Gestational trophoblastic disease

Published on 09/03/2015 by admin

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Chapter 25 Gestational trophoblastic disease

Amy Tang

Gestational trophoblastic diseases are disorders in which the normal regulatory mechanisms controlling the behaviour of trophoblastic tissue are lost.

Incidence. Incidence is 1 in 1400 pregnancies.

Hydatidiform mole

Risk factors

• varying between populations
• dietary factors
• maternal age >35 years (complete mole)
• previous molar pregnancy

Complete hydatiform mole

Chromosomes

• Origin is entirely paternal.
• It is usually a 23X duplication, with a haploid sperm fertilising an empty egg and duplicating itself.
• 46XY moles are rare.

Pathology

• no identifiable fetal tissue
• chorionic villi with generalised hydatidiform swelling and diffuse trophoblastic hyperplasia

Partial hydatidiform mole

Chromosomes

• It involves a triploid karyotype, paternal 46XX/XY and maternal 23X (i.e. a normal egg with dispermy).
• If maternal 46XX and paternal 23X or 23Y, the result is a triploid fetus.
• Thus, placental growth is dependent on paternal genetic material.

Pathology

• chorionic villi of varying size with focal hydatidiform swelling, cavitation and trophoblastic hyperplasia
• marked villous scalloping, prominent stromal trophoblastic inclusions
• identifiable fetal tissues

Presentation

• most diagnosed on ultrasound scan
• vaginal bleeding, hyperemesis
• uterus large for dates, theca lutein cysts
• pre-eclampsia, hyperthyroidism

Investigations

• full blood count, blood group and cross-match, quantitative human chorionic gonadotrophin (hCG)
• ultrasound scan of the pelvis, chest X-ray

Management

• suction curettage with oxytocics
• hysterectomy is an option if the woman has completed childbearing
• register in the trophoblastic registry

Follow-up

• involves weekly quantitative serum or 24-hour urinary hCG until normal (usually takes 8–12 weeks); then monthly hCG levels for 12 months (6 months if partial mole)
• contraception is required, and the oral contraceptive pill may be used
• advise to avoid pregnancy for at least 9 months after hCG levels return to normal

Persistent gestational trophoblastic disease

This is a complication for about 20% of women with complete moles and in up to 4% of partial moles. This condition is also known as gestational trophoblastic neoplasia.

Diagnosis and presentation

• plateau or rising hCG levels over 3 weeks after suction curettage
• delayed postevacuation bleeding
• raised hCG longer than 6 months
• evidence of metastatic disease
• presence of histologic choriocarcinoma

Investigations

• Assess risk factors and arrange further work-up: computed tomography (CT) scan of abdomen and pelvis, chest X-ray, quantitative hCG, full blood count, electrolytes, liver biochemistry.
• CT brain scan will also be required if presence of neurological symptoms or if lung/liver metastases are present.

Modified World Health Organization (WHO) scoring system for FIGO 2000 staging

This is used to determine if a patient belongs to a high-risk or low-risk group so the appropriate treatment can be offered. The prognostic factors used to calculate this score include: age, type of antecedent pregnancy, interval from index pregnancy, pretreatment hCG level, largest tumour size including uterus, site and number of metastases, and presence of previous failed chemotherapy. A score <7 indicates low-risk group and a score of ≥7 indicates high-risk group.

Management

• For low-risk patients, single-agent chemotherapy is the first-line treatment. Cure rate for these patients is almost 100%.
• Methotrexate and folinic acid: 2-weekly courses continuing for two courses after hCG returns to normal.
• About 10% of patients suffer from side effects (especially serositis and mucosal ulceration) and require a change of chemotherapy to actinomycin D every 2 weeks.
• Treatment failure rate is 10%, and this requires second-line therapy: actinomycin D if hCG levels are below 100 IU/L; etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovine (EMACO) if hCG levels are over 100 IU/L. Potential side effects include thrombocytopenia, hepatotoxicity and hair loss.
• Follow up patient with a weekly quantitative hCG until normal, and then monthly for 6–12 months.

High-risk gestational trophoblastic disease

Definition. This is a disease that is not cured by low-risk chemotherapy, or with a histological diagnosis of choriocarcinoma, or with other high-risk features such as metastatic disease in the brain or liver, over 12 months between the antecedent pregnancy and starting therapy and term antecedent pregnancy. WHO scoring =7 or more.

Investigations

• quantitative hCG, full blood count, electrolytes, liver biochemistry
• CT scans of chest, abdomen, pelvis and brain
• lumbar puncture to measure blood-to-cerebrospinal fluid hCG ratio (normally, the ratio is 65:1, but with metastases this is reversed)
• selective angiography of abdomen and pelvic organs if indicated
• histological confirmation not required

Management

• Follow the EMACO regimen.
• If the central nervous system is involved, use EMACO with 1000 mg methotrexate and intrathecal methotrexate 12.5 mg weekly.
• With a single large brain metastasis, seek neurosurgical review for possible removal before chemotherapy.
• Second-line therapy uses high-dose cisplatinum VP-16.

Follow-up

• weekly hCG tests
• four courses of chemotherapy continued after hCG returns to normal
• after chemotherapy, monthly hCG levels required for 2 years, and then 3-monthly levels for 3 years
• advise against pregnancy until hCG levels have been normal for 12 months
• cure in 80% of non-metastatic disease, 50% with metastatic disease
• if central nervous system metastases appear during or after high-risk chemotherapy, survival rate is 0%–20%

Theca lutein cysts

• These are present in 20%–25% of molar pregnancies.
• They are thin-walled benign cysts with an average size of 7 cm.
• They usually reduce in size with decreasing hCG levels.
• Complications include rupture, torsion and bleeding.
• If present after curettage, they are associated with a risk of persisting trophoblastic disease.
• Management of uncomplicated cysts is conservative.

Choriocarcinoma

• This is a malignant tumour of villous trophoblast with anaplastic syncytiotrophoblast and cytotrophoblast.
• It has a tendency to early vascular invasion and widespread dissemination.

Placental site trophoblastic tumour

• the least common form of gestational trophoblastic disease
• shows predominance of cytotrophoblast with little syncytium
• intermediate trophoblasts are present
• hCG levels are often low; human placental lactogen is produced by the tumour
• does not readily respond to standard chemotherapy
• diagnosis: by curettage
• treatment: surgically when disease confined to uterus

Further reading

Hancock B.W., Tidy J.A. Current management of molar pregnancy. Journal of Reproductive Medicine. 2002;47:347-354.

Royal College of Obstetricians and Gynaecologists (RCOG) Guidelines and Audit Committee. The management of gestational trophoblastic disease. London: RCOG; 2009. RCOG Greentop Guideline No. 38, 2nd draft, May.

Shapter A.P., McLellan R. Gestational trophoblastic disease. Obstetrics and Gynecology Clinics of North America. 2001;28:805-817.

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