Placental calcifications after coronavirus disease 2019 in first trimester of pregnancy: ultrasound and pathology findings.

The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on placental tissue is unclear. We present a case of symptomatic first trimester SARS-CoV-2 infection in which longitudinal ultrasound images demonstrated diffuse areas of echogenic foci. Her 39-week delivery, following an elective induction of labor, was uncomplicated, and placental pathol-ogy evaluation noted extensive calcifications. Such findings are sometimes seen in late and post-term pregnancies and those complicated by smoking, hypertensive disorders, diabetes, and viral infections. In this case, no other potential etiology was identified. Thus, we conclude that placental calcifications may be associated with SAR-CoV-2 infection in early pregnancy.

Histopathologic evaluation of dichorionic twin placentas in unassisted and in vitro fertilized pregnancies affected by preeclampsia.

OBJECTIVE: Pregnancies achieved with assisted reproductive technology have an increased risk of multiple gestations, preeclampsia, and placental morphologic abnormalities. Inflammatory processes affect dichorionic twin pregnancies disproportionately more than singleton gestations and have been associated with adverse pregnancy outcomes, such as fetal growth restriction and preeclampsia. Our objective is to investigate the placental morphology of dichorionic twin pregnancies complicated by preeclampsia conceived with in vitro fertilization (IVF) versus unassisted. METHODS: This is a retrospective analysis of placentas from dichorionic twin pregnancies affected by preeclampsia conceived with IVF versus without assistance from 2010 to 2016 at a tertiary care university hospital. Placental pathology findings were analyzed both independently and in aggregate stratified into composite outcome scores using a modified placental synoptic framework. Individual placental abnormalities were grouped into composite categories based on the site of origin: anatomic placental abnormalities; maternal vascular malperfusion; placental villous maldevelopment; fetal vascular malperfusion; chronic utero-placental separation; maternal-fetal interface disturbance; inflammation of infectious etiology; and inflammation of idiopathic etiology. Placental histopathological statistical analysis was performed using Fisher's exact test. Demographic variables and pregnancy outcomes were compared between groups using the Student's t test or Mann-Whitney U test, where appropriate. p < .05 defined statistical significance. RESULTS: Of 117 dichorionic twin pregnancies, 60 resulted from IVF (Group A) and 57 were conceived without assistance (Group B). Patients in Group A were older (36 [29-37] vs. 33 [32-38] respectively; p = .042) and less parous (18.3% vs. 38.6% percent parous in Group A and Group B, respectively p = .009) than Group B, respectively. No differences were found between groups regarding mode of delivery, gestational age at delivery, placental weight/birthweight, fetal growth restriction, and discordance of fetal growth. There were significantly more inflammatory changes of unknown etiology and composite inflammatory abnormalities in Group A versus Group B (26.7% vs. 10.5%, p = .02). The cumulative number of inflammatory abnormalities per patient had a significantly different distribution among groups (p = .005), and Composite Chronic Inflammation and Infection were found to be significantly more abundant in Group A versus Group B (p = .02). The distribution of placental composite anatomic placental abnormalities, maternal vascular malperfusion, placental villous maldevelopment, fetal vascular malperfusion, chronic utero-placental separation, or maternal-fetal interface disturbance was not statistically different between groups. The distribution of placental abnormalities was not different between groups for any individually analyzed pathological condition. Due to the relatively small sample size, adjustment for potential confounders was not performed. CONCLUSION: Dichorionic twin pregnancies affected by preeclampsia are associated with more placental inflammatory abnormalities if conceived with IVF versus unassisted. Further research is needed to ascertain the underlying mechanisms of these observed differences.

Histopathologic evaluation of placentas after diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection.

