Gestational Trophoblastic

Disease (GTD)
Part I : Molar Pregnancy
• Dr. Mohamed El Sherbiny
MD Ob.& Gyn. Senior Consultant
• Damietta, Egypt
Part I: Molar Pregnancy
 Definitions
Gestational Trophoblastic Disease (GTD)
It is a spectrum of trophoblastic diseases
that includes:
Complete molar pregnancy
Partial molar pregnancies
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.

RCOG Guideline No. 38 .2010

 Definitions
Gestational Trophoblastic Neoplasia (GTN)
=Malignant Gestational Trophoblastic Disease
It is a spectrum of trophoblastic diseases
that develops malignant sequelae. GTN
includes:
Persistent post molar GTD
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
Disaia &Creasman Clinical Gynecological Oncology 2007
Cunningham et al Williams Obsterics 23rd , 2010
Classifications
Gestational Trophoblastic Disease (GTD)
I-Pathologic Partial mole Invasive Chorio Placental site
mole trophoblastic
Classification Complete mole tumour
carcinoma
Pe
rsi
st en
tG G.T. Neoplasia
II-Clinical Benign TD

Classification G.T.D. Malignant G.T.D.

βhCG based:
WHO, FIGO,
ACOG 2004 & Metastatic
Non metastatic
RCOG 2010

Low risk High risk

 Gestational Trophoblastic Disease
Over the last 30 years major advances have taken place in
our understanding and management of gestational
trophoblastic disease.

1- It is now possible to diagnose a mole by

ultrasonography in minutes .
2-It became the most curable gynec. malignancy.
3-βhCG has very important role in the diagnosis,
evaluation and follow up of GTN
4- The cytogenetic profile has thrown
light on the etiology of the disease .
 Hydatidiform Mole

(H. MOLE)
-
=
Vesicular Mole
Hydatidiform Moles (H.M.)
Hydatidiform moles are abnormal
pregnancies characterized histologically
by :
 Trophoblastic proliferation &
 Edema of the villous stroma (Hydropic) .
Based on the degree and extent of these
tissue changes, hydatidiform moles are
categorized as either
Complete hydatidiform mole.
Partial hydatidiform mole.
 Features Of Partial And Complete Hydatidiform Moles
Feature Partial mole Complete mole
Most commonly Most commonly
69, XXX or - XXY 46, XX or -,XY
Karyotype
Pathology
Fetus Often present Absent
Amnion, fetal RBC Usually present Absent
Villous edema Variable, focal Diffuse
Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe
Clinical presentation
Diagnosis Missed abortion Molar gestation
Uterine size Small for dates 50% large for dates
Theca lutein cysts Rare 25-30%
Medical complications Rare 10-25%
Postmolar CTN 2.5-7.5% 6.8-20%
Disaia &Creasman Clinical Gynecological Oncology 2007
rd
Epidemiology& Risk Factors
Incidence:USA 1/1000 South East 1/100 (Hospital)
Risk Factors:
Age: <20y (2fold) , > 40y(10 fold) & >50y (50% V.mole)
Prior Molar Pregnancy
Second molar: 1% - Third molar : 20%!
Diet:↑ in low fat Vit. A or carotene diet (complete mole)
Contraception :COC double the incidence
Previous spontaneous abortion: double the incidence
Repetitive H. moles in women with different partners

Cunningham et al,Williams Obstetrics,23 ed ,2010

 Epidemiology &
Risk Factors
Partial moles have been linked to:
• Higher educational levels
• Smoking
• Irregular menstrual cycles
• Only male infants are among the
prior live births
Karyotype
 Homozygous 90%

Pathogenesis of complete H. Mole

 Heterozygous 10%

Pathogenesis of complete H. Mole

Pathogenesis of Partial H. Mole
Pathology of
Molar
Pregnancy
 Complete H. Mole
Microscopically Enlarged, edematous villi and abnormal
trophoblastic proliferation that diffusely involve the
entire villi
No fetal tissue, RBCs or amnion are produced

