We searched the Cochrane Library, Medline (via PubMed, Internet Grateful Med, OVID, and Knowledgefinder), for meta-analyses, previous systematic reviews, cohort studies (and when appropriate comparison groups), and case-control studies published in English between 1980 and 2010, with the keywords “trophoblastic disease”, “GTD”, “GTN”, “choriocarcinoma”, “molar pregnancy”, “hydatidiform mole”, “placental site trophoblastic tumor”, “genetics”, “epidemiology”, “pathology”, “treatment”,
SeminarGestational trophoblastic disease
Introduction
Hippocrates was probably the first to describe gestational trophoblastic disease around 400 BC in his description of dropsy of the uterus.1 Although other observations have been made since, Marchand first associated hydatidiform mole with pregnancy in 1895.1 Healthy trophoblastic tissue aggressively invades the endometrium and develops a rich uterine vasculature, generating an intimate connection between the fetus and the mother known as the placenta. Invasion is one of the distinct features of malignant disease, and healthy trophoblast can be detected by PCR in the maternal circulation.2 Fortunately, malignant-like behaviour is tightly controlled in healthy trophoblast. However, in gestational trophoblastic disease the regulatory mechanisms fail, resulting in tumours that are highly invasive, metastatic, and very vascular. In this Seminar we discuss the epidemiology, origins, pathological changes, and clinical behaviour of the various forms of gestational trophoblastic disease.
Section snippets
Epidemiology
Gestational trophoblastic disease arises more frequently in Asia than in North America or Europe,3, 4 which could be due to differences in prevalence, discrepancies between hospital-based and population-based data, or disparity in availability of central pathology review. In the UK, all patients are included on a national register, with central pathology review; and the incidence of complete hydatidiform mole is around one per 1000 pregnancies and three per 1000 for partial hydatidiform mole.5
Causes and genetics
In most cases, complete hydatidiform mole usually arises when an ovum without maternal chromosomes is fertilised by one sperm that then duplicates its DNA, resulting in a 46XX androgenetic karyotype, in which all chromosomes are paternally derived.25, 26, 27 About 10% of complete moles are 46XY,28 arising from fertilisation by two sperm (figure 1). Although nuclear DNA is entirely paternal, mitochondrial DNA remains maternal in origin.29 Findings from some studies30 show that patients with
Pathology
All gestational trophoblastic disease is derived from the placenta. Hydatidiform moles and choriocarcinoma arise from villous trophoblast and placental-site trophoblastic tumours from interstitial trophoblast. Most complete and partial hydatidiform moles have distinctive morphological characteristics, although diagnostic criteria have changed because evacuation is done earlier in gestation (median 8–9 weeks in the UK). First-trimester complete moles show a characteristic abnormal budding
Diagnostic ultrasound for molar pregnancy
Patients with complete hydatidiform mole most commonly present with vaginal bleeding in early pregnancy. Previously reported features such as anaemia, uterine enlargement, pre-eclampsia, hyperemesis, hyperthyroidism, and respiratory distress are now rare,60 probably because routine use of ultrasonography leads to diagnosis in the first rather than late-second trimester. Partial hydatidiform moles grow more slowly and present slightly later in the first or early second trimester than do complete
Surgical evacuation
Suction curettage is the preferred method of evacuation irrespective of uterine size in patients with suspected hydatidiform mole who want to preserve fertility.78, 79 Intraoperative ultrasonography can reduce the risk of uterine perforation. Patients who are rhesus-negative should receive rhesus immunoglobulin at the time of evacuation because rhesus D factor is expressed on trophoblast. Women who are nulliparous should not be given prostanoids to ripen the cervix since these drugs can induce
Registration for hCG surveillance
All patients with hydatidiform mole should be registered with a specialist centre for hCG surveillance, preferably one that is coordinated nationally. The UK established the first national service for gestational trophoblastic disease through a combined agreement of the Royal College of Obstetricians and Gynaecologists and the Department of Health's National Commissioning Group. Since 1973, all women with hydatidiform mole or other forms of gestational trophoblastic disease have been registered
Indications
Panel 2 shows the UK indications for treatment of gestational trophoblastic disease with chemotherapy. These recommendations are similar to those suggested by the International Federation of Gynecology and Obstetrics (FIGO)92 and include a plateaued or rising hCG (the most common reason for treatment), a persistently raised hCG at 6 months after evacuation, or histological diagnosis of choriocarcinoma. However, our experience suggests that the disease is unlikely to remit spontaneously when:
Conclusions
Although outcomes for more than 98% of women with gestational trophoblastic neoplasia are excellent, a few women die from the disease, mainly because of late presentation and diagnosis or drug resistance. Consequently, novel therapies with improved efficacy and reduced toxic effects need to be identified. Additionally, after diagnosis of molar pregnancy, women have to wait many weeks or months to find out whether they need chemotherapy. Therefore, a new prognostic test at the time of initial
Search strategy and selection criteria
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