Differentiation of atypical adenomatous hyperplasia and adenocarcinoma of the lung by use of DNA ploidy and morphometric analysis.

Atypical adenomatous hyperplasia (AAH) of the lung has been regarded as a precancerous lesion of lung adenocarcinoma, but the biologic significance of this lesion is still not well understood. In this study, DNA histogram patterns and nuclear size were examined, using an image cytometer. We studied 14 cases of Type II pneumocyte hyperplasia (HP), 7 cases of adenomatous hyperplasia with slight or no nuclear atypia (AH), 21 cases of AAH, and 26 cases of adenocarcinoma. The difference in mean nuclear sizes between the HP (32.08 microns2) and the AH (32.86 microns2) was not significant but between the AH, the AAH (38.52 microns2), and the well-differentiated adenocarcinomas with mild nuclear atypia (51.12 microns2), statistically significant differences were observed (P < 0.05). Seven (33%) of the 21 cases of AAH and 22 (85%) of the 26 cases of adenocarcinoma showed aneuploid histogram patterns. The difference in the incidence of aneuploid pattern between AAH and adenocarcinomas was statistically significant (P < 0.01). All of the cases of HP and AH were diploid. Two of the seven aneuploid cases of AAH showed hyperdiploid DNA histogram patterns, and the remaining five showed polyploid histogram patterns with diploid and hyperdiploid stemlines. In these five cases, the small-sized nuclei showed a diploid stemline and the large-sized nuclei showed a hyperdiploid stemline. Our data indicated that AAH can be distinguished from HP, AH, or adenocarcinoma by morphometric analysis and that some cases of AAH that display aneuploid histogram patterns are precancerous lesions that may lead to adenocarcinoma.