (B-hCG)
Overview
Hydatidiform Mole:
Complete
Partial
** Benign
Gestational Trophoblastic Neoplasia (GTN):
Persistent/Invasive Mole
Choriocarcinoma
Placental-Site Trophoblastic Tumor (PSTT)
** Malignant
These neoplasm's retain certain characteristic of the
normal placenta such as invasive tendencies and the
ability to make hCG hormone
Hydatidiform Mole
incidence of H.M vary dramatically in
different regions of the world
Japan : 2 per 1,000 pregnancies)
North America: 0.6-1.1 per 1000 pregnancies
Asia: 2-10 per 1000 (3x Western countries)
More common at reproductive extremes in age (>35y or
<20y)
Hydatidiform Mole
Risk Factors:
History of previous GTD
If one previous mole, 1% chance of recurrence (vs. 0.1% in
general population)
If 2 previous moles, risk of recurrence increases to 16-28%
Smoking
Vitamin A deficiency
Age
Hydatidiform Mole
Clinical Manifestations:
Amenorrhoea
Vaginal bleeding/anemia
Enlarged uterus (size > dates)
Pelvic pain
Theca lutein cysts
Hyperemesis gravidarum
Hyperthyroidism
Preeclampsia <20 weeks gestation
Vaginal passage of hydropic vesicles
Bleeding : Bleeding in early pregnancy after variable
period of amenorrhea is the most common clinical
sign of the mole (occurs in 90% of cases), with the
passage of the vesicles.
Hyperemesis gravidarum : Occurs into 25% of cases
of moles ,and appears more common when the uterus
is much enlarged and hCG levels are very high
Uterine enlargement: The uterus is commonly “large
for date”in 50% of case of moles ,
 although, in a small proportion of cases the uterus
corresponding to the gestational age or smaller than
date.
 The uterus having a doughy consistency.
 The fetal parts are not palpable, and fetal heart is
absent
Partial Mole-
Missed abortion like picture

Molar pregnancy are diagnosed early

By the U/S examination can be diagnosed from very
early pregnancy ,characterized by “Snow-storm"
appearance
The risks of hydatidiform mole are:
 Immediate hemorrhage
 Sepsis
 pre-eclampsia
 Treatment of these conditions has vastly improved
recently.
 Molar metastases :
 Choriocarcinoma
Management
The aim of treatment is to eliminate all trophoblastic
tissue from the maternal systems
Suction & curettage (S&C): The
method of choice even when
evacuation large mole
Management
Evaluate for coexisting conditions:
- History and physical
- CBC, coagulation profile, serum chemistry
- thyroid function
- blood type and crossmatch
- chest radiography
- pelvic ultrasonography
SERUM b-HCG
Evacuation of mole
- Suction curettage

If Rh negative, give rhogham

Suction evacuation
Under GA.
Cervix dilation till 12mm.and S&C induced to the
uterine cavity.
I.V oxytocin infusion is started with start of suction .
S&C started by negative pressure of about 60 to
70cmHg.
The canulla is genteelly rotated to ovoid perforation
of the soft uterus, and the majority of the molar tissue
is evacuated rapidly ,and the uterine size decreases
Medical termination of complete molar pregnancies
including cervical preparation prior to suction
evacuation, should be avoided.
Hysterectomy has been recommended as a suitable
method of treating hydatidiform mole in older women
who completed their family ,to reduce the risk of post-
molar trophoblastic disease .
F0llow-up
After the uterus has been evacuated :
 About 90% of cases ,the trophoblastic tissue die out
completely.
 About 10% of cases the trophoblastic tissue does not
die out completely and may persist or recur as :
invasive mole or choriocarcinoma.
So close follow-up by serum hCG levels after the
evacuation of the uterus

