Gestational Trophoblastic Disease

Gestational trophoblastic disease

introduction • Prior to 1969 metastatic choriocarcinoma was invariably fatal. • Virtually all patients are now potentially curable with chemotherapy. - Due to early diagnosis - Precise measurement of hCG - Availability of effective chemotherapy

definition • Trophoblastic disease is a spectrum of dz which extends from benign hydatidiform mole which usually resolve spontaneously, to lifethreatening choriocarcinoma. • Incidence – 0.5 to 2.5 per 1000 pregnancies • 3.04 per 1000 deliveries (Nigeria – Junaid 84)

Gestational trophoblastic disease • Hydropic degeneration – • Placenta site reaction an aborted conceptus – the presence of containing excessive trophoblastic cells fluid or liquefaction of and leucocytes in a placenta villus stroma placenta bed. without undue trophoblastic hyperplasia Hydropic degeneration and placenta site reaction are not complicated by malignant sequelae.

• Complete hydatidiform mole – an abnormal conceptus, without an embryo characterised by gross hydropic (generalized) swelling of the placental villi, with diffuse trophoblastic hyperplasia comprised of both cytotrophoblast and syncytial elements. • Has central cistern formation • It is avascular

• A classic mole resemble a bunch of grapes. • May either resolve or may progress to invasive mole or choriocarcinoma • Partial hydatidiform mole – an abnormal conceptus with an embryo or fetus that tend to die early. The placenta has focal villous swelling and focal trophoblastic hyperplasia with cistern formation.

The focal trophoblastic hyperplasia involves only syncytiotrophoblast The unaffected villi appear normal and vascularity of the villi disappears following fetal death. Patients with partial mole can be treated with chemotherapy for metastasis and elevated hCG Does not progress to choriocarcinoma

• Invasive mole – this is a tumour invading the myometrium – xterised by trophoblastic hyperplasia and persistence of the placental villous structure. • Commonly results from complete hydatidiform mole. • Usually does not progress to choriocarcinoma. • It may metastasize. • May resolve spontaneously

• Gestational choriocarcinoma – it is a carcinoma arising from trophoblastic epithelium that shows both syncytiotrophoblastic and cytotrophoblastic elements. • Preceding conception could result in a live birth, still-birth, abortion at any stage, ectopic pregnancy or hydatidiform mole.

• Antecedent pregnancy – 50% - complete mole - 30% - abortion - 20% - normal preg • Histology – lack of villous structure – distinguishes it from invasive mole. • Placental site trophoblastic tumour – a tumour arising from the trophoblastic tissue of the placental bed. Composed mainly of

Of cytotrophoblastic cells which accounts for the relatively low levels of hCG in this condition. • Treatment is by complete surgical excision, since this condition are not as chemosensitive as choriocarcinoma.

• Gestational trophoblastic tumour refers to conditions of trophoblastic dz, that requires more active intervention (chemotherapy) Includes – invasive mole, choriocarcinoma and placental site tumours.

genetics • Complete mole results when a haploid sperm (23x) fertilizes an empty ova (nucleus is lost or inactivated) and duplicate itself to form a 46xx complement – paternal chromosomes. • The karyotype of complete mole is usually 46xx and only in minority is it 46xy. • Complete mole is usually homozygous (xx) and less commonly heterozygous (xy)

• A complete mole with 46yy chromosome complement is never seen – b/c at least one x-chromosome is essential for cell survival. • A small percentage of complete mole results from dispermy – 2 haploid sperm (23x) fertilizing an empty egg. • Partial hydatidiform mole results from triploidy with one maternal and 2 paternal chromosome sets – diploid and tetraploid partial moles have been described.

presentation • Vag bleeding (most common) • Passage of vesicles • Hyperemesis gravidarum • Severe anaemia • Pre-eclampsia ( early onset) • Clinical hyperthyroidism • Large for date uterus

• Theca lutein cyst – abdominal pain due to torsion or rupture. Disappear in 4 months following evacuation. • Uterine perforation. • Pelvic sepsis • DIC

Physical examination • Chest – haemoptysis, pleuritic pain, and pneumonic changes – due to tumour invasion or following pulm infarction. • Dyspnoea with extensive metastasis. • Vagina inspection for suburethral nodule (next common site of metastasis after lung). • Cerebral metastasis may present as cerebrovascular accident, fits or loss of consciousness

investigations • Quantitative hCG – which is a tumour marker for trophoblastic tumours – a good assay detect as low as 2 IU/l of hCG in serum. • Pregnancy test • USS – xteristic snow storm appearance, exclude live fetus, theca lutein cyst.

