Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy

OBJECTIVE: To determine whether highly well differentiated hepatocellular carcinoma can be distinguished from benign hepatocellular lesions on fine needle aspiration biopsy (FNAB). STUDY DESIGN: Ninety-five FNABsfrom 88 patients with hepatic masses/diffuse conditions were reviewed according to new cytologic criteria established by Takenaka et al. They were classified into well-, moderately and poorly differentiated hepatocellular carcinomas (W-, M-and P-HCC) and benign aspirates and histologically verified. RESULTS: There were 21 W-HCC, 39 M-HCC, 10 P-HCC, 3 problematic and 22 benign aspirates. The most useful criteria for diagnosing highly W-HCC were architectural features on the smears/cell block sections, including hypercellularity; arborescent, cohesive clusters; broad trabeculae; transgressing and peripheral endothelium; and cytologic details of small, monotonous hepatocytes with nuclear crowding, decreased cytoplasm, increased nuclear/cytoplasmic ratio, atypical naked nuclei and tumor giant cells. Well-defined cytoplasmic borders, abundant thick and monotonous cytoplasm, eccentric nuclei, thick nuclear membranes, irregular nuclear contours, increased chromatin density, irregular chromatin distribution and macronucleoli were not always detectable in highly W-HCC. In fact, some of them were seen in dysplastic hepatocytes. Deficient reticulin patterns and diffuse sinusoidal CD34 reactivity were helpful. CONCLUSION: Experience, attention to architectural and cytologic details in smears/cell blocks and clinicopathologic correlation should reduce the number of indeterminate reports. However, there will always remain some cytohistologically challenging cases.