To ensure early recognition of persistent trophoblastic

tissue

After a molar pregnancy ,the hCG levels will usually

have returned to non pregnant levels by 9 weeks after
evacuation.
Follow-Up Care – Molar Pregnancy
Follow B-hCG levels every week until 3 consecutive
tests negative
Then monthly B-hCG every month for 6-12 months
Avoid pregnancy for at least 6 months after first
normal B-hCG
Birth control during follow-up period
Subsequent Pregnancies:
Send placenta for pathology
Check B- hCG 6 weeks postpartum
Gestational Trophoblastic Neoplasia
(GTN)
Persistent/Invasive Mole
Choriocarcinoma
Placental-Site Trophoblastic Tumor (PSTT)
** Malignant
Risk Factors for GTN After Mole
Preevacuation uterine size greater than gestationl age or
larger than 20 weeks gestation
Theca-lutein cysts larger than 6 cm
Age > 40 years
Serum hCG levels > 100,000 mIU/mL
Medical complications of molar pregnancy
Previous hydatidiform mole
Invasive Mole
Myometrial invasion by hydatidiform mole
1 in 15,000 pregnancies
10-17% of hydatidiform moles will progress to invasive
moles
Persistent Mole(PGTN)
Definition of persistent molar disease and need for
chemotherapy (at least one of the following):
Raised hCG level 6 months after evacuation
(even if falling)
hCG plateau in three consecutive serum
samples
hCG >20,000 IU/l more than 4 weeks
after evacuation
Rising hCG in two consecutive serum
samples
Pulmonary, vulval or vaginal mets unless
the hCG level is falling
Heavy PV bleeding or GI/intraperitoneal
bleeding
Histological evidence of choriocarcinoma
Brain, liver, GI mets or lung metastases
>2 cm on CXR
Choriocarcinoma
Most aggressive type of GTN
Abnormal trophoblastic hyperplasia
Absence of chorionic villi
Direct invasion of myometrium
Vascular spread to distant sites:
Lungs
Brain
Liver
Pelvis and vagina
Spleen, intestines, and kidney
Choriocarcinoma
May come from any type of pregnancy
- 25% follow abortion or tubal pregnancy
- 25% with term gestation
- 50% from hydatidiform moles
2-3% of moles progress to choriocarcinoma
Incidence 1 in 40,000 pregnancies
Placental-Site Trophoblastic Tumor (PSTT)
Originate from intermediate cytotrophoblast cells
Secrete human placental lactogen (hPL)
B-hCG often normal
Less vascular invasion, necrosis and hemorrhage than
choriocarcinoma
Lymphatic spread
Arise months to years after term pregnancy but can
occur after spontaneous abortion or molar pregnancy
Placental-Site Trophoblastic Tumor (PSTT)
Most common symptom is vaginal bleeding
Tend to:
- Remain in uterus
- Disseminate late
- Produce low levels of B-hCG compared to other GTN
- Be resistant to chemotherapy (treat with surgery)
Signs & Symptoms GTN
Continued uterine bleeding, uterine perforation,
enlarged irregular uterus, persistent bilateral ovarian
enlargement
From metastatic lesions: abdominal pain, hemoptysis,
melena, increased intracranial pressure (headaches,
seizures, hemiplegia), dyspnea, cough, chest pain
Diagnosis of GTN
Increase or plateau in B-hCG after molar pregnancy
Pathologic diagnosis by D&C or biopsy of metastatic
lesions
WARNING: biopsy of metastatic lesions can result in
massive hemorrhage
Metastatic workup: CXR (or CT chest), CT
abdomen/pelvis +/- CT/MR of brain
Classification & Staging of GTD
FIGO Staging
Describes anatomic distribution of disease
World Health Organization (WHO) Scoring Index
Describes prognosis
FIGO Staging
Stage Description
I Disease confined to the uterus

II Disease extends outside the uterus but

limited to genital structures (adnexa,
vagina, and broad ligament)

III Disease extends to the lungs with or

without genital tract involvement

IV Disease involves any other metastatic sites

WHO Prognostic Score Index
Score
Characteristic 0 1 2 4
Age <40 ≥40 - -
Antecedent preg Mole Abortion Term -
Interval from index <4 4-6 7-12 months >12 months
pregnancy months months
Pretreatment hCG <103 103- 104 104-105 >105
Largest tumor size < 3cm 3-4 cm ≥5cm -
(including uterus)
Site of metastases Lung Spleen, GI tract Liver, brain
kidney
Number of metastases - 1-4 5-8 >8
Previous failed - - Single drug ≥2 drugs
chemotherapy
Therapy for GTN
Low-risk = score ≤6
High-risk = score ≥7
Single agent therapy for nonmetastatic (stage I) or low-
risk metastatic (stage II and III) with score <7  survival
rates ~ 100%
Combination chemotherapy +/- adjuvant radiation
and/or surgery for high-risk metastatic disease or score
≥7
Therapy: Nonmetastatic GTN
Single-agent with either methotrexate or
dactinomycin
Chemotherapy continued until hCG values normal
and then 2-3 cycles beyond
Change to alternative single-agent for hCG plateaus
above normal or toxicities
If significant elevation of hCG or new metastases,
switch to multiagent
85-90% cured with initial regimen, <5% will require
hysterectomy for cure
Therapy: Low-risk Metastatic GTN
Low-risk metastatic disease can be treated with single-
agent therapy with 5-day regimens
Cure rates ~100% but 30-50% will be develop resistance
to first agent
If resistance to sequential single-agent chemotherapy
(5-10% of patients), switch to multiagent chemotherapy
Therapy:
Stage IV
High-risk Metastatic GTN
Stage II/III with score > 7
Disease refractory to single-agent chemotherapy

Combination Chemotherapy:
EMACO:
Day 1: Etoposide, Methotrexate and Dactinomycin
Day 8: Cyclophosphamide and Vincristine
(Oncovorin)
Repeat q2 weeks until remission
Continue for at least 2-3 cycles beyond first normal
hCG
MAC (Methotrexate, Dactinomycin, Cyclophosphamide)
EMA/EP – EMA + Etoposide and Cisplatin
Cure rates 80-90%
Therapy: High-risk Metastatic GTN
Hysterectomy and/or thoracotomy may be useful in
resistant setting or symptomatic management
Poorer prognosis with choriocarcinoma, metastases to
places other than lung and/or vagina, number of
metastases, and failure of previous chemotherapy
PSTT Therapy
Hysterectomy
Chemotherapy for metastatic disease or
nonmetastatic disease with poor prognosis:
- Interval from index pregnancy > 2 years
- Deep myometrial invasion
- Tumor necrosis
- Mitotic count > 6 per 10 high-power fields
Survival rates:
~100% for nonmetastatic disease
50-60% for metastatic disease
Follow-up Care
After completion of chemotherapy, follow serial hCG
every 2 weeks for three months, then monthly for one
year
Physical examinations every 6-12 months and imaging
as indicated
Reproductive Performance
Most women resume normal ovarian function
No increase risk of stillbirths, abortions, congenital
anomalies, prematurity, or major obstetric
complications
No evidence of reactivation
At increased risk for development of second episode
Summary
Hydatidiform mole is a benign condition, 80% cured
with suction D&C
Malignant GTN:
Persistent or invasive mole
Choriocarcinoma
PSTT
WHO score > 7 represents high-risk disease
GTN very sensitive to chemotherapy