e m

rs iu
Gestational

r
ou o
C rat
Trophoblastic Disease
w o
ie M
ev S
R G

Agnes L. Soriano-Estrella, MD, MHPEd, FPOGS

PO

Associate Professor
Department of Obstetris and Gynecology
College of Medicine, UP-PGH
Learning objectives

e m
rs iu
At the end of the session, the listeners should be

r
ou o
able to

C rat
 Properly
diagnose cases of gestational

w o
trophoblastic disease
 Outlineie M
a plan of management for cases of GTD
ev S
 Recommend strategies to minimize the risk for
R G

postmolar GTN
PO

 Explain the importance of beta hCG surveillance

 Discuss the management of pregnant patients with
a history of GTD
Gestational Trophoblastic Disease

e m
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r
ou o
BENIGN MALIGNANT

C rat
 Hydatidiform Mole  Gestational

w o
Trophoblastic
ie M
 Complete (CHM)
 Partial (PHM)
Neoplasia
ev S
 Invasive mole
 Placental site
R G

 Choriocarcinoma
nodule
PO

 Placental site trophoblastic

 Placental tumor (PSTT)
implantation site  Epithelioid trophoblastic
tumor (ETT)
 PO
R G
ev S
ie M
w o
C rat
ou o
r
rs iu
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Hydatidiform Mole
Definition

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 Hydatidiform mole is a general term that

ou o
C rat
includes two distinct entities, complete and
partial hydatidiform mole. Features

w o
common to both forms include a hydropic
ie M
state of some or all villi and trophoblastic
ev S
proliferation. The two forms, however,
R G

differ on the basis of chromosomal pattern,

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gross and microscopic histopathology and

clinical course.

WHO Technical Report, 1983

Pathophysiology

e m
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 Can explain the

ou o
C rat
difference in
clinical course,

w o
histopathology and
prognosis
ie M
ev S
R G
PO
Question #1

e m
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r
What is the most common karyotype of a

ou o
C rat
complete hydatidiform mole?

w o
a. 46 XX
b. 46 XY
ie M
ev S
R G

c. 69XXY
PO

d. 69XYY
Pathophysiology

e m
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r
Complete hydatidiform mole

ou o
C rat
w o
ie M 46 XX
ev S
Most common
R G
PO

46 XX
46 XY
Pathophysiology

e m
rs iu
r
Partial hydatidiform mole

ou o
C rat
w o
ie M 69 XXX
ev S
69 XXY
R G

69 XYY
PO
Question #1

e m
rs iu
r
What is the most common karyotype of a

ou o
C rat
complete hydatidiform mole?

w o
a.
✔ 46 XX
b. 46 XY
ie M
ev S
R G

c. 69XXY
PO

d. 69XYY
Risk Factors

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Previous

ou o
molar Diet

C rat
pregnancy

w o
Oral
ie M
Paternal
age
contraceptive
use
ev S
R G
PO

Maternal Hydatidiform
Race
age Mole
Question #1

e m
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r
A 27 y.o. G1P0, 8 weeks amenorrhea consults for

ou o
vaginal spotting. Pregnancy test is positive.

C rat
Examination revealed a boggy corpus enlarged to
16 weeks with no fetal heart tones. Cervix is closed.

w o
Cul de sac is full. What is your diagnosis?
ie M
a. Twin gestation
ev S
R G

b. Pregnancy with myoma uteri

PO

c. Hydatidiform mole
d. Pregnancy with polyhydramnios
Diagnosis

e m
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Physician’s high

ou o
C rat
index of suspicion
Based on the patient’s

w o
ie M clinical presentation
supported by typical
ev S
ultrasonographic
R G

findings and an
PO

elevated βhCG titer

CPG for the Diagnosis and Management of GTD, 2011

Diagnosis

e m
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SYMPTOM PERCENTAGE

ou o
C rat
Vaginal Bleeding 89-97%
Uterine size more than the age of 40-50%

w o
gestationie M
Presence of theca lutein cysts 20%
ev S
R G

Hyperemesis gravidarum 15-25%

PO

Pre-eclampsia 12-27%
Hyperthyroidism 2-7%
Respiratory failure 2%

Berkowitz RS, Goldstein DP, 2010

 Question #1

e m
rs iu
r
A 27 y.o. G1P0, 8 weeks amenorrhea consults for

ou o
vaginal spotting. Pregnancy test is positive.

