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Placental Mesenchymal Dysplasia (PMD) is a rarely encountered placental lesion often associated with high fetal mortality and morbidity. We report here a case of PMD with a favourable outcome. The salient features of diagnosis, management and literature review are discussed.

The paper describes a case of twin pregnancy with complete hydatidiform mole (CHM). According to the data available in the literature, the concurrence of CHM with a normal placenta and a viable fetus occurs in 1 per 20,000-100,000 pregnancies, requires a differential diagnosis with partial hydatidiform mole and placental mesenchymal dysplasia, and is characterized by a high rate of complications. In this concurrence, the frequency of persistent trophoblastic disease is as high as 50%. In this case, the pregnancy ended in a spontaneous abortion at 16-17 weeks of pregnancy. A morphological examination determined the fetus without congenital malformations with normal placental weight and structure and the adjacent intact placental tissue with the macro- and microscopic signs of CHM. The diagnosis was confirmed by the lack of р57 expression in the villous trophoblast and stroma in the tissue of the hydatidiform mole. The patient was diagnosed with persistent trophoblastic disease at 2 months after the abortion.Описано наблюдение полного пузырного заноса (ППЗ) при беременности двойней. Сочетание ППЗ с нормальной плацентой и жизнеспособным плодом, по данным литературы, встречается с частотой 1 случай на 20 000-100 000 беременностей, требует дифференциальной диагностики с частичным пузырным заносом и мезенхимальной дисплазией плаценты, характеризуется высокой частотой осложнений. Частота персистирующей трофобластической болезни достигает при подобном сочетании 50%. В описываемом наблюдении беременность закончилась самопроизвольным выкидышем на сроке беременности 16-17 нед. При морфологическом исследовании определялись плод без врожденных пороков с плацентой нормальной массы и строения и прилежащая к нормальной плаценте ткань, имеющая макро- и микроскопические признаки ППЗ. Диагноз подтвержден отсутствием экспрессии р57 в трофобласте и строме ворсин в ткани пузырного заноса. Через 2 мес после выкидыша у пациентки была диагностирована персистирующая трофобластическая болезнь.

Placental mesenchymal dysplasia (PMD) is an uncommon disorder that has to be differentiated histologically from a partial mole. In contrast to a hydatitiform mole, PMD can coexist with a viable fetus. Placental mesenchymal dysplasia is characterized by placentomegaly and dilatation of the chorionic vessels. In our case, multiple hepatic mesenchymal hamartomas in a preterm were associated with PMD. This association is an extremely rare anomaly. Mesenchymal hamartomas occur in 5% of all primary liver tumors in children and are generally benign lesions.

Placental mesenchymal dysplasia is a rare placental lesion characterized by stem villous cystic dilation and vesicle formation, placentomegaly, and vascular abnormalities. It can be associated with growth restriction, stillbirth, Beckwith-Wiedemann syndrome, and some chromosomal abnormalities, and needs to be distinguished from its main differential diagnosis, hydatidiform mole.

Placental mesenchymal dysplasia (PMD) is a rare placental abnormality. We report a case of PMD associated with intrauterine growth restriction (IUGR), which was diagnosed by an ultrasound scan during the second trimester of pregnancy. A 36-year-old primiparous woman with signs of placental chorioangioma was referred to our hospital at the 23th gestational week. An ultrasonography revealed a small-for-gestational-age fetus with a large multicystic placenta. A serial Doppler sonographic assessment of umbilical and uterine artery blood flow showed a compromised fetus. A female, small-for-gestational-age baby was delivered by c-section at 28 weeks, and PMD was histopathologically confirmed.

