There may be macronucleoli. However the nucleus to cytoplasmic ratio is normal

and the nuclear membranes are smooth, and mitotic activity is rare. There may be a background of necrotic debris, histiocytes and acute inflammatory cells. If exceedingly large polygonal cells with bizarre shaped nuclei, hyperchromasia and multinucleation are seen, liver cell dysplasia is suggested (nuclear volume ratios are in the 8:1 range) as seen in cirrhosis, hepatitis Inhibitors,research,lifescience,medical B or hepatocellular carcinoma. Hepatocellular carcinoma Hepatocellular carcinoma (HCC) accounts for 90% of all primary cancers of the liver. It is far more common in Africa and Asia, where it constitutes 20-40% of all malignancies, often in the 3rd-4th decade. In the Western world HCC accounts for 2% of all malignancies, and usually presents in the Panobinostat chemical structure 6th-7th decade. Serum alpha-fetoprotein (AFP) levels >1,000 ng/mL are virtually diagnostic, but are not always elevated. HCC is associated with cirrhosis, Hepatitis B

and C, and congenital metabolic diseases. Aspirates Inhibitors,research,lifescience,medical of HCC show increased cellularity and discohesiveness, with crowding and piling within cell Inhibitors,research,lifescience,medical groupings. A variable number of single cells may be present. The polygonal neoplastic hepatocytes are present in abnormally thick trabecular cords (Figure 2). Endothelial cells surround the abnormal trabecular cords, which are greater than three cell layers thick. Solid sheets, tubular or Inhibitors,research,lifescience,medical pseudoglandular structures may be present, resembling metastatic carcinoma. Tumor cells have granular cytoplasm, and there may be evidence of bile production. Atypical stripped hepatocyte nuclei may be seen (Figure 3). The hepatocyte nuclei are large round with prominent nucleoli.

Nucleus to cytoplasmic ratio is increased. Intranuclear inclusions may be present. 10% of HCC may have clear cytoplasm (resembling clear cell carcinomas from the kidney and adrenal cortex) (7). Spindle, pleomorphic and multinucleated tumor giant cells may be present. Figure Inhibitors,research,lifescience,medical 2 Hepatocellular carcinoma with abnormally thick trabecular cords (DQ stain, 200×) Figure 3 Hepatocellular carcinoma with cells displaying prominent nucleoli, increased nuclear:cytoplasmic ratios, and atypical stripped nuclei (Pap stain, 400×) Immunohistochemical stains DNA ligase are particularly helpful in differentiating HCC from benign lesions, other primary and metastatic malignancies. Polyclonal CEA (Figure 4), CD10, and villin stain normal and neoplastic hepatocytes in a canalicular pattern. HCC is AFP, alpha-1-antitrypsin, low molecular weight keratin, CAM 5.2 and Hep Par 1 positive. CD 34 immunohistochemical stain shows positivity in the lining sinusoidal cells. TTF-1 may show cytoplasmic positivity. Cytokeratin 7, high molecular weight keratin and keratin AE1-AE3 are negative (8-11).