Argyrophil Cells Research Articles

Argyrophil Cell Hyperplasia Associated with Chronic Corpus Gastritis in Gastric Ulcer Disease

Argyrophil cell (AC) hyperplasia in corpus mucosa was investigated in 53 patients with chronic gastric ulcer disease not previously treated with antisecretory drugs. Mucosal biopsies were taken stepwise from the posterior wall in the corpus area of the stomach. Of 117 biopsy sites, 28 showed gastritis without atrophy, 85 showed chronic atrophic gastritis of varying degrees while 4 biopsies showed a normal mucosa. About one third (38%) showed a normal AC pattern. Of the remaining two thirds (62%), 45% had simple AC hyperplasia, 18% had linear and 37% had micronodular AC hyperplasia. A strong association was found between focal (linear/micronodular) AC hyperplasia and chronic atrophic gastritis. It is concluded that focal AC hyperplasia is a common phenomenon in gastric ulcer patients and is inherently related to the spontaneous development of atrophy in the corpus mucosa of these patients.

Effect of the Histamine-1 Antagonist Astemizole Alone or with Omeprazole on Rat Gastric Mucosa

The stimulation of acid secretion by gastrin may in the rat be explained solely by gastrin-induced histamine release. This study was done to examine whether histamine could mediate the general trophic effect of gastrin on the oxyntic mucosa, by using a long-acting selective histamine-1 antagonist (astemizole) alone or with omeprazole-induced hypergastrinaemia for 90 days in female Sprague-Dawley rats. At day 90, isolated vascularly perfused rat stomachs were prepared to study maximal gastrin- and histamine-stimulated acid and pepsinogen outputs and maximal gastrin-stimulated histamine release. Oxyntic mucosa morphometry, mucosal histamine and pepsinogen contents, and plasma gastrin and histamine levels were also determined. For the first time, omeprazole has been found to inhibit gastric emptying and to increase plasma histamine. As compared with controls, astemizole alone did not influence plasma gastrin, increased plasma histamine in only some rats, and gave a slight increase in all other variables. Together with omeprazole, it further increased variables already stimulated by omeprazole. Thus, mucosal thickness, histamine concentration, and chief-cell density in oxyntic mucosa were significantly higher in astemizole/omeprazole-treated rats than in omeprazole-treated rats. Gastrin-stimulated histamine release was increased in both astemizole- and omeprazole-treated rats. For all rats plasma histamine was significantly correlated with plasma gastrin and with numerical fundic argyrophil cell density. In conclusion, the present study confirms the trophic effect of gastrin and shows a slight trophic effect of astemizole on the oxyntic mucosa. It also shows that plasma histamine may reflect the argyrophil cell density in the oxyntic mucosa and that omeprazole inhibits gastric emptying.

Evolution of fundic argyrophil cell hyperplasia in nonantral atrophic gastritis

Fundic argyrophil cells were studied for a mean period of 68.7 months (range, 11–170) in 18 patients with fundic atrophic gastritis and achlorhydria. Initially, 12 patients had hyperplasia of the argyrophil cells, the severity of which was assessed using a semiquantitative classification based on the number of argyrophil clusters per square millimeter. At the end of the study, the degree of hyperplasia was unchanged in 9 patients, had decreased in 2, and had increased in 1; no significant increase in the number of argyrophil clusters, precarcinoid changes, or carcinoid tumors were observed and the high level of gastrinemia [mean, 4.8 (range, 1.9–8.1) times the upper limit for normal] did not change significantly. Of the 6 patients with no hyperplasia at the outset of the study, 4 continued without hyperplasia and 2 presented a low-grade hyperplasia at the 20th and 130th month. Gastrinemia increased significantly in the last patient and stayed normal in the other 5. This study argues in favor of the stable appearance of fundic argyrophil cells in patients with atrophic gastritis and stable gastrinemia.

Small cell carcinoma of the pancreas and biliary tract

Four cases of anaplastic carcinoma of the pancreas or biliary tract were studied clinicopathologically and immunohistochemically. All four cases were intermediate cell type and contained a minimum amount of microscopic foci of differentiated glandular adenocarcinoma. Argyrophilic tumor cells were not seen in any of the four tumors. Immunohistochemically, no tumor was positive for hormonal products, but all tumors were positive for epithelial markers. These findings suggest that the anaplastic carcinoma are not derived from argyrophilic cells, but rather from adenocarcinomas which have the potential for anaplastic metaplasia. The long-term survival of one patient emphasized the importance of chemotherapy in the treatment of small cell carcinoma of the pancreas and biliary tract.

