Neuroendocrine differentiation in hepatoblastoma. An immunohistochemical investigation

Hepatoblastoma exhibits a wide range of epithelial and mesenchymal lines of differentiation. Neuroendocrine differentiation in this tumor has not previously been reported. We investigated seven hepatoblastomas of different subtypes (five pure epithelial hepatoblastomas, including one small-cell hepatoblastoma, and two mixed hepatoblastomas) using a broad panel of antibodies against epithelial, mesenchymal, neural, and neuroendocrine markers, alpha-1-antitrypsin (alpha 1-AT), alpha-1-antichymotrypsin (alpha 1-ACT), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), serotonin, and 14 regulatory peptides. Chromogranin A-immunoreactive neuroendocrine tumor cells, some of which also exhibited immunoreactivity for serotonin and somatostatin, were found in the fetal and embryonal parts of the mixed hepatoblastomas. The osteoid-like material in the mixed hepatoblastomas contained cells with immunoreactivity for chromogranin A, neuron-specific enolase, keratin, and alpha 1-AT, alpha 1-ACT, AFP, and CEA, in addition to S-100 protein and vimentin. Parallels to the neuroendocrine differentiation in hepatoblastomas are found in tumors of the gastrointestinal tract and bronchopulmonary tree. These tumors may also exhibit a neuroendocrine component; that is, multidirectional differentiation may occur, as in hepatoblastoma. The immunoreactivity of some of the cells of the osteoid-like material for keratin, alpha 1-AT, alpha 1-ACT, AFP, CEA, and chromogranin A suggests that these cells--and probably the surrounding material--are of epithelial origin.