Bui

Fig. 8.34 A Intrahepatic cholangiocarcinoma showing papillary growth pattern involving the peribiliary glands . The bile duct lumen (top and center) is free of carcinoma. B Papillary cholangiocarcinoma invading the bile duct wall.

On rare occasions, the tumour shows extensive intraluminal spread of bile ducts throughout the liver. The tumour cells can also infiltrate into the peribiliary glands of the intrahepatic large bile ducts and their conduits. It may be difficult to distinguish this lesion from reactive proliferated peribiliary glands histo-logically.

Histopathology

Most ICCs are adenocarcinomas showing tubular and/or papillary structures with a variable fibrous stroma {326}. There is no dominant histological type of ICC in cases associated with liver flukes or hepatolithiasis when compared to those in non-endemic areas.

Adenocarcinoma

This common type of ICC growing in the hepatic parenchyma and portal pedicle reveals a significant heterogeneity of histological features and degree of differentiation. At an early stage, a tubular pattern with a relatively uniform histological picture is frequent. Cord-like or micro-papillary patterns are also seen. The cells are small or large, cuboidal or columnar, and can be pleomorphic. The nucleus is small and the nucleolus is usually less prominent than that of HCC. The majority of cells have a pale, eosinophilic or vacuolated cytoplasm; sometimes, the cells have a clear and abundant cytoplasm or resemble goblet cells.

Fig. 8.35 High-grade intraepithelial neoplasia of a peribiliary gland in a patient with hepatolithiasis.

ICC arising from the large intrahepatic bile ducts shows intraductal micropapil-lary carcinoma and in situ like spread along the biliary lumen. Once there is invasion through the periductal tissue, the lesion may be well, moderately, or poorly differentiated adenocarcinoma, with considerable desmoplasia and stenosis or obliteration of the bile duct lumen.

Infrequently, a papillary tumour growing in the duct lumen is supported by fine fibrovascular cores. Cholangio-carcino-ma arising from the intrahepatic peribil-iary glands {1914} mainly involves these glands, sparing the lining epithelial cells at an early stage.

An abundant fibrous stroma is an important characteristic of ICC. Activated perisinusoidal cells (myofibroblasts) are incorporated into the tumour, producing extracellular matrix proteins that lead to fibrosis {1913}. Usually, the central parts of the tumour are more sclerotic and hypocellular, while the peripheral parts show more actively proliferating carcinoma cells. On rare occasions, the tumour cells are lost in a massive hyaline stroma, which may be focally calcified. The secretion of mucus in one form or another can be demonstrated in the majority of tumours by mucicarmine, diastase-PAS and Alcian blue staining. Mucus core (MUC) proteins 1, 2, and 3 are detectable in the carcinoma cells {1264, 1670}. ICC cells can immunoexpress cytokeratins 7 and 19, CEA, epithelial membrane antigen, and blood group antigens. Bile may be present occasionally in ICC as a result of destruction of the bile ducts or entrapment of non-neoplas-

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