M a t e r na l F l o o r I n f a rc t i o n a n d
Massive Perivillous Fibrin
Deposition
Ona Marie Faye-Petersen, MDa,*, Linda M. Ernst, MDb
KEYWORDS
Maternal floor infarction Massive perivillous fibrinoid Placental infarction Perivillous fibrin
Placental fibrin Placental ischemia
M
aternal floor infarction (MFI) and massive
perivillous fibrin deposition (MPVFD) are
pathologically overlapping placental disorders with characteristic gross and shared light
microscopic features of excessive perivillous deposition of fibrinoid material. Although rare, they
are associated with high rates of fetal growth
restriction, perinatal morbidity and mortality, and
risks of recurrence with fetal death. The cause of
the extensive fibrinoid deposition is unknown,
but evidence supports involvement of maternal alloimmune or autoimmune mechanisms. This article presents an updated discussion of features,
placental histopathologic differential diagnosis,
possible causes, clinical correlates, and adverse
outcomes of the MFI/MPVFD spectrum.
OVERVIEW
Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPVFD) are rare (incidence
0.028%–0.5% of deliveries),1–4 closely related
placental lesions of unclear etiopathogenesis but
associated with high perinatal morbidity, mortality,
and recurrence risks. MFI5 refers to a lesion grossly
characterized by a yellowish, thickened maternal
floor, and, histologically, by extensive, basal rindlike depositions of fibrin material. Although its appearance is grossly suggestive of laminar infarction,
microscopically, chorionic villi in MFI are atrophic
and widely separated by cloaks of this fibrin material, instead of displaying a predominant pattern of
ischemic injury (ie, villous crowding, excessive
syncytial knot formation, and necrosis). Thus, the
term, infarction, is a misnomer. Also, perivillous fibrinoid deposition often extends beyond the basal
plate, variably entrapping villi and obliterating the intervillous space. Fox and Elston6 proposed the
descriptive term, MPVFD, to denote this constellation of features, and Katzman and Genest7 provided
useful semiquantitative diagnostic criteria. Their
subclassifications enable diagnostic uniformity and
more meaningful, comparative clinicopathologic
and outcomes studies between MFI/MPVFD and
other entities showing excessive perivillous fibrinoid
deposition. As discussed in this article, the composition of the perivillous fibrin and/or fibrin-like
complex (fibrinoid) is incompletely understood,
and its deposition likely progresses during gestation. The terms, MFI and MPVFD, are often used
interchangeably in the literature, because most
investigators5,8 consider them variants of a common
pathologic spectrum. Thus, for the purposes of this
discussion, MPVFD is used to refer to the spectrum
of changes of MFI and MPVFD, and fibrinoid to refer
to the perivillous material.
GROSS FEATURES
MPVFD typically results in a small-for-gestational
date, dense (stiff) placenta with a firm, yellowwhite, thickened-appearing maternal surface
(Fig. 1). Serial sections of classic forms exhibit
a yellowish basal layer or rind of fibrinoid (Fig. 2).
More commonly, fibrinoid deposition is more
diffuse, with vertically oriented, pale trabeculae
a
The University of Alabama at Birmingham, 619 South 19th Street, Birmingham, AL 35249-7331, USA;
Northwestern University, Olson 2-454, 303 East Chicago Avenue, Chicago, IL 60611, USA
* Corresponding author.
E-mail address: onafp@uab.edu
b
Surgical Pathology 6 (2013) 101–114
http://dx.doi.org/10.1016/j.path.2012.10.002
1875-9181/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
surgpath.theclinics.com
ABSTRACT
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Faye-Petersen & Ernst
Key Points
OF MPVFD
1. MPVFD is also known as MFI
2. MPVFD is a rare but important lesion of unknown cause but strong evidence for involvement of auto/
alloimmune mechanisms in most studies; other etiologies possible
3. The Classic prenatal ultrasonographic findings are fetal intrauterine growth restriction, oligohydramnios, and dense hyperechoic placenta
4. MPVFD has a high morbidity and mortality rate, with high risks of neurologic injury and of recurrence
5. The placenta is usually small and dense with friable, granular trabeculae of fibrinoid deposition
6. The predominant histopathologic feature is basal deposition of abundant fibrinoid with variable
upwards extension to middle and suchorionic zones of latticework perivillous fibrinoid; villi appear
choked off by thick layers of fibrinoid that obliterate the intervillous space.
