GestationaI GestationaI TrophobIastic TrophobIastic

Disease (GTD) Disease (GTD)

ntroduction ntroduction
What is GTD ? What is GTD ?
t is a rare kind of disease in which t is a rare kind of disease in which
abnormal trophoblastic proliferation abnormal trophoblastic proliferation
occurs. occurs.
t is too among the rare human t is too among the rare human
malignancies that can be cured even malignancies that can be cured even
in the presence of widespread in the presence of widespread
metastases. metastases.
Which does it include? Which does it include?
t includes a spectrum of interrelated t includes a spectrum of interrelated
tumors, including tumors, including
hydatidiform mole (HM) hydatidiform mole (HM)
invasive mole (M) invasive mole (M)
Choriocarcinoma (CH) Choriocarcinoma (CH)
Placental Placental- -site trophoblastic tumor site trophoblastic tumor
(PSTT, borderline, very rare) (PSTT, borderline, very rare)
Relationship of HM. M. CH Relationship of HM. M. CH
hydatidiform therapeutic or hydatidiform therapeutic or
mole mole spontaneous abortion spontaneous abortion
term pregnancy term pregnancy
ectopic ectopic
invasion mole choriocarcinoma. invasion mole choriocarcinoma.
What is GTT (Gestational trophoblastic What is GTT (Gestational trophoblastic
tumor)? tumor)?
GTT is all GTD GTT is all GTD except hydatidiform except hydatidiform
mole. mole.
They has its unique pathologic They has its unique pathologic
characteristics and biological characteristics and biological
behavior. behavior.
Even the most malignant case can be Even the most malignant case can be
cured by chemotherapy. cured by chemotherapy.
Hydatidiform mole Hydatidiform mole
Hydatidiform mole Hydatidiform mole
Hydatidiform mole Hydatidiform mole
t is a neoplastic t is a neoplastic
proliferation of proliferation of
the trophoblast the trophoblast
in which the in which the
terminal villi terminal villi
are are
transformed transformed
into vesicles into vesicles
filled with clear filled with clear
viscid material. viscid material.
t is usually benign but has t is usually benign but has
malignant potentiality. malignant potentiality.
ncidence: ncidence:
south east Asia south east Asia is is 11/ /500 500- -600 600
the US and Europe: the US and Europe:11/ /500 500- -2000 2000
China: China:11/ /1238 1238
Classification Classification
t is divided into two classification t is divided into two classification
complete hydatidiform mole complete hydatidiform mole
partial hydatidiform mole partial hydatidiform mole
complete hydatidiform mole(CHM): complete hydatidiform mole(CHM):
the entire the entire
uterus uterus
filled with filled with
abnormal abnormal
vesicles, vesicles,
no signs of no signs of
fetus. fetus.
partial hydatidiform mole partial hydatidiform mole
partial partial
hydatidiform hydatidiform
mole with mole with
evidence of evidence of
a conceptus. a conceptus.
tiology tiology
Though it is not known a number of Though it is not known a number of
associated factors have been noted: associated factors have been noted:
the absence of fetal circulation; the absence of fetal circulation;
dietary protein deficiency dietary protein deficiency
viral infection; viral infection;
age:> age:>45 45 years women are years women are 10 10 times times
more likely to develop HM than more likely to develop HM than
those younger those younger
abnormal fertilization process: abnormal fertilization process:
the fertilization of a normal ovum the fertilization of a normal ovum
with a duplicated haploid with a duplicated haploid
sperm: sperm:46 46XX XX
the fertilization of an empty egg by the fertilization of an empty egg by
two sperms(dispermy): two sperms(dispermy):46 46XY XY
Chromosomes Chromosomes
complete hydatidiform moles complete hydatidiform moles
Cytogenetic studies have demonstrated Cytogenetic studies have demonstrated
that complete hydatidiform moles usually that complete hydatidiform moles usually
have a have a 46 46xx karyotype, and the molar xx karyotype, and the molar
chromosomes are entirely of paternal chromosomes are entirely of paternal
origin. origin.
Complete moles appear to arise from an Complete moles appear to arise from an
ovum that has been fertilized by a haploid ovum that has been fertilized by a haploid
sperm, which then duplicates its own sperm, which then duplicates its own
chromosomes, and the ovum nucleus may chromosomes, and the ovum nucleus may
be either absent or inactivated be either absent or inactivated
Although most complete moles have Although most complete moles have
a a 46 46xx chromosomal pattern, xx chromosomal pattern,
approximately approximately 10 10% % have a have a 46 46xy xy
karyotype. karyotype.
