Fetal Vascular Ectasia Can be an Artifact of Placental Fixation.

BACKGROUND: Placentas from outlying hospitals are formalin-fixed en route to our laboratory. We identified that chorionic, stem villus, and umbilical vessels in these fixed placentas are ectatic with greater frequency than in our in-house fresh placentas. METHODS: We searched our LIS for third trimester placentas using keywords "ectasia" or "ectatic" over a 12-month period. We fixed incoming in-house placentas over a 2-week period for 24-72 hours and tabulated the presence or absence of vascular ectasia as defined by Parast et al, 2008. RESULTS: The LIS search identified 61% of placental cases from outlying hospitals that had ectatic vessels vs 3% of in-house placentas (P < .001). Of 38 placentas fixed in a 2-week period, 45% had ectatic chorionic or stem villus vessels and 21% had umbilical vessel ectasia. In comparison, in the 2 subsequent weeks, 3.8% (P < .001) of fresh placentas had vascular ectasia. CONCLUSION: These data suggest that large fetal vessels in the placenta become engorged with blood at delivery and, if fixed soon after delivery, remain ectatic and congested when processed for pathology. The identification of artifactual ectasia is important because fetal vessel ectasia can suggest the presence of fetal vascular malperfusion (FVM) if diagnostic signs of FVM are present.

Classification and reporting guidelines for the pathology diagnosis of placenta accreta spectrum (PAS) disorders: recommendations from an expert panel.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Superior Vena Cava Syndrome and Hypoxic Ischemic Encephalopathy Secondary to a Massive, Right-Sided Immature Cervical Teratoma.

Cervical teratomas are a rare form of fetal teratoma that can grow to massive size. Generally, these masses can be surgically excised after birth with excellent physical and functional prognosis because the benign variants respect anatomical borders. The primary complications of these masses are associated with compromise of the trachea and esophagus: upper airway obstruction and polyhydramnios. We report the first documented occurrence of superior vena cava syndrome and hypoxic ischemic encephalopathy associated with a massive, right-sided cervical teratoma. This case highlights that when cervical teratomas are right-sided and sufficiently large, they can extend inferiorly and compromise central venous return to the heart. This unique presentation would likely have required fetal surgical excision to avoid catastrophic cerebral injury.

Basal Chronic Villitis and Disorders of the Placental Basal Plate: A Possible Immunological Link Between Hypertensive Disorders of Pregnancy and Morbidly Adherent Placenta.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a common cause for preterm delivery. Prior studies showed that chronic villitis (CV) is associated with intrauterine growth restriction, preeclampsia, intrauterine fetal death, and morbidly adherent placenta (MAP). The authors hypothesize that disorders of the placental basal plate, especially basal chronic villitis (BCV), are associated with HDP. METHODS: The laboratory information system was queried over 12 years to identify placentas with or without the clinical history of HDP and with or without multifocal/focal CV or BCV. As a control for tissue sampling, a similar search was performed over 5 years for placentas evaluated for MAP. RESULTS: Of 19,683 placentas identified, 14.8% had CV which was in 18.5% and 14.2% of placentas associated with or without HDP, respectively, a significant difference (P < .0001). BCV was present in 6.0% and 3.9% of placentas with or without HDP, respectively, also a significant difference (P < .0001). BCV was more likely than multifocal/focal CV to occur in HDP (32.4% vs 27.4%) when all cases of CV were analyzed (P = .025). Of 221 placentas with MAP, 64% had multifocal/focal CV and 36% had BCV. CONCLUSIONS: BCV and CV are more common in placentas with HDP than in normotensive pregnancies. They are also seen in MAP, as supported by another recent study.

Placental Chorionic Cyst Fluid Has Prothrombotic Properties and Differs From Amniotic Fluid.

