Subepithelial neuroendocrine cells and carcinoid tumours of the human small intestine and appendix. A comparative immunohistochemical study with regard to serotonin, neuron‐specific enolase and S‐100 protein reactivity

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Abstract
A comparative immunocytochemical study was performed of subepithelial neuroendocrine cells of the human small intestine and appendix and carcinoid tumours of these sites, using a monoclonal antibody to serotonin and polyclonal antisera against neuron‐specific enolase (NSE) and S‐100 protein. Subepithelial neuroendocrine cells were easily identified in the lamina propria of the appendix. These cells, which sometimes occurred in aggregates, displayed serotonin and NSE immunoreactivity and were surrounded by S‐100 protein immunoreactive cells, presumably of Schwann cell origin. In the appendix scattered cells with corresponding morphological features and immunoreactivity were also observed deep in the submucosa. In addition, subepithelial neuroendocrine cells were sparsely present in the lamina propria of the small intestine, occurring only as single cells in the deeper part of the mucosa below or between the epithelial crypts. Most appendiceal carcinoid tumours (11 of 12 examined cases) were biphasic and consisted of neuroendocrine tumour cells with intermingled S‐100 protein immunoreactive cells (Schwann cells) with long cytoplasmic extensions. However, small intestinal (11 cases) and caecal (10 cases) carcinoids lacked S‐100 protein immunoreactive cells as an integral component. The results indicate that the appendiceal carcinoids are mostly closely related structually to the subepithelial neuroendocrine and Schwann cell aggregates of the lamina propria and are thus presumed to be histogenetically related to this cell system, while the histogenesis of small‐intestinal and caecal carcinoids remains less clear.