Gestational Trophoblastic

Disease (GTD)
Department of Obs.& Gyn.,
First Hospital of Xian Jiaotong
University

Gao Shang Feng

Introduction
What is GTD ?
It is a rare kind of disease in which
abnormal trophoblastic proliferation
occurs.
It is too among the rare human
malignancies that can be cured even
in the presence of widespread
metastases.

Which does it include?

It includes a spectrum of interrelated
tumors, including
hydatidiform mole (HM)
invasive mole (IM)
Choriocarcinoma (CH)
Placental-site trophoblastic tumor
(PSTT, borderline, very rare)

Relationship of HM. IM. CH

hydatidiform

therapeutic or

mole

spontaneous abortion
term pregnancy
ectopic

invasion mole

choriocarcinoma.

What is GTT (Gestational trophoblastic

tumor)?
GTT is all GTD except hydatidiform
mole.
They has its unique pathologic
characteristics and biological
behavior.
Even the most malignant case can be
cured by chemotherapy.

Hydatidiform mole

Hydatidiform mole

Hydatidiform mole
It is a neoplastic
proliferation of
the trophoblast
in which the
terminal villi
are
transformed
into vesicles
filled with clear
viscid material.

It is usually benign but has

malignant potentiality.
Incidence:
south east Asia is 1/500-600
the US and Europe:1/500-2000
China:1/1238

Classification
It is divided into two classification
complete hydatidiform mole
partial hydatidiform mole

complete hydatidiform mole(CHM):

the entire
uterus
filled with
abnormal
vesicles, no
signs of
fetus.

partial hydatidiform mole

partial
hydatidiform
mole with
evidence of
a conceptus.

Etiology
Though it is not known a number of
associated factors have been noted:
the absence of fetal circulation;
dietary protein deficiency
viral infection;
age:>45 years women are 10 times
more likely to develop HM than
those younger

abnormal fertilization process:

the fertilization of a normal ovum
with a duplicated haploid
sperm:46XX
the fertilization of an empty egg by
two sperms(dispermy):46XY

Chromosomes

complete hydatidiform moles

Cytogenetic studies have demonstrated

that complete hydatidiform moles usually

have a 46xx karyotype, and the molar
chromosomes are entirely of paternal
origin.
Complete moles appear to arise from an
ovum that has been fertilized by a haploid
sperm, which then duplicates its own
chromosomes, and the ovum nucleus may
be either absent or inactivated

Although most complete moles have

a 46xx chromosomal pattern,
approximately 10% have a 46xy
karyotype.
Chromosomes in a 46xy complete
mole also appear to be entirely of
paternal origin, but in this
circumstance, an apparently empty
egg is fertilized by two sperm.

.
partial hydatidiform mole
partial moles usually have a triploid
karyotype (69 chromosomes ), with the
extra haploid set of chromosomes derived
from the father.
When a fetus is present in conjunction
with a partial mole, it usually exhibits the
stigmata of triploidy, including growth
retardation and multiple congenital
malformations.

Pathologic findings

complete hydatidiform mole

pathology
Complete moles lack identifiable
embryonic or fetal tissues, and
the chorionic villi exhibit
generalized hydatidiform swelling
and diffuse trophoblastic
hyperplasia.

Gross
we see a mass of
vesicles, vary in
size, grape-like
with stems, blood
and clot filling the
inter-vesicle space

partial hydatidiform mole

It are characterized by the following
pathologic features :
Chorionic villi if varying size with
focal hydatidiform swelling and
cavitation.
It contain identifiable embryonic or
fetal tissues.

Gross
we see a
mass of
vesicles,
vary in size,
grape-like
and
identifiable
embryonic
or fetal
tissues.

Microscopic

trophoblastic proliferation.
hydropic degeneration of the
stroma.
absence of blood vessels or
extreme scantiness of blood
vessels.

