Multiple gastric carcinoids and endocrine cell micronests in type A gastritis: Nuclear morphometric and immunohistochemical analysis

While the hyperplasia-neoplasia sequence of enterochromaffin-like (ECL) cells has been proposed in the pathogenesis of type I gastric carcinoids, the criteria for distinction between hyperplastic endocrine cell micronest (ECM) and neoplastic ECM have not been established. The aims of this study were to clarify differences between the hyperplasia and neoplasia of ECL cells and determine the optimal classification system for gastric ECL cell proliferations in type A gastritis. Endocrine cell lesions (n=531) from 8 surgically-resected stomachs with type A gastritis were reclassified as either atrophic ECM (n=333), hyperplastic ECM (n=168), neoplastic ECM (all ECM ≥0.1 mm in size, n=15), or typical carcinoid (n=15). Hematoxylin and eosin-stained sections were semiautomatically analyzed by nuclear morphometry. Immunohistochemical expression of bcl-2, p53 and Ki-67 was also investigated. As the histologic grade of histology advanced, the morphometric values of area, circumference and largest diameter of the nuclei significantly increased (p<0.0005), while the frequency of diffuse expression of bcl-2 significantly decreased (p<0.0001). Significant differences were also observed in all morphometric parameters and in bcl-2 positivity between the hyperplastic ECM and neoplastic ECM group. There was no expression of p53 in any of the lesions. The Ki-67 index did not differ between the neoplastic ECM and typical carcinoid groups. These results suggest that our system of classification for gastric endocrine cell proliferations in type A gastritis is appropriate. Nuclear morphometry and bcl-2 immunoexpression are useful parameters for the distinction of neoplastic ECMs from hyperplastic ECMs.