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Hepatoblastoma (HB) is the most common primary liver malignancy of childhood, and molecular investigations are limited and effective treatment options for chemoresistant disease are lacking. There is a knowledge gap in the investigation of key driver cells of HB in tumor. Here we show single cell ribonucleic acid sequencing (scRNAseq) analysis of human tumor, background liver, and patient derived xenograft (PDX) to demonstrate gene expression patterns within tumor and to identify intratumor cell subtype heterogeneity to define differing roles in pathogenesis based on intracellular signaling in pediatric HB. We have identified a driver tumor cell cluster in HB by genetic expression which can be examined to define disease mechanism and treatments. Identification of both critical mechanistic pathways combined with unique cell populations provide the basis for discovery and investigation of novel treatment strategies in vitro and in vivo.

Background Hepatoblastoma is the most common primary pediatric liver malignancy. Indocyanine green (ICG) has been described as an adjunct to resection in small series. Its utility remains undefined in larger cohorts. Methods Records for 29 patients diagnosed with hepatoblastoma who received ICG prior to surgical resection from 2017 to 2020 at a single institution were retrospectively reviewed. The primary outcome was correlation between intraoperative ICG‐avidity and histologic presence of hepatoblastoma. A secondary outcome included the histologic margin designation for resected liver specimens. Results ICG sensitivity was 91% for 120 resected thoracic specimens from 21 patients. Specificity was 57%. In 10% of operations, HB‐positive specimens were resected solely on ICG‐avidity. In an additional 40% of cases, ICG assisted in localizing a preoperatively diagnosed lesion. ICG sensitivity during thoracotomy and thoracoscopic surgery was 95 and 74%, respectively; primary and relapsed disease demonstrated sensitivity of 94 and 73%, respectively. Sensitivity was 92% for 25 resected liver specimens from nine patients with all parenchymal margins grossly negative for disease. Four multifocal lesions were identified with two resected solely by ICG‐avidity. Conclusions ICG is a sensitive adjunct for identifying local and metastatic hepatoblastoma, including lesions not visualized on preoperative imaging, and delineating margins during liver resection. False positives limit specificity; however, there were no adverse outcomes from additional resections. We noted that thoracoscopic surgery can be completed safely in patients with less significant disease burden, and conversion to thoracotomy, if necessary, is straightforward.

Fibrolamellar hepatocellular carcinoma (FLC) is a disease that occurs in children and young adults. The development of FLC is associated with creation of a fusion oncoprotein DNAJB1-PKAc kinase, which activates multiple cancerassociated pathways. The aim of this study was to examine the role of human genomic regions, called cancer-enhancing genomic regions or aggressive liver cancer domains (CEGRs/ALCDs), in the development of FLC. Previous studies revealed that CEGRs/ALCDs are located in multiple oncogenes and cancer-associated genes, regularly silenced in normal tissues. Using the regulatory element locus intersection (RELI) algorithm, we searched a large

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