Cytodiagnosis of hepatocellular carcinoma in fine-needle aspirates of the liver: its differentiation from reactive hepatocytes and metastatic adenocarcinoma

Fine-needle aspiration (FNA) cytology is a useful tool for diagnosis of primary malignancies and metastatic lesions of the liver. However, well-differentiated hepatocellular carcinoma (HCC) may resemble benign/reactive hepatocytes, and less differentiated HCC may simulate poorly differentiated adenocarcinoma, leading to difficulties in interpretation of aspirates from liver. To determine the subtle cytomorphological features which can differentiate these lesions, ultrasound-guided FNA smears from 86 cases of liver malignancy were subjected to detailed cytologic assessment. These included 20 cases of HCC, 38 cases of metastatic adenocarcinoma, and 28 cases of benign/reactive hepatocytes. The important features for separating HCC or well-differentiated HCC from benign/reactive hepatocytes were excessive cellularity, trabecular pattern vs. thin cords of hepatocytes, nuclear pleomorphism, atypical stripped nuclei, and macronucleoli (P < 0.001 to < 0.0001). The most significant features for differentiating HCC from metastatic adenocarcinoma were trabecular growth pattern, hepatocytic cells vs. columnar/cuboidal cells, eosinophilic granular cytoplasm, lipid vacuoles, bile pigments, and atypical stripped nuclei (P < 0.001 to < 0.0001). The cytomorphological features which may distinguish poorly differentiated HCC from poorly differentiated adenocarcinoma were polygonal (hepatocytic) cells, eosinophilic granular cytoplasm and lipid vacuoles in HCC, and columnar/cuboidal cells and acinar/glandular formation in adenocarcinoma (P < 0.05 to < 0.001). Diagn. Cytopathol. 1999;21:370-377.