RESUMEN La displasia mesenquimal placentaria es una entidad poco conocida, de etiologia incierta y subdiagnosti-cada. Frecuentemente, es confundida con enfermedad trofoblastica gestacional debido a que se presenta con hallazgos ultrasonograficos caracterizados por una placenta engrosada, con quistes e imagenes hi-poecogenicas y niveles de gonadotrofina corionica humana normales o levemente aumentados. El feto es frecuentemente viable y puede manifestar retraso del crecimiento intrauterino, prematurez o asociarse al sindrome de Beckwith-Wiedemann. Se presenta el caso de una mujer joven con un parto pretermino con placentomegalia, sospecha de mola hidatidiforme parcial y un recien nacido pequeno para la edad gesta-cional.PALABRAS CLAVE: Displasia mesenquimal placentaria, placentomegalia, mola hidatidiforme SUMMARY The placental mesenchymal dysplasia is a not well known entity, with an uncertain etiology and under diagnosed. It is frequently confused with gestational trophoblastic disease because of its ultrasonographic features of a thick placenta, cysts and hypoechogenic images, with normal or slightly increased levels of human chorionic gonadotrophic hormone. The fetus is often viable and can manifest intrauterine growth restriction, prematurity or be associated with Beckwith-Wiedemann syndrome. We present a case report of a young woman with a preterm delivery, placentomegaly, suspicious of a partial hydatidiform mole and a low growth newborn.KEY WORDS

La displasia mesenquimal placentaria es una entidad poco conocida, de etiología incierta y subdiagnosticada. Frecuentemente, es confundida con enfermedad trofoblástica gestacional debido a que se presenta con hallazgos ultrasonográficos caracterizados por una placenta engrosada, con quistes e imágenes hipoecogénicas y niveles de gonadotrofina coriónica humana normales o levemente aumentados. El feto es frecuentemente viable y puede manifestar retraso del crecimiento intrauterino, prematurez o asociarse al síndrome de Beckwith-Wiedemann. Se presenta el caso de una mujer joven con un parto pretérmino con placentomegalia, sospecha de mola hidatidiforme parcial y un recién nacido pequeño para la edad gestacional. The placental mesenchymal dysplasia is a not well known entity, with an uncertain etiology and under diagnosed. It is frequently confused with gestational trophoblastic disease because of its ultrasonographic features of a thick placenta, cysts and hypoechogenic images, with normal or slightly increased levels of human chorionic gonadotrophic hormone. The fetus is often viable and can manifest intrauterine growth restriction, prematurity or be associated with Beckwith-Wiedemann syndrome. We present a case report of a young woman with a preterm delivery, placentomegaly, suspicious of a partial hydatidiform mole and a low growth newborn.

Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles Aims: To describe the clinical and histological features of a series of cases of placentas originally diagnosed as partial moles in which the final diagnosis was that of placental stem villous hydrops, mesenchymal dysplasia or Beckwith–Wiedemann syndrome. Methods and results: We searched a computerized database containing cases of suspected or proven trophoblastic disease examined at the Trophoblastic Disease Unit at Charing Cross Hospital, London, to identify cases in which stem vessel hydrops was present without other histological features of partial mole. For each case, histological sections were examined and the histological features present recorded. There were 15 cases identified. Placental weight was above the 95th centile of the normal for gestation in all cases in which this information was documented. In an additional five cases the placenta was described as ‘large’. All cases had marked stem vessel hydropic change with cyst formation and in the majority of cases some terminal villous hydrops was also present. In 13 of the 15 cases there was marked aneurysmal dilatation of stem villous vessels. Nine had focal chorioangiomatoid change and in four of these extramedullary haematopoiesis was focally present in these areas. No excessive trophoblast proliferation was noted in any case and no trophoblastic inclusions typical of partial mole were identified. Conclusions: This study has identified cases of stem villous hydrops, mesenchymal dysplasia or Beckwith–Wiedemann spectrum in pregnancies initially diagnosed as partial hydatidiform mole in the second half of pregnancy and has highlighted the need for detailed pathological examination and clinicopathological correlation in all such cases.

Placental mesenchymal dysplasia (PMD) rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.

Placental mesenchymal dysplasia is a rare condition characterized by enlarged multicystic placenta with anechoic regions on ultrasound. Gross examination shows grapelike vesicles which mimics molar pregnancy. Microscopic findings shows large edematous villi with cistern formation interspersed with normal villi. The absence of trophoblastic proliferation and trophobastic inclusions differentiates it from molar pregnancy. We report a new case of placental mesenchymal dysplasia. A 31-year-old G2P1 presented with preterm vaginal bleeding at 24 5/7 weeks of gestation. Ultrasound findings show cystic placenta and placenta previa. She went into preterm labor and delivered a female baby with no dysmorphic features but later suffered from complications of prematurity. Pathologically, the placenta showed multiple grapelike cystic vesicles with unremarkable chorionic vessels. Microscopically, enlarged edematous villi with cistern formation were noted. Trophoblastic proliferation or inclusions were not seen.

