Placental Mesenchymal Dysplasia

Placental mesenchymal dysplasia (PMD) is a rare placental disorder characterized by placentomegaly, caused by mesenchymal stem villous hyperplasia on histopathology and manifesting as multicystic placental lesions, as seen on ultrasound.

The incidence of PMD is reported to be 0.02% of all pregnancies. (1) The true incidence is unknown because various terms are used in the medical literature to describe this entity. For example, it has been previously reported as “placentomegaly with massive hydrops of placental stem villi” and “pseudopartial mole with angiomatous malformation of the stem villi”.

There is a preponderance in placentas from female infants,  with a female to male ratio of 3.6-1. (2)

The underlying cause of PMD is currently unknown.

Vascular malformations associated with PMD might represent a form of congenital malformation of the mesoderm, and there may be a relation to simultaneous mesenchymal disorders of the newborn such as liver and skin haemangiomas. (3,4,5)

Fetal complications such as growth restriction and intrauterine fetal demise may occur due to vascular malformations that shunt blood away from the fetus or lead to  multiple thromboses in the villi. (8)

The association of  PMD with  Beckwith-Wiedemann syndrome ( see below)  may  suggest a similar pathogenesis, with evidence pointing toward epigenetic imprinting abnormalities involving genes on chromosome 11q15.5 (5)

Approximately 25% of cases of PMD are associated with Beckwith-Wiedemann syndrome (macrosomia, exomphalos, visceromegaly, macroglossia, omphalocele, hemihypertrophy , placentomegaly and increased susceptibility to childhood tumors) but it is also found in  phenotypically normal fetuses and is compatible with fetal life. (6). Other associations reported in the literature include trisomy 13, Klinefelter’s Syndrome, uniparental disomy 6, neonatal diabetes, and 13q12.1 deletion.  (11-15). Recently, Guenot et al, reported a case series with potential association with CHARGE syndrome, fetal pleuropulmonary blastoma and fetal skeletal dysplasia. (9)

Routine ultrasound examination may detect a thickened placenta with hypoechoic spaces and a viable fetus.

Placental mesenchymal dysplasia may be associated with different patterns of blood flow with advancing gestation. During the first two trimesters, there is an absent or low venous signal inside the placental lesion. In the third trimester, large vascular areas with turbulent blood flow were observed, either in arterial or venous patterns, located mainly under and at the level of the chorionic plate. (6)

Placental mesenchymal dysplasia is associated with either structurally normal fetus or Beckwith-Wiedemann syndrome in 25% of cases. (6)

In addition to ultrasound findings, serum markers may play a role in diagnosis. Elevated maternal serum levels of AFP and normal  or  slightly elevated hCG levels  can be found in the second and third trimesters and suggest the presence  of PMD. (10)

The final diagnosis of PMD is made on histologic examination of the placenta by enlarged, edematous stem villi with peripheral blood vessels and cisterns. The absence of trophoblast hyperplasia and trophoblastic inclusions can distinguish this entity from molar pregnancy. (1)

Placental mesenchymal dysplasia is often misdiagnosed as a partial mole, partial hydatidiform mole with the coexistent fetus, placental mosaicism, chorioangioma, subchorionic hematoma, placental infarcts, and spontaneous abortion with hydropic changes. (4)

The absent or low venous signals inside the placental lesion may be of value in differentiating PMD from chorioangioma or molar pregnancy that is characterized by high velocity blood flow, as well as from placental hematoma in which there is no blood flow inside the lesion. (6)

The triploid fetus of a partial mole may be differentiated from PMD by the finding of multiple fetal malformations  on ultrasound and confirmed by amniocentesis for karyotype.

Due to potential complications, close prenatal surveillance is recommended to prevent fetal demise.

