Clear-cell hepatocellular carcinoma

Fig. 12.3. Acinar clear-cell hepatocellular carcinoma. Clear-cell hepatocytes are arranged in glands with lumen filled by biliary plugs (X120)...

A 39-year-old army officer had bouts of palpitation and dizziness. There were no risk factors for chronic liver disease apart from a family history of hemochromatosis. His cardiovascular and nervous systems were normal but there was 5 cm hepatomegaly. Percutaneous liver biopsy showed grade 4 siderosis in parenchymal and non-parenchymal liver cells and a mild inflammatory infiltrate with minimal portal fibrosis. He had 45 liters of blood venesected over the next 18 months and a repeat biopsy 3 years later showed a non-cirrhotic liver with no stainable iron. He developed a non-resectable primary hepatocellular clear cell carcinoma 17 years after the initial diagnosis. 

Carcinomas that are almost invariably negative but may occasionally show rare CK7-positive cells include hepatocellular carcinomas, duodenal ampullary carcinomas, colon carcinomas, renal (clear cell type), prostate, and adrenal cortical tumors. 

FIGURE 8.18 Hepatocellular carcinoma with clear cell features (A) showing granular cytoplasmic positivity for HepParl (B). 

Hepatocellular carcinoma (HCC) is the single most common histologic type of epithelial primary liver tumor. Architecturally, HCC may have a number of different patterns, the most common being a trabecular or plate-like pattern. Other patterns include acinar, pseudoglandular, scirrhous, clear cell, spindle cell, and pleomorphic. ... 

Marked disturbances in the distribution of ploidy (diploid and tetraploid nuclei) have been observed in the livers of male Sprague-Dawley rats fed a dietary concentration of 100 ppm mirex (equivalent to 5 mg/kg/day) for 13 months (Abraham et al. 1983). Mirex selectively reduced the number of tetraploids with the most significant reduction noted in hepatocellular carcinomas however, nuclei in the areas adjacent to these tumors were also primarily composed of diploids. These data should be interpreted with caution since isolation of nuclei from tumors is difficult and because "of the fantastic variety of forms that tumor nuclei assume" (Smuckler et al. 1976). Similarly, the relevance to humans is not clear since human liver is mainly composed of diploid cells (99%) and contains few tetraploids (Adler et al. 1981). 

In animal studies aldrin induced an increased incidence of hepatocellular carcinoma at two dietary doses in male mice the tumors showed a significant dose-response trend and were statistically significant at the high dose. Follicular cell tumors of the thyroid and adrenal cortical cell adenomas were increased in female rats in the low-dose group but not in the high-dose group the results could not be clearly associated with treatment. ... 

The compound saikosaponin d induced apoptosis in human hepatocellular carcinoma cells (HepG2) through the activation of caspases 3 and 7, resulting in poly(ADP-ribose)-poly-merase (PARP) cleavage. DNA fragmentation was clearly noted at more than 6 hours after exposure to saikosaponin d (Chiang et al. 2003). 

ViraUy induced (exogenous) cancers (hepatocellular carcinoma hepatitis C virus-induced squamous cell carcinoma of the uterine cervix or oral cavity (HPV-induced) are preventable with vaccines-induced immunity. The exogenously enforced virally induced cancers are reacted to with the induction of strong host immune defense, whereas the endogenously induced cancers often receive support from the subverted host, a reaction that a cancer vaccine is expected to break and reverse [1994-2000]. Some cancer vaccines caused tumor enhancement. Many cancer vaccines failed [2001a]. It is not clear at all what purpose the new review Cancer Vaccines served [2001b]. 

Among the palliative therapy regimens of hepatocellular carcinoma (HCC), the intra-arterial application of iodine-131-lipiodol ( l-lipiodol) has been established, particularly in Asia and in French-speaking Europe (Lambert and Van de Wiele 2005). Lipiodol (Laboratoire Guerbet, France) is a poppy seed oil containing 38% iodine by weight. It was first used as an X-ray contrast medium for hepatic angiography and has been shown to be cleared less rapidly from HCC cells than normal liver tissue, when injected into the hepatic artery (Nakakuma et al. 1985 Okayasu et al. 1988). 

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