extending from the basal zone, into the middle and
subchorial zones, in a lattice-like network. The
parenchyma of MPVFD is friable, granular
appearing, and dense versus the spongy and
compressible texture of normal villous tissue
(Figs. 3 and 4). Although most MPVFD results in
low placental weight, due to the loss of functional
and blood-filled chorionic villi, it may also be associated with a normal or even increased weight for
dates. Heavy MPVFD is generally due to the presence of abundant fibrinoid and/or proliferation of
extravillous cytotrophoblast.1,5 All forms may
have regions of true chorionic villous ischemia or
infarction consistent with sequelae of altered
blood flow patterns and sluggish, eddy-like regions in the intervillous space, due to pathologic
perivillous fibrinoid deposition. Presumably, these
altered blood flow patterns also explain the
Fig. 1. Maternal surface
in MPVFD. Gross image
of maternal surface of
placenta with MPVFD.
Note the yellow-white,
thickened appearance of
the maternal surface.
Massive Perivillous Fibrin Deposition
Fig. 2. Classic MFI. Gross
image of cross-sections of
classic MFI with yellowwhite rind of fibrinoid material seen predominantly
along the basal (maternal)
surface of the placenta.
Note that there is also
focal extension of the fibrinoid maternal into more
central and subchorionic
regions. (Courtesy of
Stewart Cramer, MD,
University of Rochester,
Rochester, NY.)
characteristic increase in extravillous trophoblast
cysts (X-cell cysts) and intervillous, thrombohematomatous formation within the parenchyma
(Fig. 5).1 Formalin fixation highlights the pathologic
fibrinoid latticework, atrophic portions of the
villous tree, X-cell cysts, and thrombohematomas
(see Fig. 5).
MICROSCOPIC FEATURES
MPVFD is characterized by marked increase in
perivillous fibrinoid deposition in the intervillous
space adjacent to the basal plate with varying
degrees of upward extension into the midzonal
and subchorionic regions (Fig. 6). Chorionic villi
appear to stand apart, due to their circumferential
sheaths of amorphous to laminated, eosinophilic
fibrinoid and display varying degrees of atrophy,
with loss of syncytiotrophoblast, villous vascularity,
and stromal histologic detail. Although grossly, the
maternal floor has a blanket-like distribution of fibrinoid, microscopically, the pathology is often
discontinuous. Basal, encased, individuated villi
and villous clusters, however, are matted together
(so-called gitter infarct) and seem to provide scaffolding for further fibrinoid deposition (Fig. 7). A
more extensive upward distribution is more common in placentas from later, third-trimester deliveries and is compatible with a progressive
process. Excessive extravillous cytotrophoblast
(X-cell) proliferations (nodular or confluent aggregations) and X-cell cysts are common, or even the
Fig. 3. Cut surfaces of placenta, normal (A) versus MPVFD (B). Gross images of cross-sections of placenta showing
pale, granular and dense appearing parenchyma in MPVFD (B) compared with age-matched control (A) with
more spongy and red parenchyma. Also, note intervillous thrombus (arrow) and chorionic cyst (arrowhead)
within parenchyma of placenta with MPVFD.
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Fig. 4. Cut surfaces of
placenta with MPVFD,
after fixation. Closer views
of gross of cross-sections
of placenta showing pale,
granular, and dense-appearing parenchyma in
MPVFD.
Fig. 5. Cut surfaces of placenta with MPVFD, after fixation. (A) Note the vertically oriented trabeculae of fibrinoid extending through the parenchyma. (B) Closer inspection reveals the coarse granularity of the parenchyma and an intervillous
thrombus is seen (arrow).
