Hepatoblastoma and Pediatric Liver Tumors

Dear Colleagues,

Primary liver cancers are rare in children, with hepatoblastomas representing the most common liver tumor in children, comprising 1% of all pediatric cancers. Hepatoblastomas have an overall survival rate greater than 75%, which is largely related to the progress made in diagnosis and radiologic assessment using a standardized presurgical extent of disease (PRETEXT) staging system with optimization of chemotherapeutic and surgical regimens. Fortunately, the majority of hepatoblastomas respond to treatment with cisplatin and the majority of tumors are resectable following chemotherapy. Liver transplantation is an alternative for PRETEXT stage I–III tumors involving essential vascular structures or for multifocal PRETEXT stage IV tumors. While outcomes have been good for standard risk patients, the prognosis is poor for high risk patients with advanced, metastatic or recurrent disease. It is still a challenge to optimize therapies for these children at highest risk.

Hepatoblastoma is an embryonal tumor that may show histologic heterogeneity with mixed epithelial and stromal components. The epithelial component may be comprised of fetal hepatocytes or more primitive embryonal hepatocytes. In light of molecular studies, it is now recognized that a large portion of small cell undifferentiated liver tumors (SCUDs) actually represents an aggressive unrelated tumor—the malignant rhabdoid tumor, that can be diagnosed by molecular confirmation of SMARCB1 deletions and lack of protein expression of INI-1, a member of the chromatin remodeling SWI/SNF complex. With increased awareness of the molecular classification of liver tumors, there is a need for standard classification of liver tumors, incorporating routine use of immunostaining and molecular assays to correctly classify rare malignant liver tumors, that may benefit by individualized targeted therapy. To date, molecular studies performed on hepatoblastomas show recurrent mutations or deletions in CTNNB1, encoding beta catenin involved in the Wnt signaling pathway. Other mutations in genes that are involved in the Wnt signaling pathway such as APC, AXIN1 and AXIN2 have also been reported. Whole exome studies have revealed a low frequency of somatic mutations in hepatoblastomas, that currently are not therapeutically targetable. Transcriptome and methylation studies may be useful in classifying tumors, but limited studies have been performed and they are not utilized in clinical practice to date.

This Special Issue will highlight the diverse challenges encountered in understanding the pathogenesis and the clinical management of pediatric liver tumors, with primary focus on hepatoblastomas. Invited articles will cover a wide range of topics including but not restricted to the following: 1) Update on the clinical management of pediatric liver tumors (hepatoblastomas), focusing on therapies for high risk patients. 2) Utility of biomarkers for stratification into low and high-risk groups, 3) Update on the pathologic and molecular classification of hepatoblastoma. 4) Molecular studies distinguishing pediatric hepatocellular carcinoma versus hepatoblastoma and other unusual pediatric liver tumors. 5) Role of personalized genomics in discovering targets for therapy and discovering somatic versus germline mutations.

Dr. Helen Remotti
Guest Editor

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• Hepatoblastoma
• Personalized Genomics
• Pediatric liver tumor
• Hepatocellular carcinoma
• Precision Medicine