Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms

The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by the solitary neuroendocrine cells and the neuroepithelial bodies (NEBs). Immunohistochemically, neuron-specific enolase, serotonin, bombesin, and calcitonin are demonstrable in both components, whereas leu-enkephalin is demonstrable only in solitary NE cells. The precise function of and interplay between these two components under physiologic and pathologic conditions are not entirely clear. Current indications are that NEBs act as intrapulmonary chemoreceptors sensitive to hypoxia and hypercapnia, whereas solitary NE cells may have a paracrine, regulatory function. Even less clear is the possible role of solitary NE cells and NEBs in the processes associated with intrauterine and neonatal pulmonary growth and maturation. Various experimental manipulations have resulted in proliferation of solitary NE cells and NEBs. Of particular interest is the apparently selective proliferative effect on NEBs shown by several nitroso compounds. Diethylnitrosamine administration to hamsters for several weeks results in an increase in the number of NEBs and an increase in the number of cells per NEB. These hyperplastic NEBs express the same immunoreactive hormones as their normal counterparts. However, when NEB cells from diethylnitrosamine-treated hamsters are cultured in vitro a notable proportion of the resulting endocrine cells express ACTH immunoreactivity. Interestingly, the neoplasms that eventually develop in these hamsters are not comprised of NE cells. Studies on human bronchi from specimens resected for various types of neoplasms and for bronchiectasis with and without associated chronic obstructive pulmonary disease have revealed frequent hyperplasias of solitary NE cells and NEBs. In about 10% of the specimens, dysplastic aggregates of solitary NE cells and NEBs are found. Unexpected "microcarcinoids" and tumorlets are also seen. The mildly and moderately hyperplastic solitary NE cells and NEBs tend to express the hormones indigenous to the bronchi, whereas in the severely hyperplastic and dysplastic cells, "ectopic" hormones may also be expressed; the latter include predominantly ACTH and vasoactive intestinal polypeptide. A distinct hyperplasia of NEBs has been found in the lungs from individuals living at altitudes ranging from 3400 to 4300 meters; these changes may represent an adaptive response to chronic hypoxia parallel to the hyperplastic carotid paraganglia that may be found in the same type of population. Bronchopulmonary NE neoplasms comprise a spectrum that includes typical carcinoids, well-differentiated NE carcinomas, and NE carcinomas of intermediate and small cell types. Typical carcinoids are predominantly central, display little if any pleomorphism, are richly granulated by electron microscopy, and by immunohistochemistry express predominantly, although not exclusively, hormones indigenous to their site of origin.(ABSTRACT TRUNCATED AT 400 WORDS)