Massive Perivillous Fibrin Deposition
Fig. 6. Low-power photomicrograph of the basal
surface (lower surface) and
overlying placental parenchyma. Note the extensive
perivillous fibrin deposition
characterized by amorphous eosinophilic deposits
that surround and choke
the chorionic villi. In this
image, the perivillous fibrin
extends in vertical bands
toward the chorionic plate
(hematoxylin-eosin, original magnification 20).
dominant, feature (Fig. 8). X-cell proliferations,
cysts, and occasional foci of chronic chorionic
villous ischemia and infarction are likely linked to
development of abnormal blood flow patterns in
the maternal space and sites of relative secondary
ischemia. Not surprisingly, intervillous thrombohematomas may coexist or merge with areas of
perivillous fibrinoid deposition. Inflammation, when
present, is a minor component. Scattered lymphocytes and monocytes/histiocytes (Fig. 9), but not
plasma cells, may be present within or adjacent to
the villi. Degenerating villi may also elicit perivillous
neutrophilic reactions. Lymphoplasmacytic deciduitis may occasionally be seen.1,5,9–11
Fig. 7. Progression of MPVFD. This series of images illustrates how MPVFD is initiated near the basal surface of the
placenta (A) and progresses toward the midzonal (B, C) and subchorionic regions (D). Notice how the villi in the basal
zones ([A] and [B, C (lower)]) are more sclerotic than those in the midzonal region (B, C [upper]) and subchorionic
region (D). The villi in the subchorionic region are only partially surrounded by fibrinoid and still maintain some fetal
capillaries (hematoxylin-eosin, original magnifications [A] 20, [B] 100, [C] 200, and [D] 100).
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Faye-Petersen & Ernst
Fig. 8. Perivillous fibrin
deposition with prominent
proliferation of extravillous
trophoblast cells (X-cells)
(hematoxylin-eosin, original magnification 400).
DIAGNOSIS
The diagnosis of MPVFD should be suspected
when the placenta is small for the gestational
period, is diffusely firm, and shows a maternal
surface that is pale yellow-white and granular,
and serial sections display basal deposition of
granular fibrinoid material that extends upward,
toward the chorionic plate in a matted and/or
trabecular network. Light microscopically, basal
Fig. 9. Chronic inflammatory infiltrates in MPVFD.
Microscopic image of lymphohistiocytic cells within
the intervillous space adjacent to areas of MPVFD. No
significant chronic villitis
or plasma cells are seen
(hematoxylin-eosin, original magnification 20).
Massive Perivillous Fibrin Deposition
chorionic villi show encasement by thick layers of
perivillous fibrinoid, without the typical changes
of villous ischemia. The presence of villi choked
by perivillous fibrinoid is compatible with sequelae
of syncytiotrophoblastic damage, and/or alterations of or imbalances among factors that maintain the normal, fluid state of the blood in the
intervillous space. Syncytiotrophoblast damage
is the first detectable villous change, but it is
unclear if it is the initiating or merely an early event
in the cascade of MPVFD.
Perivillous fibrinoid deposition is greatest in the
basal zone, with variable penetration of the midchorionic and subchorionic zones. Accordingly,
the authors support use of semiquantitative
criteria for diagnosis of MPVFD,7 to promote diagnostic uniformity among pathologists and particularly to help distinguish it from other lesions with
fibrinoid, such as massive chronic (histiocytic
noninfectious) intervillositis (MCI), until the underlying causes of these lesions are better elucidated. The authors propose that the placental
pathology report should specify one of the
following patterns:
1. Classic—basal villous encasement by fibrinoid
along entire maternal floor and of 3 mm or
greater thickness on at least one slide
2. Borderline MPVFD—involvement of 25%–50%
of villi on at least one slide in transmural or
nearly transmural distribution
3. Transmural MPVFD—transmural perivillous
fibrinoid extension, with encasement of 50%
or greater of villi on at least one slide
MPVFD may include foci of villitis and intervillositis, lymphoplasmacytic deciduitis in the extraplacental membranes or decidua basalis, and areas of
ischemic change to frank infarction.The diagnosis
of MPVFD, however, should be made on its predominance as the histopathologic feature (see Key Points
and Differential Diagnosis). Estimates of the percentages of co-occurrence of villitis, intervillositis, and/or
ischemic damage may be included in the report,
especially if they are more than occasional findings,
because their presence may influence treatment and
frequency of clinical evaluations in subsequent pregnancies. Finally, a comment should be included indicating that MPVFD is associated with high risks for
adverse perinatal outcomes and recurrence (discussed later).
