To the Editor:
We read with great interest the recent report of an unusual primary liver carcinoma with a mixed population of malignant cells with hepatocyte as well as bile duct cell morphology throughout the tumor (Allen Type C).[1] The case sparked our curiosity regarding the immunohistochemical profile of this unusual malignancy, which could provide further evidence of its differentiation and cell of origin. Indicators of hepatocellular cell differentiation are positive immunostaining for HepPar1 (80%), a canalicular pattern of pCEA (83%), or AFP (42%), while the following markers are positive in many cholangiocarcinomas: CK 7 (98%), CK 19 (96%) and EMA (86%).[2] A single original clonal proliferation of mixed hepatocellular-cholangiocarcinomas has been suggested due to common allelic losses in both tumor components.[3] Hepatic progenitor cells have taken center stage as a possible cells of origin of primary liver carcinomas.[4, 5] Hepatic progenitor cells are small epithelial cells with an oval nucleus, scant cytoplasm and location in the bile ductules and canals of Hering, which have the potential to differentiate towards the biliary and hepatocytic lineages.[4] Further, it is thought that liver injury leads to the recruitment of bone marrow stem cells to the liver which then differentiate into oval cells.[5] Akin to the commonly used term "hematogones" for immature B-cell precursors in the bone marrow, we propose the term "hepatogones" to be used for activated liver stem cells that may originate in the bone marrow and may be the cell of origin for mixed lineage tumors such as the case described by Zhou et al.[1]