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.