Stillbirth Associated With Anomalous Origin and Course of the Left Coronary Artery: A Report of 2 Cases.

Coronary artery anomalies and their potential sequelae are not well studied in association with stillbirth. Herein, we report the autopsy findings in two term stillborn fetuses with coronary artery anomalies. Both fetuses showed identical findings consisting of an abnormal origin of the left coronary artery from the right sinus of Valsalva and an interarterial course of the left coronary artery. Histologic vascular and myocardial changes were also present. These coronary artery findings are associated with sudden death in adults and neonates, and therefore, their potential to be a cause and/or contributor to fetal death is suspected.

Integrated Analysis of Ovarian Juvenile Granulosa Cell Tumors Reveals Distinct Epigenetic Signatures and Recurrent TERT Rearrangements.

PURPOSE: Adult granulosa cell tumor (AGCT) is characterized by the somatic FOXL2 p.C134W mutation, and recurrences have been associated with TERT promoter and KMT2D-truncating mutations. Conversely, the molecular underpinnings of the rare juvenile granulosa cell tumor (JGCT) have not been well elucidated. To this end, we applied a tumor-only integrated approach to investigate the genomic, transcriptomic, and epigenomic landscape of 31 JGCTs to identify putative oncogenic drivers. EXPERIMENTAL DESIGN: Multipronged analyses of 31 JGCTs were performed utilizing a clinically validated next-generation sequencing (NGS) panel targeting 580 cancer-related genes for genomic interrogation, in addition to targeted RNA NGS for transcriptomic exploration. Genome-wide DNA methylation profiling was conducted using an Infinium Methylation EPIC array targeting 866,562 CpG methylation sites. RESULTS: We identified frequent KMT2C-truncating mutations along with other mutated genes implicated in the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, in addition to previously reported hotspot AKT1 and DICER1 mutations. Targeted transcriptome sequencing revealed recurrent TERT rearrangements (13%) involving partners CLPTM1L or DROSHA, and differential gene expression analysis showed FGFR1 upregulation in the TERT non-rearranged JGCTs under direct promoter control. Genome-wide DNA methylation rendered a clear delineation between AGCTs and JGCTs at the epigenomic level, further supporting its diagnostic utility in distinguishing among these tumors. CONCLUSIONS: This is the largest comprehensive molecular study of JGCTs, where we further expand our current understanding of JGCT pathogenesis and demonstrate putative oncogenic drivers and TERT rearrangements in a subset of tumors. Our findings further offer insights into possible targeted therapies in a rare entity.

Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach.

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.

Association of SARS-CoV-2 placental histopathology findings with maternal-fetal comorbidities and severity of COVID-19 hypoxia.

OBJECTIVE: SARS-CoV-2 is known to impact multiple organ systems, with growing data to suggest the potential for placental infection and resultant pathology. Understanding how maternal COVID-19 disease can affect placental histopathology has been limited by small study cohorts with mild disease, review by multiple pathologists, and potential confounding by maternal-fetal comorbidities that can also influence placental findings. This study aims to identify pathologic placental findings associated with COVID-19 disease and severity, as well as to distinguish them from changes related to coexisting maternal-fetal comorbidities. METHODS: This is an observational study of 61 pregnant women with confirmed SARS-CoV-2 infection who delivered and had a placental histological evaluation at NYU Langone Health between March 19, 2020 and June 30, 2020. Primary outcomes were the prevalence of placental histopathologic features and their association with maternal-fetal comorbidities and severity of COVID-19 related hypoxia. Analysis was performed using Fisher's exact test and t-test with p < 0.05 considered significant. RESULTS: Sixty-one placentas were included in the study cohort, 71% from pregnancies complicated by at least one maternal-fetal comorbidity. Twenty-five percent of placentas were small for gestational age and 77% exhibited at least one feature of maternal vascular malperfusion. None of the histopathologic features in the examined placentas were associated with the presence of any specific maternal-fetal comorbidity. Thirteen percent of the cohort required maternal respiratory support for COVID-19 related hypoxia. Villous trophoblast necrosis was associated with maternal supplemental oxygen requirement (67 vs. 33%, p = 0.04) and intubation (67 vs. 33%, p = 0.01). CONCLUSION: In pregnancies complicated by COVID-19 disease, there was a high prevalence of placental histopathologic changes identified, particularly features of maternal vascular malperfusion, which could not be attributed solely to the presence of maternal-fetal comorbidities. The significantly increased prevalence of villous trophoblast necrosis in women needing respiratory support suggests a connection to the severity of COVID-19 illness.

