Primary liver tumour of intermediate (hepatocyte—bile duct cell) phenotype: a progenitor cell tumour?

Abstract

A 57-year-old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte-type cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.In the rat, the presence of a stem cell (bipotential progenitor cell) compartment is widely accepted (1-3). These cells have a phenotype intermediate between fetal hepatocytes and bile duct cells and are also called oval cells because of their shape (4-7). In v i m and in vivo rat experiments have shown that progenitor cells (oval cells) in the rat can give rise to malignant primary liver tumours with a range of phenotypes, concordant with their multipotential nature (8-11). In human liver, we previously found evidence for the existence of a human counterpart of rat progenitor cells (12-19). We now describe a primary liver tumour, consisting of a n immature cell type, displaying features of both hepatocytes and bile duct epithelial cells. The tumour had a fulminant clinical course. The existence of such a type of primary neoplasm is another argument in favour of a human progenitor cell. Furthermore, this case illustrates the importance of immunohistochemical and ultrastructural phenotyping, since morphologically, the small relatively uniform cell type and the trabecular growth pattern posed the differential diagnostic problem with a neuroendocrine carcinoma. Case report Clinical historyA 57-year-old woman was admitted to the hospital because of painless obstructive jaundice and mild mesogastric pain irradiating t o the right flank. She complained of general weakness. These symptoms were only present for a few days prior to admission. She lost 4 kg of weight. There was n o history of gynaecological disorders, change in bowel habits, o r other sympto...

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