Fetal medicine is a multidisciplinary field in which data collected from multiple sources to formulate the best care plan possible. This issue of the Journal of Fetal Medicine (JFM) highlights perinatal pathology, a core component in any well-designed fetal medicine program. Gross and microscopic studies of the placenta and embryo, fetus, or neonate can provide invaluable insights into the etiology and/or pathogenesis of a wide range of conditions with important implications, particularly those related to genetic counseling and the management of future pregnancies. The practice of perinatal pathology requires a thorough understanding of normal developmental anatomy, ability to recognize and document deviations from the norm, knowledge of common congenital disorders, and skilled utilization of other informational and/or laboratory resources to investigate rare conditions. Proficiency in this subspecialty requires years of practice and continued education with regard to newly defined syndromes, advances in molecular genetics, and human embryology. Perinatal pathology is ideally practiced by a pathologist specifically trained to examine products of conception. However, in many communities, by necessity, the role is filled by a geneticist, obstetrician, or other professional, whose formal training may not have included pathology per se. The articles in this issue are written by experts in the field of perinatal pathology to explicitly review some fundamental practice guidelines and illustrate basic principles that guide the subspecialty. Topics were chosen with other members of the fetal medicine team in mind, including nonexperts who may be called upon to perform some type of perinatal pathology examination. Collectively, these papers provide a good overview of how to approach different aspects of the exam, the type of information that can be collected with systematic analyses, and how this data can be integrated with other laboratory studies and correlated with clinical findings. Examination of the placenta is a cornerstone of perinatal pathology, especially when a pregnancy is complicated by multiple gestation, premature delivery, intrauterine growth restriction, infection, or fetal demise. In his article on ‘‘Placental Gross Examination’’, Dr. Sunil Jaiman describes a logical step-by-step approach to examination of this organ, explaining how gross findings are used to direct microscopic evaluation. Dr. Jaiman emphasizes findings that may explain fetal demise. A common cause of fetal demise and other adverse pregnancy outcome is fetal thrombotic vasculopathy (FTV), which is the subject of the scholarly contribution by Drs. Marsden and Comstock. Readers learn how FTV is recognized and the challenges associated with distinguishing antemortem FTV from nonspecific postmortem histopathological vascular changes. They summarize conflicting published data regarding the relevance of hereditary thrombophilia to the pathogenesis of FTV and the role for a thrombophilia workup in affected pregnancies. Placental mesenchymal dysplasia is less common than FTV and less well known to many clinicians, but has garnered increased attention recently because of its sonographic confusion with molar pregnancy, clinical associations with assisted reproduction technology, and Beckwith–Wiedemann syndrome, and fascinating genetic findings. Dr. Linda Ernst’s comprehensive review of placental mesenchymal dysplasia (PMD) discusses all of these aspects. Readers will finish this paper prepared to consider & Raj P. Kapur raj.kapur@seattlechildrens.org

We present two pregnancies associated with normal livebirths and the unusual concomitance of chorangiomaand placental vascular malformation with mesenchymalhyperplasia. The enlarged placenta had the characteristicfindings of chorangioma, dilated and varicose chorionicvessels and multiple vesicle-like villi containing hyaluronicacid. The vesicle-like villi showed diploid cellular DNAcontents. Molecular genetic analysis using the poly-merase chain reaction amplification of polymorphic micro-satellite markers confirmed genetic identity among thechorangioma, the vesicle-like villi and the fetus. Bothpregnancies were complicated by polyhydramnios, pre-term labour and prematurity. One neonate suffered fromanaemia and thrombocytopenia. Another neonate sufferedfrom haemangiomatosis. Our cases demonstrate that con-comitant chorangioma and placental mesenchymal hyper-plasia are genetically identical to the fetus and can coexistwith a normal viable fetus. Since haemangiomas, chor-angiomas, chorionic vessels and villi mesenchymal cells areall derived from the mesoderm, a combination of fetalhaemangiomas, placental vascular malformation, chor-angiomas and placental mesenchymal hyperplasia mayrepresent a mixed form of congenital malformation of themesoderm.Key words: chorangioma/haemangioma/mesoderm/placentalmesenchymal hyperplasia/placental vascular malformationIntroductionPregnancy with concomitant chorangioma and placental vascu-lar malformation associated with mesenchymal hyperplasiaand a live birth is very rare. To our knowledge, only one case ofconcomitant chorangioma and placental vascular malformationwith mesenchymal hyperplasia has been reported. The enlargedplacenta has grape-like vesicles similar to partial hydatidiformmoles. The chorangioma coexists with dilated and tortuouschorionic vessels of the placenta. The rarity of this condition

