L. Usellini

Types of endocrine cells in the human colon and rectum.

SummaryAt least four types of endocrine-like cells have been detected histochemically in the mucosa of the human colon and rectum, i.e. argentaffin cells storing 5-hydroxytryptamine (5 HT) and non-argentaffin cells reacting with glucagon, somatostatin and bovine pancreatic peptide (BPP) antibodies. Ultrastructurally, four main types and three rare types of endocrine-like cells have been identified. Among the former cells were: (1) argentaffin EC1 cells, known to store 5 HT and substance P, (2) poorly argyrophil L cells, corresponding to the glucagon-immunoreactive cells storing enteroglucagon or glucagon-like immunoreactivity (GL1), (3) inconstantly argyrophil F-like cells, possibly corresponding to BPP-immunoreactive cells, and (4) fairly argyrophil H cells of unknown function. Rare D cells, corresponding to somatostatin cells, N cells, corresponding to neurotensin cells, and P cells, of unknown function, have been also found.

Ultrastructural similarity of endocrine-like cells of the human lung and some related cells of the gut

SummaryThe ultrastructure of endocrine-like cells of the human lung was compared to the ultrastructure of endocrine-like cells of the stomach and pancreas in both adult and foetal material.Three types of endocrine-like cells were found in the human foetal lung. Type 1 or P1 cells contained very small granules (about 110 nm) of two varieties, cored and vesicular; type 2 or P2 cells with cored granules measuring about 130 nm; and type 3 cells with cored granules of about 180–190 nm. In the adult lung only one type Pa cells with cored granules could be found.Cells resembling foetal P1 cells were not found in foetal or adult gastric mucosa, or in the pancreas. In the gastric mucosa cells resembling pulmonary Pa or P2 cells were moderately represented and often difficult to distinguish from each other. Thus, they were grouped together as gastric P cells. Cells with granules resembling those of pulmonary type 3 cells were found most numerous in the adult oxyntic mucosa. Cells resembling gastric P cells (and pulmonary P2 cells) were rather numerous in foetal pancreas, but very rare in adult pancreas. Few cells containing granules somewhat resembling those of pulmonary type 3 cells were present in both foetal and adult pancreas.The results were discussed in respect to 1) the similarities between some gastric or pancreatic carcinoids and lung carcinoids, 2) the gastro-pancreatic P cells as a separate cell population, 3) the possible secretion by the lung endocrine-like cells of active substances, either amines or peptides, 4) the similarity between the secretory granules of Pa and P1 cells and neurosecretory granules of the hypothalamus and between P2 cells and some endocrine cells of the pituitary.

The endocrine component of prostatic carcinomas, mixed adenocarcinoma-carcinoid tumours and non-tumour prostate. Histochemical and ultrastructural identification of the endocrine cells.

Two types of endocrine‐paracrine (EP) cells have been detected histochemically and ultrastructurally in normal and hyperplastic prostates; i.e. type 1 cells resembling intestinal EC (enterochromaffin) cells and type 2 cells similar to urethral EP cells previously reported by Casanova et al. (1974). About one‐third of the 40 prostatic carcinomas studied contained EP cells. Four tumours showed a very large number of EP cells: two of these were composite tumours exhibiting both adenocarcinomatous and carcinoid patterns. These four tumours have also been studied histochemically and ultrastructurally. ACTH and β‐endorphin immuno‐reactive cells, ultrastructurally resembling pituitary corticotrophic cells, have been identified in three tumours. Cells identical with type 1 and type 2 cells of the normal prostate were detected in two cases and in a further case, respectively.

Morphologic patterns and diagnostic criteria of VIP-producing endocrine tumors. A histologic, histochemical, ultrastructural, and biochemical study of 32 cases

Thirty‐two tumors (31 pancreatic and one jejunal) all associated with severe watery diarrhea, increased VIP levels in blood and most with hypokalemia, were investigated. The VIP content of tumor tissue ranged from 23 to 15,000 pmol/g. VIP immunoreactive cells were detected histochemically in 24 of 28 tumors investigated, PP immunoreactive cells in 11 of 28 tumors, hCG (α chain) immunoreactive cells in 12 of 25 tumors, and neuron specific enolase (NSE) immunoreactive cells in 24 of 26 tumors (the 2 negative results were due to inadequate fixation). All cases showed light microscopic features of epithelial endocrine tumors. Electron microscopy demonstrated a prevalence of agranular, poorly granulated and a minority of well granulated cells. Most secretory granules were round, small (150 ± 30 nm diameter) and of moderate electron density, resembling those of the so‐called D1 cells. By electron immunocyto‐chemistry, PP was directly localized in a subpopulation of relatively larger granules (154 ± 22 nm core diameter) showing closely applied membranes. VIP‐storing granules, directly identified only in the jejunal tumor, appear to correspond to a subpopulation of slightly smaller P‐type granules (126 ± 37 nm core diameter) showing a narrow, clear halo. The origin, behavior, and diagnostic criteria of VIPomas are discussed.

Bombesin-like immunoreactivity in the avian gut and its localisation to a distinct cell type.

