|
They occur at a frequency of 1 in 1500 pregnancies in the United States. Incidence rates ten times higher are reported in parts of far Eastern Asia. Hydatidiform mole can be of two types: "complete", which contain no fetal tissue and demonstrate excessive circumferential trophoblastic hyperplasia around the abnormal villi; and "partial" which contains some fetal tissue, usually markedly abnormal, and the villi are hydropic with focal cytotrophoblastic growth. Approximately 10-15% of hydatidiform moles will develop into invasive moles or persistent GTD (see below). Complete moles have a small risk (1-3%) of malignant transformation into choriocarcinomas. An Invasive mole is a hydatidiform mole that penetrates the myometrium, but villi formation can be seen. Invasive moles are associated with the potential for uterine perforation, catastrophic bleeding and metastasis. Persistent GTD, as the name suggests, refers to GTD that persists after therapy. Most of these are invasive moles that are treated with a superficial dilatation and curettage, thus leaving GTD in the deeper layers of the uterus. Placental site trophoblastic tumor (PSTT) is a GTD that resembles invasive moles, in that they may penetrate into the uterine myometrium, but they are comprised primarily of intermediate trophoblasts. Most PSTT tend to remain localized, and rarely spread beyond the uterus. Choriocarcinoma is a malignant form of GTD, affecting less than 1 pregnancy in 20,000. Unlike other forms of GTD, villi formation is absent and the cells are markedly pleomorphic, with little resemblance to trophoblasts in some cases. Choriocarcinoma can metastasize, particularly to the lungs, and have a characteristic bloody gross appearance. Approximately 50% of choriocarcinomas develop in association with a hydatidiform mole, and the remaining following a spontaneous or therapeutic abortion, ectopic pregnancy, or even after a normal delivery. Choriocarcinomas can develop outside the context of GTD, in the gonads or the mediastinum, in which cases it is usually a component of a mixed germ cell tumor.
Immunohistochemistry has played a major role in both diagnosis and understanding the pathogenesis of GTD, and the former is best exemplified in the differentiation of complete and partial moles. Complete moles are formed both constitutional chromosomal copies in the conceptus are derived from the father, usually because the sperm fertilize an egg that has lost its nucleus. Thus complete moles do not have any fetal parts, and are by definition diploid. In contrast, partial moles are formed when two sperms simultaneously fertilize an egg that has retained its nucleus. The ploidy of this non-viable conceptus is triploid, and usually fetal parts are identified admixed with the partial mole. Thus, assessment of DNA ploidy is a simple technique to resolve a diagnostic conundrum between complete and partial moles. Other studies have focused on the role of apoptosis in the pathogenesis of GTD. For example, complete moles and choriocarcinomas demonstrate high levels of apoptosis (and hence high levels of pro-apoptotic proteins bax, and low levels of anti-apoptotic protein bcl-2). In contrast, normal placentae and partial moles have low levels of apoptosis and low bax/bcl-2 ratios. Some studies have found strong p53 immunoreactivity to be a reliable discriminator between hydatidiform moles (usually complete) and normal placentae. |
