Appendiceal mucocele in a high-volume surgical centre: clinicopathological variables associated with neoplastic disease, surgical outcomes, and a proposed institutional management algorithm: A retrospective cohort study

Appendiceal mucocele (AM) represents a clinicopathologically heterogeneous spectrum ranging from benign retention cysts to low-grade appendiceal mucinous neoplasms (LAMN) and mucinous adenocarcinoma. Distinguishing neoplastic from benign AM preoperatively is essential to avert inadvertent perforation-related pseudomyxoma peritonei (PMP). The present study examines clinical, biological, and radiological predictors of neoplastic AM and proposes a hypothesis-generating institutional management framework. A retrospective cohort study of 4,126 consecutive appendiceal pathology cases managed at a single tertiary centre in Tunisia (January 2011–July 2022) was reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Fifty-four patients with histologically confirmed AM were identified (incidence 1.31%). Given the 14 neoplastic events, comparative findings were considered exploratory and hypothesis-generating. Benign ( n = 40) and neoplastic ( n = 14) subgroups were compared. Prespecified candidate variables were evaluated using univariable Firth’s penalized logistic regression, with bias-corrected odds ratios (OR) and 95% profile-likelihood confidence intervals (CI). The Benjamini–Hochberg false-discovery rate (FDR) procedure was applied to 15 prespecified inferential comparisons. CEA was measured selectively and was analysed as an exploratory biomarker because of verification bias; CA 19 − 9 was reported descriptively only because its group-specific ascertainment could not be reliably reconstructed. Mean patient age was 46.0 ± 14.3 years; 29 were male (53.7%). CT identified AM preoperatively in 35 patients (64.8%). Twelve patients (22.2%) underwent completed laparoscopic surgery and 42 (77.8%) underwent open surgery. Histological subtypes comprised benign AM (74.1%), LAMN (18.5%), and mucinous adenocarcinoma (7.4%). Neoplastic AM was associated with older age ( p = 0.009; Firth OR 1.05/year, 95% CI 1.01–1.11; FDR q = 0.019), larger lesion diameter ( p < 0.001; FDR q < 0.002), diameter > 6 cm (Fisher’s exact p < 0.001; Firth OR 18.6, 95% CI 2.8–124.1; FDR q < 0.001), CT base involvement (Fisher’s exact p < 0.001; Firth OR 14.9, 95% CI 2.1–104.8; FDR q < 0.001), mural nodularity (Fisher’s exact p = 0.002; Firth OR 12.3, 95% CI 1.7–90.1; FDR q = 0.006), and mural calcification (Fisher’s exact p = 0.031; Firth OR 4.7, 95% CI 1.1–19.4; FDR q = 0.058). CEA was elevated in 5/14 neoplastic patients versus 0/14 tested benign patients (Fisher’s exact p = 0.041; Firth OR 16.8, 95% profile-likelihood CI 1.6–2301.9), but this analysis was affected by verification bias (FDR q = 0.068). Six of 14 neoplastic lesions (42.9%) had none of the prespecified CT features. Two LAMN patients developed CT-documented peritoneal mucinous disease during follow-up; one had acellular peritoneal mucin already present at index resection. One patient with mucinous adenocarcinoma developed hepatic and peritoneal relapse at 14 months and subsequently died. No 30-day mortality occurred. In this exploratory single-centre cohort, older age and selected CT features were associated with neoplastic AM. The composite criterion of ≥ 2 CT features showed high specificity (95.0%) but limited sensitivity (57.1%), with a positive predictive value of 80.0%; therefore, a negative CT assessment cannot exclude neoplasia. Selective CEA testing was affected by verification bias and showed a wide uncertainty interval; it cannot be considered a validated preoperative biomarker. The findings support heightened operative caution and structured preoperative assessment but should not be interpreted as a validated diagnostic rule or as an independent determinant of the extent of resection. Prospective multicentre validation is required.