Endocrine Cell Hyperplasia Research Articles

Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia.

Clinical and experimental evidence indicates that carcinoid tumours of the stomach fundic mucosa represent another example of hormone-dependent neoplasm, gastrin being the hormone involved in tumour induction. In this context hyperplasia of fundic endocrine cells associated with chronic atrophic gastritis (CAG) and hypergastrinaemia is regarded as the most frequent preneoplastic lesion. However, the cell type involved in this hyperplasia has not been clarified. To elucidate this problem fundic endocrine cells were characterized ultrastructurally in 9 patients from which endoscopic gastric biopsies were obtained. ECL cells were the most frequent cell type in 8 cases, in 4 of which they were more numerous than all other cell types taken together. D1 cells were the most frequent type in one case while they were inconspicuous in the other cases. P cells were found with a frequency in each case intermediate between that of ECL cells and that of D1 cells. These results indicate that fundic endocrine cell hyperplasia occurring in hypergastrinaemic CAG is in most cases cytologically similar to that found in other hypergastrinemic conditions, in which the gastrin-dependent ECL cells were already found to prevail. They also explain why fundic carcinoids arising in CAG are mostly composed of ECL cells. The relation between ECL, D1 and P cells, if any, remains obscure.

4-Nitroquinoline 1-oxide-induced pulmonary endocrine cell hyperplasia in Syrian golden hamster.

The tumorigenic effects of 4-nitroquinoline 1-oxide (4NQO) on the hamster lung were examined by light and electron microscopy. The hamsters received three subcutaneous injections of 4NQO at a dose of 20 mg/kg body weight at weekly intervals, and were sacrificed at 20, 25, and 30 weeks after the first injection. Hyperplastic endocrine cell lesions were consistently demonstrated in the airway from the lobar bronchi to the bronchiolo-alveolar junctional area by serial sectioning of lung tissue slices of all the treated animals. The hyperplastic lesions contained argyrophilic cells and showed weakly positive immunoreactivity to neuron-specific enolase. Ultrastructurally, some of the cells contained small cored dense granules.

Duodenal and ampullary carcinoid tumors. A report of 12 cases with pathological characteristics, polypeptide content and relation to the MEN I syndrome and von Recklinghausen's disease (neurofibromatosis).

Twelve duodenal carcinoid tumours are presented, 4 of them located in the ampulla. Symptoms included the Zollinger-Ellison syndrome (4 patients), the carcinoid syndrome (1 patient), mechanical obstruction (3 patients), bleeding (1 patient) and abdominal pain (1 patient). Two further tumours were detected by chance. Three patients with the Zollinger-Ellison syndrome had additional endocrine tumours characteristic of the MEN I syndrome. In 2 of them the duodenal carcinoids were of very small size and were multiple. They were observed in close proximity to focal areas of endocrine cell hyperplasia. Immunohistochemical investigations showed gastrin and somatostatin to be the predominant polypeptide hormones produced by these tumours. No somatostatinoma syndrome was encountered. In half of our cases additional production of insulin, VIP or even calcitonin in smaller amounts was found. Two of our patients had cutaneous manifestations of von Recklinghausen's disease and in both of them the carcinoid was located in the ampulla. One of these patients also had a pheochromocytoma.

Epidemiologic, clinicopathologic, and economic aspects of gastroscopic screening of patients with pernicious anemia.

In a well-defined population with a known prevalence of pernicious anemia (PA), gastroscopic screening was performed in 123 patients with PA, of whom 61 were rescreened after a mean time interval of 32 months. At the primary screening the prevalence of gastric neoplasia was 8.1% and that of gastric malignancy 4.1%. No neoplasias or malignancies were diagnosed at re-screening. The estimated cost per gastric neoplasia diagnosed during primary screening was USD 850 and that per diagnosed malignancy USD 1700. Adenoma, one with early adenocarcinoma, was diagnosed in two patients, primary early adenocarcinoma in two patients, and advanced adenocarcinoma in one patient. Five patients had gastric fundic mucosal carcinoid, of which one was multicentric with a regional metastasis. Gastric carcinoids most probably are underdiagnosed in atrophic gastritis, and, when small and solitary, their clinical relevance is uncertain. Fundic mucosal endocrine cell hyperplasia and hypergastrinemia seem to be important factors in their development.

Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia

Endoscopic screening in 123 patients with pernicious anemia (PA) yielded 4 patients with solitary and 1 patient with multiple gastric carcinoid tumors. Quantitative histologic studies of multiple standardized biopsy specimens showed a significantly increased number of fundic mucosal argyrophil endocrine cells in 40 patients with PA when compared with 15 patients with simple fundic atrophic gastritis (p = 0.002) or 8 normal controls (p = 0.0001). Patients with simple atrophic gastritis had increased numbers of fundic mucosal argyrophil cells as compared with normal controls (p = 0.02). A significant difference was also noticed in the number of antral mucosal argyrophil cells between patients with PA and normal controls (p = 0.01), but not between patients with PA and patients with simple atrophic gastritis. It is concluded that, in addition to having hyperplasia of gastric mucosal argyrophil endocrine cells, patients with PA run an increased risk of developing gastric argyrophil cell carcinoid tumors, which should be regarded as potentially malignant.

Neuron specific enolase (NSE) immunostaining detection of endocrine cell hyperplasia in adult rats exposed to asbestos.

Hyperplasia of endocrine cells in the lung of the adult rat exposed to asbestos has only been characterised so far by electron microscopy as there is a lack of reliable staining techniques for their demonstration at light microscopical level. Neuron specific enolase (NSE), an isoenzyme of the glycolytic enzyme enolase has recently been shown to be present in lung endocrine cells. In this study we reveal a marked endocrine cell hyperplasia at light microscopical level in the lungs of adult rats exposed to asbestos using antibodies to NSE. Very large groups of NSE-immunoreactive cells (20-80) were only observed in the lungs of rats exposed to asbestos for 12 months. In addition smaller groups of cells (2-10) known to be present normally and to decrease with age, were rarely noted in the controls but were frequently detected in the treated rats. Immunoreactive NSE is therefore a very good marker for endocrine cell hyperplasia and thus of early neoplastic changes.

THE RELATIONSHIP OF GASTROINTESTINAL ENDOCRINE CELLS TO GASTRIC EPITHELIAL CHANGES WITH SPECIAL REFERENCE TO GASTRIC CANCER

Using advanced gastric adenocarcinoma and carcinoid as human material and gastric adenocarcinoma in rats induced by MNNG and in mice by localized X-irradiation of the stomach as experimental material, a pathological study was made on the relationship of gastric endocrine cells to gastric cancer. The results of the present study suggest that most of the endocrine cells in the cancer tissue are derived from the differentiation of cancer cells. Therefore, the following three may be given as the aformentioned relationship, that is, 1) carcinoid of endocrine cell origin, 2) endocrine cell carcinoma showing undifferentiated adenocarcinoma, and 3) endocrine cell cloning developed from the differentiation of cancer cell of adenocarcinoma. There is the possibility that most of 2) are of 3) origin and thus 2) and 3) should be discriminated from 1), having a functioning tumor in rare cases. The significance of reactive hyperplasia of endocrine cells in the non-metaplastic mucosa of the stomach around cancer and atypical epithelium is not yet determined, but that of EC cell seems at least to be related with the development of intestinal metaplasia in the gastric mucosa.

Gastrin Cell Hyperplasia in Rats With Chronic Antral Stimulation

Rats surgically prepared with the antrum transposed onto the colon were compared with suitable control rats, to investigate whether chronic antral stimulation modifies gastrin cell and other endocrine cell populations. Gastrin cell and argyrophil cell density per unit area were studied in antrum using a quantitative method after staining by immunofluorescence and Grimelius argyrophily, respectively. Both gastrin cells and argyrophil cells increased significantly in density per unit area after antrocolic transposition (P smaller than 0.001). The augmentation of gastrin cells per glandular tube (78%) was also significant (P smaller than 0.001). Electron-microscopic observations confirmed these results. On the other hand, in each group, the topographic distribution of the two categories of cells was different, and the number of gastrin cells was statistically greater than that of the argyrophil cells. Thus, it appeared evident that gastrin cells were not argyrophilic. Several hypotheses to explain the mechanism of this hyperplasia of endocrine cells are discussed. It is concluded that the increase in the gastrin cell density could be one possible explanation for the hypergastrinemia observed in the antrocolic transposition model.

Secretin cells in coeliac disease.

Immunofluorescence (anti-secretin), cytochemical, and ultrastructural studies were carried out on jejunal biopsies from 16 children with coeliac disease and from 17 controls with suspected malabsorption but normal jejunal morphology. In 11 of the 16 coeliacs there was generalized hyperplasia of endocrine cells and, specifically, of the secretin (S) cells. Further studies, on adult coeliacs as well as on children, combined with serum secretin assays, may establish whether the S cells are abnormally storing hormone because of inability to release it or because of excess production.