Macroscopically, these microscopic changes transform the

chorionic villi into clusters of vesicles with variable
dimensions “ like bunch of grapes"
No fetal or embryonic tissue are produced
Uterine enlargement in excess of gestational age .
Theca-lutein cyst associated in 30%
1-Trophoblastic proliferation

2-Hydropic Degeneration

Complete hydatidiform mole: Microscopically Enlarged,

edematous villi and abnormal trophoblastic proliferation that
diffusely involve the entire placenta
Complete hydatidiform mole: Macroscopically, these
microscopic changes transform the chorionic villi into clusters of
vesicles with variable dimensions the name hydatidiform mole
stems from this "bunch of grapes"
Complete Hydatiform Mole

Uterine wall
 Pathogenesis of
Choriocarcinoma
–Aneuploidy
–(Not a multiplication of 23
chromosome )
 Partial H. Mole
Microscopically: The enlarged, edematous villi and
abnormal trophoblastic proliferation are slight and
focal and did not involve the entire villi.
There is a scalloping of chorionic villi
Fetal or embryonic or fetal RBCs

Macroscopically: The molar pattern did not involve

the entire placenta.
Uterine enlargement in excess of gestational age is
uncommon.
Theca-lutein cysts are rare
Fetal or embryonic tissue or amnion
 Partial Hydatidiform Mole

Scalloping of chorionic villi

Trophoblastic proliferation are slight and focal

 Vesicles

Maternal side
Partial Hydatiform Mole
Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic
tissues were a partial mole
Partial H. mole.
 How Do Molar Pregnancies Present
To The Clinician?
The classic features are
Irregular vaginal bleeding
Hyperemesis
Excessive uterine enlargement &
Early failed pregnancy.
Clinicians should check a urine pregnancy test
in women presenting with such symptoms.

RCOG Guideline No. 38 ; 2010

Some women will present early with passage of molar tissue
 How Do Molar Pregnancies
Present To The Clinician?
Rarer presentations include:
Hyperthyroidism
Early onset pre-eclampsia
Abdominal distension due to theca lutein cysts
Very rarely
Acute respiratory failure
Neurological symptoms such as seizures (?
metastatic disease).

RCOG Guideline No. 38 ; 2010

What Is The Most Common Presenting
Symptom Of A Complete Molar Pregnancy?

A. Hyperemesis
B. Bilateral enlarged theca lutein cysts
C. Vaginal bleeding
D. Uterine enlargement> than expected for GA
E. Pregnancy-induced hypertension
What Is The Most Common Presenting
Symptom Of A Complete Molar Pregnancy?

A. Hyperemesis 10%

B. Bilateral enlarged theca lutein cysts 30%

C. Vaginal bleeding 85%

D. Uterine enlargement> than expected for GA 40%

E. Pregnancy-induced hypertension 1%
How Is Complete Mole Diagnosed?
U/S is helpful in making a pre-evacuation
diagnosis but the definitive diagnosis is
made by histological examination.
U/S: Early detection reduced from 16 weeks
(passage of vesicles) to 12 ws
βhCG levels > 2 multiples of the median may
be of value in the diagnosis

RCOG Guideline No. 38 ; 2010

 U/S& βhCG
Definite diagnosis on first U/S
examination
U/S alone: 68%
U/S + βhCG > threshold of
82,350 mIU/mL: 89%
Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007
TVS “Milestones” Versus βhCG
β hCG mIU/mL Weeks

Detection Level >5 3-4

Choriodecidual thickening 100 4
Gestational sac (D Zone) 1000 -1500 4-5
Yolk sac 7000 5- 6
Heart motion 10,000 6
Embryonic Movem. > 10.000 6- 7
Maximum level 50,000to 100,000 8-10
Complete Molar Pregnancy
Complete hydatidiform mole. The classic "snowstorm"
appearance is created by the multiple placental vesicles.
Complete H.Mole
(High-resolution) U/S
Complex intrauterine
mass containing many
small cysts.

