Gestational trophoblastic

disease
 introduction
• Prior to 1969 metastatic choriocarcinoma
was invariably fatal.
• Virtually all patients are now potentially
curable with chemotherapy.
- Due to early diagnosis
- Precise measurement of hCG
- Availability of effective chemotherapy
 definition
• Trophoblastic disease is a spectrum of dz
which extends from benign hydatidiform mole
which usually resolve spontaneously, to life-
threatening choriocarcinoma.

• Incidence – 0.5 to 2.5 per 1000 pregnancies

• 3.04 per 1000 deliveries (Nigeria – Junaid
84)
 Gestational trophoblastic disease
• Hydropic degeneration – • Placenta site reaction
an aborted conceptus – the presence of
containing excessive trophoblastic cells
fluid or liquefaction of and leucocytes in a
placenta villus stroma placenta bed.
without undue
trophoblastic hyperplasia Hydropic degeneration and
placenta site reaction are not
complicated by malignant
sequelae.
• Complete hydatidiform • A classic mole resemble a
mole – an abnormal bunch of grapes.
conceptus, without an • May either resolve or may
embryo characterised by progress to invasive mole
gross hydropic or choriocarcinoma
(generalized) swelling of
the placental villi, with
• Partial hydatidiform mole –
diffuse trophoblastic
hyperplasia comprised of an abnormal conceptus
both cytotrophoblast and with an embryo or fetus
syncytial elements. that tend to die early. The
placenta has focal villous
• Has central cistern
swelling and focal
formation trophoblastic hyperplasia
• It is avascular with cistern formation.
The focal trophoblastic • Invasive mole – this is a
hyperplasia involves tumour invading the
only syncytiotrophoblast myometrium – xterised by
The unaffected villi trophoblastic hyperplasia
and persistence of the
appear normal and
placental villous structure.
vascularity of the villi
disappears following • Commonly results from
fetal death. complete hydatidiform mole.
• Usually does not progress
Patients with partial mole
to choriocarcinoma.
can be treated with
• It may metastasize.
chemotherapy for
metastasis and • May resolve spontaneously
elevated hCG
Does not progress to
choriocarcinoma
• Gestational
choriocarcinoma – it is
a carcinoma arising
from trophoblastic
epithelium that shows
both
syncytiotrophoblastic
and cytotrophoblastic
elements.
• Preceding conception
could result in a live
birth, still-birth, abortion
at any stage, ectopic
pregnancy or
hydatidiform mole.
• Antecedent pregnancy
– 50% - complete mole
- 30% - abortion
- 20% - normal preg
• Histology – lack of
villous structure –
distinguishes it from
invasive mole.
• Placental site
trophoblastic tumour –
a tumour arising from
the trophoblastic tissue
of the placental bed.
Composed mainly of
Of cytotrophoblastic cells • Gestational
which accounts for the trophoblastic tumour
relatively low levels of refers to conditions of
hCG in this condition. trophoblastic dz, that
• Treatment is by requires more active
complete surgical intervention
excision, since this (chemotherapy)
condition are not as Includes – invasive mole,
chemosensitive as choriocarcinoma and
choriocarcinoma. placental site tumours.
 genetics
• Complete mole results when a haploid
sperm (23x) fertilizes an empty ova
(nucleus is lost or inactivated) and
duplicate itself to form a 46xx complement
– paternal chromosomes.
• The karyotype of complete mole is usually
46xx and only in minority is it 46xy.
• Complete mole is usually homozygous
(xx) and less commonly heterozygous (xy)
• A complete mole with 46yy chromosome
complement is never seen – b/c at least
one x-chromosome is essential for cell
survival.
• A small percentage of complete mole
results from dispermy – 2 haploid sperm
(23x) fertilizing an empty egg.

