Correspondence to editorial on “Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma” Yu-Hang Ye, Shao-Lai Zhou Clinical and Molecular Hepatology.2025; 31(1): e90. CrossRef
Backgrounds/Aims Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC.
Methods We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time.
Results We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort.
Conclusions We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.
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We report two cases of hepatocellular carcinoma with prominent lymphocytic infiltration, which has been
described as a subtype of hepatocellular carcinoma with good prognosis. One case showed lymphoid follicles
and dense lymphocytic infiltrates within the tumor and its periphery, and the other case showed marked
lymphocytic infiltration in the cancerous tissue. Piecemeal necrosis of cancer cells and atypical reactive
changes were evident. The two cases were seronegative for hepatitis B surface antigen, antibody to hepatitis
C virus, and Epstein-Barr virus DNA. One of the cases showed Clonorchis infestation. The prognostic
significance of lymphocytic stroma in hepatocellular carcinoma requires further investigation. (Korean J
Hepatol 2008;14:394-398)
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Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma with predominant lymphocytic
infiltration, which is associated with Epstein-Barr virus (EBV) in variable proportions. We report two cases
of carcinoma with predominant lymphoid stroma in hepatobiliary system. The first case was a
lymphoepithelioma-like undifferentiated carcinoma with focal differentiation of cholangiocarcinoma (cytokeratin
19+) and hepatocellular carcinoma in light microscopy. The infiltration of CD8+ T lymphocytes was observed
in the tumor and the surrounding hepatic parenchyme. In this tumor, EBV was detected and LMP1 was
positive immunohistochemically. The second case showed the mixed features of lymphoepithelioma-like
carcinoma and cholangiocarcinoma with predominant lymphoid stroma. In this case, EBV was detected. LELC
of hepatobiliary system is an entity distinguished from conventional carcinoma with lymphoid stroma, and its
association with EBV warrants further research. (Korean J Hepatol 2007;13:222-227)
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