What Are the Precursor and Early Lesions of Peripheral Intrahepatic Cholangiocarcinoma?

Abstract

Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC. In distal and perihilar CC and large duct ICC, biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm (IPN) have been proposed as precursor lesions. Peripheral ICC, bile duct adenoma (BDA), biliary adenofibroma (BAF), and von Meyenburg complexes (VMCs) are reportedly followed by development of ICCs. Herein, we surveyed these candidate precursor lesions in the background liver of 37 cases of peripheral ICC and controls (perihilar CC, 34 cases; hepatocellular carcinoma, 34 cases and combined hepatocellular cholangiocarcinoma, 25 cases). In the background liver of peripheral ICC, BDA and BAF were not found, but there were not infrequently foci of BDA-like lesions and atypical bile duct lesions involving small bile ducts (32.4% and 10.8%, resp.). VMCs were equally found in peripheral CCs and also control CCs. In conclusion, BDA, BAF, and VMCs are a possible precursor lesion of a minority of peripheral CCs, and BDA-like lesions and atypical bile duct lesions involving small bile ducts may also be related to the development of peripheral ICC. Further pathologic studies on these lesions are warranted for analysis of development of peripheral ICCs.

Pathology of intrahepatic cholangiocarcinoma

“…It is now recognized that iCC proceeds through multistepcarcinogenesis; three precursor lesions have been at present morphologically established (22)(23)(24)(25)(26)(27)(28)(29)(30)(31): (I) a flat intraepithelial bilirary neoplasia or BillN (discernible only at level of microscope) ( Figure 6A); (II) an IPNB (previously named papillomatosis) (discernible on radiologic imaging or at macroscopic examination ( Figures 4A and 6B); and (III) intraductal tubulo-papillary neoplasm (ITNB). These lesions are generally observed in large intrahepatic, hilar and extrahepatic BDs, and are infrequently observed in the septal or interlobular BDs.…”

Malignant transformation of biliary adenofibroma: a rare biliary cystic tumor

“…To our knowledge, only 11 cases of BAF have been reported in the literature (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). We performed a database search to find cases of BAF diagnosed at Mayo Clinic from years 1994 to 2016.…”

Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma

“…These classification schemes reflect the postulated cells of tumor origin with similarities between the perihilar type, conventional ductal carcinoma, bile duct type and mucin-producing type, and between the peripheral, bile ductular, cholangiolar and cholangiolocellular types [2] . ICCs may evolve from two types of premalignant biliary lesions: Biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) [3] as in the case of perihilar large duct type ICCs [4] . ICC may also evolve without definite premalignant lesions.…”