Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_100_библиотеки_им_акад_М_И_Перельмана
.pdf
390 Non-neoplastic Lesions of the Placenta, Pathology of the Placenta
https://t.me/med1917
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 48 Chorionic villi showing ground-
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 47 Villus capillaries with increased
circulating nucleated red blood cells in a placenta infected
by Parvovirus B19 (high-power view) (Photomicrograph
courtesy of Halit Pinar, MD [Women and Infants Hospital
of Rhode Island])
glass nuclear inclusions (denotedwith arrows) in the nucle-
ated red blood cells (medium-power view)
in nine affected fetuses will develop hydrops
due to the destruction of the erythroid cells and
increased central venous pressure, and 10% of
infected fetuses can progress to stillbirth without developing hydrops (Costa et al. 2020).
Macroscopy
Placentas infected by parvovirus B19 are large,
pale, and edematous.
Microscopy
Extensive chronic villitis is not usually expected
to be seen in association with parvovirus B19
infection; however, chorionic villi may be
enlarged by a chronic inflammatory infiltrate.
The primary finding is th e presence of increased
numbers of ery throid precursors (nucleated red
blood cells; Fig. 47), som e with ground-glass,
eosinophilic nuclear inclusions, which are
sometimes referred to as “ lantern cells”
(Fig. 48). This is accompanied by villous
edema and often delayed villous maturation.
Endothelial damage, villous necrosis, and
hemosiderin-laden macrophages may also be
present (Kim and Kim 2019).
Immunophenotype
Parvovirus B19 infection can be confirmed by
immunohistochemistry, in situ hybridization, or
PCR (Fig. 49) (Kim and Kim 2019).
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 49 The nuclei of infected cells stain
(brown) with antibody for parvovirus B19 (high-power
view) (Photomicrograph courtesy of Halit Pinar, MD
[Women and Infants Hospital of Rhode Island])
Molecular Features
Parvovirus B19 is a non-enveloped, linear, single-
stranded DNAvirus belonging to the Parvoviridae
family. It is among the smallest single-stranded
DNA viruses known. The 5.5 Kb genome of the
virus codes for two structural proteins, VP1 and
VP2, and a non-structural protein, NS1, which is
an early gene product and is associated with cel-
lular apoptosis (Wegner and Jordan 2004).
Differential Diagnosis
The main histologic differential diagnoses include
other causes of chronic villitis, such as the infec-
tions discussed in this chapter and villitis of
unknown etiology (discussed below). Increased
erythroid precursors can also be seen in the setting
Non-neoplastic Lesions of the Placenta, Pathology of the Placenta 391
https://t.me/med1917
of fetal hypoxic stress and anemia of other
etiologies.
Clinically, the differential diagnosis for fetal
hydrops includes other causes of fetal anemia,
such as hemolytic disease of the fetus
(erythroblastosis fetalis secondary to immunemediated hemolysis), fetomaternal hemorrhage
(discussed above), and transient abnormal
myelopoiesis (TAM) and other myeloid proliferations associated with Down syndrome. TAM will
demonstrate increased hematopoietic precursors
of all lineages in fetal circulation.
Treponema pallidum
Synonyms
Congenital syphilis; Syphilis placentitis; Treponema pallidum placentitis.
Definition
Placental infection caused by the Treponema
pallidum organism. Treponema pallidum is a
mobile spirochete that promotes low immunogenic recognition. Humans are the only natural
host for this spirochete. Infection is established
via congenital or sexual transmission (Costa
et al. 2020).
Clinical Features
• Incidence
There are two million cases of congenital
syphilis each year worldwide (Costa et al.
2020). In the United States, syphilis is the
third most common sexually transmitted bac-
terial disease after Chlamydia trachomatis
and Neisseria gonorrhoeae (Nelson 2018).
The incidence of congenital syphilis in the
United States fluctuated between 8.4 to 11.6
cases per 100,000 live births from 2008 to
2014, with a 261% increase in cases from
2013 to 2018 (Bowen et al. 2015;Kimball
et al. 2020).
• Age
Congenital syphilis is not associated with a
particular maternal or gestational age; how-
ever, the secondary stage of the disease is the
most likely to result in transmission due to the
higher numbers of circulating organisms
(Costa et al. 2020).
