Histomorphological study of chorionic villi in
products of conception following first trimester abortions
Shilpa MD1,
Supreetha MS2, Varshashree3
1Dr. Shilpa, MD, Assistant
Professor, 2Dr. Supreetha, MS, Assistant
Professor, 3Dr. Varshashree, Post graduate,
all authors are affiliated with Department of Pathology, Sri Devaraj Urs Medical
College, Tamaka, Kolar, Karnataka, India.
Corresponding Author: Dr.
Shilpa MD, Assistant Professor, Department of Pathology, Sri Devaraj Urs Medical
College, Tamaka, Kolar, Karnataka, India. Email id: mdshilpa@ gmail.com
Abstract
Background: The
common problem which occurs in first trimester of pregnancy is miscarriage. Retained
products of conception are commonly received specimen for histopathological
examination. Apart from confirmation of pregnancy, a careful examination can
provide some additional information about the cause or the conditions
associated with abortion. Aim: 1. To
study various histopathological changes occurring in chorionic villi in first
trimester spontaneous abortions and to know the pathogenesis of abortions. Materials and methods: This was a cross
sectional retrospective study carried out for over a period of 3 years from
January 2015 to January 2018. A total of 235biopsies were obtained from patient
with the diagnosis of the first trimester spontaneous abortions were included
in this study. Results: In our study
most common age group of the abortion was between 21-30 years (63%). Incomplete
abortion was the commonest type of abortion (47.7%). Many dysmorphic features
were observed in this study like hydropic change (67%), stromal fibrosis (62%),
villi with reduced blood vessels (52.7%) and perivillous fibrin deposition.
Other features seen were haemorrhage, fibrinoid degeneration, Aria Stella
reaction and calcification. Reduced blood vessels in the villi had
statistically significant association with stromal fibrosis and hydropic change
which was <0.05. Conclusion: Cases
with dysmorphic features as seen in the present study may be associated with
certain chromosomal abnormalities. Such cases can not only be filtered for
cytogenetic work up, but these features can also aid in counselling and
planning of future pregnancies. Thus histopathological examination of abortus
material is highly recommended.
Keywords:
First trimester abortion, Chorionic villi, fibrosis, Vascularity
Author Corrected: 16th November 2018 Accepted for Publication: 20th November 2018
Introduction
The
commonest complication of pregnancy is abortion. Its incidence is around 15% [1].
The higher frequency of abortions in first trimester is mainly due to genetic aberrations
and the exact etiology is still unknown [2]. The pathology of spontaneous
abortions is therefore an important aspect necessary for understanding the
etiology and pathogenesis of the abortions. Foetal and placental development
occurs hand in hand. The foetal developmental abnormalities will be reflected
with the changes observed in the foetal part of placenta and it is recognized
by the uterus as abnormal and thus the uterus expels such products giving rise
to spontaneous abortions [3]. There may be local, systemic and combined means of
pathology for abnormal placental development and induction of abortion [4]. Thus,
histopathological examination of products of conception is a routine test for management
of patients with early pregnancy failure.
The
main reasons for doing histopathological examination for products of conception
are to prove the presence of an intrauterine gestation and to understand the
etiology and pathogenesis of abortions. But still there is lot of debate on it
whether is it necessary to send for routine histopathological examination or
not. Hence the aim of the study was to see various histopathological changes occurring
in chorionic villi in first trimester spontaneous abortions and to know the
pathogenesis of abortions.
Materials and Methods
It was a
laboratory exploratory study carried out in department of pathology, R L Jalappa Hospital attached to Sri Devaraj Urs
Medical College. Institutional ethical clearance was taken from ethical
committee. The study included all the specimens of products of
conception after spontaneous abortion submitted for histopathological
examination for over a period of 3 years from January 2015 to January 2018 were
considered. Relevant clinical history was retrieved from requisition forms.
All
the specimens received in formalin were routinely fixed and stained with Hematoxylin
and eosin. These slides were examined for various histological lesions in the chorionic
villi. Special stains were used wherever necessary.
The
following histological parameters were studied which suggests villous
maldevelopment or degeneration [5,6].
1)
Villous size 2) Villous vasculature3) Trophoblastic proliferation4) Ghost villi
5) Stromal fibrosis 6) Aria Stella reaction 7) Decidualised tissue8) Perivillous
fibrin deposition 9) Hydropic degeneration 10) Hofbauer macrophages
Exclusion Criteria:
Curetted samples of spontaneous first trimester abortions and with associated
risk factors like diabetes, hypertension, and infections were excluded.
Statistical
Analysis was done by using Microsoft excel and by using SPSS 22 software analysis
and p value < 0.05 was considered significant.
Results
A
total of 235 cases were retrieved of which 15 cases were excluded who had
undergone medical termination of pregnancy voluntarily. The patient age ranged
from 18 to 40 years. Most of the cases belonged to the age group 21-30 years
which was statistically significant [Table 1].