DIFFERENTIAL DIAGNOSIS
The differential diagnosis includes
1. Normal perivillous fibrinoid deposition
2. Chorionic villous ischemia and infarction
3. Fetal thrombotic vasculopathy (FTV)12–16 and
other pathologies likely representing maternal
alloimmune graft-versus-host disorders17–24
4. Diffuse chronic villitis of unknown etiology
(VUE) and chronic villitis with obliterative vasculopathy/vasculitis (CVOV)16,21
5. MCI25–28
Some perivillous fibrinoid deposition is a normal
feature of mature placentas5 and likely reflects
wear and tear damage to the syncytiotrophoblast.
Injured trophoblast presumably releases tissue
factors and/or other mediators that activate intervillous coagulation,1 and fibrinoid plugs seal the
syncytiotrophoblast defects.5 Perivillous fibrinoid
deposition, but not obliteration of the intervillous
space, increases with advancing gestation. In
term placentas, term stem villous surfaces show
linear, thin fibrinoid profiles and patchy aggregates
of perivillous deposition of laminated type of fibrin/
fibrinoid (Fig. 10) that progress throughout gestation in the subchorionic, basal, and marginal zones
(ie, normal regions of relatively sluggish flow and/or
hypoxia, within the maternal space).5 The main
differential diagnosis for MPVFD is chorionic villous
ischemic injury (including villous infarction
secondary to placental bed underperfusion)29
because perivillous fibrinoid frequently surrounds
areas with loss villous viability (Fig. 11). In chorionic
villous ischemia/infarction, however, increased
perivillous fibrinoid deposition is concentrated
around stem villi and in zones of primary, relative
ischemia (discussed previously). With infarction,
there is collapse of the intervillous space and
syncytial knot formation and stromal loss of
nuclear detail precedes syncytiotrophoblast necrosis (Fig. 12). In MPVFD, intervillous spacing is
preserved and syncytiotrophoblast injury is the
initial feature of villous damage.1 Decidual arteriopathy of maternal hypertensive disorders (ie,
thick-walled arterioles, atherosis, and fibrinoid
necrosis) is typically absent in MPVFD.1,9
FTV (clusters or large areas of avascular, involuted-appearing distal terminal villi) is due to intermittent or sudden obstruction of blood flow within
the villous tree. In most cases, FTV does not show
perivillous fibrinoid deposition around sclerosed
villi, but long-standing lesions of FTV may have
foci of avascular villi with fibrinoid encasement
(Fig. 13). MPVFD does not, however, display propagating thrombi or fields of chorionic villous
stromal-vascular karyorrhexis with preservation
of syncytiotrophoblast.5,12,15
Diffuse VUE and CVOV represent high-grade,
destructive lymphohistiocytic villitides affecting
greater than 5% of the terminal villi of midtrimester
to late third-trimester placentas (32 weeks or
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Faye-Petersen & Ernst
Fig. 10. Pattern of normal perivillous fibrin deposition. (A) Subchorionic zone with fair amount of perivillous
fibrinoid deposition beneath the chorionic plate and surrounding the most proximal stem villi. (B) Midzonal
region with small nodules of perivillous fibrinoid, which appear most prominent around stem villi. (C) Basal
zone appears similar to midzonal region with small nodules of perivillous fibrinoid, especially around stem villi.
Only a small amount of perivillous fibrinoid is noted directly adjacent to the basal plate (hematoxylin-eosin, original magnifications [A] 20, [B] 40, and [C] 20).
greater of gestation) with perivillous fibrinoid deposition around individual and clusters of chorionic
villi (see Fig. 13). CVOV also affects distal stem villi
and includes villous lymphohistiocytic vasculitis
and thrombosis. Both show variable presence of
lymphoplasmacytic deciduitis and chronic chorioamnionitis and may include a prominent component of perivillous fibrinoid deposition.15,16,21,30
MPVFD displays scant foci of chronic villitis and
no chorionic villous stem vessel vasculitis or
thrombosis.
