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Updated: May 1, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Carcinoma with shared pathologic characteristics of both hepatocellular carcinoma and cholangiocarcinoma
Atsushi Hiraoka1, Kiyotaka Kurose1, Teru Kumagi1
1Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Background:
α-Fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), and protein induced by vitamin K absence or antagonist II (PIVKA-II) and fucosylated AFP (AFP-L3) are specific tumor markers.
Objective:
The aim of this article was to report a case of intrahepatic cholangiocarcinoma (CC) with high levels of expression of AFP, AFP-L3, and PIVKA-II.
Methods:
A 70-year-old man weighing 66 kg with a diagnosis of intrahepatic CC presented with a liver tumor 4.0 cm in diameter and elevated concentrations of carbohydrate antigen 19-9 (575 U/mL), PIVKA-II (379 mAU/mL), and AFP (497 ng/mL; AFP-L3, 88.1%). On extended medial hepatic segmentectomy, microscopy showed that the tumor was a CC without HCC. The patient subsequently underwent immunohistochemical assessments using cytokeratin-19, epithelial membrane antigen (EMA), hepatocyte paraffin-1 (HP-1), PIVKA-II, and AFP.
Results:
In all specimens, desmoplasia was observed. However, results of immunohistochemistry showed positive results for cytokeratin-19 and EMA; HP-1 results were negative. Results of PIVKA-II and AFP testing in the tumor were positive.
Conclusions:
The case presented here showed characteristics of CC and HCC, whereas the histologic expression of the tumor suggested CC. Based on the literature search, this is the first known report of a case of a CC expressing AFP and PIVKA-II confirmed on immunohistochemical staining. This case is interesting with regard to the ability of the progenitor cells to differentiate HCC and CC.
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