Lipid-rich hepatocellular carcinoma in fine-needle aspiration biopsy.

The histology of hepatocellular carcinoma is typically characterized by thickened trabeculae of malignant hepatocytes in a background of a cirrhotic liver. Hepatomas are divided by the World Health Organization into well, moderately, poorly, and undifferentiated grades. Four common architectural patterns such as trabecular, solid, pseudoglandular, and scirrhous, and three cytologic variants such as pleomorphic, clear cell, and sarcomatoid are recognized. In the clear cell variant, cytoplasmic alterations are related to glycogen and/or lipid accumulation within the lesional cells. Clear cell variants of hepatocellular carcinoma are most often low-grade. In limited cytologic samples of low grade, lipid-containing hepatic malignancies, the separation of neoplastic cells from benign steatotic cells (as may be encountered with focal hepatic steatosis) can be extremely challenging. A 78-year-old woman with a documented history of hepatocellular carcinoma presented with a new 1.5 cm, PET positive nodule in the right lobe of the liver. She had undergone left hepatic lobectomy (six years remote) for a 7-cm well-differentiated hepatocellular carcinoma and more recently (one year prior) had undergone a right hepatic lobe wedge resection for recurrent disease. A radiologically guided fine-needle aspiration biopsy of the new liver nodule was performed. The air-dried Diff-Quik stained slides revealed scattered bland hepatocytes with abundant vacuolated cytoplasm (Fig. C-1). An immediate interpretation was rendered as hepatocytes present, with a considered differential diagnosis of a lipid-containing hepatoma versus steatosis. Alcohol-fixed Papanicolaou stained slides showed a strikingly uniform and deceptively bland population of neoplastic hepatocytes with micro and macro-vesicular steatotic changes (Fig. C-2). Correlations with slides from the patient’s previously resected recurrent hepatocellular carcinoma confirmed the nuclei in the known malignant cells to be deceptively innocuous and the cytoplasm in these same cells to be lipid-rich (Fig. C-3). Differentiation of well-differentiated hepatocellular carcinoma from benign changes including steatosis has been studied by Yang et al. They found that fineneedle aspiration biopsies of benign lesions contained rigid cores and large tissue fragments in contrast to welldifferentiated hepatocellular carcinoma in which there was a breakdown of the reticulin framework with scattered cells and a fine granular appearing background. Lipid-rich hepatocellular carcinoma is an uncommon variant, and it is possible that lesional cells from this entity may be under diagnosed as simple steatosis (Fig. C-4). This case highlights this potential pitfall.