MCI is characterized by diffuse mononuclear
infiltrates (lymphocytes, monocytes, and histiocytes) in the intervillous space, the essential
absence of villitis, and may show mild villous and
intervillous fibrinoid deposition.8 Literature on this
lesion is inconsistent, however. In a recent study,
Parant and colleagues28 defined the severe
Fig. 11. Gross comparison of infarction and MPVFD. (A) Gross image of a villous infarction secondary to ischemia.
Note the wedge-shaped lesion with a tan homogeneous, firm cut surface and well- defined borders. Compare
with gross image of MPVFD (B), which shows more diffuse involvement of the parenchyma with linear and small
nodular accumulations of fibrinoid but no formation of a well-defined lesion.
Massive Perivillous Fibrin Deposition
Fig. 12. Differential diagnosis of MPVFD-comparison of MPVFD and infarction. (A) MPVFD, (B) subacute infarction, and (C) remote infarction. Note that in MPVFD the intervillous space is filled with fibrinoid, but the spacing
between the villi is preserved, and in infarction there is collapse of the intervillous space. Note also the presence
of coagulative necrosis of villi in infarct compared with the more fibrotic but not necrotic villi of MPVFD (hematoxylin-eosin, original magnifications [A] 100, [B] 200, and [C] 200).
category of pathology of chronic intervillositis of
unknown etiology (with greater than 50% of the
intervillous space on the slide showing infiltrate)
as also including “massive and confluent perivillous fibrinoid with mild mononuclear infiltrate.”
Thus, the authors propose that the diagnosis of
MPVFD and other lesions be based on the
predominant, histopathologic feature and that
any secondary feature be included as a modifier
and semiquantitated.
Fig. 13. Differential diagnosis of MPVFD—comparison of MPVFD with FTV/avascular villi and chronic villitis/VUE.
(A) MPVFD, (B) FTV/avascular villi, and (C) chronic villitis/VUE. In FTV, avascular villi (B) are characterized by
sclerotic-appearing villi with preservation of the intervillous space; however, the villi can become encircled in
small amounts of perivillous fibrinoid. Stem villous or chorionic thrombi, which can accompany avascular villi,
are typically not seen in MPVFD. In chronic villitis/VUE (C), there is perivillous fibrinoid deposition associated
with villous agglutination and chronic inflammation. MPVFD does not typically show agglutination of villi or
significant chronic inflammation of villous parenchyma (hematoxylin-eosin, original magnifications [A–C] 100).
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110
Differential Diagnosis
OF MPVFD
MPVFD
Differential Entity
1. Distal chorionic villous tree branches are
diffusely choked and normally to widely
spaced by thick layers of fibrinoid
Normal-term perivillous fibrinoid
1. Deposition is around scattered stem villi,
in thin profiles.
2. Perivillous fibrinoid is a thin layer in relatively
ischemic zone of basal and subchorionic villi;
terminal villi show occasional aggregates as
intervillous bridges.
Chronic chorionic villous ischemia/infarction
1. Grossly, a permeative network of fibrinous
1. Grossly, infarctions are triangular shaped or
material is seen based at maternal surface
rounded.
and branching upwards toward chorionic plate.
2. Chorionic villous ischemia is a minor finding
3. Distal chorionic villous tree branches are
diffusely choked, and normally to widely
spaced, by thick layers of fibrinoid
4. Atherosis/fibrinoid necrosis is not seen unless
there is a complicating comorbidity of
underlying maternal hypertension or
thrombophilia
5. MPVFD shows no necrosis of decidua of
extraplacental membranes unless there is a
comorbid condition of hypertension or primary
disorder with vasculopathy
1. Sampling artifact is much less of an issue,
because basal distribution of fibrinoid is
blanket-like grossly and
2. Distal chorionic villous tree branches are
diffusely choked and normally to widely
spaced by thick layers of fibrinoid
3. MPVFD does not show chorionic plate or stem
villous and/or propagating thrombosis.
2. The Predominant feature is chorionic villous
ischemia and infarction.
3. Villi show crowding with thin layers of
intervening fibrinoid deposition.
