Incidental Gallbladder Cancer After Cholecystectomy for Presumed Benign Biliary Disease: A Sixteen-Year Retrospective Cohort Study from a Tertiary Referral Center

Background and Objectives: Incidental gallbladder cancer (IGBC) is an uncommon but clinically important diagnosis after cholecystectomy for presumed benign biliary disease. This study aimed to determine the incidence of invasive IGBC in a large cholecystectomy cohort and to describe its clinicopathological profile, stage-specific management pathway, and exploratory univariable survival associations. Materials and Methods: We retrospectively reviewed all cholecystectomies performed between January 2010 and December 2025 at a tertiary referral center (n = 19,798). Patients with known preoperative gallbladder cancer and those with incomplete data precluding reliable staging or survival assessment were excluded. Only invasive IGBC was analyzed; dysplasia and carcinoma in situ were excluded a priori. Overall survival (OS) was defined from index surgery to death from any cause, and disease-free survival (DFS) was assessed in patients with non-metastatic disease at baseline. Survival was estimated using Kaplan–Meier methods, and associations with survival outcomes were explored using univariable Cox regression. Results: IGBC was identified in 43 patients (0.22%). Adenocarcinoma predominated, pT2 was the most frequent pathological stage, and 11 patients (25.6%) had pT3–T4 disease. Staged re-resection was performed in 12 patients (27.9%). Median OS was 48.0 months (95% CI, 34.0–62.0), and median DFS in the M0 cohort was 80.0 months (95% CI, 9.5–150.5). The 2-, 4-, and 6-year OS rates were 78.2%, 48.3%, and 38.8%, respectively; the corresponding DFS rates were 70.4%, 59.3%, and 50.8%. In exploratory univariable analyses, pathological T stage showed the most consistent unadjusted association with OS and DFS, whereas margin positivity, perineural invasion, lymphovascular invasion, and increasing tumor size were associated with worse DFS. Conclusions: Although rare, IGBC may present with advanced pathological features despite presumed benign disease. These findings support meticulous pathological assessment, structured postoperative staging, and risk-adapted multidisciplinary management. Given the limited sample size and exploratory, unadjusted analyses, survival associations should be interpreted cautiously.