Satellite lesions versus intrahepatic metastasis in multifocal intrahepatic cholangiocarcinoma: Prognostic impact and genomic profiling

作者：Tao Wei, Zhijie Ma, Shouliang Guo, Matthew J. Weiss, Irinel Popescu, Hugo P. Marques, Luca Aldrighetti, Shishir K. Maithel, Carlo Pulitanò, Todd W. Bauer, Feng Shen, George A. Poultsides, Olivier Soubrane, Guillaume Martel, Bas Groot Koerkamp, Itaru Endo, Tingbo Liang, Yi Lv, Timothy M. Pawlik, Xu‐Feng Zhang, on behalf of the Intrahepatic Cholangiocarcinoma Study Group · 发表于：Hepatology · 年份：2025 · DOI：10.1097/hep.0000000000001594 · 被引用次数：5 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Gallbladder and Bile Duct Disorders、Hepatocellular Carcinoma Treatment and Prognosis

BACKGROUND AND AIMS: Multifocal intrahepatic cholangiocarcinoma (ICC) is typically categorized as satellite lesions (SL) or intrahepatic metastasis (IM). Clinical staging and prognostic significance of multifocal ICC are topics of debate. APPROACH AND RESULTS: ICC patients with solitary or multifocal tumors undergoing curative-intent surgical resection were identified from an international multi-institutional database. SL and IM were classified according to distribution patterns. Among 1064 patients included in the cohort, 358 had multifocal tumors that were defined as IM (n=95) or SL (n=263). Isolated AJCC stage II of multifocal ICC disease was associated with shorter overall (OS) (median: 26.1 vs. 60.0 mo, p <0.001) and disease-free survival (DFS) (median DFS: 9.8 vs. 25.0 mo, p <0.01) than solitary tumors within stage II, yet had a comparable prognosis as stage III disease. Patients with IM or SL had comparable OS and DFS (both p >0.1), regardless of tumor number status. Genomic profiling demonstrated a highly concordant mutational landscape of IM and SL in 24 multifocal ICC patients. Phylogenetic and evolutionary trajectory analysis supported that multifocal lesions with different distribution patterns were of the same origin, derived from the corresponding primary tumors. In addition, single-nucleus RNA sequencing revealed that both IM and SL harbored increased levels of copy number variations compared with the primary lesion, indicative of malignant progression. CONCLUS...