Gestational

Trophoblastic
Diseases (GTDs)

Taojia
Department of Ob & Gy
The First Affiliated Hospital of
Liaoning Medical University

Definition
GTD is a diverse group of interrelated diseases
resulting in the abnormal proliferation of
trophoblastic (placental) tissue.
These also share the ability to produce human
chorionic gonadotropin (hCG)

Benign

----

hydatidiform mole

invasive mole

GTD

GTN

Malignan
t

choriocarcinoma
placental site
trophoblastic

gestational trophoblastic disease, GTD

hydatidiform mole
10%-20%

histologic
classification

invasive mole

choriocarcinoma

Clinical
classification

gestational trophoblastic
neoplasia GTN

placental site trophoblastic tumor,

PSTT

Hydatidiform mole 60% abortion 30%

term pregnancy and ectopic pregnancy 10%

Hydatidiform mole(HM)
definition

After pregnancy the placental trophoblastic cells proliferate

abnormally, there is stoma edema ,and forms vesicular which
is like grape on its appearance. Molar pregnancy.
Account for 80% of all GTD
Complete mole: 90%
Partial mole: 10%

Characters: Disease confined to the uterine cavity, did not

invade to the muscular layer, no transfer. Benign, may
develop to GTN

These tumors are unique in that the maternal tumor results

from abnormal fetal tissue rather than maternal tissue.

1 Epidemiology and Pathogenesis

Pathogenesis

The cause of molar pregnancy is unknown

Source of paternal chromosomes was the main reason for the
trophoblastic cells proliferate abnormally of complete mole

diploid ,
paternal
90% is 46XX,
10% is 46XY
no fetal tissue
and no maternal
DNA

triploid ,
69XXY,
69XXX or
69XYY.
have a fetus or
fetal cells

A partial mole arises from the simultaneous fertilization of a normal ovum

by two sperm (diandry). The resulting triploid karyotype is most
commonly 69,XXY.

2. Pathology

Histologic character
Trophoblast proliferate
Edema of villous stroma
No embryogenetic blood vessels in stroma

In complete molar pregnancy, there is abnormal

proliferation of the syncytiotrophoblasts that produce hCG
-hCG has both an alpha and a beta subunit. Although the beta subunit
is unique to hCG, the alpha subunit is also found in luteinizing
hormone
(LH),follicle-stimulating hormone (FSH), and thyroid-stimulating
hormone
(TSH).

In a partial mole,there is abnormal proliferation of the

cytotrophoblasts do not produce hCG. hCG levels are
normal or only slightly elevated compared to complete
moles.

Comparison between complete and partial

type

3. Clinical manifestation

Symptoms and signs------typical in complete mole

Symptoms:
Amenorrhea and Vaginal bleeding
The most common symptom
Vary from spotting to profuse bleeding, irregular
grape-like organization in Vaginal effluent

Abdominal pain

Excessive uterine enlargement or ovarian cysts

Hyperemesis gravidarum

Severe nausea and vomit

Hyperthyroidism

Production of thyrotropin by molar tissue , 10%

Disappear following evacuation of mole, a little need antithyroid
therapy

Preeclampsia

In the first or early second trimester

Large amounts of vasoactive substances are released from necrotic
trophoblastic tissue

 Uterus enlargement
The

uterine size is greater than the anticipated gestational

age due to the presence of tumor,hemorrhage, and clot in
the uterus

theca lutein Ovarian cysts

Bilateral,

different size,<1cm ->20cm

Regress spontaneously several weeks after uterine
evacuation, paralleling the decline of hCG level
Rupture, bleeding and infection cause acute abdominal
symptoms and indicates surgery
Partial

molar pregnancy:without the typical symptom, patients may

have similar but much less severe symptoms , vaginal bleeding is
commom.Diagnosis is often made on pathologic examination of the
products of conception.

4.Diagnosis

Symptoms and signs

Accessory examination
Ultrasound-confirm. reliable, safe, economical,
simple
Complete mole-characteristic pattern:
--no fetus or amniotic uid is present;
--multiple echoes formed by the interface between the
molar villi and the surrounding tissue
--snowstorm pattern due to swelling of chorionic villi
-- bilateral theca lutein cysts

Partial mole
-- Fetal heart sounds may be present because there is a
coexistent fetus,intrauterine growth restriction

HCG measurement:
--hCG levels is necessary for
diagnosis , treatment , and
follow up in all cases of
trophoblastic disease.
--In the presence of a molar
pregnancy, quantitative
serum hCG levels can be
extremely high. (100,000
mIU/mL),will decline to
normal within 14 weeks
following evacuation.

