GESTATIONAL

TROPHOBLASTIC DISEASE

DR RK SAXENA
 RKS 2010

GESTATIONAL
TROPHOBLASTIC DISEASE

The term gestational trophoblastic

disease refers to abnormal trophoblastic
proliferation.
Trophoblast development.
RKS 2010
 RKS 2010

GESTATIONAL TROPHOBLASTIC DISEASE (GTD)

GESTATIONAL TROPHOBLASTIC NEOPLASIA (GTN)


GTN = Persistent GTD
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Clinical classification of
Gestational trophoblastic disease.
Hydatidiform mole.
Complete
Incomplete / Partial

Gestational trophoblastic neoplasia

Invasive mole
Choriocarcinoma
Placental site tumour
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Complete Hydatidiform mole.

INCIDENCE-- 0.6 to 3.7 per 1000 pregnancies.
Japan (2 per 1,000 pregnancies) , North America (about 0.5 per 1,000 )

Attributed to nutritional and socioeconomic factors

Low dietary intake of carotene (Vit A Deficiency)
Maternal age older than 35 yrs
(2-fold increase for women > 35 yr & 10-fold for > 40 yr)
H/o Prior Molar Preg [10% risk]

KARYOTYPE
Diploid nuclear genome derived from paternal side.
[ 90% -46 XX (Androgenesis), 10% -46XY (Dispermic fertilization)]
Pathogenesis of complete 46,XX complete mole is
and partial moles
formed if a 23,X-bearing
sperm penetrates a 23,X-
containing egg whose genes
have become "inactive".

Paternal chromosomes then

duplicate to create a 46,XX
chromosomal complement
solely of paternal origin.

B. A partial mole may be

formed if two sperm, either
23,X or 23,Y, both fertilize a
23,X-containing egg. The
resulting fertilized egg is
triploid.
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Complete Hydatidiform mole.

Hydropic degeneration & swelling of the villous stroma. The
Chorionic villi transform into a mass of clear vesicles.
Absence of blood vessels in the swollen villi
Absence of fetus & amnion.
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Partial Hydatidiform Mole

Persistent embryonic or fetal elements

Placenta with a mosaic of normal appearing

villi alternating with areas of focal villous
swelling and trophoblastic hyperplasia

Karyotype :
Triploid (69 Chromosomes) The extra
haploid set of chromosomes usually is
derived from the father.
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Partial Hydatidiform mole.

Here is a partial mole in a case of triploidy.
Note the scattered grape-like masses with intervening
normal-appearing placental tissue. 

Fetal
anomalies
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Characteristics of partial & complete

hydatidiform mole
Feature Par)al
m
ole
Complete mole

1.Embryonic or fetal
tissue Present Absent

2.Hydatidiform
swelling of villi Focal Diuse

3.Trophoblastic
Focal Diuse
hyperplasia
Paternal & maternal
69 xxy, 69 xxx Paternal
4.Karyotype (FETUS: growth retarded & 46xx (90%),
Shows multiple congenital
malformations such as 46xy (10%)
syndactyly and hydrocephaly)
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Clinical Features
Increasingly being diagnosed early in pregnancy and treated
before they develop the classic clinical signs and symptoms due
to earlier ultrasound scan.

Vaginal Bleeding - >90 %. (if severe anaemia)

Hyper emesis-10%.

Increasing Uterine size

Pregnancy induced hypertension.

Thyroid dysfunction. (tachycardia, warm skin, tremor)

Spontaneous expulsion (Vesicles/ Grape like structures passed P/V)

Pain Abdomen from Theca Lutein Ovarian Cysts

Embolisation.- chest pain, dyspnea, tachypnea, tachycardia)

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Large bilateral theca lutein may undergo torsion,

infarction, and hemorrhage. With resolution of the
human chorionic gonadotropin(HCG) stimulation,
they return to normal-appearing ovaries.

Surfaces are smooth, often yellowish, and lined with lutein cells.
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Natural History
Complete Hydatidiform Mole
After evacuation -15% develop - locally Invasive Mole
- in 4% - Metastatic disease

Patients at high risk for developing post-molar tumor.

hCG level > 100,000 mIU/mL
Excessive uterine enlargement
Theca lutein cysts 6 cm in diameter
Older patients are at increased risk of developing postmolar GTT
(in 37% of women > than 40 yrs, in 56% of women > than 50 yrs)

Partial Hydatidiform Mole

2% to 4% develop Persistent tumor, usually nonmetastatic
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Diagnostic features
Clinical findings

USS Findings--- Snow storm appearance

High HCG Levels

Principles of
Management :
1) Evacuation of the mole
2) Regular follow-up
(to detect persistent
trophoblastic disease.)
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Treatment
Suction curettage
(regardless of uterine size, if desire to preserve fertility)
[Arrange Bl / Antibiotics / X-ray Chest/ done in OT]
Cervical dilation
Suction curettage [Intraoperative sonography may assist in
documenting complete evacuation.]
Oxytocin infusion [20 units of synthetic oxytocin in 1 L of
crystalloid ]

