Intervillous Thrombus Research Articles

Machine learning classification of placental villous infarction, perivillous fibrin deposition, and intervillous thrombus

IntroductionPlacental parenchymal lesions are commonly encountered and carry significant clinical associations. However, they are frequently missed or misclassified by general practice pathologists. Interpretation of pathology slides has emerged as one of the most successful applications of machine learning (ML) in medicine with applications ranging from cancer detection and prognostication to transplant medicine. The goal of this study was to use a whole-slide learning model to identify and classify placental parenchymal lesions including villous infarctions, intervillous thrombi (IVT), and perivillous fibrin deposition (PVFD). MethodsWe generated whole slide images from placental discs examined at our institution with infarct, IVT, PVFD, or no macroscopic lesion. Slides were analyzed as a set of overlapping patches. We extracted feature vectors from each patch using a pretrained convolutional neural network (EfficientNetV2L). We trained a model to assign attention to each vector and used the attentions as weights to produce a pooled feature vector. The pooled vector was classified as normal or 1 of 3 lesions using a fully connected network. Patch attention was plotted to highlight informative areas of the slide. ResultsOverall balanced accuracy in a test set of held-out slides was 0.86 with receiver-operator characteristic areas under the curve of 0.917–0.993. Cases of PVFD were frequently miscalled as normal or infarcts, the latter possibly due to the perivillous fibrin found at the periphery of infarctions. We used attention maps to further understand some errors, including one most likely due to poor tissue fixation and processing. DiscussionWe used a whole-slide learning paradigm to train models to recognize three of the most common placental parenchymal lesions. We used attention maps to gain insight into model function, which differed from intuitive explanations.

Ferumoxytol-enhanced MR demonstration of changes to internal placental structure in placenta accreta spectrum: Preliminary findings

IntroductionThe goal of this pilot study is to determine if ferumoxytol-enhanced MR might provide a new approach to the diagnosis of placenta accreta spectrum (PAS), and if so, to identify signs of PAS. MethodsTen pregnant women were referred for MRI evaluation for PAS. MR studies consisted of pre-contrast SSFSE, SSFP, DWI, and ferumoxytol-enhanced sequences. Post-contrast images were rendered as MIP and MinIP images to separately display the maternal and fetal circulations respectively. Two readers examined the images for architectural changes to placentone (fetal cotyledon) that might distinguish PAS cases from normal. Attention was given to the size and morphology of the placentone, villous tree, and vascularity. In addition, the images were examined for evidence of fibrin/fibrinoid, intervillous thrombus, basal and chorionic plate bulges. Interobserver agreement was characterized with kappa coefficients and levels of confidence for feature identification was recorded on a 10-point scale. ResultsAt delivery, there were five normal placentas and five with PAS (one accreta, two increta, two percreta). The ten changes of placental architecture in PAS included: focal/regional expansion of placentone(s); lateral displacement and compression of the villous tree; disruption of a regular pattern of normal placentones; bulging of the basal plate; bulging of the chorionic plate; transplacental stem villi; linear/nodular bands at basal plate; non-tapering villous branches; intervillous hemorrhage; and dilated subplacental vessels. All these changes were more common in PAS; the first five achieved statistical significance in this small sample. The interobserver agreement and confidence for the identification of these features was good to excellent except for dilated subplacental vessels. DiscussionFerumoxytol-enhanced MR imaging appears to depict derangements of the internal architecture of placentas with PAS, thereby suggesting a promising new strategy to diagnose PAS.

The Remediable Metarteriole - Chorangioma

Chorioangioma is a benign, non-trophoblastic, vascular neoplasm arising from the placenta. Chorangioma is associated with features such as advanced maternal age, diabetes mellitus, hypertension, preeclampsia, multiple gestations or high-altitude pregnancy. The miniature, asymptomatic chorangioma is incidentally discovered whereas giant chorangioma exceeding >4 centimeters magnitude exemplifies adverse perinatal and foetal outcomes and is associated with intrauterine growth restriction (IUGR), polyhydramnios, preterm labour, arteriovenous shunts, foetal cardiomegaly or foetal heart failure, hydrops foetalis, foetal thrombocytopenia and maternal mirror syndrome. Tumefaction is composed of foetal capillaries circumscribed by stroma and trophoblastic tissue. Foci of tumor infarction, fibrosis, hyalinization, calcification and deposition of hemosiderin pigment are observed. Chorangioma requires a segregation from chorangiosis, chorangiomatosis, inflammatory myofibroblastictumor, Leiomyoma, placental infarct, intervillous thrombus or chorangiocarcinoma. Chorangioma or giant chorioangioma can be suitably discerned with ultrasonography. Treatment options such as draining excessive amniotic fluid or surgical intervention of chorioangioma with laser coagulation and electrosurgical maneuvers may be adopted.

