Pathological classification of intrahepatic cholangiocarcinoma based on a new concept

Abstract

Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic differentiation. To date, ICC was largely classified into adenocarcinoma and rare variants. Herein, we propose to subclassify the former, based on recent progress in the study of ICC including the gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is, ICC is classifiable into the conventional (bile duct) type, the bile ductular type, the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma. Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites, IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB, particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma, mucinous/signet ring cell carcinoma, clear cell type, undifferentiated type, neuroendocrine carcinoma and so on. This classification of ICC may open up a new field of research of ICC and contribute to the clinical approach to ICC.

Keywords: Adenocarcinoma; Bile duct; Bile ductule; Intraductal neoplasm; Intrahepatic cholangiocarcinoma.

Figure 1

Gross features of intrahepatic cholangiocarcinomas. A: Mass forming type. The carcinoma forms a mass showing compressive growth; B: Periductal infiltrating type. The carcinoma spreads along the biliary tree (arrow); C: Intraductal growth type. The carcinoma shows papillary growth in the dilated intrahepatic bile duct lumen (arrow).

Figure 2

Conventional type (bile duct type) of intrahepatic cholangiocarcinoma. A: Small bile duct type. A well-differentiated tubular adenocarcinoma with a desmoplastic reaction is found; B: Large bile duct type. The carcinoma spreads along the bile duct lumen and infiltrates the bile duct wall. L: bile duct lumen.

Figure 3

Bile ductular type of intrahepatic cholangiocarcinoma. A: A small ductular carcinoma grows in fibrous stroma; B: The central part of the tumor shows a dropping-out of carcinoma cells with empty spaces; C: Ductal plate malformation type.

Figure 4

Intraductal type of intrahepatic cholangiocarcinoma. A: Intraductal papillary neoplasm of bile duct. Neoplastic biliary epithelia show papillary growth in the dilated lumen. There is no invasion into the duct wall; B: Intraductal tubular neoplasm of bile duct. The neoplasm (a) appears as a cast in the dilated lumen; C: Intraductal tubular neoplasm of bile duct. The tubular pattern is predominant. Higher magnification of Figure 4B; D: Superficial spreading type. Carcinoma cells show intraductal, intraepithelial growth with a micropapillary configuration and intraglandular involvement. There is no evident invasion into the duct wall.

Figure 5

Variants of intrahepatic cholangiocarcinoma. A: Mucinous type and carcinoma cells are floating in a mucinous lake; B: Mucinous type and in the invasive part of the intraductal papillary neoplasm of bile duct, mucinous changes are found; C: Clear cell type and clear cell carcinoma shows a tubular pattern with a desmoplastic reaction; D: Sarcomatous type and spindle cell sarcoma grows medullary.