Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma

Abstract

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare tumor with poor prognosis, with incidence ranging from 1.0%-4.7% of all primary hepatic tumors. This entity will be soon renamed as hepato-cholangiocarcinoma. The known risk factors for hepatocellular carcinoma (HCC) have been implicated for CHC including viral hepatitis and cirrhosis. It is difficult to diagnose this tumor pre-operatively. The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction. Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies (from different areas of tumor) are recommended before administering treatment. Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis, but it remains a challenging diagnosis prior to resection. There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC. The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features: Classical type and CHC with stem cell features. Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. We present a review paper on CHC highlighting the risk factors, origin, histological classification and therapeutic modalities.

Keywords: Cholangiocellular carcinoma; Classification; Combined hepatocellular-cholangiocellular carcinoma; Hepatic progenitor cell(s); Hepatocellular carcinoma; Histogenesis.

Figure 1

Representative picture classic type combined hepatocellular-cholangiocarcinoma, hematoxylin and eosin, 10 × - intermediate areas with both hepatocytic and chloangiocytic components.

Figure 2

Combined hepatocellular-cholangiocarcinoma with stem cell features, typical subtype. A: H and E, 4 × - tumor nests present on the right side with non-neoplastic liver on the left side; B: H and E, 10 × - peripheral small cells with hyperchromatic nuclei with mature appearing hepatocytes in the center; C: CK7, 4 × - scattered expression of CK7 by tumor cells; D: CK19, 4 × - patchy staining of the tumor and highlighting small tumor cells located at the periphery. Tumor was also positive for Hep-Par1 (not shown). H and E: Hematoxylin and eosin.

Figure 3

Combined hepatocellular-cholangiocarcinoma with stem cell features, intermediate subtype. A: H and E, 4 × - tumor is present in trabecular/nested pattern on the right side with ill-formed gland like structures seen on the left side; B: H and E, 10 × - tumor cells with intermediate features between hepatocytes and cholangiocytes; C: CD10, 10 × - tumor showing canalicular staining pattern for CD10 (hepatocytic marker); D: CK19, 4 × - tumor cells strongly and diffusely expressing CK19 (chlolangiocytic marker). Focal tumor cells were positive for Hep-Par1 and CD56 (not shown). H and E: Hematoxylin and eosin.

Figure 4

Combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiocellular subtype. A: H and E, 4 × - tumor cells present in tubular, anastomosing (antler-like) pattern; B: H and E, 10 × - small hyperchromatic tumor cells with high nuclear to cytoplasmic ratio present within dense fibrous stroma; C: CK7, 10 × - tumor is diffusely positive for CK7; D: CD56, 10 × - CD56 staining the cholangiolocellular component as well as the tumor cells at the periphery of the trabeculae. The tumor was diffusely positive for CK19 while negative for HepPar-1 and AFP (not shown). H and E: Hematoxylin and eosin.