Placental mesenchymal dysplasia is a rare, benign condition that shows an enlargement of the placenta with multiple vesicles that can resemble a molar pregnancy by ultrasound and gross pathologic examination. Clinical presentation is various, and fetal anomalies and fetal overgrowth can be associated with this condition. MRI could help differentiate between a complete hydatidiform mole with coexistent fetus. We present a case of a 26-year-old patient, primiparous, with sonographically suspicious hydatidiform mole. In the 16th week of pregnancy, her β-HCG levels were normal and alpha-fetoprotein values were elevated. TORCH, Parvo B-19, Lysteria, Brucellosis, and TPH were negative. Amniocentesis showed normal fetal karyotype, and triploidy, e.g. molar pregnancy was excluded. Chromosomal microarray was also normal. Serial ultrasound exams were performed with normal fetal growth pattern, extremely enlarged placenta, and lower amount of amniotic fluid. MRI showed normal fetal morphology and enlarged, multicystic placenta (AP diameter 99 mm). The delivery by emergency Caesarean section was conducted at 31 weeks of gestation due to premature rupture of fetal membranes, spontaneous onset of labour, and fetal asphyxia. An alive female fetus was born, length of 39cm, weight of 1160g, and head circumference of 28cm, Apgar score was 6/7. Placental weight was 1312g, the size was 20 × 19 × 4.5-6cm, with tumour-like formation 12 × 8 × 1cm resembling an old organised hematoma. Placental tissue was diffusely but unevenly permeated with vesicles filled with gelatinous content 5-20mm in diameter. Seventy percent of placental parenchyma was formed from devitalised, degeneratively changed and very enlarged chorionic villi with totally attenuated trophoblast. Regarding possible complications of pregnancy, placental mesenchymal dysplasia requires a comprehensive and multidisciplinary approach.
Molar pregnancy; Placental mesenchymal dysplasia; Trophoblast
Placental mesenchymal dysplasia is a rare, benign condition that shows an enlargement of the placenta with multiple vesicles that can resemble a molar pregnancy by ultrasound and gross pathologic examination [1]. Its prenatal ultrasonographic and gross pathologic features resemble those of a partial mole, but the fetus is typically normal and the placenta has a diploid, chromosomal complement. The disease etiology of the disease is poorly understood. It is characterized by aneurysmal dilatation of the chorionic blood vessels, mesenchymal proliferation, and myxomatous degeneration of the stem villi. Hyperplasia of the mesenchymal tissues, myxomatous degeneration of the stem villi, and absence of trophoblastic proliferation made the diagnosis of Placental mesenchymal dysplasia the most appropriate [2].
This condition is more than 3.5 times more often seen in female fetuses. Clinical presentation is various, from uneventful pregnancy with postnatal pathologic finding of Placental mesenchymal dysplasia, incidental ultrasonographic abnormalities of the placenta, elevated maternal serum alpha-fetoprotein concentrations, fetal growth restriction, fetal demise, vaginal bleeding, and preterm delivery. Fetal anomalies (fetal liver cysts or vascular malformations) and fetal overgrowth with Beckwith-Wiedemann syndrome, featuring placentomegaly, omphalocoele, macroglossia, visceromegaly and high incidence of embryonic tumors such as Wilm’s tumor and neuroblastomas can be associated with this condition. Although it shares radiological and gross pathological features with partial hydatidiform mole, Placental mesenchymal dysplasia doesn't necessitate termination of pregnancy.
Most frequent congenital anomaly (23% of cases) associated with Placental mesenchymal dysplasia is Beckwith-Wiedemann syndrome. Other congenital anomalies that occur in association with Placental mesenchymal dysplasia are type I diabetes mellitus, uniparental disomy 6, trisomy 13, and Klinefelter syndrome [3]. Ultrasound finding is characterized by the thickening of the placenta with multiple cystic or hypoechoic areas. Doppler findings are variable, sometimes in cases with no vascularity within the lesion further development of vascularity within can be seen possibly due to progressive dilatation of chorionic arteries and veins that become aneurysmal. MRI could help differentiate between a complete hydatidiform mole with coexistent fetus by demonstrating placental mesenchymal dysplasia as multicystic lesions within the placenta of the fetal sac, while in molar pregnancy lesions are located within an extra fetal sac.
