Primary diffuse leptomeningeal atypical teratoid/rhabdoid tumours (ATRT) of childhood: a molecularly characterised case report and literature review.

Background: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant central nervous system tumours, typically presenting in the posterior fossa of very young children. Prognosis remains poor despite current therapy, while tumorigenesis implicates both genomic and epigenetic dysregulation. Primary diffuse leptomeningeal (PDL) ATRT, characterised by the absence of an intraparenchymal mass lesion, is seldom reported but appears associated with a dismal outcome.

Emerging round cell sarcomas in children.

Several distinctive round cell sarcomas have emerged by leveraging new testing modalities to include immunohistochemistry, next-generation sequencing, methylation array, and others. While Ewing sarcoma has led the way as the prototypic round cell sarcoma, more recently described round cell sarcomas of bone and soft tissue are now recognized which have unique clinical, morphologic, immunophenotypic, and genetic signatures. While each of these entities is less common than Ewing sarcoma, it is important to distinguish these tumors for correct diagnosis, prognostication, and potential treatment management.

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults.

Background: Patients with PAX3/7-FOXO1 fusion-negative rhabdomyosarcomas (fnRMS) harbouring the rare L122R MYOD1 mutation have significantly poorer prognosis than other fnRMS. We undertook a detailed clinicopathological evaluation of a cohort of patients with MYOD1 mutated fnRMS in order to improve risk stratification and treatment options.

Procedure: Histological, mutational and clinical data from a cohort of patients with MYOD1 mutant RMS treated in Europe were analysed.

The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis.

Objective: Simultaneous activation of β2- and β3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of β1-ARs - and thus inducing cardiovascular complications - are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel β2-and β3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models.

Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism.

Gene expression is tightly regulated, with many genes exhibiting cell-specific silencing when their protein product would disrupt normal cellular function. This silencing is largely controlled by non-coding elements, and their disruption might cause human disease. We performed gene-agnostic screening of the non-coding regions to discover new molecular causes of congenital hyperinsulinism.

Pleuropulmonary blastoma (PPB) and other DICER1-associated high-grade malignancies are morphologically, genetically and epigenetically related - A comparative study of 4 PPBs and 6 sarcomas.

DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary blastomas (PPBs) and 6 sarcomas by mutation analysis, whole transcriptome sequencing and methylation profiling. 9/10 patients were female.

Embryonal sarcoma of the liver in a girl with Cockayne syndrome.

The first reported malignancy associated with Cockayne syndrome.

A Rare Case of Severe Nontropical Isolated Right Ventricular Endomyocardial Fibrosis.

We present a case of late presentation nontropical endomyocardial fibrosis isolated to the right ventricle and tricuspid valve (TV). In response to deteriorating hemodynamics, surgical debulking and TV removal were performed before initiation of centralized venoarterial extracorporeal membrane oxygenation support. Definitive endomyocardial resection with a TV prosthesis was then successfully completed.

Management and outcome of paediatric testicular tumours - A 20 year experience.

Objective: To report a 20-year experience highlighting management and outcome(s) of paediatric testicular tumours.

Patients And Methods: All males (< 19 years) with an index diagnosis of testicular tumours during the era(s) 1998-2018 in North West England were identified. Data were collected regarding age at diagnosis, disease stage, surgical operations, tumour biology and outcome(s).

Correction to "Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure".

[This corrects the article DOI: 10.1021/acsptsci.0c00003.

Infantile fibrosarcoma with TPM3-NTRK1 fusion in a boy with Bloom syndrome.

Bloom syndrome (BS) is a genomic and chromosomal instability disorder with prodigious cancer predisposition caused by pathogenic variants in BLM. We report the clinical and genetic details of a boy who first presented with infantile fibrosarcoma (IFS) at the age of 6 months and subsequently was diagnosed with BS at the age of 9 years. Molecular analysis identified the pathogenic germline BLM sequence variants (c.

Neutrophil dysfunction triggers inflammatory bowel disease in G6PC3 deficiency.

The glucose-6-phosphatase catalytic subunit 3 (G6PC3) encodes a ubiquitously expressed enzyme that regulates cytoplasmic glucose availability. Loss-of-function biallelic G6PC3 mutations cause severe congenital neutropenia and a diverse spectrum of extra-hematological manifestations, among which inflammatory bowel disease (IBD) has been anecdotally reported. Neutrophil function and clinical response to granulocyte colony-stimulating factor (G-CSF) and hematopoietic stem cell transplantation (HSCT) were investigated in 4 children with G6PC3 deficiency-associated IBD.

Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure.

Heart failure (HF) is a global pandemic with significant mortality and morbidity. Despite current medications, 50% of individuals die within 5 years of diagnosis. Of these deaths, 30-50% will be a result of sudden cardiac death from ventricular arrhythmias.

Refractory very early-onset inflammatory bowel disease associated with cytosolic isoleucyl-tRNA synthetase deficiency: A case report.

Background: Aminoacyl tRNA synthetases/ligases (ARSs) are highly conserved enzymes involved in attaching amino acids to tRNA promoting protein synthesis. Although deficiencies of ARSs localized to the mitochondria classically present with neuropathology, the clinical features of cytosolic ARS deficiencies are more variable. They have previously been associated with neonatal hepatitis, but never with early-onset inflammatory bowel disease.

Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in .

Excessive type I interferon (IFNα/β) activity is implicated in a spectrum of human disease, yet its direct role remains to be conclusively proven. We investigated two siblings with severe early-onset autoinflammatory disease and an elevated IFN signature. Whole-exome sequencing revealed a shared homozygous missense Arg148Trp variant in , a transcription factor that functions exclusively downstream of innate IFNs.

Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas.

Intracranial Angiomatoid Fibrous Histiocytoma with EWSR1-CREB Family Fusions: A Report of 2 Pediatric Cases.

Background: Intracranial angiomatoid fibrous histiocytomas (AFHs) are very rare tumors. Histologically, classical cases have been reported exclusively in adults, with myxoid variants identified only in children. Here, we report the clinical presentation, treatment, biopsy, and molecular test results for 2 children with classical intracranial AFH and combine this with a literature review of published intracranial AFH and AFH-like cases.

Clinical Diversity in Focal Congenital Hyperinsulinism in Infancy Correlates With Histological Heterogeneity of Islet Cell Lesions.

Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy and childhood. The focal form (CHI-F) of CHI can be potentially cured by pancreatic lesionectomy. While diagnostic characteristics of CHI-F pancreatic histopathology are well-recognized, correlation with clinical phenotype has not been established.

Increased Risk for Malignancies in 131 Affected Mutation Carriers.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features.

Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature.

Introduction: Craniopharyngiomas are one of the most frequently diagnosed hypothalamo-pituitary tumors in childhood. The adamantinomatous histological subtype accounts for most pediatric cases, while the papillary variant is almost exclusively diagnosed in adults. Here, we report a case of papillary craniopharyngioma in a very young child, confirmed by molecular tissue analysis.