Six new cases of placental mesenchymal dysplasia are presented and the findings compared to those reported in 16 similar cases published in the literature. Mesenchymal dysplasia was suspected when a placental scan showed a partial mole with a fetus of normal size and normal karyotype. Three fetuses of this series and nine out of 18 cases from the literature review also presented with Beckwith-Wiedemann syndrome features. 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. Ultrasound/Doppler serial investigations indicate that the circulatory imbalance is due to hypovascularization of the dysplastic lobules, found in mesenchymal dysplasia. This induces the progressive aneurysmal and varicose dilatation of chorionic vessels, however, these anatomical transformations are not associated with a change in resistance to flow in both uterine and umbilical circulations nor with an excess of obstetrical complication when the fetus is anatomically normal.

Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly and grapelike vesicles resembling a partial molar pregnancy and in most cases, a phenotypically normal fetus. Hepatic mesenchymal hamartoma (HMH) is a benign hamartomatous proliferation of mesenchymal liver tissue. PMD has been associated with HMH. Although rare, in combination, it is known to carry a poorer prognosis than in fetuses without structural abnormalities. There are only a few reported cases of PMD and associated HMH with varying management strategies and outcomes, precluding ascertainment of the most appropriate treatment plan. We present a case of PMD with associated cystic HMH resulting in fetal death. We also reviewed the published literature on this issue and explored possible management strategies to prevent adverse fetal and neonatal outcomes.

In this article, the authors present a case of intrauterine foetal death (IUFD). The post-mortem histologic examination revealed placental mesenchymal dysplasia (PMD), a rare human placental disorder. Moreover, cases of PMD are often misdiagnosed as partial mole. The mother was a 26-year-old Italian, whose pregnancy, her first, had been uneventful until week 34⁺⁴ of gestation when IUFD suddenly occurred. The 2350 g male foetus showed no external abnormalities and the karyotype was 46, XY. The placenta weighed 450 g, the chorionic disk was round shaped, measuring 19.5-20.5 cm in diameter and had many enlarged villous structures. Histologically, the parenchyma showed abnormally enlarged and focally hydropic stem villi. Many of them were also surrounded by a fibrinoid material. Neither abnormal trophoblastic proliferation nor inclusion was observed in the examined sections. Causes and pathogenesis of PMD are still unclear and it is difficult to make a diagnosis solely on prenatal ultrasound during pregnancy. Generally, the correct diagnosis is reached only after the histological analysis of the placenta. However, obstetricians and gynaecologists should consider PMD also when a normal looking foetus is accompanied by a molar placenta (index factor for placentomegaly). The authors stress the importance of cooperation and information exchange among clinical and forensic pathologists, neonatologists, obstetricians and gynaecologists to avoid medical malpractice court proceedings in cases of IUFD.

Background. Pregnancy with concomitant chorioangioma and placental mesenchymal dysplasia (PMD) coexisting with a normal viable fetus is very rare. The literature was reviewed to explore the incidence and genetic origin of this condition.Case. The case was first identified by prenatal ultrasonography, but the prenatal diagnosis only included chorioangioma. PMD was then confirmed during postnatal evaluation, which included gross and histologic examination of the placenta. The macroscopic and microscopic findings were consistent with concomitant chorioangioma and placental mesenchymal dysplasia during pregnancy. Genetic findings confirmed genetic similarity of the chorioangioma and vesicle-like villi with the fetus.Conclusions. The case represents a rare placental abnormality whose pathogenesis and molecular basis need further research. Detailed histologic and genetic analyses are essential for accurate and differential diagnosis.