INTRODUCTION: Chorionic cysts of the chorion laeve, fetal chorionic plate, septum, and free membranes have been associated with placental hypoxia, but they have no clear clinical significance. Although immunohistochemistry has identified fibronectin and collagen IV in cyst fluid, the contents have yet to be fully characterized. METHODS: Placental chorionic cysts (N = 10) were sampled by fluid extraction and hemotoxylin and eosin-stained sections. Amniotic fluid samples (N = 8) were obtained from pregnant women who had cytogenetic evaluation. The content of the cysts was tested for thrombogenicity using thromboelastography. The cyst content was tested by Luminex multiplex and ELISA assays and for known prothrombotic and proinflammatory factors. RESULTS: We identified cysts, especially those in the chorionic plate, adjacent to intervillous thrombi with apparent cyst rupture. Thromboelastography revealed a significantly shorter R time compared to whole blood control samples. Concentration of creatinine, α-fetoprotein, and surfactant D in the cyst fluid differed significantly from amniotic fluid. Cyst fluids had a significantly higher expression of all prothrombotic and some proinflammatory factors. DISCUSSION: Our data provide the first evidence that chorionic cyst fluid is prothrombotic and different from amniotic fluid. The association of ruptured cysts with adjacent thrombi and the prothrombotic properties of cyst fluid suggest a causal relationship; however, further studies are needed.

Genome-wide transcriptional profiling reveals connective tissue mast cell accumulation in bronchopulmonary dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth. Risk factors for BPD are complex and include prenatal infection and O(2) toxicity. BPD pathology is equally complex and characterized by inflammation and dysmorphic airspaces and vasculature. Due to the limited availability of clinical samples, an understanding of the molecular pathogenesis of this disease and its causal mechanisms and associated biomarkers is limited. OBJECTIVES: Apply genome-wide expression profiling to define pathways affected in BPD lungs. METHODS: Lung tissue was obtained at autopsy from 11 BPD cases and 17 age-matched control subjects without BPD. RNA isolated from these tissue samples was interrogated using microarrays. Standard gene selection and pathway analysis methods were applied to the data set. Abnormal expression patterns were validated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: We identified 159 genes differentially expressed in BPD tissues. Pathway analysis indicated previously appreciated (e.g., DNA damage regulation of cell cycle) as well as novel (e.g., B-cell development) biological functions were affected. Three of the five most highly induced genes were mast cell (MC)-specific markers. We confirmed an increased accumulation of connective tissue MC(TC) (chymase expressing) mast cells in BPD tissues. Increased expression of MC(TC) markers was also demonstrated in an animal model of BPD-like pathology. CONCLUSIONS: We present a unique genome-wide expression data set from human BPD lung tissue. Our data provide information on gene expression patterns associated with BPD and facilitated the discovery that MC(TC) accumulation is a prominent feature of this disease. These observations have significant clinical and mechanistic implications.

Midtrimester fetal herpes simplex-2 diagnosis by serology, culture and quantitative polymerase chain reaction.

The acquisition of herpes simplex virus (HSV) in utero comprises a minority of neonatal herpes infections. Prenatal diagnosis is rare. We describe a midtrimester diagnosis of fetal HSV-2 infection. Ultrasound at 20 weeks for elevated maternal serum α-fetoprotein (MSAFP) showed lagging fetal growth, echogenic bowel, echogenic myocardium, and liver with a mottled pattern of echogenicity. Amniocentesis demonstrated normal karyotype, elevated AFP and positive acetylcholinesterase. Culture isolated HSV-2 with an aberrant growth pattern. Maternal serology was positive for HSV-2. Quantitative DNA polymerase chain reaction (PCR) showed 59 million copies/ml. Fetal autopsy demonstrated widespread tissue necrosis but only sparse HSV-2 inclusions. Fetal HSV-2 infection can be suspected when an elevated MSAFP accompanies ultrasound findings suggesting perinatal infection. Maternal HSV serology, amniotic fluid culture and quantitative PCR are recommended for diagnostic certainty and counseling.

Intraplacental choriocarcinoma in a term pregnancy: Is serial postpartum hCG assessment necessary?

Intraplacental choriocarcinoma (IC), or choriocarcinoma in situ, is a rare disease on the gestational trophoblastic disease (GTD) spectrum, with <100 case reports available in the literature. We propose that many patients with IC are likely to be missed as the majority of patients do not present with metastases. Currently, there are no standardized protocols in existence for postpartum monitoring of these patients. We present a case of IC identified in the term placenta of a 21-year-old who delivered by primary cesarean due to concern for fetal intolerance of labor. Subsequently, we review the recommendations available on postpartum monitoring of this likely under-diagnosed condition.

Error codes at autopsy to study potential biases in diagnostic error.

