Immature monochorionic twin placenta with: 1. Massive intervillous histiocytosis (baby A) 2. Ischemic change (baby B)
Cynthia Kaplan, SUNY-Stony Brook Stony Brook, New York
Clinical history
These twins were born at 26 weeks gestation to a 20 year old 0+ woman with preterm labor. The placenta was
diamniotic monochorionic with a large artery-to-artery anastomosis. Cords were labeled with 1 and 2 clamps
and both inserted eccentrically into their respective portions of the disk. There was substantial
disruption of the maternal surfaces of both, with approximate weights of the portions referable to "1" and
"2" as 160 and 120 grams respectively. Baby A weighed 936 grams with initial hematocrit of 52%. In
addition to respiratory distress, the infant had thrombocytopenia the first few days of life. A grade II
intraventricular hemorrhage had largely resolved by discharge at 2 months of age. Baby B was 894 grams with
initial hematocrit of 44%. In addition to respiratory distress, neutropenia was present the first few days
of life. A grade II intraventricular hemorrhage had partially resolved by discharge at 2 months. Slides 18
and 19 are from the placenta of Baby A and Slides 20 and 21 from that of Baby B. Slide 22 is dividing
membrane.
Immature chorionic villi with massive infiltration of histiocytic cells in the maternal blood in the adjacent intervillous space.
Immature chorionic villi without intervillous histiocytosis.
Dividing membranes from diamniotic monochrionic placenta.
Diagnosis
Immature monochorionic twin placenta with:
1. Massive intervillous histiocytosis (Baby A)
2. Ischemic change (Baby B)
Discussion
This case was chosen both to highlight both the importance of careful examination of twin placentas and to
demonstrate an often missed or misdiagnosed process, massive intervillous histiocytosis (MIH).
The examination of twin placentas has proven particularly useful in understanding the importance of
intrinsic and extrinsic factors in pathologic processes and perinatal diseases. Preterm delivery is typical
of multiple gestations. While chorioamnionitis may be a factor, it is much less common in multiples than in
the entire group of preterm births. Factors related to uterine distension and relatively insufficient blood
flow are likely also important. In monochorionic twins the transfusion syndrome is an additional factor in
early delivery. Twins tend to have lower birth weights than singletons of the same gestational age. Birth
weight is slightly reduced when velamentous cord insertions or single umbilical arteries are present. Site
of implantation and relative placental size are also important.
These twins are monochorionic, and thus monozygotic, with a large artery-to-artery anastomosis. Such
equalizing connections tend to protect against severe chronic twin-twin transfusion, though permitting acute
ones. There was no history of oligohydramnios or polyhydramnios, and the birth weights were similar,
although the hematocrit of the second twin was slightly lower, possibly an acute change. Umbilical cords
were normal. The expectation from the gross examination and clinical history is for rather similar looking
placental portions microscopically. The histology is, however, markedly different between the pair.
Multiple sections clearly show an infiltration of histiocytic cells in the intervillous spaces of placenta I
(A). There is no such cellularity in II (B). The villi are otherwise generally appropriate for the
gestational age with some changes of low blood flow, particularly in placenta II.
MIH is a process of unknown etiology characterized by an infiltrate of histiocytic cells surrounding
chorionic villi with occasionally intravillous infiltration. There tends to be an associated increase in
fibrin deposition and some villous degeneration. Although the histiocytes are in the maternal spaces,
mother's blood count in no way reflects the abnormality in the placenta. This change is often seen within
the spectrum of disorders that range from massive intervillous fibrin deposition/maternal floor infarction
to extensive chronic villitis. Elements of all these processes are frequently seen in differing areas of
the same cases, with transition regions. Intervillous histiocytosis (as well as the other disorders
previously noted) are associated with intrauterine growth retardation and fetal demise, and tend to recur in
subsequent pregnancies. There is no specific treatment recognized currently for this process, but careful
fetal monitoring and early delivery on any signs of clinical compromise have yielded viable infants in some
cases. Some patients treated with heparin have also gone on to viable deliveries.
Intervillous histiocytosis in particular is recognized at a wide spectrum of gestational ages. It does
occur in the second trimester and can be identified as an etiology of recurrent fetal demise. It is
particularly difficult to recognize in fragmented placentas with extensive changes of longstanding fetal
demise.
As noted previously, the etiology of MIH and the related lesions is not clearly identified; however several
possibilities exist including infection, immune reaction, and response to altered blood flow. A prior study
of villitis in twins showed concordance in virtually all sets of monochorionic twins with only one set
displaying some difference in severity.
Difference in severity of transplacental (hematogenous-type) infection in twins is certainly recognized,
although less common in monozygotic sets. Recurrence with increasing severity is not typical of most known
placental infections. Tests for recognized agents have proved negative in such cases, but the possibility
of an unusual or unique organism remains. The infection most closely resembling MIH histologically is
maternal malaria; however parasites will be seen in such cases.
Immune reactions, similar to graft versus host reaction or "placental rejection" have been favored by many
as the etiology, partly because these processes are often recurrent and may be most prominent at the base of
the placenta, the site of close maternal-fetal interaction. The origin of the cells in villitis is not
entirely clear, whether they are intrinsically fetal or from maternal invasion. Older studies with
y-markers had suggested a maternal intravillous component. The marked discrepancy in involvement of the
placenta in this case is unexpected with an immune reaction, as presumably these fetuses are virtually
identical genetically. While this favors a non-immune etiology, there are rare cases of heterokaryotic
monozygotic twins and of apparent polar body fertilization which could lead to different genotypes.
Villitis is often described to be more frequent in pre-eclampsia. Degenerating villi adjacent to infarcts
may have a hyper-cellular appearance, which should not be confused with a true infiltrate of inflammatory
cells. (Of note, the diagnosis of villitis has a poor correlation even among experienced pathologists.)
While true villitis does appear to be increased in this population, the vast majority of villitis cases do
not show other typical changes of low maternal blood flow. The microenvironments of monochorionic twins
commonly include differences in blood flow, but discordant villitis is rare.
Thus the origin of villitis and MIH remain unknown currently, however these processes are not rare in
placental histology and may have important clinical implications. In the case presented, the placental
findings in A would usually lead to a growth retarded infant. It is actually slightly larger than B. B does
show more placental change of low blood flow, and may be smaller than its inherent potential on this basis.
Possibly, a minor degree of transfusion syndrome with B as donor (chronic and acute) was present. The
similarity in size of A to B reflects A's diminished growth from another factor (MIH). Had the pregnancy
proceeded longer, A's growth may have become more impaired. If intrauterine death of this infant occurred,
B would have been at considerable risk of vascular disruptive phenomena.
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