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What are the precursor and early lesions of peripheral intrahepatic cholangiocarcinoma?

Nakanuma Y, Tsutsui A, Ren XS, Harada K, Sato Y, Sasaki M - Int J Hepatol (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan ; Department of Pathology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Atypical small bile duct lesion. (a) Small interlobular bile duct shows cellular and nuclear atypia. HE. (b) Small interlobular bile duct shows nuclear atypia and disturbed polarity. HE.
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fig5: Atypical small bile duct lesion. (a) Small interlobular bile duct shows cellular and nuclear atypia. HE. (b) Small interlobular bile duct shows nuclear atypia and disturbed polarity. HE.

Mentions: As a precursor or premalignant lesion of CC, BilINs are known and they are usually found in intrahepatic large bile ducts and perihilar and extrahepatic bile ducts [4, 5]. BilIN lesions were histologically classified as BilIN-1 (mild atypia), BilIN-2 (moderate atypia), and BilIN-3 (severe atypia including in situ carcinoma). While histological features of BilIN lesions were documented, it remains controversial whether BilIN-1 lesions contain some reactive hyperplastic changes. So, in this histological survey, only BilIN-2 and -3 lesions evaluated as neoplastic or preinvasive epithelial lesions were surveyed. In fact, it was found in this study that BilIN-2/3 lesions were found frequently in hilar bile ducts and peribiliary glands of hilar CC (52.9% and 50%, resp.) (Table 2). However, such lesions were infrequent or rare in these biliary anatomical components of biliary tree in peripheral CC, cHC-CC, and HCC. In our clinical experience, dysplastic biliary epithelial changes sharing features of BilIN are occasionally encountered in small bile ducts in peripheral CCs (Figures 5(a) and 5(b)). They showed that pleomorphic nuclei, nuclear hyperchromasia or stratification, and this size of affected bile ducts were enlarged, but not so atypical for making a diagnosis of CC or intraductal spread of carcinoma from CC. So, we surveyed such lesions in small bile ducts remote from CC itself of peripheral CC cases. It was found in this study that such small bile ducts showing atypical features were focally found in 10.8% of peripheral ICC. Interestingly, such lesions were found in 5.6% of cHCC-CC and not found in HCC and hilar CC. Further pathological and molecular studies are warranted for such small bile duct lesions which have not been reported in the literatures.


What are the precursor and early lesions of peripheral intrahepatic cholangiocarcinoma?

Nakanuma Y, Tsutsui A, Ren XS, Harada K, Sato Y, Sasaki M - Int J Hepatol (2014)

Atypical small bile duct lesion. (a) Small interlobular bile duct shows cellular and nuclear atypia. HE. (b) Small interlobular bile duct shows nuclear atypia and disturbed polarity. HE.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4016917&req=5

fig5: Atypical small bile duct lesion. (a) Small interlobular bile duct shows cellular and nuclear atypia. HE. (b) Small interlobular bile duct shows nuclear atypia and disturbed polarity. HE.
Mentions: As a precursor or premalignant lesion of CC, BilINs are known and they are usually found in intrahepatic large bile ducts and perihilar and extrahepatic bile ducts [4, 5]. BilIN lesions were histologically classified as BilIN-1 (mild atypia), BilIN-2 (moderate atypia), and BilIN-3 (severe atypia including in situ carcinoma). While histological features of BilIN lesions were documented, it remains controversial whether BilIN-1 lesions contain some reactive hyperplastic changes. So, in this histological survey, only BilIN-2 and -3 lesions evaluated as neoplastic or preinvasive epithelial lesions were surveyed. In fact, it was found in this study that BilIN-2/3 lesions were found frequently in hilar bile ducts and peribiliary glands of hilar CC (52.9% and 50%, resp.) (Table 2). However, such lesions were infrequent or rare in these biliary anatomical components of biliary tree in peripheral CC, cHC-CC, and HCC. In our clinical experience, dysplastic biliary epithelial changes sharing features of BilIN are occasionally encountered in small bile ducts in peripheral CCs (Figures 5(a) and 5(b)). They showed that pleomorphic nuclei, nuclear hyperchromasia or stratification, and this size of affected bile ducts were enlarged, but not so atypical for making a diagnosis of CC or intraductal spread of carcinoma from CC. So, we surveyed such lesions in small bile ducts remote from CC itself of peripheral CC cases. It was found in this study that such small bile ducts showing atypical features were focally found in 10.8% of peripheral ICC. Interestingly, such lesions were found in 5.6% of cHCC-CC and not found in HCC and hilar CC. Further pathological and molecular studies are warranted for such small bile duct lesions which have not been reported in the literatures.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan ; Department of Pathology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.

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.

No MeSH data available.


Related in: MedlinePlus