Complete H.Mole
Associated theca-lutein
cysts. U/S Power Doppler
How Is Partial H .Mole Diagnosed?
In most patients with a partial mole,
the clinical and U/S diagnosis is
Usually missed or incomplete abortion.
This emphasizes the need for a
thorough histopathologic evaluation of
all missed or incomplete abortions

Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007

How Is Partial H .Mole Diagnosed?
Classically: A thickened, hydropic
placenta with fetal or embryonic tissue
Multiple soft markers, including:
 Cystic spaces in the placenta and
 Transverse to AP dimension a ratio of
the gestation sac of > 1.5, is required
for the reliable diagnosis of a partial
molar pregnancy

RCOG Guideline No. 38 ; 2010

Partial Molar Pregnancies
 Case Scenario 1

A 24-year-old 2nd Gravida ,Para 1 woman at 8 Ws

GA (Blood group: O, negative) complains of:
1-Worsening nausea, and vomiting over the last
2 weeks which is unlike her prior pregnancy .
2-Irregular vaginal bleeding over the last 7 days
She denies any abdominal or back cramps.
What does the differential diagnosis include for
this patient?
What Does The Differential Diagnosis
Include For This Patient?
The differential diagnosis of bleeding
with early pregnancy and
progressive vomiting are:
Multiple pregnancy.
Hydatidiform mole.
Threatened abortion.
Ectopic pregnancy.
Which Diagnostic Test Would Be
Most Useful?

The most useful diagnostic

test is :
U/S
Complex intrauterine mass containing many small cysts
(Snowstorm appearance)
What is the most likely diagnosis?

Hydatidiform (Vesicular) mole

 What Would One Expect To See At 
Scan If Her Pregnancy Is Normal?

Gestational (Chorionic) Sac

 What Is The Ultrasonogaphic 
Differential Diagnosis For  This Case?

U/S DD :
1-Missed 
abortion
2-Degenerated 
fibroid
 Differential Diagnosis:
 Long standing missed abortion
 with cystic degeneration of the placenta
What Is The Recommended Subsequent Test ?

β subunit hCG
The B subunit hCG assay:
195,000 mlU/mL
Then
1-What is the most likely diagnosis?
2-How can the patient be managed?
1-What Is The Most
Likely Diagnosis?
The snowstorm pattern on U/S&
The abnormally high hCG level 
are diagnostic of
Vesicular Mole
Probably complete V. mole 
Why It Is Probably Complete V. Mole? 
It demonstrates  the  typical U/S 
appearance of complete V. mole :
 a complex, echogenic intrauterine 
mass containing many small cystic 
spaces. 
Fetal tissues and amnionic sac are 
absent 
However the final differentiation is 
after histopathology.  
What Is The Plan of Management?

There are 2 important basic lines :
1-Evacuation of the mole
2-Regular follow-up to detect 
persistent trophoblastic disease
If both basic lines are done 
appropriately, mortality rates can be 
reduced to zero.
What Is The Best Method Of Evacuating This
Molar Pregnancy?
A. Cervical priming with misoprostol then suction
evacuation
B. Suction evacuation to be repeated 1-2 weeks later
C. Single suction evacuation
D. Medical trial with misoprostol &oxytocine before
suction
C.
What Is The Evidence ?
What Is The 
Evidence ?
The Management Of 
Gestational Trophoblastic 
Disease
RCOG Guideline  No. 38 ; 
2010
 What Is The Best Method Of
Evacuating A Molar Pregnancy?
For Complete mole is: 
Suction curettage

Cervical preparation with prostaglandins or 
misoprostol , should be avoided to reduce 
the risk of embolisation (No sufficient 
studies) 
RCOG Guideline  No. 38 ; 2010
 Is That The Same For Partial Mole?
For Partial mole: It depends on the fetal 
parts
Small fetal parts :Suction curettage
Large fetal parts: Medical (oxytocics) 
In partial mole the oxytocics is safe ,as the 
hazard to embolise and disseminate 
trophoblastic tissue is  very low 
Also, the needing for chemotherapy is 0.1- 
0.5%.