Placental mesenchymal dysplasia is characterized by the presence of dilated chorionic blood vessels which may be complicated by thrombosis, rupture, or hemorrhage. These vascular lesions attribute to intrauterine growth retardation and fetal death which frequently occur in association with Placental mesenchymal dysplasia [4]. ¾ of cases of Placental mesenchymal dysplasia was diagnosed in the 2nd trimester. Dilatation of the fetal chorionic vessels becomes manifest in the 3rd trimester in most of the reported cases, which may be responsible for the sudden intrauterine fetal death which is frequently observed in this gestational period, especially if the fetus didn't show gross anomalies [5].
The etiology of Placental mesenchymal dysplasia is not fully understood and several theories were adopted. The first theory postulated that Placental mesenchymal dysplasia is a congenital malformation of the mesoderm. This theory was strongly supported by the microscopic features of Placental mesenchymal dysplasia as there is mesenchymal hyperplasia in the stem villi, myxomatous degeneration in the villous stroma, and thick fibro-muscular walls of the chorionic vessels. Other evidence which supports this theory is the frequent association between Placental mesenchymal dysplasia and Beckwith-Wiedemann syndrome which is characterized by overgrowth. The second theory postulated that Placental mesenchymal dysplasia results from hypoxic conditions which occur during pregnancy due to undetermined causes. Hypoxia stimulates the production of hypoxia-inducible factors which in turn stimulate the production of vascular endothelial growth factor and angiogenesis. Hypoxia also stimulates fibroblasts to produce connective tissue fibers [6].
There have also been reports of umbilical cords, including tortuous, marked twisted cords, and excessively long cords. Absence of trophoblastic proliferation in Placental mesenchymal dysplasia placentas is the main histological difference from partial moles. Moreover, the enlargement in the surface transfer area as a result of the increased placental volume and number of vessels within the stem villi is thought to lead to an increased transfer of AFP into the maternal circulation. Differential diagnoses include partial molar pregnancy, hydropic degeneration of the placenta, complete hydatidiform mole with coexistant fetus, chorioangioma, subchorionic hematoma, placental infarcts, and spontaneous abortion with hydropic changes.
Prenatal recognition of Placental mesenchymal dysplasia during early and late gestation could prevent unnecessary termination of pregnancy [7]. The outcome of the fetus is variable ranging from a completely normal fetus to an increased risk of IUGR or fetal demise. It is important to distinguish Placental mesenchymal dysplasia from a partial mole with an abnormal triploid fetus because this diagnosis may result in termination of pregnancy due to significant morbidity to the mother (persistent gestational trophoblastic disease). This condition is associated with intrauterine growth restriction and intrauterine fetal demise. The cause of fetal death in many cases is fetal vascular obstructive pathology causing longstanding, severe fetal hypoxia characterized by chorionic vessel thrombosis [8].
We present a case of a 26-year-old patient, primiparous, who was admitted to our hospital in the 16th week of pregnancy with vaginal bleeding and a sonographically suspicious hydatidiform mole. Associated medical conditions were hypothyreosis and thrombophilia (MTHFR and PAI-1 homozygote). In the 16th week of pregnancy, her beta hCG levels were in the normal reference range and alpha-fetoprotein values were elevated (223.5mcg/L). TORCH analysis performed in the 13th week of gestation showed no active infections. Microbiological testing conducted later, including Parvo B-19, Lysteria, Brucellosis, and TPH were also negative. Genetic analysis of amniotic fluid performed in the 16th week of pregnancy shoved normal fetal karyotype, and triploidy, e.g., molar pregnancy was excluded. Microarray analysis performed in the 20th week of gestation was also normal.
Ultrasound findings at admittance showed normal fetal growth and morphology with an enlarged placenta with multiple avascular cystic changes. Serial ultrasound exams were performed weekly, with normal fetal growth pattern, extremely enlarged placenta, occupying a large portion of the uterine cavity, and, with time diminished amount of amniotic fluid, making the fetus squeezed between the uterine wall and the placenta. MRI examination conducted in the 24th week of gestation showed normal fetal morphology and enlarged, multicystic placenta (AP diameter 99mm), and reduced amount of amniotic fluid. Since the fetal growth was normal, and the condition of the patient stable we decided on expectant management. In the 28th week of gestation, artificial maturation of the fetal lungs using the Dexamethason protocol was performed.
