Pancreatic Head Cancer Masquerading as Distal Cholangiocarcinoma: Diagnostic Challenges, Tumor Characteristics, and Oncologic Outcomes

<b>Background/Objectives</b>: Differentiating pancreatic head cancer (PHC) from distal cholangiocarcinoma (dCCA) remains clinically challenging and directly influences treatment strategy. This study evaluates the clinicopathologic features and outcomes of patients with PHC who were preoperatively designated as dCCA. <b>Methods</b>: We retrospectively analyzed patients undergoing pancreatoduodenectomy for suspected dCCA or PHC from 2019 to 2023. Patients were stratified by pre- and postoperative diagnoses into three groups: confirmed dCCA (B-B), confirmed PHC (P-P), and dCCA reclassified as PHC (B-P). Clinicopathologic features, perioperative outcomes, and survival were compared. <b>Results</b>: This analysis included 159 patients, B-B = 31, P-P = 115, and B-P = 13. Despite a more advanced stage, a lower R0 rate (<i>p</i> = 0.043), and unplanned portal vein resection confined to B-P (<i>p</i> < 0.001), overall and recurrence-free survival were comparable to P-P (<i>p</i> = 0.363 and 0.183). In multivariable Cox analysis, B-P remained an independent favorable prognostic factor for overall survival (Hazard ratio 0.137, <i>p</i> = 0.020). <b>Conclusions</b>: Approximately one-third of cases initially diagnosed as dCCA were ultimately PHC. These PHC cases mimicking dCCA demonstrated comparable or even superior survival, suggesting a biologically indolent subset. Refinement of diagnostic criteria and integrated clinicopathologic assessment are essential for optimizing preoperative management strategies.