Placental Development, Indications for and Methods of Examination
Section 2 -
Phyllis C. Huettner, M.D.
Circulatory disorders of the placenta are common and are
frequently clinically important for both the mother and the baby. It is important to keep in mind that
the placenta has a dual circulation; disorders of the maternal circulation give rise to one set of
abnormalities and clinical problems and disorders of the fetal circulation to another.
Maternal Circulatory Disorders
Case 1 : Massive Perivillous Fibrin Deposition
Massive Perivillous Fibrin Deposition
Some fibrin is seen normally in most placentas and is particularly common beneath the
chorionic plate, around stem villi, and above the basal plate. This type of fibrin deposition is
thought to be due to local stasis and eddy currents in these areas and may actually reflect good
intraplacental blood flow, as this type of fibrin deposition is seen less commonly in placentas from
abnormal pregnancies such as those complicated by preterm delivery and diabetes.
Large amounts of fibrinoid material can be appreciated grossly as firm white, yellow or brown
plaques. These may be slightly granular or smooth. Often they are located in the periphery of the
placenta where they fill in the angle where the fetal membranes meet the basal plate. Much less commonly
the fibrinoid material forms thick white or grey strands that replace much of the placental parenchyma
leaving only small pockets of interspersed red villous tissue.
Microscopically, the terminal villi are widely separated and enmeshed in an abundant amount
of eosinophilic fibrinoid material that obliterates the intervillous space. In early lesions, the
syncytiotrophoblast shows signs of degeneration and eventually disappears leaving behind a thickened
trophoblastic basement membrane. The cytotrophoblast show a marked degree of proliferation and extends
out into the perivillous fibrin. The villous stroma becomes progressively more fibrotic and eventually
there is obliteration of fetal vessels.
In order to separate the normal amount of fibrin seen in the placenta from fibrin deposition
that is likely to be clinically significant, Katzman and Genest have proposed some quantitative
definitions. Transmural massive perivillous fibrin deposition (MFD) is defined as perivillous fibrinoid
material that extends from the maternal to the fetal surface encasing greater than or equal to 50% of the
villi on at least
one slide. Borderline MFD is transmural or nearly transmural and encases 25% to 50% of the villi on
at least one slide.
The differential diagnostic considerations include maternal floor infarct, placental infarct,
fibrin associated with chronic villitis and fibrinoid deposition after fetal death with retained
placenta. Maternal floor infarct has similar microscopic features, shares similar clinical features and
often is associated with massive perivillous fibrin deposition. By definition, maternal floor infarct
involves the villi near the maternal surface. Infarcts may be difficult to distinguish from perivillous
fibrin deposition grossly, although they tend to be more sharply circumscribed and abut the maternal
surface of the placenta. Microscopically, infarcts show collapse rather than expansion of the
intervillous space, no thickening of the trophoblastic basement membrane, no cytotrophoblast hyperplasia,
and necrosis rather than fibrosis of the villous stroma. Cases of fibrin deposition associated with
chronic villitis usually have areas of active villits.
MFD, while quite rare, estimated to involve 0.28 to 0.5% of examined placentas, is an
important lesion for pathologists to recognize because it is associated with an adverse fetal outcome.
What is likely to be clinically significant is the location of the perivillous fibrin and the number of
villi that are ischemic as a result of it. Redline and Patterson observed that perivillous fibrin that
entrapped more than 20% of the terminal villi in the central basal portion of the placenta, which is
thought to be the major nutrient-exchanging region, was significantly associated with intrauterine fetal
growth retardation and low placental weight. Although not as carefully localized or quantitated, a study
by Fuke et al also found a significant relationship between massive perivillous fibrin deposition and
intrauterine growth retardation. These workers observed that the combination of intrauterine growth
retardation and MFD could recur in subsequent pregnancies and could be prevented with anticoagulant
therapy. Katzman and Genest reported a 31% incidence of IUGR in cases with MFD. About 14% of their
cases had recurrent MFD or maternal floor infarct in subsequent 2nd or 3rd
trimester placentas and 50% had increased perivillous fibrin or maternal floor infarct in 1st
trimester placentas. Kumazaki et al found a significant relationship between MFD in the placentas of
preterm infants and periventricular leukomalacia.
