Gestational

trophoblastic disease (GTD) encompasses a large

group of neoplastic diseases arising from
trophoblastic tissue. The most common diseases are
the following:
1 Hydatidiform mole-Complete and Incomplete
mole
2 Invasive mole (Chorioadenoma destruens)
3 Choriocarcinoma
4 Epithelioid trophoblastic tumor
5 Placental site trophoblastic tumor
In addition, there are some proliferations of
trophoblastic tissue which are benign but may
histologically mimic disease.
Miscellaneous trophoblastic lesions:
Exaggerated placental site
Placental site nodule or plaque
Patients with molar pregancy, the most
common form of GTD, may present with
vaginal bleeding and excessive uterine
enlargement for gestational age, usually
between 11-25 weeks of pregnancy. Pregnancy
induced hypertension may occur in 1/4 of
patients. Other presenting signs include
hyperthyroidism and hyperemesis gravidarum.
Characteristically, the serum HCG is elevated.

An ultrasound of the uterus reveals a

characteristic snowstorm pattern, representing
the hydropic chorionic villi which characterizes
the disease. After evacuation of the uterus,
careful clinical followup with serial
measurements of the serum HCG is necessary
to ensure there is no recurrence and all of the
disease has been removed.
The clinical presentations of the other forms of
GTD are covered in the following discussion
and tables.

OUTLINE
Epidemiology
Disease
Associations
Pathogenesis
Gross Appearance
and Clinical
Variants
Histopathological
Features and
Variants
Laboratory/Radiol
ogic/Other
Diagnostic Testing
Differential
Diagnosis

Prognosis and
Treatment
Commonly Used
Terms
Internet Links

EPIDEMIOLO
CHARACTERIZATION
GY
INCIDENCE
1/1000 pregnancies
Complete Most frequent form of
mole molar pregnancy and
GTD
Incomplete 25-74% of all molar
mole pregnancies
1/20,000 pregnancies
The more abnormal the
pregnancy, the more
likely this will occur
Choriocarcin
oma 1/160,000 normal
getstations
1/15386 abortions
1/5333 ectopic
pregnancies
1/40 molar pregnancies
Epithelioid
trophoblastic Very rare
tumor
Placental Rarest form of GTD

site
trophoblastic
tumor
Usually disorders of
reproductive age

AGE RANGEIncreased risk of moles

MEDIAN
at the extremes of
reproductive age
Complete 11-25 weeks of
mole pregnancy
Incomplete 9-34th weeks of
mole pregnancy
May occur
Invasive simultaneously with
mole intracavitary molar
pregnancy
GEOGRAPHYHydatidiform Rate per 1000
mole
Indonesia9.9 pregnancies
Taiwan8.3 deliveries
Philippines5.0 deliveries
Mexico4.6 pregnancies
Nigeria2.6 deliveries
Japan1.9 pregnancies
Australia1.4 pregnancies
USA1.1 pregnancies
Israel0.8 live births
Sweeden0.6 pregnancies

Paraguay0.2 pregnancies
EPIDEMIOLO
GIC
ASSOCIATION
S
Low
socioeconom
ic conditions
Possible dietary
Diet
deficiency of carotene
Blood groups
Choriocarcinoma more
frequent
Stronger for women of
A type A and husbands of
type O and conversely
for group O women and
type A husbands
B or ABWorse prognosis

DISEASE
ASSOCIATIO
NS
History of
prior
spontaneou
s abortions
Term

CHARACTERIZATION
More common in
hydatidiform mole and
choriocarcinoma
Protective effect

pregnancy
and live
births

Increases with an
increased number of live
births

PATHOGENE
CHARACTERIZATION
SIS
46XX with both X
chromosomes androgenic
or paternal origin-Results
from duplication of the
haploid sperm in an
empty ovum
COMPLETE
3-13% have normal 46XY
MOLE
but both XY
chromosomes are
paternal-Results from
dispermy, fertilization of
an empty ovum by two
sperm

Hydatidiform moles are

pregnancies
characterized by
abnormal development of
both embryonic and
extraembryonic tissues
and are associated with
the misexpression of
imprinted genes. The
vast majority of complete

hydatidiform moles are

diploid and androgenetic,
whereas partial
hydatidiform moles are
triploid, with an extra set
of chromosomes of
paternal origin.

Triploidy (69
chromosomes) with
maternal chromosome
complement
Most are 69XXY, 69XXX,
and rarely 69XYY
Results from fertilization
INCOMPLETE of an egg with a haploid
MOLE
set of chromosomes by
either two sperms, each
with a haploid set of
chromosomes or by a
single sperm with a
diploid genome of 46 XY
(diandric-paternally
derived triploidy)
PLACENTAL
SITE
TROPHOBLA
STIC TUMOR

Placental site
trophoblastic tumour
(PSTT) is a neoplastic
proliferation of the
implantation
intermediate trophoblast.
Although
clinicopathological
studies are not
uncommon in case
reports or small series,
molecular and genetic
studies are quite limited.

LABORATOR
Y/
RADIOLOGIC CHARACTERIZATION
/
OTHER
FISH
Determinati
on of DNA
ploidy by
In the past 20 years, the
fluorescenc diagnosis of hydatidiform
e in situ
moles has become more
hybridizatio difficult because of the

n (FISH) in
hydatidifor
m moles:
Evaluation
of FISH on
isolated
nuclei.

widespread use of early

uterine evacuation.
Differentiating hydropic
degeneration, partial, and
complete moles is
important because of
their different prognosis.
However, clinical
diagnosis is less obvious,
and the pathologist has to
separate the different
entities on the basis of
very subtle morphologic
criteria.
In difficult cases, ploidy
may be determined by
various methods,
including fluorescence in
situ hybridization (FISH)
on routine histological
sections from paraffinembedded specimens.
However, FISH analysis is
often difficult because of
the presence of numerous
truncated nuclei. In this
context, we have tested
the advantages of FISH on
isolated nuclei, a wellknown variant of the
technique that might be
more sensitive.

