Discussion
Placental mesenchymal disorder is an uncommon vascular anomaly affecting
the placenta and its development (6). PMD is mainly detected after 13
weeks of GA when the placenta appears multicystic (1). Its etiology and
pathogenesis are yet to be fully characterized (6).
Due to the low incidence of this disease as well as the lack of sizable
studies preventing from issuing guidelines, diagnosis, management and
follow-up might prove to be challenging for the medical team and the
parents.
Here, we present a case where PMD was considered as a diagnosis since
the earliest stages of the pregnancy, at only 9 weeks and 6 days,
resulting in prompt management and eventually leading to the delivery of
a healthy female baby.
When morphological placental anomaly is identified on ultrasound during
the first trimester, the differential diagnosis must include partial
molar pregnancy, complete mole with a coexisting normal fetus and PMD.
These entities share similar ultrasound features such as enlarged or
thickened placenta with multi cystic and grape-like hypo echoic lesions
(1).
Anatomopathology
Macroscopically, pathologic examination of PMD reveals placentomegaly
associated with dilatation of fetal chorionic vessels. Microscopically,
the analysis shows thrombosis and oedematous stem villi without
trophoblastic proliferation or hyperplasia, this last characteristic
formally excluding a molar pregnancy (6).
Since the diagnosis is only confirmed by the pathologist’s team after
birth, an early antenatal rigorous diagnostic approach should be adopted
by the multidisciplinary medical team.
Firstly, invasive testing with CVS should be performed for genetic
analysis.
Genetic testing
On a genetic level, a complete mole is characterized by an androgenetic
diploid conception where the ovum is either fertilized by one duplicated
sperm or, more rarely, by two sperms and has lost its maternal DNA (7).
A partial mole originates from a diandric triploid conception where one
ovum is fertilized by two sperms or one duplicated sperm, thus the
genetic arrangement is built by two paternal and one maternal
chromosomal complements (7). Therefore, PCR based DNA genotyping (STR)
compared to the maternal and paternal, when possible, genomes can also
be useful to distinguish complete moles, thanks to their androgenetic
constitution, from the diandric triploidy nature of partial moles and
both of these from the biparental allelic balance of non molar
pregnancies like PMD (7).
As shown in the review of 66 cases of PMD conducted by Cohen et al, the
majority of fetuses had a normal karyotype (78%), while 23% were
affected by BWS and finally only 3 cases of chromosomal anomalies were
reported, one triploidy (69, XXX), one Klinefelter Syndrome (47, XXY)
and one trisomy 13 (8).
Therefore, if a normal karyotype is obtained, the differential diagnosis
should rule out a partial hydatidiform mole.
The next challenge is to differentiate PMD and complete mole with a
coexisting normal fetus with a normal karyotype and a multi-cystic
appearing placenta. A molar pregnancy with a live fetus carries a high
malignancy risk with a significant maternal morbidity (3). Persistent
gestational trophoblastic disease can occur in up to 20% of these
pregnancies (3), and this is why it is important to correctly diagnose
the disease.
While CVS is primarily performed for a genetic analysis, it could also
be used to obtain larger villi samples for a histological examination. A
well known marker, p57, is a cyclin-dependent kinase inhibitor, derived
from the maternally expressed and paternally imprinted CDKN1C gene located on chromosome 11p15.5 (9).
Due to the lack of contribution of maternal DNA in complete moles, the
p57 expression is absent in villous stromal cells and cytotrophoblast
and this characteristic may be exploited in an immunohistochemistry
analysis to differentiate between PMD and complete mole (7, 9). These
two entities can therefore be distinguished by p57 immunostaining
combined with DNA genotyping. This is not performed as a matter of
routine, but could be an extra option in some complicated cases.
Biological data
Along with the early invasive testing, hCG and MSAFP dosage performed
right after the first trimester ultrasound had a valuable role for the
PMD diagnosis. MSAFP levels have been shown to be elevated in PMD. It is
hypothesized that the enlarged placental volume resulting in a
substantial surface area combined with thin walled arteries, enables an
increased transfer of AFP into the maternal circulation, while HCG
levels can be normal to slightly elevated for GA (7).
Imaging
Magnetic Resonance Imaging (MRI) is an additional diagnostic tool
allowing a thorough and wider placental evaluation as well as obtaining
a more detailed fetal view, thanks to its relative independence from the
patient’s body mass index (BMI) and high contrast resolution (10). MRI
findings of PMD include an enlarged placenta with dilated vessels as
well as heterogeneous signals (10, 11). Hemorrhage within the cystic
part of the placenta might be associated with a molar pregnancy although
it is not a specific sign (11). In our case, a large cystic area in the
apical zone of the placenta was noted, supporting a PMD diagnosis.
Maternal and fetal complications
In the review of 64 reported cases conducted by Nayeri et al. it is
reported that only a small number of pregnancies (9%) affected by PMD
are free from feto-maternal complications (3). Maternal complications
include gestational hypertension, preeclampsia, HELLP syndrome
(hemolysis, elevated liver enzymes, low platelets) and eclampsia (1-3,
6).
Thus, a daily regimen of low dose aspirin was introduced at only 13
weeks of GA by our team to lower our patient’s risk of developing
preeclampsia. In our current knowledge, no other team has done the same.
Fetal complications consist of induced premature labor, spontaneous
preterm delivery, in utero fetal growth restriction (IUGR), in utero
fetal demise (IUFD) and BWS (1-3, 6). Neonatal complications include
hematological disorders, such as anemia and thrombocytopenia and liver
tumors, specifically mesenchymal hamartomas (1).
Up to 23% of fetuses can be affected by BWS (8), a multisystem genomic
imprinting disorder characterized by mosaic genetic and epigenetic
defects within the 11p15.5 region, which contains genes such asCDKN1C and IGF2 , regulators of fetal growth (12). Fetal
clinical expression of BWS may be wide, with macrosomia, macroglossia,
exomphalos and organomegaly as main suggestive features, if present
(12). Although molecular testing is possible with CVS and amniocentesis,
a negative result should not falsely reassure the medical team due to
the genetic mosaicism of BWS.
Lastly, the rate of IUFD in a review of 109 cases was found to be as
high as 29,4% at the median age of 31 weeks of GA (13). It is theorized
that the combination of vascular malformations of the placental vessels
and thrombosis in the stem villi blood vessels as well as their
decreased functional capacity, leads to chronic hypoxia (14).
Joined to the high risk of hemorrhage secondary to the rupture of thin
walled and dilated chorionic vessels, PMD ultimately might conduct to
IUFD (1).
Hence our team’s decision to induce labor as soon as a novel thrombotic
zone was noted in association with a subjective decrease in fetal
movements.
PMD is a rare condition affecting the placenta’s histology, anatomy and
function, altering the exchanges’ quality between mother and fetus and
leading to a multitude of feto-maternal complications.
While it is essential to include PMD in the differential diagnosis when
the placenta appears enlarged, thick and multicystic with a normal fetus
to avoid an unnecessary pregnancy termination, it is also of the utmost
importance to rule out gestational trophoblastic disease in light of the
high maternal malignancy risk.
A multidisciplinary team involving obstetricians, pediatricians, MFM
specialists, geneticists, radiologists, pathologists, midwives and
psychologists is key to the diagnosis and a tailored management of the
pregnancy in order to minimize fetal and/or maternal adverse outcomes.