Norma
l
tropho
blastic

l
partia mole
orm
f
i
d
i
t
hyda

comp
hydat lete
idifor
mole m

trophoblastic proliferation is
considered the most important single
criteria.
Ovaries respond to hCG stimulation ,
30-50% theca-lutein cysts develop,
bilateral

Clinical course

It has eight of
symptoms and
physical signs.

 amenorrhea
because it is a pregnancy.
vaginal bleeding
after a period of amenorrhea
(average 12 weeks) may continue
intermittently for several weeks--profuse bleeding---anemia and
infection.
abdominal cramps

 abnormally

enlarged and
soft uterus
in about half the
cases, the
uterus growth is
rapid, it is larger
than the dates
suggest.

 ovarian cyst
torsion
when we do pelvic
examination
adnexal masses
may be found. it is
theca lutein cyst in
about one third of
the cases

 severe and early onset PIH

(Pregnancy Induced Hypertension

syndrome)
hyperthyroidism
plasma thyroxin concentration
elevates
exaggerated early pregnancy
symptoms
nausea, vomit etc

Diagnosis
suspicion:
abnormal bleeding after amenorrhea
inappropriately enlarged uterus;
absence of fetal heart sounds or
could not feel fetal parts by palpation
between 16-20th week
hyperemesis gravidarum
bilateral ovarian cysts

serum hCG monitor

an unusually high titer of chorionic
gonadotropin, especially after the
one-hundredth day of pregnancy,
help to confirm the diagnosis of HM.

Ultrasonography:
It is a reliable and sensitive technique
for the diagnosis of complete molar
pregnancy. Because the chorionic villi
exhibit diffuse hydatidiform swelling.
Complete moles produce a
characteristic vesicular sonographic
pattern, usually referred to as a
snowstorm pattern.

Ultrasonography may also

contribute to the diagnosis of
partial molar pregnancy by
demonstrating focal cystic spaces
in the placental tissues and an
increase in the transverse
diameter of the gestational sac.

Differential diagnosis
abortion;
multiple
pregnancy;
polyhydramnios

Treatment

the uterus should be evacuated as

soon as possible after the diagnosis

is made.(by suction curettage)
suction;
oxytocin administration:we can use
blood transfusion or/and fluid
infusion.it is used to decrease the
size of the uterus;

tissue sent for histology:

it should be routine
practice with all cases of
incomplete miscarriage;
acute pulmonary
complications

 total abdominal
hysterectomy
in older multiparas
hysterectomy may
be indicated.

management of theca-

lutein cysts
these tumors should not be
excised because they
regress after the
trophoblastic tissue has
been removed.

chemotherapy
HM dont need usually
chemotherapy because
HM is benign disease.

 Follow-up examinations
follow up mode in the 2
years after discharge
on each follow-up
check, the following
should be addressed

 symptom

abnormal vaginal bleeding,

cough, hemoptysis
signs of metastasis
pelvic examination
hCG evaluation
B-ultrasound
chest X-ray film

contraceptive method
required for 1-2 years
condom is recommended.
IUD (intrauterine device)and
pills are contraindicated for their
potentiality of causing abnormal
vaginal bleeding.

Ask question
1. What is the etiology of GTD?
2. What is the classification of HM?
3. What is the main pathologic
changes of HM?
4. What is the clinical course of
HM?
5. How Follow-up examinations is
we?

About 80% of the cases of HM

have a benign course. one-half
of patients become pregnant
subsequently. about 16% of HM
become invasion moles and
some 2.5% progress into
choriocarcinoma

Invasion Mole

Introduction

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

differentiation between invasive

mole and choriocarcinoma lies in
whether the villous pattern is
preserved:
if we see villi, it must be
invasion mole;
if we cant see villi, it is
choriocarcinoma.

Clinical course
Symptoms caused by primary lesions
vaginal bleeding
pelvic examination reveals delayed
involution of the uterus, persisting
cyst .
abdominal pain
intra-abdominal hemorrhage,
penetration of the uterus .