The effect of Zollinger-Ellison syndrome and omeprazole therapy on gastric oxyntic endocrine cells

In 1983, all trials of omeprazole in humans were stopped because rats given the drug developed gastric endocrine cell hyperplasia and carcinoid tumors. Further studies in rats showed that druginduced achlorhydria and hypergastrinemia caused these changes. Because data in humans are limited, we compared the numbers of endocrine cells, as judged by silver staining (argyrophilia), in the gastric mucosa of patients with Zollinger-Ellison syndrome, who are hypergastrinemic, and in normogastrinemic patients with idiopathic acid-peptic diseases. In addition, we analyzed the number of gastric endocrine cells in patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years. Patients with Zollinger-Ellison syndrome had 15.7% ± 6.9% argyrophil cells in biopsies of gastric oxyntic mucosa, and patients with idiopathic acid-peptic disease had 7.8% ± 2.3% (P < 0.01). In patients with Zollinger-Ellison syndrome, the percentage of argyrophil cells was not related to serum gastrin concentration, duration of symptoms, time since diagnosis, basal or maximal acid output, extent of tumor, or age. There was a tendency for patients with multiple endocrine neoplasia type 1 to have a greater percent of argyrophil cells than patients with sporadic Zollinger-Ellison syndrome. Considering the biopsies from both normogastrinemic and hypergastrinemic patients, there was a significant relationship between the percentage of argyrophil cells and the serum concentration of gastrin (P < 0.01). Patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years developed no significant changes in percentage of argyrophil cells, no carcinoid tumors, and no changes in serum concentrations of gastrin. The present study shows that patients with Zollinger-Ellison syndrome have an increased percentage of argyrophil cells in oxyntic mucosa and that omeprazole does not increase this percentage. In periods of up to 3 years, omeprazole had no effects on gastric morphology in patients with Zollinger-Ellison syndrome.

A case of coexisting malignant carcinoid tumor and adenocarcinoma in the papilla of vater

A 47-year-old Japanese woman in whom obstructive jaundice had already been diagnosed, was found to have a dome-shaped elevated tumor approximately 3 cm in diameter located in the area very close to the papilla of Vater on endoscopical and radiographical investigations. Histopathologically, the resected tumor was composed mainly of solid nests of atypical argyrophilic cells, and partially of an area of well differentiated tubular adenocarcinoma, showing mutual transition in the mucosal layer. Both immunohistochemical and ultrastructural analyses confirmed the difference in character of tumor cells between these two areas: neuroendocrine cell carcinoma and tubular adenocarcinoma of common type in the intestine. To the best of our knowledge, this is only the third case reported to be a coexisting malignant carcinoid tumor and adenocarcinoma arising in the periampullary region.

Visceral Neuropathies Responsible for Chronic Intestinal Pseudo-Obstruction Syndrome in Pediatric Practice

Twenty-six children aged from 1 day to 15 years (18 boys and 8 girls) with visceral neuropathies are analyzed. Clinical symptomatology is dominated by abdominal distension, attacks of occlusion, abdominal pain, and malnutrition. Intestine bacterial overgrowth is frequent. From aspiration biopsies, surgical rectal biopsies, and, in some cases, ileal or ileocolic biopsies, histopathological studies revealed two patterns. One group had abnormalities of the myenteric plexus identified by conventional light microscopic studies, with two patterns: [myenteric plexus hyperplasia (9 patients), characterized by large ganglionic nodes, penetration into the mucosal zone, and altered argyrophilic neurons]. Clinically this pattern was observed in four patients with multiple endocrine neoplasia syndrome with risk of medullary thyroid carcinoma. The second pattern observed was characterized by glial cell hyperplasia (15 patients). Ganglion cells are present but are small and sparse, often infiltrated by collagen tissue; Schwann nerve fibers are hypertrophic. Eleven patients presented with neonatal intestinal obstruction. The second group is characterized by normal conventional light microscopic examination, but silver stains revealed important abnormalities of argyrophobic cells (one case) or argyrophilic cells (one case). In the two groups, most of the patients needed intestinal derivation and prolonged nutritional support with total parenteral nutrition.