• Partial hydatidiform mole results from

triploidy with one maternal and 2 paternal
chromosome sets – diploid and tetraploid
partial moles have been described.
 presentation
• Vag bleeding (most common) • Theca lutein cyst –
• Passage of vesicles abdominal pain due to
• Hyperemesis torsion or rupture.
gravidarum Disappear in 4
months following
• Severe anaemia
evacuation.
• Pre-eclampsia ( early onset)
• Uterine perforation.
• Clinical hyperthyroidism
• Pelvic sepsis
• Large for date uterus
• DIC
 Physical examination
• Chest – haemoptysis, pleuritic pain, and
pneumonic changes – due to tumour
invasion or following pulm infarction.
• Dyspnoea with extensive metastasis.
• Vagina inspection for suburethral nodule
(next common site of metastasis after
lung).
• Cerebral metastasis may present as
cerebrovascular accident, fits or loss of
consciousness
 investigations
• Quantitative hCG – • Chest x-ray
which is a tumour • Full blood count
marker for • T3 and T4 assay prior
trophoblastic tumours to surgery, if there is
– a good assay detect any suspicion of
as low as 2 IU/l of thyrotoxicosis.
hCG in serum.
• Liver function test
• Pregnancy test
• Serum E/U/Cr
• USS – xteristic snow
storm appearance, • Group and xmatch 2
exclude live fetus, units prior to
theca lutein cyst. evacuation.
• CSF hCG is measured • Blood group of patient
in high risk prognostic and sponse – for
group or in the middle prognostic score.
risk group with lung
metastasis.
• CT- scan – if there is
clinical suspicion of
brain metastasis
• MRI – done if despite
suspicion, the CT-scan
is normal. This is the
investigation of choice
in suspected spinal
metastasis.
 FIGO staging for trophoblastic dz

• Stage 0 – molar pregnancy

• Stage 1 – lesion confined to uterus without
metastasis.
• Stage 2 – lesion extend outside uterus,
but confined to genital organs
• Stage 3 – lung metastasis
• Stage 4 – other metastatic site
The risk of hydatidiform mole progressing to
choriocarcinoma increases

• Pre-evacuation hCG level >100000IU/l

• Uterine size greater than gestational age
• Large (>6cm) theca lutein cyst
• Maternal age >40yrs
• Use of oral contraceptive pill before hCG
level falls to undetectable level
• Medical induction, hysterectomy or
hysterotomy
 treatment
• Hydatidiform mole – resuscitation
- Suction evacuation.
- If bleeding is severe after evacuation give
ergometrine or repeat evacuation in 2 wks.
Note: medical induction, hysterectomy or
hysterotomy increases the need for
chemotherapy.
Follow-up for hydatidiform mole
• Choriocarcinoma occurs in 3% of cases of
complete hydatidiform mole, the risk is low
with partial mole.
• Follow-up is necessary to detect those
who require chemotherapy for invasive
mole or choriocarcinoma.
• The serum hCG is assayed 2 weekly until
it becomes undetectable (< 2IU/l), then
monthly in the 1st year after evacuation
and every 3 months in the 2nd year after
evacuation.
• The hCG measurement should continue
for at least 6 months after it has become
undetectable.
• The hCG must have been undetectable for
6months before starting another
pregnancy.
• After all subsequent pregnancy monitor
hCG – due to risk of hydatidiform mole
and choriocarcinoma.
• Post chemotherapy – hCG follow-up is for
life.
 Criteria for chemotherapy after
hydatidiform mole
• High hCG level more than 4 weeks after
evacuation. Serum level > 20,000IU/l or urine
level > 30,000IU/l
• Progressively rising hCG levels at anytime after
evacuation.
• Persistent uterine bleeding and positive hCG
levels
• Histological diagnosis of choriocarcinoma or
evidence of CNS, renal, hepatic, GIT or
pulmonary metastasis > 2cm in diameter or >3
in number.
 Criteria for chemotherapy after
hydatidiform mole
• Beta-hCG levels rising for 2 successive
weeks or constant for 3 successive weeks.
• Beta-hCG levels elevated at 15 weeks
postevacuation.
• Rising Beta-hCG titer after reaching
normal levels.
 Prognostic scoring factor
• Age • Largest tumour size
• Antecedent • Site of metastasis
pregnancy • Number of metastasis
• Interval between • Prior chemotherapy.
pregnancy and start
of chemotherapy
• hCG level
• ABO blood group of
both sponse
 Total score
• <4 – low prognostic group
• 5-7 – medium prognostic group
• >8 – high prognostic group

• Low prognostic group – single agent

chemotherapy – methotrexate with folinic acid
rescue – ensure the renal and liver function are
normal.
• 8-day course of treatment, then 6-day interval
before another course to prevent relapse.
 Medium and high risk prognostic
group
• Combination chemotherapy – MAC III,
CHAMOCA, EMA/CO

• Patient are advised against pregnancy for

a year after chemotherapy – to avoid
confusing a pregnancy with a relapse, to
reduce the risk of delayed teratogenicity.
 Role of surgery in mgt of
trophoblastic diseases
• Evacuation
• Uterine perforation managed by local
resection of tumour and uterine repair.
• Hysterectomy may be required for
persistent heavy bleeding – but usually
responds to chemotherapy
• Surgical removal of drug-resistant disease
in resectable site.