Placental mesenchymal dysplasia (PMD) is a rare placental abnormality characterised by placentomegaly and grape-like vesicles resembling partial mole by ultrasonography, but in contrast to partial mole can co-exist with a viable fetus. Although the karyotype is normal, the fetus is at increased risk for intrauterine growth restriction, intrauterine fetal demise or perinatal death and Beckwith-Wiedemann syndrome. Prenatal diagnosis is difficult and the final diagnosis is usually achieved by postpartum histological examination of the placenta. We present two recent cases of placental mesenchymal dysplasia with poor obstetric outcome. One fetus presented with reduced growth parameters, while the other fetus showed hepatosplenomegaly and early hydropic changes that appear to be associated with Beckwith-Wiedemann syndrome. In this report, the clinico-pathological features of two cases of PMD are discussed and the differentiation from a partial mole is highlighted. This study also supports the utility of cytogenetic ploidy analysis and p57KIP2 protein staining in the evaluation of pregnancies with PMD.

Introduction: placental mesenchymal dysplasia (PMD) is a rare placental anomaly characterized by placentomegaly and grapelike vesicles which resemble molar pregnancy. Case: we report the case of 33-year-old woman (1-gravid) who visited our clinic at 11 weeks of gestation due to a suspected molar pregnancy. Ultrasound examination showed an enlarged placenta with multiple vesicular lesions. Maternal human chorionic gonadotropin level was normal and chorionic villus sampling showed a normal male karyotype (46 XY). The fetus exhibited no specific anomalies and fetal growth was normal during pregnancy with no signs of fetal suffering. At 31 weeks, the pregnancy ended owing to intrauterine fetal death (IUFD). The patient delivered a normal-sized male fetus (1800g) with no definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia. Conclusion: in the presence of placental ultrasound anomalies with no other sign of fetal suffering, the pregnancy should be considered at risk and, therefore, should be monitored carefully including the option of hospitalization.

Summary Aims Placental mesenchymal dysplasia (PMD) is a rare condition which is associated with the disparate fetal outcomes of Beckwith-Wiedemann syndrome (BWS), fetal growth restriction or intrauterine and neonatal death. We aimed to investigate the potential epigenetic/genetic anomalies associated with PMD and their relationship with the different causes of BWS. Methods Eight archival cases in which PMD, BWS or both were diagnosed were investigated by correlating morphology with p57 KIP2 expression, XY fluorescence in situ hybridisation (FISH) analysis and DNA genotyping. Results Placentae from BWS cases caused by aberrant IC2 methylation, leading to abnormal p57 KIP2 expression, did not show PMD but had a striking excess of extravillous trophoblast. PMD in the absence of BWS was caused by androgenetic/biparental mosaicism. The single case of BWS with PMD was due to mosaic uniparental disomy of 11p15.5. In the latter two aetiologies, our results indicate that the uniparental disomy is confined to the villous mesenchyme. Conclusions These results suggest that the link between PMD and BWS is uniparental disomy of genes confined to the telomeric IC1 region of 11p15.5. A strong candidate gene is IGF2, a known growth factor of placental mesenchyme.

The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This report presents a case of PMD with a female fetus complicated with intrauterine growth restriction (IUGR). The ultrasound findings were similar to molar pregnancies, but PMD was suspected based on the presence of low β-hCG levels and a normal karyotype. After delivery, pathological examination of the placenta showed dilated villi and thick-walled vessels lacking trophoblast proliferation, which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was found to have increased in the abnormal villi. Whether this is an incidental or X-linked gene specific event in, IUGR complicated, PMD pathogenesis warrants further investigation of VEGF-D expression in PMD.

Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD) with fetal omphalocele in a 22-year-old patient is reported.Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia.Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.

Summary We here report a case o f placental vascular malformation with mesenchymal hyperplasiaof the villi and a localized chorioangioma. After an uneventful pregnancy our patient delivered a non-malformed live femaleinfant. The placenta was grossly enlarged, and macroscopically it was characterized by strongly enlarged varicous chorionic vessels. On the maternal plate vesicle-like structures, giving the impression o f partial mole, were seen. At microscopy level, areas of normal looking tissue alternated with areas of excessivelyenlarged villi, in which the ground substance contained large amounts of acid mucopolysaccharide, corresponding to “mesenchymal hyperplasia”. Moreover, a localized chorioangioma was found. In none of the histological sections were cisterns, abnormal trophoblastic proliferation, stunted ramification or stromal trophoblastic inclusions observed. In week 15 maternal se-AFP was elevated to 3.03 multiples o f the median. Geneticanalyses revealed a normal female karyotype and biparental genomic contributions to 7 unlinked loci. Placental vascular malformation with mesenchymal hyperplasia is a differential diagnosis to partial mole which should be considered when vesicle like placental enlargement is observed along with a living fetus.

