Pre-Malignant Trophoblast Disease

Molar Pregnancy

The incidence of molar pregnancies in Europe and North America is in the order of 0.2-1.5 per 1000 live births although these figures are of limited accuracy (Smith and Kim 2003). There may be a higher incidence of molar pregnancies in Africa and Asia, however the varying standards in the frequency and accuracy of pathology and demographics make accurate comparisons difficult.

The relative risk of molar pregnancy is highest in those pregnancies at the extremes of the reproductive age group. There is a modestly increased incidence in teenagers (1.3 fold) but a 10 fold increased risk in those aged 40 and over. The risk of a complete molar pregnancy increases more than the risk of developing a partial mole (Sebire 2002).

Historically the relative incidence of partial and complete molar pregnancies have been reported as approximately 3:1000 and 1:1000. This situation may well represent an over diagnosis of partial mole as data from CXH demonstrates that nearly 40% of partial moles referred for expert review are reclassified as either complete moles or non-molar pathologies (Paradinas 1994).

Partial Mole (PM)

Partial moles are triploid with 2 sets of paternal and 1 set of maternal chromosomes as shown in Fig 1. Macroscopically PM may resemble the normal products of conception with initially an embryo present, which dies by week 8-9. The histology shows less swelling of the chorionic villi than in complete mole and there are usually only focal changes. As a result the diagnosis of PM can often be missed after an apparently straightforward miscarriage or termination.

The clinical presentation of partial mole is most frequently via irregular bleeding or by detection on routine ultrasound. The obstetric management is by suction or medical evacuation and these all PM patients should be followed up with serial hCG measurement arranged through the Trophoblast service in the UK.

Fortunately PM rarely becomes malignant with generally only one or two cases of malignant disease seen per year at CXH with an overall risk of 0.5% of requiring chemotherapy after a PM (Seckl 2000).

Complete Mole (CM)

In most complete moles the genetic material is entirely male in origin and results from the fertilisation of an empty ovum lacking maternal genes. The chromosome complement is most commonly 46XX, which results from one sperm that duplicates its DNA, or less frequently 46XX or 46XY from the presence of two different sperm. On very rare occasions CM can be biparental with genetic contributions from both the mother and father (ref). Whilst this type is extremely rare, biparental mole is associated with a high risk of further molar pregnancies and patients who have had more than 2 molar pregnancies may benefit from investigation at an expert centre. At Charing Cross we are able to perform genetic tests to investigate if this rare condition is present and to offer appropriate advice.

The diagnosis of CM is most often made as a result of bleeding, a large for dates uterus, or an abnormal ultrasound. Macroscopically there is no foetus and the histology shows the characteristic oedematous villous stroma. However the textbook ‘bunch of grapes’ appearance is seen in the second trimester and as now most cases are diagnosed earlier, this is rarely seen in the UK. The obstetric management is by suction evacuation followed by serial hCG measurement and surveillance registration.

In contrast to PM, CM more frequently proceeds to invasive disease with 8-20% of patients requiring chemotherapy.

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