Combined hepatocellular‐cholangiocarcinoma: A clinicopathological study

Abstract

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16-79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n = 18) of tumours were 'mixed' tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a 'fibrolamellar' tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin-producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin-negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum alpha-fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC-CC were short. In conclusion, HCC-CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.

Clinicopathologic study of mixed hepatocellular and cholangiocellular carcinoma: Modes of spreading and choice of surgical treatment by reference to macroscopic type

“…In addition, Maeda et al [2] demonstrated that the prognosis of cHCC-CCC, including MHC, is intermediate between that of standard HCC and that of CCC. Only a few studies of MHC have been reported [4,6,7,10]. To date, the clinicopathologic features, appropriate surgical treatment, and outcome of cases of MHC have not been fully clari®ed.…”

“…Some investigators have suggested that the clinical features of cHCC-CCC, including MHC, resemble those of HCC rather than CCC since most cases of MHC are accompanied by chronic liver disease related to hepatitis due to viral infection, as well as elevated serum levels of alpha-fetoprotein (AFP) [2,4]. In addition, Maeda et al [2] demonstrated that the prognosis of cHCC-CCC, including MHC, is intermediate between that of standard HCC and that of CCC.…”

A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma

“…Although this entity does demonstrate pathologic features of its well-established biphenotypic counterparts, the characteristics of this neoplasm make diagnosis challenging using conventional radiologic imaging and serologic markers. Moreover, accurate prognostic information is affected by the low frequency of this tumor, which restricts available clinical information even within Original Article A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma large medical centers (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Prior studies have examined the role of cytoskeletal stability, apoptosis, and the inflammatory cascade in HCC-CC (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Additionally, as HCC-CC poses a diagnostic dilemma for radiologists, tumor specific biomarker may assist in the diagnosis of this neoplasm and prognostic assessment (23,24).…”

Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

“…HCC is hepatocyto-origin, and ICC is from the epithelium of the intrahepatic bile duct. CHC is a rare type of liver cancer with features of both hepatocellular and biliary differentiation (1)(2)(3). The pathological structure of CHC is composed of hepatocellular element showing bile production, an intercellular bile canaliculi or trabecular growth pattern and cholangiocellular component showing mucin production or gland formation.…”