Pathologic Observations of Intrahepatic Peribiliary Glands in 1000 Consecutive Autopsy Livers: Heterotopic Pancreas in the Liver

One thousand consecutively autopsied livers were examined for intrahepatic heterotopic pancreas. Heterotopic pancreas in the liver was found in 41 (4.1%) of the 1000 livers. It occurred with nearly equal frequency in "normal" livers and variously diseased livers. Histologically, heterotopic pancreas was situated exclusively in the large- and medium-sized portal tracts, and its size ranged from 250-900 microns in diameter. It was intermingled with intrahepatic peribiliary glands and appeared to communicate with bile duct lumina. Heterotopic pancreas consisted of three cell types: acinar cells with eosinophilic zymogenlike granules, clear cells resembling centriacinar cells, and ductular elements. Langerhans' islets were not found in any cases. Immunohistochemically, constituent cells of heterotopic pancreas contained pancreatic alpha-amylase and trypsin but lacked argentaffin and argyrophilic cells as well as insulin-, glucagon-, and somatostatin-immunoreactive endocrine cells. Ultrastructurally, acinar cells contained many dense granules regarded as zymogen granules. It is indicated that intrahepatic heterotopic pancreas occurs in large portal tracts. It may modify hepatic bile by secreting pancreatic enzymes into intrahepatic bile duct lumina.

The effect of low-level toluene exposure on the developing hippocampal region of the rat: Histological evidence and volumetric findings

With the intention of investigating possible morphological alterations effected by toluene in the developing CNS, rat pups were exposed to 100 ppm and 500 ppm of atmosphoric toluene from postnatal day 1 until sacrifice at postnatal day 28, when the hippocampal region (area dentata, Ammon's horn, subiculum) was examined light microscopically and alterations in the volumes of the layers of the subdivisions were determined. The layers of Ammon's horn and the subiculum were not affected qualitatively or quantitatively by the 500 ppm exposure. Within the area dentata, the volume of the granule cell layer was 6% smaller in animals exposed to 100 ppm and 13% smaller in animals exposed to 500 ppm than they were in controls. The volumes of the hilus, which is a terminal field of granule cell axons, and the commissural-associational zone of the dentate molecular layer, which is the terminal field of the hilar projection to the granule cells, were smaller (12% and 19%) in animals exposed to 500 ppm than they were in controls. Argyrophilic cells were found in the granule cell layer of all animals exposed to 500 ppm. Pronounced granule cell degeneration was found in one animal exposed to 500 ppm. The granule cell layer of animals exposed to 100 ppm appeared qualitatively normal. The alterations reported her support the few earlier reports of morphological alterations in the CNS of adult laboratory animals. Effects of toluene similar to those described, that is alterations in specific neuron populations and their afferent and efferent terminal fields may complement changes in neurophysiology and behavior that have been observed in prenatally and perinatally exposed rodent pups. Causal relationships, however, remain to be elucidated.

The endocrine‐paracrine cells of von Brunn's nests and glandular metaplasia in the supramontanal prostatic urethra

Endocrine-paracrine (EP) cells are normal cellular constituents of the human genitourinary tract. We examined the distribution and immunostaining profile of EP cells in von Brunn's nests and glandular metaplasia in the supramontanal (proximal) prostatic urethra of adult males and in prostatic ducts of the male fetal urethra. In 15/17 transurethral prostatic resection specimens there were argyrophilic cells and/or serotonin and neuronspecific enolase containing cells in von Brunn's nests/glandular metaplasia and in the supramontanal prostatic urethra. All seven fetal specimens examined contained EP cells and five had focal calcitonin immunoreactivity in prostatic ducts and ductal buds. One adult resection specimen had focal staining for human chorionic gonadotrophin and no case showed staining for somatostatin. These results further support the contention that von Brunn's nests and glandular metaplasia are probably normal urothelial variants in the adult supramontanal prostatic urethra.

Histochemical and ultrastructural studies on the enterochromaffin-like cell in the gastric mucosa of the opossum Didelphis albiventris (Marsupialia)

An ultrastructural study of enterochromaffin-like (ECL) cells in the gastric mucosa of the white-belly opossum Didelphis albiventris (Marsupialia) was carried out. In parallel, histochemical methods were used at the light-microscopical level to demonstrate argentaffin cells, argyrophilic cells, and serotonin- and histamine-immunoreactive elements. Argentaffin and serotonin-immunoreactive cells were scattered, and argyrophilic cells were numerous, within the full thickness of the mucosa. Argyrophilic cell distribution was similar to that of histamine-immunoreactive elements. At the electron-microscopical level, the oxyntic mucosa of D. albiventris presented endocrine cells with secretory granules morphologically similar to those of the ECL cell of eutherian mammals. However, in this marsupial, the ECL cell exhibited a variable mixture of two distinct types of secretory granules: (1) granules with the morphological appearance of the eutherian ECL cell, and (2) granules morphologically similar to those of the eutherian enterochromaffin (EC) cells. Based on this morphological pattern of the ECL cell granules, it is proposed that in the oxyntic mucosa of the opossum D. albiventris, the EC and ECL cells represent distinct steps in the same line of cell differentiation; the ECL cell should also be a site of histamine storage.

