J Liver Cancer.  2024 Mar;24(1):17-22. 10.17998/jlc.2023.12.11.

Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist

• Komuta M

• KMID: 2553814
• DOI: http://doi.org/10.17998/jlc.2023.12.11

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice.

Keyword

Genetic heterogeneity; Liver neoplasms; Fibroblast growth factor receptors 2; Pathology, surgical; Diagnosis, differential

Figure

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  Figure 1. Heterogeneity of cholangiocytes. The cholangiocytes are mucin-producing, cylindrically shaped cells in the large bile duct (A). In contrast, the small duct contains mucin-negative, cuboidal cholangiocytes (C). The different phenotype is clearly visible with epithelial membrane antigen (EMA) staining. Apical staining in the small duct (D), and cytoplasmic expression in the large bile duct (B) (A, B: hematoxylin- eosin; C, D: EMA immunohistochemistry; A-D: 200×; modified from Komuta12 with permission).

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  Figure 2. Histological variation of cholangiocarcinoma (CCA). Hilar CC shows mucin producing CCA, similar to those from intrahepatic cholangiocarcinoma (iCCA) with mucin producing features. In contrast, tumor heterogeneity is a feature of cholangiolocellular carcinoma (CLC) and mixed-iCCA. Reused from Komuta et al.7 with permission. WHO, World Health Organization; CC, cholangiocarcinoma; Muc-iCCA, mucin-production intrahepatic cholangiocarcinoma.

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  Figure 3. The large duct type. Macroscopically, the tumor demonstrates periductal infiltrating type (PI) (A), and PI and mass-forming type (B). The tumor exhibits a clear glandular structure with mucin production (C), and cytoplasmic expression with epithelial membrane antigen (EMA) staining (D) (C: hematoxylin-eosin; D: EMA immunohistochemistry; C: 40×; D: 100×; modified from Komuta12 with permission).

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  Figure 4. The small duct type. The tumor shows mass-forming aspect (A), often arising from chronic liver diseases. The tumor is characterized by small uniform glandular structure (B) or ductular reaction-like structure (C) without mucin production. Epithelial membrane antigen (EMA) staining shows an apical expression pattern (D) (B, C: hematoxylin-eosin; D: EMA immunohistochemistry; B-D: 40×; modified from Komuta12 with permission).

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  Figure 5. A case of metastatic colon cancer of the liver. A liver tumor biopsy from a patient with a liver tumor and a clinical diagnosis of intrahepatic cholangiocarcinoma (iCCA). The tumor biopsy shows trabecular/glandular structures composed of tumor cells with enlarged nuclei. Necrosis is also seen (A). Immunohistochemically, the tumor cells are positive for CDX2, indicating its colorectal origin (insert). A colonoscopy revealed a tumor whose morphology mimicked that of the liver tumor, confirming metastatic liver cancer from the colon (B) (A, B: hematoxylin-eosin stain, 40×; inset: CDX2, 100×).

Reference

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