Atypical adenomatous hyperplasia of the lung and its differentiation from adenocarcinoma. Characterization of atypical cells by morphometry and multivariate cluster analysis.

BACKGROUND: Atypical adenomatous hyperplasia (AAH) of the human lung is considered to be an important lesion preceding adenocarcinoma, but its difference from well-differentiated adenocarcinomas is so subtle as to cause diagnostic uncertainty. In view of this, the authors undertook to establish reproducible microscopic criteria for AAH, Type II pneumocyte type, and Clara cell type adenocarcinomas.
METHODS: Twelve-parameter morphometry of atypical cells was performed on 97 lesions selected from 303 surgical specimens of lung by routine microscopic examination: all were considered by premorphometry examination to correspond to one of the above three diseases. Measurements were performed on photomicrographs using a digital image analyzer. The data of morphometry were subjected to 12-variate cluster analysis using a mainframe computer.
RESULTS: It was demonstrated that the lesions were classifiable into three groups: Cluster 1 (Type II cell adenocarcinoma and AAH), Cluster 2 (AAH), and Cluster 3 (Clara cell adenocarcinoma). Whereas the latter two were created as homogeneous clusters, Cluster 1 was a mixture of Type II tumors and AAH.
CONCLUSIONS: AAH in the strict sense of the word is definable by the features of those classified into Cluster 2, with atypia milder than overt adenocarcinomas. These AAH are likely to correspond to one of the steps of carcinogenesis forgoing the final one. The lesions, diagnosed as AAH before morphometry and being assigned to Cluster 1 and therefore not separable from Type II carcinoma, are considered to have been Type II carcinoma from the very beginning, which were however underdiagnosed in routine microscopic examination.