Increased Incidence of Barotrauma in Patients with COVID-19 on Invasive Mechanical Ventilation.

Background A high number of patients with coronavirus disease 2019 (COVID-19) pneumonia who had barotrauma related to invasive mechanical ventilation at the authors' institution were observed. Purpose To determine if the rate of barotrauma in patients with COVID-19 infection was greater than in other patients requiring invasive mechanical ventilation at the authors' institution. Materials and Methods In this retrospective study, clinical and imaging data of patients seen between March 1, 2020, and April 6, 2020, who tested positive for COVID-19 and experienced barotrauma associated with invasive mechanical ventilation, were compared with patients without COVID-19 infection during the same period. Historical comparison was made to barotrauma rates of patients with acute respiratory distress syndrome from February 1, 2016, to February 1, 2020, at the authors' institution. Comparison of patient groups was performed using categoric or continuous statistical testing as appropriate, with multivariable regression analysis. Patient survival was assessed using Kaplan-Meier curves analysis. Results A total of 601 patients with COVID-19 infection underwent invasive mechanical ventilation (mean age, 63 years ± 15 [standard deviation]; 71% men). Of the total, there were 89 (15%) patients with one or more barotrauma events for a total of 145 barotrauma events (24% overall events) (95% confidence interval [CI]: 21%, 28%). During the same period, 196 patients without COVID-19 infection (mean age, 64 years ± 19; 52% men) with invasive mechanical ventilation had one barotrauma event (0.5%; 95% CI: 0%, 3%; P < .001 vs the group with COVID-19 infection). Of 285 patients with acute respiratory distress syndrome on invasive mechanical ventilation during the previous 4 years (mean age, 68 years ± 17; 60% men), 28 patients (10%) had 31 barotrauma events, with an overall barotrauma rate of 11% (95% CI: 8%, 15%; P < .001 vs the group with COVID-19 infection). Barotrauma is an independent risk factor for death in COVID-19 (odds ratio = 2.2; P = .03) and is associated with a longer hospital stay (odds ratio = 0.92; P < .001). Conclusion Patients with coronavirus disease 2019 (COVID-19) infection and invasive mechanical ventilation had a higher rate of barotrauma than patients with acute respiratory distress syndrome and patients without COVID-19 infection. © RSNA, 2020 Online supplemental material is available for this article.

Persistent organic pollutant exposure and celiac disease: A pilot study.

Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.

Pathologic Evaluation of Breast Tissue From Transmasculine Individuals Undergoing Gender-Affirming Chest Masculinization.

CONTEXT.­: Bilateral mastectomy for chest masculinization is one of the gender-affirming procedures for transmasculine individuals. OBJECTIVE.­: To optimize gross handling protocols and assess histopathologic findings in transmasculine breast tissue specimens. DESIGN.­: We identified all gender-affirming mastectomies from 2015 to 2018. We sequentially identified reduction mammoplasty (RM) cases for macromastia from the same period as control. Significant findings were defined as atypical ductal or lobular hyperplasia (ADH, ALH), ductal or lobular carcinoma in situ (DCIS, LCIS), or invasive carcinoma. RESULTS.­: Significant findings were present in 6 of 211 gender-affirming mastectomies (2.8%) as follows: ADH (n = 5) and LCIS together with ALH (n = 1). By comparison, 19 of 273 RM specimens (7%) yielded significant findings as follows: ALH (n = 11), ADH (n = 4), LCIS (n = 2), DCIS (n = 1), and invasive lobular carcinoma (n = 1). In the gender-affirming group, 142 transmen underwent androgen therapy before surgery, of whom 2 had significant pathologic findings. Thirty and 41 individuals had a family history of breast cancer in the gender-affirming and RM group, of whom 1 and 3 individuals had significant pathologic findings, respectively. CONCLUSIONS.­: Our study demonstrates that we handle transmasculine mastectomy specimens by examining 2.8 times more slides on average than for RMs, with a 2.5 times lower rate of significant pathologic findings. Prior family history of breast cancer or the use of androgen therapy before surgery in gender-affirming individuals did not increase the risk of identifying significant breast lesions. We recommend submitting 4 tissue blocks per mastectomy for individuals undergoing gender-affirming breast surgery.