Gestational Trophoblastic Disease Flashcards
Definition of gestational trophoblastic disease
Excessive trophoblastic tissue. Comprises a group of disorders spanning the premalignant conditions of complete and partial molar pregnancies (‘hydatidiform moles’) through to the malignant conditions of invasive mole, choriocarcinoma and placental site trophoblastic tumour, epithelioid trophoblastic tumour (rare.)
Definition of getstational trophoblastic neoplasia
Characterised by persistent elevation of serum hCG after primary treatment.
Pathophysiology of a complete mole
Complete mole occurs after duplication of a sperm cell following fertilisation an ‘empty’ ovum that contains no genetic material. Sperm combine genetic material and cells start to divide to form a tumour (complete mole). No foetal material will form
* 20-25% can arise after dispermic fertilisation of an empty ovum
* Diploid and androgenic
* 46xx (90%), 46xy (10%)
* 8-20% require chemotherapy
Pathophysiology of a partial mole
Partial mole occurs following dispermic fertilisation of an ovum. The resultant cell will be triploid. In a partial mole, some foetal material may form.
* 69xxx (90%), 69xxy (10%)
* 0.5% require chemotherapy
* For the diagnosis of a partial mole, there must be histopathological evidence of trophoblast hyperplasia
Incidence of GTD
Uncommon in the UK, 1 in 714 live births (higher incidence in women from Asia). There is a higher incidence with increased maternal age
Classification of gestational trophoblastic neoplasia
Invasive hydatiform mole (IHM)- Invades the myometrium (HcG persists following primary treatment)
* Locally invasive, non-metastasising (chorionic villi become oedematous)
* Always follows a molar pregnancy
Choriocarcinoma- Malignant and metastatic. May occur following complete mole or non-molar pregnancy. Chorionic villi will not be oedematous
Placental site trophoblastic tumour (PTT)
* <1% of GTNs. Usually occurs after a normal term pregnancy.
* Late presentation- 3-4 years later (better prognosis the earlier it presents)
* May be slow growing OR metastatic- usually curable
Presentation of GTD
The use of ultrasound in early pregnancy has led to the earlier diagnosis of molar pregnancy
* Vaginal bleeding (‘prune juice appearance’) is the most common presenting symptom and is associated with around 60% of presentations.
* Significantly elevated hCG levels
Positive pregnancy test and supporting ultrasonographic evidence:
* Complete molar pregnancy- ‘snowstorm appearance,’ polypoid mass between 5 and 7 weeks gestation and thickened cystic appearance of villous tissue after 8 weeks with no gestational sac.
* Partial mole- enlarged placenta or cystic changes, an amniotic cavity either empty or containing small foetal echoes. ‘Presence of a well-formed but growth-retarded fetus, either dead or alive with hydropic degeneration of fetal parts being frequently present’
Other presentations: hyperemesis, excessive uterine enlargement, hyperthyroidism. Early-onset PET, abdominal distension.
Very rarely: haemoptysis, respiratory failure (other resp symptoms), seizures (other neuro symptoms (metastatic disease)
Investigations for GTD
Definitive diagnosis can only be made through histological examination:
* Complete mole- Absence of foetal tissue, extensive hydropic changes to the villi, excess trophoblast proliferation
* Partial mole- Prescence of foetal tissue, focal change to villi and some excess trophoblast proliferation
Ploidy status and immunohistochemistry staining for p57, a paternally imprinted gene, may help in distinguishing partial from complete molar pregnancies
Management of complete molar pregnancy
- Complete molar pregnancies are not associated with foetal parts, therefore, suction removal, is the method of choice for uterine removal irrespective of uterine size.
- Medical management should be avoided in complete mole- significantly increases the risk of malignant disease (16x higher risk). There is also concern over potential for dissemination of trophoblastic tissue when using oxytocic agents
Management of partial molar pregnancy
- Suction curettage is also the method of choice for removal of partial molar pregnancies except when the size of foetal parts deters the use of suction curettage and then medical removal can be used
Process of suction curretage in management of molar pregnancy
- Cervix is mechanically dilated (can consider using prostaglandins)
- Uterine contents suctioned out
- Curettage to scrape out remaining tissue from uterine walls
- If the woman is experiencing significant haemorrhage prior to or during removal, surgical removal should be expedited and the need for oxytocin infusion weighed up against the risk of tissue embolization
- Ripening of the cervix with either physical dilators or prostaglandins prior to uterine removal is not associated with an increased risk of developing GTN
Management of twin pregnancy with non-molar pregnancy alongside molar pregnancy
- If the woman has decided to terminate the pregnancy (or there has been demise of the coexisting twin) and the size of the foetal parts deters the use of suction curettage, medical removal can be used
- Women diagnosed with a combined molar pregnancy and viable twin, or where there is diagnostic doubt, should be referred to a foetal medicine and GTD centre
- The woman should be counselled about the potential increased risk of perinatal morbidity and the outcome for GTN
Need for anti-D prophylaxis during suction curretage
- Anti-D prophylaxis Is recommended following the removal of all molar pregnancies (not actually required for complete mole due to poor vascularisation of villi, but confirmation of diagnosis may not occur for some time- should give if diagnosis can’t be established within 72 hours)
Prevention of GTN
- The histological assessment of material obtained from the medical or surgical management of all miscarriages is recommended to exclude trophoblastic neoplasia if no fetal parts are identified at any stage of the pregnancy (no need after therapeutic abortion)
- Women who receive management for miscarriage should also do a urinary pregnancy test 3 weeks afterwards
- Referral to a GTD centre should be considered for all women with persistently elevated hCG either after an ectopic pregnancy has been excluded, or after two consecutive treatments with methotrexate for a pregnancy of unknown location
- GTN can develop after a pregnancy event
- Any woman who develops persistent vaginal bleeding after a pregnancy event is at risk of having a GTN
- A urine hCG test should be performed in all cases of persistent or irregular vaginal bleeding lasting more than 8 weeks after a pregnancy event
- Symptoms from metastatic disease, such as dyspnoea and haemoptysis, or new onset of seizures or paralysis, can occur very rarely
Treatment of GTN
- Assessed using the FIGO 2000 scoring system (women who score 6 or less are at low risk and can be given single-agent IM methotrexate)
- Multi-agent chemo for scores >6 includes combinations of methotrexate, dactinomycin, etoposide, cyclophosphamide and vincristine
- Single-agent or multi-agent chemotherapy
- PSTT and ETT are now recognised as variants of GTN. They may be treated with surgery (hysterectomy) because they are less sensitive to chemotherapy
