联合性肝细胞胆管癌（cHCC-CC）是一种罕见的肝脏肿瘤，在同一肿瘤内同时表现出肝细胞和胆管分化。对复发性/转移性 cHCC-CC 的组织学和基因组改变知之甚少。我们选择了 6 名经组织学证实复发或转移性肿瘤的 cHCC-CC 患者。包括四名典型 cHCC-CC 患者和两名中间细胞癌 (IC) 患者。评估了临床病理特征，并对 17 个多区域和纵向肿瘤样本进行了下一代测序。经典 cHCC-CC 的复发/转移性病变的组织学各不相同：1 名 (25.0%) 患者观察到肝细胞癌 (HCC)，1 名 (25.0%) 患者观察到 cHCC-CC，2 名 (50.0%) 患者观察到胆管癌 (CC) ％） 患者。在来自 4 名经典 cHCC-CC 患者的 13 个样本中，最常见的病理变异是 TP53（46.2%）、TERT 启动子（38.5%）、ARID1A 突变（23.1%）和 MET 扩增（30.8%）。在每个 HCC 和 CC 成分的测序分析中，四种经典 cHCC-CC 中的三种 (75.0%) 共有致病变异。每个 HCC 和 CC 成分都共有很大一部分突变，包括致病性突变和意义未确定的突变。关于IC，在一名患者中检测到ATM突变。总之，复发/转移性 cHCC-CC 的组织学是异质的。经典 cHCC-CC 的基因组分析揭示了与 HCC 相似的基因组改变。在每个 HCC 和 CC 成分中观察到相当大的重叠基因组改变，表明单克隆起源。 IC 中的基因改变与 HCC 或 CC 中的基因改变不同，表明这种肿瘤的独特性质。© 2023 John Wiley

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of liver tumour that exhibits both hepatocytic and biliary differentiation within the same tumour. The histology and genomic alterations of recurrent/metastatic cHCC-CC are poorly understood. We selected six patients with cHCC-CC whose recurrent or metastatic tumours were histologically confirmed. Four patients with classic cHCC-CCs and two with intermediate cell carcinomas (ICs) were included. The clinicopathological features were evaluated, and next-generation sequencing was performed in 17 multiregional and longitudinal tumour samples. The histology of recurrent/metastatic lesions of classic cHCC-CCs was variable: hepatocellular carcinoma (HCC) was observed in one (25.0%) patient, cHCC-CC in one (25.0%) patient, and cholangiocarcinoma (CC) in two (50.0%) patients. Among 13 samples from four classic cHCC-CC patients, the most frequent pathological variants were TP53 (46.2%), TERT promoter (38.5%), ARID1A mutations (23.1%), and MET amplification (30.8%). In the sequencing analysis of each HCC and CC component, three (75.0%) of the four classic cHCC-CCs shared pathogenic variants. A large proportion of mutations, both pathogenic and those of undetermined significance, were shared by each HCC and CC component. Regarding ICs, the ATM mutation was detected in one patient. In conclusion, the histology of recurrent/metastatic cHCC-CCs was heterogeneous. Genomic profiling of classic cHCC-CCs revealed similar genomic alterations to those of HCC. Considerable overlapping genomic alterations in each HCC and CC component were observed, suggesting a monoclonal origin. Genetic alterations in ICs were different from those in either HCC or CC, suggesting the distinct nature of this tumour.© 2023 John Wiley & Sons Ltd.