• Chest x-ray • Full blood count • T3 and T4 assay prior to surgery, if there is any suspicion of thyrotoxicosis. • Liver function test • Serum E/U/Cr • Group and xmatch 2 units prior to evacuation.

• CSF hCG is measured in high risk prognostic group or in the middle risk group with lung metastasis. • CT- scan – if there is clinical suspicion of brain metastasis • MRI – done if despite suspicion, the CT-scan is normal. This is the investigation of choice in suspected spinal metastasis.

• Blood group of patient and sponse – for prognostic score.

FIGO staging for trophoblastic dz • Stage 0 – molar pregnancy • Stage 1 – lesion confined to uterus without metastasis. • Stage 2 – lesion extend outside uterus, but confined to genital organs • Stage 3 – lung metastasis • Stage 4 – other metastatic site

The risk of hydatidiform mole progressing to choriocarcinoma increases • • • • •

Pre-evacuation hCG level >100000IU/l Uterine size greater than gestational age Large (>6cm) theca lutein cyst Maternal age >40yrs Use of oral contraceptive pill before hCG level falls to undetectable level • Medical induction, hysterectomy or hysterotomy

treatment • Hydatidiform mole – resuscitation - Suction evacuation. - If bleeding is severe after evacuation give ergometrine or repeat evacuation in 2 wks. Note: medical induction, hysterectomy or hysterotomy increases the need for chemotherapy.

Follow-up for hydatidiform mole • Choriocarcinoma occurs in 3% of cases of complete hydatidiform mole, the risk is low with partial mole. • Follow-up is necessary to detect those who require chemotherapy for invasive mole or choriocarcinoma. • The serum hCG is assayed 2 weekly until it becomes undetectable (< 2IU/l), then monthly in the 1st year after evacuation and every 3 months in the 2nd year after evacuation.

• The hCG measurement should continue for at least 6 months after it has become undetectable. • The hCG must have been undetectable for 6months before starting another pregnancy. • After all subsequent pregnancy monitor hCG – due to risk of hydatidiform mole and choriocarcinoma. • Post chemotherapy – hCG follow-up is for life.

Criteria for chemotherapy after hydatidiform mole • High hCG level more than 4 weeks after evacuation. Serum level > 20,000IU/l or urine level > 30,000IU/l • Progressively rising hCG levels at anytime after evacuation. • Persistent uterine bleeding and positive hCG levels • Histological diagnosis of choriocarcinoma or evidence of CNS, renal, hepatic, GIT or pulmonary metastasis > 2cm in diameter or >3 in number.

Criteria for chemotherapy after hydatidiform mole • Beta-hCG levels rising for 2 successive weeks or constant for 3 successive weeks. • Beta-hCG levels elevated at 15 weeks postevacuation. • Rising Beta-hCG titer after reaching normal levels.

Prognostic scoring factor • Age • Antecedent pregnancy • Interval between pregnancy and start of chemotherapy • hCG level • ABO blood group of both sponse

• • • •

Largest tumour size Site of metastasis Number of metastasis Prior chemotherapy.

Total score • <4 – low prognostic group • 5-7 – medium prognostic group • >8 – high prognostic group • Low prognostic group – single agent chemotherapy – methotrexate with folinic acid rescue – ensure the renal and liver function are normal. • 8-day course of treatment, then 6-day interval before another course to prevent relapse.

Medium and high risk prognostic group • Combination chemotherapy – MAC III, CHAMOCA, EMA/CO • Patient are advised against pregnancy for a year after chemotherapy – to avoid confusing a pregnancy with a relapse, to reduce the risk of delayed teratogenicity.

Role of surgery in mgt of trophoblastic diseases • Evacuation • Uterine perforation managed by local resection of tumour and uterine repair. • Hysterectomy may be required for persistent heavy bleeding – but usually responds to chemotherapy • Surgical removal of drug-resistant disease in resectable site.