Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma

Abstract

Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis.

Clinicopathologic Study of Biliary Intraepithelial Neoplasia in Cholangiocarcinoma

“…Studies of molecular alteration reported that BilIN showed a step-wise increased expression of oncogene-related molecules such as p21, p53, and cyclin D, and a stepwise decreased expression of Smad4 during the progression of the grades of BilIN [13]. In other studies, Ki67 proliferative index was reported to range from 11 to 84.8% in intrahepatic CC [14,15].…”

“…Biliary intraepithelial neoplasia (BilIN) is a precursor to both intrahepatic and extrahepatic CC, and it has been associated with several conditions known to predispose to CC [2,3].…”

The promising role of epigenetic mediators and microRNAs in the early diagnosis of cholangiocarcinoma (Review)

“…This method for the detection of CC has a sensitivity of 83% and a specificity of 100% (13,114,115). Screening for the genetic and epigenetic alterations in the precursor lesions, including intraductal papillary neoplasm of the bile duct (IPNB) and biliary intraepithelial neoplasia (BilIN), as discussed by Ettel et al, may also be beneficial (116). The diagnostic and treatment challenges are also due to the heterogeneity of clinical presentations, which may be due to the origin of CC from topographically heterogeneous cholangiocytes.…”

Intraductal papillary neoplasm of the bile duct: A rare precursor of cholangiocarcinoma

“…However, mucin production is uncommon in IPNB. Pancreatobiliary subtype is the most frequent phenotype in the Western population . Nearly 40% of IPNBs are associated with cholangiocarcinoma, and this is more prevalent in the pancreatobiliary than in other subtypes .…”

“…Pancreatobiliary subtype is the most frequent phenotype in the Western population. 2 Nearly 40% of IPNBs are associated with cholangiocarcinoma, and this is more prevalent in the pancreatobiliary than in other subtypes. 3 Moreover, synchronous and metachronous lesions are common along the biliary tree in patients with IPNB requiring careful pathological and radiological assessment.…”