The hypervascularity in the placenta may lead to fetal growth restriction or intrauterine fetal death and maternal hypertension. (4)

The fetal outcome in PMD cases with inadequate fetal growth may be determined by the relative size and growth of the remaining functional normal placenta and not necessarily by the extent on the PMD. (3)

In cases of PMD, maternal complications are less common, however, it can be associated with pre-eeclampsia/gestational hypertension, HELLP Symdone and eclampsia (8,9,16)

The common fetal complications reported with PMD are preterm delivery (52%), fetal growth restriction (33%), genetic syndromes such as the Beckwith-Wiedemann syndrome (28%), and fetal death (13%)   (4,7)

In cases where Beckwith-Wiedemann syndrome has been  ruled out, a high rate of fetal growth restriction  is noted (50%) and  in up to 40% can  result in fetal demise or neonatal death. Many of the fetal and neonatal deaths were not associated with fetal growth restriction however. (3)

The pregnancy outcome depends mainly on the ultrasound findings and associated anomalies. The hypervascularity in the placenta may lead to fetal growth restriction or intrauterine fetal death combined with maternal hypertension. (4)

The optimal perinatal management of PMD has not been established however, it is often associated with adverse pregnancy outcomes. Therefore, maternal surveillance for hypertensive diseases of pregnancy along with  genetic counselling/investigation,  serial ultrasound assessment of fetal growth assessment, and third-trimester assessment of well-being should be considered.

1. Lokan J, Chan YF, Agnesta F. Placental mesenchymal dysplasia. Pathology 2002 ; 34/375-378

2. Cohen MC, Roper EC, Sebire NJ et al. Placental mesenchymal dysplasia associated with fetal aneuploidy. Prenat Diagn 2005 ; 25 :187-192

3. Pham T, Steele J, Stayboldt C et al. Placental mesenchymal dysplasia is associated with high rates of intrauterine growth restriction and fetal demise ; A report of 11 new cases and review of the literature. Am J Clin Pathol. 2006 ;126(1) :67-78

4. Parveen Z, Tongson-Ignacio JE, Fraser CR et al. Placental Mesenchymal Dysplasia, Arch Pathol Lab Med 2007 ;131 ;131-7

5. Paradinas FJ, Sebire NJ, Fisher RA et al. Pseudo-partial moles : placental stem vessel hydrops and the association with BWS and complete moles. Histopathology. 2001 ;39(5) :447-54

6. Jauniaux E, Nicolaides KH, Hustin J. Perinatal features associated with placental mesenchymal dysplasia. Placenta. 1997 ; 18(8) :701-6

7. Nayeri UA, West AB, Grossetta Nardini HK et al. Systematic review of sonographic findings of placental mesenchymal dysplasia and subsequent pregnancy outcome. Ultrasound Obstet Gynecol 2013 Apr; 41(4):366-74

8.  McNailly, L. et al. Differentiating complete hydatidiform mole and coexistent fetus and mesenchymal dysplasia: A series of 9 cases and review of the literature. Gynecologic Oncology Reports 37 (2021) 100811

9.  Guenot C. et al. Placental mesenchymal dysplasia: An underdiagnosed placental pathology with various clinical outcomes. Eur J Obstet Gynecol Reprod Biol. 2019 Mar;234:155-164

10. Kodera C.et al. Clinical manifestation of placental mesenchymal dysplasia in Japan: A multicenter case series. J. Obstet. Gynecol. Res. 2021

11. Johnson SL, Walters-Sen LC, Stanek JW. Placental Pathology in Placental Mesenchymal Dysplasia with 13q12.11 Deletion and a 25-Week Gestation Female Infant. Am J Case Rep. 2018 Mar 29;19:369-373. doi: 10.12659/AJCR.907329. PMID: 29593209; PMCID: PMC5890614.

12. Pawoo N, Heller DS. Placental mesenchymal dysplasia. Arch Pathol Lab Med. 2014;138:1247–49

13. Paradinas FJ, Sebire NJ, Fisher RA, et al. Pseudo-partial moles: Placental stem vessel hydrops and the association with Beckwith-Wiedemann syndrome and complete moles. Histopathology. 2001;39:447–54

14.  Lange JM. Placentomegaly with massive hydrops of placental stem villi, diploid DNA content, and fetal omphaloceles: Possible association with Beckwith-Wiedemann syndrome. Hum Pathol. 1991;22:591–97

15. Cohen MC, Roper EC, Sebire NJ, et al. Placental mesenchymal dysplasia associated with fetal aneuploidy. Prenatal Diagnosis. 2005;25:187–92. 

16. Colpaert RM, Ramseyer AM, Luu T, Quick CM, Frye LT, Magann EF. Diagnosis and Management of Placental Mesenchymal Disease. A Review of the Literature. Obstet Gynecol Surv. 2019 Oct;74(10):611-622. doi: 10.1097/OGX.0000000000000716. PMID: 31670834.

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