The delivery by emergency cesarean section was conducted in 31st week of gestation due to premature rupture of fetal membranes, spontaneous onset of labor, and fetal asphyxia. An alive female fetus was born, length of 39cm, weight of 1160g, and head circumference of 28cm, Apgar score was 6/7. The procedure went uneventfully, and after the standard postoperative course, our patient was discharged from the hospital five days after the delivery. The newborn was taken care of regarding prematurity protocols. Pathohistological finding: Placental weight was 1312g, the size was 20x19x4.5-6cm, with tumor-like formation 12x8x1cm resembling an old organized hematoma. Insertion of the umbilical cord was paramarginal, with three blood vessels. Placental tissue was diffusely but unevenly permeated with vesicles filled with gelatinous content 5-20mm in diameter. 30% of placental parenchyma was formed from vital chorionic villi of regular histological structure. The remaining parenchyma was made of devitalized, degeneratively changed and very enlarged chorionic villi, some of them formed only from blood vessels without stroma resembling chorangioma or vascular malformations. Some of them have central cistern which make the most of the villi. The trophoblast of this villi was totally attenuated. Part of the big stem villi has loose myxoid stroma with numerous fibroblasts. Pathohistological diagnosis: Dysplasia mesenchymal placentae.
Placental mesenchymal dysplasia is a rare condition, but regarding possible complications of pregnancy, it requires a comprehensive and multidisciplinary approach. Definitive diagnosis in most cases can be made only after pregnancy termination, so in order to achieve a good perinatal outcome focus must be directed to the mother and fetal wellbeing using all available diagnostic tools (Figures 1-3).
Figure 1: Ultrasound appearance of the placenta in 24th and 28th week of gestation.
Figure 2: MRI appearance of the placenta in 24th week of gestation.
Figure 3: Gross appearance of placenta with mesenchymal dysplasia with characteristic grape-like vesicles.
Placental mesenchymal dysplasia is a rare placental disease with chorionic vascular abnormalities. It is characterized by placentomegaly and placental cystic spaces similar to those in partial Hydatidiform mole [9]. The incidence is about 0.02% of all pregnancies, but it is probably underestimated [10]. It was introduced in 1991 as stem villous hyperplasia with elevated maternal serum alpha fetoprotein levels and enlarged placentas with corresponding ultrasonographic features resembling the partial mole [11]. There were aneurysmally dilated vessels on the fetal surfaces of the placentas and dilated stem villi filled with clear gelatinous material in the subchorionic region. Histologically these placentas are distinguished from partial moles due to absence of trophoblastic proliferation.
Placental mesenchymal dysplasia was previously know as “placentomegaly with massive hydrops of placental stem villi” and “Pseudopartial moles”. The incidence is estimated to be 0.02%, but it is probably underdiagnosed and underreported [12]. Placental mesenchymal dysplasia represents a congenital malformation of the mesoderm. About 23% of Placental mesenchymal dysplasia cases are associated with Beckwith-Wiedemann syndrome, so they are considered as phenotypic changes of common etiology. In some cases phenotypic changes of Placental mesenchymal dysplasia are limited to the placenta and Beckwith-Wiedemann syndrome, in others they are affecting both placenta and fetus [13].
Androgenetic/biparental mosaicism has been proposed as the cause of Placental mesenchymal dysplasia. Abnormal expression or disruption of 1 or more of the imprinting genes on chromosome 11p15.5 (Beckwith-Wiedemann syndrome candidate gene) might be the major underlying problem. The most commonly involved genes are CDKN1C (p57KIP2), H19, IGF-II, and KVLQT. In Placental mesenchymal dysplasia without fetal anomalies, the underlying 11p15 abnormality is confined to the placenta. The genomic imprinting of these genes is influenced by parent of origin. The CDKN1C (p57KIP2) gene is expressed in the maternal genome, whereas the paternal allele is transcriptionally silent [14].
The overgrowth of the placental tissue is due to abnormalities of Insulin-like growth factor II (IGF-II) gene or IGF-II receptor gene leading to up-regulation of IGF-II. Overproduction of IGF-II is the result of an aberration in normal maternal suppression or, in rare cases, because of the presence of two paternal copies of the IGF-II gene. It is suggested that IGF-II and p57KIP2 act in the same pathway but in an opposing manner to control the cell cycle. A gain in function of IGF-II or a loss in the function of p57KIP2 would have similar effect - somatic overgrowth [15]. Hypoxia and hypoperfusion of unknown etiology may give rise to the phenotypic findings in placentas with Placental mesenchymal dysplasia. During hypoxia, fibroblasts are stimulated to produce increased connective tissue fibers with subsequent increased production of vascular endothelial growth factor by villous macrophages leading to angiogenesis. Vascular Endothelial Growth Factors (VEGFs) have a major role in normal angiogenesis, while increased angiogenesis lead to of vascular malformations described in Placental mesenchymal dysplasia [16].