5.Differential diagnosis
Abortion
Multiple pregnancy
Polyhydramnios

6. Treatment
A. emptying uterine cavity:
Suction curettage (D&C):
Dilate the cervix Sufficient
Intravenous oxytocin should be given after a moderate amount

of tissue has been removed

Preparing for blood transfusion and operation
The size of uterine body<G12w, one time; >G12w, the second
curettage 1 week later .
Tissue from the decidua basalis for pathologic study

B. Prophylactic chemotherapy
It is not Conventional treatment ,not recommoned .only
recommend for complete mole with high-risk factors and cannot
follow-up.

C. Surgery
hysterectomy, can not avoid metastasis.
Theca lutein cysts: generally regress in 2-4months.No surgical

intervention unless an acute episode occurs.

The high-risk factors includes:

(i).-HCG>100,000IU/L;
(ii). Uterine size is obviously larger than that with the
same gestational time.
(iii). Theca lutein cysts is >6cm.
(iv). Age >40 years
(v). Repeated mole: morbidity of invasion and
metastasis increase 3~4 times.

7.follow-up

complete mole has the latent risk of local invasion or

metastasis. The incidence of malignant disease is 10% for
invasive mole, 5% for choriocarcinoma.

Content
Serial -hCG determination
Weekly intervals after evacuation until serum hCG declines to

nondetectable levels on 3 successive weeks

If remission within 14 weeks, -hCG should then be followed
monthly for 6 months
Then followed every 2 months for a total 1 year
Physical examination including pelvic examination, ultrasound and
chest X-ray

Continue contraception during surveillance for 1 year:

OCPs,condom.

Gestational Throphoblastic
neoplasia
(GTN)
Invasive mole
and
choriocarcinoma

OVERVIEW

Benign
80%

hydatidiform mole
invasive mole

GTD

GTN

Malignan
t
local invasion
and metastasis

choriocarcinoma
placental site
trophoblastic
tumor

Gestational Throphoblastic neoplasia (GTN)

Hydatidiform mole 60% abortion 30%

term pregnancy and ectopic pregnancy 10%

Pathogenesis

Invasive mole :

Invasive moles almost always occur after the evacuation of a

molar pregnancy.
Invasive moles are characterized by the penetration of large,
swollen (hydropic) villi and trophoblasts into the myometrium.

Invasive moles rarely metastasize and are capable of

spontaneous regression.

Choriconoma:

Choriocarcinoma is a malignant necrotizing tumor that can

arise weeks to years after any type of pregnancy.
Choriocarcinoma is a pure epithelial tumor
Choriocarcinoma invades the uterine wall and uterine
vasculature, causing destruction of uterine tissue, necrosis,
and potentially severe hemorrhage.
These tumors are often metastatic and usually spread
hematogenously to the lungs, vagina, pelvis, brain, liver,
intestines,
and kidneys. These lesions tend to be very vascular and bleed
easily.

One of the rare malignancies that are highly curable even with
widespread metastases

Pathology

Invasive mole
Vesicles and locally invasive in gross
Microscopically, proliferative trophoblastic invasion of the

myometrium with identifiable villous structure

choriocarcinoma
Grossly red and granular, extensive necrosis and bleeding
Microscopically, no villi, disordered array of trophoblast, frequent

mitoses

gestational trophoblastic neoplasia GTN

Clinical classification (FIGO,2000)

For the purpose of treatment and prognosis, malignant

GTD or GTN can be classified as:

non metastatic GTN (low risk)

lesions confined to the uterus

metastatic GTN (high risk)

Lesions occur outside the uterus
good prognosis or poor prognosis

Clinical findings

Non-metastic GTN-----most of them were caused by

hydatidiform mole ,confined to the uterus.
Vaginal bleeding: irregular
Enlargement or subinvolution of uterus
Theca lutein cysts
Abdominal pain: rarely, perforation of uterus cause pain

and hemorrhage, torsion or rupture of cysts

Symptoms of pregnancy: pseudopregnancy

Metastatic GTN---most from non-HM

manifestation:
symptoms and body signs depends upon the location of
the metastatic focus. the most site is lung(80%) then
vagina(30%),parauterus(20%), brain(10%) or liver(10%)
metastasis
i). pulmonary metastasis :with or without symptom, CT,X-ray
ii). vaginal metastasis : Vaginal wall nodule, purplish blue
iii). brain metastasis:
iv). liver metastasis: bad prognosis
v). metastasis to other organs

Diagnosis

Symptoms and signs

Most patients with choriocarcinoma are identifed as aresult

of plateauing or rising hCG after molar pregnancy, abortion ,

term pregnancy and ectopic pregnancy, irregular Vaginal
bleeding and symptoms of metastases.
Most patients with invasive moles are identifed as aresult of
plateauing or rising hCG after treatment for a molar
pregnancy and are usually asymptomatic at the time of
diagnosis. The most common symptom is abnormal uterine
bleeding

serum -hCG

Ultrasound
Invasive mole- may reveal one or more intrauterine masses with

possible invasion of the myometrium. Doppler examination

typically shows high vascular ow.
Choriocarcinoma- may reveal a uterine mass with hemorrhage
and necrosis. These tumors are typically highly vascular as
demonstrated by Doppler analysis

