Massive Perivillous Fibrin Deposition Research Articles

Massive Perivillous Fibrin Deposition of an Enterovirus A-Infected Placenta Associated With Stillbirth: A Case Report

Massive perivillous fibrin deposition (MFD) is a morphologically defined severe placental lesion associated with perinatal morbidity and mortality. The etiology is unknown, and recurrence risk in subsequent pregnancies is assumed to be high. In most cases, a pathologic immune reaction is supposed to be responsible for the lesion. We report a case of a pregnant woman's suffering from hand, foot, and mouth disease in the 20th gestational week. Subsequently, MFD developed in the placenta and was followed by intrauterine growth restriction and stillbirth in the 29th gestational week. Enterovirus A with high homology to Coxsackievirus A16 was detected in the placenta by means of immunohistochemisty and reverse transcription polymerase chain reaction. This infection could be a rare cause of MFD and should be taken into consideration in the differential diagnosis of the individual etiology. Recurrence risk of virus-related MFD is expected to be lower than in MFD without infectious association.

Placental pathologic lesions with a significant recurrence risk - what not to miss!

Here, we review three important placental pathologies with significant clinical implications and recurrence risks. They are, in order of most to least frequently seen, villitis of unknown etiology, chronic histiocytic intervillositis, and massive perivillous fibrin deposition (also known as maternal floor infarction). These entities occur in both preterm and term gestations and are observed more frequently with maternal and obstetric disorders including prior pregnancy loss, hypertension/preeclampsia, and autoimmune disease. They are associated with, and probably the cause of, significant perinatal morbidity and mortality including intrauterine growth restriction, fetal and neonatal demise, and fetal/neonatal neurocompromise (seizures and cerebral palsy). All three entities have high recurrence risks, with recurrence rates ranging from 34 to 100%. The histologic features of villitis of unknown etiology, chronic histiocytic intervillositis, and massive perivillous fibrin deposition are described herein. We discuss the clinical associations and suggest the subsequent clinical and pathological evaluation. Hypotheses as to the biology of these lesions are reviewed.

The Frequency and Clinicopathological Characteristics of Miscarriages Featuring Placental Massive Perivillous Fibrin Deposition

The Frequency and Clinicopathological Characteristics of Miscarriages Featuring Placental Massive Perivillous Fibrin Deposition

Perinatal outcome of placental massive perivillous fibrin deposition: a case-control study.

The objectives of the study are to describe the obstetric outcomes associated with massive perivillous fibrin deposition (MFD) compared with a control series and to determine if outcome differs according to the extent of fibrin deposition. Retrospective case-control study based on placentas analyzed over a consecutive 12-year period. MFD was considered severe if it extended over more than 50% of the placenta and moderate between 25% and 50%. During the study period, MFD was observed on 71 placentas, 39 severe and 32 moderate. Compared with the 142 control women, the 39 women with severe MFD more often had histories of autoimmune disease and intrauterine fetal death. The case women with MFD were associated with elevated levels of maternal alpha-fetoprotein and with a high risk of severe growth restriction and/or intrauterine death. Compared with the infants with moderate MFD, those with severe MFD had also more abnormal umbilical artery Doppler velocimetry findings and more often intrauterine deaths and lower birthweights. Regardless of their extent, MFD that covered at least 25% of the placenta was almost always accompanied by severe growth restriction and by a high risk of intrauterine fetal death. Moreover, severe MFD tend to be associated with autoimmune diseases of the mothers, and pregnancies show more often a pathologic Doppler of the umbilical arteries and more often intrauterine fetal death that the moderate form. © 2017 John Wiley & Sons, Ltd.

Placental Pathology in Relation to Uterine Artery Doppler Findings in Pregnancies with Severe Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler Changes.

