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bioRxiv · 10.1101/2021.07.15.445600

Hepatoblastomas with carcinoma features (HBCs) represent a biological spectrum of aggressive neoplasms in children and young adults

Sumazin, P.·Lopez-Terrada, D.
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Abstract

Malignant hepatocellular cancers are the most common primary liver malignancies in children, and hepatoblastomas (HBs) account for more than two-thirds of these cases. While most HBs respond to chemotherapy and have favorable outcomes, the 3-year overall survival rate for high-risk HBs is below 50% and guidelines for their classification and treatment are still evolving. HB risk-stratification efforts using clinical, histological, and molecular parameters have been reported to help identify patients that require more or less aggressive therapies in retrospective studies, and are being validated in clinical trials. However, risk assessment is particularly challenging for cancers with certain histologies, including tumors in the recently proposed provisional hepatocellular neoplasm not otherwise specified (HCN NOS) category. HCN NOSs exhibit either intermediate or combined HB and hepatocellular carcinoma (HCC) histological features, and while neoplasms with such features were observed over a decade ago, only a handful have been characterized and little is known about their biology and clinical features. Here, we molecularly characterized a series of clinically annotated HCN NOSs that demonstrated either intermediate HB/HCC histology or distinct coexisting areas with HB and HCC histological features. In addition, molecular profiling of HBs demonstrating focal pleomorphism or anaplasia (HB FPA) revealed underlying biological features previously observed in HCCs. Our study suggested that HCN NOSs and HB FPAs are aggressive tumors, irrespective of patient age or resectability. Consequently, we designated them collectively as HBs with carcinoma features (HBCs) and outlined histological and molecular characteristics for their diagnosis and treatment. In our single-institution study, transplanted HBC patients were significantly and more than twice as likely to have good outcomes, highlighting the importance of molecular testing and aggressive early intervention.

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Sumazin, P., Lopez-Terrada, D.. 2021-07-16. Hepatoblastomas with carcinoma features (HBCs) represent a biological spectrum of aggressive neoplasms in children and young adults. https://doi.org/10.1101/2021.07.15.445600

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