Shallow Placentation: A Distinct Category of Placental Lesions.

Shallow placental implantation (SPI) features placental maldistribution of extravillous trophoblasts and includes excessive amount of extravillous trophoblasts, chorionic microcysts in the membranes and chorionic disc, and decidual clusters of multinucleate trophoblasts. The histological lesions were previously and individually reported in association with various clinical and placental abnormalities. This retrospective statistical analysis of a large placental database from high-risk pregnancy statistically compares placentas with and without a composite group of features of SPI. Twenty-four independent abnormal clinical and 44 other than SPI placental phenotypes were compared between 4,930 placentas without (group 1) and 1,283 placentas with one or more histological features of SPI (composite SPI group; group 2). Placentas were received for pathology examination at a discretion of obstetricians. Placental lesion terminology was consistent with the Amsterdam criteria, with addition of other lesions described more recently. Cases of group 2 featured statistically and significantly (p < 0.001after Bonferroni's correction) more common than group 1 on the following measures: gestational hypertension, preeclampsia, oligohydramnios, polyhydramnios, abnormal Dopplers, induction of labor, cesarean section, perinatal mortality, fetal growth restriction, stay in neonatal intensive care unit (NICU), congenital malformation, deep meconium penetration, intravillous hemorrhage, villous infarction, membrane laminar necrosis, fetal blood erythroblastosis, decidual arteriopathy (hypertrophic and atherosis), chronic hypoxic injury (uterine and postuterine), intervillous thrombus, segmental and global fetal vascular malperfusion, various umbilical cord abnormalities, and basal plate myometrial fibers. SPI placentas were statistically and significantly associated with 48% abnormal independent clinical and 51% independent abnormal placental phenotypes such as acute and chronic hypoxic lesions, fetal vascular malperfusion, umbilical cord abnormalities, and basal plate myometrial fibers among others. Therefore, SPI should be regarded as a category of placental lesions related to maternal vascular malperfusion and the "Great Obstetrical Syndromes." · SPI reflects abnormal distribution of extravillous trophoblasts.. · SPI features abnormal clinical and placental phenotypes.. · SPI portends increased risk of complicated perinatal outcome..

Signs of Poor Placental Perfusion In Placental Pathology in Stillbirth Fetuses [19B

INTRODUCTION: Over 50% stillbirths have preceding growth restriction. Our objective was to determine whether placental changes commonly seen in fetal growth restriction are associated with placentas of stillbirth infants. METHODS: Secondary analysis of a retrospective chart review on singleton placentas January 2011-January 2016. Exclusion criteria were less than 24 weeks’ gestation, multiple gestations, known aneuploidy. Primary outcome was decreased placental weight. Secondary outcomes were infarcts, villitis, fibrin deposition, calcium deposition, villous hypermaturity, meconium staining, intervillous thrombus. Pathology reports, and demographics from the electronic medical records were reviewed. Chi square was used for categorical variables and logistic regression for adjusted analyses. RESULTS: 3111 placental reports met inclusion/exclusion criteria. There were 78 stillbirths were noted in the study period, 71 (91%) with placenta evaluation. Nineteen (28%) of stillbirths were born SGA at birth. Placentas of stillbirths were more likely to have decreased placental weight (44% vs 20%), more than 2 (54% vs 26%) and 3 placental outcomes (28% vs 7%), p &lt;0.01. Of the 67 with documented fetal weight at delivery, those placentas associated with small for gestational age (SGA) fetus were more likely to have decreased placental weight, infarcts, calcium deposition, and greater than 2 and 3 placental outcomes. CONCLUSION: Placentas from pregnancies with stillbirth have increased rates of placental pathology. Those stillbirths born SGA were more likely to have decreased placental weight, infarcts, calcium deposition and greater than 2 and 3 placental outcomes. These placental findings have been associated with poor placental perfusion and may represent cases of placental insufficiency prior to demise.

