Gestational trophoblastic disease (incl. choriocarcinoma)

Question 1

Define gestational trophoblastic disease (GTD).

Answer 1

Spectrum of conditions originating from the placental trophoblast that includes:

• complete hydatidiform mole
• partial hyatidiform mole
• invasive mole
• choriocarcinoma

Question 2

Which GTDs are benign vs invasive?

Answer 2

Complete, partial and invasive moles = hydatidiform moles which are part of benign GTD

Choriocarcinoma = a type of gestational trophoblastic neoplasia which is invasve and can metastasise.

Question 3

Define hydatidiform mole.

Answer 3

Chromosomally abnormal pregnancies that have the potential to become malignant (gestational trophoblastic neoplasia).

Question 4

How common is GTD?

Answer 4

Rare - less than 1 in 1000 pregnancies affected

Modest increase in incidence in if maternal age <20 years

Question 5

What are the risk factors for GTD?

Answer 5

• Previous molar pregnancy
• High or low maternal age
• Asian origin

Question 6

What are the clinical features/findings in GTD?

Answer 6

Ultrasound features of intrauterine vesicles (‘cluster of grapes’)

Persistently raised hCG levels after miscarriage

Question 7

What is a complete hydatidiform mole?

Answer 7

46 XX or 46 XY karyotype that is derived entirely of paternal DNA

typically the result of fertilisation of a chromosomally empty egg with a haploid sperm that then duplicates

Question 8

What is a partial hydatidiform mole? How does it arise?

Answer 8

partial hydatidiform moles contain a karyotype of either 69 XXX or 69 XXY, and contain both maternal and paternal genetic material

usually arises from fertilisation of a haploid ovum by a single sperm, and duplication of paternal haploid chromosomes

Question 9

Compare and contrast the other characteristics of partial and complete moles.

Answer 9

Partial may contain evidence of fetal parts, circulation and fetal RBCs whereas complete do not have these components

Complete mole produces more hCG due to more chornionic villi and increased trophoblast volume than partial mole. This is what causes more severe symptoms.

Question 10

What are the consequences of high hCG in molar pregancy?

Answer 10

• hyperemesis gravidarum,
• early-onset gestational hypertension,
• theca lutein cysts,
• hyperthyroidism
• headache and photophobia

Question 11

What is the diagnosis?

An 18-year-old pregnant woman presents at 10 weeks’ with PV bleeding. Vital signs indicate sinus tachy and HTN. On pelvic examination the uterus is enlarged to 16 weeks’ gestational size with a palpable left adnexal cyst of about 9 cm diameter. Pelvic USS reveals a mixed echogenic (snow-storm) pattern with no fetus and thin-walled cysts in the left ovary.

Answer 11

Complete molar pregnancy = diffuse echogenic pattern described as a snow-storm pattern, which is created by intermingling of hydropic villi and blood clots

Question 12

What are the risk factors for GTD?

Answer 12

Extremes of maternal age (<20 and >35)

Prior GTD (x10 risk)

Question 13

What are the clinical features of GTD?

Answer 13

• 1st trimester
• Missed period
• PV bleeding
• Unusually large uterus for gestational age

Others:

• Headache and photophobia - pre-eclampsia-like symptoms
• SOB and resp distress - due to high output cardiac failure from anaemia
• hyperemesis gravidarum
• tachycardia, tremor, insomnia, diarrhoea
• HTN
• pelvic pain - due to theca lutein cysts

Question 14

Why do GTD cases present with features of hyperthyroidism e.g. tremor, insomnia, diarrhoea, tachycardia?

Answer 14

There is molecular homology between subunits of TSH and beta hCG so may stimulate production of thyroid hormone

Question 15

How would you diagnose GTD?

Answer 15

Serum beta hCG - often >100,000IU/L

Pelvic USS - abnormal with uterine enlargement, may have ovarian cysts. Characteristic snow-storm appearance of uterine cavity and absence of fetal parts (complete( or small placenta with partial fetal development (partial).

Histological examination of miscarriage tissue - often an incidental diagnosis is made on evaluation of an evacuated dilation and evacuation (D&E) specimen

Question 16

What laboratory investigations should also be done in suspected GTD?

Answer 16

• Serum beta hCG
• FBC - severe anaemia may occur due to PV bleeding or dilutional effects of increased blood volume
• Serum PT and PTT - to assess risk of serious bleeding at evaculation for GTD
• Serum urea, creatinine, LFTs - if malignancy requires later treatment
• Blood type with antibody screen - in event of heamorrhage
• Thyroid function tests.

Question 17

What produces beta hCG? Why is it important to monitor post-molar pregnancy?

Answer 17

Secreted by syncytiotrophoblasts, which proliferate excessively in molar pregnancy.

Normal pregnancies are associated with a peak serum beta hCG of <100,000 IU/L (100,000 mIU/mL)

Serum beta hCG acts as a tumour marker to follow post-molar regression, and to identify post-molar gestational trophoblastic neoplasia.

Question 18

What is the management of GTD?

Answer 18

Depends on desires to maintain fertility or not.

1. Fertility preserving - D&E (dilation and evacuation)
2. Not desiring future pregnancy - hysterectomy
3. Management of other complications e.g. nausea, hyperthyroidism, anaemia.

Registration a nationally recognized centre for treatment of GTD

Question 19

What are the chances of malignant progression of GTD?

Answer 19

About 20% of patients with complete molar pregnancies and 5% of patients with partial molar pregnancies will develop malignant sequelae and require chemotherapy.

Question 20

How long after GTD should the patient avoid pregnancy for?

Answer 20

12 months - strict adherence to a RELIABLE form of contraception should be enforced e.g. COCP/POP. This is given as soon as beta hCG normalises.

Question 21

How do you counsel a patient about GTD?

Answer 21

1. Explain the diagnosis (when the foetus doesn’t form properly, and a baby doesn’t develop, instead there is an irregular mass of pregnancy tissue)
2. Explain risks (important to treat because it can invade and damage other tissues)
3. Explain immediate management (suction curettage) o Explain follow-up (referral to trophoblastic screening centre to monitor pregnancy hormone levels)
4. Molar pregnancy does not affect fertility (but there is a 1 in 80 chance of recurrence)
5. Do not try to get pregnant until after follow-up is complete

Question 22

What follow up in necessary post evacuation of the mole?

Answer 22

1. Weekly blood serum hCG until levels normalise to <5IU/L for 3 weeks
2. Then, monthly beta hCG for 6 months

6-12 months of normal beta hCG levels is generally adequate to exclude post-molar GTN

Question 23

How is invasive gestational trophoblastic neoplasia diagnosed?

Answer 23

Involves invasion of hydatidiform mole beyond the normal placentation site (into the myometrium with venous penetration)

Diagnosed when beta hCG levels persist after evacuation of molar pregnancy i.e.

• plateau in levels for 3 consecutive weeks
• OR rise of 10% or more over 2 weeks
• OR positive beta-hCG after 6 months post-evacuation.

Question 24

What are the histological findings in choriocarcinoma?

Answer 24

Presence of both cytotrophoblasts and syncytiotrophoblasts, but chorionic villi are absent (which differentiates the condition from an invasive mole)

Question 25

What are the complications of GTD and its treatment?

Answer 25

• Pre-eclampsia
• Choriocarcinoma or invasive gestational trophoblastic neoplasia
• Other tumour
• Embolisation of trophoblastic tissue –> post-evacuation respiratory ditress syndrome
• Asherman’s syndrome
• Metastases (esp to brain, lungs, abdo and pelvis)