X-ray,CT, MRI
Pulmonary metastasis
Brain, lung liver and renal metastasis

Histology: not necessary

with villi------invasive mole
without villi----choriocarcinoma

Differential diagnosis

Invasive mole and choriocarcinoma

Time and nature of previous pregnancy
Histology: villi present or not

term
pregnancy

abortion

ectopic
pregnancy

No villi
choriocarcinoma

hydatidiform
mole
Willi
invasive mole

Clinical staging
FIGO Staging System for Gestational Trophoblastic Tumors
Stage

Description

Limited to uterine corpus

Extends to the uterine adnexae, outside the

uterus, but limited to the genital structures

Extends to the lungs with or without genital

tract

All other metastatic sites

FIGO/ WHO Prognosis Scoring System(2000)

0

age

<40

>=40

--

--

Antecedent
pregnancy

HM

abortion

term

--

Interval (m)

<4

4-<7

7-12

>12

<1,000

1,00010,000

10,000-100,000

>100,000

--

3-<5cm

>=5cm

lung

Spleen,
kidney

GI tract

liver
brain

1-4

5-8

>8

One drug

Two or
more
drugs

hCG(IU/L)
Largest tumor
Site of
metastases
Number of
metastases
Prior
chemotherap
y

Low-risk <=6 good-prognosis ,

High-risk>=7 poor-

Treatment

Medicine

dose way Period of treatment

Treatment
interval

MTX

0.4mg/(kgd), IM 5d

2Week

Weekly MTX

50mg/m2 IM

1Week

MTX +

1mg/(kgd) IM Day 1,3,5,7

2Week

(CF)

0.1mg/(kgd)IM day 2,4,6,8

MTX

250mg iv, persist 12h

Act-D

10 12g/(kgd) IV 5d

2Week

5-Fu

28 30mg/(kgd) IV 8 10d

2Week

high-risk GTN Combined chemotherapy.

EMA-CO(etoposide, dactinomycin, MTX, vincristine,
CTX);
5-Fu+KSM.

Medicine

dose way Period of

treatment

5-Fu+KSM

Treatment interval
3 Week

5-Fu

26 28mg/kgd iv 8d

KSM

6g/kgd iv 8d

indications of stopping Chemotherapy

Low-risk GTN: symptoms and body signs disappeared,3 successive

HCG measurement (once a week) are all normal, and then continues 23 course, at least 1 course.

high-risk GTN: symptoms and body signs disappeared,3 successive

HCG measurement (once a week) are all normal , and then continues 3
course, the first course must be combined chemotherapy .

2 operation

Mainly as adjuvant therapy

To control the bleeding and other complications, eliminate
resistance lesions, reduce tumor load and shorten the
chemotherapy regimen, etc, have certain effect
Hysterectomy
Removal of lesions in tuerus
Pummonary lobectomy

3.

Radiotherapy

For metastasis in the liver or brain

For chemo-resistant lesion in the lung

Follow-up

Close follow-up, the contents are the same with

hydatidiform mole

FIGO suggest:
Stage I III 1year stage IV 2year
Contraception should be maintained for at least 1 year.
Chemotherapy stop >= 12 months ,may pregnant

HM

Invasive mole

choriocarc
inoma

Retained
placenta

Previous
pregnancy

no

HM

various

Abortion, term

Latent phase

no

<6m

>12m

no

villi

have

have

no

Have,
degeneration

Proliferative
trophoblast

Slight
severe

Slightsevere
ecluster

Sever,
cluster

no

Depth of
infiltration

decidua

myometrium

myo

decidua

necrosis

no

have

have

no

metastasis

no

have

have

no

Metastasis of
liver, brain

no

a little

easily

no

HCG

+ or

Placenta Site Trophoblastic

Tumor (PSTT)

Pathogenesis

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

exercise
1

Which of the following is the

diagnosis of hydatidiform mole ?

A: Uterine is larger then normal, without fetal hrart rate.

B: Irregular vaginal bleeding after menopause
C:grape-like organization in Vaginal effluent
D: Severe nausea and vomit in early pregnancy,with
Preeclampsia

2 Which of the following is the most reliable

way of diagnosing hydatidiform mole ?

A -HCG
B X-ray
C ultrosound
D CT

3 which method is not suggested for

contraception for hydatidiform mole
patients
A . IUD
B Oral medicine of contraception
C Tools for contraception, such as condom,

4 Female 42 Hydatidiform mole, The

size of uterine body>G14w,the best treatment
is ?