Prevalence of Intervillous Thrombi Is Increased in Placentas from Pregnancies Complicated by Diabetes.

Intervillous thrombus (IVT) is a placental pathology of unclear cause. One possible cause is that IVT protects against fetomaternal transfusion due to trophoblastic disruption. A role for hyperglycemia in trophoblast apoptosis has been suggested. We sought to determine whether placentas from pregnancies complicated by diabetes had an increased incidence of IVT. Medical records of 206 patients with type 1 diabetes (n = 39), type 2 diabetes (n = 37), and gestational diabetes (GDM, n = 130) at the Massachusetts General Hospital were identified. Placental pathology reports were reviewed to determine prevalence of IVT. Gestational and maternal age-matched controls were selected from the pathology archives consisting of placentas examined only for the indication of group B streptococcus screen positivity; controls were confirmed euglycemic and reviewed for IVT. Fisher exact test was used for statistical analysis. An increased incidence of IVT was present in all diabetics (type 1, type 2, and GDM; 32 of 206; 15.5%; P = 0.04) and GDM exclusively (22 of 130; 16.9%; P = 0.03) versus controls (7 of 99; 7.1%). IVT were also increased in patients with type 1 diabetes (4 of 39; 10.3%) and type 2 diabetes (6 of 37; 16.2%) compared to controls (7 of 99; 7.1%), but the results did not attain statistical significance (P = 0.73 and 0.19, respectively). The incidence of IVT was increased in the placentas of patients with diabetes as a group (type 1, type 2, and GDM), and in patients with GDM in particular. This is the first report of an association between diabetes and an increased incidence of placental IVT.

Nosology: infarction hematoma, a placental infarction encasing a hematoma

Six cases of mothers whose placentas demonstrate multiple infarctions with a central intraparenchymal hematoma are presented. The histology is distinct from intervillous thrombus and Kline hemorrhage. The mothers have a history of multiple fetal losses, eclampsia/preeclampsia, and at least 1 case of documented recurrence. A distinct name is proposed for this lesion, infarction hematoma, which would help clarify further studies.

Relationship between placental morphology and histological findings in an unselected population near term

Whilst individual histological features are well described, there are no universally agreed criteria as to what constitutes a clinically significant histological lesion of the placenta in an uncomplicated pregnancy, nor has the presence of such histological findings been systematically related to quantitative morphological characteristics of the placenta (such as placental shape, cord insertion and cord coiling). This study aims to explore this relationship and further to describe the incidence of predefined categories of histological lesions of the placenta in an unselected obstetric population recruited prior to delivery. The study is based upon the placental examination of 1,156 women with singleton pregnancies recruited prospectively in a single unit. Placentas were analysed where deliveries occurred between 34-43weeks. The incidence of normal histological findings and specific histological categories, such as ascending genital tract infection, chronic placental underperfusion, intervillous thrombus and villitis of unknown aetiology, were noted. The relationship between placental morphological indices: coiling index, cord centrality index (distance of cord insertion on the chorionic plate from the centre) and eccentricity (shape of the placenta) and histological lesions was investigated. There were no significant differences between cord centrality and eccentricity between placentas with and without histological lesions except an association between hypercoiling of the umbilical cord and intervillous thrombosis and villitis of unknown aetiology (p = 0.024 and p = 0.009, respectively). The macroscopic morphological features of the placenta cannot predict the presence or absence of the histological placental lesions, nor are these lesions in general associated with differences in cord centrality, placental eccentricity or cord coiling.

Antenatal detection of placental pathology by ultrasound.

