Terashima Takeshi, Harada Kenichi, Yamashita Taro
Department of Gastroenterology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, 13-1, Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
Jpn J Clin Oncol. 2025 Apr 6;55(4):327-333. doi: 10.1093/jjco/hyaf029.
The concept and definition of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), an extremely rare condition accounting for only 1% of all primary liver cancers, has shifted in recent years. The latest World Health Organization Classification (fifth edition) includes two types of cHCC-CCAs, (i) the classical type described in the previous edition, which contains a mixture of distinctly differentiated components of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and (ii) intermediate cell carcinoma wherein all cells comprising the tumor express both hepatocellular and cholangiocellular features. However, the pathogenesis of cHCC-CCA, including its origins, remains controversial even among experts. Treatment strategies for cHCC-CCA in clinical practice have been determined based on imaging findings, tumor markers, and pathologically predominant tumor components for either HCC or ICC, suggesting that cHCC-CCA has yet to be been established as an independent disease entity. As with HCC and ICC, the treatment strategy for HCC-CCA involves initially considering resectability. Although systemic therapy has been considered for patients unsuitable for local treatment, no prospective clinical trials have evaluated the efficacy and safety of systemic therapy for cHCC-CCA, which could explain the lack of a standard of care. In recent years, however, studies have demonstrated the efficacy of immune checkpoint inhibitors for HCC and ICC, with therapeutic results having been reported for cHCC-CCA. Hence, further accumulation of cases is expected to facilitate the establishment of a consensus on treatment strategies in the near future.
肝细胞胆管癌（cHCC-CCA）极为罕见，仅占所有原发性肝癌的1%，其概念和定义近年来有所变化。世界卫生组织最新分类（第五版）包括两种类型的cHCC-CCA：（i）上一版中描述的经典类型，它包含肝细胞癌（HCC）和肝内胆管癌（ICC）两种明显分化成分的混合物；（ii）中间细胞癌，其中构成肿瘤的所有细胞均表达肝细胞和胆管细胞特征。然而，即使在专家中，cHCC-CCA的发病机制，包括其起源，仍存在争议。临床实践中cHCC-CCA的治疗策略是根据影像学检查结果、肿瘤标志物以及HCC或ICC在病理上占主导地位的肿瘤成分来确定的，这表明cHCC-CCA尚未被确立为一个独立的疾病实体。与HCC和ICC一样，cHCC-CCA的治疗策略最初包括考虑是否可切除。尽管对于不适合局部治疗的患者已考虑进行全身治疗，但尚无前瞻性临床试验评估全身治疗对cHCC-CCA的疗效和安全性，这可能解释了为何缺乏标准治疗方案。然而，近年来的研究已证明免疫检查点抑制剂对HCC和ICC有效，也有关于cHCC-CCA治疗结果的报道。因此，预计在不久的将来，病例的进一步积累将有助于就治疗策略达成共识。