Maternal Floor Infarct
The term maternal floor infarct (MFI) is a misnomer in that no true infarction is seen.
Grossly, the maternal surface of the placenta is covered by a thickened yellow plaque. Microscopically,
there is heavy deposition of fibrin around the villi near the maternal surface of the placenta and in the
decidua basalis. Often the perivillous fibrin extensively surrounds villi in the parenchyma of the
placenta. The villi surrounded by fibrin eventually become ischemic. As mentioned above, there is
significant overlap with MFD and these entities are not always clearly separated in the literature.
Katzman and Genest have proposed a quantitative definition for classic MFI requiring that basal villi of
the entire maternal floor be encased in perivillous fibrinoid greater than or equal to 3 mm in thickness
on at least one slide.
In a large study of over 39,000 placentas, MFI, defined as involving at least one third of
the maternal surface, was identified in about 1 in 200 cases. In other series it is much less common.
Katzman and Genest found that many cases diagnosed as MFI represent MFD or other entities.
MFI is an important disorder for pathologists to be aware of. It is associated with stillbirth in 13 to
50% of cases. Many of the liveborn infants, 24% to 100%, are growth retarded, many of them profoundly
so. Preterm delivery occurs in 26% to 60% of cases. MFI in preterm infants has been shown to be an
independent predictor of neurodevelopmental impairment. MFI can recur in subsequent pregnancies in as
many as 12% to 78% of cases. It is very important that pathologists correctly diagnose maternal floor
infarction so that these subsequent pregnancies can be carefully monitored. Maternal floor infarct often
develops very rapidly in the third trimester but studies have shown that intervention at the first sign
of trouble can result in successful outcomes in these subsequent pregnancies. For this reason
pathologists should look for maternal floor infarct in all cases of growth retardation, preterm delivery
and fetal death so that if found, subsequent pregnancies can be followed carefully.
The pathogenesis of MFI and MFD are likely related and will be considered together here. The
material deposited in the intervillous space is composed of fibrin thought to be of maternal origin,
other proteins from the coagulation cascade and extracellular matrix proteins that may have a fetal,
placental or maternal origin. It is almost certainly the presence of this material in the intervillous
space, interfering with nutrient exchange between mother and fetus, that causes the adverse effect on the
fetus. What causes this material to be deposited is unclear. Many patients have coagulation
abnormalities or autoimmune disorders such as anti-phospholipid antibodies. Some cases are associated
with infection. It has recently been proposed that fetal disorders may contribute as MFI has been
described in a fetus with long chain 3-hydroxyacyl-CoA dehydrogenase deficiency and in only one of
Plaques of subchorionic fibrin are seen in about 20% of placentas. On gross examination
these appear as laminated white plaques that are roughly triangular with the broad base immediately
beneath the chorionic plate. The area closest to the intervillous space may show fresh red clot.
Microscopically, subchorionic fibrin plaques are sharply demarcated from the surrounding
tissue and contain no villi. They consist of laminated layers of fibrin with red cells at the junction
with the intervillous space. The overlying chorionic plate shows no evidence of degeneration. The
pathogenesis of this lesion is also thought to be secondary to stasis of maternal blood in the apex of
the intervillous space. Most agree that subchorionic fibrin is of no clinical significance but Naeye has
documented decreased subchorionic fibrin in conditions associated with decreased fetal movements and has
suggested that fetal movements that strike the chorionic plate may play a role in the formation of
Placental infarcts are common lesions seen in about 10% to 25% of placentas from normal
pregnancies. Infarcts can vary in size and shape but are usually somewhat triangular with the broad edge
abutting the basal plate. They are more commonly found in the peripheral regions of the placenta, where
blood flow is les optimal. Recent infarcts are dark red, firm and granular. With age they become yellow
and eventually white. Occasionally, central hemorrhage with cavitation is seen.
Microscopically, in early infarction the villi become crowded with narrowing of the
intervillous space. The fetal vessels in the affected area are dilated and congested. The
syncytiotrophoblast nuclei show signs of degeneration such as nuclear pyknosis and karyorrhexis. With
time, the villous stroma and syncytiotrophoblast degenerate and eventually only "ghosts" of villi
remain. The intervillous space no longer contains maternal red cells. Neutrophils and macrophages may
be seen at the periphery of a longstanding infarct but no true organization occurs.
