Cholangiocarcinoma: Is Preoperative Histologic Confirmation Mandatory Before Major Hepatobiliary Surgery?

Cholangiocarcinoma is an aggressive malignancy of the biliary epithelium frequently diagnosed at advanced stages. Establishing a definitive preoperative histologic diagnosis remains challenging, particularly in perihilar and infiltrative tumors, as currently available diagnostic techniques may not reliably exclude malignancy. Although positive cytologic and biopsy results strongly support the presence of cancer, negative findings do not consistently rule it out. This diagnostic uncertainty raises an important clinical question regarding whether histologic confirmation is mandatory before major hepatobiliary resection. A narrative literature review was conducted using the PubMed/MEDLINE, Scopus, and Web of Science databases, including studies published in English between January 1990 and January 2026. Relevant articles evaluating diagnostic modalities, cytologic accuracy, surgical management, perioperative outcomes, and survival in patients with suspected or confirmed cholangiocarcinoma were reviewed. Available evidence demonstrates substantial limitations in preoperative tissue diagnosis. Imaging modalities and tumor markers provide supportive but non-definitive diagnostic information, while biliary cytology and biopsy remain suboptimal for definitively excluding malignancy. Surgical series consistently report that a proportion of patients undergoing resection for presumed malignancy ultimately have benign disease on final pathology; nevertheless, outcomes following timely surgical exploration and resection in appropriately selected patients appear superior to those of patients managed without surgery. Resection remains the only established potentially curative treatment. Preoperative histologic confirmation may not be mandatory in carefully selected patients with high clinical and radiologic suspicion of cholangiocarcinoma and technically resectable disease. Timely surgical intervention within a multidisciplinary framework, particularly in experienced hepatobiliary centers, may help avoid loss of curative opportunity.