Enterochromaffin-Like Cell Carcinoids in the Rat Gastric Mucosa following Long-Term Administration of Ranitidine

Long-term administration of some long-acting inhibitors of gastric acid secretion has been associated with the development of gastric enterochromaffin-like (ECL)-cell carcinoids in the rat. It has been argued that short-acting, surmountable histamine H2-receptor blockers such as ranitidine do not cause carcinoids. In this study, female rats (n = 100) were treated for 2 years with the histamine H2-receptor blocker ranitidine, 2 g/kg/day in the diet. Specimens from the stomachs of all rats, including 50 controls, were stained for argyrophil cells. Plasma gastrin and ranitidine levels were measured in separate groups of rats at different times during the study. The mean plasma level of ranitidine was 37.5 mumol/l, measured at midnight when the maximal level after food intake was expected. The resulting acid inhibition was associated with an approximately 3-fold increase in plasma gastrin which persisted throughout the whole period of the study. The ranitidine treatment resulted in a pronounced hyperplasia of gastric ECL cells. In 19 rats carcinoids were found, 4 of which were micro-invasive. No carcinoids were found in the control animals. The results provide further support for the gastrin mechanism, i.e. that the development of ECL-cell carcinoids in the rat gastric mucosa is a consequence of prolonged hypergastrinaemia and is not a unique effect of any individual acid-inhibiting drug.

Efficacy and Safety of Omeprazole in the Long-Term Treatment of Peptic Ulcer and Reflux Oesophagitis Resistant to Ranitidine

A total of 143 patients with peptic ulceration of the duodenum, stomach and oesophagus who did not respond to 3 or more months of high-dose treatment with ranitidine, 450 mg or more daily, were treated with oral omeprazole, 40 mg daily. In 94% of the patients, ulcers healed within 2-8 weeks. After healing, 133 patients underwent long-term maintenance treatment with omeprazole, 40 mg daily, for 1-5 years (continuing). During maintenance therapy with omeprazole, no endoscopically verified relapses occurred, and no drug-related adverse effects were seen. There were no significant changes in routine laboratory tests in any patient, including 27 with concomitant liver cirrhosis. Basal serum gastrin levels, which were already elevated by the previous high-dose ranitidine treatment, rose to 4 times normal levels after 4 months of treatment with omeprazole. Thereafter, no further increases in basal serum gastrin levels were observed, even after 5 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased during omeprazole treatment, but no dysplasia of the gastric enterochromaffin-like cells was seen. In conclusion, omeprazole was highly effective in healing ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with omeprazole, 40 mg daily, was found to be effective and safe over the period observed.

Solid teratomas and mixed Mullerian tumors of the ovary: A clinical, histological, and immunocytochemical comparative study

The differential diagnosis between solid teratomas and malignant mixed Mullerian tumors (MMTs) can be difficult, because both tumours have an epithelial as well as a mesenchymal component. Sometimes an MMT is incorrectly diagnosed as a solid teratoma. This has prognostic and therapeutic consequences, because MMTs have a worse prognosis. In this study 20 solid ovarian teratomas and 15 MMTs of the ovary have been compared according to their clinical, histomorphological, and immunocytochemical characteristics. Teratomas occur in the younger age group and are characterized by the presence of argyrophil cells which are immunoreactive to a wide range of neurohormonal peptides and are in addition characterized by the presence of GFAP immunoreactive tissues (glial fibrillar acidic protein). MMTs occur in the older age group and are characterized by the presence of sarcomatous elements and by the absence of an organoid arrangement, neuroectoderm, skin, argyrophilia, and immunoreactivity to GFAP and neurofilament.

Demonstration of Neuroendocrine Cells in Ovarian Mucinous Tumors

The frequency of argyrophil cells in mucinous cystadenocarcinomas, borderline tumors (MBT) and cystadenomas was 29.8% (14 of 47), 46.7% (7 of 15) and 11.1% (2 of 18), respectively. These were statistically higher than the frequencies in 17 clear cell carcinomas, 43 serous cystadenocarcinomas, and 24 metastatic carcinomas. Immunoreactive cells for serotonin, somatostatin, gastrin, pancreatic polypeptide, growth hormone-releasing hormone, metenkephalin, neuron-specific enolase, and chromogranin-A were detected in almost all these cases with argyrophil cells. However, immunoreactivities for glucagon, vasoactive intestinal polypeptide, and adrenocorticotropic hormone were negative in ovarian mucinous tumors. Immunohistochemical multiplicity of neurohormones was remarkable in 15 MBT (including 5 müllerian and 10 intestinal MBT) and it was not related to the number of argyrophil cells per unit tumor cells. Individual hormones demonstrated here seemed to be present in different cells, but certain cells were immunoreactive for both gastrin and somatostatin by double immunostaining. Based on the high frequency of endocrine cells, borderline tumors seemed to be unique in the spectrum of mucinous ovarian tumors.

