Recognition and the histopathologic classification of ECL cell proliferations.

Among the nineteen functionally distinct endocrine cell types that populate the gastrointestinal mucosa, some (e.g., the serotonin-producing enterochromaffin (EC)b cells, and the somatostatin-producing D cells, etc.) are dispersed diffusely all along its length, while others (e.g., the histamine-producing enterochromaffin-like (ECL) cells, the gastrinproducing G cells, the secretin-producing S cells and the cholecystokinin-producing I cells) have a much more restricted distribution and are confined to specific segments or anatomic locations (Figure 1). Since the secretory products of these cells act as chemical messengers to orchestrate the absorptive, secretory and propulsive functions of the gut, both the distributional pattern and the numerical density of the various cell types is preordained by the physiologic needs pertinent to a given anatomic segment or site [1]. Thus the oxyntic (acid-producing) portion of the human gastric mucosa contains at least six ultrastructurally distinct endocrine cells types: the EC cells, the ECL cells, the D cells, the D1 cells, the P and the X cells. The vast majority of these cells are dispersed randomly in the middleand lower-third of the mucosal thickness, and only occasional endocrine cells are seen in the superflcial third of the oxyntic mucosa. Rare stray endocrine cells have additionally also been described in association with nerve fibers and Schwann cells (neuroendocrine complexes) in the lamina propria [2, 3]. The entire endocrine cell population of the oxyntic mucosa can be visualized by immunohistochemical stains for such markers of neuroendocrine differentiation as chromogranin A, neuron specific enolase, synaptophysin and pancreatostatin, etc., and can be dissected into its component cell types by their specific histochemical or immunohistochemical profiles (Figure 2). Histochemically, while these cells are argyrophil in nature, not all of them can be simultaneously identified by any one argyrophil stain. Thus, the Grimelius stain identifies all oxyntic endocrine cells except the D cells that show argyrophilia only with the Hellerstrom-Hellman technique. The Sevier-Munger technique for argyrophilia, on the other hand, selectively stains the ECL cells and a small subset of the EC and D1 cells (Figure 2). However, since the relative proportion of the EC and D1 cells stained by this technique is negligible, the Sevier-Munger stain is currently regarded as more or less specific for ECL cells in formalin-fixed, paraffin-embedded tissues processed for light microscopy. However, since the Sevier-Munger stain is technically difficult and somewhat capricious, most workers rely on the Grimelius stain for visualizing ECL cells, realizing fully well that the number of positively stained cells is not an accurate depiction of their numbers since this technique also stains other argyrophil cells in the oxyntic