GESTATIONAL

TROPHOBLASTIC
DISEASE
GESTATIONAL TROPHOBLASTIC DISEASE
 GESTATIONAL TROPHOBLASTIC DISEASE
term used to encompass a group of tumors typified by abnormal trophoblast
proliferation.
 GESTATIONAL TROPHOBLASTIC DISEASE
term used to encompass a group of tumors typified by abnormal trophoblast
proliferation.

Trophoblast produce human chorionic gonadotropin (hCG) measurement of this

peptide hormone in serum is essential for GTD diagnosis, management, and
surveillance.
 GESTATIONAL TROPHOBLASTIC DISEASE
term used to encompass a group of tumors typified by abnormal trophoblast
proliferation.

Trophoblast produce human chorionic gonadotropin (hCG) measurement of this

peptide hormone in serum is essential for GTD diagnosis, management, and
surveillance.

Histologically:
• hydatidiform moles (has villi)
• non molar trophoblastic neoplasms (lacks villi)
• invasive mole
 GESTATIONAL TROPHOBLASTIC DISEASE
Invasive mole: malignant due to its marked penetration into and destruction of
the myovmetrium as well as its ability to metastasize
 GESTATIONAL TROPHOBLASTIC DISEASE
Invasive mole: malignant due to its marked penetration into and destruction of
the myovmetrium as well as its ability to metastasize

Nonmolartrophoblastic neoplasms: differentiated by the type of trophoblast

they contain)
• choriocarcinoma
• placental site trophoblastic tumor
• epithelioid trophoblastic tumor
 GESTATIONAL TROPHOBLASTIC DISEASE
Gestational trophoblastic neoplasia (GTN): malignant forms of gestational
trophoblastic disease
• invasive mole
• choriocarcinoma
• placental site trophoblastic tumor
• epithelioid trophoblastic
 GESTATIONAL TROPHOBLASTIC DISEASE
Gestational trophoblastic neoplasia (GTN): malignant forms of gestational
trophoblastic disease
• invasive mole
• choriocarcinoma
• placental site trophoblastic tumor
• epithelioid trophoblastic

Develop weeks or years following any type of pregnancy, but frequently follow a
hydatidiform mole.
 GESTATIONAL TROPHOBLASTIC DISEASE
Gestational trophoblastic neoplasia (GTN): malignant forms of gestational
trophoblastic disease
• invasive mole
• choriocarcinoma
• placental site trophoblastic tumor
• epithelioid trophoblastic

Develop weeks or years following any type of pregnancy, but frequently follow a
hydatidiform mole.

GTN is often identified and efectively treated as a group

 GESTATIONAL TROPHOBLASTIC DISEASE
Gestational trophoblastic neoplasia (GTN): malignant forms of gestational
trophoblastic disease
• invasive mole
• choriocarcinoma
• placental site trophoblastic tumor
• epithelioid trophoblastic

Develop weeks or years following any type of pregnancy, but frequently follow a
hydatidiform mole.

GTN is often identified and efectively treated as a group

Early-stage GTN: single-agent chemotherapy

Later stage disease :usually responds to combination chemotherapy
 HYDATIDIFORM MOLE
Classic histological findings include villous stromal edema and trophoblast proliferation.
 HYDATIDIFORM MOLE
Classic histological findings include villous stromal edema and trophoblast proliferation.
Elements are used to classify them as either complete or partial moles
 HYDATIDIFORM MOLE
Classic histological findings include villous stromal edema and trophoblast proliferation.
Elements are used to classify them as either complete or partial moles
• degree of histological changes
• karyotypic differences
• absence or presence of embryonic elements
 HYDATIDIFORM MOLE
Classic histological findings include villous stromal edema and trophoblast proliferation.
Elements are used to classify them as either complete or partial moles
• degree of histological changes
• karyotypic differences
• absence or presence of embryonic elements
Complete mole has abnormal chorionic villi that grossly appear as a mass of clear
 vesicles (vary in size and often hang in clusters from thin pedicles)
 HYDATIDIFORM MOLE
Classic histological findings include villous stromal edema and trophoblast proliferation.
Elements are used to classify them as either complete or partial moles
• degree of histological changes
• karyotypic differences
• absence or presence of embryonic elements
Complete mole has abnormal chorionic villi that grossly appear as a mass of clear
 vesicles (vary in size and often hang in clusters from thin pedicles)
• GTN more frequently follows complete hydatidiform mole
 HYDATIDIFORM MOLE
Classic histological findings include villous stromal edema and trophoblast proliferation.
Elements are used to classify them as either complete or partial moles
• degree of histological changes
• karyotypic differences
• absence or presence of embryonic elements
Complete mole has abnormal chorionic villi that grossly appear as a mass of clear
 vesicles (vary in size and often hang in clusters from thin pedicles)
• GTN more frequently follows complete hydatidiform mole

