[The role of perisinusoidal (Ito) cells in the course of hepatocellular carcinoma: light and electron microscopic data to the pathogenesis of hepatocellular carcinoma].

The clinical history of a 49 year old female patient suggested a multifocal, rapidly progressive liver disease of one month duration, apparently due to metastatic tumour. An open needle biopsy of the liver revealed a primary hepatocellular carcinoma of low grade malignancy; the diagnosis was confirmed by histological, immunohistochemical and electron microscopic studies. Besides the ultrastructural examination of the liver biopsy disclosed an unusually marked proliferation of perisinusoidal (Ito)-cells. The authors assume that the myofibroblast proliferation and transformation of Ito-cells in the noncirrhotic liver led to the formation of multifocal areas. The perisinusoidal cell proliferation was presumably due to vitamin A intoxication caused by an extreme vegetarian diet (daily consumption of large amounts of carrot juice for years, as disclosed by a retrospectively obtained history). It is assumed that the vitamin A abuse, and perisinusoidal cell proliferation may have promoted the unusually rapid progression of the multifocal, but histologically low grade hepatocellular tumour. Spectacular clinical improvement could be observed after chemotherapy, combined with local hyperthermic treatment. Presumably, the change in diet (cessation of excessive retinol and carotene intake) also may have had a beneficial effect. After one year the clinical course suggests a slower progression of tumour growth which would be more in keeping with the prognosis based on the histologic appearance of the low grade hepatocellular carcinoma. This patient's case illustrates the importance of electron microscopy supplementing diagnostic histological and immunohistochemical examinations.