There is no specific clinical symptomatology associated with Placental mesenchymal dysplasia. Most cases of Placental mesenchymal dysplasia in early pregnancy are diagnosed prenatally by ultrasound during routine prenatal checkup. Elevated level of maternal serum alpha fetoprotein, which is of fetal origin, is due to increase in the surface transfer area because of enlarged placental volume and vessels within the stem villi. The level of β-human chorionic gonadotropin is usually normal or slightly increased throughout gestation. Later in the pregnancy common finding is fetal growth restriction or fetal demise. In some cases polyhydramnios are observed because fetus has swallowing difficulty as part of Beckwith-Wiedemann syndrome. Many cases are asymptomatic and are diagnosed postpartum after the delivery of an abnormally large placenta. The placenta is thickened with multiple cystic or hypoechoic areas. Doppler findings are variable. There are many documented cases of no vascularity within the lesion and further development of vascularity within. These changes could be due to progressive dilatation of chorionic arteries and veins that become aneurysmal [17].
Placental mesenchymal dysplasia should be included in the differential diagnosis of cystic lesions of the placenta on USG. Placenta may appear thickened. The placenta of a complete mole with coexisting normal fetus and partial molar pregnancy appears heterogeneous, with partially solid and cystic areas. On USG, a chorioangioma is a focal lesion and is hypoechoic compared to the rest of the placenta. It is typically located on the fetal surface of the placenta [13]. Placental mesenchymal dysplasia in the first trimester shows no blood flow in the cystic spaces of the placenta on color Doppler. However, in the third trimester, large vascular areas with turbulent blood flow are observed (either arterial or venous), which are located mainly under and at the level of the chorionic plate. These changes are due to the progressive dilatation of chorionic arteries and veins, which become aneurysmal [18]. Low or absent venous signals may be associated with Placental mesenchymal dysplasia during the first two trimesters, as seen in our case also.
On color Doppler, high velocity and low resistance flow is seen in the molar mass and large feeding vessel or increased vascularity is seen in the mass of chorioangioma, although no blood flow is seen within the mass in hematoma [19]. Differentiation of Placental mesenchymal dysplasia from a twin pregnancy with a complete mole and coexistent fetus is difficult. On the first trimester sonography, documentation of two gestation sacs, a lesion that constitute the entire thickness of the placenta, and the lack of blood flow signals suggest the diagnosis of complete mole with coexistent fetus. The sonographic finding of thickened placenta with hypoechoic spaces are classical sonographic findings of both Placental mesenchymal dysplasia and molar pregnancies. The other differential diagnoses o include chorioangiomas and subchorionic hematomas. The finding of a large cystic placenta with phenotypically well-formed fetus is highly unlikely in molar pregnancy and should raise the suspicion of Placental mesenchymal dysplasia [18]. MRI could helpful in differentiation between Complete Hydatidiform Mole with Coexistent Fetus (CHMCF) by demonstrating Placental mesenchymal dysplasia as multicystic lesions within the placenta of the fetal sac, and CHMCF with multicystic lesions located within an extra fetal sac [20].
Invasive testing (chorionic villus sampling or amniocentesis) should be performed to confirm a normal karyotype and exclude partial molar pregnancies. Partial molar pregnancies demonstrate triploidy, which is rare in Placental mesenchymal dysplasia. Triploidy associated with Placental mesenchymal dysplasia is presumed to occur either as a result of maternal-derived triploidy or due to placental mosaicism. Low incidence of aneuploidy may occur in association with Placental mesenchymal dysplasia. Cohen et al., reviewed a total of 66 cases of Placental mesenchymal dysplasia. Normal karyotype was seen in 78% of the cases, chromosomal abnormalities in 3 cases (Trisomy13, Klinefelter syndrome and triploidy), and Beckwith-Wiedemann syndrome in 15 cases (23%) [13]. Although ß-HCG levels are always elevated in molar pregnancies, Placental mesenchymal dysplasia may also present with increased ß-HCG levels. Placental mesenchymal dysplasia is more likely to be associated with elevated maternal serum AFP levels, as seen in our case.