[Give Anti-D: trophoblast cells express RhD factor after 6 wks]

[may be withheld if the diagnosis of complete mole is certain ]
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Prophylactic Chemotherapy
Controversial
For:
Decrease in persistent tumour was detected in patients with
high risk complete mole who received prophylactic
chemotherapy (50% versus 14%)

Against:
Exposing all patients to potentially toxic treatment
Only about 20% are at risk of developing persistent tumour
Long-term prognosis for women with hydatidiform mole is
not improved may delay Diagnosis & increase risk score

Consider giving when:

Patient is likely to be lost to follow up
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Follow-up
hCG assessments
Baseline -hCG level obtained 48 hrs after evacuation
Weekly - till normal for 3 consecutive weeks,
Monthly - till normal for 6 consecutive months.
[average time to achieve the 1st normal hCG level after evacuation - 9 wks ]

Every Visit
H/o irregular bleeding P/V
O/E Metastasis (vagina / lungs)

Contraception
Barrier or OC Pills -Till follow-up is over
[No IUCD]
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Follow-up
hCG assessments
If after six monthly check-ups hCG remains normal -
Considered Cured, allow further pregnancy or continue
OC Pills [A]
INDICATIONS FOR CHEMOTHERAPY.
1.Static or rising hCG level at any time after uterine evacuation.
[Static: hCG level (10 percent) for four measurements during a
period of 3 weeks or longerdays 1, 7, 14, 21 [B]
Rising: Rise of serum -hCG > 10 percent during three weekly
consecutive measurements or longer, during a period of 2 weeks or
moredays 1, 7, 14.] [C]

2. Raised hCG level 6 mth after evacuation [D]

3.Metastasis in the Liver, Lung, Brain or GI.
4. Histological diagnosis of Choriocarcinoma.
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GESTATIONAL
TROPHOBLASTIC NEOPLASIA
 RKS 2010

GESTATIONAL
TROPHOBLASTIC NEOPLASIA
Characterized by their aggressive invasion into
the myometrium and propensity to metastasize
May follow an abortion, normal pregnancy, or
even an ectopic pregnancy
Includes:
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
 Important Features RKS 2010

Invasive mole :
Locally invasive (Myometrium/Peritonium), but lack the
tendency to widespread metastasis [100% after Molar
Preg]
Choriocarcinoma :
Extremely malignant, Metastases develop early & is
blood-borne to Lung / Vagina/GI/ Liver, Ovarian theca-
lutein cysts +
Placental site trophoblastic tumor :
Rare, from placental implantation site of normal preg,
abortion, ectopic, molar preg, hCG levels are relatively
low, resistant to chemotherapy & hysterectomy is
advised.
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Criteria for Diagnosis of Gestational

Trophoblastic Neoplasia or Postmolar Gestational
Trophoblastic Disease [FIGO 2002]

Plateau of serum -hCG level (10 percent) for four

measurements during a period of 3 weeks or longer
days 1, 7, 14, 21.

Rise of serum -hCG > 10 percent during three weekly

consecutive measurements or longer, during a period
of 2 weeks or moredays 1, 7, 14.

The serum -hCG level remains detectable for 6

months or more.

Histological criteria for choriocarcinoma.

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Clinical Features

Irregular bleeding associated with uterine

subinvolution

May cause intraperitoneal hemorrhage

Metastatic lesions to the vagina / vulva /

Lungs / Brain
 Role of Hysterectomy

1. Primary Treatment for
Placental site trophoblastic tumors,
Chemotherapy-resistant disease.

2. Severe uncontrollable vaginal or intra-abdominal
bleeding

3. Patients with disease apparently conned to the
uterus who do not desire future fertility should be
oered this option. (Adjuvant hysterectomy decreases
the total dose of chemotherapy needed to achieve clinical
remission in low-risk GTN).

RKS 2010
 RKS 2010

Protocol for Treatment of Gestational Trophoblastic Tumor

Initial Single-agent chemotherapy or hysterectomy with

adjunctive chemo

Adjuvant chemotherapy is administered for three

reasons:
To reduce the likelihood of disseminating viable
tumor cells at surgery
To maintain a cytotoxic level of chemotherapy in the
bloodstream and tissues in case viable tumor cells
are disseminated at surgery
To treat any occult metastases that may already be
present at the time of surgery

Combination Chemotherapy
 Methotrexate

Methotrexate is a folic acid antagonist that inhibits
DNA synthesis by causing an acute intracellular
deciency of folate coenzymes.
Mild stomatitis is the most common side eect, but
other serosal symptoms, especially pleurisy, develop in
up to one quarter of patients treated with low-dose
methotrexate.
Pericarditis, peritonitis, and pneumonitis are infrequent
Toxicity develops more frequently with the more
intense daily regimens compared with weekly
administration despite routine folinic acid "rescue" of
normal mucosal and serosal cells RKS 2010
 Dierential Diagnosis

Bleeding in early pregnancy
Threatened Miscarriage
Ectopic Pregnancy
Molar Pregnancy

Hyperemesis Gravidarum
Multiple Pregnancy
Molar Pregnancy

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