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. 2020 Dec;19(4):478-485.
doi: 10.1007/s11901-020-00556-4. Epub 2020 Oct 31.

A Contemporary Approach to Diagnosis and Treatment of Combined Hepatocellular-Cholangiocarcinoma

Olga Raevskaya  1 , Henry Appelman  2 , Nataliya Razumilava  1
Affiliations

A Contemporary Approach to Diagnosis and Treatment of Combined Hepatocellular-Cholangiocarcinoma

Olga Raevskaya et al. Curr Hepatol Rep. 2020 Dec.

Abstract

Purpose of review: To provide updates on terminology, epidemiology, diagnosis, and treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA).

Recent findings: cHCC-CCAs are tumors that in the same nodule contain a variable degree of HCC and CCA components with a transition zone. cHCC-CCAs develop in cirrhotic and non-cirrhotic livers like and is associated with poor outcomes. Mutations in TP53, TERT promoter, and ARID1A are the most common genetic aberrations in cHCC-CCA. Fusion gene PTMS-AP1G1 is unique for cHCC-CCA. A biopsy is required for diagnosis. Surgical resection remains treatment of choice, while liver transplantation for early cHCC-CCA is associated with favorable outcomes. Gemcitabine-based therapy shows benefits for advanced cHCC-CCA.

Summary: cHCC-CCAs are a heterogeneous group of primary liver cancers with unique biological behavior. Multicenter studies are required for a molecular analysis to inform novel therapeutic approaches, and understand epidemiology and benefits of liver transplantation, liver-directed and targeted therapies for this rare aggressive cancer.

Keywords: genetic aberrations; liver transplantation; loco-regional therapy; mixed liver cancer; primary liver cancer.

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Conflict of interest statement

Conflict of Interest Olga Raevskaya, Henry Appelman, and Natalita Razumilava declare that they have no conflict of interest

Figures

Figure 1.
Figure 1.
Combined hepatocellular and cholangiocellular carcinoma (hematoxylin and eosin staining). A. Hepatocellular (arrows) and cholangiocellular (arrowheads) components are present in the same tumor (100x magnification). B. A cholangiocellular tumor component demonstrates distinct tubular structures with lumens (arrowheads; 200x magnification). C. A hepatocellular tumor component demonstrates Mallory-Denk bodies (arrows; 400x magnification).
Figure 2.
Figure 2.
Characteristics of cHCC-CCA.
See this image and copyright information in PMC

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References

    1. H.G W, Primary carcinoma of the liver. Am.J.M.Sc, 1903. 26(126): p. 403–417.
    1. Brunt E, et al., cHCC-CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology, 2018. 68(1): p. 113–126. - PMC - PubMed

    2. A latest consensus document on a uniform cHCC-CCA terminology.

    1. Nagtegaal ID, et al., The 2019 WHO classification of tumours of the digestive system. Histopathology, 2020. 76(2): p. 182–188. - PMC - PubMed

    2. A manuscript summarizing the World Helath Organization recommendations on cHCC-CCA classification and diagnosis.

    1. Sasaki M, Sato Y, and Nakanuma Y, Mutational landscape of combined hepatocellular carcinoma and cholangiocarcinoma, and its clinicopathological significance. Histopathology, 2017. 70(3): p. 423–434. - PubMed

    2. An important work providing information on genetic abbeartions in cHCC-CCAs.

    1. Moeini A, et al., Mixed hepatocellular cholangiocarcinoma tumors: Cholangiolocellular carcinoma is a distinct molecular entity. J Hepatol, 2017. 66(5): p. 952–961. - PubMed

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