Like infarcts elsewhere in the body placental infarcts are caused by an interruption of the
blood supply to a portion of the placenta. It is maternal blood, percolating in the intervillous space
that supplies and nourishes the placenta. When this blood supply is cut off, the relatively well
circumscribed area of villous tissue supplied by a particular maternal vessel or group of vessels
undergoes infarction. This can occur because of vascular narrowing or occlusion of the vessel as in
atherosis, with or without superimposed acute thrombosis, or because the supplying maternal vessel is
physically separated from the placenta, as in retroplacental hematoma. Histologic sections of the
decidua beneath an infarct may demonstrate these pathologic changes. Often the decidua is extensively
necrotic indicating that the involved vessel is deep,
near the myometrial-decidual junction. McDermott and Gillian have presented evidence that infarcts
are also accompanied by a concomitant reduction in fetal blood flow to the villi in the infarcted area.
Extensive infarction, large infarcts (>3 cm), central infarcts, and infarcts in the first
and second trimester are usually associated with significant underlying maternal disease. Preeclampsia
represents a major risk factor for infarction. There is a strong relationship between the severity of
preeclampsia and the extent of infarction. Increased rates of placental infarction have also been
reported in a variety of thrombophilic conditions including factor V Leiden mutation heterozygosity,
prothrombin gene variants, hyperhomocyteinemia, and antiphospholipid antibodies.
Extensive infarction may have serious consequences for the fetus including intrauterine fetal
demise, hypoxia, and intrauterine growth retardation. It is thought that the normal placenta can
withstand the loss of as much as 15 to 20% of the villous tissue without adversely affecting the fetus,
but in conditions in which there is already low flow to the placenta, such as preeclampsia, even lesser
degrees of infarction may be detrimental to the fetus. Extensive infarction in the placentas of preterm
infants has been significantly associated with periventricular leukomalacia. High rates of infarction
(85%) and low flow changes (55%) were also noted in a series of stillborn infants with ischemic cerebral
injury. However, at least one study has found no correlation between placental infarcts and growth or
neurodevelopmental abnormalities in the first year of life in growth restricted infants.
A retroplacental hematoma is a blood clot that lies between the basal plate of the placenta
and the uterine wall and indents the overlying placental parenchyma. It may be large, covering most of
the maternal surface, or small, best visualized on serial sections. A recent retroplacental hematoma
will be soft and red and will easily separate from the placenta. An indentation, a disrupted maternal
surface, a large amount of clot in the specimen container, the delivering physician's impression of the
placenta when delivered or at the time of Cesarean section may all point to the diagnosis in the absence
of adherent clot. Older hematomas are firm, brown and adherent. Sometimes the placental parenchyma
overlying older hematomas is infarcted. Occasionally a hematoma may rupture and dissect into adjacent
villous tissue. In a very recent retroplacental bleed there may be no clot adherent to the placenta and
no deformation of the maternal surface.
Microscopically, early hematomas are composed of red cells while older ones contain varying
amounts of fibrin, degenerated red cells, hemosiderin-laden macrophages and neutrophils. The overlying
decidua may be necrotic. Villous stromal hemorrhage and villous edema may be seen adjacent to
retroplacental hematoma, particularly when the hematoma occurs earlier in gestation (16 to 28 weeks).
Retroplacental hematoma is related to, but not synonymous with, the clinical syndrome of
placental abruption (abruptio placentae). The features of this clinical syndrome include vaginal
bleeding, increased uterine tone, uterine tenderness, diminished fetal heart tones and if severe,
maternal hypovolemia, consumptive coagulopathy, and fetal death. The incidence of abruption is about
11.5/1000 deliveries. It is associated with a 20% to 40% fetal mortality rate and accounts for 10% of
all stillbirths and 6% of all maternal deaths. The rate of placental abruption in the United States has
increased in the last few decades.
Retroplacental hematoma and placental abruption share many of the same risk factors and a
clear distinction between them has not always been made in the literature. In only about a third of the
cases with a clinical diagnosis of abruption can a retroplacental hematoma be demonstrated on placental
examination, probably because of the rapidity of development and subsequent delivery. Conversely, in
only about a third of cases in which the pathologist identifies a retroplacental hematoma will the
clinical syndrome of placental abruption have been diagnosed. These probably represent smaller,
clinically insignificant hematomas.
