Diagnostic and Prognostic Value of DNA Ploidy and Cell Nuclearity in Ultrasound-guided Liver Biopsies

Background: Focal nodule lesions in patients with cirrhotic livers may be visualized by using imaging techniques; however, the diagnostic and prognostic judgment of biopsies from borderline lesions may be difficult using conventional histologic criteria.

Methods: The diagnostic and prognostic value of DNA ploidy analysis determined by image cytometry of Feulgen-stained isolated hepatocytes was investigated in ultrasound-guided biopsies from 50 nodular lesions found in patients with cirrhotic livers (39 hepatocellular carcinomas [HCCs] and 11 macroregenerative nodules) and from 10 patients with livers affected by viral chronic hepatitis. Of the 11 macroregenerative nodules, 7 presented a subsequent neoplastic behavior. Specimens from the morphologically normal livers of five patients who underwent liver surgery served as control tissues. Image cytometry was performed on Feulgen-stained cytologic preparations, obtained by enzymatic digestion of formalin fixed biopsies. The DNA ploidy of the main stem line and the distribution of mononucleated and binucleated hepatocytes (nuclearity) were compared using histologic diagnosis, Edmondson's grade, tumor size, and patient follow-up.

Results: The main stem line was peridiploid in all benign specimens and in 31 clinically confirmed HCCs, peritetraploid in 11 HCCs, perioctaploid in 1 HCC, and aneuploid in 3 HCCs. The fraction of mononucleated polyploid hepatocytes was found to be the best diagnostic parameter in euploid HCCs and was significantly correlated with the Edmondson grade and the nodular size. Survival information was available for 43 patients, with a median observation period of 350 days. A DNA ploidy value of the main stem line greater than 3c was an important determinant of survival as a single parameter and in association with histologic grade and greatest dimension of tumor.

Conclusions: This study suggests that the ploidy distribution analysis of mononucleated and binucleated hepatocytes can provide valuable information for making correct diagnoses and for predicting survival outcome for patients with HCCs.