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GESTATIONAL TROPHOBLASTIC DISEASE

Gestational Trophoblastic
Disease

-is a heterogenous spectrum of diseases of

abnormal trophoblas5c prolifera5on ranging
from benign to malignant, with varying
predilec5ons toward local invasion and distant
metastasis

-Trophoblast produce human chorionic

gonadotropin (hCG)

Histologically Divided into:

1. Hyda5diform mole
2. Non-molar lesions
Hydatidiform Mole
Abnormal conceptions with excessive placental, and little
or no fetal, development.

Classical histological findings:

1. Villous stromal edema
2. Trophoblast proliferation

Two types of Molar Pregnancy:

1. Complete mole
2. Partial Mole
 COMPLETE MOLE

Gross findings
-include massively enlarged,
edematous villi that give the
classic grape-like appearance to
the placenta and lack embryonic
5ssue.

Histopathologic features
-Include hydrophobic swelling in
the majority of villi,
accompanied by a variable
degree of trophoblas5c
prolifera5on.
• Most oJen have diploid chromosomal
composi5on (46,XX)

• Result from androgenesis

• Ovum is fer5lized by a haploid sperm

w/c then duplicates its own
chromosomes aJer meiosis.

• The chromosomes of the ovum are

either absent or inac5vated

• Less commonly, the chromosomal

paSern may be 46,XY / 46,XX

• Due to fer5liza5on by two sperm,

dispermic fer/liza/on/ dispermy

PATHOGENESIS of Complete Molar Pregnancy

 PARTIAL MOLE

Gross findings
-Thickened, mul5cys5c placenta
along with a fetus or at least fetal 5ssue.
-Subtle abnormali5es w/ generally

smaller volume of hydropic villi and

possible presence of fetus/fetal 5ssue.

Histopathologic features
- Presence of fetal or embryonic
5ssues
- Less diffuse, focal hydropic swelling
of villi
- Focal trophoblas5c hyperplasia
- Less pronounced trophoblas5c atypia
at the molar implanta5on site
-Presence of trophoblas5c scalloping
and stromal
• Have a triploid karyotype (69,XXX /
69,XXY) — most common

• Less commonly 69,XYY

• Composed of 2 paternal haploid sets

of chromosome contributed by
dispermy and 1 maternal haploid set

PATHOGENESIS of Partial Molar Pregnancy

CLINICAL FINDINGS

COMPLETE MOLE
-Typically presents in the 1st trimester as vaginal bleeding with or without
passage of molar vesicles
-Large-for-date uterus
-Absence of fetal movements
-Gesta5onal hypertension before 20 wks gesta5on
-Presence of theca lutein cysts
-Hyperemesis
-Hyperthyroidism
-Respiratory distress
PARTIAL MOLE
-usually presents incidentally following histopathologic examina5on of the
products of concep5on from uterine evacua5on of a suspected missed or
therapeu5c abor5on

-medical complica5ons such as gesta5onal hypertension, hyperthyroidism,

theca lutein cyst, respiratory distress are rare
COMPLETE MOLE
- Diagnosed at a mean of 10 weeks
> Gemer and colleagues (2000) reported
that:
a. 41 percent were asymptoma>c
b. 58 percent had vaginal bleeding
c. 2 percent had anemia/hyperemesis

- Untreated molar pregnancies will almost

always cause uterine bleeding that varies
from spoFng to profuse hemorrhage

- Bleeding may presage spontaneous molar

abor5on

- More oJen it follows an intermiSent course

for weeks to months
 DIAGNOSIS
Serum β-HCG Measurements

>Complete mole: serum β-hCG levels are commonly elevated above

those expected for gesta5onal age

>Par5al mole: β-hCG levels may also be significantly elevated, but

more commonly concentra5ons fall into ranges expected for
gesta5onal age
Sonography
-mainstay of trophoblas5c disease diagnosis
>Complete mole: appears as an echogenic uterine mass with numerous
anechoic cys5c spaces but without a fetus or amnionic sac
-appearance is oJen described as “snowstorm”

>Par5al mole: thickened, mul5cys5c placenta along with a fetus or at least

fetal 5ssue
PATHOLOGICAL DIAGNOSIS
- Although ultrasound and B hCG 5ters can be helpful in the
diagnosis of molar pregnancies, histological confirma/on is mandatory
for the diagnosis of hyda5diform mole.

a. COMPLETE MOLE
Hisopathologic characteris/cs:
- Lack fetal/ embryonic 5ssues
- Hydropic (edematous) villi
- Diffuse trophoblas5c hyperplasia
- Marked atypia of trophoblasts at the implanta5on site
- Absence of trophoblas5c stromal inclusions
b. PARTIAL MOLE

Histopathologic features:
- Presence of fetal or embryonic 5ssues
- Less diffuse, focal hydropic swelling of villi
- Focal trophoblas5c hyperplasia
- Less pronounced trophoblas5c atypia at the molar
implanta5on site
- Presence of trophoblas5c scalloping and stromal
Histological Immunostaining
- to iden5fy p57KIP2 nuclear protein
- the gene that expresses p57KIP2 is paternally imprinted, only
maternally donated genes are expressed

*Complete mole: diploid/p57KIP2-nega5ve

*Par5al mole: triploid/p57KIP2-posi5ve

*Spontaneous abor5on with hydropic placental degenera5on (diploid/

p57KIP2-positive)
 MANAGEMENT
The Following Medical Complica5ons should be promptly recognized and
treated:

• Anemia
• Preeclampsia
• Hyperthyroidism
• Electrolyte imbalance
• Hyperemesis gravidarum
• Pulmonary Insufficiency
• Disseminated Intravascular Coagula5on
 LABORATORY EXAMINATIONS

•CBC with differen5al and platelet counts

•Liver func5on test (ALT,AST)
•Renal func5on tests (BUN, Crea5nine)
•Thyroid func5on tests (FT3,FT4,FTSH)
•Urinalysis
•Blood typing
•ECG
•Chest x-ray PA and lateral
 TERMINATION of MOLAR PREGNANCY

Suc5on cureSage- Preferred method to evacuate molar products regardless of

uterine size.

