00:00
The topic of this presentation
00:02
is on hydatidiform moles.
00:04
A hydatidiform mole, also known
00:06
as a molar pregnancy,
00:08
is a relatively rare condition
00:10
whereby there is
00:10
abnormal proliferation
00:12
of the placenta in a pregnancy,
00:14
resulting in a massive cyst
00:16
in the uterus rather than
00:17
a viable pregnancy.
00:19
Today we’ll be talking about two
00:20
types of moles, complete moles
00:22
and pasture moles,
00:23
as well as their complications.
00:25

00:28
Some of the risk factors
00:29
for molar pregnancies
00:31
include extremes of age.
00:33
That is below 20 or above 35.
00:36
A prior history
00:37
of gestational trophoblastic
00:39
disease, nulliparity, a diet
00:42
low in beta carotene,
00:44
folic acid, and animal
00:45
fat, smoking, and usage of OCPs.
00:49

00:52
There are two types of molar
00:54
pregnancies,
00:54
complete and incomplete.
00:56
A complete mole is a result
00:58
of the fertilization
00:59
of an enucleate ovum.
01:00
That is an ovum with a missing
01:02
or nonfunctional nucleus
01:04
with a normal sperm which then
01:06
replicates itself.
01:07
More rarely a complete mole
01:09
can be formed
01:10
by the fertilization
01:11
of an enucleate egg
01:12
with two normal sperms.
01:14
In both cases the chromosomes
01:16
in a complete mole
01:17
are all paternally derived.
01:19
Complete moles are the more
01:21
common molar pregnancy,
01:23
accounting for 90% of molar
01:25
pregnancies.
01:26
Among them the most
01:27
common karyotype is 46XX.
01:29

01:33
In a complete mole
01:34
there
01:34
is
01:35
noninvasive trophoblastic
01:36
proliferation, which leads
01:38
to diffused swelling
01:39
of the chorionic villi and
01:40
hydropic degeneration.
01:42
This gives the mole
01:43
its characteristic appearance
01:45
of grape-like vesicles
01:46
filling the uterus.
01:47
Notably, in a complete mole
01:49
there’s an absence of fetus,
01:51
fetal villi, or fetal red blood
01:53
cells.
01:54
In addition, there’s
01:55
abnormal proliferation
01:57
of syncytial trophoblasts
01:59
which produces high levels
02:00
of hCG.
02:02
hCG has both alpha and beta
02:04
levels, and the alpha sub unit
02:07
can be found in LH, FSH,
02:09
and TSH.
02:10
Because of this, they can act
02:12
as homologues to LH and FSH
02:15
and stimulate development
02:16
of large theca lutein cysts.
02:18
Likewise, they can also act
02:20
as homologues to TSH to cause
02:22
hypothyroidism.
02:24
The high hCG levels can also
02:26
cause hyperemesis gravidarum
02:29
and early pre-eclampsia.
02:31
15% to 20% of complete
02:33
moles progress to malignancy.
02:34

02:38
On the other hand,
02:39
a partial or incomplete mole
02:41
is formed when a normal ovum is
02:43
fertilized by two sperms
02:45
simultaneously.
02:46
The most common karyotype
02:47
associated with it is 69XXY.
02:51
An incomplete mole results
02:53
in placenta abnormality
02:54
characterized
02:55
by focal hydropic villi,
02:58
and trophoblastic hyperplasia,
03:00
primarily
03:01
of the cytotrophoblasts.
03:03
In contrast to a complete mole,
03:05
there’s normal or only slightly
03:08
elevated hCG
03:09
since cytotrophoblasts do not
03:11
produce hCG.
03:13
Uniquely incomplete moles are
03:15
associated with the presence
03:17
of a fetus.
03:18
In fact, amniotic fluid
03:19
and fetal heart rate
03:20
may also be present.
03:23
However, the fetus often has
03:25
multiple structural
03:26
abnormalities,
03:27
and it’s likely to be growth
03:29
restricted.
03:30
Furthermore, most fetuses
03:31
survive only several weeks
03:33
in vitro
03:34
before being spontaneously
03:36
aborted
03:36
in the late first or early
03:38
second trimester.
03:40
It is worthy to note
03:41
that partial moles are almost
03:42
always benign
03:44
and have a much lower malignancy
03:46
potential than a complete mole.
03:48
Compared to the 15% to 20%
03:50
who progress
03:51
to a persistent mole,
03:52
less than 5%
03:53
of patients with partial moles
03:55
will develop
03:55
persistent malignant disease.
03:56