A Suction &curettage:
B hysterectomy directly
C Suction first and then hysterectomy
D Prophylactic chemotherapy first ,and Suction

5 which is not suitable for Suction &curettage

of hydatidiform mole?

A:once confirmed, Suction &curettage timely

B:prepare blood for transfusion
C:try ones best to clean the tissues at one time
D:Tissues from the decidua basalis for pathologic study

A 27-year-old woman presents to your office with a positive home

pregnancy test and a 3-day history of vaginal bleeding. She is
concerned that she may be having a miscarriage. On examination, the
uterine fundus is at the level of the umbilicus. By her last period, she
should be around 8 weeks gestation. On pelvic examination, there is a
moderate amount of blood and vesicle-like tissue in the vaginal vault,
and the cervix is closed. The lab then calls you to say that her serum
-hCG result is greater than 1,000,000 mIU/mL.
1. Which of the following is the best next step in this patients
evaluation?
a. Complete pelvic ultrasound
b. Determination of Rh status
c. Surgical intervention (suction curettage)
d. Methotrexate administration
e. Schedule a follow-up visit in 2 to 4 weeks to recheck a -hCG leve

2. The patient undergoes an uncomplicated suction D&C.

The pathology report is available the next day and is
consistent with a complete molar gestation. What is the
best next step in the care of this patients condition.
a. Repeat pelvic imaging
b. Radiation therapy
c. Chemotherapy
d. Surveillance of serum -hCG
e. No further follow-up is required

3. During post-operative surveillance, you meet with her in

your office about 3 months after the index visit. Which of
the following interventions is most important to emphasize
during her follow up period?
a. No further pregnancies are recommended
b. Await pregnancy attempt for 2 years
c. Reliable contraception during surveillance
d. Prophylactic antibiotic use during surveillance
e. Prophylactic chemotherapy to decrease the risk of
persistent and recurrent disease

A 42-year-old G4 P3 woman presents to your emergency department

with a 6-month history of irregular bleeding and a new onset of
coughing up blood. Her history reveals three term vaginal deliveries,
her last being approximately 6 months ago. That delivery was
uncomplicated. On physical examination her uterus is approximately
10 to 12 weeks size, and there is a moderate amount of blood in the
vaginal vault. CT shows a new single nodule in the left lower lobe of
lung, suspicious for a metastatic lesion from unknown location
1. Which of the following laboratory tests will most likely assist in
her diagnosis?
a. CA 125
b. Serum -hCG
c. CBC
d. Prothrombin time
e. Fibrinogen

2. The quantitative serum -hCG is 108,000 mIU/mL. Which of the

following is the most likely diagnosis?
a. Incomplete molar pregnancy
b. Complete molar pregnancy
c. Persistent molar pregnancy
d. Choriocarcinoma
e. Placental site trophoblastic tumor
3. The pelvic ultrasound reveals bilateral multicystic ovarian masses
along with an enlarged uterus. What is the most likely diagnosis and most
appropriate management of this fnding?
a. Metastatic lesions/surgical intervention
b. Primary epithelial ovarian carcinoma/surgical intervention
c. Theca lutein cysts/percutaneous drainage
d. Metastatic lesions/chemotherapy
e. Theca lutein cysts/conservative surveillance

4. You refer the patient to a gynecologic oncologist for

evaluation and management of choriocarcinoma. What is
the most likely intervention to be recommended?
a. Total abdominal hysterectomy
b. Serum -hCG surveillance
c. Chemotherapy
d. Whole pelvis radiation
e. Pulmonary wedge resection

A 17-year-old G1 P0 patient presents to your offce with vaginal bleeding

at approximately 10 weeks gestation by her last menstrual period. Her
examination is benign with a 10-week-sized uterus, a closed cervical os,
and a small amount of blood within the vaginal vault. You order a
complete pelvic ultrasound that shows an intrauterine gestational with a
fetus measuring approximately 8 weeks gestation. A yolk sac is identifed.
Doppler sonography is unable to demonstrate any fetal heart beat. The
placenta demonstrates marked thickening and increased echogenicity
with suggestion of small cystic spaces within the placenta. A serum -hCG
is 282,000 mIU/mL
1. What is the most likely diagnosis?
a. Missed abortion
b. Inevitable abortion
c. Incomplete abortion
d. Complete molar pregnancy
e. Incomplete molar pregnancy

2. You decide to perform a suction D&C. When giving informed

consent, you discuss the risk most commonly encountered in
this operation. Which of the following is the most common risk
associated with suction D&C?
a. Infection
b. Uterine perforation
c. Uterine bleeding
d. Damage to the bladder
e. Need for future surgery