A study of the histopathogenesis of carcinoid tumors of the small intestine and appendix

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Abstract
A specimen from the small intestine with multiple (three) classic carcinoid tumors and one appendiceal carcinoid tumor displaying argentaffinity, argyrophilia (Grimelius stain), and serotonin and neuron specific enolase immunoreactivity was examined by light microscopy with regard to the tumor cell histopathogenesis. The smallest tumor (diameter 0.5 cm) from the small intenstine was cut into 512 and the appendiceal tumor into 511 serial sections, which were stained with the argyrophil technique. In the small intestine an increased number of endocrine cells and small proliferating aggregates of endocrine cells were observed among nonendocrine enterocytes in the crypts of Lieberkühn. They seemed to grow initially inside the crypts and to later infiltrate through the basement membrane into the lamina propria of the mucosa. This finding suggests that classic carcinoid tumors of the small intestine develop from mucosal endocrine (enterochromaffin) cells. Since proliferating argentaffin cells were also seen in the mucosal crypts in one of the other two carcinoid tumors (2 cm in diameter) in the same intestine specimen, it is suggested that when multiple carcinoid tumors occur in the small intestine they arise from multiple sites. There was no apparent connection between the mucosal crypts and the carcinoid tumor of the appendix. Thus in this particular case, the appendiceal carcinoid tumor did not appear to derive from the mucosal endocrine cells but from the subepithelial endocrine cells that are present in the lamina propria and submucosa of the appendix wall. Supporting this view is the fact that S-100 protein immunoreactive cells are found both in close relation to subepithelial endocrine cells and as an integral component of appendiceal carcinoid tumors.