Immunohistochemical Differentiation Between Intra-hepatic Cholangiocarcinoma and Hepatocellular Carcinoma: Insights From a Local Center's Expertise

Background: The study aimed to investigate the use of immunohistochemistry (IHC) to distinguish between intra-hepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) due to the rising incidence of iCCA and the limitations of radiological features in differentiation.

Methods: A retrospective study was conducted on patients diagnosed with iCCA and HCC through guided biopsy interventions between 2018 and 2024 at the Pathology and Oncology Departments of Zagazig University, Egypt.

Results:

There were 42 patients in each of the two groups; the iCCA group and the HCC group.

Most of HCC patients were HCV positive and cirrhotic (88.1% and 92.9%, respectively) compared to iCCA patients (50% and 52.4%). Tumor size >5 cm and multiple tumors were more common in HCC patients (73.8% and 88.1%) than in iCCA patients (64.3% and 78.6%). The median number of IHC stains was 5.68±2.07 for iCCA patients and 3.79±1.63 for HCC patients. Key IHC markers for iCCA were CK7, CK19, and CA19.9, while for HCC they were Hep Par 1, Arg-1, and GPC3. In iCCA patients, two specimens tested positive for GPC3, three for Arg-1, and two for Hep Par 1, all with low intensity expression. In HCC patients, one specimen tested positive for CK19, another for CK7, and a third for CA19.9, all showing weak positivity.

Conclusion:

CK7, CK19, and CA19.9 showed strong positivity in iCCA, while Hep Par 1, Arg-1, and GPC 3 were strongly positive in HCC. However, an accurate diagnosis relies on clinical context. Panels of stains provide more comprehensive information than individual stains.