Objectives Current guidelines for diagnosis and management of early-onset intrauterine growth restriction (IUGR) rely on umbilical artery Doppler (UAD), without including uterine artery Doppler (UtAD). We hypothesized that IUGR cases with abnormal UAD but normal UtAD has a different spectrum of placental pathology compared with those with abnormal UtAD. Study Design Retrospective review of pregnancies with sonographic evidence of IUGR and abnormal UAD prior to delivery. Cases with ≥ 1 UtAD record(s) after 18+0 weeks' gestation and placental pathology were included. Cases were stratified according to initial UtAD pulsatility index (PI) values (n = 196): normal (n = 19; PI < 95th centile for gestational age/no notching), intermediate (n = 69; PI ≥ 95th centile/no/unilateral notching) and abnormal (n = 108; PI ≥ 95th centile/bilateral notching). Pregnancy outcomes and placental pathology were compared between groups. Results Women in the normal group delivered later than those in the abnormal group (30.1 ± 3.5 vs. 28.0 ± 3.5 weeks; mean ± standard deviation; p = 0.03). Their placentas exhibited higher rates of chronic intervillositis (15.8 vs. 0.9%; p = 0.01), chorangiosis (15.8 vs. 0.9%; p < 0.0001), and massive perivillous fibrin deposition (21.1 vs. 7.4%; p = 0.05), but had lower rates of uteroplacental vascular insufficiency (26.3 vs. 79.6%; p < 0.0001). Conclusion Approximately 10% of pregnancies with early-onset IUGR and abnormal UAD exhibited normal UtAD waveforms. They delivered later, and their placentas exhibited unusual placental pathologies.

Pathoanatomical and clinical aspects of the placenta in preterm birth

Prematurely born children show a clearly elevated risk for perinatal morbidity, long-term pediatric morbidities and development of chronic diseases in adulthood compared to babies born at term. The pathoanatomical investigation of placentas from preterm births is useful for assessing the etiology, the risk of recurrence and the prognosis for the child. The focus is on presenting the clinical and pathoanatomical characteristics of acute chorioamnionitis as a frequent cause of preterm induction of labor and pregnancy-induced hypertension, in particular preeclampsia as a frequent reason for elective cesarean section. Other lesions, sometimes of unclear etiology associated with preterm birth and substantially elevated risk of recurrence are reviewed. The clinical correlations and therapeutic options of the various diseases are discussed taking the risk of recurrence into consideration. Examination of placentas, association with the clinical course and a literature search. Acute chorioamnionitis and omphalovasculitis can be histologically subdivided into different stages which correlate with the clinical severity and the prognosis for the newborn child. Chronic deciduitis, chronic chorioamnionitis, villitis of unknown etiology, massive perivillous fibrin deposition and chronic histiocytic intervillositis are entities of unclear etiology associated with recurrent abortion and preterm birth. Autoimmune diseases and thrombophilia are occasionally associated with these pathologically defined lesions. Pregnancy-associated hypertensive disease and particularly preeclampsia as the cause of intrauterine developmental delay and elective cesarean section often show characteristic pathoanatomical placental lesions, which can give indications for the severity and duration of the disease and the prognosis for the child. Early onset (<34 weeks of gestation) and late onset preeclampsia show clinical and morphological differences. Subsequent pregnancies are classified as being at risk and screening for preeclampsia should be clinically performed.

Abnormal TREC-Based Newborn Screening Test in a Premature Neonate with Massive Perivillous Fibrin Deposition of the Placenta

Severe combined immunodeficiency (SCID), a primary immunodeficiency arising from variable defects in lymphocyte development and survival, is characterized by significant deficiency of thymus derived (T-) lymphocytes and variable defects in the B-lymphocyte population. Newborn screening for SCID is based on detection of low numbers of T-cell receptor excision circles (TRECs) by real time quantitative PCR (RT-qPCR). This screening allows for early identification of individuals with SCID and other disorders characterized by T-lymphopenia. Higher rates of abnormal screens are commonly seen in premature and critically ill neonates, often representing false positives. It is possible that many abnormal screens seen in these populations are result of conditions that are characterized by systemic inflammation or stress, possibly in the context of stress-induced thymic involution. We present a case of a male infant delivered at 27 weeks, 6 days of gestation, with severe intrauterine growth restriction who had an abnormal TREC screen and a massive perivillous fibrin deposition (MPFD) of the placenta. This association has not been reported previously. We are raising the awareness to the fact that conditions, such as MPFD, that can create adverse intrauterine environment are capable of causing severe stress-induced thymic involution of the fetus which can present with abnormal TREC results on newborn screening.

