Intrahepatic Cholangiocarcinoma With Predominant “Ductal Plate Malformation” Pattern

Abstract

Ten cases of intrahepatic cholangiocarcinoma showing a highly differentiated adenocarcinoma mimicking ductal plate malformation (DPM) are reported. The patients included 7 males and 3 females with an average age of 69.5 years. Six cases were associated with chronic liver disease and the remaining 4 cases showed mild fatty change in the parenchyma and/or minimal to mild portal inflammation. Grossly, the tumor was a single nodule 1.5 to 6.6 cm in diameter, and was whitish and solid without a fibrous capsule. Microscopically, the tumor was composed of many vague, small nodular carcinomatous areas with desmoplastic reactions, and neoplastic glands had an irregularly dilated lumen lined with a single layer of cuboidal or low columnar carcinoma cells and irregular protrusions and bulges, resembling DPM. At its border, the carcinoma seemed to replace the non-neoplastic hepatic lobules or regenerative nodules. The central parts of the tumor were variably hypocellular and fibrotic. Although these carcinomas were negative for mucin and HepParI, they were frequently positive for CK19, epithelial cell adhesion molecule, and epithelial membrane antigen. Neural cell adhesion molecule was also expressed variably. The Ki-67 labeling index was <10% and p53 was scarcely expressed. In conclusion, a new subtype of intrahepatic cholangiocarcinoma with predominant DPM pattern was identified.

Intrahepatic cholangiocarcinoma and cholangiolocellular carcinoma in cirrhosis and chronic viral hepatitis

“…The small glandular formation is as small as or smaller than the normal interlobular ductules [76]. The CoCC cells sometimes form antler-like anastomosing and ductal plate malformation-like patterns [26,36,77]. CoCC cells are further confirmed by either positive staining for cytokeratin 19 (CK19), membranous positive staining for mucin core protein 1 (MUC-1), and/or membranous positive staining for epithelial membrane antigen (EMA) [25,76,78].…”

What Are the Precursor and Early Lesions of Peripheral Intrahepatic Cholangiocarcinoma?

“…In addition, low grade biliary epithelial malignancies such as those with ductal plate malformation- (DPM-) like features and cholangiolocellular carcinoma (bile ductular carcinoma) are known to contain the foci of classical or conventional CC [13, 18], suggesting their progression from low grade biliary epithelial malignancies to conventional CC with more malignant biological behaviors [13, 19]. …”

Human ductal plate and its derivatives express antigens of cholangiocellular, hepatocellular, hepatic stellate/progenitor cell, stem cell, and neuroendocrine lineages, and proliferative antigens

“…HGF is known to be produced by mesenchymal cells. [46][47][48][49][50][51][52][53][54][55] In the liver, portal mesenchyme may be the sites of HGF production. The capillary and sinusoidal endothelial cells are also candidates.…”

“…[18][19][20][21][38][39][40][41][42][43] DP is also seen in ductular reactions [44][45][46] and DPM in some liver hamartoma 45 and cholangiocarcinoma. 47 The DP in ductular reaction of focal nodular hyperplasia interestingly may express KIT, 46 a receptor of stem cell factor (SCF). 48 Recent evidence has suggested the presence of hepatic stellate/progenitor cell (HSC) in human as well as in animal livers.…”