Intracholecystic Papillary Neoplasms (ICPNs): Systematic Review and Meta-analysis of Epidemiological, Diagnostic,...

Intracholecystic papillary-tubular neoplasms (ICPNs) are infrequent preinvasive gallbladder lesions. The literature lacks standard reporting criteria and is limited to single-center series and case reports. This systematic review and meta-analysis aimed to synthesize the available evidence on their epidemiology, pathology, and possible association between high-grade dysplasia and invasive carcinoma.

MEDLINE, Scopus, and Web of Science were searched on the June 9, 2025, for "intracholecystic papillary neoplasm" OR "intracholecystic papillary-tubular neoplasm" OR "ICPN" (PROSPERO ID: CRD420250636493). Human studies reporting histologically confirmed ICPNs were included, and case reports, reviews, and animal studies were excluded. Pooled proportions were calculated using generalized linear mixed models with random effects and restricted maximum likelihood.

A total of 17 retrospective series, including 15,018 cholecystectomies and 620 ICPN cases, met the criteria. In four studies (13,559 cholecystectomies), the pooled incidence of ICPNs was 1.5% (95% confidence interval [CI] 0.8-2.8). The patients were mainly female (56%), with a mean age of 65 years. Papillary architecture and biliary or gastric phenotypes were also predominant. High-grade dysplasia was observed in the 35.4% of the lesions (six studies) and concomitant gallbladder adenocarcinoma in 26.9% (nine studies). Lymph node metastases were present in 18% of invasive cases, and the 5-year overall survival ranged from 46.7% to 89.7%.

ICPNs are uncommon but clinically relevant preinvasive gallbladder neoplasms that frequently harbor high-grade dysplasia or invasive carcinoma. Future research should aim to improve the preoperative diagnostic accuracy, define possible pathological-clinical correlations, and optimize the surgical management.