C rat
Examination revealed a boggy corpus enlarged to
16 weeks with no fetal heart tones. Cervix is closed.

w o
Cul de sac is full. What is your diagnosis?
ie M
a. Twin gestation
ev S
R G

b. Pregnancy with myoma uteri

PO

✔c. Hydatidiform mole

d. Pregnancy with polyhydramnios
Diagnosis

e m
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Ultrasound

ou o
C rat
 Theoverall
sensitivity : 50-86%

w o
 Factors ie M
that influence
ev S
diagnosis
R G

• gestational age
PO

• operator
expertise
• type of h-mole
Diagnosis

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Ultrasound for

ou o
CHM

C rat
w o
 Diagnosed in
ie M
approximately 80%
of the cases
ev S
particularly during
R G

the second trimester

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when the grape-like

or hydropic villous
change occurs

Alhamdan D, Bignardi T, Condous G, 2009

Diagnosis

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ULTRASOUND IN PHM

ou o
C rat
 Less accurate

w o
 As much as 70% of cases may be missed
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 Twosonographic findings are significantly
ev S
associated with the diagnosis of PHM:
R G

 focal cystic changes in the placenta

PO

 a ratio of the transverse to antero-posterior

dimension of the gestational sac >1.5.

Alhamdan D, Bignardi T, Condous G , 2009; Fine C, et al, 1989

Diagnosis

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Ultrasound of PHM

ou o
C rat
 May show the
presence of a

w o
ie M
growth retarded
fetus with multiple
ev S
congenital
R G

anomalies attached
PO

to a hydropic
placenta
Diagnosis

e m
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Serum beta hCG

ou o
C rat
 Correlation of the
ultrasonographic

w o
findings with βHCG
ie M
levels can further
ev S
improve the
R G

recognition of a
molar pregnancy
PO

prior to surgical
evacuation

CPG for the Diagnosis and Management of GTD, 2011

Diagnosis

e m
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 Measurement of a high hCG (>100,000U/L)

ou o
C rat
in association with vaginal bleeding and
uterine enlargement highly suggests

w o
complete hydatidiform mole.
ie M
ev S
 Incontrast, partial hydatidiform mole is less
R G

commonly associated with markedly

PO

elevated hCG values.

Diagnosis

e m
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Gold standard for diagnosis is still based on

ou o
histopatholgic evaluation

C rat
Confirmatory tests

w o
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 Immunostaining may be performed in cases
where the histologic diagnosis is in doubt
ev S
R G

 p57kip2
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 Cytogeneticexaminations are recommended

when the diagnosis of hydatidiform mole is in
doubt.
Management

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ou o
C rat
Complete and partial moles differ

w o
histopathologically, cytogenetically and in
ie M
clinical behavior. However, management is
ev S
similar for both types of hydatidiform mole.
R G
PO
Management

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Diagnosed Case of Hydatidiform Mole

r
ou o
C rat
• CBC
Baseline Laboratory

w o
• Blood typing, Rh
Examination
ie M • BUN, Crea
• SGOT, SGPT
ev S
R G

Evaluate for and Treat • Quantitative

PO

Medical Complications serum βhCG

• Urinalysis
• Chest Xray
Prompt Surgical Evacuation
MANAGEMENT
Laboratory Examinations

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Other examinations (if indicated):

ou o
C rat
 Serum electrolytes

w o
 12-lead ie M
ECG
ev S
 Arterial blood gas
R G

 PT, PTT
PO

 FT4, TSH

PSSTD CPG, 2011; Sasaki, Best Practice and Research Clin Obstet Gynecol, 2003
Management

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Diagnosed Case of Hydatidiform Mole

r
ou o
C rat
• Anemia
Baseline Laboratory • Hyperemesis

w o
Examination
ie M •
gravidarum
Pre-eclampsia
ev S
• Hyperthyroidism
R G

Evaluate for and Treat • Respiratory

PO

Medical Complications insufficiency

• DIC

Prompt Surgical Evacuation

Management

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Evacuation of molar products

ou o
C rat
 definitive therapy

w o
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 Confirms pathologic diagnosis
ev S
 Relieves symptoms
R G

 Prevents
PO

complications

PSSTD CPG, 2011; RCOG, 2011; Rabbie K et al, 2010

Question #3

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A 27 y.o. G1P0, 8 weeks AOG consulted due to

ou o
vaginal spotting. Examination revealed a boggy

C rat
corpus enlarged to 16 weeks with no fetal heart

w o
tones. Cervix is closed. Ultrasound showed a snow
ie M
storm pattern and beta hCG was 154,000 nIU.ml.
What is the best mode of molar evacuation for her?
ev S
a. Medical induction
R G

b. Hysterotomy
PO

c. Suction curettage
d. Hysterectomy
Management

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Suction curettage Hysterectomy

ou o
C rat
 Preferred method  Option for patients
with completed family

w o
regardless of the size
ie M
patient’s age and  For patients with life-
uterine size threatening
ev S
hemorrhage
R G