• Sex
A particular fetal sex has not been associated
with increased risk of Treponema pallidum
infection.
• Site
Vertical transmission to the fetus occurs via the
placenta. Transmission rate during pregnancy
directly relates to the stage of syphilis, with
nearly 100% of vertical transmission occurring
in untreated mothers with the secondary stage
of the disease (Costa et al. 2020). Fetal infection occurs in >50% of untreated early syphilis
and 35% of untreated latent disease. Fetal
ultrasound at >20 weeks of gestation may
reveal certain abnormalities that, while characteristic, are not specific to congenital syphilis.
The reported fetal abnormalities seen on ultrasound include hepatomegaly, elevated peak
systolic velocity of the middle cerebral artery
by Doppler ultrasound, placentomegaly, polyhydramnios, ascites, and fetal hydrops (Rac
et al. 2017). It is unknown whether
T. pallidum gains access to the placenta primarily through the bloodstream in the intervillous
space, through decidual tissue, or both
(Heerema-McKenney 2018).
•
Treatment
Benzathine penicillin G (BPG) remains the
only highly efficacious and recommended
treatment of maternal syphilis and prevention.
Treatment can prevent 98% of congenital
infections across all stages of syphilis if instituted at least 30 days before delivery (Rac et al.
2017; Costa et al. 2020).
• Outcome
Syphilis in pregnancy can cause low birth
weight, prematurity, and early neonatal death
or stillbirth if left untreated. Infants affected
with congenital syphilis may present with
deformed bones, severe anemia, enlarged
liver and spleen, jaundice, blindness, deafness,
meningitis, and skin rashes (CDC 2016).
Macroscopy
Placentas infected by T. pallidum may be massively enlarged, bulky, and pale secondary to
N
392 Non-neoplastic Lesions of the Placenta, Pathology of the Placenta
https://t.me/med1917
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 50 Placentas infected by Treponema
pallidum classically appear enlarged, bulky, and pale secondary to fetal anemia (Photograph courtesy of Halit Pinar,
MD [Women and Infants Hospital of Rhode Island])
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 51 Edematous, immature-appearing
villi of a placenta infected by Treponema pallidum
(low-power view) (Photomicrograph courtesy of Halit
Pinar, MD [Women and Infants Hospital of Rhode Island])
fetal anemia (Fig. 50) (Kim and Kim 2019). These
gross placental findings however are not specific
to syphilis.
Microscopy
Microscopic placental features are subtle and
non-specific, but a combination of findings
most suggestive of T. pallidum placentitis
includes edematous, hypercellular, immatureappearing villi with prominent Hofbauer cells,
thickened villous capillaries with “onionskinning” of perivascular connective tissue, and
acute or chronic villitis (Figs. 51 and 52).
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 52 Thickened villous capillaries with
“onion-skinning” of the perivascular connective tissue in a
placenta infected by Treponema pallidum (high-power
view) (Photomicrograph courtesy of Halit Pinar, MD
[Women and Infants Hospital of Rhode Island])
A predominantly lymphohistiocytic villous
inflammatory infiltrate is commonly reported
(Heerema-McKenney 2018;Costaetal.2020;
Kim and Kim 2019). Perivascular inflammation
with concentric sclerosis (proliferative endovasculitis) may be seen in the stem villi (Kim
and Kim 2019). Necrotizing funisitis, plasma cell
deciduitis, and acute chorioamnionitis are
observed when amniotic fluid infectionis present
(Heerema-McKenney 2018). Decidua may show
lymphoplasmacytic inflammation and perivascular proliferation of fibroblasts with necrosis
(Kim and Kim 2019).
Immunophenotype
The inflammatory infiltrate of the chorionic
villi is mostly of maternal origin, with CD3+/
CD8+ T-cells and CD68+ macrophages as
the predominant inflammatory cells. CD20+
B-cells a re rare (Kim and Kim 2019). Demonstration of spirochetes is important as there
are no pathognomonic histopa thologic features
in placentas infected by syphilis. Spirochetes
stain with silver-nitrate-based Warthin-Starry
stain. Immunostaining (immunofluoresc ence
and immunohistochemistry) using the antiTreponema pallidum antibody is reported to
be superior to the Warthin-Starry stain in identifying the organisms (Epstein and King
1985;Ohyamaetal.1990)(Fig.53).