04:00
A molar pregnancy usually
04:02
presents with the following
04:03
symptoms.
04:04
First vaginal bleeding, which
04:06
is caused by the separation
04:07
of the tumor
04:08
from underlying desidual,
04:10
leading to disruption
04:11
of maternal vessels.
04:13
In cases of prolonged bleeding,
04:14
signs and symptoms of anemia
04:16
may be observed.
04:17
One may also observe passage
04:18
of molar vesicles, nausea
04:20
and vomiting caused
04:22
by hyperemesis gravidarum.
04:25
On physical examination
04:26
one may observe hypertension
04:28
due to pre-eclampsia,
04:30
and a uterine size which is more
04:31
than gestational age, which may
04:33
be caused by tumors, blood
04:35
clots, or hemorrhage.
04:38
Partial or incomplete moles
04:39
present in the same way.
04:41
However the symptoms are less
04:42
severe from that
04:43
of complete moles,
04:45
as the hCG levels are only
04:47
slightly elevated.
04:49
As such, they are diagnosed
04:50
later than complete moles.
04:52
90% of them will present
04:54
with vaginal bleeding
04:55
from miscarriage or incomplete
04:57
abortion in late first
04:59
or early second trimester.
05:01
As such incomplete moles are
05:03
often diagnosed later
05:04
than complete moles.
05:05
Unlike complete moles,
05:07
the abdomen is smaller
05:08
for its gestational age,
05:10
due to the presence
05:11
of complications
05:12
such as intrauterine growth
05:13
restriction.
05:14

05:17
Because hCG levels are extremely
05:20
high in complete moles
05:21
relative to values
05:22
for normal pregnancy
05:24
and correlate with tumor size,
05:26
they can be used to diagnose
05:28
and assess treatment
05:29
effectiveness.
05:30
A serum hCG level above 100,000
05:33
is indicative of a molar
05:35
pregnancy.
05:37
Under pelvic ultrasound
05:38
no fetus or amniotic fluid
05:40
is seen.
05:41
Instead the intrauterine tissue
05:43
has a snowstorm appearance
05:44
due to the swelling
05:45
of chorionic villi.
05:48
In the figure on the left we see
05:49
the classically described
05:51
snowstorm appearance
05:52
of a complete mole
05:53
in the region label M.
05:55
In addition the skin may also
05:57
reveal [INAUDIBLE]
05:58
bilateral theca lutein cysts.
06:01
However,
06:01
the definitive diagnosis
06:03
of molar pregnancy
06:04
is made
06:05
on pathological examination
06:07
of intrauterine tissue
06:09
after the uterus has been
06:10
evacuated.
06:10

06:14
In diagnosing
06:15
an incomplete molar pregnancy
06:18
serum hCG levels
06:19
are likely to be relatively
06:20
normal.
06:21
Pelvic ultrasound may reveal
06:23
a fetus with a heartbeat.
06:25
In addition, intrauterine tissue
06:26
has a Swiss cheese appearance.
06:29
Similar to complete moles,
06:30
a definite diagnosis can only
06:32
be made
06:33
on pathological examination
06:34
of the intrauterine tissue
06:36
after evacuation.
06:36

06:40
The management
06:41
of complete and partial moles
06:42
are similar.
06:44
The definitive treatment
06:45
involves the immediate removal
06:47
of uterine contents
06:48
by suction curettage.
06:50
In older women who have
06:51
completed their family
06:53
a hysterectomy may be performed
06:55
instead.
06:56
Following evacuation
06:57
or hysterectomy patients
06:58
have to be followed up closely
07:00
for persistent disease, which
07:02
occurs in 15% to 25%
07:05
of patients
07:05
with a complete mole.
07:07
Serial hCG titers are measured
07:09
within 48 hours of evacuation.
07:12
And then weekly until negative
07:14
for three consecutive weeks.
07:16
hCG levels are then followed
07:18
monthly for six months.
07:20
Any plateau or rise in hCG
07:22
levels during this period
07:23
is
07:24
indicative
07:24
of a persistent or invasive
07:26
mole.
07:27
Because it is
07:28
critical to monitor hCG levels,
07:30
pregnancy must be avoided
07:32
in the follow up period
07:33
with reliable contraception
07:35
such as oral contraceptive
07:37
pills.
07:38
Subsequent pregnancies should be
07:39
closely monitored
07:40
with early ultrasound and hCG
07:43
monitoring
07:44
to exclude recurrent disease.
07:46