Chromosomes in a Chromosomes in a 46 46xy complete xy complete
mole also appear to be entirely of mole also appear to be entirely of
paternal origin, but in this paternal origin, but in this
circumstance, an apparently empty circumstance, an apparently empty
egg is fertilized by two sperm. egg is fertilized by two sperm.
..
partial hydatidiform mole partial hydatidiform mole
partial moles usually have a triploid partial moles usually have a triploid
karyotype ( karyotype (69 69 chromosomes ), with the chromosomes ), with the
extra haploid set of chromosomes derived extra haploid set of chromosomes derived
from the father. from the father.
When a fetus is present in conjunction When a fetus is present in conjunction
with a partial mole, it usually exhibits the with a partial mole, it usually exhibits the
stigmata of triploidy, including growth stigmata of triploidy, including growth
retardation and multiple congenital retardation and multiple congenital
malformations. malformations.
!athologic findings !athologic findings
compIete hydatidiform moIe compIete hydatidiform moIe
pathology pathology
Complete moles lack identifiable Complete moles lack identifiable
embryonic or fetal tissues, and embryonic or fetal tissues, and
the chorionic villi exhibit the chorionic villi exhibit
generalized hydatidiform swelling generalized hydatidiform swelling
and diffuse trophoblastic and diffuse trophoblastic
hyperplasia. hyperplasia.
Gross Gross
we see a mass of we see a mass of
vesicles, vary in vesicles, vary in
size, grape size, grape- -like like
with stems, blood with stems, blood
and clot filling the and clot filling the
inter inter- -vesicle space vesicle space
partial hydatidiform mole partial hydatidiform mole
t are characterized by the following t are characterized by the following
pathologic features : pathologic features :
Chorionic villi if varying size with Chorionic villi if varying size with
focal hydatidiform swelling and focal hydatidiform swelling and
cavitation. cavitation.
t contain identifiable embryonic or t contain identifiable embryonic or
fetal tissues. fetal tissues.
Gross Gross
we see a we see a
mass of mass of
vesicles, vesicles,
vary in size, vary in size,
grape grape- -like like
and and
identifiable identifiable
embryonic embryonic
or fetal or fetal
tissues. tissues.
icroscopic icroscopic
trophoblastic proliferation. trophoblastic proliferation.
hydropic degeneration of hydropic degeneration of
the stroma. the stroma.
absence of blood vessels or absence of blood vessels or
extreme scantiness of blood extreme scantiness of blood
vessels. vessels.

trophoblastic proliferation is trophoblastic proliferation is

considered the considered the most important single most important single
criteria. criteria.
Ovaries respond to hCG Ovaries respond to hCG
stimulation , stimulation ,30 30- -50 50% % theca theca- -lutein lutein
cysts develop, bilateral cysts develop, bilateral
Clinical course Clinical course
t has t has eight eight of of
symptoms and symptoms and
physical signs. physical signs.
amenorrhea amenorrhea
because it is a pregnancy. because it is a pregnancy.
vaginal bleeding vaginal bleeding
after a period of amenorrhea after a period of amenorrhea
(average (average 12 12 weeks) may continue weeks) may continue
intermittently for several weeks intermittently for several weeks--- ---
profuse bleeding profuse bleeding--- ---anemia and anemia and
infection. infection.
abdominal cramps abdominal cramps
abnormally abnormally
enlarged and enlarged and
soft uterus soft uterus
in about half the in about half the
cases, the cases, the
uterus growth is uterus growth is
rapid, it is larger rapid, it is larger
than the dates than the dates
suggest. suggest.
ovarian cyst ovarian cyst
torsion torsion
when we do pelvic when we do pelvic
examination examination
adnexal masses adnexal masses
may be found. it is may be found. it is
theca lutein cyst in theca lutein cyst in
about one third of about one third of
the cases the cases
severe and early severe and early onset PH onset PH
( (Pregnancy nduced Hypertension Pregnancy nduced Hypertension
syndrome) syndrome)
hyperthyroidism hyperthyroidism
plasma thyroxin concentration plasma thyroxin concentration
elevates elevates
exaggerated early pregnancy exaggerated early pregnancy
symptoms symptoms
nausea, nausea, vomit etc vomit etc
Diagnosis Diagnosis
suspicion: suspicion:
abnormal bleeding after amenorrhea abnormal bleeding after amenorrhea
inappropriately enlarged uterus; inappropriately enlarged uterus;
absence of fetal heart sounds or absence of fetal heart sounds or
could not feel fetal parts by palpation could not feel fetal parts by palpation
between between 16 16- -20 20
th th
week week
hyperemesis gravidarum hyperemesis gravidarum
bilateral ovarian cysts bilateral ovarian cysts
serum hCG monitor serum hCG monitor
an unusually high titer of chorionic an unusually high titer of chorionic
gonadotropin, especially after the gonadotropin, especially after the
one one- -hundredth day of pregnancy, hundredth day of pregnancy,
help to confirm the diagnosis of HM. help to confirm the diagnosis of HM.
