Key-words:
Calcification - chorioangiosis - chorionic villi - fibrosis - Hofbauer macrophages
- hydropic change - partial mole
Introduction
The placenta is an organ that aids nutrient and gas exchange between the maternal
based and fetal-related compartments, produces hormones that help the fetus to grow
and develop, and gives some protection against infection.[[1]] The chorionic villi are the efficient unit of the placenta, their histological
appearance varies with the gestational age, but the basic villous structure is the
same regardless stage of development and maturation of the villous tree.[[2]] Maternal diseases and disorders such as diabetes, hypertension, anemias, and infections
in pregnancy can contribute to fetal morbidity and mortality through the affection
of the placenta structure and function.[[3]]
Gestational trophoblastic disease characterized by the proliferation of trophoblastic
tissue of the placenta, of which hydatidiform moles are the premalignant and most
common form. Malignant lesions (invasive moles and choriocarcinoma) can occur as well.[[4]]
Fifteen percent of recognized pregnancies terminate in spontaneous abortion and maybe
many more in early pregnancies.[[5]] A blighted ovum is the leading cause of spontaneous abortion in 50% of cases.[[6]]
Therefore, the histopathological examination of the placentae may give an idea about
the type and frequency of pathologic changes, and hence a clue to the cause of abortion,
fetal death, and pregnancy complications.[[7]]
Materials and Methods
A retrospective study of 92 specimens of products of conception that were collected
from a private histopathology laboratory in Benghazi. The samples, which submitted
to the pathology laboratory over the period from January 01, 2016 to December 31,
2018, reviewed. All specimens received in formalin were routinely fixed, paraffin-embedded,
and stained with h and e (H and E) stain. The histopathological examination carried
out using light microscope Nikon 50i to obtain information about different abnormal
histological changes in chorionic villi.[[8]] Normal placentae were taken as a control group. The study was descriptive.
Statistical analysis
Statistical analysis was carried out using the IBM SPSS Statistics for Windows, version
22 (IBM Corp., Armonk, N.Y., USA). Continuous variables were expressed as mean ± standard
deviation, whereas categorical variables expressed as numbers and percentages.
Results
During the study period, a total number of cases of abortions were 92; their clinicopathological
findings as follows:
Histopathological findings
In the present work, [[Chart 1]] revealed that six cases (6.5%) of specimens showed no histological lesions in chorionic
villi (normal placentae) [[Figure 1]]a, whereas 86 cases (93.5%) of specimens showed one of the abnormality listed in
[[Table 1]]. Two percent of chorionic villi showed abnormal premature calcification [[Figure 1]]b, 8% had numerous Hofbauer macrophages [[Figure 1]]c, 10% showed fibrosis and 13% of the chorionic villi had increased vascularity
(chorioangiosis) [[Figure 2]]a, [[Figure 2]]b, [[Figure 2]]c, [[Figure 2]]d compared to a normal control [[Figure 1]]a. Nineteen percent of chorionic villi showed hydropic changes [[Figure 1]]d, and 48% showed partial mole [[Figure 1]]e and [[Figure 1]]f; in form of nonpolar trophoblastic proliferation with central cisterna and trophoblast
inclusions in the stroma.
Figure 1: (a) Light microscopic appearance of chorionic villi - normal product of conception
with syncytiotrophoblast and cytotrophoblast layers (H and E, original magnification
x100) (b) Light microscopic appearance of an irregular calcification (dark violet)
in placenta (H and E, original magnifications x100) (c) Light microscopic appearance
of a chorionic villus with prominent Hofbauer cells (H and E, original magnification
x200) (d) Light microscopic appearance of villous distension and core edema (H and
E, original magnifications x100) (e) Light microscopic appearance of partial mole
showing small and large villous size, syncytial knots and hydropic villi with cistern
formation (H and E, original magnifications x100) (f) Light microscopic appearance
of partial mole showing edematous villus with inclusion (H and E, original magnifications
x100)
Table 1: The number, percentage, and types of histological changes in chorionic villi
Figure 2: (a-d) Light microscopic appearance of chorionic villi showing increased vascularity
(chorioangiosis) in four different noninfarcted areas (H and E, original magnification
x100)
Chart 1: The percentage of normal and abnormal placentae
Clinical findings
Patients' ages range between 20 and 45 years in cases of partial mole with mean age
33.5 ± 6.26 years. Most of the cases (73%) of partial mole found at an older age group
≥30 years as shown in [[Chart 2]]. The two cases of immature calcification were seen at the age of 43 and 45 years,
whereas (50%) of the histopathological findings had no specific age limits.[INLINE:2]
Chart 2: The frequency and percentage of partial mole in different age groups
Discussion
Mindful pathologic examinations of villi and the intervillous space in the placental
specimens provide definitive diagnosis or confirm the clinical diagnosis, and help
to understand the etiology and pathogenesis of the abortions.
