Studies on co-localization of 7B2 and pancreatic hormones in normal and tumoural islet cells.

The distribution of protein 7B2, a protein with structural characteristics of GTP-binding proteins, has been studied in normal pancreatic islets and in a series of 70 pancreatic endocrine tumours with emphasis on the co-localization of 7B2 and the different pancreatic hormones. Although all cell types of normal islets were found to store 7B2, variations from intense expression to absence of reaction were seen within each cell type. In particular, B cells showed intense immunostaining for 7B2 in small compact islets and weak or no staining in larger islets with lobular arrangement. Pancreatic polypeptide (PP) cells expressed 7B2 intensely in the PP-rich area of ventral embryological origin, but were mostly non-reactive in the PP-poor area. The A cells, located along intralobular blood vessels, were more frequently immunoreactive for 7B2 than those at the periphery of the islets. Immuno-electron microscopy revealed a preferential localization of 7B2 in secretory granules of islet cells, with more intense localization in the peripheral halo of alpha granules. Benign islet cell tumours more frequently expressed 7B2 than their malignant counterparts. Although often expressed in a lower number of tumour cells than the tumour-specific hormone, 7B2 was usually co-localized with the latter. In contrast, no relationship was found with the localization of proinsulin. It is concluded that 7B2 is a non-permanent component of the cell granule compartment, probably involved in events related to exocytosis and without relationship to intracellular prohormone processing.

Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases.

A histologic and immunohistochemical study was carried out in 23 unselected nonantral gastric carcinoids and their precursor lesions classified according to Solcia et al. None of the patients showed Zollinger-Ellison syndrome. Two variants of carcinoids showing distinctive pathologic and pathogenetic characteristics were identified on the basis of presence or absence of associated chronic atrophic gastritis type A (A-CAG). Chronic atrophic gastritis type A was found in 19 cases showing either single or multiple neoplasms, tumor extension limited to the mucosa or submucosa, consistent endocrine cell precursor changes in extratumoral mucosa, and consistent hypergastrinemia and/or G cell hyperplasia. Associated precursor lesions were only hyperplastic in all but two cases with single carcinoids whereas they were also dysplastic in all but one case with multiple carcinoids. The four tumors arising in nonatrophic mucosa were all single, more aggressive, and not associated with extratumoral endocrine cell proliferations or with signs of gastrin hypersecretion. Tumor cells were diffusely immunoreactive for chromogranin A and synaptophysin but usually negative for chromogranin B or HISL-19. Scattered serotonin cells were found in ten carcinoids. They were more frequent in infiltrating than in intramucosal tumors as were the less represented pancreatic polypeptide cells whereas the reverse was found for alpha-subunit-containing cells. These results are of relevance for tumor pathogenesis and may provide the rationale for a less aggressive therapeutic approach in the patients.

Mandibular leiomyoma in an infant. Report of a case.

A case of mandibular leiomyoma in a 8-month-old baby is reported. This is the 5th case of intrabony leiomyoma of the jaws reported so far. The tumor presented as a symptomless swelling of the mandibular ramus and required a limited resection. The pertinent literature is reviewed and the histological features discussed.

Quantitative ultrastructure of endocrine cells of oxyntic mucosa in Zollinger-Ellison syndrome. Correspondence with light microscopic findings.

The endocrine cells of the oxyntic mucosa of five patients with longstanding Zollinger-Ellison syndrome were quantitatively investigated with electron microscopy and two light microscopic methods (Grimelius and immunostaining for chromogranin A). Ultrastructurally, the volume density of endocrine cells was 3.2% +/- 1.1% of the mucosal epithelial component, a 168% increase (P less than 0.001) over the value found in normal subjects. Of the six endocrine cell types of human oxyntic mucosa, only enterochromaffinlike cells increased in cell density (65% +/- 15% of the total endocrine cell mass), size, and number of cell profiles per unit area. The enterochromaffinlike cells also underwent morphological changes of secretory granules with a decrease in vacuolated forms, increase in elongated profiles, and appearance of granules with a punctate structure of the core. The latter variety of granules was previously observed only in carcinoid tumors of the oxyntic mucosa and is possibly related to the enterochromaffinlike cell hyperplasia-neoplasia sequence seen in hypergastrinemic patients. A positive relationship was found between endocrine cell densities evaluated ultrastructurally and with chromogranin A immunostaining. It is concluded that in Zollinger-Ellison syndrome, the trophic effects induced by longstanding hypergastrinemia are strictly selective for enterochromaffinlike cells and are associated with ultrastructural features typical for enterochromaffinlike cell tumors.