 Decreases the risk for

PO

local invasion (3-5%)

 Does not eliminate the
need for post-
evacuation monitoring
Management

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Hysterotomy Medical Induction

ou o
C rat
• More bleeding • More bleeding

w o
• Subsequent
ie M • incomplete
operative evacuation
ev S
deliveries
R G

• higher risk of
PO

• higher risk of postmolar GTN

postmolar GTN
 Question #3

e m
rs iu
r
A 27 y.o. G1P0, 8 weeks AOG consulted due to

ou o
vaginal spotting. Examination revealed a boggy

C rat
corpus enlarged to 16 weeks with no fetal heart

w o
tones. Cervix is closed. Ultrasound showed a snow
ie M
storm pattern and beta hCG was 154,000 nIU.ml.
What is the best mode of molar evacuation for her?
ev S
a. Medical induction
R G

b. Hysterotomy
PO

✔c. Suction curettage

d. Hysterectomy
Management

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General guidelines:

r
ou o
C rat
 Cervical ripening done only through mechanical means
 Theca lutein cysts are best left alone during laparotomy.

w o

ie M
Patients who are Rh negative should receive Rh immune
globulin at the time of evacuation because the Rh D factor is
expressed on trophoblast.
ev S
R G

 All tissues obtained during molar evacuation should be

submitted for histologic evaluation.
PO

 Routine repeat curettage after the diagnosis of a molar

pregnancy is not warranted.

CPG for the Diagnosis and Management of GTD, 2011

Prognosis

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 Riskof malignant degeneration

ou o
C rat
 Complete mole :15-25%
 Partial mole : 0.5-4%

w o
 Risk ie M
is high especially among those with signs and
symptoms of marked trophoblastic proliferation
ev S
R G

CHEMOPROPHYLAXIS
PO

Sebire NJ, Seckl MJ, 2008; Garner EI et al, 2007

Chemoprophylaxis

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 May be useful in

ou o
situations where:

C rat
• patients are at high risk
of postmolar GTD

w o
ie M
• when post-evacuation
surveillance is doubtful
ev S
Methotrexate is the drug
R G

of choice
PO

Does not remove the

need for post-evacuation
hCG surveillance.

Lurain JR, AJOG, 2010; CPG for the Diagnosis and Management of GTD, 2011
Chemoprophylaxis

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Indication:

ou o
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1. Age > 35 y.o.
2. Gravidity of 4 or more

w o
3. Uterine size > 6 wks larger than AOG
ie M
4. Theca lutein cysts > 6 cm
ev S
5. Medical complications
R G

6. Recurrent mole
PO

7. Serum hCG > 100,000 mIU/l

8. Poor follow-up
CPG for the Diagnosis and Management of GTD, 2011
 FOLLOW-UP

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 Aftermolar evacuation, all patients must have

ou o
C rat
serial βhCG monitoring to detect malignant
degeneration

w o
ie M
ev S
R G
PO
 MOLAR EVACUATION

e m
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Serum βhCG after 1 week

ou o
C rat
Every 2 weeks until 3 Normal titers

w o
ie M
ev S
Serum βhCG every month for 6 months
R G
PO

Serum βhCG every other month to

complete 12 months
CPG for the Diagnosis and Management of GTD, 2011
 FOLLOW-UP

e m
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 Itis important to

ou o
use a reliable

C rat
contraception

w o
during the entire
ie M
follow up period
ev S
 Pregnancy may be
R G

allowed after 6
PO

months of normal
hCG titer
 FUTURE PREGNANCIES

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 Risk of another mole: 1-2% after 1 HM

ou o
C rat
15-20% after two HM

w o
 Risk
for stillbirth, prematurity, spontaneous abortion,
ie M
and congenital malformation is similar to that in the
general population
ev S
R G
PO

Lee C et al, 2010; Garrett LA et al, 2008

 FUTURE PREGNANCIES

e m
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r
ou o
 Anearly ultrasound should be performed

C rat
because of the risk of another molar

w o
pregnancy.
 βhCG
ie M
should be monitored at 6 weeks
ev S
postpartum
R G
PO

 Placentashould be submitted for

histopathologic examination
CPG for the Diagnosis and Management of GTD, 2011
 INDICATIONS FOR REFERRAL

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 High levels of ßhCG more than 4 weeks post-

ou o
evacuation (serum level of 20,000mIU/ml; urine

C rat
level of 30,000 mIU/ml)

w o
A ie M
rise in ßhCG of 10% or greater (2
consecutive weekly determinations)
ev S
R G

 PlateauingßhCG values (<10% decline or rise)

PO

at any time after evacuation (minimum of 3

consecutive weekly determinations)
CPG for the Diagnosis and Management of GTD, 2011
 INDICATIONS FOR REFERRAL

e m
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ou o
 Clinical or histologic evidence of metastasis at

C rat
any site.

w o
 Persistently
elevated ßhCG titer at 14 weeks
ie M
post-evacuation.
ev S
 Elevationof a previously normal ßhCG titer
R G

after evacuation provided the diagnosis of

PO

pregnancy is excluded.