07:50
In 20% of patients with a molar
07:52
pregnancy, the hydatitiform mole
07:54
undergoes
07:55
malignant transformation
07:57
to cause persistent or invasive
07:58
disease.
07:59

08:02
Some of the risk factors
08:04
for malignant transformation
08:06
include a maternal age above 40
08:08
years old, extremely high
08:11
beta hCG levels,
08:12
and the presence of theca lutein
08:15
cysts larger than 6 cm
08:16
in diameter.
08:18
Invasive moles are therefore
08:20
more commonly associated
08:21
with complete molar pregnancies.
08:23

08:26
Invasive moles occur when there
08:28
is local uterine invasion
08:30
of a complete or incomplete
08:31
mole, and make up 75%
08:33
of gestational trophoblastic
08:35
neoplasia.
08:36
They are characterized
08:38
by penetration
08:39
of large swollen villi
08:40
and trophoblasts
08:41
into the myometrium
08:43
via direct extension
08:44
through tissue or venous
08:46
channels.
08:47
Most of the invasive moles
08:49
are nonmetastatic, with about
08:51
15% metastasizing to the lungs
08:53
or vagina.
08:54
Patients with invasive moles
08:56
are usually
08:57
asymptomatic at the time
08:58
of diagnosis.
08:59
However, they may sometimes
09:01
present with abnormal uterine
09:02
bleeding.
09:03

09:06
Another form
09:07
of malignant trophoblastic
09:08
disease is choriocarcinoma.
09:11
It is a highly malignant tumor,
09:13
where the trophoblastic tumors
09:14
travel via the blood stream
09:16
to achieve extra uterine spread
09:18
to distant organs.
09:19
50% of choriocarcinoma
09:21
is preceded by hydatitiform
09:23
moles,
09:24
and 25% from normal pregnancy,
09:27
and 25% from miscarriage,
09:29
abortion,
09:30
or ectopic pregnancies.
09:32
Histologically choriocarcinomas
09:35
are characterized by sheets
09:37
of trophoblastic cells formed
09:39
from both the inner cyto
09:41
and outer syncytial layers
09:44
of the trophoblastic cells
09:46
without apparent villi
09:47
formation.
09:48
Necrosis and severe hemorrhage
09:50
may be seen as the cancer cells
09:52
destroy the uterine wall
09:53
and vasculature.
09:55
Metastatic disease is also
09:56
common with potential metastasis
09:59
to organs such as the lungs,
10:01
vagina, pelvis, brain, liver,
10:04
intestines, and kidneys.
10:05

10:09
Patients with choriocarcinoma
10:11
commonly present with post
10:12
partum bleeding or irregular
10:14
uterine bleeding years
10:16
after pregnancy.
10:17
It is also known
10:18
as the great imitator,
10:20
because patients can present
10:21
with signs and symptoms
10:22
of many disease entities.
10:25
The diagnosis of choriocarcinoma
10:26
of the placenta
10:27
is similar to invasive moles.
10:30
And metastasis should be
10:31
assessed with a full blood
10:33
count, coagulation profiles,
10:35
renal panel, and liver function
10:37
tests.
10:38
Imaging studies are also
10:39
helpful in determining
10:41
the metastatic sites.
10:43
If vagina or lung metastasis are
10:45
present, a CT or MRI brain
10:48
should be obtained.
10:49
The treatment mortalities
10:50
for choriocarcinoma
10:53
of the placenta
10:53
is similar to that
10:54
of invasive moles,
10:56
with low risk patients treated
10:57
with single agent chemotherapy,
11:00
and high risk patients treated
11:01
with multi agent chemotherapy.
11:03

11:06
With that we have come
11:07
to the end of our presentation.
11:09
Below are the references used
11:10
for this topic.
11:11
And we hope this has been
11:13
informative.
11:13

11:16
Thank you.