The pathology of gestational trophoblastic disease: recent advances

When inundated with numerous specimens of products of conception as the consequence of miscarriage, it is all too easy for histopathologists to forget that the biology of trophoblast and the events of early placental implantation continue to fascinate because of the inherently invasive properties of the non-villous (extravillous) trophoblast. However, unlike the invasion of a malignant tumour, the invasion of trophoblast is controlled. The failure of adequate conversion of maternal uteroplacental arteries is a major pathogenetic phenomenon of important disorders of pregnancy including pre-eclampsia. However, it is in the field of gestational trophoblastic disease that diagnostic acumen is most called for. There are several problematic areas that give rise to diagnostic error; e.g., the diagnosis of early complete mole as partial mole, the over-diagnosis of hydatidiform mole in tubal pregnancy and the diagnosis of placental site non-villous trophoblast as placental site trophoblastic tumour or choriocarcinoma, particularly if associated with atypia, as frequently observed in complete mole. The chorionic villi of early diploid complete mole show characteristic features of villous profile, stromal mucin and stromal nuclear debris. The distinction between complete mole and triploid partial mole can be facilitated by ploidy analysis and immunohistochemistry for the product of the paternally imprinted, maternally expressed gene, p57kip2. Persistent trophoblastic disease (PTD) is a clinical not a histopathological diagnosis and the role of the histopathologist once a diagnosis of PTD has been made is limited. Invasive mole and choriocarcinoma are encompassed by PTD. Tumours of the non-villous trophoblast are placental site trophoblastic tumour and the more recently recognised epithelioid trophoblastic tumour. The role of immunohistochemistry in the elucidation of trophoblastic lesions is discussed pragmatically.