Gestational Trophoblastic Disease (GTD).

Adissu.G
 GTD
Gestational trophoblastic disease include the
tumor spectrum arise from the trophoblastic
elements
Keep secretion of the human chorionic
gonadotropin (hCG)
 Pathologic and clinical classifications for
gestational trophoblastic disease

PATHOLOGIC CLINICAL
CLASSIFICATION CLASSIFICATION
Hydatidiform mole Benign gestational
*complete trophoblastic disease
*incomplete

Malignant
Invasive mole Nonmetastatic
trophoblastic disease
Placental site
trophoblastic Metastatic
tumor

Choriocarcinoma High risk Low risk

 Hydatidiform mole

 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
 There is an increased risk of molar pregnancy for
women over the age 40
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
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)
Clinical risk factors for molar pregnancy
Age (extremes of reproductive years)
<20
>40
Reproductive history
prior hydatidiform mole
prior spontaneous abortion
Diet
Vitamin A deficiency
 classification
 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.
Cytogenetic
Complete molar
pregnancy
Chromosomes are
paternal , diploid
46,XX in 90% cases
46,XY in a small part
Hydatidiform mole
 Complete hydatidiform
mole demonstrating
enlarged villi of various
size
A large amount of villi in the uterus.
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)
Cytogenetic
Partial molar
pregnancy
Chromosomes are
paternal and maternal,
triploid.
69,XXY 80%
69,XXX or 69,XYY
10-20%.
Partial hydartidiform mole
 Here is a partial mole in a case of triploidy. Note the
scattered grape-like masses with intervening normal-
appearing placental tissue.
 Comparative Pathologic Features of Complete and
Partial Hydatidiform Mole
Feature Complete Mole Partial Mole
Karyotype Usually diploid 46XX Usually triploid 69XXX most
common.
Villi All villi hydropic; no Normal adjacent villi may be
normal adjacent villi present
vessels present they contain no blood cells
fetal blood cells
Fetal tissue Not present Usually present

Trophoblast Hyperplasia usually Hyperplasia mild and focal

present to variable
degrees
 Signs and Symptoms Hydatidiform Mole
 Vaginal bleeding
 Hyper emesis ( severe vomiting)
 Size inconsistent with gestational
age( with no fetal heart beating and fetal
movement)
 Preeclampsia
 Theca lutein ovarian cysts
 investigation
CBC
Blood group and Rh
Serum ß HCG
OFT
U/A
Electrolytes
TFH
C-xray
Pelvic US
Histological examination of specimen
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
A sonographic findings of a molar pregnancy. The
characteristic “snowstorm” pattern is evident.
Differential diagnosis
 Abortion
 Ectopic pregnancy at early GA.
 Multiple pregnancy
 Polyhydramnios
 Management

 Admitt the patient

 Correct hypotension/shock
 Suction curettage
 An oxyton agent should be infused intravenously after the
start of evacuation and continued for several hours to
enhance uterine contractility
 Removal of the uterus (hysterectomy) : used rarely to treat
hydatidiform moles if future pregnancy is no longer
desired
Chemotherapy with a single-agent drug
Treat the complication and concomitant conditions
Post evacuation surveillance /Follow up
Follow-up
Patients with hudatidiform mole are cured over 80%
by treatment with evacuation.
The follow-up after evacuation is mandatory.
uterine involution, ovarian cyst regression and
cessation of bleeding
 Follow-up
History and physical examination in each visit
Quantitative serum hCG levels with in 48 hrs of
evacuation should be obtained and every 1-2 weeks
until negative for three consecutive determinations,
The monthly for 6 months
Followed by every 3 months for 1 years.
Avoid pregnancy /Contraception should be practiced
during this follow-up period
 persistent disease 
Any of the following findings during the period of
gonadotropin follow-up is suggestive of malignant
GTN and warrants treatment
 A plateau in the serum hCG concentration for at least
four values over three weeks; eg, on days 1,7,14, and 21
 A serum hCG concentration that rises (by 10 percent or
greater) for three values or more over at least two
consecutive weeks; eg, on days 1,7, and 14
Persistence of detectable serum hCG for more than six
months after molar evacuation
 Histologic confirmation of choriocarcinoma.
Invasive mole
 Invasive mole
 Invasion Mole arises from HM
 it has malignant potentialities, invades the
myometrium and penetrates the uterine wall,
extends into the broad ligament or peritoneal
cavity.
in half or more of all cases invasive mole
metastasizes through the peripheral
circulation to distant sites, mostly to the lung
Pathologic findings
 excessive trophoblastic
proliferation and invasiveness
 the degree of anaplasia is
variable: completely benign---
highly malignant
 Invasive mole
Tissue invades into the Invasive hydatidiform
myometrium with mole infiltrating the
bleeding myometrium
Choriocarcinoma
 Choriocarcinoma
 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.
Characterized by abnormal trophoblastic hyperplasia
and anaplasia , absence of chorionic villi
Gross specimen of choriocarcinoma
 Symptoms and signs
 Bleeding
 Infection
 Abdominal swelling
 Vaginal mass
 Lung symptoms
 Symptoms from other metastases
 WHO Prognostic Scoring
Score System
Prognostic factor 0 1 2 4
Age(years) ≤39 >39 — —
Hydatidiform Abortion, Term
Pregnancy history —
mole ectopic pregnancy
Interval (months) of
<4 4-6 7-12 >12
treatment
Initial hCG(mIU/ml) <103 103-104 104-105 >105