Non-neoplastic Lesions of the Placenta, Pathology of the Placenta 393
https://t.me/med1917
pregnancy, the incidence of which is between
0.6% and 4%. Maternal asymptomatic primary or secondary HSV occurs in 2–4/1000
deliveries. Most of these are due to HSV-2. It
has also been shown that 2% of mothers seroconvert during pregnancy. Perinatal transmission most commonly occurs via maternal
genital tract secretions during delivery. Intrauterine transmission of HSV occurs in less
than 5% of primary infections (Avgil and
Ornoy 2006).
• Age
Neonatal infection is rare, due to the protection
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 53 An example of positive immuno-
histochemistry for Treponema pallidum, highlighting the
classic spirochetal morphology
that maternal IgG antibodies usually provide;
this is why risk of neonatal infection is greatest
when primary maternal infection occurs close
to term before these antibodies can be generated (Costa et al. 2020).
Molecular Features
PCR of placental tissue is available and may identify additional cases of congenital syphilis where
confirmatory histological features are absent
(Genest et al. 1996).
• Sex
HSV infection is not associated with a particular fetal sex.
• Site
Chorionic villi, decidua, extravillous trophoblast; syncytiotrophoblast has been shown to
Differential Diagnosis
The main histologic differential diagnoses include
other causes of chronic villitis, such as the infections discussed in this chapter and villitis of
unknown etiology (discussed below).
be resistant to HSV infection, as it does not
express the entry mediators needed for colonization (Avgil and Ornoy 2006; Costa et al. 2020).
• Treatment
Antiviral therapy is recommended in mothers
with known infection during the last four
Herpes Simplex Virus
weeks of pregnancy to reduce viral shedding.
Additionally, it is recommended anytime in
Synonyms
Congenital HSV infection; HSV placentitis; HSV
villitis.
pregnancy for acute, primary infection (Costa
et al. 2020).
• Outcome
Intrauterine HSV infection is associated with
Definition
Inflammation of the chorionic villi due to infection
to herpes simplex virus (HSV) type 1 or type
2. These viruses typically infect epithelial cells of
spontaneous abortion, preterm birth, fetal
growth restriction, congenital anomalies, skin
lesions, meningoencephalitis, and fetal demise
(Avgil and Ornoy 2006).
the skin and mucosa as well as neurons and occasionally the central nervous system (Avgil and
Ornoy 2006).
Macroscopy
Most cases will appear grossly normal; however, severe cases might demonstrate evidence
Clinical Features
of acute chorioamnionitis (e.g., green discoloration an d opacity of the membranes) or necro-
• Incidence
Recurrent genital herpes is the most common
form of maternal genital HSV infection in
tizing funisitis/vasculitis (e.g., yellow
chalkiness of vasculature) (Heifetz and Bau man
1994).
N
394 Non-neoplastic Lesions of the Placenta, Pathology of the Placenta
https://t.me/med1917
Definition
Placental infection by Toxoplasma gondii
(T. gondii) – a coccidian protozoa whose defini-
tive hosts are felines.
Clinical Features
• Incidence
Toxoplasmo sis is the most common protozoan
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 54 Necrotic debris containing cells
with classic HSV viral cytopathic changes (“The 3Ms”:
Multinucleation, nuclear Moulding, and chromatin
Margination)
infection worldwide, particularly in underresourced settings, with a reported prevalence
of infection ranging from 30% to 90% in continental Europe, Central America, and South
America. Most infections are asymp-
Microscopy
Thepresenceoftheclassicviralinclusionsisrare
(Fig. 54), and histologic findings range from
being mild and nonspecific, including deciduitis
and chronic villitis, to severe necrotizing acute
chorioamnionitis, necrotizing funisitis, and necrotizing villitis. In severe cases, it can infect
extravillous cytotrophoblast; however, HSV
does not infect syncytiotrophoblast as it does
not express the HSV entry m ediators (HveA,
HveB, and HveC) (Avgil and Ornoy 2006;
Costa et al. 2020).
tomatic. Only 10–20% of infected pregnant
women have flu-like symptoms (Costa
et al. 2020).