Retroplacental hematomas are common, occurring in as many as 4.5% of placentas. The most
consistently identified risk factors for retroplacental bleeding include preeclampsia with a three fold
increase, abdominal trauma, cigarette smoking, both maternal and of male partner, a previous history of
abruption, extremes of maternal age, multiparity, poor nutrition, low socioeconomic status, acute
chorioamnionitis, severe fetal growth retardation, maternal thrombophilic conditions, and cocaine abuse.
The pathogenesis of retroplacental hematoma is not well understood. It is thought that in
cases of preeclampsia the associated atherosis may weaken the vessels increasing the likelihood of
rupture. Cigarette smoking and cocaine abuse may also damage vessels walls. Hyperhomocysteinemia and
hereditary deficiencies in various factors involved in normal coagulation may also lead to thrombosis and
possibly vascular damage.
The clinical significance of retroplacental hematoma is largely dependant on the size and the
amount of placenta that is infarcted, keeping in mind that in a background of chronic uteroplacental
ischemia, such as with preeclampsia, the functional reserve of the placenta will be exceeded with lesser
degrees of infarction. Extensive retroplacental hematoma may result in fetal death and has been
associated with periventricular leukomalacia in preterm infants.
Marginal hematoma is a crescent-shaped hematoma at the lateral edge of the placenta where the
fetal membranes meet the edge of the placental disc. The blood clot may be adherent to the fetal
membranes or extend as a thin layer over an adjacent area of maternal surface without indentation of this
surface. Microscopically, marginal hematomas are composed of blood, fibrin and occasional neutrophils.
Fox reports that marginal hematomas are found in 1.9% of placentas. The bleeding is the
result of rupture of uteroplacental veins at the margin during separation of the spongy and compact
layers of the decidua. This occurs most commonly in patients with lateral placenta previa, or low lying
Intervillous thrombohematomas, are seen in from 3% to 50% of uncomplicated pregnancies and in
up to 78% of pregnancies with complications. They are particularly common in the third trimester.
Grossly, they are round to oval and may range in size from a few millimeters to 5 cm with a mean size of
1.5 cm. They are most often located midway between the basal plate and the chorionic plate but may abut
the basal plate. Early intervillous thrombohematomas are dark red and soft. With age they become firmer
and progressively more pale and laminated. Microscopically, intervillous thrombohematomas consist of
degenerated red cells between lamina of fibrin. The lesion itself contains no villi but compressed or
infarcted villi sometimes rim the periphery.
An immunohistochemical study utilizing antibody to fetal hemoglobin demonstrated that
intervillous thrombohematomas contain both fetal and maternal blood. Careful histologic examination of
villi from normal placentas has demonstrated breaks in the trophoblast overlying vasculosyncytial
membranes often covered with a blob of fibrin in up to 60% of cases, providing a mechanism for entry of
fetal blood into the intervillous space. The formation of a clot may serve a protective role in that it
limits the amount of fetal hemorrhage and reduces the amount of potentially antigenic fetal blood that
can enter the maternal circulation.
Intervillous thrombohematomas themselves are not the cause of increased fetal morbidity or
mortality. Their significance is as a marker for fetal hemorrhage and entry of fetal blood into the
maternal circulation. There is good correlation between the number of intervillous thrombohematomas and
the degree of fetomaternal hemorrhage as measured by the Kleihauer-Betke test on maternal blood.
Occasionally, fetal hemorrhage can be extensive and result in intrauterine demise or severe anemia.
Although Rh isoimmunization is uncommon now thanks to the widespread use of Rhogam, fetomaternal
hemorrhage may still sensitize a mother against uncommon and private fetal antigens with adverse
consequences for subsequent pregnancies.
