Primary Children's Hospital

Embryonal rhabdomyosarcoma arising from the ureter is exceedingly rare. We report the case of a 20-year-old female who presented with flank pain and hematuria, initially attributed to ureteral stones. Subsequent evaluation revealed an embryonal rhabdomyosarcoma (botryoid subtype) of the ureter. Following surgical resection and chemotherapy, the patient achieved remission and experienced minor complications including neuropathy and bladder irritation. This case highlights the classification and management of ureteral rhabdomyosarcoma. While the prognosis for ureteral rhabdomyosarcoma appears favorable based on limited literature, long-term surveillance is crucial for monitoring recurrence and managing potential complications.

Next-generation sequencing (NGS) tests are integral to oncology care. To address the need for clinical and NGS data management, interpretation, and reporting, we developed iCatalog for the multi-institutional Individualized Cancer Therapy 2/Genomic Assessment Informs Novel Therapy Consortium (GAIN) pediatric precision oncology (PO) study. We designed iCatalog as a secure, web-based clinical decision support application that stores and integrates clinical, specimen, and molecular data from multiple sources at the patient level. The knowledge base (KB) and centralized patient/test database are intended to manage information for the 825 patients expected to enroll in the GAIN study. User permissions and access are controlled. Gene- and variant-level interpretation is facilitated through linked external resources and an internal KB that can be updated during application use. iCatalog generates editable, study-specific patient reports for each molecular test. Launched to support the GAIN study, iCatalog integrates genomic data from eight NGS platforms, generates 1002 clinical interpretation reports, and stores data for 1194 tests involving 777 patients with pediatric solid tumors across 133 diagnoses. The KB contains pediatric cancer-specific curations, authored by the research team, spanning 581 genes and 2659 variants (including 2146 single-nucleotide variants and insertions-deletions, 235 copy-number variants, 278 structural variants). iCatalog is a robust tool designed and proven to support a PO study. It integrates clinical and genomic data to facilitate the clinical interpretation and reporting of variants identified through NGS testing while maintaining a pediatric-specific KB generated during the study. As a scalable, modular platform, iCatalog can accelerate clinical decision-making and elevate PO insights across studies.

Tumor cell plasticity drives metastasis and therapy resistance, yet its regulation by oncoprotein dosage dynamics remains poorly understood. In Ewing sarcoma (EwS), variations in EWS::FLI1 (EF) fusion oncoprotein activity have been associated with epithelial-mesenchymal plasticity (EMP). Using degron technology, we precisely modulated endogenous EF in EwS cells and linked phenotypic states to distinct oncoprotein dosages. Strikingly, modest EF depletion promoted a pro-metastatic phenotype that diminished upon near-complete EF loss, revealing a paradoxical effect of submaximal EF inhibition. Nascent RNA-sequencing uncovered distinct gene clusters with heterogenous transcriptional responses to graded EF loss. Genes most sensitive to subtle EF depletion harbored GGAA microsatellites within EF-bound enhancers, while chromatin profiling uncovered candidate cofactors regulating EF-repressed EMP programs. Transient EF depletion followed by rapid restoration, modelling oncoprotein fluctuations, caused persistent dysregulation of genes functionally linked to enhanced extravasation and metastatic burden in preclinical models. This study highlights the therapeutic challenge of incomplete EF elimination, serving a paradigm in which oncoprotein dosage dynamics act as non-genetic drivers of disease progression and reveal novel vulnerabilities of advanced disease.

Low back pain (LBP) in the absence of acute trauma is a common pediatric presentation. Although LBP is frequently due to benign causes, red-flag signs and symptoms may indicate more serious causes, including infections, neoplasms, and inflammatory conditions, that necessitate more urgent management. MRI is the mainstay imaging test for the evaluation of pediatric LBP, and increased radiologist awareness of the imaging findings of key causes of pediatric LBP can expedite diagnosis and treatment and thereby decrease morbidity and mortality. Although imaging plays a key role in the diagnostic workup of LBP in the pediatric age group, imaging must be used judiciously, as excessive advanced imaging may be associated with unnecessary costs and additional patient risk without substantial positive effect on clinical outcome. In this AJR Expert Panel Narrative Review, we provide an overview of the appropriate use of imaging for the workup of a child presenting with LBP, highlighting the utility of different modalities, optimal imaging techniques, and advanced methods that may aid problem solving. We also review the classic imaging features of common and critical causes of LBP in this age group, focusing on pediatric-specific organic causes while addressing certain uncommon diagnoses that radiologists should not miss.