Pravastatin to prevent recurrent fetal death in massive perivillous fibrin deposition of the placenta (MPFD)

Massive perivillous fibrin deposition of the placenta (MPFD) or maternal floor infarction (MFI) is a serious condition associated with recurrent complications including fetal death and severe fetal growth restriction. There is no method to evaluate the risk of adverse outcome in subsequent pregnancies, or effective prevention. Recent observations suggest that MFI is characterized by an imbalance in angiogenic/anti-angiogenic factors in early pregnancy; therefore, determination of these biomarkers may identify the patient at risk for recurrence. We report the case of a pregnant woman with a history of four consecutive pregnancy losses, the last of which was affected by MFI. Abnormalities of the anti-angiogenic factor, sVEGFR-1, and soluble endoglin (sEng) were detected early in the index pregnancy, and treatment with pravastatin corrected the abnormalities. Treatment resulted in a live birth infant at 34 weeks of gestation who had normal biometric parameters and developmental milestones at the age of 2. This is the first reported successful use of pravastatin to reverse an angiogenic/anti-angiogenic imbalance and prevent fetal death.

Pre-eclampsia part 1: current understanding of its pathophysiology.

Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia.

Index of Suspicion in the Nursery

A female preterm infant was born at 28-weeks’ gestation to a G3P2A1 mother (third degree consanguineous marriage) by emergency cesarean delivery due to severe fetal growth restriction, oligohydramnios, and increasing liver transaminase levels in the mother. First conception was miscarriage at 12-weeks’ gestation. The second conception was intrauterine fetal demise at 30-weeks’ gestation; the pregnancy was complicated with acute fatty liver of pregnancy (AFLP) and acute kidney injury. Placenta showed massive perivillous fibrin deposition. Present pregnancy was spontaneously conceived. Pre-pregnancy, mother was diagnosed as hypothyroid and was started on thyroxine. She had also been started on aspirin since the last pregnancy and had received a complete course of antenatal steroids at 27-weeks’ gestation. Blood pressure of the mother at the time of admission was 140/90 mm Hg. This pregnancy was also complicated with AFLP, with serum glutamic-pyruvic transaminase levels of 586 U/L and lactate dehydrogenase levels of 863 U/L. The infant at birth weighed 960 g, required resuscitation with bag and mask for 30 seconds, and had Apgar scores of 5 and 7 at 1 minute and 5 minutes, respectively. Immediately after resuscitation, the infant was noted to have respiratory distress (Silverman-Andersen score of 8 of 10). In view of this distress, the infant was shifted to the NICU on a T-piece resuscitator and was started on continuous positive airway pressure at 15 minutes of age with a positive end-expiratory pressure of 5 cm and fraction of inspired oxygen of 0.50. Chest radiograph revealed surfactant deficiency. Surfactant (INSURE [intubation, surfactant administration, and extubation]) was given at 2 and 6 hours after birth in view of persistent respiratory distress and increased fraction of inspired oxygen requirement, respectively. She also had poor circulation, was off-color, and had increased capillary perfusion starting from 2 hours after birth. This shock was initially managed with a …

Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy

The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics.

Recurrent Massive Perivillous Fibrin Deposition in the Placenta Associated with Fetal Renal Tubular Dysgenesis: Case Report and Literature Review

Massive perivillous fibrin deposition (MPVFD) of the placenta and renal tubular dysgenesis (RTD) are relatively rare diseases with potential recurrent risks that have not previously associated in the literature. Herein, we report the clinical course, autopsy findings, and placental pathologic features from 3 consecutive pregnancies delivered in 1 woman, all showing recurrent MPVFD in the placenta and RTD in the bilateral fetal kidneys.

Maternal Floor Infarction/Massive Perivillous Fibrin Deposition: A Manifestation of Maternal Antifetal Rejection?

Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) are related placental lesions often associated with fetal death and fetal growth restriction. A tendency to recur in subsequent pregnancies has been reported. This study was conducted to determine whether this complication of pregnancy could reflect maternal antifetal rejection. Pregnancies with MPFD were identified (n = 10). Controls consisted of women with uncomplicated pregnancies who delivered at term without MPFD (n = 175). Second-trimester maternal plasma was analyzed for panel-reactive anti-HLA class I and class II antibodies. The prevalence of chronic chorioamnionitis, villitis of unknown etiology, and plasma cell deciduitis was compared between cases and controls. Immunohistochemistry was performed on available umbilical vein segments from cases with MPFD (n = 4) to determine whether there was evidence of complement activation (C4d deposition). Specific maternal HLA-antibody and fetal HLA-antigen status were also determined in paired specimens (n = 6). Plasma CXCL-10 concentrations were measured in longitudinal samples of cases (n = 28 specimens) and controls (n = 749 specimens) by ELISA. Linear mixed-effects models were used to test for differences in plasma CXCL-10 concentration. (i) The prevalence of plasma cell deciduitis in the placenta was significantly higher in cases with MPFD than in those with uncomplicated term deliveries (40% versus 8.6%, P = 0.01), (ii) patients with MPFD had a significantly higher frequency of maternal anti-HLA class I positivity during the second trimester than those with uncomplicated term deliveries (80% versus 36%, P = 0.01); (iii) strongly positive C4d deposition was observed on umbilical vein endothelium in cases of MPFD, (iv) a specific maternal antibody against fetal HLA antigen class I or II was identified in all cases of MPFD; and 5) the mean maternal plasma concentration of CXCL-10 was higher in patients with evidence of MPFD than in those without evidence of MFPD (P < 0.001). A subset of patients with MPFD has evidence of maternal antifetal rejection.

Evidence of an imbalance of angiogenic/antiangiogenic factors in massive perivillous fibrin deposition (maternal floor infarction): a placental lesion associated with recurrent miscarriage and fetal death

Massive perivillous fibrin deposition (MPFD) is associated with serious complications of pregnancy including recurrent spontaneous abortion, fetal growth restriction, and fetal demise. The aim of this study was to determine whether maternal plasma concentrations of angiogenic/antiangiogenic factors in MPFD differ from those of uncomplicated pregnancies. This retrospective longitudinal case-control study included MPFD cases (n = 10) and control patients (n = 175) with uncomplicated pregnancies who were enrolled in a longitudinal study and delivered at term. Serial plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 were determined by an enzyme-linked immunosorbent assay (cases, n = 28 samples; controls, n = 723 samples). Individual analyte concentrations were averaged across gestational age at specimen collection intervals. Linear mixed models were used to test for differences in log-transformed mean analyte concentrations both overall and as a function of time. The following results were found: (1) patients with MPFD had a lower mean plasma PlGF concentration (P = .03) and higher mean plasma concentrations of sVEGFR-1 and sEng (both P < .01) than controls, adjusted for potential confounders; (2) the mean plasma concentration of PlGF differed further among cases and controls as a function of gestational age interval (P < .0001); however, mean sVEGFR-1 and sEng group differences as a function of gestational age interval approached but did not reach significance (P = .09 and P = .11, respectively); (3) patients with MPFD had lower mean plasma concentrations of PlGF/sVEGFR-1 (P < .0001) and PlGF/sEng (P < .001): both of these relationships differed further as a function of gestational age interval (both P < .0001); and (4) differences in mean sVEGFR-1, sEng, and the ratios of PlGF to sVEGFR-1 and PlGF to sEng were observed before 20 weeks of gestation. An imbalance of angiogenic/antiangiogenic factors is present in patients with MPFD prior to the diagnosis. We propose that these changes participate in the mechanisms responsible for adverse pregnancy outcomes in patients with MPFD.

