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

Acta Cytol. Jan-Feb 2003;47(1):16-26. doi: 10.1159/000326470.


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 FNABs from 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.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Adolescent
  • Aged
  • Aged, 80 and over
  • Biopsy, Needle*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / pathology
  • Cell Differentiation / physiology
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Female
  • Focal Nodular Hyperplasia / diagnosis
  • Focal Nodular Hyperplasia / pathology
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Pregnancy
  • Ultrasonography