RCOG Guideline  No. 38 ; 2010
 Can Oxytocic Infusions Be Used
During Surgical Evacuation?
• The use of oxytocic infusion prior to 
completion of the evacuation is not 
recommended (fear of embolisation).
• If the woman is experiencing significant 
haemorrhage prior to evacuation, surgical 
evacuation should be expedited and the 
need for oxytocin infusion weighed up 
against the risk of tumour embolisation.

RCOG Guideline  No. 38 ; 2010
 Should Products Of Conception Be
Examined Histologically?
Histological examination is indicated in:
Failed pregnancies (missed or 
molar) :All medically or surgical managed 
cases
Products of conception, obtained after all 
repeat evacuations (post abortive or 
p.partum)
There is no need after therapeutic termination 
: provided that fetal parts is identified on 
U/SRCOG Guideline  No. 38 ; 2010
 Return to Case Scenario 1
Suction curettage has been performed
using 10mm canula under U/S guidance

10mm

Canula up to a maximum of 12 mm, is usually

sufficient to evacuate all complete molar pregnancies.
Other seats of suction curettage
Suction curettage has been performed
using 10mm canula under U/S guidance :
El SHERBINY HOSP

Canula
U/S Guided Suction Curettage

Suction curettage can be 
performed under U/S 
guidance to:

Facilitate the procedure

 Confirm  complete 
evacuation of contents. 
Garner UpToDate 2010
The Molar Content For Histopathological Examination
Meticulous histopathological examination revealed:
Villi have extensive stromal edema
Abnormal trophoblastic proliferation
No embryonic or fetal tissue or RBCs

These findings
are diagnostic
of:
Complete
Hydatidiform
Mole
The Case is Now Confirmed Histopathological
As A Complete H. Mole
What Is The Most Appropriate Management?

A- Surveillance :Weekly then monthly βhCG

B-Hysterectomy
C-Transvaginal U/S examination
D-Repeated curettage &Biopsy
E-Prompt chemotherapy

A.
 Hysterectomy may be preferred to
suction curettage at age ≥ 40 with no
desire for further pregnancies especially
with other risk factors for GTN as :
 Large theca lutein cysts( >6 cm)
 Significant uterine enlargement
 Pretreatment βhCG ≥ 105.
Although hysterectomy does not eliminate
possibility of GTN this, it markedly
reduces its likelihood.
Soper. Obstet Gynecol 108:176, 2006 Garner UpToDate 2010

Cunningham et al,Williams Obstetrics,23 ed ,2010

Complete H. Mole with
large for date uterus&
Theca-lutein cyst Complete H. Mole
After Hysterectomy
Patient was 42 years
5th G P5 initial
BhCG:195,000mIU/mL
Theca-lutein cyst associated with a complete H. mole in >30%
Second Uterine Evacuation :There is no
clinical indication for the routine use of
second uterine evacuation
RCOG Guideline No. 38 ; 2010

Prophylactic Chemotherapy: The long-term

prognosis for women with a H. mole is not
improved with prophylactic chemotherapy.
Because toxicity—including death—may be
significant, it is not recommended routinely *
It may be useful in the high-risk cases when follow-
up are unavailable or unreliable. * *
American College of Obstetricians and Gynecologists, 2004*
Is Anti-D Prophylaxis Required For
This Case?
No
When Anti-D Is Required?
It is required in partial due to the
presence of fetal RBCs
In complete mole: if diagnosis is not
confirmed histopathologically
RCOG Guideline No. 38 ; 2010
 Post-evacuation
Surveillance
Why?
To determine when pregnancy
can be allowed
To detect persistent
trophoblastic disease (i.e. GTN)
The Post-evacuation Surveillance. How?
A baseline serum β -hCG level is obtained
within 48 hours after evacuation.
Levels are monitored every 1 to 2 weeks
while still elevated to detect persistent
trophoblastic disease (GTN).
These levels should progressively fall to
an undetectable level (<5 mu/ml).
If symptoms are persistent, more frequent β hCG
estimation and U/S examination ± D&C are
advised
RCOG Guideline No. 38 ; 2010
Cunningham et al,Williams Obstetrics,23 ed ,2010
At the 9 week follow up the β hCG level : 2u/L
Is this level sufficient to stop follow up ?