Abnormalities of the placenta

Normal placental structure and function is essential for a healthy pregnancy; the placenta is responsible for nutrient and oxygen transport, removal of waste products, protection from infection, modulation of the maternal immune system and hormone production to maintain pregnancy. The human placenta is structurally adapted to fulfil this role as it is haemomonochorial, minimising the distance between maternal and fetal circulations to maximise exchange. Disorders of the placenta including: FGR, pre-eclampsia, placental abruption and abnormal (velamentous) cord insertion are associated with over 50% of stillbirths and are frequently cited as the primary cause of death [1-3]. Abnormal placental structure and function significantly increases the risk of stillbirth. Levels of pregnancy associated plasma protein A (PAPP-A) in the lowest 5% and alpha fetoprotein (AFP) in the highest 5% increase the risk of stillbirth by 50-fold and 2.8-fold respectively [4,5]. In women at high-risk of pregnancy complications, abnormal placental structure and/or blood flow seen by ultrasound scan at 19-23 weeks preceded 15 out of 22 stillbirths [6]. There are few studies of microscopic placental structure in stillbirth. However, microscopic structure and cell turnover of the villous trophoblast are disrupted in FGR and pre-eclampsia [7-9]. Evidence from genetic analyses demonstrated that gene imprinting in the placenta is altered in pregnancy loss [10]. The importance of placenta genetics and epigenetics is supported by the observation of increased stillbirth and pregnancy loss in confined placental mosaicism where genetic abnormalities are only present in the placenta [11]. Due to its central role in determining pregnancy outcome, detailed examination of the placenta can give useful information about the cause of stillbirth and is recommended by the Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG) and Perinatal Society of Australia and New Zealand (PSANZ) [12,13]. Examination of the placenta reduces the proportion of unexplained stillbirths [14]. Consequently, examination of the placenta is one of the most common investigations undertaken after a stillbirth and is one of the most valuable [2,15]. Despite the value of placental examination to identify conditions associated with stillbirth including: fetal thrombotic vasculopathy, chronic intervillositis, villitis, chorioamnionitis, funisitis, infarction, massive perivillous fibrin deposition, villous dysmaturity (increased syncytial knot formation), villous immaturity and cord lesions further research is needed to increase the understanding of placental pathology in stillbirth. This is reflected in the research priorities for high-income countries synthesised by an international panel of experts which mention need for repositories of well-phenotyped samples from stillbirths and from well-matched controls and the need to understand the pathophysiological pathways in common conditions associated with stillbirth including: diabetes, cigarette smoking and maternal obesity [16]. An important goal of translational medicine is to use the increased understanding of placental dysfunction to develop improved tests of pregnancy wellbeing. For example, factors derived from the placenta, such as human placental lactogen or placental growth factor may provide novel means to identify pregnancies at highest risk of stillbirth [17]. Discovery-based technologies such as proteomics or metabolomics offer the opportunity to analyse biofluids and tissue in hypothesis-generating studies to provide a more holistic understanding of fetal and placental dysfunction. Better understanding of the role of the placenta in stillbirth offers the opportunity to develop strategies to identify placental dysfunction in pregnancies, in order that intervention may be targeted to prevent stillbirth.

Frequency and clinical significance of placental histological lesions in an unselected population at or near term

Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of the several common, objective and predefined histological abnormalities of the placenta as identified by pathologists blinded to all clinical information. A total 1,153 women were recruited from an unselected population delivering at 34-43 weeks. Histological findings in common obstetric outcome groups were compared to those of the unselected population, and odds ratios and predictive values were calculated. Normal histological findings were present in 72.1% of pregnancies with normal outcomes and in 79.1%, 66.6%, 80%, and 74.8% of pregnancies affected by pre-eclampsia (PET), pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small for gestational age (SGA), respectively. Chronic placental underperfusion was seen more frequently in PIH (odds ratio (OR) 2) and SGA (OR 1.4), while villitis of unknown aetiology was observed more commonly in cases with PIH (OR 3.2). Fetal thrombotic vasculopathy was twice as common in cases with GDM whilst massive perivillous fibrin deposition was much more frequent in those with PET (OR 20.2) and SGA (OR 8.9). Chorangiomata were 13 times more common in pregnancies with PET. However, in all cases, positive predictive values were low, with the majority of cases with histological abnormalities being associated with normal outcome. At term, specific placental histological lesions are significantly more common in complicated pregnancies, but the clinical significance of such lesions in a specific case remains uncertain, since the majority will be identified from clinically uncomplicated normal pregnancies.

Thrombophilic genetic polymorphisms and placental histomorphology in pregnancies conceived by assisted reproductive technology

Inherited thrombophilia is a condition that predisposes individuals to thrombosis and thromboembolism particularly during pregnancy. Infarction of maternal placental surface (MFI) and massive perivillous fibrin deposition (MPVFD) represents specific placental lesions associated with recurrent adverse fetal outcomes and maternal thrombophilic condition.