4. Decidual arteriopathy is a feature in ischemiainduced pathology due to placental bed
under perfusion.
5. Decidual laminar-like or leukocytoclastic
necrosis in membranes is often present.
FTV
1. Sampling affects detection of chorionic
plate or stem villous thrombi and distal
villous sclerosis in cases of FTV, and
sampling artifact may lead to errors in
interpretation of small perivillous fibrinoid
depositions.
2. Characteristically, FTV shows scant to no
perivillous fibrinoid deposition around
sclerosed villi; the sclerosed villi remain
isolated and free floating.
3. Occasionally, presumably long-standing
clusters of sclerotic villi of FTV may show
fibrinoid encasement.
1. MFPVD shows foci or patchy chronic villitis and
intervillositis.
2. MPVFD does not show stem villous vasculitis/
thrombosis as a dominant feature.
3. The occasional focus of chronic villitis or
intervillositis may reflect an overlap in aspects
of pathologic mechanisms or pathways leading
to DVUE, CVOV, and MPVFD.
1. MPVD can contain foci or patchy presence of
chronic lymphocytic/monocytic intervillositis.
2. The occasional focus of chronic intervillositis
may reflect an overlap in aspects of pathologic
mechanisms or triggers of pathways leading to
MCI and MPVFD, respectively.
Diffuse chronic VUE and CVOV
1. The dominant histopathologic pattern is
diffuse villitis and/or obliterative vasculitis/
vasculopathy.
2. CVOV has stem villous vasculitis or
thrombosis as a dominant feature.
MCI
1. MCI is diffusely present in all zones of the
maternal space (subchorionic, middle, and
basal).
Massive Perivillous Fibrin Deposition
IMPACT AND UPDATES IN PATHOGENESIS
MPVFD is associated with high rates of adverse perinatal outcomes, such as prematurity (preterm
delivery in 26%–60%), intrauterine growth restriction
(24%–100%), spontaneous abortion, stillbirth (13%–
50%), neonatal death, and long-term neurologic
impairment.3,4,31–34 Women delivering placentas
with MPVFD more frequently have poor past reproductive histories (with or without documented
placental examination).4,35 Studies have correspondingly revealed that MPVFD exhibits high recurrence risks (12%–78%),2–4,7,35–37 with earlier onset
and more rapid progression by ultrasonographic
examination.2,4,11,31 Prenatal, ultrasonographic findings of oligohydramnios; fetal intrauterine growth
restriction (especially early onset); and a dense, hypoechogenic placenta have been noted as strongly
suggestive of MPVFD,31 but Uxa and colleagues38
did not find these a consistent constellation of antenatal features. The classic triad, however, of these
ultrasonographic findings may reflect the onset,
extent, and rapidity of fibrinoid deposition, period
of gestation, and compromise of fetal renal blood
flow due to hypovolemia associated with decline in
placental function. Taweevisit and Thorner39 linked
MPVFD, fetal cystic renal dysplasia, and oligohydramnios and suggested that fetoplacental factors
may also play a role in the pathogenesis of MPVFD,
possibly through alterations in uterine hydrostatic
pressure gradients.
As discussed previously, the causes of the
excessive accumulations of amorphous fibrinoid
material encasing chorionic villi and features of
loss of syncytiotrophoblast viability are incompletely understood. Elements of the maternal blood
and trophoblast-generated procoagulant and
anticoagulant molecules and matrix contribute to
a normal villous surface and maintenance of a fluid
intervillous space. The amorphous, perivillous
material, normally present in the intervillous space,
immunohistochemically and ultrastructurally appears to be a combination of serum fibrin of
the maternal coagulation cascade (a laminated
fibrin-type fibrinoid) and trophoblast-derived extracellular substance (matrix-predominant type fibrinoid).5–7,9,10,40 Abnormal amounts of fibrin or
fibrinoid dominant deposition may partly reflect
the relative numbers of proliferating or neighboring
cytotrophoblasts and decidual cells.1
The microscopic features of MPVFD are highly
suggestive of either direct damage to the syncytiotrophoblast and/or disturbances in the balance of
dually derived intervillous procoagulant/anticoagulant factors necessary to maintain the fluid state
of the blood in the maternal space. To date, there
is evidence that at least some MPVFD represents sequelae of a maternal autoimmune or alloimmune condition. In addition to its high risks
of recurrence,
1. MPVFD is more common in women antiphospholipid (APL) antibody syndrome and
other autoimmune disorders with or without
thrombophilia.8,41–45
2. Women with a prior diagnosis of MPVFD and
APL syndrome, treated with intravenous immunoglobulin, have had improved pregnancy
outcomes.44
3. MPVFD may be discordant in dichorionic9 or
monochorionic2 twin placentas.
