Cytohistology of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a heterogeneous tumor that is often but not invariably associated with cirrhosis. Pre-operative diagnosis by fine needle aspiration or core biopsy is not mandated if dynamic imaging criteria concur with clinical expectations. Classic HCC can be well-, moderately or poorly differentiated. Variants and special types of HCCs exist. The cytohistological diagnosis of HCC can be challenging on small tissue samples. At the highly well-differentiated end, the hepatocytic histogenesis is obvious but the malignant status may not be evident. At the poorly differentiated end, malignancy is obvious but the histogenesis may be obscure. Tumor size, location and heterogeneity, radiological guidance, operator skill, type of needle, on-site cytology service with optimal sample preparation, availability of ancillary tests, and interpreter experience all contribute to the accuracy of the final diagnosis. A problem-based clinicopathological approach is recommended. Key cytohistological features, differential diagnoses, diagnostic pitfalls, and utility of ancillary tests are presented.