Ultrasonography: Ultrasonography:
t is a reliable and sensitive technique t is a reliable and sensitive technique
for the diagnosis of complete molar for the diagnosis of complete molar
pregnancy. Because the chorionic villi pregnancy. Because the chorionic villi
exhibit diffuse hydatidiform swelling. exhibit diffuse hydatidiform swelling.
Complete moles produce a Complete moles produce a
characteristic vesicular sonographic characteristic vesicular sonographic
pattern, usually referred to as a pattern, usually referred to as a
snowstorm snowstorm pattern. pattern.
Ultrasonography may also Ultrasonography may also
contribute to the diagnosis of contribute to the diagnosis of
partial molar pregnancy by partial molar pregnancy by
demonstrating focal cystic demonstrating focal cystic
spaces in the placental tissues spaces in the placental tissues
and an increase in the transverse and an increase in the transverse
diameter of the gestational sac. diameter of the gestational sac.
ifferential diagnosis ifferential diagnosis
abortion; abortion;
multiple pregnancy; multiple pregnancy;
polyhydramnios polyhydramnios
%reatment %reatment
the uterus should be evacuated as the uterus should be evacuated as
soon as possible after the diagnosis soon as possible after the diagnosis
is made.(by suction curettage) is made.(by suction curettage)
suction; suction;
oxytocin administration:we can use oxytocin administration:we can use
blood transfusion or/and fluid blood transfusion or/and fluid
infusion.it is used to decrease the infusion.it is used to decrease the
size of the uterus; size of the uterus;
tissue sent for histology: tissue sent for histology:
it should be routine it should be routine
practice with all cases of practice with all cases of
incomplete miscarriage; incomplete miscarriage;
acute pulmonary acute pulmonary
complications complications
total abdominal total abdominal
hysterectomy hysterectomy
in older in older
multiparas multiparas
hysterectomy may hysterectomy may
be indicated. be indicated.
management of theca management of theca- -lutein lutein
cysts cysts
these tumors should not be these tumors should not be
excised because they excised because they
regress after the regress after the
trophoblastic tissue has trophoblastic tissue has
been removed. been removed.
chemotherapy chemotherapy
HM don HM don t need usually t need usually
chemotherapy because chemotherapy because
HM is benign disease. HM is benign disease.
ollow ollow- -up examinations up examinations
follow up mode in the follow up mode in the 2 2
years after discharge years after discharge
on each follow on each follow- -up up
check, check, the following the following
should be addressed should be addressed
symptom symptom
abnormal abnormal vaginal bleeding, vaginal bleeding,
cough, cough, hemoptysis hemoptysis
signs of metastasis signs of metastasis
pelvic examination pelvic examination
hCG evaluation hCG evaluation
BB- -ultrasound ultrasound
chest X chest X- -ray film ray film
contraceptive method contraceptive method
required for required for 11- -2 2 years years
condom is recommended. condom is recommended.
UD (intrauterine device)and pills UD (intrauterine device)and pills
are relatively contraindicated for are relatively contraindicated for
their potentiality of causing their potentiality of causing
abnormal vaginal bleeding. abnormal vaginal bleeding.
sk question sk question
1. 1. What is the etiology of GTD? What is the etiology of GTD?
2. 2. What is the classification of HM? What is the classification of HM?
3. 3. What is What is the main pathologic the main pathologic
changes of HM? changes of HM?
4. 4. What is the clinical course of What is the clinical course of
HM? HM?
5. 5. How Follow How Follow- -up examinations up examinations
will be done? will be done?
About About 80 80% % of the cases of HM of the cases of HM
have a benign course. one have a benign course. one- -half half
of patients become pregnant of patients become pregnant
subsequently. about subsequently. about 16 16% % of HM of HM
become invasion moles and become invasion moles and
some some 22..55% progress into % progress into
choriocarcinoma choriocarcinoma
nvasive Mole nvasive Mole
ntroduction ntroduction
nvasive Mole nvasive Mole arises from HM arises from HM
it has malignant potentialities, it has malignant potentialities,
invades the invades the myometrium myometrium and and
penetrates the uterine wall, penetrates the uterine wall,
extends into the broad ligament extends into the broad ligament
or peritoneal cavity. or peritoneal cavity.
in half or more of all cases in half or more of all cases
invasive mole metastasizes invasive mole metastasizes
through the peripheral through the peripheral
circulation to distant sites, circulation to distant sites,
mostly to the lung. mostly to the lung.
