Ultrasound Obstet Gynecol 2013; 41: 366–374 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.12359
Systematic review of sonographic findings of placental mesenchymal dysplasia and subsequent pregnancy outcome U. A. NAYERI*, A. B. WEST†, H. K. GROSSETTA NARDINI‡, J. A. COPEL§ and A. K. SFAKIANAKI§ *Department of Obstetrics and Gynecology, SUNY Upstate Medical University, Syracuse, NY, USA; †Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; ‡Cushing/Whitney Medical Library, Yale University, New Haven, CT, USA; §Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
K E Y W O R D S: molar pregnancy; placental mesenchymal dysplasia; stem villous hyperplasia
ABSTRACT Objective To describe the sonographic features and pregnancy outcomes of placental mesenchymal dysplasia (PMD), an entity often misdiagnosed as molar pregnancy. Methods We reviewed PMD cases from our institution and performed a systematic review of the existing literature. Inclusion criteria for the review were diagnosis of PMD as defined by placental pathology, description of placental morphology on antenatal ultrasound and reporting of pregnancy outcomes. Results We found three cases of PMD at our institution. Patient 1 had elevated human chorionic gonadotropin (hCG) and an enlarged, hydropic placenta at 13 weeks, suggestive of a molar pregnancy. Patient 2 also had elevated hCG with large, vascular placental lakes on ultrasound suggesting placenta accreta or molar pregnancy. Case 3 involved placentomegaly and fetal anomalies suggestive of Beckwith–Wiedemann syndrome. From the literature review, 61 cases met the inclusion criteria. The most common sonographic features included enlarged (50%) and cystic (80%) placenta with dilated chorionic vessels. Biochemical aneuploidy screening abnormalities were relatively common as were fetal anomalies, Beckwith–Wiedemann syndrome and other genetic abnormalities. Pregnancy complications included intrauterine growth restriction (IUGR; 33%), intrauterine fetal death (IUFD; 13%), and preterm labor (33%). Pregnancies without fetal anomalies, IUGR, IUFD or preterm labor had normal neonatal outcomes despite PMD (9%). Conclusions The differential diagnosis of PMD includes molar pregnancy and other placental vascular anomalies. PMD is associated with adverse pregnancy outcome, so heightened surveillance with genetic evaluation, serial growth scans and third-trimester assessment of wellbeing should be considered. PMD must be differentiated from
gestational trophoblastic disease because management and outcomes differ. Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.
INTRODUCTION Placental mesenchymal dysplasia (PMD), also known as mesenchymal stem villous hyperplasia, is a rare placental vascular anomaly that was initially described by Moscoso et al. in 19911 . PMD is probably under-diagnosed and under-reported because many healthcare providers, including pathologists and sonologists, are unfamiliar with the clinical entity. One report estimated the incidence at about 0.02%2 . PMD is often mistaken for gestational trophoblastic disease because of the similar sonographic findings of the two entities3 . Owing to the relatively recent recognition of PMD, there are limited data on outcome of affected pregnancies, and consistent diagnostic criteria are not established. In reviewing PMD cases diagnosed at our institution and performing a systematic review of the existing literature, our objectives were to identify sonographic findings indicative of PMD. We also sought to investigate the outcomes of pregnancies associated with PMD. By collecting and systematically reviewing the data we are able to provide clinicians with more detailed information for counseling patients on the implications and prognosis of PMD.
CASE REVIEWS We searched the pathology database at Yale-New Haven Hospital for cases of PMD from January 1998 to May 2012. The cases were then identified in an established, well-maintained ultrasound database. The study was approved by the Yale University Human Investigation Committee.
Correspondence to: Dr U. A. Nayeri, Department of Obstetrics and Gynecology, SUNY Upstate Medical University, 3RD FL University Health Care Center, 90 Presidential Plaza Syracuse, NY 13202, USA (e-mail:
[email protected]) Accepted: 13 November 2012
Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.
SYSTEMATIC REVIEW
Placental mesenchymal dysplasia
Case 1 A 35-year-old African-American woman, gravida 2 (term births 0, premature births 0, abortus 1, living children 0 (TPAL)) presented at 12 + 4 weeks for a suspected molar pregnancy. The pregnancy originated as a twin gestation following in-vitro fertilization with the spontaneous death of one twin. The quantitative human chorionic gonadotropin (hCG) level was elevated at 337 000 mIU/mL. Nuchal translucency (NT) measurement was 1.6 mm. The placenta was enlarged and hydropic, and the dead twin was not visible. The patient underwent chorionic villus sampling and the karyotype was 46,XX. Genotyping ruled out a molar pregnancy. A followup ultrasound at 14 weeks’ gestation again revealed an enlarged placenta with multiple cystic areas (Figure 1). The patient’s hCG level was 398 000 mIU/mL. The patient was counseled on the possible diagnosis of a diploid mole co-existent with a normal fetus. She continued to opt for expectant management. At 18 + 3 weeks, she presented to the labor floor complaining of vaginal spotting with her cervix dilated 2 cm. The patient was counseled on the poor prognosis for the pregnancy, including the risks of infection, and still desired expectant management. She returned at 19 weeks with preterm premature rupture of membranes (PPROM) and was dilated 3–4 cm. The patient chose termination of pregnancy
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and underwent dilation and evacuation. Under general anesthesia, we performed a manual extraction of a nonviable fetus and placenta as well as curettage for retained placental fragments. Postoperatively, the patient’s hCG level was 6220 mIU/mL and it normalized after 6 weeks. The placenta was enlarged at 175 g (expected weight = 100 g) with dilated chorionic plate vessels. The stem villi were edematous with prominent thick-walled blood vessels and the terminal villi were focally hydropic. Trophoblastic proliferation and stromal inclusions were not observed. There were no fetal anatomic abnormalities. DNA methylation studies for Beckwith–Wiedemann syndrome (BWS) were also normal, ruling out genemethylation abnormalities and uniparental disomy, which account for approximately 80% of cases of BWS. Although a confirmatory fetal karyotype could not be obtained because of inadequate growth of cultured fetal cells, tissue genotyping was performed and again ruled out molar pregnancy. Based on sonographic and histological findings, the final diagnosis was PMD.
Case 2 A 32-year-old Caucasian woman, gravida 5 (TPAL = 2022), with two previous Cesarean deliveries, presented at 12 + 6 weeks’ gestation for first-trimester
Figure 1 Ultrasound findings in Case 1. (a) Placentomegaly. (b) Enlarged, thickened placenta. The size of the placenta is appreciated when compared with the size of the fetal abdomen. (c) Cystic placenta. (d) Dilated chorionic vessels.
Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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screening. The NT was 1.9 mm, pregnancy-associated plasma protein-A (PAPP-A) was 0.97 multiples of the median (MoM) and hCG was 1.13 MoM, which resulted in a Down syndrome risk of 1:3500 and a trisomy 18 risk of