Chorionic Disk Extravillous Trophoblasts in Placental Diagnosis

To study clinical and placental associations of increased amount of chorionic disk extravillous trophoblast (IAEVT), the frequency of selected clinical and placental parameters of 189 consecutive cases with IAEVT, defined as more than 5 cell islands and/or placental septa per placental section, were compared with those for all remaining 1,006 placentas examined during the same period. IAEVT was statistically significantly associated with preeclampsia, decidual arteriolopathy, placental infarction, and several chronic placental hypoxic lesions (uterine hypoxic pattern of hypoxic placental injury, microscopic chorionic pseudocysts, massive perivillous fibrin deposition, and trophoblastic multinucleated giant cells in decidua) and absence of meconium staining and umbilical cord abnormalities. The amount of chorionic disk extravillous trophoblast is increased in association with clinical conditions and placental lesions associated with chronic hypoxia of uterine origin, ie, placental malperfusion. Counting placental septa and cell islands is a valuable surrogate test of chronic placental hypoxia.

Placental Membrane and Placental Disc Microscopic Chorionic Cysts Share Similar Clinicopathologic Associations

Placental membrane microscopic chorionic cysts (MCC) are associated with clinical conditions and placental features of in utero hypoxia. Those occurring in the cell islands, chorionic plate, placental septa, and maternal floor of the chorionic disc have been thought to have degenerative/liquefactive or secretory etiology and no clinical significance. To study the clinical and placental associations of MCC, 24 clinical (maternal and fetal) and 46 gross and microscopic placental features were statistically compared among 266 consecutive cases with MCC (study group, SG) and 656 consecutive placentas without MCC (control group, CG). The SG was further subdivided into (A) 139 placentas with chorionic disc MCC (at least 3 cysts per 1 placental parenchyma section), (B) 93 cases with membrane MCC (at least 3 chorionic lakes per membrane roll), and (C) 34 cases with both membrane and chorionic disc MCC in the same placenta. The SG contained more cases than the CG of diabetes mellitus, fewer cases with preterm premature ruptures of membranes, more multiple pregnancies, less chorioamnionitis, more cases of massive perivillous fibrin deposition, and more cases involving an excessive amount of chorionic disc extravillous trophoblasts. Within the SG, statistically significant differences among SGA, SGB, and SGC groups were found in terms of maternal diabetes mellitus, total perinatal mortality, neonatal mortality, cesarean deliveries, chorioamnionitis, histological meconium staining, chorangiosis, and excessive amount of chorionic disc extravillous trophoblast, respectively. Both membrane and chorionic disc MCC, frequently associated with an excessive amount of extravillous trophoblast, should be regarded as members of the family of extravillous trophoblastic lesions associated with chronic placental hypoxia.

Genetic Polymorphisms in the Fibrinolytic System of Placentas with Massive Perivillous Fibrin Deposition

Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) of the placenta are rare related conditions associated with poor perinatal outcome including antepartum stillbirth. The diseases are characterized by pathologic accumulation of fibrinoid deposits that surround the placental villi (in the case of MFI predominantly in the basal regions adjacent to the decidual plate). These findings suggest either overproduction and/or defective clearance of fibrinoid within the intervillous space. Recently genetic polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene have been found in association with impaired fibrinolysis in the pelvis predisposing to endometriosis. We hypothesized that polymorphisms in one or more of four genes that regulate fibrinolysis were associated with MPFD and MFI placentas. We retrospectively identified 20 consecutive cases of MPFD/MFI from our placental pathology database and generated 2 random gestational age-matched controls for each case. Clinical charts were reviewed. DNA was extracted from archived paraffin blocks of placental tissue from cases and controls. Single nucleotide repeat polymorphisms (SNPs) in loci within PAI-1 gene, thrombin activated fibrinolysis inhibitor (TAFI) gene, plasminogen activator urokinase (u-PA) gene and plasminogen activator tissue (t-PA) gene were studied using PCR methods. Outcomes in the study group included perinatal death (8), preterm IUGR (6), preeclampsia (4) and only 3 normal term deliveries. A spectrum of placental ultrasound abnormalities was observed. No SNP polymorphism was found to associate with MPFD/MFI. MPFD/MFI are associated with significant abnormal perinatal outcomes but have not been shown to be mediated by polymorphisms in candidate genes that are predicted to impair fibrinolysis in our study.