• Age
The rate of vertical transmission of infection
varies depending on when infection is acquired
during pregnancy. The rate of maternal-fetal
transmission is below 6% during the first trimester, 22–40% in the second trimester, and
58–72% in the third trimester. However, severe
fetal infection is more likely when acute maternal infection occurs earlier. Transmission is
rare from mothers who were infected prior to
Immunophenotype
Immunohistochemistry for HSV type 1 and type
2 is commonly employed in diagnosis.
pregnancy (Carlier et al. 2012).
• Sex
A particular fetal sex has not been associated
with transmission of T. gondii.
• Site
Molecular Features
HSV type 1 and 2 are large, enveloped, doublestranded DNA viruses (Avgil and Ornoy 2006).
Humans acquire toxoplasmosis through consumption of sporulated oocysts from water,
soil, or food contaminated by feces of the
definitive host. In vitro studies suggest that
Differential Diagnosis
HSV should be differentiated from other causes
of chronic villitis, particularly other i nfectious
etiologies, such as TORCH infections, which
may have a significant impact on clinical
outcome.
the extravillous trophoblast is the most vulnerable to infection. Villous cytotrophoblast
appears to be less susceptible, with syncytiotrophoblast being the least susceptible to
infection. T. gondii
can infect and multiply as
bradyzoites within villous trophoblast and
release new tachyzoites into the villous stroma
Toxoplasma gondii
(Carlier et al. 2012).
• Treatment
Synonyms
Placental toxoplasmosis; Toxoplasmosis.
Combined therapy with pyrimethamine, sulfadiazine, and folinic acid should be considered
Non-neoplastic Lesions of the Placenta, Pathology of the Placenta 395
https://t.me/med1917
for women with highly suspected or confirmed
fetal infection (Costa et al. 2020).
• Outcome
Infection early in the pregnancy can result in
abortions. Severe fetal infection manifests
with intracranial calcifications, ventriculomegaly, microcephaly, hydrocephalus,
chorioretinitis, hepatosplenomegaly, cardiomegaly, and subsequent postnatal blindness,
cognitive deficit, and deafness (Costa
et al. 2020).
Macroscopy
Placentas infected by T. gondii do not display any
specific gross features.
Microscopy
Infected placenta shows lymphohistiocytic
chronic villitis wi th diffuse inflammation and
granulomas. Tachyzoites (Fig. 55) and pseudocysts can be seen under conventional microscopy
with H&E and staining with periodic acid-Schiff
(Costa et al. 2020).
Immunophenotype
Immunohistochemistry for T. gondii is available.
Detection of primary toxoplasmosis in pregnant
women is based on serologic detection of IgG and
IgM antibodies or measuring the avidity of IgG
antibodies (Carlier et al. 2012).
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 55 T. gondii trachyzoites (arrows)
Molecular Features
Three genotypes of T. gondii exist, with type II
being the most common in Eur ope and the United
States, and the major type responsible for congenital infection. Fetal infection can be confirmed
with positive amniotic fluid polymerase chain
reaction (PCR) (Costa et al. 2020).
Differential Diagnosis
T. gondii infection should be differentiated from
other infectious causes of chronic villitis and
villitis of unknown etiology (discuss below).
Trypanosoma cruzi, another protozoan, can also
cause congenital infections via transplacental
transmission (congenital Chagas disease). The
basophilic kinetoplast of its amastigotes helps to
differentiate them from Toxoplasma trophozoites.
Intervillositis
Synonyms
Infectious intervillositis; Intervillousinflammation.
Definition
Inflammation within the intervillous space that
surrounds but does not involve the chorionic
villi (Redline 2015).
Clinical Features
• Incidence
Intervillositis has been described in cases of
malaria, CMV, dengue fever, psittacosis, and
SARS-CoV-2 (Ordi et al. 1998; Taweevisit
et al. 2012; Ribeiro et al. 2017; Janssen et al.
2006; Schwartz et al. 2020).
• Age
Intervillositis is not associated with a specific
maternal or gestational age.