Table-1: Age distribution
Age |
N% |
p-value |
≤20 |
54(24.5%) |
<0.05 |
21-30 |
140(63%) |
|
31-40 |
26(11.8%) |
The
types of abortion were classified as shown in the [Table 2]. The most common type
of abortion seen in this study was incomplete abortion which was seen in 105
patients which formed the highest percentage while inevitable abortion formed
the lowest percentage.
Table-2: Types of abortion
Type
of abortion |
Number |
Percentage |
Incomplete |
105 |
47.7% |
Missed |
70 |
31.8% |
Complete |
36 |
16.3% |
Inevitable |
9 |
0.04% |
Total |
220 |
100% |
The present study on
histomorphological analysis showed that the most common size of the villi was
the intermediate size which was seen in 144 cases (65.5%)[Fig 1]followed by
large and small villi [Table 3]. Among villous vascularity grade 3 was the
commonest i.e., a plastic or hypoplastic villi which was seen in 116 cases (57.9%).
Other common morphological findings which were seen are hydropic change [Fig 2]
followed by stromal fibrosis [Fig 3&4], fibrinoid degeneration, per
villousfibrin, intervillous haemorrhage and Hofbauermacrophages [Table 4]. Molar
pregnancies were seen in 15cases.
|
Fig 1: Microphotograph of chorionic villi with small and intermediate sized villi H&E stain (100X) Fig 2: Microphotograph of chorionic villi with hydropic degeneration H&E stain (100X) |
Fig 3: Microphotograph of chorionic villi with stromal fibrosis H&E stain (100X) Fig-4: Microphotograph of Chorionic villi- Masson Trichrome stain highlighting the fibrosis (400X) |
Acknowledgement: Nil
Table-3: Histomorphology of
chorionic villi
Villous
Size |
Number |
Percent |
Small |
37 |
16.8 |
Intermediate |
144 |
65.5 |
Large |
39 |
17.7 |
Total |
220 |
100 |
Villous
Vascularity |
||
Grade 1 |
41 |
18.6 |
Grade 2 |
63 |
28.6 |
Grade 3 |
116 |
52.7 |
Total |
220 |
100 |
Table-4: Other morphological
findings
Histological
findings |
Number |
Percentage |
Hydropic change |
149 |
67 |
Stromal fibrosis |
139 |
63.1 |
Fibrinoid degeneration |
105 |
47.7 |
Hofbauer cells |
102 |
46.3 |
Decidual inflammation |
74 |
33.6 |
Haemorrhage |
68 |
30.9 |
Perivillous fibrin |
68 |
30.9 |
Hyalinized villi |
30 |
13.6 |
Molar changes |
15 |
0.06 |
Aria Stella reaction |
12 |
0.05 |
Calcification |
10 |
0.04 |
Table-5: Association between
villous vasculature and stromal fibrosis
Villous vasculature |
Stromal
fibrosis |
P value |
||
Present |
absent |
Total |
p<0.05 |
|
Grade I |
24 |
17 |
41 |
|
Grade II |
35 |
28 |
63 |
|
Grade III |
85 |
31 |
116 |
|
Total |
144 |
76 |
220 |
Table-6: Association between
villous vasculature and hydropic degeneration
Villous vasculature |
Hydropic
degeneration |
P value |
||
Present |
Absent |
Total |
P<0.05 |
|
Grade I |
23 |
18 |
41 |
|
Grade II |
30 |
33 |
63 |
|
Grade III |
96 |
20 |
116 |
|
Total |
149 |
71 |
220 |
Aria-
Stellareaction was seen in 12cases. Decidual reaction i.e., Inflammatory
reaction consisting of mixture of neutrophils, lymphocytes and plasma cells in
the decidua were seen in 74 cases. Ghost villi or hyalinized villi were seen in
30 cases and calcification was seen in 10 cases. Statistical analysis was done
and it was seen that there was statistical significance between the villous
vasculature and stromal fibrosis[Table 5] i.e., the villi having grade III
vascularity showed increased stromal fibrosis. This significance was also seen
with villous vasculature and hydropic change i.e., villi showing grade III
vascularity had increased hydropic change[Table 6]. Stromal fibrosis was highlighted
by special stain Masson's trichrome stain.
Discussion
The
functional unit of placenta is chorionic villi which develops from chorion and
has got a maximum contact with maternal blood and provides nutrition and oxygen
to the foetus similar to lung acinus and also serves as an excretory unit like
renal glomerulus [1]. WHO (World Health Organization) defines spontaneous
miscarriage as expulsion or extraction of an embryo or foetus weighing 500
grams or less from its mother which occurs before the foetus has reached a
viable gestational age[8, 9].
