Discussion

Gestational
Trophoblastic Disease
group of tumors characterized by
abnormal trophoblast proliferation
human chorionic gonadotropin (hCG)

Classification of Gestational
Trophoblastic Disease
Hydatidiform mole
Complete
Partial

Gestational trophoblastic neoplasiaa

Invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor

Hydatidiform mole
histological findings
villous stromal edema
Trophoblast proliferation

Gross
vesicles of variable size

Risk factors

Hydatidiform mole
Complete Hydatidiform Mole
chorionic villi appear as a
mass of clear vesicles

- Histologically:

hydropic degeneration and

villous edema
absence of villous blood vessels;
varying degrees of proliferation
of the trophoblastic epithelium
absence of embryonic elements
such as a fetus and amnion.

Ploidy
diploid and of paternal
origin
(85%) 46,XX with both sets
of chromosomes paternal in
origin
androgenesis, the ovum
is fertilized by a haploid
sperm, which duplicates its
own chromosomes after
meiosis
chromosomes of the ovum
are either absent or
inactivated
complete moles, the
chromosomal pattern may
be 46,XY due to dispermic
fertilization

GESTATIONAL TROPHOBLASTIC
NEOPLASIA

invasive mole
Choriocarcinoma
placental site trophoblastic tumor
epithelioid trophoblastic tumor

GESTATIONAL TROPHOBLASTIC
NEOPLASIA
almost always develop with or follow
some form of recognized pregnancy
hydatidiform mole (50%)
miscarriage or tubal pregnancy (25%)
preterm or term pregnancy (25%)

Criteria for Diagnosis of Gestational

Trophoblastic Neoplasia

IRREGULAR BLEEDING associated

with uterine subinvolution - most
common finding
continuous or intermittent, with sudden and
sometimes massive hemorrhage
intraperitoneal hemorrhage - myometrial
perforation

Diagnosis
persistent bleeding after any type of
pregnancy
Measurement of serum -hCG levels
diagnostic curettage

bluish vascular masses

*lower genital tract metastases

Criteria for Diagnosis of Gestational

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

Diagnosis
search for local disease and
metastases
tests of liver and renal function
transvaginal sonography
chest CT scan or radiograph
brain and abdominopelvic CT scan
MR imaging

Staging
FIGO Staging and Diagnostic Scoring
System for
Gestational Trophoblastic Neoplasia
Stage
I

Disease confined to the uterus

Stage
II

GTN extends outside of the uterus, but is limited to the

genital structures (adnexa, vagina, broad ligament)

Stage
III

GTN extends to the lungs, with or without known

genital tract involvement

Stage
IV

All other metastatic sites

Modified WHO Prognostic Scoring

System
Scores

Age

<40

40

Antecedent
pregnancy

mole

abortion

term

<4

46

712

>12

<103

103104

104105

>105

Largest tumor size

(including uterus)

<3

34 cm

5 cm

Site of metastases

lung

spleen,
kidney

GI

liver, brain

Number of
metastases

14

58

>8

Previous failed
chemotherapy

single drug

2 drugs

Interval months
from index
pregnancy
Pretreatment serum
hCG (iu/1)

Histological
Classification

Invasive Mole

chorioadenoma
destruens
AKA

most common trophoblastic neoplasms

extensive tissue invasion by trophoblast and
whole villi
locally aggressive
less prone to metastasize

Gestational
Choriocarcinoma
Composition:
cells reminiscent of early cytotrophoblast and
syncytiotrophoblast
contains no villi

hemorrhage & necrosis

invades myometrium and blood vessels

Metastases
Early
Hematogenous route
LUNGS & VAGINA - most common sites
vulva, kidneys, liver, ovaries, brain, and bowel

Placental Site Trophoblastic

Tumor (PSST)
uncommon tumor
Locally invasive tumors

arises from implantation siteintermediate trophoblast

-hCG levels - modestly elevated
usually resistant to chemotherapy
HYSTERECTOMY

Epithelioid Trophoblastic
Tumor
rare
develops from chorionic-type
intermediate trophoblast
grows in a nodular fashion

relatively resistant to chemotherapy

HYSTERECTOMY

Treatment
Chemotherapy - primary treatment
repeat evacuation is not recommended
risks for uterine perforation, bleeding,
infection, or intrauterine adhesion formation

effective contraception
to avoid any teratogenic effects to the fetus
Avoid confusion from rising -hCG levels
once serum -hCG levels are undetectable,
serosurveillance is continued for 1 year

Treatment
Single-agent chemotherapy
nonmetastatic or low-risk metastatic
neoplasia
Drugs
Methotrexate
inhibits the synthesis ofDNA,RNA andproteins
by competitively inhibitingdihydrofolate
reductase(DHFR), anenzymethat participates
in thetetrahydrofolate synthesis

Actinomycin D
inhibittranscription by bindingDNAat the
transcription initiation complex and preventing
elongation ofRNAchain byRNA polymerase

Treatment
Combination chemotherapy
for high-risk disease

EMA-CO
Etoposide
causes errors inDNA synthesisand promotes apoptosisof the
cancer cell

Methotrexate
actinomycin D
Cyclophosphamide
Causes interstrand and intrastrand crosslinkages leading to
cellapoptosis

oncovin (vincristine)
inhibiting assembly ofmicrotubulestructures and
arrestingmitosisinmetaphase

SUBSEQUENT
PREGNANCY
prior GTD or successfully treated
neoplasia
do not have impaired fertility
pregnancy outcomes are usually normal

Sonographic evaluation
In early pregnancy

At delivery
the placenta or products of conception pathological evaluation
serum -hCG level is measured 6 weeks
postpartum