Extraepithelial intraneural endocrine cells as starting-points for gastrointestinal carcinoids

Endocrine cells can be demonstrated by light- and electron microscopy in the lamina propria of the mucosa of the appendix. They are always in direct contact with a nerve fibre. The endocrine cell (type EC1 and EC2 cell) and the polyaxonal non-myelinated nerve fibre are separated from the interstitial connective tissue by a common continuous basal lamina. The term "ECC-NF complex" ("EC cell-nerve fibre complex") is suggested by the authors to describe this morphological unit. The intraneural endocrine cells may be derived from neuroendocrine-programmed ectoblasts (Pearse, 1977). The electron microscopic demonstration of these "ECC-NF complexes" in carcinoid tumours of the appendix and of similarly structured "eC-NF complexes" ("endocrine cell-nerve fibre complexes") in carcinoids of the rectum allows us, following the demonstration of small nerve fibres within carcinoids of the appendix, caecum and rectum (and bronchus) to propose a hypothetical pathogenesis of gastrointestinal carcinoid tumours from these intraneural endocrine cells. Carcinoid tumours may develop by proliferation of the intraneural endocrine cells with microcarcinoids as intermediate stages. In this way the histogenesis of the carcinoids is located a priori in the subepithelial stroma. Nerve fibres are morphological markers of this proposed mechanism. Assuming a neuroectodermal cytogenesis for the intraneural endocrine cells we therefore also postulate a histogenesis of the carcinoids from the neuroectoderm.