Partial molar pregnancy has focal and less advanced hydatidiform changes and
contains some fetal tissue
HYDATIDIFORM MOLE
 EPIDEMIOLOGY AND RISK FACTORS
1-2/1000
Increased prevalence in Asians, Hispanics, and American Indians

Age and a history of prior hydatidiform mole: are strongest risk factors
adolescents and women aged 36 to 40yr: t wofold risk
older than 40: almos tenfold risk
prior complete mole: risk of .0.9 percent
previous partial mole: risk of 0.3 percent

After t wo prior molar pregnancies, Berkowitz and associates (1998) reported

that 20 percent of women had a third mole
 PATHOGENESIS
Molar pregnancies arise from chromosomally abnormal fertilizations

Complete moles most often have a diploid chromosomal composition (usually 46,XX
and are paternal in origin)

Androgenesis both sets of chromosomes are paternal in origin

 PATHOGENESIS
Complete moles

Less commonly, the chromosomal pattern

may be 46,Y or 46,X and due to fertilization
by t wo sperm, that is, dispermicertilization
or dispermy

duplicates its
Chromosomes of the ovum is
own chromo
ovum are either fertilized by a
somes after
absent or inactivated. haploid sperm
meiosis
 PATHOGENESIS
Partial moles: have a triploid karyotype-69 XXX 69,XXY-or much less
, ,

commonly, 69XYY
Less frequently, a similar haploid egg
may be fertilized by an unreduced
diploid 46,XY sperm
These triploid zygotes result in some
embryonic development, however, it
ultimately is a lethal fetal condition

two sperm -23,X - or fertil ized egg is diandry

23,Y-bearing-both triploid with two
fertilize (dispermy) a chromosome
23,X-containing sets being Fetuses that reach advanced ages have
haploid egg whose donated by the severe growth restriction, multiple
genes have not been father. congenital anomalies, or both.
inactivated.
PATHOGENESIS
 TWIN PREGNANCY
One chromosomally normal fetus is paired with a complete diploid molar pregnancy

Important to distinguish it from a single partial molar pregnancy with its abnormal associated
fetus. Amniocentesis and fetal karyotyping is used to confirm the diagnosis

Sur vival of the normal fetus is variable and dependent on

complications that commonly develop from the molar component (most worrisome are
preeclampsia and hemorrhage)

Possible risk for developing subsequent GTN.

 CLINICAL FINDINGS
Usually 1 to 2 months of amenorrhea before discovery
As gestation advances, symptoms tend to be more pro nounced with complete compared with partial moles