• Sex
Intervillositis is not associated with a particular
fetal sex.
• Site
Intervillous space.
• Treatment
Antimicrobial therapy may be needed in the
setting of congenital infection.
N
396 Non-neoplastic Lesions of the Placenta, Pathology of the Placenta
https://t.me/med1917
Immune/Idiopathic Inflammatory Lesions
Definition
Non-infectious inflammatory lesions of the
placenta.
Villitis of Unknown Etiology and Related/
Associated Lesions
Chronic Villitis/Villitis of Unknown Etiology
Synonyms
Chronic nonspecific villitis; Chronic villitis of
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 56 Neutrophil-rich intervillositis in a
case of preterm delivery due to severe maternal sepsis with
Staphylococcus aureus bacteremia
unknown etiology; Idiopathic chronic villitis;
Noninfectious chronic villitis.
Definition
Villitis of unknown etiology (VUE) is a pattern of
• Outcome
Malarial infection is associated with low birth
weight (Ordi et al. 1998). CMV, dengue fever,
and COVID-19 have all been associated with
intrauterine fetal demise (Taweevisit et al. 2012;
placental injury characterized by the infiltration of
maternal T cells into the chorionic villi in the
context of destructive villous inflammation and
exclusion of infectious etiologies (Redline et al.
2021; Kim and Kim 2019).
Ribeiro et al. 2017; Schwartz et al. 2020).
Clinical Features
Macroscopy
Intervillositis does not typically give rise to gross
abnormality.
• Incidence
VUE is reported to occur in up to 15% of term
pregnancies (Derricott et al. 2016)orin
Microscopy
Collections of inflammatory cells within the
intervillous space (Fig. 56), which is often
histiocyte-rich. In the case of malarial infection,
histiocytes may contain malarial pigment.
76–136 per 1000 term and near-term pregnancies (Redline 2007). A large study from
New Zealand found VUE to be more common
in mothers of European ethnicity than in those
of Maori, Indian, and Chinese ethnicity. The
same study found a BMI greater than 25 was
Immunophenotype
Immunohistochemistry and special stains for
microorganisms are often employed.
associated with increased risk of VUE (Becroft
et al. 2005). VUE is reported to occur more
frequently in multigravida mothers and is more
likely to be diffuse (Redline 2007). Notably,
Molecular Features
Polymerase chain reaction (PCR) may be used for
diagnosis or speciation of certain microorganisms.
the incidence of VUE is higher in placentas
from pregnancies resulting from ovum donation than in those with non-donor oocytes (Kim
and Kim 2019).
Differential Diagnosis
The differential diagnosis for infectious
intervillositis is chronic histiocytic intervillositis,
an idiopathic inflammatory lesion described below.
• Age
More than 80% of VUE cases are observed in
placentas at greater than 37 weeks gesta tion,
with virtually all the remaining cases
Non-neoplastic Lesions of the Placenta, Pathology of the Placenta 397
https://t.me/med1917
presenting after 32 weeks gestation (Redline
2007).
• Sex
In the setting of maternal obesity, VUE has
been reported to be more prevalent when the
fetus is female (Redline et al. 2021).
• Site
Studies have shown that the inflammatory cells
infiltrating into the fetal chorionic villi are
maternal CD8+ cytotoxic T cells (Kim and
Kim 2019). It is not completely understood
what stimulus causes the entry of maternal
T cells into the chorionic villi. There are, however, several proposed mechanisms of how this
can happen. The trophoblastic barrier may be
damaged, seen as shedding of syncytial knots
from the third-trimester villi, which can denude
the villous stroma. Ischemic damage either
from maternal or fetal causes can damage the
trophoblastic barrier. Additionally, abnormal
adhesion molecular expression in syncytiotrophoblast has been seen in the context
of VUE (Redline 2007). Placental macrophages (Hofbauer cells) become activated in
the process of VUE, as shown by expression of
CD14. Previous studies have shown that these
activated placental macrophages are of fetal
origin. Thus, VUE is a unique inflammatory
process with involvement of T cells from the
mother and macrophages from the fetus (Kim
et al. 2015a). One study found that a significant
increase in the number of macrophages was
present in the placentas from stillborn fetuses
with VUE compared to healthy controls
(Derricott et al. 2016). VUE is essentially
fetal tis sue damage by maternal T cells based
on alloimmune respon se (Kim and Kim 2019).
