Complete hydatidiform moles exhibit characteristic swelling and trophoblastic hyperplasia (Fig. 39.1). They usually have a 46,XX karyotype, but about 10% have a 46,XY karyotype (12,13). The molar chromosomes are entirely of paternal origin, with mitochondrial DNA of maternal origin (Fig. 39.2) (14). Complete moles usually arise from an ovum fertilized by a haploid sperm, which duplicates its own chromosomes. The ovum nucleus may be absent or inactivated (15).
Partial Hydatidiform Mole Partial hydatidiform mole is characterized by the following pathologic features (16) (Fig. 39.3): 1.
Chorionic villi of varying size with focal hydatidiform swelling, cavitation, and trophoblastic hyperplasia 2.
3.
4.
Partial moles have a triploid karyotype (69 chromosomes); the extra haploid set of chromosomes usually is derived from the father (Fig. 39.4) (17). It is possible that nontriploid partial moles do not exist (18). When a fetus is present in conjunction with a partial mole, it
Figure 39.1 Photomicrograph of complete mole demonstrating enlarged villous with central cavitation and surrounding trophoblastic hyperplasia.
Figure 39.2 The karyotype of complete hydatidiform mole.
Figure 39.3 Photomicrograph of partial mole showing marked disparity in villous size, trophoblastic inclusions (center), and mild trophoblastic hyperplasia. (From Berkowitz RS, Goldstein OP. Gestational trophoblastic diseases. In: Ryan KJ, BerkowitzR, Barbieri R, eds. Kistner’s gynecology principles and practice, 5th ed. Chicago: Year Book Medical Publishers, 1990:433, with permission.) generally exhibits the stigmata of triploidy, including growth retardation and multiple congenital malformations such as syndactyly and hydrocephaly (Fig. 39.5).
When molar pregnancy is diagnosed early in the first trimester, the pathologist can have difficulty distinguishing complete hydatidiform mole from partial hydatidiform mole or hydropic abortions because of smaller villi, less trophoblastic hyperplasia, more primitive villous stroma, and less global necrosis (19,20). Accurate diagnosis can be facilitated through the use of ﬂow cytometry to determine ploidy (i.e., diploid vs. triploid moles) (21) and through assessment of biomarkers of paternally imprinted and maternally expressed gene products (22). Biomarkers that take advantage of imprinted genes to distinguish complete mole and hydropic abortions from other gestations are identified. Because complete moles generally have no maternal chromosomes, paternally imprinted gene products normally expressed only by maternal chromosomes, should be absent. In complete moles, the nuclei of the villous stroma and cytotrophoblastic cells do not express p57, whereas all other gestations, including partial moles, are characterized by nuclear immunostaining in these cells. Thus, a complete mole is diploid and negative for p57, a hydropic abortion is diploid (sometimes triploid) and positive for p57, and a partial mole is triploid and positive for p57.