Université Paris Cité, INSERM UMR-1149, Paris, France; Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
Centre de Recherche des Cordeliers, Sorbonne Université-Université Paris Cité, INSERM, Paris, France; Team Fungest, Equipe labellisée Ligue Nationale Contre le Cancer, Labex immuno-Oncology, Paris, France.
Mod Pathol. 2023 Sep;36(9):100211. doi: 10.1016/j.modpat.2023.100211. Epub 2023 May 9.
Borderline hepatocellular adenomas (BL-HCA) are characterized by focal architectural/cytologic atypia and reticulin loss, features that are insufficient for a definitive diagnosis of hepatocellular carcinoma (HCC). The diagnosis and management of BL-HCA are challenging as their biological behavior, especially in terms of malignant potential, is still debated. We aimed to compare the clinicopathologic and molecular features of BL-HCA with those of typical HCA (T-HCA), HCA with malignant transformation (HCC on HCA), and HCC to assess the risk of malignancy. One hundred six liver resection specimens were retrospectively selected from 2 reference centers, including 39 BL-HCA, 42 T-HCA, 12 HCC on HCA, and 13 HCC specimens. Somatic mutations, including TERT promoter mutations associated with HCA malignant transformation and the gene expression levels of 96 genes, were investigated in 93 frozen samples. Additionally, TERT promoter mutations were investigated in 44 formalin-fixed, paraffin-embedded samples. The clinical features of patients with BL-HCA were similar to those of patients with T-HCA, patients being mainly women (69%) with a median age of 37 years. The median tumor size was 7.5 cm, 64% of patients had a single nodule, and no recurrence was observed. Compared with T-HCA, BL-HCA was significantly enriched in β-catenin-mutated HCA in exon 3 (41% vs 6%; P < .001). Unsupervised statistical analysis based on gene expression showed that BL-HCA overlapped with T-HCA and HCC on HCA, favoring a molecular continuum of the tumors. TERT promoter mutations were observed only in HCC on HCA (42%) and in HCC (38%). In conclusion, these results suggest that despite their worrisome morphologic features, the clinicopathologic and molecular features of BL-HCA are much closer to those of T-HCA than those of HCC on HCA or HCC. This strongly supports the usefulness of combining morphologic and molecular analyses in a practical diagnostic approach for guiding the management of BL-HCA.
交界性肝细胞腺瘤（BL-HCA）的特征是局灶性结构/细胞学异型性和网状纤维丢失，这些特征不足以明确诊断肝细胞癌（HCC）。BL-HCA 的诊断和治疗具有挑战性，因为其生物学行为，特别是恶性潜能，仍存在争议。我们旨在比较 BL-HCA 与典型肝细胞腺瘤（T-HCA）、肝细胞癌伴恶性转化（HCA 伴 HCC）和 HCC 的临床病理和分子特征，以评估恶性肿瘤的风险。我们从 2 个参考中心回顾性选择了 106 例肝切除术标本，包括 39 例 BL-HCA、42 例 T-HCA、12 例 HCA 伴 HCC 和 13 例 HCC 标本。在 93 例冷冻样本中检测了包括与 HCA 恶性转化相关的 TERT 启动子突变在内的体细胞突变以及 96 个基因的基因表达水平。此外，在 44 例福尔马林固定、石蜡包埋样本中检测了 TERT 启动子突变。BL-HCA 患者的临床特征与 T-HCA 患者相似，患者主要为女性（69%），中位年龄为 37 岁。肿瘤中位大小为 7.5cm，64%的患者为单个结节，无复发。与 T-HCA 相比，BL-HCA 在β-catenin 突变的 HCA 中明显富集于外显子 3（41% vs 6%；P <.001）。基于基因表达的无监督统计分析表明，BL-HCA 与 T-HCA 和 HCA 伴 HCC 重叠，倾向于肿瘤的分子连续性。TERT 启动子突变仅在 HCC 伴 HCC（42%）和 HCC（38%）中观察到。总之，这些结果表明，尽管形态学特征令人担忧，但 BL-HCA 的临床病理和分子特征与 T-HCA 更接近，而与 HCC 伴 HCC 或 HCC 更接近。这强烈支持在实际诊断方法中结合形态学和分子分析，以指导 BL-HCA 的管理。
