Intracholecystic Papillary Tubular Neoplasm of the Gallbladder With Microinvasive Carcinoma

Abstract

For the intramucosal mass-forming preinvasive neoplasms (tumoral intraepithelial neoplasms) of the gallbladder, the term intracholecystic papillary tubular neoplasm (ICPN) has been proposed as a unifying category to embrace all the entities described in the World Health Organization 2010 classification as “adenoma,” “intracystic papillary neoplasm,” and “papillary adenocarcinoma.” In essence, this category represents the gallbladder counterpart of the tumors known as intraductal papillary and intraductal tubulopapillary neoplasms in the pancreas and bile ducts. They are distinguished from nontumoral (“flat”) dysplasia by their exophytic tumor formation. They show a spectrum of dysplastic changes (adenoma-carcinoma sequence), various growth patterns, often in a mixture (papillary, tubular, and tubulopapillary), and a variety of cell lineages including biliary (MUC1+), pyloric-mucinous (MUC6+), complex-tubular (pyloric nonmucinous; MUC6+; with morule formation and β-catenin nuclear positivity), gastric-foveolar, occasionally intestinal (MUC2/CDX2), and even more rarely oncocytic, often but not always with corresponding immunophenotypic changes. Invasive carcinoma is often encountered in association with these tumors (65% of the cases), and an estimated 6% to 8% of invasive carcinomas arise from ICPNs. Invasion is common in papillary examples and those with biliary or gastric-foveolar appearance, whereas it is very low, if at all, in complex tubular-pyloric examples (although the latter often shows striking cytoarchitectural atypia as well). Extensive sampling is warranted to rule out invasive carcinoma. Carcinomas confined to above the tunica muscularis (early gallbladder carcinomas, which correspond to Tis/T1a/T1b cases) have a fairly good prognosis, especially if the possibility of T2 carcinoma (invasion through the muscularis) is ruled out by thorough sampling. More invasive examples have an aggressive behavior but still appear to be better behaving than ordinary adenocarcinomas without ICPNs, presumably partly due to early discovery of invasive carcinomas, but also partly due to differences in biologic behavior.