Divergent differentiative histogenetic lines in lung tumors: identification of histotypes with pure or mixed ultrastructural phenotype and their prognostic significance.

We performed an electron microscopic study of 50 lung tumors, previously diagnosed by light microscopy, and compared the results of the two techniques. Data analysis identified two ultrastructural phenotypes: pure and mixed. The former was characterized by a constant differentiative pattern and the latter by diverging differentiative histogenetic lines. We observed six differentiative lines as follows: squamous, glandular, neuroendocrine, villopodial, intestinal, and apocrine sudoriparous. Features of divergent differentiative lines were observed in 36 cases (64%), throughout the histotypes, sometimes with coexpression of more than one differentiation in a single case and/or cell. Adenocarcinoma was the histotype most frequently observed in pure form whereas most squamous cell carcinomas showed a mixed phenotype. This suggests that the histotype of the different lung tumors arises from a single glandular pluripotent cell, able to differentiate toward divergent differentiative lines. The clinical stage at onset and at the end of the follow-up indicates that the biologic behavior of lung tumors varies according to whether the ultrastructural phenotype is pure or mixed.