Gestational Trophoblastic Disease

Max Brinsmead MB BS PhD

March 2015

Gestational Trophoblastic Disease (GTD) is… A spectrum of disorders in which trophoblastic

tissue (usually of pregnancy origin) proliferates abnormally

The spectrum includes: Hydatidiform mole

Complete and Partial Invasive mole Placental site trophoblastic tumour Choriocarcinoma

Persisting or recurrent disease is better termed Gestational Trophoblastic Neoplasia or GTN

Gestational Trophoblastic Neoplasia (GTN) is remarkable because…

There are marked geographical and ethnic differences in its incidence that have A presumed genetic and Possibly environmental origins

There are identified chromosomal abnormalities Has a tumour marker (beta HCG) that is…

highly sensitive and 100% specific (normal pregnancy excluded)

Has very high rates of response to chemotherapy

Molar Pregnancies

Complete Mole Diploid chromosomes No fetal tissue present Androgenic (paternal) in origin

75% arise from duplication of a monospermic fertilization 25% arise from dispermic fertilization of an “empty ovum”

Partial Mole 90% are triploid and 10% tetraploid or mosaic

Arise when there is dispermic fertilization of a “normal ovum”

Usually have a fetus or some fetal tissue Chromosome studies and P57 immunochemical

histology helps to distinguish the two

GTD Incidence and Risk of Malignancy

Incidence of ≈ 1:750 Caucasian pregnancies ≈ 1:400 Asian pregnancies May be as many as 1:110 pregnancies in SE Asia 10-fold more common when maternal age is >40 years Complete mole has a 15% risk of GTN Partial mole has a 0.5% risk of GTN But only 1:50,000 normal pregnancies go on to GTN

Common Presentations of GTD

Bleeding in early pregnancy “Large for dates” and no fetus or FH found As an incidental finding during routine early

pregnancy ultrasound Placenta has a “snow-storm” appearance Partial mole more difficult and may be diagnosed

only after histology of failed 1st trimester pregnancy tissue

Occurs more commonly with twin pregnancies

Uncommon Presentations of GTD

*Hyperemesis **Early onset pre eclampsia (<20w) Thyrotoxicosis

Due to a TSH-effect of abundant HCG Abdominal distension with theca lutein cysts *Secondary postpartum haemorrhage or ongoing

PV bleeding after any pregnancy Seizures (from brain metastases) or haemoptysis

(from lung metatases)# Acute respiratory failure*Most of these are not GTD#Choriocarcinoma **Classically with triploidy

Management of Molar Pregnancies

Suction curettage preferred over medical evacuation

Because of the risk of trophoblastic embolisation Cervical ripening with PG’s acceptable Oxytocin infusion for life threatening haemorrhage

Large fetal parts with a partial mole will require prostaglandins

Mole plus a normal twin pregnancy presents dilemmas

But the prognosis for the normal twin is very grim But risk of GTN is not increased and there is a normal

response to chemotherapy if required

Don’t forget the Anti-D if Rh negative

Never miss a mole or GTN by… Always send “products of conception” for histology

When passed spontaneously When curetted after failed pregnancy After curette for secondary postpartum haemorrhage

Not required after termination of pregnancy When there has been a normal ultrasound before TOP Or fetal parts are identified

Do a urine test for HCG 3 weeks after all non-surgically managed failed pregnancy

And no POC for histology

And do a HCG for any abnormal bleeding within 3 months of any pregnancy

Or the woman presents with a weird tumour

Follow up of molar pregnancies: Monitor for GTN after complete mole by…

Weekly HCG until 3 consecutive are negative Or at 8w if negative before Then monthly for 6m No pregnancy please for 6m from time of 1st negative test

For Partial Mole May stop weekly HCG’s when negative No pregnancy for 6m please

COC increases the risk of GTN by RR 1.19 Barrier contraceptives best But only until the HCG returns to normal And any contraceptive is better than another pregnancy

Management of Gestational Trophoblastic Neoplasia Best done by registering all molar

pregnancies with a Specialist Centre

Methotrexate is the 1st line drug but treatment requires individualization

And multi-agent chemotherapy may be required

Second curette rarely necessary A few patients require surgery as part of their

care

FIGO 2000 Score for GTN

Chemotherapy for GTN is based on FIGO Score.. For score ≤ 6 Methotrexate only:

Alternate daily for a week With Folinic acid rescue on the alternate days Then rest for 6 days and measure HCG Repeat as necessary until HCG is normal Then weekly HCG for 6w and monthly for 12m

For score ≥ 7 Multi-agent chemotherapy: Dactinomycin Cyclophosphamide Vincristine Etoposide

Prognosis after chemotherapy for GTN Cure rates in excess of 97% should be possible Risk of another molar pregnancy is 1:80 No increased obstetric risk Unless the pregnancy is conceived within 12m of

chemotherapy Increased risk of pregnancy loss (some by TOP) But no increased risk of fetal malformation

Menopause occurs slightly earlier By a mean of 12m or 3 yrs after multi-agent chemo

And some women at risk of developing secondary cancers if chemo continued >6m

Leukemia (RR 16.6) Ca colon (RR 4.6), melanoma (RR 3.4), Ca breast (RR 5.6)

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