OBJECTIVES: Current autopsy practice guidelines do not provide a mechanism to identify potential causes of diagnostic error (DE). We used our autopsy data registry to ask if gender or race were related to the frequency of diagnostic error found at autopsy. METHODS: Our autopsy reports include International Classification of Diseases (ICD) 9 or ICD 10 diagnostic codes for major diagnoses as well as codes that identify types of error. From 2012 to mid-2015 only 2 codes were used: UNDOC (major undocumented diagnoses) and UNCON (major unconfirmed diagnoses). Major diagnoses contributed to death or would have been treated if known. Since mid-2015, codes included specific diagnoses, i.e. undiagnosed or unconfirmed myocardial infarction, infection, pulmonary thromboembolism, malignancy, or other diagnosis as well as cause of death. Adult autopsy cases from 2012 to 2019 were assessed for DE associated with reported sex or race (nonwhite or white). 528 cases were evaluated between 2012 and 2015 and 699 between 2015 and 2019. RESULTS: Major DEs were identified at autopsy in 65.9 % of cases from 2012 to 2015 and in 72.1 % from 2015 to 2019. From 2012 to 2015, female autopsy cases showed a greater frequency in 4 parameters of DE, i.e., in the total number of cases with any error (p=0.0001), in the number of cases with UNDOC errors (p=0.0038) or UNCON errors (p=0.0006), and in the relative proportions of total numbers of errors (p=0.0001). From 2015 to 2019 undocumented malignancy was greater among males (p=0.0065); no other sex-related error was identified. In the same period some DE parameters were greater among nonwhite than among white subjects, including unconfirmed cause of death (p=0.035), and proportion of total error diagnoses (p=0.0003), UNCON diagnoses (p=0.0093), and UNDOC diagnoses (p=0.035). CONCLUSIONS: Coding for DE at autopsy can identify potential effects of biases on diagnostic error.

Pathologic examination of the placenta and observed practice.

OBJECTIVE: To estimate the percentage of deliveries eligible for pathologic examination of the placenta and compare with observed practice using the College of American Pathologists' (CAP) 1997 guidelines for examination of the placenta. METHODS: Records were reviewed from all live-birth deliveries 20 weeks or more of gestation in 2001 at Strong Memorial Hospital. The expected number of deliveries with CAP recommended indications was determined and compared with the observed number of deliveries in which the placenta was actually examined. Descriptive statistics, independent t tests, chi(2) tests, difference between two population proportions test, odds ratios, 95% confidence intervals, and multiple logistic regression were used to analyze the data. RESULTS: The observed number and percentage of deliveries with CAP recommended indications that had pathologic placental examination, 575 and 18.2% (95% confidence interval 16.9-19.6), was significantly lower (P<.001) than expected, 1,185 and 37.5% (95% confidence interval 35.8-39.2). The placenta was examined less frequently than expected in 9 of 14 categories. Independent predictors of examination of the placenta were gross placental abnormalities, multiple gestation, prematurity, peripartum fever, neonatal intensive care unit care of infant, cesarean delivery, and delivery by a maternal-fetal medicine specialist. CONCLUSION: Using the CAP guidelines for submission of the placenta would result in pathologic examination in 37.5% of all deliveries. Less than one half of all deliveries in which the placenta was eligible for submission were actually examined. Current advances in our understanding of pathologic conditions of the placenta and their relation to infant outcomes may warrant re-evaluating policy on placental examination at institutional and national levels. LEVEL OF EVIDENCE: II.

Chorionic Histiocytic Hyperplasia is Associated With Chronic Inflammatory Lesions in the Placenta.

Background Chorionic histiocytic hyperplasia (CHH) is a cellular proliferation at the base of the chorion that was identified by the authors in examining placentas for chronic chorioamnionitis (CC). This study is a retrospective review of cases diagnosed with CHH, describing its incidence alone and with associated lesions, and the immunophenotype of lesional cells. Design In this retrospective study, a laboratory information system search over a 34-month period using the key phrase "chorionic stromal" was performed. Cases identified were reviewed for presence of the following: CC, chronic villitis (CV), chronic deciduitis (CD), maternal (MIR), and fetal (FIR) acute inflammatory responses, meconium deposition; and whether CD3 immunostaining was performed. Incidences were tabulated and compared with known prevalences in our population. Select cases were stained with various immunostains to identify cell lineage and X and Y fluorescent probes to identify fetal or maternal cell origin in cases with male infants. Results Eighty cases of CHH were identified during the study period. Incidences of inflammatory lesions associated with CHH were: CV (54/80, 68%), CD (32/80, 40%), CC (25/80, 31%), MIR (39/80, 49%), and FIR (9/80, 11%). Only chronic inflammatory lesions had a significant correlation with the co-incidence of CHH. CC was identified alongside CHH in 12 of 22 cases in which a CD3 immunostain was performed. The cell population in CHH was vimentin+, CD68+, CD3-, CD45-, CD56-, hPL-, SMA-, OCT 3/4- and, in some cases, variably mixed with CD3+ lymphocytes. The cells had a male genotype by fluorescent in situ hybridization analysis. Conclusion The association of CHH with acute and chronic inflammatory conditions and its immunophenotype suggest that it may be a reactive process. CD3 immunostaining is helpful to identify concurrent CC.

