1. 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
GESTATIONAL
TROPHOBLASTIC
DISEASE

2. DEFINITION
• 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
malignant potential.

3. • 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
GESTATIONAL
TROPHOBLASTIC
DISEASE

4. INCIDENCE
• 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)

5. RISK
FACTORS
FOR
MOLER
PREGNANCY
• Extremes of reproductive years( maternal age )
• Prior moler mole
• Prior spontaneous abortion
• Vit A deficiency
• Smooking
• Infertility
• Nulliparity
• OCP
• Race

6. CLINICAL
PATHOLOGY
OF
GESTATIONAL
TROPHOBLASTIC
DISEASE
• 1- Cytotrophoblast and syncytiotrophoblast cells
proliferation
Moler pregnancy ( complete – partial )
Invasive mole
Choriocarcinoma
• 2- Intermediate trophoblastic cells derivative
Placental – site tumor

7. ETIOLOGY
• 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
increase risk

8. ETIOLOGY
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
antibody.
ü Cytogenic abnormality

9. Diandric diploidy
• 5 % result from
dispermic fertilization
of empty egg which can
result into either 46 xx
or 46 xy
• Infrequently the
chromosomal pattern
maybe 46xx or 45x

12. Diandric triploidy

13. HISTOLOGIC
FEATURES
• COMPLETE MOLE
• No fetal tissue
• Diffuse chorionic villi
swelling with
trophoblastic
hyperplasia
• 46XX(90%) or 46XY
entirely of paternal origin
• PARTIAL H.MOLE
• Fetal tissue present
• Focal chorionic villi
swelling with
trophoblastic
hyperplasia
• Triploid(90%) 69 XXY, 69
XXX, 69 XYY).

16. HISTOLOGICAL
FINDINGS
• Complete Mole( triad):
Fetal tissue is absent,
severe trophoblastic proliferation,
hydropic villi.
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.

18. • Partial Mole:
Fetal tissue is often present as well as amnion and fetal
red blood cells.
Hydropic villi and trophoblastic proliferation are not alot.

19. CASE PRESENTATION
• 36 y.o P4 + 0
• She had H/o amenorrhea for 16 wks ,
presented with mild PV bleeding and lower
abdominal pain
• 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
masses
• HCG= 200,000
• u/s

20. CLINICAL
FEATURES
COMPLETE
MOLE
• 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

21. • Twinning with complete mole and a fetus with normal
placenta has been reported. Cases of healthy infant in
these circumstances have been reported.

22. PARTIAL
MOLE
• - Uterine enlargement and pre eclamsia is reported in only
3% of patients.
- Theca lutein cyst, hyperemesis and hyperthyroidism are
rare.

23. 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.

24. LABARATORY
STUDIES
• 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.

25. IMAGING
STUDIES
• The classic image is of
a snowstorm pattern

26. MANAGEMENT
OF
MOLER
PREGNANCY

27. PATIENT
COUNSELLING
• Explain
• Consent
• preoperative preparation

28. PRIOR
TO
EVACUATION
v CBC
v Type and screen
v Quantitative BhCG
v TSH,LFT,RFT
v CXR

29. MANAGEMENT
Ø Suction curettage.
Ø when the size of the fetal parts deters the use of suction
curettage and then medical evacuation can be used.

30. MANAGEMENT
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.

31. FOLLOW
UP
POST
EVACUATION
• 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
surveillance.
• The histological assessment of material obtained

32. GTN
RISK
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

33. 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
cyst

34. • Prophylactic chemotherapy for hydatidiform mole?

35. FIGO
CRITERIA
FOR
THE
DIAGNOSIS
OF
POST
MOLAR
GTN
• ■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.

36.
PERSISTENT
GTD
• 90 % invasive mole
• <10 percent are choriocarcinomas
• PSTTs are rare.

37. GTN
• Malignant transformation of trophoblastic tissue is probably
related to activation of oncogenes and inactivation of tumor
suppressor genes
• The presence of metastatic disease usually implies the
presence of choriocarcinoma rather than invasive mole

38. CASE
PRESENTATION
• 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.

39. CHOICES
• Repeat D and C
• Start chemotherapy
• Do work up then decide

40. • 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

41. INVESTIGATIVE
TOOLS
TO
DIAGNOSE
METASTASES
• High-risk sites of metastases rarely occur without
pulmonary metastases.
Cancer 1990
• 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

42. CASE
PRESENTATION
• 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

44. SECOND
UTERINE
EVACUATION
Ø No clinical indication for the routine use of second uterine
evacuation
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