In the present study, 92 placentae examined, of which 6.5% were histologically normal
placentae. A 2% of cases recorded to have calcification in this study; they were at
an older age group (>40 years) compared to a study by Hassan et al.[[2]] that revealed deposits of calcification in 12.5% of cases. The presence of these
deposits is common in abortion specimens, explained by poor transport through the
trophoblasts; which not utilized by the fetus due to termination of capillary flow
in villi.[[9]]
Hofbauer cells are tissue-resident immune cells present in placental villi throughout
pregnancy. They have a role in regulating pregnancy and placental development[[10]] and reveals an association with complications of pregnancy, as in cases of abortions,
chorioamnionitis, and villitis.[[11]] However, the exact role of these cells and functions still unclear.[[11]] The present study showed an increased number of Hofbauer macrophages in 8% of cases,
while a study done by Ul Haque et al.[[12]], including the placentae of spontaneous abortions, showed 67% of cases had prominent
Hofbauer macrophages. Another study conducted by Lakshmi and Raghupathy,[[8]] including all the aborted placentae within the first trimester, showed abundant
Hofbauer macrophages in 66% of cases. These are high percent compared to this study
indicating their role in different diseases and disorders.
Fibrosis is the end-result of long-lasting or chronic inflammatory reactions induced
by a variety of stimuli and a feature of progressive diseases that end by organ failure.
The current study showed stromal fibrosis in 10% of cases, in contrast to a study
by Shetty and Narasimha[[13]] showed significant stromal fibrosis in 32% of the cases and mild fibrosis in 28%
of cases. Another study conducted by Ul Haque et al.[[12]] in which stromal fibrosis was found in 83% of cases. This finding occurs as a consequence
of regression after intrauterine fetal death or from impairment of placental circulation.[[12]]
Chorangiosis categorized by an abundance of blood vessels (normally 8–10 vessels per
villous) within the chorionic villi owing to chronic placental hypoperfusion or low-grade
tissue hypoxemia as in cases of maternal anemia, preeclampsia, diabetes mellitus,
urinary tract infections, and drugs intake.[[14]] In this study, increased vascularity (chorioangiosis) was in 13% of cases; however,
no vascular abnormality detected in the rest of the cases. By reviewing other studies,
a study performed by Hassan et al.[[2]] showed areas of placental chorioangiosis in 2.5% of cases, whereas a study by Shetty
and Narasimha[[13]] and a study by Ul Haque et al.[[12]] revealed a markedly reduced vascularity in 72% and 75% of cases. These findings
explained by defective vasculogenesis or secondary to fibrosis when stratified according
to the weeks of abortion in these studies.
The hydropic changes were seen in 19% of studied cases, comparing to different studies,
different percentages of hydropic changes, 32% in a study conducted by Shetty and
Narasimha[[13]], and 5% in a study conducted by Hassan et al.[[2]] These findings explained by reduced or loss of the villous vascular supply when
categorized to the weeks of abortion since the hydropic change is more likely to be
present with early embryonic death when the villi are not well vascularized.[[9]]
Partial mole detected in 48% of studied cases with mean age 33.5 ± 6.3 years. Most
of the cases were seen at the older age group (≥30 years). In a study performed by
Hassan et al.,[[2]] molar changes were found in 5% of cases while a study conducted by Alsibiani[[15]] showed that partial mole was found in 0.2% of cases with mean age 33.7 ± 7.5 years
that is similar to the mean age of cases in this study. However, the low incidence
of molar change in the region of the study was due to sociomedical improvements.[[15]] Another study done by Jagtap et al.[[4]] showed that complete mole was the most common (57.3%), whereas the partial mole
was the second (41.3%) found at younger age groups (20–25 years), the finding explained
by early marriage at the region of study. A study done by Chauhan et al.[[16]] revealed only one case of partial mole.
The variation in the percentage of different histologic findings in the placental
tissues in different regions may be due to many factors and diseases that are common
in those areas. Histopathological examination of the product of conception has recognizable
medical importance, to rule out the presence of trophoblastic disease and, therefore,
its consequences. In addition, the examination of the product of conception can help
to prove the clinical diagnosis.
Conclusion
Most of the cases of abortion have abnormalities in chorionic villi; the most common
abnormality observed is the partial mole, occurring mostly at the age group ≥30 years,
followed by hydropic change then increased vascularity, fibrosis, and numerous Hofbauer
macrophages. Abnormal premature calcification is the least finding. Histopathological
examination is an important implement to diagnose molar pregnancy, to give a clue
about the associated maternal disease that affects the placenta, predicting the next
pregnancy outcome and necessary intervention needed. Cases that should be evaluated
cytogenetically can be selected through the histologic examination of the product
of conception is one more benefit.
Limitation of the study
Limitation of this study is shortage of information about maternal status, gestational
age, laboratory investigations, treatment options, and follow-up data.