No further therapy is generally required when dysplasia is identified during routine cholecystectomy [13]. As this recommendation is predicated on the absence of invasive carcinoma, it is important that the pathologist thoroughly evaluates the resected specimen; this especially applies to cases with extensive high-grade dysplasia. However, data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute suggest that one-third of patients with carcinoma in situ of the gallbladder died of tumor after 10 years [14]. This may be the result of an unsampled invasive component of the tumor. However, a more likely scenario is the genesis of a second malignancy of the biliary tract, a consequence of a field defect within the biliary system.

There are several analogies that could be drawn between adenomas of the colon and those of the gallbladder; most significantly, both lesions may progress to invasive carcinoma. However, in contrast to colonic carcinoma, only a minority of gallbladder carcinomas arise from adenomas [6].

Adenomas of the gallbladder are a poorly characterized entity, primarily because of their low prevalence. A wide array of terms have been used to designate adenomas of the gallbladder including “pyloric gland adenoma,” “papillary adenoma,” “tubular papillary adenoma,” “papillary neoplasm,” “papillary carcinoma,” and “intracystic papillary neoplasm.” A selection of these terms is based on growth patterns, while others are based on the morphological appearance of the lining epithelium and its resemblance to epithelium lining the gastrointestinal tract. In a recent analysis of 123 gallbladder adenomas, Adsay and colleagues suggest the unifying term intracholecystic papillary-tubular neoplasm (ICPN) to encompass all neoplastic mass-forming precursor lesions of gallbladder [6]. This argument has merit since all of these mass-forming neoplasms of the gallbladder are associated with a significant risk of invasion. However, there appeared to be some minor variations in the risk of invasive carcinoma among the various subcategories of gallbladder adenomas. It is important to emphasize that some de novo invasive gallbladder carcinomas may present as a polypoid mass. Therefore, pathologists must draw a clear distinction between this entity, polypoidal carcinoma, and a precursor neoplastic polyp associated with an invasive carcinoma; the latter category is associated with a slightly better prognosis.

The World Health Organization’s classification of tumors of the digestive system recognizes an intracystic papillary neoplasm as a distinct entity and distinguishes them from adenomas of the gallbladder [16]. Intracystic papillary neoplasms show a prominent intraluminal proliferation of papillary epithelium, generally with high-grade atypia (Fig. 4). However, in many cases, there is no clear distinction between this entity and an adenoma of the gallbladder. Similar to the adenomas of the gallbladder, intracystic papillary neoplasms that lack invasion are associated with an excellent prognosis [17].

Mucinous cystic neoplasms are seen in adult females. This neoplasm is more frequently seen in the pancreas; the hepatic and gallbladder counterparts are extremely uncommon [18]. Histologically, these cystic neoplasms are lined by mucinous epithelium with varying grades of atypia. These neoplasms are defined by the presence of ovarian-type stroma. Similar to the pancreas, non-invasive lesions are associated with an excellent outcome, while invasive adenocarcinomas arising in mucinous cystic neoplasms are associated with a risk of metastasis and death.

Neoplastic polyps constitute only a minority of gallbladder polyps; the majority of gallbladder polyps are non-neoplastic. The two most common non-neoplastic polyps of the gallbladder are cholesterol polyp and adenomyoma.

Most malignant epithelial neoplasms of the extrahepatic biliary tract arise within the gallbladder. The majority of gallbladder carcinomas are adenocarcinomas, most commonly of the biliary type, although several other histologic subtypes have been defined by the World Health Organization [16] (Table 1).