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.

Clinical and pathological features of combined hepatocellular–cholangiocarcinoma compared with other liver cancers

“…Our results showed that the OS of patients with CHC was significantly poorer than that of patients with HCC but not significantly different from patients with ICC, while CHC was associated with a significantly poorer DFS than either HCC or ICC. Adverse clinicopathological prognostic factors associated with tumor recurrence and survival have been reported in several studies and included large tumor size (> 5 cm), presence of satellite nodules, lymph node involvement, multifocality, vascular invasion, portal vein invasion, high tumor stage, high levels of CA19‐9, decreased capsule formation, and free surgical margins < 2 cm . However, many of these factors were not significant according to multivariate analysis.…”

“…Combined hepatocellular–cholangiocarcinoma is difficult to diagnose preoperatively due to its heterogeneous imaging characteristics, with features that overlap both HCC and ICC . Thus, most CHC cases are initially misdiagnosed as either HCC or ICC, and the correct diagnosis is only reached after examination of surgical specimens.…”

“…Minor or major hepatic resection, with or without lymph node dissection, is currently the consensus recommended treatment for CHC . The outcomes following liver transplantation are consistently poorer in patients with CHC compared with HCC, and one study found no survival benefit of transplant over resection in patients with CHC .…”

Sarcomatoid combined hepatocellular carcinoma and cholangiocarcinoma of liver with spontaneous intra-tumor bleeding: a case report

“…In this case, we preoperatively considered the diagnosis of cHC based on the combined radiological features of hepatocellular carcinoma and cholangiocarcinoma, together with raised levels of both tumor markers 4) ; however, the accurate diagnosis of this rare disease remains clinically difficult. In particular, sarcomatoid changes within cHC are rarer still and more reported cases are needed to establish diagnostic radiological features.…”

Gross and microscopic changes of liver neoplasms and background hepatic structures following neoadjuvant therapy

“…Studies which have evaluated the prevalence of these tumours suggest that they comprise between 2% and 5% of all primary liver malignancies,12 22–25 and interestingly, they have been reported to occur in both cirrhotic and non-cirrhotic livers 25–27. Of note, there is minimal evidence evaluating liver transplantation and the use of neoadjuvant therapy in these tumours; when these tumours are found in hepatic explants, it is typically incidental in nature or are from patients who were misdiagnosed as having traditional HCC 28. As discussed by Brunt et al , there is a need to study the outcome of these mixed tumours following hepatic transplantation as well as their response to various locoregional therapies and modern targeted treatments 21.…”