The
products of conception which are passed during spontaneous abortion should be
sent for histopathological examination and it should become a routine practice
since it has got a great value not only in confirmation of pregnancy but also
ruling out molar, ectopic pregnancies and most important is gestational
trophoblastic diseases which needs further follow up [5]. The chorionic villi
is lined by inner layer of cytotrophoblast and outer layer of
syncytiotrophoblast. During early stages of pregnancy most of the pathological
lesions occur [8, 10]. Many authors have concluded that histopathological
examination of products of conceptions helps to diagnose important pathologies more
effectively when compared to clinical examination so that mortality can be
reduced [11, 12]. In this study we have tried to evaluate the histological
findings in the chorionic villi of first trimester spontaneous abortions.
In
the present study, the majority of women belonged to age group between 21-30
years which was statistically significant p< 0.05 with minimum age of 18
years and maximum age of 40 years. Similar findings were also noted in a study
done by Makaju et al[8]. In our study incomplete abortion was the most common
type which was seen in 105 cases. This was in accordance to the study done on
100 cases [13]. The least common was inevitable abortion.
The
most important morphological villous criteria used to investigate early pregnancy
loss were regularity of the villous size, villousvas culture, stromal fibrosis
and perivillous fibrin deposition. Small sized villi with increased syncytial
knots, decreased vascularity and irregular contour are features of trisomies [13].
In the present study small sized villi were seen in 16.5% of the cases. For confirmation
karyotyping was not done in this study and majority of the villi were of
intermediate size.
Other
histological findings which were seen on light microscopy are hydropic villi,
poorly vascularized villi, villous haemorrhages, perivillous and intravillous
fibrin deposition, Hofbauer macrophages, ghost villi and calcification. Out of
these most important finding was stromal fibrosis and hydropic change which
were statistically significant with the villous vascularity.
First
trimester chorionic villi show 8-10 vessels per villous. In our study majority
had decreased vessels and it was the significant finding and statistical
significance was found between villous vascularity and stromal fibrosis.
Avascular or hypovascular villi means poor blood supply to the foetus and will
result in foetal retardation [7, 13].
Stromal
fibrosis was another significant finding which was observed. It is the final
common pathway for all form of diseases that progress towards end stage
failure. This is caused by the activation of the basement membrane material and
extracellular matrix molecules like collagen I, II, III, fibronectin IV and
proteoglycans by the resident cells of the chorionic villi. This is a feature
associated with preeclampsia and diabetic pregnancies. It is also a finding
seen after intrauterine foetal death regression [13, 14]. This fibrosis can
lead to decreased blood vessels in the villi.
Hydropic
degeneration is a tissue reaction to the pathological insult. In this study
there was statistical significance between villous vascularity and hydropic change.
This explains that initially there is stromal edema and later the avascular
villi become edematous and causes blighted ova [15]. Extreme hydropic change is
a characteristic finding in molar pregnancy[1]. In our study it was seen in 12
cases.
Perivillous
and intervillous haemorrhage usually occurs due break of numerous barriers from
the foetal circulation into the maternal intervillous space [15,16]. These
findings were also seen in our study. Haemorrhages seeps through adjacent
decidua and forms a membrane like sheet around the chorionic villi. At few
places it breaks into the villous stroma and forms fibrin deposition leading to
fibrinoid degeneration [7]. Perivillous and intervillous fibrin formed from these
haemorrhages. Increased peri villous fibrin causes entrapment of the villi
which become infarcted due decreased blood supply [13, 14].
Hofbauer
cells also called as placental macrophages, which are found to be derived from foetal
hematopoietic cells in liver and yolk sac. They help in biologic events of
placenta like fluid balance, immunologic and inflammatory processes. It is said
that increase in hofbauer cells in can cause immunologic or inflammatory insult
leading to missed abortion [17]. In our study it was seen in 55 cases. Decrease
in number of Hofbauercells along with avascularity of the chorionic villi can
cause hypoxia which leads to blighted ovum.
Aria
Stella reaction and decidual inflammation are the other features which were
observed. Decidual inflammation is defined as diffuse lymphocytic infiltrate of
the basal plate or any infiltrate in the decidua basalis which includes plasma
cells [15].
Another
feature observed was calcification. The cause for calcification is the ischemic
hypoxia degeneration and necrosis followed by calcium deposition in the
necrotic area. In this study it was seen in only few cases.
Conclusion
The
microscopic analysis of villous features helps in confirmation of pregnancy and
also identifies the cause for first trimester abortions which can be either
small size of the villi, stromalfibrosis, and decreased vascularity of the villi.
This helps further in cytogenetic evaluation of these cases which can be done
and it predicts the future of subsequent pregnancies so that proper
intervention and counselling can be given. It also provides a clue of
unsuspected molar pregnancies and associated clinical conditions like diabetes
and preeclampsia so that proper treatment can be given. Hence careful
microscopic examination of the products of conception after spontaneous
abortion can be a useful guide to identify many important lesions and also
provides useful information so that proper treatment can be provided further.
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How to cite this article?
Shilpa, MD, Supreetha, MS, Varshashree. Histomorphological study of chorionic villi in products of conception
following first trimester abortions. Trop J Path Micro 2018;4(7):499-504.doi:10.17511/ jopm. 2018.i7.04.