These are deep purple collections of liquid blood that pool between the amnion and the
chorion. They are usually small and are thought to be the result of recent trauma to surface veins on
the chorionic plate during delivery such as from umbilical cord traction. Since this occurs after
delivery of the baby, they are not clinically significant for the infant. Occasionally subamniotic
hematoma may be the result of laceration of a vessel at the time of amniocentesis. Careful examination
of the vessels may localize the site of trauma. In this situation, there may be consequences for the
Massive Subchorial Thrombosis
This condition, also known as massive subchorionic thrombohematoma or Breus' mole, is by
definition a red thrombus measuring at least 1 cm in thickness situated immediately beneath the chorionic
plate. Often the fetal plate shows bulging elevations where the thrombus protrudes into the amniotic
cavity. Extension deep into the placental parenchyma may also be seen. Microscopically, massive
subchorial thrombosis is composed of clotted red cells that separate the chorionic plate from the
underlying villi over much of its area.
Massive subchorial thrombosis is quite rare, occurring in 0.53 per 1000 placentas from one
large series. It is often associated with stillbirth and neonatal death although it is no longer thought
to be secondary to fetal death as it once was. As many as 41% of cases have intrauterine growth
The pathogenesis of Breus' mole is uncertain. Some speculate that it is the result of
sudden, marked stasis of maternal blood in the intervillous space such as could occur by obliteration of
venous channels draining this space, but the cause of such obliteration is unknown. Others believe it is
due to rupture of a large vessel on the chorionic plate or in a stem villus. It is thought that a large
clot near the umbilical cord could impede flow through the cord resulting in growth restriction or
Fetal Circulatory Disorders
Case 2: Fetal Thrombotic Vasculopathy
Fetal Vascular Obstruction
Occlusion of vessels in the fetal circulatory system can involve vessels at any level - large
umbilical cord vessels, their branches on the chorionic plate, or smaller fetal vessels within the
chorionic villi. Remember that during gestation there is one continuous circulation between the fetus
and the placenta. The term fetal vascular obstruction used in this discussion refers to thrombi or
related lesions in the fetal portion of the placental circulation. It has become increasingly clear that
thrombotic lesions in the placental part of this fetal circulation may be associated with, and could
serve as a marker for, thrombotic or embolic lesions
in the circulation of the fetus itself, sometimes with devastating consequences for the fetus. For
this reason, it is important for pathologists to become familiar with the gross and microscopic
appearance of fetal vascular obstructive lesions in the placenta.
On gross examination, areas of fetal vascular obstruction in the placenta form well
circumscribed, pale areas with the same spongy consistency as the surrounding tissue. This contrasts
with the increased firmess characteristic of infarcts, which may also be pale and well circumscribed.
Microscopically, the affected villi are avascular and sharply demarcated from adjacent normal villi.
There is an increased amount of bland stromal hyaline fibrosis. The villi are normally spaced within the
intervillous space, not compact as would be seen in an infarct.
Redline et al recently proposed diagnostic terminology with precise, reproducible definitions
for lesions of fetal vascular obstruction. The term uniformly avascular villi is used when three or more
foci of two terminal villi show avascularity. Another form of fetal vascular obstruction that manifests
in distal villi has been termed villous stromal-vascular karyorrhexis. This can be diagnosed when three
or more foci of two or more terminal villi show karyorrhexis of fetal cells – endothelium, stromal cells
or blood cell elements. Often the villi are hypovascular with degenerating capillaries and fragmented
red cells. This lesion has been termed hemorrhagic endovasculitis in the past. It is now thought to
represent part of the spectrum of changes in fetal vascular obstruction as both patterns coexist and both
share the same predisposing risk factors and carry similar implications for the fetus. A third pattern
termed villitis of unknown etiology (VUE) with obliterative fetal vasculopathy is diagnosed when VUE
extends to stem villi and is associated with stem villus vasculitis and vascular occlusion with
associated avascular villi in the downstream villi. All of these villous changes are considered severe
when there are more than two foci that average 15 or more villi per focus per slide. It is recommended
that the term fetal thrombotic vasculopathy be reserved for those cases in which the villous vascular
obstruction is extensive.
Studies have shown that the thrombosed large vessel upstream from avascular terminal villi or
villous stromal-vascular karyorrhexis can only be demonstrated in about 30% of cases when extensive
avascular villi are present. The distal villous changes have been shown to be more sensitive and
reproducible than large vessel lesions. A thrombus in a large vessel can be reliably diagnosed when two
of three features are present: fibrin strands, glassy texture or endothelial adherence.
