https://pubmed.ncbi.nlm.nih.gov/35577029/ hepatoblastoma

J Hepatol. 2022 May 13;S0168-8278(22)00275-6.
doi: 10.1016/j.jhep.2022.04.035.Online ahead of print.

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

Pavel Sumazin 1, Tricia L Peters 2, Stephen F Sarabia 2, Hyunjae R Kim 3, Martin Urbicain 2, Emporia Faith Hollingsworth 4, Karla R Alvarez 4, Cintia R Perez 4, Alice Pozza 5, Mohammad Javad Najaf Panah 3, Jessica L Epps 3, Kathy Scorsone 3, Barry Zorman 3, Howard Katzenstein 6, Allison F O'Neill 7, Rebecka Meyers 8, Greg Tiao 9, Jim Geller 9, Sarangarajan Ranganathan 9, Arun A Rangaswami 10, Sarah E Woodfield 11, John A Goss 12, Sanjeev A Vasudevan 11, Andras Heczey 3, Angshumoy Roy 2, Kevin E Fisher 2, Rita Alaggio 5, Kalyani R Patel 2, Milton J Finegold 13, Dolores H López-Terrada 14

Abstract

Background & aims: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant types of liver cancers in children. HB and HCC outcomes and treatment options differ dramatically and most HBs have favorable outcomes following treatment by a combination of chemotherapy and resection. Risk-stratification using a combination of clinical, histological, and molecular parameters can improve therapy selection for these patients, but it is particularly challenging for tumors with mixed HB and HCC histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category. We aimed to produce the first molecular characterization of clinically annotated HCN NOSs.

Methods: We tested whether these histological features are associated with genetic alterations, cancer-gene dysregulation, and outcomes. Namely, we compared the molecular features of HCN NOSs, including copy number alterations, mutations, and gene-expression profiles, with those in other pediatric hepatocellular neoplasms, including, HBs and HCCs, as well as HBs demonstrating focal atypia or pleomorphism (HB FPAs), and HBs diagnosed in older children (>8).

Results: Molecular profiles of HCN NOSs and HB FPAs revealed common underlying biological features that were previously observed in HCCs. Consequently, we designated these tumor types collectively as HBs with HCC features (HBCs) and outlined histological and molecular characteristics for their classification.

Conclusions: Our single-institution study suggested that histological features seen in HBCs are associated with combined HB and HCC molecular features, that HBCs have poor outcomes irrespective of patient age, and that transplanted HBCs are more likely to have good outcomes than HBCs that are treated with chemotherapy and surgery alone. These findings highlight the importance of molecular testing and early therapeutic intervention for aggressive childhood hepatocellular neoplasms.