• Treatment
No specific treatment in primigravid mothers is
currently proposed as no specific clinical signs
or symptoms suggest a diagnosis VUE.
Women with recurrent VUE have been
reported to respond to immunomodulatory
agents such as progesterone, corticosteroids,
low-dose heparin, and intravenous immunoglobulin, although the efficacy of these treatments has not been established by controlled
studies (Redline 2007).
• Outcome
VUE is general ly associated with a normal
pregnancy outcome. Extensive involvement
of the placenta by VUE, however, has been
associated with preterm and term fetal growth
restriction, spontaneous preterm delivery, preeclampsia, and i ntrauterine fetal demise (Kim
et al. 2015a). Short- and long-term neurologic
abnormalities such as neonatal encephalopathy and cerebral palsy have been associated
with VUE with obliterative fetal vasculopathy
(see below). In subsequent pregnancies, VUE
is reported to recur in 10–15% of cases, not
uncommonly with greater severity (Redline
2007). Moreover, recurrent VUE cases may
have a higher frequency of reproductive loss
(upto60%)comparedtononrecurrentcases
of VUE (Redline et al. 2021;KimandKim
2019).
Macroscopy
No specific gross placental characteristics have
been associated with VUE . Sometimes placentas
are small for gestational age, and occasionally,
when a large area of parenchyma is involved, an
area of induration (pale, fi
noted. Necrosis is rare (Redline et al. 2021;
Katzman 2015).
Microscopy
Affected chorionic villi are generally easily recognized from low power view due to the destructive nature of the lesion and increased cellularity
from the inflammatory infiltrate (Fig. 57). Villi are
infiltrated by small lymphocytes with associated
fibrosis, edema, and/or vascular obliteration.
Clusters of villi tend to be clearly demarcated
from the surrounding normal villi, often with
associated perivillous fibrin. Redline reported
several microscopic patterns of involvement by
VUE. Roughly half of all cases are exclusively
localized to the distal (terminal and mature intermediate) villi while sparing the chorionic plate,
proximal stem villi, and the anchoring villi. The
second most frequent pattern is chronic villitis
involving the proximal stem villi, typically
together with the distal villi. This is also the pattern most commonly associated with fetal
rm parenchyma) may be
N
398 Non-neoplastic Lesions of the Placenta, Pathology of the Placenta
https://t.me/med1917
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 57 Low-power view of VUE showing
chorionic villi with increased cellularity secondary to a
chronic inflammatory infiltrate
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 58 An example of a focus of avascu-
lar villi that may be seen downstream of VUE due to fetal
vascular lumen obliteration and/or thrombosis as a result of
inflammation (medium-power view)
vascular obstructive lesions known as obliterative
fetal vasculopathy, which is characterized by perivasculitis and varying degrees of true vasculitis
involving the stem villous and/or chorionic vessels. Obliteration of the lumen and/or thrombosis
of the affected fetal vessels as a result of inflammation leads to regions of downstream avascular
villi (Fig. 58). The least common variant of VUE
is known as basal villit is, in which chronic inflammation predominantly involves anchoring villi
embedded in the basal plate and adjacent terminal
villi. Almost invariably, basal villitis is encountered together with chronic deciduitis, typically
with considerable number of plasma cells
(lymphoplasmacytic deciduitis – discussed
below) (Redline 2007; Redline et al. 2021;
Khong et al. 2016).
VUE should be graded when more than one
focus is present to evaluate, with low-grade VUE
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 59 Low-power view of VUE. The
cellularity of the chorionic villi is clearly increased by
chronic inflammatory cells and more than 10 contiguous
villi per focus are affected, consistent with high-grade VUE
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 60 Medium-power view of high-
grade VUE showing theincreased cellularity dueto inflammatory cells
being defined as involving lessthan 10 contiguous
villi per focus. Low-grade VUE is further characterized as focal if all foci are present on a single
slide, or multifocal if it is seen on more than one
slide. High-grade VUE involves 10 or more contiguous villi per focus (Figs. 59, 60, and 61) and
can be further characterized as patchy or diffuse,
with the latter term applying when more than 30%
of the distal villi are involved. If only one focus is
present, the lesion should be reported as
“ungradable,” but can be further characterized as
“possible low-grade” or “possible high-grade”
based on the number of contiguous villi involved
(Redline 2007; Redline et al. 2021; Khong et al.