CPG for the Diagnosis and Management of GTD, 2011

 e m
rs iu
r
ou o
C rat
w o
ie M
ev S
R G
PO

Gestational Trophoblastic Neoplasia

Diagnosis

e m
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r
Signs and Symptoms

ou o
• Vaginal bleeding

C rat
• Anemia
Uterine enlargement

w o
•
• ie M
Acute abdomen
secondary to tumor
ev S
perforation
R G

• Signs and symptoms

PO

referable to the site of

metastasis
DIAGNOSIS

e m
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r
ou o
Blood and urine Metastatic work-
Initial tests:

C rat
tests up

w o
• Baseline serum • CBC • Chest x-ray
ie M
beta hCG
• Transvaginal
• blood typing
• liver function
• Whole
abdomen CT
ev S
ultrasound, test scan or UTS
R G

preferrably • renal function • Chest CT scan

with Doppler test • Brain CT scan
PO

studies • thyroid
function test
• urinalysis

CPG for the Diagnosis and Management of GTD, 2011

Diagnosis

e m
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r
ou o
C rat
All patients must be staged and scored

w o
using the FIGO 2000 Anatomic Staging
ie M
and WHO Prognostic Scoring System.
ev S
R G
PO
Management

e m
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 Histopathologic

r
ou o
confirmation is not

C rat
necessary to start
treatment

w o
ie M
 Chemotherapy is the
principal mode of
ev S
treatment
R G

 Surgeryand
PO

radiotherapy are
adjunctive
treatments
MANAGEMENT

e m
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Chemotherapeutic Regimens

r
ou o
C rat
Stage I/Stage II or III, Low Risk

w o
ie M
• Single Agent Chemotherapy (Methotrexate)
• 2 consolidation therapies
ev S
R G

Metastatic, High Risk

PO

• Multi agent chemotherapy (EMACO)

• 3 consolidation therapies
Management

e m
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Hysterectomy

ou o
C rat
 Adjunctive treatment
 Indications

w o
 Remove a resistant focus
ie M
 Uterine perforation
ev S
 Profuse vaginal
R G

bleeding
 Reduce tumor load in a
PO

patient with completed

family size
Management

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 Administeredconcurrent

ou o
with chemotherapy

C rat
 Done in cases of brain

w o
and liver metastasis
ie M
 Advantages
ev S
R G

 Tumoricidal
PO

 Hemostatic
 Synergistic
effect with
chemotherapy
hCG MONITORING

e m
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Monthly for the 6 months

ou o
C rat
w o
Every 2 months for 6 months
ie M
ev S
R G

Every 3 months for 1 year

PO

Every 6 months thereafter

CPG for the Diagnosis and Management of GTD, 2011

 MANAGEMENT

e m
rs iu
r
ou o
C rat
w o
ie M
ev S
R G
PO

Avoid pregnancy Reliable

for 2 years contraception

CPG for the Diagnosis and Management of GTD, 2011

PSTT and ETT

e m
rs iu
r
 Almostalways cause irregular uterine

ou o
C rat
bleeding often distant from a preceding
nonmolar gestation

w o
 Rarelyie M
virilization or nephrotic syndrome
ev S
 Uterus is usually symmetrically enlarged
R G
PO

 Serum hCG levels are only slightly elevated

PSTT and ETT

e m
rs iu
r
 Established through histopathologic

ou o
C rat
examination
 PSTT : implantation-type intermediate

w o
ie M
trophoblast
 ETT : Chorionic-type intermediate
ev S
trophoblasts
R G
PO

 Immunostaining
 PSTT : diffuse presence of cytokeratin and
hPL ; focal staining with hCG
PSTT and ETT

e m
rs iu
r
Management

ou o
C rat
 Patients are classified using the FIGO staging
system only

w o
 Hysterectomy is the treatment of choice
ie M
 Chemotherapy is given in the form of EMACO
ev S
 hCG is used to monitor the disease/response
R G

to treatment
PO

 Same follow-up protocol as Choriocarcinoma

and Invasive Mole
 PO
R G
ev S
ie M
w o
C rat
ou o
r
rs iu
e m
Thank you for
your attention