In gross examination the placenta is usually extremely large for gestational age, in more than 90% of the cases placental weights of more than the 90th percentile. In both early and late gestation Placental mesenchymal dysplasia, placental parenchyma may have pale and friable areas with streaks of prominent stem villi and multiple cysts oriented perpendicular to the chorionic plate, like seen in molar pregnancis are size from 0.3 to 2.5 cm and are usually visible grossly, which carries significant morbidity to the mother (persistent GTD). Despite its resemblance to partial moles on gross examination, Placental mesenchymal dysplasia can be distinguished from the former by careful histologic examination. The histopathologic findings in placentas with Placental mesenchymal dysplasia are similar irrespective of fetal association with Beckwith-Wiedemann syndrome and vary with the gestational age. Third trimester Placental mesenchymal dysplasia placentas have dilated thick-walled chorionic plate vessels with fibromuscular hyperplasia and may have fresh or organizing thrombi with varying degrees of luminal obliteration [21].
Thrombosis may be present in both the veins and arteries of the chorionic plate. The vessel walls usually show some degree of fibrinoid necrosis. The parenchymal vascular malformations show dilated vessels and may have fresh or organizing thrombosis. The stem villi are enlarged in both early and late gestation Placental mesenchymal dysplasia placentas and, at times, may be up to 10 times the size of normal stem villi late in gestation. These enlarged stem villi have central cisterns filled with gelatinous material and fibromuscular vessels at the periphery. These thick-walled vessels develop during time as pregnancy advances and may show fibrinoid necrosis and degenerative changes in the vessel wall. Irrespective of gestational age, the stem villi in Placental mesenchymal dysplasia have loose and myxoid stroma with an overgrowth of fibroblasts and foci of myxoid degeneration unlike the normal stem villi, which are mostly fibrous. Similar to the stem villi, the terminal villi may also show mesenchymal cell hypercellularity and stromal fibrosis. However, scattered between dilated stem villi may be a mixture of normal-appearing and hydropic secondary and tertiary villi. Early in gestation these changes are not as well-developed and the stem villi show dilated cisterns surrounded by loose myxomatous stroma, which has delicate vessels under the trophoblastic layer. Some stem villi reveal intravillous fibrin deposition and lack distinct fetal vessels because of fetal vessel thrombosis. Recanalization of stem villus thrombosed vessels has also been described.
The important diagnostic features of Placental mesenchymal dysplasia include the absence of trophoblastic proliferation, stromal trophoblastic inclusions, and scalloping of the villous surface, which are characteristics of a molar pregnancy. The vascular pattern in the hydropic villi in Placental mesenchymal dysplasia range from normal to chorangiomatosis or myxoangiomatous to decreased or obliterated vasculature. Discrete chorangiomas may be identified. In rare cases, extramedullary hematopoiesis is identified. Nucleated red cells are seen mostly in areas of chorangiosis/chorangiomas at a stage when nucleated red cells are not normally seen in the fetal vessels. These changes are thought to represent a consequence of placental hypoxia. Villous hemorrhage has been identified in some cases.
The diagnosis of Placental mesenchymal dysplasia is only confirmed after evaluation of placental pathology. Grossly, it is characterized by placentomegaly, dilated or aneurysmal chorionic vessels, and fibromuscular hyperplasia or cystic villi [22]. Microscopic findings include mesenchymal hyperplasia and edema of stem-cell villi, which contain thick-walled vessels. These findings were seen in the present case along with characteristic absence of trophoblastic hyperplasia, which is a diagnostic hallmark of GTD. The villi do not show proliferation of trophoblasts or stromal trophoblastic inclusions in Placental mesenchymal dysplasia. There are no abnormal fetal vessels in the stem villi seen in cases of twin pregnancies with one complete mole, as in Placental mesenchymal dysplasia.
Stromal cells in the large stem villi of Placental mesenchymal dysplasia placentas are positive for vimentin and desmin and negative for alpha-smooth muscle actin, whereas the stromal cells in the surrounding normal-appearing stem villi are positive for vimentin, desmin, and α-smooth muscle actin. There is also a strong reaction to Alcian blue stains indicating the presence of large amounts of acid mucopolysaccharides. Macrophages in the stroma also contain Alcian blue positive vacuoles in their cytoplasm. The p57KIP2 protein is a potential marker that may prove helpful in distinguishing Placental mesenchymal dysplasia from molar pregnancy [23]. Some immunohistochemical and invasive tests are helpful for the diagnosis of Placental mesenchymal dysplasia. Immunohistochemical tests using antibodies against p57K1P2 protein (an imprinting gene only expressed in the maternal genome) might prove helpful in distinguishing Placental mesenchymal dysplasia from molar pregnancies [24]. In a complete mole, the villous cytotrophoblastic cells lack maternal genome and are negative for this test [25].
