Tumoral Versus Flat Intraepithelial Neoplasia of Pancreatobiliary Tract, Gallbladder, and Ampulla of Vater

Abstract

Context.-The identification of a precursor lesion is important to understanding the histopathologic and genetic alterations in carcinogenesis. There are a plethora of terminologies that describe precursor lesions of the pancreatobiliary tract, ampulla of Vater, and gallbladder. The current terminologies for precursor lesions may make it difficult to understand the tumor biology. Here, we propose the concept of tumoral and flat intraepithelial neoplasia to improve our understanding of precursor lesions of many epithelial organs, including the pancreatobiliary tract, ampulla of Vater, and gallbladder.Objective.-To understand the dichotomous pattern of tumoral and flat intraepithelial neoplasia in carcinogenesis of pancreatobiliary tract, ampulla of Vater, and gallbladder.Data Sources.-Review of relevant literatures indexed in PubMed.Conclusions.-Tumoral intraepithelial neoplasia presents as an intraluminal or intraductal, mass-forming, polypoid lesion or a macroscopic, visible, cystic lesion without intracystic papillae. Microscopically, tumoral intraepithelial neoplasia shows various proportions of papillary and tubular architecture, often with a mixed pattern, such as papillary, tubular, and papillary-tubular. The malignant potential depends on the degree of dysplasia and the cell phenotype of the epithelium. Flat intraepithelial neoplasia presents as a flat or superficial, spreading, mucosal lesion that is frequently accompanied by an invasive carcinoma. Tumoral and flat intraepithelial neoplasias are not homogeneous entities and may exhibit histopathologic spectrum changes and different genetic profiles. Although intraepithelial neoplasia showed a dichotomous pattern in the tumoral versus flat types, they can coexist. Tumoral and flat intraepithelial neoplasia can be interpreted as part of a spectrum of changes in the carcinogenesis pathway of each organ. A denoma is the prototype precursor lesion in carcinogenesis. The adenoma-carcinoma sequence is one of the well-characterized models of the carcinogenesis pathway. Through the adenoma-carcinoma sequence, many histopathologic and genetic alterations have been characterized in colorectal carcinogenesis.1,2 Another prototype precursor lesion is uterine cervix dysplasia, which also progresses to invasive squamous cell carcinoma of the uterine cervix through multistep carcinogenesis. Both colon adenoma and uterine cervix dysplasia correspond to intraepithelial neoplasia (IN), which can lead to invasive carcinoma. Most colorectal adenomas present as a polypoid lesion, whereas uterine cervix dysplasia presents as a nonpolypoid, flat, mucosal lesion. We think colon adenoma and uterine cervix dysplasia represent a mass-forming tumoral IN and a nonmass-forming, flat IN, respectively. In general, tumoral IN corresponds to a macroscopic or mass-forming lesion, and flat IN presents as invisible or microscopic lesions. Flat adenomas have been reported in the colorectum, which is much closer to a flat IN, and papillary squamous cell carcinoma of the uterine cervix, which is...

A rare case of symptomatic grossly-visible biliary intraepithelial neoplasia mimicking cholangiocarcinoma

“…To improve this outcome, it is important to be familiar with precancerous lesions for cancer therapy. The precursor lesions of carcinoma have been advocated as adenoma in the gastrointestinal tract, intraepithelial neoplasia in uterine cervical cancer, and leukoplakia in oral cancer [3, 4]. Biliary intraepithelial neoplasia (BilIN) has been described in the World Health Organization 2010 gastrointestinal tumor classification as one of the precursor lesions of CC along with intraductal papillary neoplasm (IPNB), mucinous cystic neoplasm (MCN), and adenoma [5–7].…”

Precursor Lesions of Cholangiocarcinoma: A Clinicopathologic Review

“…30 Biliary intraepithelial neoplasia has been considered as a flat type of intraepithelial neoplasia or flat dysplasia, which unlike the tumoral counterpart of intraepithelial neoplasia such as colonic adenoma will not produce significant clinical manifestations. 31 Intraductal papillary neoplasm of the bile duct is a tumoral type of precursor lesions of CCA which causes papillary ingrowth within the biliary tract and can produce mass lesions and clinical manifestations related to the mass and biliary dilatation. 31 These lesions have been reported to produce symptoms such as abdominal discomfort, abdominal pain, pyrexia, anorexia, and even jaundice.…”

“…31 Intraductal papillary neoplasm of the bile duct is a tumoral type of precursor lesions of CCA which causes papillary ingrowth within the biliary tract and can produce mass lesions and clinical manifestations related to the mass and biliary dilatation. 31 These lesions have been reported to produce symptoms such as abdominal discomfort, abdominal pain, pyrexia, anorexia, and even jaundice. 32,33 Therefore, although the main precursors of the CCA are the lesions of BilIN, however, BilINs are mostly asymptomatic but less common IPNB cases can produce clinical sign and symptoms related to tumoral dysplasia.…”

“…30 Biliary intraepithelial neoplasia has been considered as a flat type of intraepithelial neoplasia or flat dysplasia, which unlike the tumoral counterpart of intraepithelial neoplasia such as colonic adenoma will not produce significant clinical manifestations. 31…”

Intraductal Tubulopapillary Neoplasm of the Pancreas: An Overview

“…5 Microscopically, formation of tubules and absence of mucin production are the main differences between ITPN and IPMN, although some IPMNs, including low-grade branch duct-type IPMNs, can exhibit tubule formation. 13 Intraductal tubulopapillary neoplasms also often exhibit uniform high-grade dysplasia, which is less common in IPMNs, with the exception of the pancreatobiliary subtype of IPMN, and hence the main differential diagnosis of ITPN is the pancreatobiliary subtype of IPMN. Gastric and intestinal types of IPMNs can be distinguished from ITPNs by mucin profiles with MUC2 and MUC5AC positivity, whereas ITPNs are negative for these mucin stains and positive for MUC1 and MUC6.…”