Abstract
Accurate diagnosis and treatment of hepatocellular neoplasm, not otherwise specified (HCN-NOS), poses significant challenges. Our study aimed to investigate the clinicopathological and genomic similarities and differences between HCN-NOS and hepatoblastoma (HB) to guide diagnostic and treatment strategies. The clinicopathological characteristics of 16 patients with HCN-NOS and 23 patients with HB were compared. Molecular studies, including the OncoKids® DNA and RNA-based next-generation sequencing panel, chromosomal microarray, and targeted Sanger sequencing analyses of CTNNB1 and TERT promoter, were employed. We found that patients with HCN-NOS were older (p<0.001) and more frequently classified as high-risk (p<0.01), yet they showed no significant differences in alpha-fetoprotein (AFP) levels or survival outcomes compared to those with HB. HCN-NOS and HB had a comparable frequency of sequence variants, with CTNNB1 mutations being predominant in both groups. Notably, TERT promoter mutations (37.5%) and rare clinically significant variants (BRAF, NRAS, and KMT2D) were exclusive to HCN-NOS. HCN-NOS demonstrated a higher prevalence of gains in 1q, encompassing the MDM4 locus (17/17 vs. 11/24, p<0.001), as well as loss/loss of heterozygosity (LOH) of 1p (11/17 vs. 6/24, p<0.05) and chromosome 11 (7/17 vs. 1/24, p<0.01) when compared to HB. Furthermore, recurrent loss/LOH of chromosome 3, 4p, 9, 15q, and Y were only observed in HCN-NOS. However, no significant differences were noted in gains of chromosomes 2, 8, and 20, or loss/LOH of 4q and 11p between the two groups. Notably, no clinically significant gene fusions were detected in either group. In conclusion, our study reveals that HCN-NOS exhibits high-risk clinicopathological features and greater structural complexity compared to HB. However, patients with HCN-NOS exhibit comparable AFP levels at diagnosis, CTNNB1 mutation rates, and survival outcomes when subjected to aggressive treatment, as compared to those with HB. These findings have the potential to enhance diagnostic accuracy and inform more effective treatments for HCN-NOS.
Published Version
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