Brenner tumor of the ovary: A correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuronspecific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

An immunohistochemical study of neuroendocrine cells in gynecologic tumors

Various gynecologic tumors with argyrophilia were studied immunohistochemically for chromogranin using two antibodies, antichromogranin and antineuroendocrine. Of seven small cell carcinomas of the cervix, four were immunoreactive with antichromogranin and seven with antineuorendocrine. Argyrophil cells of six cervical adenocarcinomas were all immunoractive with both antibodies. Type I argyrophil cells of 20 endometrial carcinomas were likewise stained positively. However, of the 30 endometrial carcinomas with type II argyrophil cells, 19 showed positive immunoreactivity for chromogranin and 22 for neuroendocrine. Of the ovarian tumors tested, argyrophil cells of 11 mucinous tumors, three carcinoid tumors, and the pancreatic tissue of a malignant mixed germ cell tumor were all chromogranin- and neuroendocrine-immunoreactive. Type I argyrophil cells of five endometrioid carcinomas of the ovary were also immunoreactive with both antibodies. Of the 13 endometrioid carcinomas with type II argyrophil cells, only four showed positive immunoreactivity for chromogranin and only five for neuroendocrine. In conclusion, both antichromogranin and antineuroendocrine detect the specific neuroendocrine markers in close association with argyrophilia in gynecologic tumors, the latter being more sensitive for small cell carcinoma of the cervix, and for type II argyrophil cells in adenocarcinoma of the endometrium and endometrioid carcinoma of the ovary.

C Cell Carcinoma of the Thyroid Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immunohistochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma.

Solid teratomas and mixed Müllerian tumors of the ovary: A clinical histological, and immunocytochemical comparative study

The differential diagnosis between solid teratomas and malignant mixed Müllerian tumors (MMTs) can be difficult, because both tumors have an epithelial as well as a mesenchymal component. Sometimes an MMT is incorrectly diagnosed as a solid teratoma. This has prognostic and therapeutic consequences, because MMTs have a worse prognosis. In this study 20 solid ovarian teratomas and 15 MMTs of the ovary have been compared according to their clinical, histomorphological, and immunocytochemical characteristics. Teratomas occur in the younger age group and are characterized by the presence of argyrophil cells which are immunoreactive to a wide range of neurohormonal peptides and are in addition characterized by the presence of GFAP inununoreactive tissues (glial fibrillar acidic protein). MMTs occur in the older age group and are characterized by the presence of sarcomatous elements and by the absence of an organoid arrangement, neuroectoderm, skin, argyrophilia, and immunoreactivity to GFAP and neurofilament.

Mucosal argyrophil endocrine cells in pernicious anaemia and upper gastrointestinal carcinoid tumours.

The number and density of argyrophil endocrine cells were morphometrically calculated in gastric fundal mucosal biopsy specimens taken from 64 patients with pernicious anaemia (five with gastric carcinoids, 15 with nodular argyrophil cell hyperplasia, 44 with diffuse argyrophil cell hyperplasia) and from 14 healthy controls. Similar calculations were also made on the ileal mucosa away from the tumour of 10 patients with ileal carcinoids and 10 controls. In the stomach, the argyrophil cell counts were twice as high in the patients with pernicious anaemia than in controls and the densities in the whole mucosa or in the epithelial structures were similarly three to five times higher. The cell counts in the patients showed positive correlation with the serum gastrin concentration. The patients with nodular argyrophil cell hyperplasia and gastric carcinoids formed a uniform group with the highest cell counts and serum gastrin concentrations; the difference between the groups was in the longer duration of pernicious anaemia in the patients with carcinoid tumours. On the other hand, no endocrine cell hyperplasia was seen in those with ileal carcinoids. It is concluded that fundal mucosal endocrine cells show an increase in patients with pernicious anaemia that is related to the gastrin concentration. This phenomenon may favour the development of hyperplastic endocrine cell nodules and, eventually, carcinoid tumours.