GROSS
APPEARANC
E/
CHARACTERIZATION
CLINICAL
VARIANTS
Complete
Hydropic chorionic villi
mole
Large for dates uterus
Often small for dates
uterus, resembling a
missed abortion
Volume of tissue usually
<200 ml

Incomplete
mole
Villi are grossly enlarged
but smaller than seen in a
complete mole
Fragments of normal
placenta and a fetus may
be found
Requires demonstration
of molar villi invading into
Invasive
the myometrium or
mole
deported to extrauterine
sites
Choriocarcin Usually presents with

oma

abnormal uterine
bleeding but symptoms of
metastases may be the
first symptom
Dark red hemorrhagic
mass with a shaggy
irregular surface
Similar presentation as
choriocarcinoma and
invades the myometrium
in an expansile rather
than permeative growth

Epithelioid
trophoblasti
c tumor
Not associated with
central necrosis or
hemorrhage

Elevated serum HCG

Variable in size but may
present with diffuse
nodular enlargement of
the myometriumPlacental
occasionally polypoid
site
projecting into the uterine
trophoblasti cavity
c tumor
Invasive tumor frequently
extends into the uterine
serosa and adnexal
structures
SITES
BROAD
LIGAMENT

Epithelioid
Trophoblasti
c n.
TESTIS
Placental site
trophoblastic tumor
(PSTT) is a well-defined
Placental
entity in the female
site
trophoblasti genital tract. In the male
c tumor in a genital tract, a single
case of PSTT in the testis
late
recurrence of a young boy has been
reported. Despite its very
of a
nonsemino rare occurrence, PSTT of
the testis has been
matous
incorporated in the latest
germ cell
tumor of the WHO classification of
tumors of the male
testis.
genital tract.

HISTOLOGIC
CHARACTERIZATION
AL TYPES
Complete
Enlarged edematous
mole
chorionic villi with central
cisterns
Usually avascular villi
Haphazard

circumferential
trophoblastic proliferation
around the villus
Molar change is focal with
a mixture of edematous
villi and small relatively
normal sized villi
Central cisterns are less
conspicuous
Incomplete Smaller villi with stromal
mole
fibrosis

Invasive
mole

Invaginations of
trophoblast into the
villous stroma giving a
scalloped appearance,
appearing as inclusions
within the stroma
Molar villi with
trophoblast within the
myometrium or at an
extrauterine stie

Villi are usually 4-5 mm in

diameter but hydropic
changes are not as
marked as in complete
moles
Choriocarcin Masses and sheets of
oma
trophoblastic cells without
villi invading the
surrounding tissue and

permeating vascular
spaces
Central hemorrhage and
necrosis with a rim of
viable tumor
Admixture of
intermediate, cyto- and
syncytio-trophoblastic
cells with considerable
nuclear atypia
Epithelioid
trophoblasti
c tumor
Epithelioid
Trophoblasti
c.A.
Abundant extracellular
eosinophilic fibrinoid is
present within the tumor
Placental
Blood vessel walls are
site
extensively replaced by
trophoblasti
trophoblastic cells and
c tumor
fibrinoid material
Extensive necrosis may
be present

PROGNOSIS
AND
CHARACTERIZATION
TREATMENT
Prognostic
Factors
In more than 60% of
patients who required
chemotherapy, there
were large for dates uteri
and ovarian enlargment
secondary to theca-lutein
cysts
Complete
mole
16% develop into invasive
moles and 2.5% develop
into choriocarcinoma
0.6-1.5% of patients are
at risk of having recurrent
molar pregnancies
5% will have persistent or
Incomplete metastatic GTD requiring
chemotherapy
mole

Invasive
mole

Choriocarcinoma is rare
Choriocarcinoma occurs
6-10x more frequently
than following a
hydatidiform mole

Metastases may occur in

20-40% of cases
Choriocarcin Metastases especially to
oma
brain and liver can occur

in 20-60% of patients
With chemotherapy,
overall survival rate is
about 90%
Death usually occurs from
hemorrhage and
pulmonary insufficiency
Epithelioid
May have course similar
trophoblasti
to choriocarcinoma
c tumor
May cause perforation of
the uterus
About15-20% die of
metastastic disease and
may not be sensitive to
chemotherapy-aggressive
cases may have extensive
necrosis with high mitotic
rates
Serum HCG>100,000
Risk factors mlU/ml
affecting
Duration of disease>6
staging
months from termination
of antecedent pregnancy
STAGE
CHARACTERIZATION
Placental
site
trophoblasti
c tumor

Disease confined to the

uterus
Confined to uterus with
IA
no risk factors

Confined to uterus with 1

risk factor
Confined to uterus with 2
IC
risk factors
Tumor extending outside
uterus but limited to
genital structures
(adnexa, vagina, broad
ligament)
IIANo risk factors
IIB1 risk factor
IIC2 risk factors
Tumor extending to lungs
with or without known
genital tract involvement
IIIANo risk factors
IIIB1 risk factor
IIIC2 risk factors
All other metastatic sites
IVANo risk factors
IVB1 risk factor
IVC2 risk factors
In diseases treated with
surgery and combination
chemotherapy:
IB

II

III

IV

5 Year
Survival

Metastasis

Disease confined to
uterus-100%
Metastatic disease-83%
Lungs, brain, liver

Treatment

Combination surgery with

chemotherapy
MAC-methotrexate,
actinomycin D, and
chlorambucil