4. MPVFD may coexist with chronic intervillositis.28,46
The syncytiotrophoblast may be the primary
target of maternal antitrophoblast antibodies47
and release factors, such as tissue necrosis factor
or Hageman factor, that activate coagulation.
Somewhat challenging is the observation that
MPVFD may be associated with maternal primary
hypertension and preeclampsia.4,37,48 These associations, however, may represent overlap among
maternal risk factors for MPVFD and hypertension,
because hypertensive disorders and APL syndrome can co-occur. Alternatively, the sequelae
of trophoblastic or villous hypoxic damage could
result in confounding activation of abnormal coagulation in the intervillous space1,5 and potentiate an
otherwise insignificant or low-grade trophoblastic
abnormality or process of fibrinoid deposition.
As a corollary to the above discussion, MPFVD
has also been linked to primary maternal inherited
coagulation factor deficiencies and abnormalities45,49–51 and long-chain 3-hydroxyacyl-CoA
dehydrogenase (LCHAD) deficiency52 with mutations in LCHAD gene.53 Thus, blood flow in the
maternal space may become compromised by
an intervillous process initiated by imbalances
among the components and activities of the intervillous
procoagulant/anticoagulant
factors.
Women, with or without an underlying autoimmune disease but with a history of a prior pregnancy complicated by a placental diagnosis of
MPVFD, who were treated with low-dose heparin
and aspirin during their subsequent pregnancies
have had improved gestational outcomes.54 Anticoagulant therapy may prove to be protective
against the recurrence or severity of MPVFD.
In conclusion, the fibrinoid deposition of MPVFD
likely represents the outcome of a final common
pathway potentially triggered by a variety of conditions or pathologies that disturb the normal and
inducible factors that maintain the integrity of the
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Faye-Petersen & Ernst
Pitfalls
Massive perivillous fibrinoid
deposition/MFI
! Most common misdiagnosis is chorionic villous ischemia/infarction.
Grossly placental bed ischemia due to maternal vascular disease
creates triangular-shaped or rounded masses of infarcted villi
whose broadest aspects lie along maternal surface; MPVFD has
a diffuse pattern of distribution of fibrinoid along basal plate.
Chorionic villous ischemia shows thin layers of intervening fibrinoid deposition or small, nodular excrescences that bridge to
other villi and predominantly involves stem villi and subchorionic
regions. MPVFD isolates chorionic villi and obliterates intervillous
space, from basal plate upward.
Infarction displays collapse of the intervillous space with fibrinoid
depsosition and villous necrosis. MPVFD shows individuated villi
surrounded by fibrin without coagulative necrosis.
MPVFD can result in abnormal channels of blood flow in maternal
space and create zones of ischemia that compromise chorionic villi
and result in foci of infarction.
! MPVD can contain foci of chronic villitis and MCI.
The occasional focus of chronic intervillositis may reflect an overlap in the portions of pathologic pathways between MCI and
MPVFD.
! MPFVD may show rare focus of chorionic villous thrombosis.
syncytiotrophoblast and the fluidity of blood in the
maternal space. Ongoing damage and accelerating compromise of the blood flow within the
intervillous space may obscure the inciting
pathology or combine with elements of chronic villitis. The triggers, however, are likely potent and/or
in high concentrations, because they seem to
irreversibly commit the perivillous space to a process of marked fibrinoid deposition and accumulation. The rarity of MPVFD suggests that there
are many sites of duplication within the normal
villous protective and reparative systems, which
guard against pathologic amounts of fibrinoid
deposition.55–57
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