2016).
Immunophenotype
While not routinely necessary for diagnosis, the
T lymphocytes infiltrating chorionic villi can be
Non-neoplastic Lesions of the Placenta, Pathology of the Placenta 399
https://t.me/med1917
obliteration. Histologically, this pattern can be
indistinguishable from that associated with fetal
vascular malperfusion. The presence of inflammation characteristic of VUE should be a key feature
in differentiating the two (Kim and Kim 2019).
Differentiating VUE from chronic villitis of
infectious etiology is important. The nonuniform
involvement of placental parenchyma by VUE is
the cardi nal feature distinguishing the process
from infectious villitis (Redline 2007). Generally,
Non-neoplastic Lesions of the Placenta, Pathology of
the Placenta, Fig. 61 High-power view of high-grade
chronic villitis of unknown etiology. The cellularity of the
chorionic villi is clearly increased by lymphohistiocytic
inflammation
infectious villitis is found earlier in pregnancy and
has a much lower recurrence chance in subsequent
pregnancy compared to VUE. Immunostaining
for the common infectious organisms such as
syphilis, CMV, and parvovirus B19 (in addition
highlighted by CD3 and CD8 immunostaining.
The CD8+ T cells predominate over the CD4+
T cells (CD4/CD8 ratio ranges from 0.1 to 0.5)
(Redline 2007). Hofbauer cells, however, are
CD4+, as are other macrophages. Hofbauer cells
demonstrate increased expression of CD14 and
high Ki-67 labeling, indicating the activated,
pro-inflammatory phenotype. Interestingly, linear
expression of C4d along the syncytiotrophoblast
is consistent in VUE, strongly suggesting that
complement activation is one of the mechanisms
of villous injury in VUE (Kim and Kim 2019).
to identifying classic cytopathic features) is par-
ticularly valuable (Kim and Kim 2019).
Finally, a common pitfall in the diagnosis of
VUE is over-diagnosing increased villous
Hofbauer cells. These can beincreased in a variety
of settings, including acute chorioamnionitis,
hydrops, maternal vascular malperfusion, delayed
villous maturation, and chronic abruption. The
differentiating histologic feature is that they are
histiocytes (rather than small, mature lymphocytes) and tend to have a symmetric distribution,
in contrast to VUE which is often an asymmetric
infiltrate. Imm unostaining for CD68 (for
Molecular Features
Genetic testing is not routinely used in the diagnosis of VUE. However, gene expression profiling of
placentas affected by VUE reveals overexpression
Hofbauer cells, which are fetal histiocytes) and
CD3 (for T lymphocytes) can also be employed to
help distinguish the two different inflammatory
cell populations (Redline et al. 2021).
of genes seen in immune response. Thus, major
T-cell chemokines and their receptors such as
Chronic Chorioamnionitis
CXCR3 are overexpressed. Hofbauer cells show
overexpression of CXCL9, CXCL10, and
CXCL11 (other T-cell chemokines). Using transcriptomic analysis, placentas affected by VUE
have been shown to have enrichment of genes
involved in antigen presentation (such as class II
major histocompatibility antigens or HLA-DM,
-DO, -DP, -DQ, -DR) and overexpression of class
I molecules (HLA-B, -C, -G) (Kim et al. 2015a).
Synonyms
Chronic lymphocytic chorioamnionitis.
Definition
Lymphocytic inflammation of the fetal chorionic
layer of unclear etiology (Katzman 2015).
Clinical Features
N
Differential Diagnosis
Fetal vascular obliteration or thrombotic occlusions due to vasculitis can also be observed with
VUE and is termed villitis with stem vessel
• Incidence
Studies have shown that chronic chorioam-
nionitis (CC) is the most common lesion in
Соседние файлы в папке Библиотека им академика М.И. Перельмана