HISTOGENESIS OF THE PAPILLARY CLARA CELL ADENOMA

Abstract

Mouse lung adenomas have 2 characteristic histologic patients, alveolar and bronchiolar or papillary. Differences in biologic behavior have been noted in tumors of different histologic form, in that papillary tumors were said to grow faster and become larger and possibly malignant. Progressive development from the alveolar to the papillary tumors has been proposed, involving a step-wise transformation from benign to malignant tumors. Evidence was presented from ultrastructural studies that the different histologic patterns were related to the cell of origin; the bronchiolar tumors consisted of Clara cells, while the alveolar tumors were made up of Type II alveolar epithelium. In the present study, designed to evaluate the histologic patterns of tumors during their development, multiple lung adenomas were induced in fetal Bagg-Webster mice on the 16th day of gestation by a single transplacental exposure to ethylnitrosourea. The animals were killed from the 7th postnatal day to 185 days of age; their tumors were counted and categorized histologically. Analysis of serial-step sections of the right lower lobes of young postnatal mice showed tumors with an alveolar (37%) or a bronchiolar pattern (63%). Two forms of the latter were recognized, tubular and papillary. Between day 80 and day 186 papillary adenomas increased, tubular tumors decreased and alveolar adenomas remained relatively constant in number. At the end of the 6 mo. observation period the overall proportion of alveolar and Clara cell tumors was similar to that found in the first 3 wk of life. Alveolar and papillary tumors apparently arise from different cell lines, the papillary tumors exclusively from Clara cells.