Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Pathology and Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
Mod Pathol. 2024 Feb;37(2):100385. doi: 10.1016/j.modpat.2023.100385. Epub 2023 Nov 20.
Accurate diagnosis and treatment of hepatocellular neoplasm, not otherwise specified (HCN-NOS), poses significant challenges. Our study aimed to investigate the clinicopathologic and genomic similarities and differences between HCN-NOS and hepatoblastoma (HB) to guide diagnostic and treatment strategies. The clinicopathologic 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 promoters, were employed. We found that patients with HCN-NOS were older (P < .001) and more frequently classified as high risk (P < .01), yet they showed no significant differences in alpha fetoprotein levels or survival outcomes compared with 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 < .001), as well as loss/loss of heterozygosity (LOH) of 1p (11/17 vs 6/24; P < .05) and chromosome 11 (7/17 vs 1/24; P < .01) when compared with HB. Furthermore, the recurrent loss/LOH of chromosomes 3, 4p, 9, 15q, and Y was 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 2 groups. Notably, no clinically significant gene fusions were detected in either group. In conclusion, our study reveals that HCN-NOS exhibits high-risk clinicopathologic features and greater structural complexity compared with HB. However, patients with HCN-NOS exhibit comparable alpha fetoprotein levels at diagnosis, CTNNB1 mutation rates, and survival outcomes when subjected to aggressive treatment, as compared with those with HB. These findings have the potential to enhance diagnostic accuracy and inform more effective treatments for HCN-NOS.
肝细胞肿瘤，未特指（HCN-NOS）的准确诊断和治疗存在重大挑战。我们的研究旨在探讨 HCN-NOS 和肝母细胞瘤（HB）之间的临床病理和基因组相似性和差异，以指导诊断和治疗策略。比较了 16 例 HCN-NOS 患者和 23 例 HB 患者的临床病理特征。进行了分子研究，包括 OncoKids DNA 和 RNA 下一代测序面板、染色体微阵列和 CTNNB1 和 TERT 启动子的靶向 Sanger 测序分析。我们发现，HCN-NOS 患者年龄较大（P<0.001），更常被归类为高危（P<0.01），但与 HB 患者相比，其甲胎蛋白水平或生存结果无显著差异。HCN-NOS 和 HB 具有相似的序列变异频率，CTNNB1 突变在两组中均占主导地位。值得注意的是，TERT 启动子突变（37.5%）和罕见的临床显著变异（BRAF、NRAS 和 KMT2D）仅存在于 HCN-NOS。HCN-NOS 显示 1q 增益的发生率更高，包括 MDM4 基因座（17/17 与 11/24；P<0.001），以及 1p 杂合性丢失（11/17 与 6/24；P<0.05）和 11 号染色体（7/17 与 1/24；P<0.01）。此外，与 HB 相比，HCN-NOS 还观察到染色体 3、4p、9、15q 和 Y 的反复缺失/杂合性丢失。然而，两组之间在染色体 2、8 和 20 的增益或染色体 4q 和 11p 的缺失/杂合性丢失方面没有显著差异。值得注意的是，两组均未检测到临床显著的基因融合。总之，我们的研究表明，与 HB 相比，HCN-NOS 表现出高危临床病理特征和更大的结构复杂性。然而，与 HB 患者相比，接受积极治疗的 HCN-NOS 患者在诊断时的甲胎蛋白水平、CTNNB1 突变率和生存结果相似。这些发现有可能提高 HCN-NOS 的诊断准确性，并为其提供更有效的治疗方法。
