Update on the Diagnosis and Treatment of Combined Hepatocellular Cholangiocarcinoma

Abstract

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern. Histopathological examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA, and comprehensive examination of resection or biopsy specimens is crucial for an accurate diagnosis. Currently, there is no standard treatment for cHCC-CCA, and surgery is the mainstay. Anatomic hepatectomy with lymphadenectomy is among the recommended surgical procedures. The role of liver transplantation in the management of cHCC-CCA is still uncertain. Transarterial chemoembolization may be effective for unresectable cHCC-CCA, particularly for hypervascular tumors. However, the available evidence does not support systemic therapy for advanced cHCC-CCA. The prognosis of cHCC-CCA is generally poor, and there is no established staging system. Further research is needed to better understand the histogenesis and clinical management of cHCC-CCA. This review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics, pathological diagnosis, and management.

Keywords: Clinical characteristics; Combined hepatocellular-cholangiocarcinoma; Imaging characteristics; Pathological diagnosis; Treatment.

Fig. 1. A cHCC-CCA lesion as shown on MRI.

(A) An irregular hyperintensity tumor on T2-weighted imaging. During contrast study, the lesion shows heterogenous enhancement in the arterial phase (B), and mixed washout and persistent enhancement in the portal phase (C) and delayed phase (D). cHCC-CCA, combined hepatocellular cholangiocarcinoma; MRI, magnetic resonance imaging.

Fig. 2. Figure 2.

A cHCC-CCA lesion as shown on CT. A low-density lesion on non-contrast images (A) and a heterogenous enhancement pattern in the nodule in the arterial phase (B). The enhancement of the lesion is persistent on the portal (C) and delayed phase (D). cHCC-CCA, combined hepatocellular cholangiocarcinoma; CT, computed tomography.

Fig. 3. Combined hepatocellular cholangiocarcinoma without transition zone.

(A) The HCC component shows a trabecular pattern, and the ICC component shows a tubular pattern (HE staining, 40×). (B) There is no transition zone between the HCC and ICC components (HE staining, 100×). HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocellular carcinoma; HE, hematoxylin and eosin.

Fig. 4. Combined hepatocellular-cholangiocarcinoma with a transition zone.

(A) The tumor shows both a hepatocytic differentiation area of the trabecular pattern and a cholangiocytic differentiation area of the tubular pattern (HE staining, 40×). (B) There is a transition zone between the HCC and ICC components (arrow; HE staining, 100×). HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocellular carcinoma; HE, hematoxylin and eosin.