!athologic findings !athologic findings
excessive trophoblastic excessive trophoblastic
proliferation and proliferation and
invasiveness invasiveness
the degree of anaplasia is the degree of anaplasia is
variable: completely benign variable: completely benign- -
-- --highly malignant highly malignant
differentiation between invasive differentiation between invasive
mole and choriocarcinoma lies in mole and choriocarcinoma lies in
whether the villous pattern is whether the villous pattern is
preserved: preserved:
if we see villi, it must be if we see villi, it must be
invasion mole; invasion mole;
if we can if we can t see villi, it is t see villi, it is
choriocarcinoma. choriocarcinoma.
Clinical course Clinical course
Symptoms caused by primary lesions Symptoms caused by primary lesions
vaginal bleeding vaginal bleeding
pelvic examination reveals delayed pelvic examination reveals delayed
involution of the uterus, persisting involution of the uterus, persisting
cyst . cyst .
abdominal pain abdominal pain
intra intra--abdominal hemorrhage, abdominal hemorrhage,
penetration of the uterus . penetration of the uterus .
Metastatic symptoms Metastatic symptoms
- -cough, cough, hemoptysis hemoptysis--- ---positive X positive X- -ray ray
signs signs
- -profuse vaginal bleeding profuse vaginal bleeding--- ---vaginal vaginal
or cervical metastasis, we can see or cervical metastasis, we can see
bluish nodule bluish nodule in vagina in vagina
- -headache, nausea, headache, nausea, vomit, paralysis vomit, paralysis
or coma or comait is caused by cerebral it is caused by cerebral
lesion. lesion.
iagnosis iagnosis
history and clinical manifestation history and clinical manifestation
hCG assay: hCG assay:
diagnosis suspected if hCG titers diagnosis suspected if hCG titers
persist to be high persist to be high 12 12 weeks after weeks after
evacuation of a HM, or once evacuation of a HM, or once
regress to normal range but rise regress to normal range but rise
rapidly. rapidly.
possible reasons : retained HM possible reasons : retained HM
pregnancy pregnancy
huge theca huge theca- -lutein lutein cyst persist cyst persist
when we remove these reasons when we remove these reasons
we can diagnose invasive mole we can diagnose invasive mole
other measurement other measurement
BB- -ultrasound ultrasound
X X- -ray ray
!rophylaxis !rophylaxis
respond well to chemotherapeutic respond well to chemotherapeutic
agents agents
main causes of death: main causes of death:
hemorrhage, hemorrhage, metastasis and metastasis and
infection infection
%reatment: %reatment:
dentical to that for dentical to that for
choriocarcinoma choriocarcinoma
Choriocarcinoma Choriocarcinoma
t is highly malignant GTT t is highly malignant GTT
t may follow HM, t may follow HM,
invasion mole, abortion, invasion mole, abortion,
normal pregnancy, ectopic normal pregnancy, ectopic
pregnancy. pregnancy.
!athologic findings !athologic findings
ross inspection ross inspection
irregular or circumscribed irregular or circumscribed
hemorrhagic growth hemorrhagic growth in the uterine in the uterine
wall wall
ulcerating surface opens into the ulcerating surface opens into the
endometrial cavity (rarely endometrial cavity (rarely
embedded in myometrium) embedded in myometrium)
penetration into broad ligament or penetration into broad ligament or
the peritoneal cavity the peritoneal cavity
dark red blood:.it is filled dark red blood:.it is filled
metastatic nodules metastatic nodules
ulcerating ulcerating
surface opens surface opens
into the into the
endometrial endometrial
cavity (rarely cavity (rarely
embedded in embedded in
myometrium) myometrium)
istologic findings istologic findings
we see masses of anaplastic we see masses of anaplastic
trophblastic cells in microscopy; trophblastic cells in microscopy;
invasion into the uterine wall, invasion into the uterine wall,
destroying vessels, muscle tissue destroying vessels, muscle tissue
prominent necrosis and prominent necrosis and
hemorrhage hemorrhage
villi can not be recognized villi can not be recognized
spread through circulation spread through circulation
Clinical Manifestations Clinical Manifestations
irregular bleeding after irregular bleeding after
preceding gestation; preceding gestation;
malignant tumor cells enter the malignant tumor cells enter the
circulation through the open circulation through the open
blood vessels and are blood vessels and are
transported to lungs, brain or to transported to lungs, brain or to
other distant sites. other distant sites.