This placental anomaly is more commonly associated with a 46,XX karyotype. Comparable placental histopathological features in cases of mesenchymal dysplasia with or without congenital anomalies diagnostic of Beckwith-Wiedemann syndrome suggest that in some of these cases the overgrowth of specific fetal tissue is limited to the placenta and the fetus remains unaffected. Histological similarity between mesenchymal dysplasia and cellular chorioangioma suggests a common embryologic origin for both these placental abnormalities [18]. Previous studies have described the characteristic placental pathology and the possible genetic basis for the placental abnormality in Placental mesenchymal dysplasia. Placental mesenchymal dysplasia cases with Beckwith–Wiedemann syndrome are associated with paternal isodisomy of the 11p15.5 region. In addition to association with Beckwith-Wiedemann syndrome, there are multiple case reports in the literature describing the coexistence of Placental mesenchymal dysplasia with fetal hepatic mesenchymal tumors, suggesting a common pathogenetic origin for the two anomalies [14].
The majority of the cases where cytogenetics analyses were performed were diploid [26]. In contrast to Placental mesenchymal dysplasia, the majority of the partial moles are triploid, so DNA ploidy studies are not be helpful in distinguishing Placental mesenchymal dysplasia from complete moles or spontaneous abortions with hydropic changes because most of these cases will have a diploid karyotype. Most are karyotypically and phenotypically normal females (46, XX). With rare exceptions, no major chromosomal abnormalities are identified. In some trisomy 13, Klinefelter syndrome (47, XXY), triploidy (69, XXX), and 46, XXp- were found.
Distinguish Placental mesenchymal dysplasia from molar pregnancy is important to avoid unnecessary termination of pregnancy especially in cases suggestive of molar pregnancy with morphologically normal fetus. The main differential diagnoses of Placental mesenchymal dysplasia are partial hydatidiform moles, a twin gestation with complete mole, spontaneous abortion with hydropic changes, and confined placental mosaicism. The placenta in Placental mesenchymal dysplasia is almost always diploid and histologically the villi do not show proliferation of trophoblasts or stromal trophoblastic inclusions. The triploid fetus associated with a partial mole shows growth restriction with a variety of external and internal defects. In twin gestations with complete moles, the abnormal fetal vessels in the stem villi characteristic of Placental mesenchymal dysplasia are absent even though the fetus may have a diploid karyotype. Complete hydatidiform moles may also exhibit high levels of IGF-II expression and loss of expression of p57KIP2, but these are purely androgenetic and the entire genome is paternally derived. Spontaneous abortion with hydropic change may have vesicle formation and can be confused with early Placental mesenchymal dysplasia. The vesicles in hydropic spontaneous abortion, if present, are usually small and are not diffuse. Second, the histology of spontaneous abortions shows degenerative changes without the classic histopathologic features of Placental mesenchymal dysplasia [27].
It is very difficult to determine whether the complications of pregnacies with Placental mesenchymal dysplasia are true complications of the disease or just coincidental findings. Because approximately one fourth of cases of Placental mesenchymal dysplasia are associated with Beckwith-Wiedemann syndrome, some of the complications seen in fetuses born with Placental mesenchymal dysplasia are secondary to Beckwith-Wiedemann syndrome without fully developed phenotypic features. For example, hyperinsulinemic hypoglycemia seen in neonates with Placental mesenchymal dysplasia is secondary to islet cell hyperplasia of the pancreas, which is a frequent finding in Beckwith-Wiedemann syndrome [28]. The common fetal complications reported in phenotypically normal fetuses associated with Placental mesenchymal dysplasia are prematurity, intrauterine growth restriction, and intrauterine fetal demise. Severe intrauterine growth restriction may be related to diversion of fetal blood within the vascular malformations or stem villi blood vessel thrombosis resulting in hypoperfusion and hypoxia that ultimately leads to intrauterine growth restriction [29].
