Anatomic subsets of cholangiocarcinoma: More different than alike.

Journal: Hepatology (Baltimore, Md.)
Published Date: Jan 12, 2026

Abstract

Cholangiocarcinoma (CCA) represents a biologically and clinically heterogeneous group of biliary tract malignancies. Growing evidence underscores that the 3 major anatomic subtypes-intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA)-are distinct tumor entities rather than a single disease. Each subtype differs in embryologic origin, carcinogenesis mechanisms, molecular landscape, and immunogenic profile, all of which contribute to variability in diagnosis, treatment responsiveness, and prognosis. The importance of understanding these distinctions is reinforced by the rising global incidence of CCA, which highlights the need for precision medicine approaches based on these subtypes. Recent advances have deepened our insight into subtype-specific risk factors, including chronic biliary diseases and metabolic conditions, while artificial intelligence-driven tools are improving diagnostic accuracy and risk stratification. Surgical innovations now allow for more tailored resections and perioperative care, and therapeutic strategies are increasingly guided by molecular and immune profiling. Emerging strategies for early diagnosis and chemoprevention in high-risk populations further emphasize the significance of recognizing the unique biology of each subtype. In this review, we provide a comprehensive overview of the distinct anatomic subsets of CCA, integrating their molecular and biological foundations with clinical management to inform practice and guide future research.

Authors

  • Yawen Dong
    Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria.
  • Hannah E Stumpf
    Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA.
  • Rory L Smoot
    Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA.
  • Patrick P Starlinger
    Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Minnesota, Rochester, USA.
  • Mark M Yarchoan
    Department of Oncology, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Gregory J Gores
    Division of Gastroenterology &, Hepatology Mayo Clinic, Rochester, MN.
  • Sumera I Ilyas
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

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