Largest tumor(cm) <3 3-5 >5 —

Spleen,
Sites of metastasis Lung GI tract, liver Brain
kidney
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
SONG’S CLASSIFICATION
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.Priortherapy,serumhCG>100,000 mlU/ml
2. Duration of disease >6 months
IIa

IIb
IIIa<3cm or locate in half lung
IIIb disease beyond IIIa
 Common Sites for Metastatic
Gestational Trophoblastic Tumors
Site Per cent
Lung 60-95
Vagina 40-50
Vulva/cervix 10-15
Brain 5-15
Liver 5-15
Kidney 0-5
Spleen 0-5
Gastrointestinal 0-5
Treatment
Non-metastatic 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 Non- metastatic 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

 FIGO 1982 FIGO 1992 revised

Stag Stage
e I Confined to the uterus corpus
I Confined to the IA: without risk factors
uterus corpus IB: one risk factor
IC: two risk factors
II Metastases to pelvis
and vagina II Metastases to pelvis and vagina
IA: without risk factors
III Metastases to lung
IB: one risk factor
IV Distant Metastases IC: two risk factors
III Metastases to lungIA: without
risk factors
Risk Factors: IB: one risk factor
IC: two risk factors
- BetaHCG> 100000 mU/ml
- Interval > 6 months IV Distant MetastasesIA: without
risk factors
IB: one risk factor
IC: two risk factors
FIGO STAGING 2000
Stage

I Confined to the corpus uteri

II Metastases to pelvis and vagina

III Lung metastases

IV Distant metastases
COMBINED FIGO STAGING+RISK FACTOR SCORING WHO
 Treatment of Low-Risk Metastatic GTD

Single-agent chemotherapy with MTX or actinomycin-D 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 single-agent
chemotherapy will require combination chemotherapy with
or without surgery to achieve remission
 Treatment of High-Risk Metastatic GTD
Multi-agent chemotherapy with or without
adjuvant radiotherapy or surgery should be the
initial treatment for patients with high-rist
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
IV daily×2 days
Etoposide(VP-16) 100mg/M2 (over 30-45
minutes)
IV losding dose,
Methotrexate 100mg/M2 then 200mg/M2
over 12 hours day 1
Actinomycin D 0.5mg IV daily×2 days
15mg IM or p.o. q 12 hours×4 starting 24
Folinic acid
hours after starting methotrexate
Cyclophosphamide 600mg/M2 IV on day8

Oncovin (vincristine) 1mg/M2 IV on day8

(Repeat every 15 days as toxicity permits)

Prognosis
Cure rates should approach 100% in non-metastatic
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.
Placenta Site Trophoblastic
Tumor (PSTT)
 Definition
Placenta Site Trophoblastic Tumor is an extremely
rare tumor that arises from the placental
implantation site
Tumor cells infiltrate the myometrium and grow
between smooth-muscle cells
 Diagnosis and treatment
Serum 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
10Q YOU!!!