Background: The impact of maternal severe acute respiratory syndrome coronavirus 2 infection on placental histopathology is not well known. Objective: To determine if any significant placental histopathologic changes occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection during pregnancy and whether these changes are correlated with the presence or absence of symptoms associated with the infection. Study Design: A retrospective cohort study of women diagnosed as having severe acute respiratory syndrome coronavirus 2 infection who delivered at a single center from April 9, 2020 to April 27, 2020, and had placental specimens reviewed by the Department of Pathology. Women with singleton gestations and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for inclusion. Historical controls selected from a cohort of women who delivered 6 months before the study period were matched in a 1:1 fashion by weeks of gestation at delivery. Histopathologic characteristics were evaluated in each placenta, and the incidence of these findings was compared between placentas of those who received a diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection and historical controls, and between placentas from patients with or without typical symptoms related to the infection. Statistical analyses included the use of Wilcoxon rank-sum test and Fisher's exact test for the comparison of categorical and continuous variables. Statistical significance was defined as a P value of <.05. Results: A total of 50 placentas after the diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection and 50 historical controls were analyzed. Among the placentas from patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection, 3 (6%) were preterm (33 3/7, 34 6/7, and 36 6/7 weeks of gestation), 16 (32%) were from patients with typical symptoms related to the infection, and 34 (68%) were from patients without typical symptoms related to the infection. All patients had received a diagnosis of severe acute respiratory syndrome coronavirus 2 infection in the third trimester. Decidual vasculopathy was not visualized in any of the placentas from patients diagnosed as having severe acute respiratory syndrome coronavirus 2 infection. There was no statistically significant difference in placental histopathologic characteristics between the groups. Severe acute respiratory syndrome coronavirus 2 test results for all neonates at 24 hours of life were negative. Conclusion: Based on the results of this study, there are no significant placental histopathologic changes that occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection in women during the third trimester of pregnancy compared with a gestational age-matched historical control group. Similar incidences of histopathologic findings were also discovered when comparing placentas from patients with severe acute respiratory syndrome coronavirus 2 infection with or without the presence of symptoms typically related to the infection.

Hemorrhage from Umbilical Cord Ulceration Identified on Real-Time Ultrasound in a Fetus with Duodenal Atresia.

Umbilical cord ulceration has been associated with congenital upper intestinal (duodenal or jejunal) atresia and can lead to fatal fetal intrauterine hemorrhage. We report a case of spontaneous hemorrhage from the umbilical cord, incidentally noted at the time of ultrasound in a 33-week fetus with suspected duodenal atresia, in which immediate delivery resulted in a good outcome. Despite many reports in the literature of congenital upper intestinal atresia and its association with umbilical cord ulceration, the propensity for this lesion for fetal hemorrhage, and the resulting perinatal morbidity and mortality, there appears to be a gap in the dissemination of this knowledge. In fetuses with suspected congenital upper intestinal atresia, recognition of the entity of umbilical cord ulceration may be improved by ultrasound with special attention to the amount of Wharton's jelly within the cord. Routine antepartum fetal surveillance may reduce perinatal morbidity and mortality from this condition. A high index of suspicion is needed to make the diagnosis of umbilical cord ulceration in association with congenital upper intestinal atresia. The role of amniotic fluid bile acids in the genesis of this disorder needs further study.

Accuracy of fetal anatomy survey in the diagnosis of velamentous cord insertion: a case-control study.

OBJECTIVE: Our objective was to determine the accuracy of ultrasound at the time of the fetal anatomy survey in the diagnosis of velamentous cord insertion (VCI). STUDY DESIGN: This retrospective case-control study identified placentas with VCI (cases) and randomly selected placentas with normal placental cord insertion (PCI) (controls) as documented by placental pathology for mothers delivered from 2002 through 2015. Archived ultrasound images for PCI at the time of the fetal anatomy survey were reviewed. Data analysis was by calculation of sensitivity, specificity, and accuracy and their 95% CI for the ultrasound diagnosis of VCI. RESULTS: The prevalence of VCI was 1.6% of placentas submitted for pathologic examination. There were 122 cases of VCI and 347 controls with normal PCI. The performance criteria calculated for the diagnosis of VCI at the time of fetal anatomy survey were as follows: sensitivity 33.6%; 95% CI: 25.3, 42.7; specificity 99.7%; 95% CI: 98.4, 99.9 and accuracy 82.5; 95% CI: 80.5, 82.9. CONCLUSION: The identification of a VCI at the time of fetal anatomy survey is highly specific for the presence of a VCI as documented by placental pathology. The sensitivity in this study was less than expected. Sensitivity could be improved by reducing the number of nonvisualized PCIs, creating an awareness of risk factors for VCI, and obtaining more detailed images in the case of an apparent marginal PCI.

Diagnosis and imaging characteristics of a juvenile fibroadenoma in a 2-year-old patient: a case report.

Fibroadenomas are abundantly reported in the literature with several papers documenting the natural progression and clinical outcomes of thousands of cases. Juvenile fibroadenomas (also called cellular fibroadenomas) are frequently characterized by rapid growth, often described as 5-10 cm in size. They constitute approximately 7%-8% of fibroadenomas. They often measure greater than 5 cm. Pathologically, they show similar features to fibroadenomas but can resemble phyllodes. There have been few documented cases of breast masses in early childhood. Furthermore, there are scant radiology publications focused on the imaging features of juvenile fibroadenomas in patients younger than 5 years old. Our patient presented at 2 years of age with a unilateral right breast mass. Two ultrasound examinations were completed over a period of 5 months, and a magnetic resonance imaging was performed prior to surgical intervention. Eventual surgical excision yielded a final pathologic diagnosis of juvenile fibroadenoma. In this report, we will discuss the imaging and pathology of juvenile fibroadenomas, and we will address important differential considerations both from a pathologic and radiologic standpoint.