Thirty-seven patients who had anterior placentae were scanned within one week of delivery. The ultrasonic appearances of the placentae were correlated with the radiological, gross and histological appearances of the placentae after delivery. Calcification, perivillous fibrin deposition and subchorionic fibrin, ischaemic villous necrosis, intervillous thrombus, septal cysts, avillous spaces and placental septae with calcification or fibrin deposition were all able to be identified by ultrasound examination. The most obvious placental changes on ultrasound examination are those of calcification and perivillous and subchorionic fibrin deposition and are clinically the least significant. Because of the inaccuracies in detecting significant placental pathology such as ischaemic villous necrosis by ultrasound routine antenatal examination of the placenta cannot be recommended. There was no correlation between changes observed by ultrasound examination and fetal problems in this study.

Diagnosis of placental abruption: relationship between clinical and histopathological findings

Objective We evaluated the extent to which histologic lesions bearing a diagnosis of abruption conform to a diagnosis based on established clinical criteria. We further examined the profile of chronic and acute histologic lesions associated with clinical abruption. Methods Data from the New Jersey-Placental Abruption Study – a multi-center, case-control study – were utilized to compare the clinical and histologic criteria for abruption. The study was based on 162 women with clinically diagnosed abruption and 173 controls. We examined the concordance between clinical indicators for abruption with those of a histopathological diagnosis. The clinical criteria for a diagnosis of abruption included (i) evidence of retroplacental clot(s); (ii) abruption diagnosed on prenatal ultrasound; or (iii) vaginal bleeding accompanied by nonreassuring fetal status or uterine hypertonicity. The pathological criteria for abruption diagnosis included hematoma, fibrin deposition, compressed villi, and hemosiderin-laden histiocytes in cases with older hematomas. Acute lesions included chorioamnionitis, funisitis, acute deciduitis, meconium stained membranes, villous stromal hemorrhage, and villous edema. Chronic lesions included chronic deciduitis, decidual necrosis, decidual vasculopathy, placental infarctions, villous mal-development (delayed or accelerated maturation), hemosiderin deposition, intervillous thrombus, and chronic villitis. Results Of clinically diagnosed cases, the sensitivity and specificity for a histologic confirmation of abruption were 30.2% and 100%, respectively. Presence of retroplacental clots remained the single most common finding (77.1%) among clinically diagnosed cases. Among the acute lesions, chorioamnionitis and funisitis were associated with abruption. The only chronic histologic lesion associated with abruption was placental infarctions. Conclusions The concordance between clinical and pathologic criteria for abruption diagnosis is poor. The criteria for diagnosing a clinical abruption should include sonographic visualization of abruption, evidence of retroplacental clots, or vaginal bleeding accompanied by nonreassuring fetal status or uterine hypertonicity.

The influence of maternal cigarette smoking on placental pathology in pregnancies complicated by abruption

The purpose of this study was to evaluate the effect of maternal cigarette smoking on placental histology in women with abruption. Data were derived from the New Jersey-Placental Abruption Study (NJ-PAS)--an ongoing, case-control study, conducted since August 2002 in 2 large hospitals in NJ. Abruption cases were identified based on a clinical diagnosis. Histologic evaluations were performed by 2 perinatal pathologists who were blinded to the abruption status. Maternal smoking during pregnancy was determined based on patient's self-report. Among abruption cases, histologic findings were compared between smokers and nonsmokers, and the association expressed as odds ratio (OR) with 95% confidence interval (CI). All analyses were adjusted for potential confounders. A total of 189 abruption cases were available for analysis, of which 10.6% (n = 20) were smokers. Intervillous thrombus was more common in women who smoked (20%) than in nonsmokers (3.0%) (OR, 17.5; 95% CI, 3.1-99.4). However, placental infarcts were seen less frequently among smokers than nonsmokers (10.0% vs 32.5%; OR, 0.2; 95% CI, 0.1-0.8). These findings suggest that different pathologic mechanisms may be responsible for the histologic findings between smokers and nonsmokers diagnosed with placental abruption.

