Cholangiocarcinoma - Morphology, Immunohistochemistry, and Genetics

Area of Science:

• Gastroenterology and Hepatology
• Oncology
• Molecular Pathology

Background:

• Cholangiocarcinoma (CCA) encompasses diverse bile duct cancers with increasing global incidence.
• Risk factors include liver fluke infections, PSC, viral hepatitis, and cirrhosis, often leading to late-stage diagnosis and poor prognosis.
• Accurate classification and differential diagnosis of CCA and biliary precancerous lesions (BilIN) are crucial.

Purpose of the Study:

• To summarize CCA classification systems, morphology, molecular profiles, and clinical implications.
• To review differential diagnoses of CCA subtypes and related cancers.
• To highlight the role of immunohistochemistry and molecular pathology in CCA diagnosis and treatment.

Main Methods:

• Review of literature and institutional experiences with immunohistochemical markers (CRP, S100P, IMP3).
• Analysis of molecular pathology, focusing on mutation profiles across anatomical CCA subtypes.
• Overview of targetable genetic alterations and current oncological therapies.

Main Results:

• CCA mutation profiles differ significantly: intrahepatic CCA shows IDH1/2, FGFR, BAP1 mutations; perihilar/extrahepatic CCA exhibits TP53, KRAS, ERBB2 mutations.
• FGFR2 and IDH1 alterations correlate with better prognosis, while TP53 and KRAS mutations indicate worse outcomes.
• Intrahepatic CCA presents more therapeutic targets, including ALK and RET fusions, unlike perihilar/extrahepatic CCA.

Conclusions:

• Molecular subtyping of CCA is essential for understanding prognosis and guiding targeted therapy.
• Intrahepatic CCA shows promise for personalized medicine, potentially mirroring advances seen in non-small cell lung cancer.
• Further research into targeted therapies for all CCA subtypes is warranted to improve patient outcomes.