Although many obstetrical complications such as polyhydramnios, fetal hydrops, gestational diabetes, and pre-eclampsia may be associated with a large placenta, placentomegaly in Placental mesenchymal dysplasia, in and of itself, is thought not to be the cause of fetal complications [18]. The causes of Intrauterine Fetal Death (IUFD) currently remain unclear and may be heterogeneous. Thrombosis of chorionic vessels and umbilical cord anomalies are thought to be likely causes of IUFD in Placental mesenchymal dysplasia cases, and IUFD may be explained by a potentially chronic hypoxia which is a consequence of obstructive fetal vascular thrombosis and a decrease in maternal-fetal gas exchange as a result of an insufficient amount of normal chorionic 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 a hemorrhage and the formation of a hematoma. Although fetal thrombotic vasculopathy was found in a part of the affected lesion, this hemorrhage was thought to have provoked sudden death of the fetus at late gestational age (31 weeks) because no significant chronic hypoxic anomaly of the fetus, including growth restriction, was observed [30].
No direct association of placental weight and fetal or maternal complications have been identified. Rather, the complications are thought to be related to the degree of vascularity and excessive vascular shunting into the chorangiomatosis areas. Cases associated with chorangiomas are thought to be associated with a higher rate of fetal complications including anemia and thrombocytopenia, which in turn are thought to be secondary to microangiopathic hemolytic anemia because of abnormal shunting of the blood [31]. Chromosomal abnormalities may be found in a few fetuses, but most are karyotypically and phenotypically normal females. Rare cases of fetal congenital adrenal hyperplasia, vascular hamartoma, and hepatic mesenchymal hamartoma have been described. Phenotypically normal newborns with Placental mesenchymal dysplasia should be followed up for development of Beckwith-Wiedemann syndrome features or other mesenchymal tumors. Follow-up of most of the normal-appearing infants has shown no developmental problems.
Maternal complications associated with Placental mesenchymal dysplasia are comparatively rare. Gestational proteinuric hypertension has been reported, but it is believed that hypertension in these cases is probably a coincidental finding rather than any specific association with Placental mesenchymal dysplasia. Similarly, polyhydramnios may occur as a result of swallowing-related problems because of macroglossia in a Beckwith–Wiedemann syndrome fetus. A 5-year follow-up of mothers with Placental mesenchymal dysplasia showed no sign of trophoblastic disease or recurrence of Placental mesenchymal dysplasia in subsequent pregnancies [3]. However, it should be noted that 15% of Beckwith-Wiedemann syndrome cases are familial, and theoretically there is a small increased chance of having recurrence of Placental mesenchymal dysplasia in such families.
Although Placental mesenchymal dysplasia may be associated with fetal growth restriction or paradoxically with features of overgrowth, it is important to identify these cases prenatally to reduce fetal morbidity and mortality. It is also important to recognize the detailed gross and histopathologic features of this rare disease entity and be able to differentiate this condition from cases presenting as possible partial hydatidiform moles especially in the first half of pregnancy. Prenatal recognition of Placental mesenchymal dysplasia during early as well as late gestation could prevent unnecessary termination of pregnancy. Placental mesenchymal dysplasia in early pregnancy is more likely to be mistaken for a partial mole especially by ultrasonographic examination. Ultrasonographic findings suggestive of a molar pregnancy because of hypoechoic spaces in the placenta in the presence of an apparently normal fetus, a fetus with growth restriction, or a fetus with features of overgrowth should raise the possibility of Placental mesenchymal dysplasia.
Because Placental mesenchymal dysplasia is associated with adverse pregnancy outcome, surveillance with serial growth scans, genetic evaluation, and third-trimester assessment of wellbeing should be considered. When the prenatal characteristics of Placental mesenchymal dysplasia are detected (such as an elevated AFP and normal hCG level in the mother, a normal karyotype revealed by villocentesis and dilated subchorionic vessels revealed by ultrasonography during the third trimester), labour at an optimal time before term could be considered, since sudden intrauterine fetal death might occur. An accurate monitoring, including the hospitalization of the patient when necessary, could save the life of the fetus.
Citation: Petronijevic M, Vrzic Petronijevic S, Bratic D, Kadija S, Gojnic Dugalic M, et al. (2024) Placental Mesenchymal Dysplasia - From Diagnosis to Delivery. J Reprod Med Gynecol Obstet 9: 178.
Copyright: © 2024 Petronijevic M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.