The main differential diagnostic consideration is with the villous changes associated with
intrauterine fetal demise. The microscopic changes are the same but with intrauterine fetal demise, the
process is generalized involving all villi and all vessels of a similar size to the same degree, in
contrast to the sharply demarcated areas of avascularity in fetal vascular obstruction.
The pathogenesis fetal vascular obstruction in the placenta is usually related to stasis,
hypercoagulability or vascular damage. There is an association with a variety of cord abnormalities
including velamentous cord insertion, excessive cord twisting, nuchal cord, other encirclements, and very
long cords. In these situations, clot may propagate downstream from an area of thrombosis in the cord or
from the intramembranous segments of the cord vessels that are not protected by Wharton's jelly and
therefore are prone to thrombosis. There is also an association with chorioamnionitis. The mediators of
the inflammatory process trigger the coagulation cascade at several points. The incidence of thrombosis
in the placental part of the fetal circulation is also increased in the placentas of diabetic mothers for
reasons that are not well understood. There is some evidence that fetal vascular obstructive lesions in
the fetal circulation of the placenta may be associated with abnormalities of fetal coagulation, but an
inherited coagulopathy in the fetus probably acts as an additional factor tipping the balance towards
thrombosis because a recent study found no increase in these lesions in infants known to harbor mutations
in hereditary thrombophilic disorders.
Fetal vascular obstructive lesions in fetal circulation of the placenta may be associated
with thrombotic lesions in the fetus itself or with fetal conditions such as cerebral palsy that may have
thrombosis as part of its pathogenesis. Redline and Pappin, using avascular villi as a marker of this
process, found that cases with extensive areas of avascular villi were significantly associated with
fetal growth retardation, oligohydramnios in the absence of membrane rupture and acute and chronic
monitoring abnormalities. In a subset of this group that was over 34 weeks, did not have malformations
and did not have other major
placental pathology, the presence of very large areas of avascular villi, diffuse platelet aggregates
or intravascular fibrin strands was highly associated with major thrombotic events in the fetus. In a
study of term, singleton infants with neonatal encephalopathy, McDonald et al found that fetal thrombotic
vasculopathy, endothelial cushions and accelerated villous maturation were all independently and
significantly associated with neonatal encephalopathy. Kraus has described a high rate of downstream
avascular villi and thrombi in fetal placental vessels in a selected group of infants with cerebral palsy
referred for the purpose of litigation. Redline et al, studying a similar population, also found
extensive avascular villi in about 18% of term cases with long-term neurologic impairment. Potentially
obstructing umbilical cord abnormalities were much more likely in infants with fetal thrombotic
vasculopathy. In a study of 84 consecutive perinatal autopsies, Kraus found fetal vascular obstructive
lesions in the placentas of 16 cases. The areas of fetal vascular obstructive lesions were extensive in
the placentas of all cases and occupied 25 to 40% of the placenta in four cases. In these four cases,
the extensive fetal vascular obstructive lesions were the only explanation for the fetal death. Six of
these cases had thrombi in fetal organs including the brain, kidney and lungs. Eight of the mothers had
an extensive work up for coagulopathy and five had one or more coagulation abnormalities. One study,
analyzing placental tissue from cases of fetal thrombotic vasculopathy, found an increased incidence of
factor V Leiden and prothrombin mutations in the fetal tissue, indicating that the fetus may have
inherited a coagulopathy. In another series, however, there was no correlation between the presence of
the most common hereditary thrombophilic mutations in the fetus and/or the mother and fetal avascular
lesions in the placenta.
These findings indicate that fetal vascular obstructive lesions in the placenta, particularly if
extensive, may be a reliable indicator of the potential for thrombi in the circulation of the fetus or
newborn and may explain adverse perinatal outcome and some perinatal deaths. Prospective studies will be
needed to determine the predictive value of fetal vascular obstructive lesions for various adverse fetal
outcomes such as neurologic impairment. Further studies are also needed to determine the clinically
significant amount of avascular villi, the appropriate work up for this finding, and what role, if any,
there is for treatment in subsequent pregnancies.
