Cholangiocarcinoma Pathologic and Molecular Classification in the Era of Precision Medicine

Purva Gopal, Marie E. Robert, Xuchen Zhang

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

Context.-Cholangiocarcinoma (CCA) is a heterogeneous cancer of the bile duct, and its diagnosis is often challenging. Objective.-To provide insights into state-of-the-art approaches for the diagnosis of CCA. Data Sources.-Literature review via PubMed search and authors' experiences. Conclusions.-CCA can be categorized as intrahepatic or extrahepatic. Intrahepatic CCA is further classified into small-duct-type and large-duct-type, whereas extrahepatic CCA is classified into distal and perihilar according to site of origin within the extrahepatic biliary tree. Tumor growth patterns include mass forming, periductal infiltrating, and intraductal tumors. The clinical diagnosis of CCA is challenging and usually occurs at an advanced tumor stage. Pathologic diagnosis is made difficult by tumor inaccessibility and challenges in distinguishing CCA from metastatic adenocarcinoma to the liver. Immunohistochemical stains can assist in differentiating CCA from other malignancies, such as hepatocellular carcinoma, but no distinctive CCA-specific immunohistochemical profile has been identified. Recent advances in next-generation sequencing-based high-throughput assays have identified distinct genomic profiles of CCA subtypes, including genomic alterations that are susceptible to targeted therapies or immune checkpoint inhibitors. Detailed histopathologic and molecular evaluations of CCA by pathologists are critical for correct diagnosis, subclassification, therapeutic decision-making, and prognostication. The first step toward achieving these goals is to acquire a detailed understanding of the histologic and genetic subtypes of this heterogeneous tumor group. Here, we review state-of-the-art approaches that should be applied to establish a diagnosis of CCA, including clinical presentation, histopathology, staging, and the practical use of genetic testing methodologies.

Original languageEnglish (US)
Pages (from-to)359-370
Number of pages12
JournalArchives of Pathology and Laboratory Medicine
Volume148
Issue number3
DOIs
StatePublished - Mar 2024

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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