Immunohistochemical and Ultrastructural Analysis of Bronchopulmonary Neuroendocrine Neoplasms. I. Carcinoids

Abstract
Strictly defined bronchopulmonary carcinoids (25) were studied for NSE (neuron-specific enolast), serotonin, and a broad spectrum of neuropeptides. Of the 25 cases 23 showed immunostaining for NSE, and 24 displayed immunostaining for at least 2 of the hormones tested for; the single case that failed to show hormonal immunoreactivity was however positive for NSE and had granules by EM. Serotonin was the most frequently demonstrated hormone followed by bombesin, vasoactive intestinal peptide, gastrin, leuenkephalin, .alpha.-MSH, somatostatin, substance P, and calcitonin. In several cases, adjacent-step sections stained for different hormones strongly indicated immunoreactivity for > 1 hormone in single neoplastic cells. By EM, all 18 cases studied showed generally abundant neurosecretory granules, which, however, displayed considerable heterogeneity in their size, shape and density. Twelve cases displayed evidence of squamous differentiation and 10 showed characteristic exocrine lumina. Single neuroendocrine tumor cells can produce > 1 immunoreactive hormone; these broad capabilities are certainly reflected in the heterogeneous granule populations seen by EM. The synchronous presence of squamous and exocrine features in bronchopulmonary carcinoids indicates that they too are capable of multidirectional differentiation, which should not detract from their being regarded basically as well-differentiated neuroendocrine neoplasms. The clinical significance of strictly defining bronchial carcinoids is underscored by the fact that of, 25 cases followed for 2-13 yr, only one developed metastases 9 yr postoperatively.