GESTATIONAL TROPHOBLASTIC DISEASE

Gestational trophoblastic disease is a group of rare pregnancy related

tumours. Gestational trophoblastic disease is as a result of abnormal
trophoblastic cells inside the uterus after conception. Gestational
trophoblastic disease is mainly divided into pre malignant conditions
such as pre molar pregnancy and molar pregnancy and malignant
conditions of gestational disease are invasive mole, choriocarcinoma,
placental trophoblastic site tumour and epithelioid trophoblastic
tumour.

EPIDEMIOLOGY

The pre malignant gestational trophoblastic conditions such as molar

pregnancy are very common while the malignant gestational
trophoblastic conditions such as choriocarcinoma are very rare. Broad
variations in the distribution of gestational trophoblastic diseases (GTD)
exist worldwide, with higher frequencies in some parts of Asia, the
Middle East and Africa. Women below 20 years of age and those above
40 years of age are the mostly affected by gestational trophoblastic
diseases.

CLINICAL FEATURES

 Abnormal vaginal bleeding during or after pregnancy

 A uterus that is larger than expected at a given point in the

pregnancy

 Severe nausea or vomiting during pregnancy

 High blood pressure at an early point in the pregnancy, which may

include headaches and/or swelling of the feet and hands
 A pregnancy where the baby has not moved at the expected time

 Pain or pressure in the pelvic area

 Abdominal swelling

 Anemia, which is a low red blood cell count that can cause fatigue,
dizziness, shortness of breath, or an irregular heartbeat

 Anxiety or irritability, including feeling shaky or severe sweating

 Sleep problems

 Unexplained weight loss

ETIOLOGY

 Molar pregnancies (Hydatidiform mole GTD) arise when one or

more sperm cells fertilize an egg without any nucleus or DNA.
Fetal tissue may not be produced during two-sperm fertilization.
Single-sperm fertilization may produce fetal tissue, but without a
viable fetus.

 Invasive moles occur when hydatidiform moles penetrate the

muscle layer of uterus.

 Chriocarcinoma (Malignant GTD) has a fast dispersion and often

spreads outside the uterus. It can occur from a hydatidiform mole
after a pregnancy (full-term or one that has been prematurely
terminated).

 Placental site trophoblastic tumor generally occurs after

pregnancy, after the placenta gets attached to the uterus.

PATHOGENESIS
Molar Pregnancies

In normal conception, the fetus is formed from 23 maternal

chromosomes and 23 paternal chromosomes. A molar pregnancy
arises from an abnormality in chromosomal number during
fertilisation:

 Partial molar pregnancy – where one ovum with 23 chromosomes

is fertilised by two sperm, each with 23 chromosomes. This
produces cells with 69 chromosomes (triploidy).

o Note: A partial mole may exist with a viable fetus. The fetus
and placenta are usually triploid, however mosaicism can
exist where the fetus has a normal karyotype and the
triploidy is confined to the placenta.

 Complete molar pregnancy – where one ovum without any

chromosomes is fertilised by one sperm which duplicates, or (less
commonly) two different sperm. This leads to 46 chromosomes of
paternal origin alone.

These tumours are usually benign, but can become malignant –

invading into the uterine myometrium, and disseminating around
the body. These are known as invasive moles.

Other Types of Gestational Trophoblastic Disease

There are three main other forms of gestational trophoblastic

disease:

 Choriocarcinoma – a malignancy of the trophoblastic cells of the

placenta. It commonly, but not exclusively, co-exists with a molar
pregnancy.
 o This type of gestational trophoblastic tumour
characteristically metastasises to the lungs.

 Placental site trophoblastic tumour – a malignancy of the

intermediate trophoblasts, which are normally responsible for
anchoring the placenta to the uterus.

o They can occur after a normal pregnancy (most common), a

molar pregnancy or a miscarriage.

 Epithelioid trophoblastic tumour – a malignancy of the

trophoblastic placental cells, which can be very difficult to
distinguish from choriocarcinoma. It mimics the cytological
features of squamous cell carcinoma.

DIFFERENTIAL DIAGNOSIS

Ectopic pregnancy, normal pregnancy

TREATMENT AND MANAGEMENT

Invasive moles and choriocarcinomas are treated based on risk

groups. The stage of the invasive mole or choriocarcinoma is one
factor used to determine risk group. Other factors include the
following:

 The age of the patient when the diagnosis is made.

 Whether the gestational trophoblastic neoplasia occurred after

a molar pregnancy, miscarriage, or normal pregnancy.

 How soon the tumor was diagnosed after the pregnancy began.
 The level of beta human chorionic gonadotropin (β-hCG) in the
blood.

 The size of the largest tumor.

 Where the tumor has spread to and the number of tumors in the
body.

 How many chemotherapy drugs the tumor has been treated with

(for recurrent or resistant tumors).

There are two risk groups for invasive moles and choriocarcinomas:
low risk and high risk. Patients with low-risk disease usually receive
less aggressive treatment than patients with high-risk disease.

Placental-site trophoblastic tumor (PSTT) and epithelioid

trophoblastic tumor (ETT) treatments depend on the stage of
disease.

PROGNOSIS

Women with a hydatidiform mole have an excellent prognosis while

women with a malignant form of gestational trophoblastic disease
usually have a poor prognosis.

REFERENCE

https://www.thelancet.com/journals/lanonc/article/PIIS1470-
2045(03)01245-2/fulltext

https://www.cancer.gov/types/gestational-
trophoblastic/patient/gtd-treatment-pdq