Gestational

Trophoblastic Disease
Current management

Background
Incidence

U.S. and Europe 1/1500

South East Asia 1/150

( Carotene, animal fat and Vit. A)

Can follow any gestational event abortion, miscarriage, ectopic, normal

pregnancy
Curable in vast majority chemotherapy 1956
Complete & partial mole
Invasive mole
Placental-site trophoblastic tumour
Choriocarcinoma ( always if follows term pregnancy 1/50,000 )
Latter 3 usually derive from molar pregnancy

Complete Mole
Pathology:

Generalized hydatidiform swelling and trophoblastic hyperplasia

fetal/embryonic tissue absent

Karyotype:

90% 46XX

haploid sperm fertilizes ovum and duplicates

ovum nucleus either absent or inactivated

10% 46XY
Clinical:

Diagnosis:

Vaginal bleeding
95%
Enlarged uterus
50%
Theca lutein cysts 50%
Hyperemesis
25%
PET
25%
Hyperthyroidism
5%
Trophoblastic emboli 2%

(prune juice, anaemia)

(often >6cm.- may take 3 months)
(no reported case of eclampsia)
(if free T4 - B-blockade)

U/S usually very sensitive generalized swelling (snow-storm )

Complete Mole

Complete Mole Histology

Partial Mole
Triploid karyotype extra haploid set paternal
Sometimes fetus present usually triploid
Pathology differs from complete:

growth restricted / multiple anomalies

focal hydatidiform swelling

varying size of chorionic villi
marked villous scalloping
focal trophoblastic hyperplasia
identifiable embryonic or fetal tissues

Clinical: Usually as a regular incomplete or missed abortion

Excessive uterine enlargement / PET very rare
No hyperemesis / hyperthyroidism / theca-lutein cysts
Diagnosis:

U/S may detect focal cystic spaces of varying diameter

Diagnosis on histology of curettings

Partial Mole Histology

Management
Pre-operative assessment medical complications / CXR
Evacuation -

oxytocin infusion after curettage

heavy bleeding should not deter from cervical dilatation
suction curettage (fundal massage)
uterus usually dramatically reduces in size / bleeding controlled
complete with sharp curettage
Histological evaluation of all tissue

Natural history:

Complete - 15% local uterine invasion

4% metastatic disease
High risk - hCG > 100000
(40%)
large uterus
30% local invasion
theca lutein cysts > 6cm. 9% metastases

Partial mole -

4% local uterine persistence/no cases choriocarcinoma

Many centres have abandoned follow-up

Follow up
Weekly -hCG (syncytiotrophoblast)
levels until
normal for 3 consecutive weeks
Can take 12-14 weeks
Then monthly until normal
for 6 months
Contraception:

Immediate

Oral / barrier / permanent

No IUCD until hCG normal (perforation)
No persistent disease on OCP and
regression time not influenced

GTN Follow-up

WHO Prognostic Scoring

Original assessment and scoring system 1984 changed in 2000
Metastatic disease occurs in 4% patients with molar pregnancy
Plateau: 4 values over 3 weeks
Rise:
10% for 3 values over 2 weeks
Clinical examination especially pelvis, vagina and vulva
U/S to exclude pregnancy
Brain MRI superior to CT scan
Chest CXR adequate for counting metastases / CT scan also acceptable
Abdomen CT scan

WHO Prognostic Scoring

Prognostic factor
Age
Antecedent pregnancy
Interval (months)
Pre-treatment -hCG (log)
Largest tumour
Site of metastases
Number of metastases
Previous Chemo. Failed
Changes:

0
<39
Mole
4
<3

Prognostic score
1
>39
Abortion
4-6
<4
3-4
Spleen
Kidney
1-4

Term pregnancy
7-12
<5
>5
5
GI tract
Brain
Liver
5-8
>8
Single drug
2 or more

ABO group deleted, Liver mets score upgraded, no medium risk group

Low risk = 6
High risk = 7

single agent chemotherapy

combination chemotherapy

FIGO Staging
Stage 1

Tumour confined to uterus

Stage 2

Tumour confined to pelvis

Stage 3

Metastases to lung ( with/without pelvic metastases )

Stage 4

Distant organ metastases ( with/without lung metastases )

Chemotherapy
Low-risk

If non-metastatic - always curable

( Hysterectomy if chemo fails)

Methotrexate:

Many regimes
I.M. Methotrexate 1mg/Kg days 1,3,5,7
I.M./ P.O. Folinic acid 0.1mg/Kg days 2,4,6,8
I.M. Methotrexate 40mg/m weekly

Actinomycin D:

I.V. push 1.25mg/m every 14 days

Follow-up:

-hCG, FBC, LFTs and U/Es, creatinine prior to each cycle

Continue treatment cycle for 1-3 weeks after normal -hCG
Check -hCG monthly for 12 months, then 2 monthly for 12 months
Contraception for 12 months

Complete remission in 85-90%

80% require only one course

Toxicity: Thrombocytopenia 2%, neutropenia 6% and hepatotoxicity 14%

High Risk GTN

Invasive mole:

invades myometrium / diagnosed at hysterectomy / can metastasize

mets may be choriocarcinoma

Placental site trophoblastic tumour:

Locally invasive composed of cytotrophopblast

small if any rise in hCG (<3000)
vaginal bleeding usually after amenorrhoea
Large polypoid tumour / insensitive to chemotherapy
Curettage sometimes successful / Hysterectomy

Choriocarcinoma:

Accounts for majority of metastatic disease

Early vascular invasion and widespread dissemination
Fragile vessels haemorrhagic complications
80% have lung mets any respiratory symptom
30% have vaginal mets highly vascular (avoid biopsy)
10% have liver mets usually only with extensive tumour elsewhere
10% have brain mets never isolated ( lung / vagina)

Treatment:
Prognosis:

EMA-CO chemotherapy +/- surgical resection / radiotherapy

75% complete response rate
Salvage chemo BEP varying success

Pregnancy After GTN

No evidence of increased congenital anomalies after one year contraception
Recent Japanese data

Women who concieved during follow-up period < 1 year

No adverse effect on anomalies nor preterm delivery

Risk of further molar pregnancy:

0.5-2.5% if one previous molar

33% if two previous molar
3 molar pregnancies poor live birth rate

Risk of molar pregnancy increases with number of previous spontaneous abortions

Previous term pregnancies reduce risk of GTN

Conclusions
GTN is rare
Ultrasound diagnosis becoming more common
Senior staff should perform ERPC ( suction and sharp curettage)
Follow-up clinical and serum -hCG measurements in specialized clinics
Chemotherapy curative in vast majority low risk patients