Placental chorangioma is best considered a hamartomatous rather than neoplastic collection of
fetal blood vessels of varying types. Large chorangiomas are uncommon, recognized grossly in 1 in 13,000
deliveries. About 1% of carefully sampled, microscopically examined placentas, however, will contain
Grossly, large nodules of firm red or gray-pink tissue may bulge from the fetal or maternal
surfaces. The cut surface is homogeneous. Smaller lesions may be difficult to identify, grossly,
however, especially in the unfixed placenta. Microscopically, they are composed predominantly of
thin-walled, capillary-type vessels. Chorangiomas without many red cells will appear more cellular.
Rarely, chorangiomas exhibit cytologic atypia and increased mitotic activity but biologic aggressiveness
has not been reported.
Isolated small chorangiomas and most large ones are without clinical significance. Some large
chorangiomas may, however, be associated with polyhydramnios, preterm delivery, antepartum bleeding,
hydrops fetalis, anemia, thrombocytopenia, and cardiomegaly. One study has found a relationship between
the size of the chorangioma and the presence of intrauterine growth retardation. Sometimes a large
chorangioma or multiple small ones is the only explanation for growth retardation. Large chorangiomas
are not usually associated with fetal anomalies although the incidence of hemangiomas elsewhere in the
fetus is about six times that expected. Some have postulated that infantile hemangiomas may be of
The fetal and neonatal mortality rate associated with large chorangiomas is as high as 40%.
Occasionally chorangiomas recur in successive pregnancies. In these cases the chorangiomas are
frequently multiple and the fetal outcome is often poor.
This vascular lesion may alter fetal hemodynamics in two ways. The tumor may act as a left
to right shunt increasing the workload of the fetal heart culminating in heart failure. Alternatively,
blood that has passed through the chorangioma which, if large, is not in contact with the maternal blood
in the intervillous space, will be low in oxygen when returned to the fetus resulting in chronic hypoxia.
Various treatments for chorangiomas that are adversely affecting fetal hemodynamics have been
described in the literature including ligation, laser, and injection of absolute alcohol into the feeding
vessel or lesion and cordocentesis to treat the resulting anemia. These have been variably successful.
Chorangiosis and Chorangiomatosis
Chorangiosis is defined as the presence of more than 10 capillaries per terminal villus in 10
terminal villi in at least three different regions of the placenta. Care should be taken to distinguish
this lesion from congestion. In fact, in many cases with true chorangiosis, the villi contain many more
than 10 capillaries. The stem villi in this process do not show an increased number of capillaries.
Each capillary is surrounded by a distinct basement membrane but not by smooth muscle actin positive
Chorangiosis is found predominantly in placentas from gestations of at least 37 weeks. The
prevalence of this finding is estimated to be about 5%. Associated placental findings include large
placental size, delayed villous maturation, chronic villitis, lesions associated with acute and chronic
placental ischemia and cord lesions. Associated clinical findings include maternal diabetes, congenital
anomalies, delivery at high altitude, maternal anemia, maternal smoking and twin gestations.
The pathogenesis of chorangiosis is still not understood. One possibility is that capillary
proliferation occurs in response to hypoxia or chronic inflammation. Another possibility is that the
increased capillary proliferation is related to increased intramural pressure due to venous obstruction
at the level of the umbilical cord or fetal heart. Still another possibility is that cytokines released
from inflammatory cells, in cases with chronic villitis, trigger capillary proliferation.
Chorangiomatosis is a recently described, morphologically similar lesion. In contrast to
chorangiosis in which the vessel proliferation occurs in the terminal villi, in chorangiomatosis, there
is endothelial and perithelial proliferation in multiple stem villi and terminal villi. The lesion is
not nodular and expansile like a chorangioma, however. A distinct basement membrane is not seen around
each vessel but there is a uniform layer of SMA-positive pericytes around each capillary.
Chorangiomatosis is thought to arise from the subtrophoblastic rim of connective tissue in immature stem
villi. The pathogenesis is not known.
Chorangiomastosis is uncommon, occurring in about 1% of placentas and appears to be more
closely related to chorangioma; these two lesions are commonly associated with each other. This lesion
is most common between 32 and 36 weeks of gestation. It is associated with preeclampsia and multiple
gestation but not with maternal diabetes. Diffuse, multifocal chorangiomatosis occurs at even earlier
gestational ages and is associated with intrauterine growth retardation and congenital malformations.
Maternal Floor Infarct:
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