Preopera>ve cervical dilata>on: mechanically dilate to allow inser5on of a

10-14mm suc5on cureSe

Intraopera>ve bleeding: greater in molar pregnancy

-as evacua5on begun, OXYTOCIN is infused to limit bleeding
GUIDELINES for SUCTION CURETTAGE

•AJer induc5on, place in semi-fowler’s dorsolithotomy posi5on

•Mechanical cervical dilata5on with 12mm cannula
•Oxytocin infusion
•Surgeon’s other hand posi5oned on uterine fundus to assess size and tone
•Do sharp cureSage aJer suc5on cureSage
•RH (-) pa5ents should receive Rh immune globulin at the 5me of evacua5on
•Rou5ne repeat cureSage aJer the diagnosis of a molar pregnancy is not
warranted
•Pulmonary emboliza5on and dissemina5on of trophoblas5c cells
•Avoid using the hysterometer for measurement of pre and post- uterine
depth→ may lead to uterine fracture.
Hysterectomy

-with ovarian preserva5on may be preferable for women who have

completed childbearing

-women age >40 y.o: reduces risk of developing GTN

 POSTEVACUATION SURVEILLANCE

Biochemical surveillance is by serial measurements of serum β-hCG to detect

persistent or renewed trophoblas5c prolifera5on

-Ini5al: w/in 48 hrs aJer evacua5on (baseline)

-compared to β-hCG quan5fica5on done thereaJer every 1 to 2 weeks un5l levels

progressively decline to become undetectable
>mean resolu5on:
a. Complete mole- 9 weeks
b. Par5al mole- 7 weeks

-Once β-hCG is undetectable: this is confirmed with monthly determina5ons for

another 6 months
 RISKS for DEVELOPING GTN AFTER
EVACUATION

•Complete mole: 15-20%

•Par5al mole: 1-5%
•Advance maternal age ≥ 35
•Gravidity of ≥ 40yo
•Uterine size larger than gesta5on by ≥ 6 weeks
•Serum BhCG 5ter ≥ 100,000 mIU/ml
•Theca lutein cyst ≥ 6cm
•Presence of any medical complica5ons
•Repeat molar pregnancy
 GESTATIONAL TROPHOBLASTIC NEOPLASIA

a. Invasive mole
b. Choriocarcionoma
c. Placental site trophoblas5c tumor
d. Epithelioid trophoblas5c tumor
CLINICAL FINDINGS

-Aggressive invasion into myometrium and propensity to metastasize

-Irregular bleeding: con5nuous/ intermiSent

TABLE 20-3. Criteria for Diagnosis of Gesta>onal Trophoblas>c Neoplasia

1. Plateau of serum β-hCG level (± 10 percent) for four measurements during a
period of 3 weeks or longer—days 1, 7, 14, 21
2. Rise of serum β-hCG level > 10 percent during three weekly consecu5ve
measurements or longer, during a period of 2 weeks or more—days 1, 7, 14
3. Serum β-hCG level remains detectable for 6 months or more
4. Histological criteria for choriocarcinoma
 INVASIVE MOLE

-These are the most common trophoblas5c neoplasms that follow

hyda5diform moles, and almost all invasive moles arise from par5al or
complete moles
-characterized by extensive 5ssue invasion by trophoblast and whole
villi
-There is penetra5on deep into the myometrium some5mes with
involvement of the peritoneum, adjacent parametrium, or vaginal vault
-locally aggressive; invasive moles are less prone to metastasize such as
with choriocarcinoma
 GESTATIONAL CHORIOCARCINOMA

-This is the most common type of trophoblas5c neoplasm to follow a term

pregnancy or a miscarriage, and only a third of cases follow a molar gesta5on

- Composed of cells reminiscent of early cytotrophoblast and syncy5otrophoblast;

it contains no villi

-rapidly growing tumor invades both myometrium and blood vessels to create
hemorrhage and necrosis

-Myometrial tumor may spread outward and become visible on the uterine
surface as dark, irregular nodules

-metastases oJen develop early & generally blood-borne: lungs, vagina, vulva,
kidney, liver, ovaries, brain, bowel
 PLACENTAL SITE TROPHOBLASTIC TUMOR

-This uncommon tumor arises from implanta5on site-intermediate trophoblast.

-These tumors have associated serum β-hCG levels that may be only modestly elevated,
but they produce variant forms of hCG, and iden5fica5on of a high propor5on of free β-
hCG (> 30 percent) is considered diagnos5c

-Treatment of placental site trophoblas5c tumor by hysterectomy is preferred because

these locally invasive tumors are usually resistant to chemotherapy
 EPITHELIOID TROPHOBLASTIC TUMOR

-This rare tumor develops from chorionic-type intermediate

trophoblast

-Grossly the tumor grows in a nodular fashion

-Primary treatment is hysterectomy because this tumor is rela5vely

resistant to chemotherapy
 TREATMENT
Chemotherapy is usually the primary treatment, and repeat evacua5on is
not recommended by most because of risks for uterine perfora5on, bleeding,
infec5on, or intrauterine adhesion forma5on
a. Single-Agent Chemotherapy: for non-metasta5c or low-risk metasta5c neoplasia
b. Combina5on chemotherapy: for high-risk disease