K H A L I D S A I T
C H A I R M A N O F S C I E N T I F I C C H A I R O F P R O F . A B D U L L A H H U S S A I N
B A S A L A M A H F O R G Y N E C O L O G Y O N C O L O G Y
D I R E C T O R O F G Y N E C O L O G Y O N C O L O G Y U N I T
P R O F E S S O R
F A C U L T Y O F M E D I C I N E
K I N G A B D U L A Z I Z U N I V E R S I T Y
• It is an abnormal condition of the ovum where there are
partly degeneration and partly hyperplastic changes in the
young chorionic villi, these result in the formation of small
cysts of varying size.
• Because of its superficial resemblance to a hydatid cyst, it
is named as hydatidiform mole.
• It is best regarded as a benign neoplasia of the chorion with
• H Y D AT I D I F O R M M O L E
• P E R S I S T E N T / I N VA S I V E
• C H O R I O C A R C I N O M A
• P L A C E N TA L S I T E T R O P H O B L A S T I C T U M O R S
• In Western countries, 1 per 1000-1500 pregnancies
• 1/20-30000 pregnancies in Canada.
• Latin American nations often have high rates
(1 per 12 to 500 pregnancies).
• Twofold increased risk in Saudi Arabia and Japan compared
to other population
• In Saudi Arabia, 1.2 per 1000 pregnancies
• Japan has 2 per 1000 pregnacies.
• In the Far east, 1 per 120 pregnancies. ( Indonesia 1:85)
• Extremes of reproductive years( maternal age )
• Prior moler mole
• Prior spontaneous abortion
• Vit A deficiency
• The cause is not definitely known, but it appers to be
related to the ovular defect as it sometimes affect 1 ovum
of a twin pregnancy.
Suggested hypothesis are:
ü Its prevalence is highest in teenage pregnancies and in
those women > 35yrs.
ü Faulty nutrition caused by inadequate intake of high class
protein could partly explain its prevalence in the oriental
countries low dietary intake of carotene is associated with
ü Disturbed maternal immune mechanism suggested by:
Ø Rise in gamma globulin level in absence of hepatic disease
Ø Increased association of of AB blood group which posses no ABO
ü Cytogenic abnormality
• 5 % result from
of empty egg which can
result into either 46 xx
or 46 xy
• Infrequently the
maybe 46xx or 45x
• COMPLETE MOLE
• No fetal tissue
• Diffuse chorionic villi
• 46XX(90%) or 46XY
entirely of paternal origin
• PARTIAL H.MOLE
• Fetal tissue present
• Focal chorionic villi
• Triploid(90%) 69 XXY, 69
XXX, 69 XYY).
• Complete Mole( triad):
Fetal tissue is absent,
severe trophoblastic proliferation,
Additionally, complete moles show over expression of several
growth factors, including c-myc, epidermal growth factor,
and c-erb B-2, compared to normal placenta.
• Partial Mole:
Fetal tissue is often present as well as amnion and fetal
red blood cells.
Hydropic villi and trophoblastic proliferation are not alot.
• 36 y.o P4 + 0
• She had H/o amenorrhea for 16 wks ,
presented with mild PV bleeding and lower
• Examination pulse 100/min BP120/80
• Abd/ soft, not tender - 24 weeks uterus
• V/E minimal bleeding, cervix normal and
close , uterus 20 weeks size and no adnexial
• HCG= 200,000
• Large for date 50 %
• Hyper emesis 20 %
• Early PIH 5%
• Absent FH ( except in partial mole or twin pregnancy)
• Hyperthyroidism symptom and sign 5%
• Rarely presented with metastasis symptom and sign
• Theca Lutein Cysts regress after treatment
• 3 % asymptomatic of cases
• Twinning with complete mole and a fetus with normal
placenta has been reported. Cases of healthy infant in
these circumstances have been reported.
• - Uterine enlargement and pre eclamsia is reported in only
3% of patients.
- Theca lutein cyst, hyperemesis and hyperthyroidism are
Ø Very rarely, women can present with acute respiratory
failure or neurological symptoms such as seizures; these
are likely to be due to metastatic disease.
• Quantitative beta-HCG levels greater than 100,000mlu/ml
indicate exuberant trophoblastic growth and raise suspicion
• A molar pregnancy may also have a normal HCG level.
• The classic image is of
a snowstorm pattern
v Type and screen
v Quantitative BhCG
Ø Suction curettage.
Ø when the size of the fetal parts deters the use of suction
curettage and then medical evacuation can be used.
Ø Preparation of the cervix immediately prior
to evacuation is safe.
