Pancreatic cancer, cholangiocarcinoma and hepatocellular carcinoma have different biology and are treated using different therapeutic strategies. Establishing the exact diagnosis and anatomical site of origin is therefore fundamental before treatment is selected.

Not in the same way for every disease. In cholangiocarcinoma, particularly in advanced disease, molecular profiling of the tumour is important because it can identify actionable alterations and influence subsequent treatment choices. In pancreatic cancer, genetic and molecular testing can also have therapeutic relevance in selected clinical settings, including alterations related to DNA-repair mechanisms and other potentially actionable biomarkers. The need for and type of testing depend on the stage and treatment setting. In contrast, broad molecular profiling is not currently a routine prerequisite for selecting established systemic therapy in hepatocellular carcinoma. Treatment strategy is based mainly on disease stage, liver function and the patient's general condition.

Whether surgery is possible depends on the type of tumour, its anatomical location, the extent of disease and the patient's general condition. Internationally accepted criteria and guideline recommendations are used to assess resectability, but the final assessment is not based on these alone. It requires careful interpretation of imaging and review by an experienced surgeon, usually within a multidisciplinary team. In some cases, resectability can be reassessed after systemic treatment.

Complex cases may require a combination of systemic treatment, surgery, interventional procedures or other local therapies. Discussion between the relevant specialties helps assess the available options and determine the most appropriate sequence in which to use them.

Not always. Some cholangiocarcinomas and pancreatic adenocarcinomas can have substantial morphological and immunohistochemical similarities, particularly when the diagnosis is based on a small biopsy sample. In these situations, pathology should not be interpreted in isolation. The exact location and site of origin on imaging, endoscopic or surgical findings and, where needed, additional pathological or molecular testing are considered together to establish the most accurate diagnosis. Making the correct distinction is important because it can influence both the choice of systemic treatment and the appropriate molecular testing.