metastatic symptoms metastatic symptoms
pulmonary lesions pulmonary lesions
cerebral lesions cerebral lesions
metastatic nodule in the vagina, metastatic nodule in the vagina,
vulva or cervix ,it is vulva or cervix ,it is bluish bluish
nodule nodule filled dark red blood. filled dark red blood.
iagnosis iagnosis
Diagnosis must be suspected as Diagnosis must be suspected as
a possible reason for continued a possible reason for continued
(irregular) bleeding after any (irregular) bleeding after any
form of pregnancy. form of pregnancy.
we assay hCG , the time of hCG we assay hCG , the time of hCG
change into normal is different in change into normal is different in
various diseases. various diseases.
hCG change hCG change
HM: HM:84 84- -100 100 days days
Artificial abortion: Artificial abortion:30 30 days days
Spontaneous abortion: Spontaneous abortion:19 19
days days
Normal delivery: Normal delivery:12 12 days days
Ectopic pregnancy: Ectopic pregnancy:88- -9 9 days days
$taging $taging
nternational staging of WHO may be nternational staging of WHO may be
summarized as follows: summarized as follows:
: : lesion localized in uterus, no lesion localized in uterus, no
metastasis; metastasis;
: : lesion extends beyond uterus, but lesion extends beyond uterus, but
still confined to internal genitalias; still confined to internal genitalias;
: : pulmonary lesion pulmonary lesion
: : metastasis to other distant sites. metastasis to other distant sites.
%reatment %reatment
highly sensitive to chemotherapy, highly sensitive to chemotherapy,
which is invariably the treatment which is invariably the treatment
choice. choice.
surgery has little place (because of surgery has little place (because of
the high vascularity and the the high vascularity and the
effectiveness of chemotherapy). it is effectiveness of chemotherapy). it is
indicated for tumor resistant to indicated for tumor resistant to
chemotherapy and single metastases chemotherapy and single metastases
persisting despite chemotherapy. persisting despite chemotherapy.
Chemotherapy Chemotherapy
most often used drugs most often used drugs
methotrexate (MTX) methotrexate (MTX)
actinomycin D (Act actinomycin D (Act- -D) D)
55- -fluorouracil ( fluorouracil (55- -Fu) Fu)
vincristine (VCR) vincristine (VCR)
cyclophosphamide (CTX) cyclophosphamide (CTX)
chlo chlo- -ranbucil, ranbucil, etc etc
principles principles
low low- -risk patients are usually treated with a risk patients are usually treated with a
single agent single agent
medium medium- -risk patients are usually treated risk patients are usually treated
with EMA with EMA- -CO regimen with CO regimen with 80 80- -90 90% %
survival rate. (Etoposide, survival rate. (Etoposide,
Methotrexate,Actinomycin,Cyclophospham Methotrexate,Actinomycin,Cyclophospham
ide,Vincristin) ide,Vincristin)
toxic reaction: toxic reaction: marrow depression ; marrow depression ;
gastrointestinal ulceration; gastrointestinal ulceration;
change in liver and renal function change in liver and renal function
$tandard for discharge $tandard for discharge
three consecutive weekly assays three consecutive weekly assays
for hC are negative for hC are negative
two more courses for two more courses for
consolidation consolidation
all symptoms and signs all symptoms and signs
disappear disappear
peration peration
unresponsive or drug fails to unresponsive or drug fails to
reach the tumor; reach the tumor;
if the tumor can be eradicated if the tumor can be eradicated
by drug therapy, esp.in young by drug therapy, esp.in young
women, there is no reason to women, there is no reason to
remove the uterus; remove the uterus;
the ovaries need not be the ovaries need not be
removed removed. .
ollow ollow- -up examinations up examinations
at at 11- -month interval for month interval for 1 1 year: year:
at at 33- -month interval for month interval for 2 2 years years
at at 11- -year interval for year interval for 3 3 years years
at at 22- -year interval afterwards. year interval afterwards.
pelvic examination pelvic examination
chest X chest X- -ray film ray film
hCG hCG
sk question : sk question :
What are the basic What are the basic
histologic and pathologic histologic and pathologic
differences between differences between
invasive mole and invasive mole and
choriocarcinoma? choriocarcinoma?