Glycoprotein hormone alpha subunit in endocrine cells of human oxyntic mucosa. Studies on its relation to neuroendocrine tumors.

Expression of the alpha-subunit of glycoprotein hormones is an acquired feature of the endocrine cells of the oxyntic mucosa in patients with sustained serum levels of gastrin, and may be related to the hyperplasia-carcinoid sequence occurring in these patients. In the present study we have investigated the intragastric cellular localization and the circulating levels of alpha-subunit in a patient with Zollinger-Ellison syndrome. In this patient we have found that: 1) Endocrine cells accounted for 2.29% +/- 1.44% of the total oxyntic mucosal volume (normal value: 0.9% +/- 0.4%), with the ECL cells representing 63.22% +/- 10.9% of the total endocrine cell volume (normal value: 29.8 +/- 8.8%). 2) Cells immunoreactive for the alpha-subunit were found to correspond ultrastructurally to a subpopulation of enterochromaffin-like cells, indistinguishable from similar cells devoid of significant immuno-electron microscopic labeling. 3) Immunoreactive cells included a portion of oxyntic endocrine cells with punctate granules, a feature previously observed only in carcinoid tumors of the oxyntic mucosa. 4) In consecutive sections of freeze-dried vapor-fixed biopsies a fraction of alpha-subunit storing cells was found to co-express histamine. 5) The serum alpha-subunit levels were abnormally elevated and paralleled those of gastrin in a secretin-stimulation test. Analysis of similar curves in two other patients with Zollinger-Ellison syndrome, and five patients with hypergastrinemic atrophic gastritis, all presenting alpha-subunit containing oxyntic endocrine cells, showed significant alpha-subunit elevations only in the patients with ulcerogenic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Composite carcinoid-adenocarcinoma of the stomach associated with multiple gastric carcinoids and nonantral gastric atrophy.

A case of multiple gastric carcinoids and nonantral atrophic gastritis in which the larger tumor was a composite carcinoid-adenocarcinoma is presented. The two components of the composite tumor immunohistochemically showed clear-cut diverging functional differentiations although the available evidence supported a common histogenesis from the metaplastic intestinal epithelium of the gastric mucosa. The carcinoid tissue of the composite tumor, which showed "atypical" features, also differed from the other, pure carcinoids, in which the histologic appearance was "typical." Total gastrectomy performed 1 month after the original gastric resection with antrectomy disclosed regressive changes in the endocrine cell proliferations of the gastric stump consistent with the withdrawal of a stimulating effect of the antral gastrin.

Structure and function of endocrine cells in the oxyntic (acid-secreting) mucosa of human stomach.

The morphological and functional characteristics of the endocrine cells of the oxyntic (acid-secreting) mucosa of the human stomach, a target of the trophic effect of gastrin, are reviewed. In healthy subjects these cells account for 0.90 +/- 0.35% of the volume of the entire mucosa and for 1.21 +/- 0.44% of the volume of the epithelial mucosal component alone. The cells show no extension to the glandular lumen and show an intimate anatomic relationship with contiguous non-endocrine epithelial cells. This configuration indicates undefined local functions of the paracrine type not influenced by the gastric lumen content. Seven cell types were identified ultrastructurally, three of which (enterochromaffin-like (ECL), P and D) cumulatively account for more than 75% of the total endocrine cell mass. The secretory product(s) of the endocrine cells has not been demonstrated definitively with the exception of minor cell populations producing glucagon (only in the fetal life), somatostatin and 5-HT. Recently, production of histamine and glycoprotein hormone alpha-subunit by oxyntic endocrine cells of man have been reported. However, histamine seems to occur in these cells normally, whereas the production of glycoprotein hormone alpha-subunit appears to be virtually restricted to cells of patients with hypergastrinaemic conditions.