45. HYSTERECTOMY
•

46. MANAGEMENT OF MOLAR
PREGNANCY
Risk of Persistent
GTT
Procedure
20 %Suction
Evacuation
5%Hysterectomy

47. MALIGNANT
GTD(
GTN)
• Invasive mole
• Choriocarcinoma
• PSTT

48. INVASIVE
MOLE
• Typically appears as one or more poorly defined masses in
the uterus with anechoic areas.
• Color Doppler of the anechoic areas reveals high vascular
flow.
• Invasion into the myometrium may be visualized
• Rarely metastasis

50. PLACENTA
SITE
TROPHOBLASTIC
(TUMORS(
PSTT
Slowly-growing malignant tumors ,
can metastasis
• derived from intermediate
cytotrophoblast cells
• <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
involvement) .
• 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

51. CHORIOCARCINOMA
• 50% of choriocarcinoma cases
follow a hyatidiform mole
• 25% form after an aborted
pregnancy
• 25% form after a term pregnancy.
Klatt, et al. Cancer 3-15-1990;65:1456-9.

53. DISCUSSION
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
Metastatic choriocarcinoma.

58. MANAGEMENT
OF
PERSISTANT
GTD
• Hysterectomy
• D and C
• Give oral methoraxate
• Do risk assessment and start chemotherapy accordingly

59. MODIFIED WHO PROGNOSTIC SCORING SYSTEM AS ADOPTED BY FIGO
score 0 1 2 4
Age < 40 ≥ 40 - -
Antecedent
pregnancy
H-mole abortion Term pregnancy -
Interval (mo) from
index pregnancy
<4 4 - 6 7 - 12 >12
hCG level <103 103 - 104 >104 - 105 >105
Largest tumor size
(including uterus)
- 3 - 4 cm ≥5 cm -
Site of metastases - kidney, spleen GI tract brain, liver
Number of
metastases
- 1 - 4 5 – 8 >8
Previous failed
chemotherapy
- - Single drug two or more drugs
• low-risk group (score ≤ 6)
• High-risk group (score ≥7)

60. REMINDER

62. THE
CHEMOTHERAPY
Ø Women with scores ≤ 6 are at low risk and are treated with
single-agent chemotherapy.
Ø Women with scores ≥ 7 are at high risk and are treated with
intravenous multi-agent chemotherapy

63. 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

64. • 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
specialized center.

65. MULTI AGENT CHEMOTHERAPY
- MAC
- CHAMOMA( Bagshawe 1970) met/cyclo/
doxoru/hydroxyurea and vincrestin
- Modified CHAMOMA(Surwit)
melphalan
- EMA-CO ( Charing Cross Hospital in London)

68. REMISSION
OF
GTN
Disease 5 year survival
• Low risk 100%
• High risk 86%

69. FOLLOW-­‐UP
POST
TREATMENT
• 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.

70. • Successful pregnancy has been reported even in
patient who survived after chemotherapy for high
risk metastatic disease

71. TREATMENT FAILURE FACTORS
1) Extensive disease
2) Inadequate initial treatment:
3) Interruption of treatment cycles

72. RECURRENCE OF GTN
DISEASE RECURRENCE
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

73. POST
CHEMO
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
cancers.

74. THE
MOST
IMPORTANT
FACTORS
TO
ASSURE
SUCCESSFUL
THERAPY
• Experience with gestational trophoblastic disease
• Experience with chemotherapy
• Patient’s compliance

75. WE
DO
HAVE
PROBLEM…..
• No Proper initial treatment of initial of diagnosis of moler
pregnancy
• 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
GTD ??????
• Improper selection of chemotherapy
• Improper management of patient during and after
chemotherapy

76. SAUDI
GTD
REGISTRY
Gynecology oncology unit

77. SAUDI
GTD
REGISTRY
Objective
• To get exact incidence of GTD in Saudi Arabia
• If GTN diagnosed treatment is coordinated with gynecology
oncology

78. WHO
SHOULD
REGISTERED
?
• All cases of molar pregnancy or GTN ie partial ,complete
mole and choriocarcinoma
• Patient with unexplained elevation of hCG titer can also be
registered
• The registry provides services to women and physician in
western region in Saudi Arabia and well accept registration
from all region in Saudi Arabia

79. SAUDI
GTD
REGISTRY
How to get registered?
• Registration is accepted fro all sources
v Gynecology
v General practitioner
v Pathologist
• Registration form fax to gynecology oncology unit at KAUH
Fax 026401000 ext 11480 E-mil
gou_kauh@yahoo.com
• Follow up recommendation is then made to the responsible
physician

81. CASE
PRESENTATION
• 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 ?

82. PHANTOM
HCG
• 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
avoided

83. KEY
WORDS
• Group of disease with wide range of neoplastic potential
• Create a lot of challenge for us in term of diagnosis and
treatment
• 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
METASTASES

84. THANK YOU