Placental Mesenchymal Dysplasia, An Exceedingly Rare Entity and Challenging Diagnosis

Introduction/Objective Placental mesenchymal dysplasia (PMD) is an extremely rare entity with an incidence of only 0.02/1000 deliveries. Methods/Case Report We present a case of a 26 year-old female Gravida 3, Para 1 with intrauterine pregnancy at 37 weeks of gestation. Fetal ultrasound showed mildly cystic upper portion of the placenta. The noninvasive prenatal testing was negative for triploidy. A viable healthy female infant was delivered with no maternal complications. On gross examination, placenta was heavy with approximately 25% incomplete cotyledons. Placental maternal surface showed, spongiform cut surfaces admixed with multiple cystic structures ranging in size from 0.5 to 1.5 cm and markedly dilated blood vessels. Histopathologic examination revealed markedly enlarged villi, mesenchymal hyperplasia, and hyper vascularity of small vessels. No trophoblast proliferation was identified. Subsequently, the diagnosis of PMD was made. Results (if a Case Study enter NA) NA Conclusion PMD is a rare anomaly which is characterized by placentomegaly and grape like vesicles resembling molar pregnancy. Etiologies include imbalance of paternal and maternal alleles, androgenetic and bi-parental mosaicism, and Beckwith Weidman Syndrome (BWS). Differential diagnosis includes partial molar pregnancy, complete mole with co-existing normal fetus, hemangioma, subchorionic hematoma, confined placental mosaicism and hydropic complications. Histologic features, ancillary studies including immunohistochemistry and genetic testing are helpful in differentiating PMD. PMD is an underdiagnosed entity with increased risk of premature delivery and intrauterine fetal death. It is pertinent for the clinicians to be aware of this entity for optimal patient management.

Placental mesenchymal dysplasia- A case report

Placental mesenchymal dysplasia is a rare disorder mainly characterized by enlarged placenta. Patients on antenatal visits present with normal or slightly raised Beta-HCG, raised Alfa-fetoprotein and cystic structures on USG resembling a molar pregnancy. It has to be differentiated from molar pregnancies to avoid unnecessary termination of pregnancy. This condition is associated with IUGR or IUFD. Mostly the fetus are females. Due to lack of awareness of this condition it remains underreported. Here we present a case report of 20 years old female 37 week pregnant with IUGR with clinical suspicion of molar pregnancy gave birth to alive female fetus and on histopathological examination of placenta was diagnosed with PMD.

Fetal Beckwith-Wiedemann syndrome associated with abnormal quad test, placental mesenchymal dysplasia and HELLP syndrome

We describe a unique case of Beckwith-Wiedemann syndrome (BWS). A 29-year-old woman with ultrasound and clinical findings, specific to BWS is described. Important insights gained from this study are as follows: (1) quad test may be very useful to increase awareness of BWS. This is the first report, which demonstrated that elevated inhibin-A is related to BWS. Unexplained elevation of serum biomarkers, especially all the four markers, should raise awareness of BWS. (2) Early provisional diagnosis in this case was based on the findings of omphalocele, placental mesenchymal dysplasia and abnormal quad test. (3) Follow-up scans are important for late-occurring supportive findings, such as macroglossia, ear abnormalities and visceromegaly. (4) BWS is strongly associated with preeclampsia, which tended to be more severe and of earlier-onset. (5) Molecular genetic analysis is helpful, but not always necessary in cases of fulfilment of clinical criteria like in this case.

Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.