Intestinal histopathology in pediatric PSC-IBD: Characterization of phenotype and assessment of the Nancy Index.

Background: We aimed to characterize the histologic gut phenotype of pediatric primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) against non-PSC colitis, and to assess Nancy Index (NI) performance in pediatric PSC-IBD.

Methods: Single-center retrospective cohort study including children diagnosed with PSC-IBD or non-PSC colitis (ulcerative colitis [UC] or IBD-unclassified) from 2000 to 2018, with diagnostic intestinal biopsies. Biopsies were re-reviewed by two independent pathologists who assessed microscopic disease distribution, NI scores, and specific histological features in the right and left colons, overall and stratified by endoscopic severity (moderate-severe vs.

Antisense Oligonucleotide Therapy for Calmodulinopathy.

Background: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in , , or , which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.

Methods: We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of pathogenic variants.

Professional Master of Health Science in Laboratory Medicine: Training Clinical Laboratory Scientists in an Integrated Program at a Research-Intensive University.

A 2-year professional master of health science program at the University of Toronto provides a unique integrated educational program to train allied health science personnel to practice as physician extenders and health care professionals in two high-demand clinical laboratory disciplines, Pathologists' Assistant (PA) and Clinical Embryologist (CE). This report describes an integrated graduate program developed and delivered in a research-intensive laboratory medicine department. The core courses in fundamental biomedical science and in general medical laboratory function and operations formed the foundation on which the requisite clinical skills required to practice as a PA or CE were subsequently delivered as comprehensive CE and PA specialty courses and practicums.

Survey Data and Experience from a Pediatric Pathology Workshop in Indonesia: Understanding Practice Needs and Utility of Outreach Teachings.

We aimed to share the post-workshop survey results of a pediatric pathology course held in Jakarta, Indonesia. Questionnaires were distributed to participants; responses from practicing pathologists and pathologists-in-training were analyzed. Results: The respondents (107 pathologists of 143 attendees) were predominantly female (83.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months.

Using Deep Learning to Automate Eosinophil Counting in Pediatric Ulcerative Colitis Histopathological Images.

Background: Accurate identification of inflammatory cells from mucosal histopathology images is important in diagnosing ulcerative colitis. The identification of eosinophils in the colonic mucosa has been associated with disease course. Cell counting is not only time-consuming but can also be subjective to human biases.

Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

Background: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative.

Methods: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019.

Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy.

We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dCas9 (i.e., "dead" Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy.

A case of neonatal sweet syndrome associated with mevalonate kinase deficiency.

Background: Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS.

Splenic Lymphatic Malformation With Papillary Endothelial Proliferation: A Rare Histologic Variant or a Unique Entity?

Lymphatic malformations (LMs) are congenital anomalies of the lymphatic system due to abnormalities that occur during the development of the lymphovascular system. Also known as lymphangiomas, they are usually multifocal, affect multiple organ systems, and are seen in a variety of developmental or overgrowth syndromes. Splenic lymphangiomas are uncommon and usually occur in the context of multiorgan lymphangiomatosis.

Spectrum of Liver Pathology in Dyskeratosis Congenita.

Dyskeratosis congenita (DC) is a rare multisystemic disorder associated with defective telomere maintenance. Frequent clinical manifestations of DC include reticular skin pigmentation, dystrophic nails, oral leukoplakia, and bone marrow failure. Hepatic disturbances are reported to occur in 7% of DC patients.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

Background And Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

Approach And Results: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.

Paediatric non-alcoholic fatty liver disease: an approach to pathological evaluation.

Non-alcoholic fatty liver disease (NAFLD) is becoming an increasingly important healthcare issue along with the rising rates of obesity worldwide. It is the most common chronic liver disease in the paediatric population and the fastest growing indication for liver transplant in young adults. The pathogenesis is complex with contributions from multiple factors and genetic predisposition.

Pediatric Acute Liver Failure: A Clinicopathological Perspective.

Pediatric acute liver failure (PALF) is a life-threatening disorder characterized by acute hepatocellular injury occurring in children without recognized underlying liver disease. The clinicopathologic evaluation of PALF requires a different approach from that in adults. The diagnostic considerations differ depending on the age, personal and family history, geographical region, and clinical presentation.

Innocent until proven guilty? Longstanding atrial ectopy preceding cardiac rhabdomyoma diagnosis in tuberous sclerosis complex: a case report.

Background: Cardiac rhabdomyoma are the most common cardiac tumour in childhood and are associated with tuberous sclerosis complex (TSC) up to 96% of infant cases. They classically manifest in the foetal and neonatal period, undergo spontaneous regression in the first years of life and are associated with arrhythmia in part due to interruption of normal conduction pathways by the tumour.

Case Summary: We present a case of a 3-year-old boy with a long-standing history of atrial ectopy who was incidentally found to be in atrial flutter due to a new, rapidly growing cardiac rhabdomyoma impacting ventricular function.

Meningothelial Hamartoma of the Scalp in a Child With Gorlin Syndrome.

Meningothelial hamartoma of the scalp is a rare entity characterized by a mix of meningothelial tissue and various connective tissue elements. To the best of the authors' knowledge, there has only been one reported case of meningothelial hamartoma of the scalp in the setting of Gorlin syndrome in the literature. In this report, we describe the case of a 3-year-old boy with Gorlin syndrome who presented with a congenital scalp lesion.

Prospective Evaluation of Endoscopic and Histologic Indices in Pediatric Ulcerative Colitis Using Centralized Review.

Introduction: We aimed to evaluate the reliability and validity of the Ulcerative Colitis (UC) Endoscopic Index of Severity (UCEIS) and Mayo Endoscopy Score (MES) and to validate the Robarts Histopathology Index (RHI) and Nancy Index (NI) in pediatric UC. We examined rectosigmoid and pancolonic versions of each instrument.

Methods: Single-center cross-sectional study of 60 prospectively enrolled participants.

Assessment of BCOR Internal Tandem Duplications in Pediatric Cancers by Targeted RNA Sequencing.

Alterations in the BCOR gene, including internal tandem duplications (ITDs) of exon 15 have emerged as important oncogenic changes that define several diagnostic entities. In pediatric cancers, BCOR ITDs have recurrently been described in clear cell sarcoma of kidney (CCSK), primitive myxoid mesenchymal tumor of infancy (PMMTI), and central nervous system high-grade neuroepithelial tumor with BCOR ITD in exon 15 (HGNET-BCOR ITDex15). In adults, BCOR ITDs are also reported in endometrial and other sarcomas.

Lingual Choristoma with Gastric Epithelium Revisited.

The term 'choristoma' refers to normal appearing tissue in an abnormal location. We describe a case of choristoma with gastric epithelium of the dorsal tongue in a pediatric patient. Lingual choristomas are uncommon cystic or solid lesions which may demonstrate different types of tissue (e.

Primary malignant vascular tumors of the liver in children: Angiosarcoma and epithelioid hemangioendothelioma.

Primary malignant vascular neoplasms of the liver, angiosarcoma and epithelioid hemangioendothelioma, are extremely rare entities in the pediatric population. International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group. In this article, we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population.