Metastatic symptoms
cough, hemoptysis---positive X-ray
signs
profuse vaginal bleeding---vaginal
or cervical metastasis, we can see
bluish nodule in vaginal
headache, nausea, vomit, paralysis
or comait is caused by cerebral
lesion.

Diagnosis
history and clinical manifestation
hCG assay:
diagnosis suspected if hCG titers
persist to be high 12 weeks after
evacuation of a HM, or once
regress to normal range but rise
rapidly.

possible reasons : retained HM

pregnancy
huge theca-lutein cyst persist
when we remove these reasons we
can diagnosis invasive mole
other measurement
B-ultrasound
X-ray

Prophylaxis
respond well to chemotherapeutic
agents
main causes of death:
hemorrhage, metastasis and
infection

Treatment:

Identical to that for

choriocarcinoma

Choriocarcinoma
It is highly malignant GTT
It may follow HM,
invasion mole, abortion,
normal pregnancy, ectopic
pregnancy.

Pathologic findings
Gross inspection

irregular or circumscribed

hemorrhagic growth in the uterine wall

ulcerating surface opens into the
endometrial cavity (rarely embedded in
myometrium)
penetration into broad ligament or the
peritoneal cavity
dark red blood:.it is filled metastatic
nodules

ulcerating

surface opens
into the
endometrial
cavity (rarely
embedded in
myometrium)

Histologic findings

we see masses of anaplastic

trophblastic cells in microscopy;

invasion into the uterine wall,
destroying vessels, muscle tissue
prominent necrosis and
hemorrhage
villi can not be recognized
spread through circulation

Clinical Manifestations
irregular bleeding after
preceding gestation;
malignant tumor cells enter the
circulation through the open
blood vessels and are
transported to lungs, brain or to
other distant sites.

metastatic symptoms
pulmonary lesions
cerebral lesions
metastatic nodule in the vagina,
vulva or cervix ,it is bluish
nodule filled dark red blood.

Diagnosis
Diagnosis must be suspected as
a possible reason for continued
(irregular) bleeding after any
form of pregnancy.
we assay hCG , the time of hCG
change into normal is different in
various diseases.

hCG change
HM:84-100 days
Artificial abortion:30 days
Spontaneous abortion:19
days
Normal delivery:12 days
Ectopic pregnancy:8-9 days

Staging
International staging of WHO may be
summarized as follows:
: lesion localized in uterus, no
metastasis;
: lesion extends beyond uterus, but
still confined to internal genitalias;
: pulmonary lesion
: metastasis to other distant sites.

Treatment
highly sensitive to chemotherapy,
which is invariably the treatment
choice.
surgery has little place (because of
the high vascularity and the
effectiveness of chemotherapy). it is
indicated for tumor resistant to
chemotherapy and single metastases
persisting despite chemotherapy.

Chemotherapy
most often used drugs
methotrexate (MTX)
actinomycin D (Act-D)
5-fluorouracil (5-Fu)
vincristine (VCR)
cyclophosphamide (CTX)
chlo-ranbucil, etc

principles
low-risk patients are usually treated with a
single agent
medium-risk patients are usually treated
with EMA-CO regimen with 80-90%
survival rate. (Etoposide,
Methotrexate,Actinomycin,Cyclophosphami
de,Vincristin)
toxic reaction: marrow depression ;
gastrointestinal ulceration;
change in liver and renal function

Standard for discharge

three consecutive weekly assays

for hCG are negative
two more courses for
consolidation
all symptoms and signs
disappear

Operation
unresponsive or drug fails to
reach the tumor;
if the tumor can be eradicated
by drug therapy, esp.in young
women, there is no reason to
remove the uterus;
the ovaries need not be
removed.

Follow-up examinations
at 1-month interval for 1 year:
at 3-month interval for 2 years
at 1-year interval for 3 years
at 2-year interval afterwards.
pelvic examination
chest X-ray film
hCG

Ask question :

What are the basic

histologic and pathologic
differences between
invasive mole and
choriocarcinoma?