Ø a senior surgeon directly supervising
surgical evacuation is advised
Ø The use of oxytocic infusion prior to the
evacuation is not recommended.
• Serum level ,within 48 hours of evacuation
• Weekly untill hCG become normal for three weeks
• Monthly for 6-12 months
• Reliable contraception recommended during hCG
• The histological assessment of material obtained
Ø The need for chemotherapy following a complete mole is
15%( 10 % LOCALIZED DISEASE AND 5 % METS) and 1 %
after a partial mole.
Ø The development of postpartum GTN requiring
chemotherapy occurs at a rate of 1/50 000 births
FACTORS THAT PREDICT THAT PATIENT WITH MOLAR
PREGNANCY MAY REQUIRE CHEMOTHERAPY:
1- Age more than 35
2- Uterine size more than 20 weeks
3- Initial B HCG more than 100,000 miu/ml
4- Presence of bilateral theca luteal ovarian
• Prophylactic chemotherapy for hydatidiform mole?
• ■A serum hCG concentration that plateaus (decline of less
than 10 percent for over three weeks)
• ■A serum hCG concentration that rises (increase more than
10 percent of three values over two consecutive weeks eg,
day 1, 7, 14)
• ■Persistence of detectable serum hCG for more than six
months after molar evacuation
* Presence of choriocarcinoma histopathology
J Reprod Med 2002; 47:445.
• 90 % invasive mole
• <10 percent are choriocarcinomas
• PSTTs are rare.
• Malignant transformation of trophoblastic tissue is probably
related to activation of oncogenes and inactivation of tumor
• The presence of metastatic disease usually implies the
presence of choriocarcinoma rather than invasive mole
• A patient diagnosed with complete mole after evacuation
and during the follow up her HCG were not decrease
( 14000. 13800.13850)over three weeks period.
• Repeat D and C
• Start chemotherapy
• Do work up then decide
• To diagnose metastases:
• CXR or CT Scan shows lung lesions will be acceptable, CXR to count
the lung lesions
• CT Scan or U/S to document liver metastases will be acceptable
• For brain metastases MRI is superior to CT even with cuts <1cm
• High-risk sites of metastases rarely occur without
• Cerebral metastases are rare unless there are concurrent
lung or vaginal metastases.
• Therefore CT or MRI brain scans may be omitted in those
patients without vaginal or lung metastases on chest X-ray.
Best Practice & Research Clinical Obstetrics and Gynaecology 2003
• 40 year Indian patient G7 P5 +1
• Referred from Makah as case of GTN
• She is five months post evacuation of complete mole
• follow up ??
• Quantitative BhCG 200.000
• CT abdomen showed multiple liver mets
Ø No clinical indication for the routine use of second uterine
Ø Some case series have found that there may be a role for
second evacuation in selected cases when the hCG is less
than 5000 units/lit. and patient severely bleeding
• Typically appears as one or more poorly defined masses in
the uterus with anechoic areas.
• Color Doppler of the anechoic areas reveals high vascular
• Invasion into the myometrium may be visualized
• Rarely metastasis
Slowly-growing malignant tumors ,
• derived from intermediate
• <0.2 %
• 30 percent of patients already have
metastases at presentation
• Lymph node metastases occur in 6
• IF persist after evacuation will
required hysterectomy because it is
highly resistant to chemotherapy.
• Mets disease mortality up to 50 %
• PSTT generally present months to
years after a term gestation.
• Irregular vaginal bleeding and an
enlarged uterus are common, a
mass in the uterus ( myometrium
• virilization may occur, and nephrotic
syndrome has been reported
• The serum hCG concentration in
PSTT is relatively low relative to the
tumor volume ( less than 100)
• Secrete HPL
• 50% of choriocarcinoma cases
follow a hyatidiform mole
• 25% form after an aborted
• 25% form after a term pregnancy.
Klatt, et al. Cancer 3-15-1990;65:1456-9.
• Metastasis from choriocarcinoma is common:
• 80% have lung lesions
• 30% have vaginal lesions
• 20% have pelvic lesions
• 10% have brain lesions
• 10% have liver lesions and bowel
• kidney and spleen are affected in less than 5%.
