Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors.

Most malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features. Their outcomes and cellular composition remain an open question.

Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers.

Interleukin-15 (IL-15) promotes the survival of T lymphocytes and enhances the antitumour properties of chimeric antigen receptor (CAR) T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy. Glypican-3 (GPC3) is expressed in a group of solid cancers, and here we report the evaluation in humans of the effects of IL-15 co-expression on GPC3-expressing CAR T cells (hereafter GPC3 CAR T cells). Cohort 1 patients ( NCT02905188 and NCT02932956 ) received GPC3 CAR T cells, which were safe but produced no objective antitumour responses and reached peak expansion at 2 weeks.

The "genetic test request": A genomic stewardship intervention for inpatient exome and genome orders at a tertiary pediatric hospital.

Purpose: Exome sequencing (ES) and genome sequencing (GS) are useful tests to diagnose rare diseases in pediatric patients in critical care settings. Genomic test stewardship can increase the appropriate use of these tests leading to improved diagnostics and cost savings.

Methods: A mandatory review of ES and GS orders for admitted patients was implemented in March 2023.

The implementation of molecular tumor profiling in the practice of pediatric cancer pathology: The pathologists' experience.

Background: The increased accessibility and utilization of molecular testing including next-generation sequencing (NGS) has impacted the practice of pediatric pathology, with diagnostic, prognostic, and therapeutic implications for our patients. This survey is the first to describe the utilization of molecular testing in the routine practice of pediatric pathology for the care of children with known or suspected solid tumors.

Procedure: The Society for Pediatric Pathology Practice Committee distributed a survey to our membership asking 25 questions about training, practice setting, molecular ordering practices, and barriers to testing.

Rapid gene fusion testing using the NanoString nCounter platform to improve pediatric leukemia diagnoses in Sub-Saharan Africa.

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity.

An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer.

Background: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery.

Interleukin-15-armored GPC3-CAR T cells for patients with solid cancers.

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy. Glypican-3 (GPC3) is expressed in a group of solid cancers, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks.

Histopathologic and immunophenotypic characterization of patient-derived pediatric malignant hepatocellular tumor xenografts (PDXs).

Advances in targeted therapies for pediatric hepatocellular tumors have been limited due to a paucity of clinically relevant models. Establishment and validation of intrahepatic patient-derived xenograft (PDX) models would help bridging this gap. The aim of this study is to compare the histomorphologic and immunophenotypic fidelity of patient tumors and their corresponding intrahepatic PDX models.

A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

Background & Aims: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition.

Comparative Clinicopathologic and Genomic Analysis of Hepatocellular Neoplasm, Not Otherwise Specified, and Hepatoblastoma.

Accurate diagnosis and treatment of hepatocellular neoplasm, not otherwise specified (HCN-NOS), poses significant challenges. Our study aimed to investigate the clinicopathologic and genomic similarities and differences between HCN-NOS and hepatoblastoma (HB) to guide diagnostic and treatment strategies. The clinicopathologic characteristics of 16 patients with HCN-NOS and 23 patients with HB were compared.

Navigating relapsed hepatoblastoma: Predictive factors and surgical treatment strategy.

Objective: Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high-risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center.

Molecular Profiling of a Hepatocellular Neoplasm Not Otherwise Specified (HCN-NOS) Demonstrates Distinct Molecular Features in Hepatoblastoma and HCC-Like Components.

Hepatoblastomas (HB) are embryonal tumors with quiet genomes diagnosed mostly in children under 3 years of age and often cured by surgical resection and chemotherapy. However, a subset of HBs behave aggressively, displaying characteristic histologic features and higher genomic instability. Hepatocellular neoplasm-not otherwise specified (HCN-NOS) is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma (HCC) histological features.

Circadian dysfunction induces NAFLD-related human liver cancer in a mouse model.

Background & Aims: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

Methods: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes.

Pediatric Hepatocellular Adenomas: What Is Known and What Is New?

Current understanding and classification of pediatric hepatocellular adenomas (HCA) are largely based on adult data. HCAs are rare in children and, unlike in adults, are often seen in the context of syndromes or abnormal background liver. Attempts to apply the adult classification to pediatric tumors have led to several "unclassifiable" lesions.

An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer.

Background And Aims: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common malignant hepatocellular tumors seen in children. The aim of this work was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide information about the real-time state of tumors in response to therapies.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye that is used clinically to identify malignant liver cells in the body during surgery.

Consensus classification of pediatric hepatocellular tumors: A report from the Children's Hepatic tumors International Collaboration (CHIC).

Background: Liver tumors are rare in children with histologic heterogeneity that makes diagnosis challenging. Systematic histopathological review, performed as part of collaborative therapeutic protocols, identified relevant histologic subtypes that are important to distinguish. The Children's Hepatic tumors International Collaboration (CHIC) was established to study pediatric liver tumors on a global scale and led to establishment of a provisional consensus classification for use in international clinical trials.

Clinical genome sequencing: Three years' experience at a tertiary children's hospital.

Purpose: Genome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in nonresearch settings remains limited. Texas Children's Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study GS utilization, possibilities for test optimization, and testing outcomes.

Methods: We retrospectively reviewed GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022.

Hereditary pulmonary arterial hypertension burden in pediatrics: A single referral center experience.

Introduction: Hereditary pulmonary arterial hypertension (HPAH) is a rare yet serious type of pulmonary arterial hypertension (PAH). The burden in the pediatric population remains high yet underreported. The objective of this study is to describe the distribution of mutations found on targeted PAH panel testing at a large pediatric referral center.

CD203c is expressed by human fetal hepatoblasts and distinguishes subsets of hepatoblastoma.

Background & Aims: Hepatocytic cells found during prenatal development have unique features compared to their adult counterparts, and are believed to be the precursors of pediatric hepatoblastoma. The cell-surface phenotype of hepatoblasts and hepatoblastoma cell lines was evaluated to discover new markers of these cells and gain insight into the development of hepatocytic cells and the phenotypes and origins of hepatoblastoma.

Methods: Human midgestation livers and four pediatric hepatoblastoma cell lines were screened using flow cytometry.