Combined hepatocellular cholangiocarcinoma: Controversies to be addressed

Table 1 Evolution of classification of combined hepatocellular cholangiocarcinoma

Ref.	Classification
Allen et al[5], 1949	Separate masses
	Contiguous but independent masses
	Intimate intermingling of hepatocellular and glandular element
Goodman et al[3], 1985	Collision tumors, a coincidental occurrence of both HCC and CC in same patient
	Transitional tumors including areas of intermediate differentiation
	Fibrolamellar tumors, having features of fibrolamellar HCC and CC
Liver Cancer Study Group of Japan[10] 1989	Double cancer
	Combined type
	Mixed type
WHO[6] 2010	CHC-classical: typical HCC and typical CC
	CHC-SC
	CHC-SC-typical: nests of mature looking hepatocytes with peripheral clusters of small cells that have a high nucleus:cytoplasm ratio and hyperchromatic nuclei
	CHC-SC-int: tumor cells show features intermediate between hepatocytes and cholangiocytes. These tumor cells show strands, solid nests and/or trabeculae of small, uniform cells with scant cytoplasm and hyperchromatic nuclei
	CHC-SC-CLC: admixtures of small monotonous glands, antler-like anastomosing patterns. Each tumor cell is cuboidal, smaller in size than normal hepatocytes, with a high nucleus: cytoplasm ratio, and distinct nucleoli

CHC: Combined hepatocellular-cholangiocarcinoma; CHC-SC-typical: Combined hepatocellular-cholangiocarcinoma, stem cell features, typical subtype; CHC-SC-int: Combined hepatocellular-cholangiocarcinoma, stem cell features, intermediate cell subtype; CHC-SC-CLC: Combined hepatocellular-cholangiocarcinoma, stem cell features, cholangiolocellular subtype; HCC: Hepatocellular carcinoma; CC: Cholangiocarcinoma.