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Int J Clin Exp Pathol 2013;6(4):737-748

Case Report
Combined hepatocellular-cholangiocarcinoma with stem cell features, ductal plate
malformation subtype: a case report and proposal of a new subtype

Tadashi Terada

Departments of Pathology, Shizuoka City Shimizu Hospital, Shizuoka, Japan

Received January 4, 2013; Accepted February 17, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: In the current WHO blue book, combined hepatocellular-cholangiocarcinoma (C-HCC-CC) was classified into two types; classical
type and type with stem cell features. The latter is extremely rare, and is subcategorized into the following three subtypes; typical subtype,
intermediate cell subtype, and cholangiocellular subtype. Recently, intrahepatic cholangiocarcinoma (ICC) with features of ductal plate
malformations (DPM) have been reported, and the ICC with DPM was proposed as a subtype of ICC. The author herein reports a case of
C-HCC-CC with stem cell features. Characteristically, the CC element showed features of DPM. A 51-year-old man of HBV carrier was found to
have high AFP. A laboratory test showed an elevated AFP (395 ng/ml, normal 9-10) and hepatitis B virus-related antigens and antibodies. Liver
and ductal enzymes and PIVKAII were within normal ranges. Imaging modalities including CT identified a small liver tumor. Hepatocellular
carcinoma (HCC) was suspected, and the resection of the hepatic tumor was performed. Grossly, the liver tumor is well-defined white solid
tumor measuring 22x16x23 mm. Microscopically, the tumor was a C-HCC-CC, and was composed of following three elements: well
differentiated HCC, well differentiated cholangiocarcinoma (CC), and intermediate tumor element. Characteristically, the CC cells formed
tortuous markedly irregular tubules with intraluminal cell projections, bridge formations, intraluminal tumor biliary cells; such features very
resembled the ductal plate (DP) and DPM. Immunohistochemically, the cells of CC element were positive for stem cell antigens (KIT (CD117),
CD56, EMA, CD34), HepPar1, EpCAM, cytokeratin (CK) CAM5.2, AE1/3, CK34BE12 (focal), CK7, CK8, CK18, CK19, CA19-9, p53, MUC1, MUC2,
MUC5AC, MUC6, and Ki-67 (labeling=25%). They were negative for CEA, CK5/6, CK20, NSE, chromogranin, synaptophysin, and p63. No
mucins were found by histochemically. The background liver showed chronic hepatitis B (a1, f3). Very interestingly, many DPMs were scattered
in the non-tumorous parenchyma. This type of C-HCC-CC with DPM features has not been reported. The author herein proposes that this
tumor should be included or added in the C-HCC-CC subtype as C-HCC-CC with stem cell features, DMP subtype. (IJCEP1301004).

Keywords: Combined hepatocellular cholangiocarcinoma, liver stem cells, ductal plate, ductal plate malformation, histopathology,

Address correspondence to: Dr. Tadashi Terada, Department of Pathology, Shizuoka City Shimizu Hospital, Miyakami 1231 Shimizu-Ku,
Shi-zuoka 424-8636, Japan. Tel: +81-54-336-1111; Fax: +81-54-334-1173; E-mail: piyo0111jp@yahoo.co.jp