SummaryThe distribution of a bombesin-like immunoreactive peptide in the avian gastro-intestinal tract was analysed by combined radioimmunoassay and immunocytochemistry. Radioimmunoassay of tissue extracts showed that the largest quantities of bombesin-like immunoreactivity were present in the proventriculus (64.5±6.0 pmol/g) with smaller but still considerable amounts in the gizzard (40.0±6.0 pmol/g). Immunocytochemically the extractable bombesin-like immunoreactivity was localised in numerous endocrine cells. These, in the proventriculus, were found mainly in the deeper layers of the mucosa. Further study of these cells by the semi-thin/thin technique revealed the presence of characteristic secretory granules. The functional name BN is proposed for this cell type.

Endorcine cells producing regulatory peptides

Recent data on the immunologication of regulatory peptides and related propeptide sequences in endocrine cells and tumours of the gastrointestinal tract pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory beenrevised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptidesare the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, α-MSH and CLIP (corticotropoin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenalin-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

Ovarian mucinous tumors frequently express markers of gastric, intestinal, and pancreatobiliary epithelial cells

In 100 mucinous tumors of the ovary (37 benign, 24 borderline, and 39 malignant), the authors determined by histochemical and immunohistochemical techniques the frequencies and patterns of expression of a total of nine markers of gastric, intestinal, and pancreatobiliary duct epithelial cells. M1, a mucin antigen, and cathepsin E (CaE), an aspartic proteinase, two markers of normal gastric superficial/foveolar epithelial cells, were expressed in 95 and 92 tumors, respectively. Periodic acid‐concanavalin A—reactive much or pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, were found in 79 tumors. All of these tumors also expressed M1 or CaE. DU‐PAN‐2 and the N‐terminal epitope of gastrin‐releasing peptide, markers of normal pancreatobiliary duct cells, were found in 70 and 49 tumors, respectively, and CAR‐5 and M3SI, markers of intestinal mucin, were expressed in 51 and 30 tumors, respectively. All tumors expressed at least two of the nine markers studied; none expressed PG I, a marker of gastric chief cells. The mucopeptic cell marker, PG II, was significantly more common in benign and borderline than in malignant tumors (P < 0.005), whereas CAR‐5 and M3SI, markers of intestinal mucin, were expressed significantly more often in malignant than in benign and borderline tumors (P < 0.001). By electron microscopic examination, many tumor cells had fine structural features characteristic of gastric superficial/foveolar and pyloric gland cells, intestinal columnar or goblet cells, and endocervical cells. The results indicate that gastroenteropancreatic cell differentiation—and, in particular, gastric type differentiation—is a prominent feature of ovarian mucinous tumors.

The endocrine cells of the pancreas and related tumours

Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either of “active” or “stem cell” type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.

Histopathology, hormone products, and clinicopathological profile of endocrine tumors of the upper small intestine: A study of 44 cases

Forty-two duodenal and 3 upper jejunum tumors from 44 patients were investigated. All tumors were tested immunohistochemically for gastroenteropancreatic hormones and general endocrine cell markers. Twenty-eight of the 45 tumors (62%) proved to be gastrin cell tumors, with (12 cases) or without (16 cases) associated Zollinger-Ellison syndrome. Zollinger-Ellison syndrome was part of type 1 multiple endocrine neoplasia syndrome in 3 cases. Twenty-three of the 28 gastrin cell tumors (82%) were from proximal duodenum, 2 were from the second part of the duodenum, and 3 were from the upper jejunum. Seven cases were somatostatin cell tumors, 6 of which were from the ampullary region; 5 cases were associated with biliary tract disease and 2 with associated cutaneous neurofibromatosis. Four ganglioneuromatous paragangliomas, from the ampullary region or nearby duodenum, showed somatostatin cells, coupled with pancreatic polypeptide cells in 2 cases. Two serotonin-producing argentaffin carcinoids were also identified. In addition to the main cell type, 30 tumors showed one or more, usually minor, cell populations producing somatostatin, serotonin, cholecystokinin, pancreatic polypeptide, insulin, neurotensin, or the alpha chain of human chorionic gonadotropin. Only 3 tumors lacked hormone immunoreactivity. Some correlation has been noted between histological structure and hormone content of tumor cells, with prevalence of broad gyriform trabeculae and vascular pseudorosettes among gastrin cell tumors, tubuloacinar patterns among somatostatin cell tumors, thin parallel trabeculae among PP cell growths, and a solid nest pattern among argentaffin carcinoids. Deep infiltration of the intestinal wall was observed in 22 tumors, 6 of which also had metastases to local lymph nodes. All metastatic cases were among ZES tumors or ampullary somatostatin cell tumors. Ganglioneuromatous paragangliomas and nonfunctioning gastrin cell tumors had essentially benign behavior, even when involving deep strata of the intestinal wall. Post operative follow-up study of 36 cases, including all metastatic tumors, showed no evidence of tumor-related death or progressive tumor disease.

Parafollicular cells of rabbit thyroid store both calcitonin and somatostatin and resemble gut D cells ultrastructurally

SummaryBoth calcitonin and somatostatin have been detected immunohistochemically in rabbit parafollicular cells; only calcitonin has been found in the same cells of the dog, guinea-pig and man. Large amounts of a peptide radioimmunochemically identical with synthetic somatostatin have been detected in extracts of rabbit thyroid. The ultrastructural and staining features of rabbit parafollicular cells differ from those of parafollicular cells in other species, while resembling in part those of somatostatin D cells scattered in the rabbit stomach.