Genetic re-classification of combined hepatocellular-cholangiocarcinoma and small duct type intrahepatic cholangiocarcinoma

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-05-08 DOI:10.1016/j.prp.2025.155999

Motoko Sasaki , Yasunori Sato , Yasuni Nakanuma

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引用次数: 0

Abstract

Background

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) shares various features with small duct type intrahepatic cholangiocarcinoma (SmD-iCCA) and sometimes histological diagnosis may be difficult.

Methods

We examined genetic alterations such as hTERT promoter (hTERT), p53, and fibroblast growth factor receptor 2 (FGFR2) in 103 PLCs diagnosed as cHCC-CCA or SmD-iCCA. A cluster analysis was performed on the R software for re-classification of PLCs including cHCC-CCA and SmD-iCCA.

Results

The primary liver carcinomas (PLCs) were divided into 5 clusters; 19 tumors (18 %) in Cluster-1 (with alterations in hTERT and/or p53), 24 (23 %) in Cluster-2 (FGFR2 and/or p53), 13 (13 %) in Cluster-3 (IDH2 or null), 19 (18 %) in Cluster-4 (MTAP and/or FGFR2), 28 (27 %) in Cluster-5 (ARID1A and/or PBRM1), being based on genetic alterations. Cluster-1 and Clusters-2 to- 5 formed distinct 2 groups. Cluster-1 was characterized by significantly bigger size, rich and higher histological grade of HCC component, significantly less cholangiolocellular carcinoma (CLC)-component, ductal plate malformation pattern and bile duct adenoma in the background livers. No SmD-iCCA was included in Cluster-1, whereas SmD-iCCA distributed evenly in Clusters 2–5. Cluster-4 was characterized by higher prevalence of hepatitis B and higher histological diversity scores.

Conclusion

PLCs diagnosed as cHCC-CCA or SmD-iCCAs could be divided into 5 clusters based on genetic alterations. Cluster-1 was HCC-like cluster characterized by hTERT alteration, rich and higher grade of HCC and bigger size. Clusters-2–5 may be iCCA-like clusters characterized by different genetic alterations. cHCC-CCA in Cluster-1 and Clusters-2–5 may be handled separately for further analysis and treatment.

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肝细胞胆管合并癌和小管型肝内胆管癌的基因再分类

肝细胞胆管合并癌（cHCC-CCA）与小管型肝内胆管癌（SmD-iCCA）具有多种特征，有时组织学诊断可能很困难。方法在103例诊断为cHCC-CCA或SmD-iCCA的plc中检测了hTERT启动子（hTERT）、p53和成纤维细胞生长因子受体2 （FGFR2）等遗传改变。在R软件上进行聚类分析，重新分类plc，包括cHCC-CCA和SmD-iCCA。结果原发性肝癌（plc）分为5组；基于遗传改变，Cluster-1中有19例肿瘤（18 %）（hTERT和/或p53发生改变），Cluster-2中有24例（23 %）（FGFR2和/或p53）， Cluster-3中有13例（13 %）（IDH2或null）， Cluster-4中有19例（18 %）（MTAP和/或FGFR2）， Cluster-5中有28例（27 %）（ARID1A和/或PBRM1）。Cluster-1和cluster -2至cluster - 5形成了不同的组。Cluster-1的特点是肝细胞癌（HCC）成分明显较大、丰富且组织学分级较高，背景肝中胆管细胞癌（CLC）成分、胆管板畸形型和胆管腺瘤明显较少。Cluster-1中没有SmD-iCCA，而cluster - 2-5中SmD-iCCA分布均匀。第4组的特点是乙型肝炎患病率较高，组织学多样性评分较高。结论诊断为cHCC-CCA或smd - icca的plc可根据遗传改变分为5类。cluster -1为hTERT改变、HCC丰富、分级高、体积大的HCC样簇。簇-2 - 5可能是具有不同遗传改变特征的icca样簇。Cluster-1和cluster -2 - 5中的cHCC-CCA可单独处理，以便进一步分析和处理。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.