Carcinoma in situ and dysplasia of the gallbladder

Gallbladder cancer develops through a metaplasia, dysplasia, carcinoma sequence in chronically inflamed mucosa (Lewis 2007; Hundal 2014). The WHO classification (5th edition, 2019; Nagtegaal 2020) names the flat precursor biliary intraepithelial neoplasia, graded low or high, with high-grade lesions equivalent to carcinoma in situ, and the mass-forming precursor the intracholecystic papillary neoplasm (Adsay 2012). In TNM 8th edition carcinoma in situ is Tis, stage 0: cancer cells confined to the lining with no invasion, rarely found except when a gallbladder is removed for other reasons (CRUK stages and grades). Early carcinomas confined to or above the muscle layer (Tis, T1a, T1b) are usually invisible to the naked eye (60 percent of 190 cases), occur about a decade younger than advanced cancers (mean 57.9 years) and have excellent outcomes: 92.3 percent five-year and 90.4 percent ten-year survival in a high-incidence series that sampled every specimen fully. The exception is extension of the intraepithelial tumour into Rokitansky-Aschoff sinuses, present in 17.8 percent, after which 39 percent died of disease against 4 percent without, often years later (Roa 2013). In primary sclerosing cholangitis dysplasia and carcinoma are common enough (37 and 14 percent of explanted gallbladders) that guidelines advise cholecystectomy for any polyp; a later cohort found most such polyps benign and proposed short-interval surveillance before surgery in the absence of high-risk features (Lewis 2007; van Erp 2020).

What differs in treatment: Tis with a clear cystic duct margin needs no operation beyond the cholecystectomy already done. A positive cystic duct margin, or high-grade dysplasia running into the cystic duct, prompts consideration of bile duct margin re-excision, and Rokitansky-Aschoff sinus involvement is a reason to consider further surgery and to follow the patient for years (Roa 2013). The pathology protocol matters: at least three sections and the cystic duct margin from every routine specimen in high-incidence settings, and complete embedding when dysplasia or cancer is found (Aloia 2015).