Untreated molar pregnancies: will almost always cause uterine bleeding (from spotting to
profuse hemorrhage)
•
Moderate iron-deficiency anemia: In considerable concealed uterine hemorrhage, develops in
more advanced moles
Significant nausea and vomiin
•
PE:
Rapid uterine growth. Enlarged uterus has a soft consistency, but typically no fetal
heart motion is detected wih complee moles
•
Ovaries: fuller and cysic from muliple theca-lutein cysts in complete mole
(regress following pregnancy evacuation)
 thyrotropin-like effects of hCG->serum free thyroxine (fT4) levels to be
elevated and thyroid stimulating hormone (TSH) levels to be decreased
•
serum free T4 levels rapidly normalize after uterine evacuation
•
Severe preeclampsia and eclampsia are relatively common with large molar
pregnancies
•
Severe preeclampsia frequently mandates preterm delivery
 DIAGNOSIS
•
Most women initially have amenorrhea that is followed by irregular
bleeding that almost always prompts pregnancy testing and sonography.
•
Some women will present with spontaneous passage of molar tissue.
 DIAGNOSIS
 – 
SERUM
Β
-HCG MEASUREMENTS
•
Complete molar pregnancy -> serum ß-hCGlevels are commonly elevated
above those expected for gestational age.
•
more advanced moles, values in the millions are not unusual.
•
high values can lead to erroneous false-negative urine pregnancy test
results because of oversaturation of the test assay by excessive ß-hCG
hormone
•
partial mole ->ß-hCGlevels may also be significantly elevated, but more
commonly concentrations fall into ranges expected for gestational age.
 DIAGNOSIS -SONOGRAPHY 
•
sonographic imaging is the mainstay of trophoblastic disease diagnosis
•
a complete mole appears as an echogenic uterine mass with numerous anechoic cystic spaces
but
 without a fetus or amnionic
sac. (often described as “snowstorm”)
•
 A partial mole has features that include a thickened, multicysticplacenta along with a fetus
or at
least fetal tissue
•
In early pregnancy, however, these sonographic characteristics are seen in fewer than half of
hydatidiform moles
•
most common misdiagnosis is incomplete or missed abortion
•
Occasionally, molar pregnancy may be confused for a multifetal pregnancy or a uterine
leiomyoma
 •
In pregnancies before 10 weeks, classic molar changes may not be apparent because villi may
not be enlarged and
molar stroma may not yet be edematous and avascular
•
One takes advantage of the differing ploidy to distinguish partial (triploid) moles from diploid
entities. Complete
moles and nonmolarpregnancies with hydropic placental degeneration are both diploid
•
 Another technique -> histological immunostaining to identify the p57KIP2 nuclear protein
(this gene is paternally
imprinted -> only maternally donated genes are expressed)
•
complete moles contain only paternal genetic material, they cannot express this gene; do not
produce p57 KIP2; and
thus, do not pick up this immunostain
•
this nuclear protein is strongly expressed in partial moles and in nonmolarpregnancies with
hydropic change
•
 MANAGEMENT
•
Molar evacuation by suction curettage is usually the preferred treatment
•
Dokterumum-> rujukkespesialisobsgyn
 Biochemical surveillance is by serial measurements of serum ß-hCG. initial ß-hCGlevel is
obtained within 48 hours after evacuation. This
serves as the baseline
•
he baseline sithen compared with ß-hCGquantification done thereafter every 1 to 2 weeks
until levels progressively decline to become
undetectable.
•
dian time for such resolution is 7 weeks for partial moles and 9 weeks for complete moles
•
Once ß-hCGis undetectable, this is confirmed with monthly determinations for another 6
months. After this, surveillance is discontinued
and pregnancy allowed (has a high non-compliance rate)
•
uncated approach -> , it was shown that no woman with a partial or complete mole whose
serum ß-hCGlevel became undetectable
subsequently developed neoplasia
•
During the time during which ß-hCGlevels are monitored, either increasing or persistently
plateaued levels mandate evaluation for
 GESTATIONAL TROPHOBLASTIC NEOPLASIA 
•
Includes invasive mole, choriocarcinoma, placentalsite trophoblastic tumor,
and epithelioid trophoblastic tumor.
•
almost always develop with or follow some form of recognized pregnancy
•
Half follow hydatidiform mole, a fourth follow miscarriage or tubal
pregnancy, and another fourth develop after a preterm or term pregnancy
 CLINICAL FINDINGS AND DIAGNOSIS
•
characterized clinically by their aggressive invasion into the myometrium
and propensity to metastasize
•
most common finding with gestational trophoblastic neoplasms is irregular
bleeding associated with uterine subinvolution
G AND SCORING SYSTEM
 TREATMENT
•
Chemotherapy is usually the primary treatment, and repeat evacuation is
not recommended by most because of risks for uterine perforation,
bleeding, infection, or intrauterine adhesion formation.
•
Dokterumum-> rujukkespesialisobsgy
 SUBSEQUENT PREGNANCIES
•
Women with prior gestational trophoblastic disease or success fully treated
neoplasia usually do not have impaired fertility, and their pregnancy
outcomes are usually normal
•
primary concern in these women is their 2-percent risk for developing
trophoblastic disease in a subsequent pregnancy
•
Sonographic evaluation is recommended in early pregnancy
•
 At delivery, the placenta or products of conception are sent for pathological
evaluation, and a serum ß-hCGlevel is measured 6 weeks post partum.