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WHO Classification of Tumours
Intraductal papillary neoplasm (IPN) with high-grade intraepithelial neoplasia
Liver and intrahepatic bile ducts


Definition

Intraductal papillary neoplasms (IPN) of the bile ducts includes the previous categories of biliary papilloma and papillomatosis, and is characterized by dilated intrahepatic bile ducts filled with a noninvasive papillary or villous biliary neoplasm covering delicate fibrovascular stalks
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Abraham SC, Lee JH, Boitnott JK, Argani P, Furth EE, Wu TT (2002)
Microsatellite instability in intraductal papillary neoplasms of the biliary tract.
Mod Pathol 15: 1309-17




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Abraham SC, Lee JH, Hruban RH, Argani P, Furth EE, Wu TT (2003)
Molecular and immunohistochemical analysis of intraductal papillary neoplasms of the biliary tract.
Hum Pathol 34: 902-10




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Chen TC, Nakanuma Y, Zen Y, Chen MF, Jan YY, Yeh TS, Chiu CT, Kuo TT, Kamiya J, Oda K, Hamaguchi M, Ohno Y, Hsieh LL, Nimura Y (2001)
Intraductal papillary neoplasia of the liver associated with hepatolithiasis.
Hepatology 34: 651-8




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Itatsu K, Zen Y, Ohira S, Ishikawa A, Sato Y, Harada K, Ikeda H, Sasaki M, Nimura Y, Nakanuma Y (2007)
Immunohistochemical analysis of the progression of flat and papillary preneoplastic lesions in intrahepatic cholangiocarcinogenesis in hepatolithiasis.
Liver Int 27: 1174-84




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Zen Y, Fujii T, Itatsu K, Nakamura K, Konishi F, Masuda S, Mitsui T, Asada Y, Miura S, Miyayama S, Uehara T, Katsuyama T, Ohta T, Minato H, Nakanuma Y (2006)
Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct.
Mod Pathol 19: 1243-54




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Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006)
Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.
Hepatology 44: 1333-43




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Zen Y, Sasaki M, Fujii T, Chen TC, Chen MF, Yeh TS, Jan YY, Huang SF, Nimura Y, Nakanuma Y (2006)
Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct--an immunohistochemical study of 110 cases of hepatolithiasis.
J Hepatol 44: 350-8



. Dilated bile ducts are fusiform or cystic (unilocular or multilocular). The papillary lesions are soft and white, red or tan. Similar neoplasia can develop in the hilar and extrahepatic bile ducts, and synchronous and metachronous IPNs can develop in the intrahepatic and extrahepatic biliary tree. About one third of IPNs secrete mucin in the duct lumen (mucin secreting biliary tumour)
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Shibahara H, Tamada S, Goto M, Oda K, Nagino M, Nagasaka T, Batra SK, Hollingsworth MA, Imai K, Nimura Y, Yonezawa S (2004)
Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms.
Am J Surg Pathol 28: 327-38




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Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006)
Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.
Hepatology 44: 1333-43



.

Although IPN of the bile ducts is usually not so mucinous, there are a number of parallels between IPN of the bile ducts and intraductal papillary mucinous neoplasm (IPMN) of the pancreas

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Klöppel G, Kosmahl M (2006)
Is the intraductal papillary mucinous neoplasia of the biliary tract a counterpart of pancreatic papillary mucinous neoplasm?
J Hepatol 44: 249-50




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Shibahara H, Tamada S, Goto M, Oda K, Nagino M, Nagasaka T, Batra SK, Hollingsworth MA, Imai K, Nimura Y, Yonezawa S (2004)
Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms.
Am J Surg Pathol 28: 327-38




Click to access Pubmed
Zen Y, Fujii T, Itatsu K, Nakamura K, Konishi F, Masuda S, Mitsui T, Asada Y, Miura S, Miyayama S, Uehara T, Katsuyama T, Ohta T, Minato H, Nakanuma Y (2006)
Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct.
Mod Pathol 19: 1243-54




Click to access Pubmed
Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006)
Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.
Hepatology 44: 1333-43



. Both lesions are papillary and intraductal, both show similar range of possible differentiation of the neoplastic cells (pancreatobiliary type, intestinal type, oncocytic type, and gastric type), and both have similar types of assocated invasive carcinomas
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Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006)
Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.
Hepatology 44: 1333-43



. The pancreatobiliary type is the most common type of IPN of the bile ducts. As in the pancreas, when associated with an invasive carcinoma, the pancreatobiliary type of bile-duct IPN is usually associated with a tubular adenocarcinoma, while the intestinal type of bile-duct IPN is usually associated with a colloid type of invasive carcinoma
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Klöppel G, Kosmahl M (2006)
Is the intraductal papillary mucinous neoplasia of the biliary tract a counterpart of pancreatic papillary mucinous neoplasm?
J Hepatol 44: 249-50




Click to access Pubmed
Shibahara H, Tamada S, Goto M, Oda K, Nagino M, Nagasaka T, Batra SK, Hollingsworth MA, Imai K, Nimura Y, Yonezawa S (2004)
Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms.
Am J Surg Pathol 28: 327-38



.

IPN with cystic luminal dilatation can be distiniguished from biliary mucinous cystic neoplasm (biliary cystadenoma/ cystadenocarcinoma) applying the criteria used in the differentiation of IPMN of pancreas from pancreatic mucinous cystic neoplasm, namely the presence of ovarian- type stroma and female sex are supportive of biliary mucinous cystic neoplasm, while luminal communication with the bile ducts and absence of ovarian-type stroma support the diagnosis of IPN

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Zen Y, Fujii T, Itatsu K, Nakamura K, Konishi F, Masuda S, Mitsui T, Asada Y, Miura S, Miyayama S, Uehara T, Katsuyama T, Ohta T, Minato H, Nakanuma Y (2006)
Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct.
Mod Pathol 19: 1243-54




Click to access Pubmed
Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006)
Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.
Hepatology 44: 1333-43



.

IPN of the bile ducts is classifiable as low, intermediate or high grade on the basis of degree of cellular and nuclear atypia

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Nakanishi Y, Zen Y, Kondo S, Itoh T, Itatsu K, Nakanuma Y (2008)
Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm.
Hum Pathol 39: 1153-61




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Zen Y, Fujii T, Itatsu K, Nakamura K, Konishi F, Masuda S, Mitsui T, Asada Y, Miura S, Miyayama S, Uehara T, Katsuyama T, Ohta T, Minato H, Nakanuma Y (2006)
Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct.
Mod Pathol 19: 1243-54




Click to access Pubmed
Zen Y, Fujii T, Itatsu K, Nakamura K, Minato H, Kasashima S, Kurumaya H, Katayanagi K, Kawashima A, Masuda S, Niwa H, Mitsui T, Asada Y, Miura S, Ohta T, Nakanuma Y (2006)
Biliary papillary tumors share pathological features with intraductal papillary mucinous neoplasm of the pancreas.
Hepatology 44: 1333-43



. IPNs are not infrequently associated with invasive carcinoma (IPN with an associated invasive ICC ). IPN with an associated invasive ICC in the intrahepatic bile ducts corresponds to the IG (intraductal-growth) type of ICC. When an invasive carcinoma is present, it should be separately designated and staged
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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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Commentary: Preneoplastic lesions of the digestive system