A case of vasculopathy of unknown etiology associated with fatal hydrops fetalis and review of the literature on intimomedial mucoid degeneration.

Non-immune hydrops fetalis (NIHF) has a high mortality rate [1]. Many etiologies of NIHF have been identified, including cardiovascular abnormalities, severe anemia, and genetic defects. In patients with cardiovascular etiology, structural malformations lead to fluid accumulation resulting in increased intravascular hydrostatic pressure. We report a fatal case of NIHF in a 31 week gestational age, Caucasian neonate with heart remodeling associated with a stenotic vasculopathy of the right pulmonary artery. The artery revealed partial occlusion with vascular wall abnormalities, including disarrayed smooth muscle fibers, hyperplasia within the tunica media, and myxoid change within the media and intima. Identical vasculopathy was also identified within a mesenteric artery, and this contributed to hemorrhage and early ischemic necrosis of the small intestine, discovered on postmortem examination.

The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors.

Multiple therapies currently exist for renal cell carcinoma, however, most do not result in cure and the development of acquired resistance is the rule rather than the exception. CDK4/6 and PIM1 kinases are potential new therapeutic targets in RCC. Abemaciclib is a potent CDK4/6 and PIM1 kinase inhibitor, thus we evaluated the effects of abemaciclib on renal cell carcinoma. In vitro, abemaciclib causes decreased cellular viability, increased apoptosis, and alterations in autophagy in renal cell carcinoma cell lines. A pre-clinical mouse model of RCC shows abemaciclib in combination with sunitinib to cause dramatic reduction in tumor sizes without overt toxicity. Thus abemaciclib is active in renal cell carcinoma and should be evaluated in a clinical trial in combination with sunitinib. Additionally, CDK4/6 and PIM1 kinase appear to be viable clinical targets in renal cell carcinoma.

Suspected Fetal Growth Restriction at 37 Weeks: A Comparison of Doppler and Placental Pathology.

Objective. Our objective was determining if abnormal Doppler evaluation had a higher prevalence of placental pathology compared to normal Doppler in suspected fetal growth restriction (FGR) of cases delivered at 37 weeks. Study Design. This retrospective cohort study of suspected FGR singletons with antenatal Doppler evaluation delivered at 37 weeks had a primary outcome of the prevalence of placental pathology related to FGR. Significance was defined as p ≤ 0.05. Results. Of 100 pregnancies 46 and 54 were in the abnormal and normal Doppler cohorts, respectively. Placental pathology was more prevalent with any abnormal Doppler, 84.8% versus 55.6%, odds ratio (OR) 4.46, 95% confidence interval (CI): 1.55, 13.22, and p = 0.002. Abnormal middle cerebral artery (MCA) Doppler had a higher prevalence: 96.2% versus 54.8%, OR 20.7, 95% CI: 2.54, 447.1, and p < 0.001. Conclusion. Abnormal Doppler was associated with more placental pathology in comparison to normal Doppler in fetuses with suspected FGR. Abnormal MCA Doppler had the strongest association.

Delayed Presentation of Jejuno-Jejunal Fistula With Stricture After Physical Child Abuse.

Small intestinal injury is seldom described in the context of child abuse. Signs and symptoms are subtle, often leading to delays in diagnosis. We describe a 3-year-old boy initially admitted with severe blunt abdominal trauma from physical child abuse. He was successfully managed nonoperatively. The child was then hospitalized several times for nonspecific abdominal symptoms until diagnostic laparoscopy discovered a jejunal stricture with a proximal jejuno-jejunal fistula. Symptoms fully resolved after resection. Delayed presentation of small intestinal injury should remain on the differential diagnosis in the evaluation of persistent abdominal symptoms in a child with a prior history of physical abuse, even if imaging studies do not reveal specific abnormalities.

Mimics of duplication cysts: intraperitoneal nodules in a 14-year-old boy.

