Histogenesis of the papillary Clara cell adenoma.

Mouse lung adenomas have two characteristic histologic patterns, 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. The author recently presented evidence 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 sixteenth day of gestation by a single transplacental exposure to ethyl-nitrosourea. The animals were killed from the seventh 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 either 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-month observation period the overall proportion of alveolar and Clara cell tumors was similar to that found in the first 3 weeks of life. These data support the concept that alveolar and papillary tumors arise from different cell lines, the papillary tumors exclusively from Clara cells.