Placental mesenchymal dysplasia is a rare disorder characterized by an increased size placenta with cystic villi and ectasic vessels. The correct diagnosis is very important, because placental mesenchymal dysplasia is usually compatible with a normal foetal morphology and a good materno-foetal outcome. An accurate ultrasound evaluation can help in the identification of characteristic patterns associated to this trophoblastic disease, particularly to distinguish it from its main differential diagnosis, i.e. hydatidiform mole. We report an early second-trimester ultrasound diagnosis of placental mesenchymal dysplasia complicated by foetal growth restriction, but with normal female karyotype and good healthy baby.

Placental mesenchymal dysplasia is a benign condition that can be confused with a molar pregnancy by ultrasound scanning and gross examination. Conservative management should be considered with a normal-appearing singleton fetus and a cystic-appearing placenta. We present a case of placental mesenchymal dysplasia with a favorable outcome.

We report a 32-year-old woman (1-gravid, 1-para) with a vesicular lesion in her uterus that was pointed out on ultrasound at 8 weeks' gestation. Amniocentesis at 15 weeks' gestation showed a normal female karyotype, 46XX. As the pregnancy advanced, the mole-like lesion became relatively reduced. Throughout gestation, the maternal human chorionic gonadotropin level was normal, but the serum alpha fetoprotein level rose as her pregnancy progressed. Her fetus did not exhibit any remarkable anomalies. The patient visited our hospital complaining of a diminished feeling of fetal movements at 36 weeks 5 days' gestation, and intrauterine fetal death (IUFD) was confirmed. She delivered a 2336-g female without any definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia, and androgenetic/biparental mosaicism in the placenta was identified using p57kip2 immunohistochemical staining. And it also revealed that the rupture of the cirsoid chorionic vessels had led to IUFD. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1030203924510721.

We present an extremely rare case of partial molar pregnancy with a chromosomically and phenotypically normal embryo and review of the literature. A 31-year-old nulliparous was referred to us at 30 weeks of gestation due to absence of fetal movements and subsequent ultrasound examination revealed intrauterine demise. Prenatal amniocentesis due to raised maternal serum α-fetoprotein had shown a karyotypically normal female embryo and second trimester ultrasound demonstrated no anatomic abnormalities. Upon induction of labor with misoprostol, a phenotypically normal embryo was delivered and the placenta showed intermixed areas of marked hydatidiform villous change and normal parenchyma. Pathologic examination of the placenta confirmed the molar change of placenta. Two are the main theories discussed herein that explain the placental molar changes in singleton pregnancies: confined placental mosaicism (one case reported to date) and placental mesenchymal dysplasia (70 cases reported). Differential diagnosis is based on histopathologic features and genetic analysis of placenta.

Extensive use of ultrasound in early pregnancy has given rise to increased diagnostic dilemma, particularly the differential diagnosis of early complete mole, partial mole and abnormal nonmolar villous lesions. The rare entities of placental mesenchymal dysplasia, twin pregnancy with one complete mole further pose problems. Overdiagnosis of hydatidiform mole in ectopic pregnancy should also be avoided. Molecular cytogenetic studies, besides enhancing our understanding of pathogenesis, also facilitate diagnosis and management. Laboratory techniques including microsatellite analysis, flow cytometry, in situ hybridization, sequencing, comparative genomic hybridization, and imprinting gene studies have been applied. Vast majority of complete moles are diploid and purely androgenic while most partial moles are triploid having excessive paternal genome with maternal contribution. Adjunct techniques, such as p57kip2 immunohistochemistry as well as ploidy and microsatellite analysis, have become more commonly applied to facilitate diagnosis of GTD. Molecular cytogenetic studies are also useful in distinguishing gestational and non-gestational trophoblastic choriocarcinoma with implication on chemotherapy regimes. However, we should understand clearly the diagnostic pattern and limitation of such tests to avoid misinterpretation. The basic prerequisite of processing adequate or all evacuated material for histopathological evaluation as well as correlation with clinical, radiological and biochemical findings remains the most important diagnostic approach.

