Fine-needle aspiration cytomorphology of clear-cell hepatocellular carcinoma

The clear-cell type of hepatocellular carcinoma is an uncommon variant of hepatoma that can be confused with other clear-cell malignancies. We report on 4 cases of clear-cell hepatocellular carcinoma diagnosed by computed tomography (CT)-guided fine-needle aspiration (FNA) biopsy. All 4 patients were men with a median age of 71 yr (age range 66-76 yr). Three patients presented with a solitary liver mass and no known extrahepatic primary malignancies. The fourth patient, previously diagnosed with non-A, non-B posttransfusion hepatitis, presented with an irregular firm liver and abnormal serum liver function tests. Cytologically, all cases were characterized by hypercellular smears consisting of loosely cohesive groups and individually scattered malignant cells demonstrating anisonucleosis, nuclear hyperchromasia and irregularity, prominent nucleoli, and abundant finely vacuolated to clear cytoplasm. Immunocytochemical staining in three cases revealed focal positivity of the malignant cells for cytokeratin (AE1/3) and alpha-fetoprotein in one case. Electron microscopy (EM) was performed in all cases and revealed ultrastructural features consistent with hepatocellular differentiation. The cytologic differentiation of clear-cell hepatocellular carcinoma from metastatic clear-cell malignancies of renal, ovarian, and adrenal origin, among others, is presented. In addition, EM and immunocytochemistry study of the aspirated material can aid in establishing the correct diagnosis, thereby facilitating appropriate clinical management.