Confined placental mosaicism as a risk factor among newborns with fetal growth restriction

To delineate the frequency and clinical presentation of confined placental mosaicism (CPM) among newborns with idiopathic intrauterine growth restriction (IUGR) as compared to infants with appropriate fetal growth. 70 newborns with IUGR (birth weight < 10%) were matched by maternal age (+/-5 years) and gestational age (+/-7 days) to an equal number of infants of normal size. From both populations, placental samples underwent karyotype analysis following standard culture. CPM occurred significantly more often in the placentas from IUGR infants compared to controls, 11/70 (15.7%) and 1/70 (1.4%) respectively (p = 0.008). High-level tetraploidy (>20% in a primary culture) predominated among the IUGR placentas, while autosomal aneuploidy occurred only once in each population. Placental histology revealed significantly greater decidual vasculopathy, infarction, and intervillous thrombus formation in the karyotypically abnormal placentas (p = 0.03). Maternal age, gestational age at delivery, degree of growth restriction and ponderal index did not vary with the presence of CPM. CPM, and principally high-level tetraploidy, is found significantly more often among the placentas of newborns with IUGR. Infants with IUGR and CPM are clinically diverse although the placentas display pathologic changes suggestive of chronic impairment of uteroplacental function.

Discrepancy in Pathologic Diagnosis of Placental Lesions

Placentas are routinely examined by surgical pathologists, but peer review of placental diagnosis is rarely performed. To determine the frequency of discrepant placental diagnosis between general surgical pathologists and a pediatric pathologist. One hundred fourteen placentas from infants with intrauterine growth restriction (IUGR) and 170 placentas from infants appropriate for gestational age (AGA) were reviewed for 10 lesion types using standardized criteria. The review diagnosis was compared with original reports. The review identified 333 lesions, 168 in the IUGR group and 165 in AGA group. Discrepant diagnosis occurred in 137 lesions (41.1%). There was no significant difference in the frequency of discrepant diagnosis between the IUGR (44.7%) and AGA groups (37.6%) (P >.05). Most discrepancies (92.7%) were due to underdiagnosis (identified on review but not mentioned in original diagnosis), but a few (7.3%) were due to misdiagnosis (mentioned in original report but disagreed on review). The common underdiagnoses with their corresponding rates were as follows: hemorrhagic endovasculitis (84.6%), fetal thrombotic vasculopathy (75%), massive perivillous fibrin deposition (68.4%), maternal floor infarction (66.7%), retroplacental hemorrhage (60.6%), intervillous thrombus (57.1%), decidual angiopathy (33.3%), placental infarction (25.4%), acute chorioamnionitis (22.7%), and chronic villitis (21.7%). Misdiagnosis was found in 10 cases: 5 cases of infarction (review diagnosis was perivillous fibrin deposits in 4, intervillous thrombus in 1), 3 cases of acute chorioamnionitis, and 2 cases of decidual angiopathy. Among the 8 general surgical pathologists involved, the frequency of discrepant diagnosis ranged from 31.5% to 58.6% (P >.05). The intraobserver discrepancy rate for the reviewer was 4.8%, significantly lower than the discrepancy rate for the 8 general surgical pathologists. It is common for general surgical pathologists not to recognize placental lesions, which may have clinical significance. Awareness of this deficiency, standardization of diagnostic criteria, and increased knowledge in placental pathology may improve the quality of diagnosis in this area.

The ultrasound display of intervillous circulation

An ultrasonographic study of acoustic holes in the placenta shows that these contain maternal blood. The pattern of the maternal circulation can be visualized by ultrasonography, maternal blood entering the intervillous space in a continuous fashion with only a slight pulsatile pattern. Stasis of maternal blood and intervillous thrombus formation can also be distinguished.

An immunohistochemical, scanning, and transmission electron microscopical study of intervillous thrombus.

AbstractTwenty‐one placentae were examined by light microscopic immunohistochemistry, scanning electron microscopy, transmission electron microscopy, and immunoelectron microscopy for the histogenesis of intervillous thrombus formation. Two possible mechanisms were investigated to explain the structural initiation of intervillous thrombus formation. Either the thrombus occurs precisely on the intravillous stromal fibril or the basal lamina, directly facing the intervillous space, and is derived from the degenerated trophoblastic epithelium in a similar fashion to conventional intravascular thrombus formation, or the thrombus is formed on the degenerated trophoblastic epithelium without any trophoblastic epithelial defects. The villous trophoblastic epithelium is, furthermore, thought to behave in the process of thrombus formation as the endothe‐lium in conventional intravascular thrombosis because the villous trophoblastic epithelium had the same stainability as the endothelium in ultrastructural localization of Factor VIII.