Cleavage-stage embryos often have nuclear abnormalities, one of the most common being binucleate blastomeres, which may contain two diploid or two haploid nuclei. Biopsied cells from preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) cycles were studied to determine the relative frequency of binucleate cells with two haploid versus two diploid nuclei. The frequency of mononucleate haploid biopsied blastomeres was also recorded. In the chromosomal PGD cycles 45.2% of the biopsied binucleate cells were overall diploid and 38.7% were overall tetraploid, compared with 50.0% and 29.2% for the PGS group, respectively. Placental mesenchymal dysplasia is a rare condition associated with intrauterine growth restriction, prematurity and intrauterine death. Recent work suggests that androgenetic diploid/haploid mosaicism may be a causal mechanism. There are two possible origins of haploid nuclei, either the cell contained only one parental genome initially or they may be derived from the cytokinesis of binucleate cells with two haploid nuclei. Binucleate formation therefore may be a way of doubling up the haploid genome, to produce diploid cells of androgenetic origin as seen in placental mesenchymal dysplasia.

This report describes a 31-week stillborn female infant with placental mesen-chymal dysplasia (PMD) in association with hepatic mesenchymal hamartoma (HMH) and pulmonary hamartoma. Placental mesenchymal dysplasia was initially misdiagnosed as a partial mole. However, histologically, no trophoblastic proliferation or inclusions were observed. Differential diagnosis of the hepatic mass with similar tumors is discussed. To our knowledge, this is the first case of lung hamartoma reported in a fetus and the first case related to PMD and HMH. A common anomalous development of the mesoderm, a reparative post-injury process and a genetic mechanism, have been proposed to explain their pathogenesis.

An imbalance of imprinted gene expression within 11p15.5 is observed in Beckwith-Wiedemann syndrome (BWS), as well as in a variety of placental abnormalities including complete hydatidiform mole (CHM), placental mesenchymal dysplasia (PMD) and triploidy. To facilitate the diagnosis of epigenetic errors and chromosomal imbalance of 11p15.5, we validated a pyrosequencing assay to measure methylation at KvDMR1 using blood samples from 13 BWS cases, 8 of which showed reduced methylation as compared to control blood. An imbalance between maternal and paternal genomes as is found in triploidy, CHM or PMD was also associated with altered KvDMR1 methylation. A reciprocal pattern of methylation was obtained in the triploid cases by assaying the proximal 11p15.5 ICR associated with H19. To distinguish chromosome 11 specific alterations from whole genome imbalance, other imprinted differentially methylated regions (DMRs) can be utilized. Thus, pyrosequencing assays for DMRs associated with SGCE, SNRPN, and MEST were also compared for their utility in diagnosing parental imbalance in placental samples. While each of these assays could successfully distinguish parental origin of triploidy, SGCE showed the clearest separation between groups. The combined use of a chromosome 11p15.5 assay (e.g. KvDMR1 or H19-ICR) and non-chromosome 11 assay (e.g. SGCE) provides a potentially valuable diagnostic tool in the rapid screening of methylation errors in placental disorders. These results also show the maintenance of imprinting status at these loci in the human placenta, even in the presence of abnormal pathology.

Placental mesenchymal dysplasia (PMD) is a rare human disorder associated with stillbirth, intrauterine growth restriction (IUGR) and Beckwith-Wiedemann syndrome. Although the morphology of this condition has been described in 86 cases, the underlying cellular origin is unclear. We investigate the placental cell type involved in a case of PMD associated with a live born female infant with IUGR. In PMD intermediate villi contain cisternae, lined by non-proliferative cells. Immunostaining reveals they are not of trophoblast or vascular endothelial origin. There is positive immunostaining for lymphatic endothelium; this abnormal lymphangiogenesis is in concordance with current hypotheses regarding the aetiology of PMD. Furthermore, such observations suggest that placental villous mesenchyme may differentiate into various cell types, even those not normally found in the human placenta.