• Intracardiac tumors are very occasionally identified as
• D and C
• Give oral methoraxate
• Do risk assessment and start chemotherapy accordingly
MODIFIED WHO PROGNOSTIC SCORING SYSTEM AS ADOPTED BY FIGO
score 0 1 2 4
Age < 40 ≥ 40 - -
H-mole abortion Term pregnancy -
Interval (mo) from
<4 4 - 6 7 - 12 >12
hCG level <103 103 - 104 >104 - 105 >105
Largest tumor size
- 3 - 4 cm ≥5 cm -
Site of metastases - kidney, spleen GI tract brain, liver
- 1 - 4 5 – 8 >8
- - Single drug two or more drugs
• low-risk group (score ≤ 6)
• High-risk group (score ≥7)
Ø Women with scores ≤ 6 are at low risk and are treated with
Ø Women with scores ≥ 7 are at high risk and are treated with
intravenous multi-agent chemotherapy
SINGLE AGENT CHEMOTHERAPY
1) Methorexate 1gm/kg on day 1,2,3 and 7
Folinic acid 0,1mg/kg IM on day 2,4,6 and 8
( repeat every 7 days if possible)
3) Methotraxate 30-50 mg/m2 IM weekly
2) Dactinomycin 1,25 mg/m2 iv Q 2 w max 2 mg
3) Etoposide 200mg/m2 po Q12 days
• If hCG values have not decreased by 10%, treatment should
be changed to alternative single-agent regimen.
• In case of failure, the patient should be referred to
MULTI AGENT CHEMOTHERAPY
- CHAMOMA( Bagshawe 1970) met/cyclo/
doxoru/hydroxyurea and vincrestin
- Modified CHAMOMA(Surwit)
- EMA-CO ( Charing Cross Hospital in London)
Disease 5 year survival
• Low risk 100%
• High risk 86%
• Low Risk (Treated):
HCG’s weekly until 3 (neg), then monthly for 12 months, then q 3 months
X 1 yr. (for an additional year of follow up).
Pregnancy allowed after 12 months of normal titres and US is
recommended to confirm the pregnancy.
At the completion of pregnancy, the placenta/currettings must be
examined histological with a report sent to the registry, Beta HCG 6 weeks
after pregnancy, irrespective of outcome.
• High Risk (Treated):
HCG’s weekly until 3 (neg), then monthly for 2 years, q 3 months for the 3rd
year, q 6 months for the 4th year, then yearly thereafter.
Pregnancy allowed after 24 months of normal titres and US is
recommended to confirm the pregnancy. Beta HCG 6 weeks after
pregnancy, irrespective of outcome.
• Successful pregnancy has been reported even in
patient who survived after chemotherapy for high
risk metastatic disease
RECURRENCE OF GTN
Moler pregnancy 2 %
Low rish GTD 5 %
High risk GTD 15 %
The mean time to recurrence from the last non-detectable hCG
level was 6 months
Ø Women who receive chemotherapy for GTN are likely to
have an earlier menopause
Ø Women with high-risk GTN who require multi-agent
chemotherapy which includes etoposide should be advised
that they may be at increased risk of developing secondary
• Experience with gestational trophoblastic disease
• Experience with chemotherapy
• Patient’s compliance
• No Proper initial treatment of initial of diagnosis of moler
• No Proper follow up with HCG
• No good Interpretation of the HCG drop
• Tendency of repeating D and C ????
• Thinking that Hysterectomy is the answer for persistent
• Improper selection of chemotherapy
• Improper management of patient during and after
• To get exact incidence of GTD in Saudi Arabia
• If GTN diagnosed treatment is coordinated with gynecology
• All cases of molar pregnancy or GTN ie partial ,complete
mole and choriocarcinoma
• Patient with unexplained elevation of hCG titer can also be
• The registry provides services to women and physician in
western region in Saudi Arabia and well accept registration
from all region in Saudi Arabia
How to get registered?
• Registration is accepted fro all sources
v General practitioner
• Registration form fax to gynecology oncology unit at KAUH
Fax 026401000 ext 11480 E-mil
• Follow up recommendation is then made to the responsible
• 40 years old was diagnosed with low risk GTD received
single agent methoraxate
• Hcg was reched 80
• A week after was 75
• A week later was 78
• What to do ?
• Falsely elevated hCG can occur due to heterophilic
antibodies in the assay. This is due to human anti-mouse Ab
(HAMA), reacting with mouse Ab used in assays.
• It does not pass into urine so hCG should be negative.
• Another way to rule out this lab error is to retest with
another type of assay that uses serial dilutions(competitive
RIA. (HCG REFERANCE CENTER IN USA)
• Unnecessary chemotherapy or surgical intervention can be
• Group of disease with wide range of neoplastic potential
• Create a lot of challenge for us in term of diagnosis and
• Diagnosis and management will depends on the history,
HCG level and metastasis work up
• Women with metastatic GTD should be referred to
specialized with experience treating the disease
• GTD IS A RARE ENTITY THAT IS HIGHLY CURABLE ,
EVEN IN THE PRESENCE OF WIDESPREAD