Leclercia adecarboxylata Sepsis and Cerebral Herniation.

Leclercia adecarboxylata, a gram-negative bacillus of the Enterobacteriaceae family, is rarely identified as a pathogen in humans. We describe a fatal case of L adecarboxylata sepsis in a child. This is the first reported pediatric death associated with infection due to L adecarboxylata.

Fetal inflammatory response is often present at early stages of intra-amniotic infection, and its distribution along cord is variable.

This study investigates the hypotheses that (1) the fetal inflammatory response to intra-amniotic infection can occur in early stages of maternal inflammatory response and (2) a difference in early cord inflammation exists at different sites in the cord. Placentas accessioned in our department over a 4-year period with a differential in umbilical vessel inflammation between proximal and distal sections were evaluated for cord inflammation using a 0 to 4 graded scale. Cases were also evaluated for acute chorionic vasculitis and extent of maternal inflammatory response. Of 5566 placentas, 1004 (18%) had some degree of cord inflammation; 120 (12%) had a differential in inflammation between the 2 cord sites. Greater cord inflammation was divided almost equally between proximal (59) and distal (61) sections. Twenty-two cases had 1 or both arteries involved in 1 cord section only. The proximal section had the greater degree of inflammation in 21 (95%) of these cases. Early or no maternal inflammatory response was seen in 63 of 120 cases (52%). Acute chorionic vasculitis was identified in 57 of 106 cases (54%) with at least 2 chorionic vessels present. Fetal inflammatory response can be seen in early amniotic infection, occasionally without finding maternal inflammatory response. The absence of differences in cord vein inflammation depending on cord site and the finding that arteritis occurs close to the placental cord insertion site suggest that cord vessel blood flow dynamics play a role in neutrophil margination. At least 2 cord sections representing proximal and distal sites are recommended to exclude fetal inflammatory response.

Large-scale propagation of ultrasound in a 3-D breast model based on high-resolution MRI data.

A 40 x 35 x 25-mm(3) specimen of human breast consisting mostly of fat and connective tissue was imaged using a 3-T magnetic resonance scanner. The resolutions in the image plane and in the orthogonal direction were 130 microm and 150 microm, respectively. Initial processing to prepare the data for segmentation consisted of contrast inversion, interpolation, and noise reduction. Noise reduction used a multilevel bidirectional median filter to preserve edges. The volume of data was segmented into regions of fat and connective tissue by using a combination of local and global thresholding. Local thresholding was performed to preserve fine detail, while global thresholding was performed to minimize the interclass variance between voxels classified as background and voxels classified as object. After smoothing the data to avoid aliasing artifacts, the segmented data volume was visualized using isosurfaces. The isosurfaces were enhanced using transparency, lighting, shading, reflectance, and animation. Computations of pulse propagation through the model illustrate its utility for the study of ultrasound aberration. The results show the feasibility of using the described combination of methods to demonstrate tissue morphology in a form that provides insight about the way ultrasound beams are aberrated in three dimensions by tissue.

Multidisciplinary pediatric pathology rotations in a residency training program.

The pediatric pathology residency rotations described herein represent an innovative multidisciplinary approach to residency education that combines concepts from anatomic pathology and laboratory medicine, and utilizes faculty members from pathology, pediatrics, and obstetrics/gynecology to teach pathology residents the clinicopathological highlights of antenatal, perinatal, and postnatal pathology. Training is provided through a combination of didactic interactions, laboratory experiences, and current clinical cases. As such, it can be a model for other multidisciplinary residency rotations that could span graduate medical education in pathology to permit a more thorough, informative, and stimulating residency experience.