Evaluating the Role of Morphological Subtypes in the Classification of Periampullary Adenocarcinomas

<b>Background</b>: Morphological subclassification may refine prognosis after curative pancreaticoduodenectomy (PD) for periampullary cancers. <b>Methods</b>: We conducted a single-center retrospective cohort including 120 consecutive PDs performed between 2005 and 2022. Tumors were classified as intestinal (INT), pancreatobiliary (PB), or pancreatic ductal adenocarcinoma (PAN). Clinicopathologic variables included T stage, margin status, lymphovascular and perineural invasion, and lymph node ratio (LNR; cutoff 0.154 determined by ROC/Youden). Overall survival (OS) was the primary endpoint and was analyzed using Kaplan-Meier with log-rank tests and multivariable Cox regression. <b>Results</b>: INT tumors were associated with earlier T stage, fewer adverse histologic features, and higher R0 resection rates compared with PB and PAN. In multivariable analysis, mortality risk was higher for PB (HR 4.41; 95% CI 1.25-15.53) and PAN (HR 13.96; 95% CI 3.99-48.75) relative to INT. LNR ≥ 0.154 independently predicted worse OS (HR 1.93; 95% CI 1.11-3.35). Mean OS was 108.8 months for INT, 62.0 months for PB, and 22.7 months for PAN (log-rank <i>p</i> < 0.001). <b>Conclusions</b>: Morphological subtype and LNR are independent prognostic factors after PD for periampullary malignancies. Integrating morphology and nodal burden into risk models may improve postoperative stratification and guide adjuvant therapy.