Placental mesenchymal dysplasia (PMD) is a rare placental abnormality with sonographic and macroscopic features similar to those seen in a partial hydatidiform mole, and which has usually been reported with a normal female karyotype. We report a case of prenatally suspected PMD associated with trisomy 13. Sonography performed at 17 weeks' gestation showed multiple cystic spaces in the placenta resembling molar tissue, and a fetus with postaxial polydactyly and an atrial septal defect. An amniocentesis revealed a fetal karyotype of 46,XY,der(13), t(13;13)(q11;q11)[20]/47,XY,+13[11], consistent with trisomy 13. Cordocentesis confirmed the cytogenetic diagnosis. Histopathologic examination of the placenta following termination of the pregnancy at 22 weeks' gestation showed enlarged stem villi with loose connective tissue and cistern formation and no evidence of trophoblastic hyperplasia or stromal trophoblastic inclusions, which was consistent with PMD. PMD should be considered in the differential diagnoses of a placenta showing multiple cystic lesions on prenatal sonography, and karyotypic analysis should be performed.

Objective To demonstrate a role for microsatellite analysis in the evaluation of prenatal cases with possible placental mesenchymal dysplasia (PMD). Methods We present a case report in which several molecular analyses of amniocytes and products of conception were used in combination with cytogenetic and ultrasound studies to evaluate a pregnancy with a clinical suspicion of PMD. A combination of Southern blotting analysis, methylation-sensitive polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) was utilized to evaluate methylation patterns in the Beckwith–Wiedemann syndrome (BWS) and Prader–Willi/Angelman syndrome (PW/AS) critical regions. A series of microsatellite markers were used to evaluate the possibility of an androgenetic cell line. Results Methylation studies performed for the BWS and PW/AS critical regions were abnormal and consistent with a molecular diagnosis of BWS and Angelman syndrome. Further studies of amniocytes using microsatellite markers identified androgenetic and biparental cell lines in approximately a 10:1 ratio, respectively. Conclusions Prenatal ultrasonography, karyotyping and molecular genetic evaluation for BWS alone were not sufficient to identify the underlying etiology of PMD in this case. The androgenetic cell line was only identified after microsatellite analysis. Copyright © 2007 John Wiley & Sons, Ltd.

Placental mesenchymal dysplasia (PMD) is a distinct syndrome of unknown etiology that is associated with substantial fetal morbidity and mortality. It is characterized by an enlarged, hydropic placenta, depicting multiple cysts and tangles of intestinelike chorionic vessels on gross examination. The sonographic features are usually suggestive of a partial mole. Intrauterine growth restriction (IUGR) is common, yet, paradoxically, Beckwith-Wiedemann syndrome (BWS) has been diagnosed in many fetuses and neonates. Cystic changes in the placenta are relatively uncommon findings and are mostly related to chorioangiomas or trophoblastic disease. We report an early second-trimester (16 weeks' gestation) diagnosis of PMD in a monochorionic diamniotic twin pregnancy. There are fewer than 100 reported PMD cases in the literature.1 A review of the etiology of cystic changes of the placenta is presented, with emphasis on maternal and fetal aspects as well as genetic counseling and other tests to be considered. We expand on the differential diagnosis and implications of diffuse cystic changes in the placenta.

Placental mesenchymal dysplasia is a very rare disorder in which the placenta is enlarged and contains cystic villi and dilated vasculature. The authors present a new case report of placental mesenchymal dysplasia with severe fetal growth restriction.

BACKGROUND: Placental hemangioma (chorioangioma) and congenital hemangioma are relatively common tumors, which on rare occasions may occur together. Very little is known about the pathogenetic mechanisms underlying these lesions. CASE: Herein we describe a rare case of a stillborn infant with chorioangioma, placental mesenchymal dysplasia, and liver cavernous hemangioma. In addition, we present the findings of the karyotype analysis of these lesions, which was done with the bacterial artificial chromosome arrays using the comparative genomic hybridization method. The chromosomal abnormalities that we found were deletions at 2q13 and 7p21.1 and were common to both placental and liver lesions. CONCLUSIONS: None of the identified chromosomal aberrations have been previously associated with chorioangiomas or hemangiomas. Important genes that lie in these DNA regions may be implicated in the pathogenesis of congenital hemangiomas and mesenchymal dysplasia. Birth Defects Research (Part A) 2007. © 2006 Wiley-Liss, Inc.

preoperative imaging in a low risk population for endometrial cancer is low. However, themortality associatedwith undiagnosed pulmonary metastases is sufficiently high to warrant evaluation with radiographic imaging. Learning objective: Learners will be able to identify a low risk population for having distant disease and evaluate if their practice warrants preoperative imaging on this population.