Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

Objectives: Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis.

Methods: The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules.

Purpose: Molecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations.

Hepatocellular Adenoma: Report of 2 Cases That Highlight the Relevance of Phenotype-Genotype Correlation in the Pediatric Population.

Background: Hepatocellular adenoma (HCA) in the pediatric population is very rare and there are only limited studies, especially with molecular characterization of the tumors. Main HCA subtypes recognized in the current WHO classification include -inactivated HCA (H-HCA), inflammatory HCA (IHCA), β-catenin-activated HCA (b-HCA), and β-catenin-activated IHCA (b-IHCA) and sonic hedgehog HCA (shHCA) is reported as an emerging subtype.

Methods: Clinical history, pathological information, and molecular studies for a series of 2 cases of pediatric HCA were reviewed.

Isolated Terminal Ileitis in Children.

Isolated terminal ileitis in adults is a well described entity that rarely progresses to Crohn disease (CD), and pediatric literature on this topic is very limited. We describe the prevalence, clinical, endoscopic, histologic, and radiological features, along with long-term outcome of isolated terminal ileitis in our institution. We reviewed charts of 956 children who underwent colonoscopy from 2013 to 2017.

Transcriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in children. The mechanisms that drive NAFLD disease progression in this specific patient population remain poorly defined. In this study, we obtained liver biopsy samples from a multiethnic cohort of pediatric patients with NAFLD (n = 52, mean age = 13.

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury.

Context.—: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear.

Objective.

Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review.

Study Objective: To study the progression of benign ovarian lesions to mucinous borderline ovarian tumors (mBOTs); analyze the clinicopathologic features, diagnosis, and management of mBOTs in pediatric and adolescent girls; and provide a review of the literature on mBOTs in this population.

Design: Retrospective chart review of female adolescents younger than 18 years diagnosed with mBOTs between July 2017 and February 2021.

Setting: Yale New Haven Hospital, New Haven, Connecticut; and Yale New Haven Health Bridgeport Hospital, Bridgeport, Connecticut.

Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation.

Transcription factors specialized to limit the destructive potential of inflammatory immune cells remain ill-defined. We discovered loss-of-function variants in the X-linked ETS transcription factor gene ELF4 in multiple unrelated male patients with early onset mucosal autoinflammation and inflammatory bowel disease (IBD) characteristics, including fevers and ulcers that responded to interleukin-1 (IL-1), tumor necrosis factor or IL-12p40 blockade. Using cells from patients and newly generated mouse models, we uncovered ELF4-mutant macrophages having hyperinflammatory responses to a range of innate stimuli.

Hofbauer Cells and COVID-19 in Pregnancy.

Context.—: SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2.

Complete Hydatidiform Mole and Coexisting Fetus With Gastroschisis: A Case Report Highlighting the Importance of Diagnostic Genotyping.

Twin pregnancy with a complete hydatidiform mole and a coexisting fetus (CHMCF) is an extremely rare occurrence, described only by a handful of published series and cases reports. The majority of the literature on CHMCF examines prenatal care and follow-up in relation to the increased risk of gestational trophoblastic neoplasia (GTN). At present, few reports elaborate on the diagnostic process and differential diagnosis, especially in the context of recent molecular advances in risk stratification for GTN.

Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface.

Background: Pregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this increased morbidity and its potential effect on the developing fetus is not well understood.

Methods: We assessed placental histology, ACE2 expression, and viral and immune dynamics at the term placenta in pregnant women with and without respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Findings: The majority (13 of 15) of placentas analyzed had no detectable viral RNA.

Placenta Teratoma or Acardiac Fetus Amorphous: A Case Study by DNA Genotyping.

To date, 40 cases of placental teratoma and 21 cases of umbilical cord teratoma have been reported in the literature. Such entities are purportedly described as originating from ectopically derived totipotential germ cells forming 1 or more of 3 germ layers, similar to teratomas arising in other sites. These entities have been described as distinct from acardiac twins based on the absence of both an axial skeleton and/or separate umbilical cord attachment.

SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface.

Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term.

Gastrointestinal Zygomycosis in a Preterm Neonate Associated With Contaminated Probiotics.

A neonate of 29 weeks' gestation who received probiotics developed clinical signs suggesting surgical necrotizing enterocolitis. A specimen of resected ileum revealed fungal forms within the bowel wall. Rhizopus oryzae was detected via DNA sequencing from probiotic powder and tissue specimens from the infant.

Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Live-Born and Stillborn Infants.

Context.—: The number of neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasing, and in a few there are reports of intrauterine infection.

Objective.

Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology-histopathology correlation in 7 patients.

Background: Germline and somatic mutations of DICER1 have been identified in various types of neoplastic lesions, with germline DICER1 mutation being linked to autosomal dominant hereditary pleiotropic tumor syndrome (DICER1 syndrome). Patients with DICER1 syndrome are at increased risk of developing thyroid disease, including thyroid cancer. The goal of this study was to identify diagnostic cytologic features in thyroid fine-needle aspiration (FNA) samples from patients with DICER1 mutation.

Human Small Intestine Transplantation: Segmental Susceptibility to Ischemia Using Different Preservation Solutions and Conditions.

Background And Aims: Among all transplanted abdominal organs, the small intestine is one of the most ischemia sensitive. Appropriate graft selection, procurement, and preservation are crucial for optimum graft and patient survival. We evaluated ischemic damage in human small intestine grafts under different hypothermic preservation conditions (cold static and continuous perfusion) and solutions: histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW).

Pediatric unilobar resection in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) causes chronic infections and progressive bronchiectasis that can lead to severe lung disease. Because there are no cures or regenerative therapy options for PCD, treatment of severe lung disease in PCD is focused on managing symptoms, including aggressive administration of antibiotics and diligent airway clearance. The Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) does not recommend routine lobectomy, reserving its use for "rare cases of PCD with severe, localized bronchiectasis" and warns that a lobectomy should be treated with caution.

Autopsy Services and Emergency Preparedness of a Tertiary Academic Hospital Mortuary for the COVID-19 Public Health Emergency: The Yale Plan.

Pathology Autopsy and Mortuary Services have been front and center in the severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) pandemic. The sheer number of fatalities from the pandemic have been unlike any other in recent memory and needed the rapid creation of new protocols and paradigms to manage the situation. This required rapidly escalating mortuary capacity to manage the increased fatalities from the pandemic with the establishment of lines of communication and networking with governmental entities, institution of new policies for patient flow, and implementation of worker infection control and well-being plans.