Hemangiomas are the most common primary hepatic tumors, but there are few reports of their occurrence elsewhere in the abdomen. The concurrent existence of multiple fibrous nodules of the omentum, mesentery, and porta hepatis, along with a gastric hemangioma, in a child raises the question of syndromic association. Our search of the English literature revealed only rare mentions of hemangiomas involving the stomach and mesentery or omentum. These lesions have attracted clinical attention by symptoms of obstruction, gastrointestinal bleeding, intussusception, infection, perforation, or vague abdominal pain. Although some tumors exist unnoticed for many decades and are identified only incidentally, others present emergently and require immediate surgical attention. We report the case of a 14-year-old boy who presented with symptoms similar to those for appendicitis or duplication cyst, who was found to have a torsed gastric hemangioma and multiple benign fibrous nodules in the abdomen. The presence of multiple vascular or fibrous lesions is associated with genetic syndromes that can have lifelong and reproductive repercussions; so it is imperative that these tumors be recognized by diagnosticians.

Occult coronary ostial obstruction late after arterial switch operation.

Occult coronary artery obstruction can be a late source of morbidity and mortality following the arterial switch operation for transposition of the great arteries. We describe a case of undiagnosed left coronary ostial obstruction in a teenager which may have contributed to perioperative ventricular dysfunction and subsequent mortality following a reoperation many years after arterial switch.

Type 2 congenital pulmonary airway malformation and congenital nephrotic syndrome: report of a new association.

Type 2 congenital pulmonary airway malformation (CPAM) has been reported in association with many other congenital anomalies. To the best of our knowledge, however, an association of type 2 CPAM with congenital nephrotic syndrome has not been heretofore reported. We present the 1st report of such an association in a boy who had a prenatal diagnosis of cystic lung malformation and was found to have congenital nephrotic syndrome (diffuse mesangial sclerosis) at 1 month of age. A prenatal ultrasonogram had also shown oligohydramnios, and additionally the child had cleft lip and palate. There was no family history of childhood renal or pulmonary disease, and genetic testing for genes mutated in congenital nephrotic syndrome was negative.

Chemotherapy-related leiomyopathy: a suggested morphological explanation for the intestinal dysmotility affecting patients treated with anthracyclines.

Anthracycline, used in oncological chemotherapy, has one well-known side effect: cardiotoxicity. Another is abnormal intestinal motility such as constipation and ileus, the pathogenesis of which, to our knowledge, has not been morphologically investigated. We conducted a study in search of morphological evidence that might shed some light on the pathogenesis of the motility dysfunction. Autopsies performed between 2002 and 2007 were reviewed to select cases of children who had received anthracycline therapy for various neoplasms. The seven patients found had leukemias, lymphomas, or renal solid tumors. They all suffered from constipation or intestinal dysmotility, and no case of anthracyclin-treated neoplasia without the side effect was found in the files. Tissue samples from the heart, gastrointestinal tract, uterus, urinary bladder, and skeletal muscles were examined by light and electron microscopy. As described by others, the myocardium of all anthracycline-treated patients showed loss of myofilaments, fibrosis, mitochondrial proliferation, and pools of accumulated Z-band material. In the gastrointestinal tract and other smooth muscle-endowed organs such as muscular blood vessels, bladder and uterus, the muscularis displayed hyalinization and disorganization, including loss of myofilaments and moderate-severe fibrosis. This study illustrates changes in the smooth muscle, and that of the gastrointestinal tracts and their vessels in particular, in patients treated with anthracycline, who had experienced motility dysfunction associated with their chemotherapy, suggesting that, in addition to the heart, anthracycline may also damage smooth muscle fibers and thus be instrumental in the pathogenesis of the side effects.

Role of chromosome 1 pericentric heterochromatin (1q) in pathogenesis of myelodysplastic syndromes: report of 2 new cases.

Chromosome 1 pericentromeric heterochromatin (1q) has been shown to play an important role in the pathogenesis of non-Hodgkin lymphoma and multiple myeloma. Myelodysplastic syndrome (MDS) results from marrow failure in two or more cell lineages. Although trisomy 1q has been reported in MDS, it is usually present with additional common abnormalities such as trisomy 8, monosomy 5 or monosomy 7, leading to speculation that 1q abnormalities are mostly secondary events representing clonal evolution. We report two cases of MDS in which consistent involvement of 1q heterochromatin is seen as the primary clonal abnormality. Both patients presented with fatigue and pancytopenia. Based on the published reports and our cases, we propose that the 1q heterochromatin plays a vital role in the pathophysiology of MDS. Abnormalities involving 1q result in aberrant heterochromatin/euchromatin junctions, leading to gene dosage abnormalities. Further studies of 1q abnormalities in MDS might provide specific insights as to the exact role of the excess 1q heterochromatin in the etiology of MDS.