No

4-

The Scenario case

Cunningham et al,Williams Obstetrics,23 ed ,2010
What Is The Optimum Follow-up Period
Following Normalization of β hCG?
A. For 6 months from the date of uterine
evacuation.
B. For 6 months from normalization of the β hCG
level.
C. For 12 months from the date of uterine
evacuation.
B
What Is The Optimum Follow-up Period
After Which Pregnancy Is Allowed?
It depends upon when hCG has reverted to normal
 ≤ 56 days of the pregnancy event: Follow up is
6 months from the date of uterine evacuation.
 >56 days of the pregnancy event :Follow up is
6 months from normalization of the hCG level.

RCOG Guideline No. 38 ; 2010

At this period levels of βhCG are monitored every month

Practically once βhCG has normalized after molar
evacuation, the possibility of GTN developing is very low.
What Is Safe Contraception Following GTD?
Barrier methods until normal β hCG level.
Once βhCG level have normalized:Combined
oral contraceptive (COC ) pill may be used.
If oral COC was started before the diagnosis of
GTD ,COC can be continue as its potential to
increase risk of GTN is very low
IUCD should not be used until β hCG levels are
normal to reduce uterine perforation.

RCOG Guideline No. 38 ; 2010

 Case Scenario 2

A 34-year-old woman, married for 7 years

3rd Gravida ,Para 0 at 14 Ws GA.

The previous abortions were at 7&8 weeks.

She complains of:

1-Mild vaginal bleeding for 4 days
2-Nausea, and moderate vomiting
Pulse 95/m, Bp 140/85
 US scanning revealed

What Is The U/S Differential Diagnosis?

What Is The U/S Differential Diagnosis?

Complete mole with a coexisting

normal twin
Partial mole
Other placental abnormalities
Rtroplacental hematoma
Degenerating myoma
What Are The Required Investigations?

Quantities serum β hCG

Free T4
Protein in urine
Rescanning after one week in a
tertiary or fetal medicine center for
diagnosis & screening.
 β hCG :80,000 mµ/ml
Free T4 : 2µg/ml (N 0.3-1.7µg/ml)
Protein in urine: Negative

U/S Tertiary center report:

Molar pregnancy with a coexisting normal
twin
The mole is mostly complete ,to be
confirmed histopathologicaly (After
termination).
U/S Fetal screening: No detectable
anomalies
Follow up is recommended .
 How Cane We Council The Couple?
1-Counseling for the increased risk of
perinatal morbidity :
• Bleeding
• Pre-eclampsia5-20%
• Hyperthyrodism 5%
• premature labor 35%
• Early fetal loss 40%
• Live birth only :25%.
2-Counseling for the increased risk of GTN
outcome and need of serial surveillance .
RCOG Guideline No. 38 ; 2010
The Patients Elects To Continue The
Pregnancy. How Can We Manage?
Close maternal surveillance for
development of preeclampsia or
hyperthyroidism.
Fetal karyotype may be considered if
follow up screening is not assuring
Serial hCG level for detection of GTN.
A chest x-ray to exclude pulmonary
metastases (choriocarcinoma)
Postpartum: the placenta should be sent
for evaluation by a pathologist
Garner UpToDate ,2010
When Must Pregnancy Be Terminated ?

Development of preeclampsia or
hyperthyroidism.
Fetal karyotype is not normal dioploidy
β hCG level levels consistent with GTN.
Evidence of metastases
(choriocarcinoma)
Accidental hemorrhage

Garner UpToDate ,2010

Thank You

Egypt