GESTATIONAL TROPHOBLASTIC DISEASE - HYDATIDIFORM MOLE

Done by : Duaa Migdadi

Give rise to the embryo Give rise to the placenta

Trophoblast are cells forming the outer layer of a blastocyst , which provide nutrients to the embryo and develop into a large part of the placenta.

Introduction

The trophoblast proliferates and differentiates into 2 cell layers at approximately 6 days after fertilization for humans:

Layer Location Description

Cytotrophoblast

Syncytiotrophoblast

Intermediate trophoblast (IT)

inner layer

outer layer

implantation site , chorion, villi (dependent on subtype)

Single celled

Thick layer that lacks cell and grows into the

endometrial stroma.

It implant into uterus , come into contact with maternal

blood and form chorionic villi and seccrete hCG to

maintain progesterone secretion and sustain a

pregnancy.

anchor placenta (implantation site IT), unknown (chorionic & villus IT)

HCG :a hormone produced by the placenta after implantation and if positive indicates an implanted blastocyst and mammalian embryogenesis

GTD/GTN: Abnormal proliferation of trophoblastic cells of the placenta. In

simple words; GTNs are tumors that originate from the placenta

o The majority of patients (80-90%) with GTD have a benign course. o This diverse group of diseases has a sensitive tumor marker, human chorionic gonadotropin (hCG), that

allows accurate follow-up and assessment of the diseases.

Molar pregnancy is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the

uterus and will fail to come to term.

They typically arise from the abnormal fertilization of the ovum.

A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has

swollen chorionic villi. These villi grow in clusters that resemble grapes(NON-INVASIVE)

Hydatidiform mole

Proliferates within the uterus without myometrial infiltration or hematogenic dissemination .

May develop malignant traits and become an invasive mole ( 20% risk )

No histologic signs of malignancy in the primary tumor .

Trophoblasts infiltrate the myometrium and gain access to the vascular system.

Hematogenic dissemination leads to metastatic growth in different organs (brain, lungs, liver).

RISK FACTORE

• Previous molar pregnancy

The risk of the development of a second molar pregnancy is 1-3%, or as much as 40 times greater than the

risk of developing the first molar pregnancy.

• High or low maternal age(<20 or >40)

result from defective fertilization process that is more common in both younger and older individuals.

• Asian origin

• smoking

• Diet may play a causative role.

The incidence of molar pregnancy has been noted to be higher in geographic areas where people consume

less β-carotene (a retinoid) and folic acid.

• Most molar pregnancies are sporadic, but a familial syndrome of recurrent hydatidiform mole has been

described and is reported to be strongly associated with a mutation in the NLRP7 gene

Complete hydatidiform mole

The majority of hydatidiform moles are “complete” moles

Does not contain any fetal or embryonic parts

Caused by fertilization of an empty egg that does not carry

any chromosomes → The (physiological) haploid chromosome set

contributed by the sperm is subsequently duplicated.

In rare cases, the formation of a complete mole may also result from

simultaneous fertilization of an empty egg by two sperms.

Fetal karyotype

46XX: more common (∼ 90% of cases)

46XY: less common (∼ 10% of cases)

46YY karyotype has never been observed because it is

nonviable.

COMPLETE MOLE IS THE RESULT OF PATERNAL DISOMY( A GENOTYPIC ANOMALY IN WHICH AN INDIVIDUAL

RECEIVES TWO COPIES OF ONE CHROMOSOME FROM A SINGLE PARENT AND NO COPIES FROM THE OTHER)

Pathophysiology

Placental abnormality

severe hyperplasia of trophoblasts (Cytotrophoblast and Syncytiotrophoblast )

hydropic (swollen) of chorionic villi

hydropic degeneration that lead to grape-like vesicles filling uterus

Absent fetus tissue

High hCG levels (>100,000mlU/ml) (Serum hCG is excessively high with complete moles )

caused by abnormal proliferation of Syncytiotrophoblast

Large theca cysts >6cm

Hyperthyroidism

Hyperemesis gravidarum

Early pre-eclampsia

15-20% progress to malignancy

NOTE

SIGNS AND SYMPTOMS

Vaginal bleeding (irregular or heavy vaginal bleeding during the first or early second trimester of

pregnancy . The bleeding is usually painless, although it can be associated with uterine contractions)

Uterus size greater than normal for gestational age and feel very soft and boggy .

Passage of vesicles that may resemble bunch of grapes through the vagina

Endocrine symptoms

hyperthyroidism ( Nervousness tremors because B-HCG structurally resemble TSH „thyrotropic

activity‟)

Preeclampsia (irritability , dizziness and photophobia ) before 20 weeks of gestation .

Preeclampsia tend to occur in the 2nd and 3rd trimester , so if it occur in 1st trimester think of molar

pregnancy

Hyperemesis gravidarum ( a condition of severe persistent nausea and vomiting that may lead to

loss >5% of pre-pregnancy weight and severe dehydration .

More common among (young women , primigravida , multiple gestation and molar pregnancy )

• Ovarian theca lutein cyst : bilateral , large ,

cystic , adnexal masses that are tender to touch

(a type of functional ovarian cyst that is thought

to originate from excessive amount of circulation

gonadotropins ( B-HCG) . Typically multiple and

seen bilaterally with a high association with GTD

and multiple gestation . Usually resolve

spontaneously once the source of B-HCG is

removed Ultrasound shows bilateral enlarged multilocular cystic masses of the ovaries

The typical clinical presentation of complete molar pregnancies has changed with the advent of high-resolution ultrasonography.

Most moles are now diagnosed in the first trimester before the onset of the classic signs and symptoms

Lab test : initial test of choice

Β-HCG level measurement that is markedly elevated (higher than expected for gestational age )

Some mole may not produce B-HCG at all !!

Trans vaginal Ultrasound (the most reliable and sensitive technique )

o Theca lutein cyst

o ‘Snowstorm’ = swiss cheese = honeycombed uterus = bunch of grapes appearance of mixed echogenicity , representing hydropic villi and intrauterine hemorrhage.

o No amniotic fluid

o Lack of fetal heart tone

Ct scan

Histopathology : definitive diagnosis

DIAGNOSIS

To rule out lung mets

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