Atypical endocrine tumors of the lung: a histologic, ultrastructural, and clinical study of 19 cases.

Lung cancers are divided by light microscopic criteria into several categories, but only two categories are recognized clinically--small cell and non-small cell carcinomas. Transmission electron microscopy has revealed unexpected complexity within each category, blurring the distinctions between them. The present study was undertaken to determine the incidence of dense-core, neuroendocrine-type granules in lung tumors diagnosed by light microscopy as non-small cell carcinomas, i.e., atypical endocrine tumors, and the clinical significance of their identification. Of 205 consecutive primary and metastatic lung cancers, 19 (9 per cent) diagnosed as non-small cell carcinomas by light microscopy were seen to contain neuroendocrine-type granules by electron microscopy and thus were reclassified as atypical endocrine tumors of the lung. Staining with silver stains, periodic acid-Schiff (PAS), PAS with diastase digestion, and mucicarmine was positive in 18, 15, 14, and eight of the 19 cases, respectively. Electron microscopy revealed glandular differentiation in 12 cases and tonofilaments in eight cases, although none of the tumors met the criteria for identification as squamous cell carcinomas. Clinically, the cancers appeared to resemble non-small cell carcinoma more closely than small cell carcinoma. Median survival (12 months) and response to combination chemotherapy (22 per cent) were in the range reported for non-small cell carcinoma. There were no complete responses, despite the use in some cases of regimens active against small cell carcinoma. However, one patient, the only one to date so treated, had a dramatic response to streptozotocin/5-fluorouracil, suggesting that, as in metastatic carcinoid, this combination may have value in the treatment of atypical endocrine tumors of the lung.