The main differential diagnoses of PMD are partial hydatidiform mole, dichorionic twins of a normal fetus and complete mole, and confined placental mosaicism. When a prenatal ultrasonographic examination detects a vesicular lesion in the presence of a fetus in uterus, whether a single or twin pregnancy is present should be determined. A twin pregnancy would consist of dichorionic twins of a normal fetus and complete mole. In the present case, ultrasound appeared to reveal a single pregnancy. Unlike partial moles, the majority of PMD are diploid . In 70 - 80% of cases, the partial moles are triploid, often with 2 sets of paternal genes and 1 set of maternal genes as a result of dispermy fertilization . Cases of confined placental mosaicism involving trisomy 16 have been reported as exhibiting cystic villi on ultrasound, but these cases can be diagnosed accurately by karyotyping . In the present case, an amniocentesis performed at 15 weeks' gestation showed a normal female karyotype, 46XX. The characteristic laboratory test for PMD includes an increased level of maternal serum AFP. The increase in the surface transfer area as a result of the increased placental volume and the increased number of vessels within the stem villi is thought to lead to an increased transfer of AFP into the maternal circulation . On the other hand, unlike with moles, the level of hCG in patients with PMD is normal to slightly increased throughout gestation . In this case, although the maternal hCG level was normal throughout gestation, the serum AFP level increased as her pregnancy progressed. These prenatal findings suggested a diagnosis of PMD.
The placenta is usually extremely large for the gestational age and the umbilical cord is relatively long in cases with PMD [2, 3]. The gross placental findings for PMD vary with gestational age. To our knowledge, no previous report has detected a vesicular lesion in a patient with PMD prior to 13 weeks' gestation. In the present case, a vesicular lesion was detected at 8 weeks' gestation. Thus, the morphological changes in the villi appear to begin early during gestation. During the third trimester, the chorionic plate vessels in a PMD placenta are aneurysmally dilated and tortuous . However, in cases terminated before 20 weeks of gestation, the chorionic plate vessels are not dilated, and the normal and abnormal areas are not clearly delineated, suggesting that the vascular malformations develop progressively . As the pregnancy advances, tangled congested vessels grossly resembling gray-white or dark-red wormlike structures may be identified within the parenchyma and are often most prominent in the subchorionic plate region near the fetal surface . An ultrasound performed at 33 weeks' gestation seemingly detected this finding (Figure 2).
Although morphologic gross findings of PMD placentas are so often mimicked by features of partial hydatidiform moles, PMD placentas are markedly enlarged and macroscopic vascular anomalies such as cirsoid dilated chorionic vessels with or without thrombi and umbilical cord anomalies like a long umbilical cord that were observed in our case are often co-existence in PMD placentas, but they are not usual in molar pregnancies [2, 13]. Microscopically, PMD placentas typically reveal large stem villi with hydropic swelling and cistern formation interspersed with unaffected terminal villi. Similarly, mixture of hydropic villi with cistern formation and unaffected villi are also found in partial hydatidiform moles, however, trophoblastic stromal inclusions and proliferations, which are absent in PMD placentas, are also characteristic of molar pregnancies. Not only macroscopic but also microscopic vascular anomalies such as fetal thrombotic vasculopathy that was found in our case, villous chorangiosis and chorangioma, are also characteristic together hydropic villi in PMD placentas, but not in molar pregnancies [2, 3, 13]. These morphological characteristics of PMD placenta supported to diagnose our case as PMD. Immunohistochemistry using antibodies against products of paternal imprinting genes such as the antibody against p57kip2 protein is a potential marker that may prove helpful in distinguishing PMD from molar pregnancy. The immunohistochemical detection of androgenetic/biparental mosaicism in stromal cells suggests to a diagnosis of PMD, because this mosaicism is unusual in molar pregnancies . Dichorionic twin placentas with a normal fetus and complete mole may also be needed to pathologically distinguish to PMD. But, vascular anomalies seen in PMD placentas are absent in their placentas and complete moles are purely androgenetic. Spontaneous abortion with hydropic change may have vesicle formation and can also be confused with early PMD, however, the vesicles, if present, are usually small. Also, spontaneous abortion shows degenerative changes .
PMD has distinct clinicopathological features. According to Truc et al. , 82% of the affected fetuses are female and about 20% of cases with PMD also have BWS. Among the PMD cases without BWS, the FGR and the IUFD rate are 50% and 36%, respectively. IUFD can occur throughout gestation (before 21 weeks, 14.3%; 22~27 weeks, 23.8%; 28~33 weeks, 33.3%; after 34 weeks, 28.6%). The cause of IUFD is currently unclear and may be heterogeneous. Thrombosis of chorionic vessels and umbilical cord anomalies are thought to be likely causes of IUFD in PMD cases, and Truc et al. reported that IUFD may be explained by a potentially chronic hypoxia secondary to obstructive fetal vascular thrombosis and a decrease in maternal-fetal gas exchange as a result of an insufficient amount of normal chorionic villi and the shunting of blood from the exchange surface in chorioangiomas and dysplastic villi . In our case, histological examination revealed that the dilated cirsoid chorionic vessels were fragile and that part of the vessel wall had ruptured, resulting in hemorrhage with hematoma formation. Although fetal thrombotic vasculopathy was found in a part of the affected lesion, this hemorrhage was thought to have led to sudden death of the fetus at the late gestational age (36 weeks 5 days) because no significant chronic hypoxic anomaly of the fetus including FGR was observed.
The underlying cause of PMD is currently unknown. Recently, Kaiser-Rogers et al. proposed androgenetic/biparental mosaicism as the origin of some cases of PMD and suggested that the phenotype of androgenetic mosaicism can presumably range from mild PMD, which may not even be diagnosed, to the typical findings of a complete hydatidiform mole, depending on the extent and distribution of the androgenetic lineage . The authors hypothesized that such mosaicism arose as the result of a failure in the replication of the maternal genome prior to the first cleavage, with normal replication and segregation of the paternal genome, resulting in two types of daughter cells, one with normal biparental genes and the other with only paternal genes. Such failed division would produce a diploid/haploid mosaic embryo, and endoreduplication of the haploid paternal-only daughter cell could then occur to produce the diploid androgenetic lineage, while the female and male haploid complements would merge to form a daughter cell with normal biparental inheritance. The phenotypic features of PMD, including the preponderance of females, the absence of trophoblastic hyperplasia, and the association with BWS, can all be explained by this mechanism. Since an androgenic 46, YY cell line would be nonviable, PMD cases would show the marked female predominance. The abnormal androgenetic cells would be confined to the chorionic mesoderm, membranes, and vessels, whereas the trophoblastic cells would be normal with no evidence of androgenetic cells . This feature would explain the absence of trophoblast overgrowth in PMD in contrast to complete moles, in which androgenetic cells are identified in the trophoblastic cell layer. BWS is a condition of constitutional overgrowth with genetic linkage to chromosome 11p15.5. . Insulin-like growth factor-2 is located in this lesion, and the maternal allele is normally suppressed so that only the paternal gene is expressed. Thus, the loss of 11p15.5. gene imprinting could lead to PMD in some cases.