Gestational trophoblastic diseases

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Gestational
Trophoblastic
Diseases
Dr Njoroge Waithaka

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 These are diseases arising from
the trophoblastic tissue.
 The trophoblastic tissue consist of
synciotrophoblast and
cytotrophoblast
Definition

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Types of GTDs
1. Hydatidiform Mole
2. Invasive Mole
3. Choriocarcinoma
4. Placental Site Tumor

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Incidence
 Hydatidiform Mole is the
commonest of these diseases.
 In Taiwan the incidence is 1:125
deliveries
 USA 1:1500 deliveries
 Kenya 1:370 deliveries
 The incidence of choriocarcinoma
in Kenya is 1: 847

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Associated Factors
 More common at ages below 20yrs and
above 40yrs
 Low socioeconomic status
 Low protein and low folic acid diets
 Occur in less than 5%of subsequent
pregnancy
 A blood group A woman with a group O
spouse has a x10 higher risk
 Blood group AB have a poor prognosis

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In choriocarcinoma:-
 50% follow Hmole
 25% follow abortion
 25%follow term pregnancy

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classification
Hydatidiform Mole –
• (True Molar) abnormal pregnancy
characterized by multiple grapelike
vesicles filling and distending the uterus
in absence of an intact
fetus.chromosome are paternal 46xx
• Partial Mole occurs when the placenta
has molar transformation in the 2nd or
3rd trimester in presence of a fetus

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microscopy
 There is edema of the villi stroma,
avascular villi,nests of proliferating
synciotrophoblast and
cytotrophoblast elements
surrounding the villi. The likely
hood of malignant transformation
depends on degree of proliferation
and anaplasia

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Invasive
Mole(chorioadenoma
destruens)
 This is a Hmole that has invaded
into the myometrium
 Diagnosis is made histologically
from hysterectomy spacemen

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choriocarcinoma
 Malignant GTD
 This is a pure epithelial tumor
composed of synciotrophoblast
and cytotrophoblast cells.
 Histology :- sheets of trophoblastic
cells in a hemorrhagic background.
Degree of mitotic activity determine
degree of malignancy

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Clinical Features
 90% present with pv bleeding
 80% present with passage of
vesicles
 14.3% present with hyper emesis
 PET 10-12%
 Hyperthyroidism 10%
 Multiple ovarian cysts 15-30%

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Diagnostic tests
1. HCG is used for diagnosis and follow
up
 One tumor cell produces 0.00005-
0.0005i.u/24hrs of hcg
 One needs 4mil cells for a usual preg
test to be positive.
2. X-ray with dye will show a honey comb
appearance
3. Ultrasound will show a snow storm
appearance in the uterus with no fetal
parts.

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Differential diagnosis
 Normal pregnancy
 Multiple pregnancy

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Treatment
1. Hydatidiform mole
 Suction evacuation of the uterus
under high dose syntocinon
 Hysterectomy if uncontrollable
hemorrhage

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Follow up
 Follow up with weekly hcg levels till
three normal levels are achieved
 once monthly for at least 6months
or one year
 Give effective contraceptive
preferably from the last negative
result

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Malignant GTD
1. GTN may be diagnosed* when the
plateau of human chorionic
gonadotropin (hCG) lasts for 4
measurements over a period of 3
weeks or longer, that is for days
1,7,14,21.
2. GTN may be diagnosed* when there is
a rise of hCG of three weekly
consecutive measurements or longer,
over a period of at least two weeks or
more, that is before days 1,7,14.

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GTD diagnosis cont
3. GTN is diagnosed when the hCG
level remains elevated for 6
months or more**. The actual
level of hCG or the amount of rise
will be determined by the
individual investigator.
4. GTN is diagnosed if there is
histological diagnosis of
choriocarcinoma.

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GTD staging
 Stage I: Disease confined to the
uterus
 Stage II: GTN extends outside the
uterus but is limited to the genital
structures (adnexa, vagina, broad
ligament)
 Stage III: GTN extends to the lungs
with or without genital tract
involvement.
 Stage IV: All other metastatic sites.

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FIGO Risk Factor Scores
SCORE 0 1 2 4
Age (yrs) <40 40 >40
Antecedent
pregnancy
Hydatid
iform
Mole
Abortio
n
Term
Interval
Months from
Index
Pregnancy
<4 4-6 7-12

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FIGO Risk Factor Score
SCORE 0 1 2 4
Pre-treatment HCG
miu/ml
<1000 1000-
10000
10000-
100000
>100000
Largest tumor size
including uterus
3-4cm 5cm
Site of metastases SPLEEN
KIDNEY
GI
TRACT
BRAIN
LIVER

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FIGO Risk Factor Score
SCORE 0 1 2 4
Number of
metastases
identified
0 1-4 5-8 >8
Previous failed
chemotherapy
Single
drug
Two Or
More

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Interpretation of score
 4or below is low risk
 5-7 medium risk
 8 or > high risk

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REPORTING
 FIGO reporting system
 Stage: Score

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Treatment
Treatment depends on the score
And the presence of metastases.
Presence of brain metastases may
be inferred if the CSF:Serum HCG
is >1:60
Ultrasound scan or MRI can be used
to diagnose other organ
metastases

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Treatment cont.
Non Metastatic GTN
 Single drug therapy
1. Methotrexate 0.4mg/kg daily for 5days
2. Methotrexate1mg/kg daily on days
1,3,5,7. With folinic acid 0.1 mg/kg
I.M/oral on days 2,4,6,8.
3. Methotrexate 40mg/m weekly
4. Actinomycin-D 10-13mcg/kg I.V daily
for 5days
5. Actinomycin-D 1.25mg/m once every
two weeks

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Treatment cont.
Metastatic low risk
 Single drug therapy as in above.if
resistance develops then
combination therapy

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Treatment cont.
Moderate risk
 Recommended treatment is
combination therapy but some
centers have used single therapy
with success

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Treatment cont.
High Risk
Combination therapy is
recommended this include
 MAC
 EMA/CO
 EP/EMA

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Treatment cont.
MAC regimen
 Methotrexate usually on the higher
dose with rescue
 Actinomycin-D
 Cyclophosphamide

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Treatment cont.
EMA/CO
 EMA
Day1
 Etoposide 100mg /m I.V infusion in
250mls nsaline over 30min
 Actinomycin-D 0.5mg I,.V bolus
 Methotrexate 100mg/m bolus then
200mg/m infusion over 12hrs

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Treatment cont.
Day2
 Etoposide 100mg/m infusion
 Actinomycin-D 0.5mg I.V bolus
 Folinic acid 15mg I.M 12hrly for4
doses start 24hrs after
Methotrexate

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Treatment cont.
Day 8 CO
 Cyclophosphamide 600mg/m IV in
nsaline
 Vincristine 1.0mg/m bolus

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Follow Up
 This follows the same pattern but
is for 2yrs
 After three negative results one
starts follow up as for Hmole with
contraceptive

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prognosis
A. Low risk non metastatic 85-90%
cure rate. The rest will respond to
change of drugs
B. Low risk metastatic 30-50% will
develop resistance to first drug
requiring change of drugs. 5-15%
will require combination
chemotherapy

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Prognosis cont.
C. High Risk 86% 5 yrs survival rate. 17%
will develop drug resistance but 70% of
this will respond to surgery to remove
metastases site and additional
chemotherapy
D. CNS metastases grouped as
 Early when diagnosed before treatment
survival 80%
 Late (during or after treatment) survival
25%

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THE END