Mucinous cystadenocarcinoma of the pancreas. Morphologic and immunocytochemical observations.

Twenty mucinous cystadenocarcinomas of the pancreas, most of which occurred in the tail of the pancreas in middle-aged women, were examined histologically and by immunohistochemical stains. Thirteen tumors displayed a marked histological heterogeneity and expressed intestinal differentiation as shown by the colonic appearance of the glands both at the light- and electron-microscopic levels. Other intestinal features included varying numbers of goblet cells, argyrophil and argentaffin cells, and even Paneth cells. By immunohistochemistry, endocrine cells were present in 13 of the 20 tumors (65%) and were more numerous in the poorly differentiated than in the well-differentiated epithelial component of the tumors. Serotonin-containing cells were the most common endocrine cells, followed by somatostatin-containing cells and cells that showed immunoreactivity for pancreatic polypeptide and gastrin. However, none of the patients had clinical manifestations of carcinoid, somatostatinoma, or the Zollinger-Ellison syndrome. The findings support the hypothesis that mucinous cystadenocarcinomas of the pancreas arise from an "endodermal stem cell" that differentiates into cells with intestinal phenotypes.

Hyperplastic lesions of the gastrointestinal endocrine cells.

A substantial body of knowledge is presently available on the morphologic, histochemical, ultrastructural, and functional characteristics of both the normal endocrine cell population of the gut and their related endocrine tumors. In contrast to this, we have only recently begun to recognize the existence of hyperplastic proliferations of various endocrine cell types, and information is therefore steadily accumulating on the morphologic criteria for their recognition, their clinicopathologic correlates and the clinical relevance of this morphologic finding. Hyperplastic proliferations of various endocrine cell types most often develop as a secondary phenomenon in a variety of clinical situations, and may modify the clinical course of the associated condition in a manner that underscores the functional interrelationships these endocrine cells have not only with each other but with other cell types as well. However, similar proliferations may also occur as a primary event (e.g. primary antral G-cell hyperplasia) and give rise to clinical and biochemical features attributable to the overproduction of their specific hormonal product (e.g. Zollinger-Ellison Syndrome, type I). This communication provides a broad overview of the current state of our knowledge of hyperplastic lesions of a variety of gut endocrine cell types in humans, their pathophysiologic significance, their relationship (if any) to the subsequent development of endocrine tumors (i.e. the hyperplasia-neoplasia sequence), and the utility of certain experimental models for the study of such proliferations in a variety of animal species.

Primary gastrin cell hyperplasia. Report of five cases and a review of the literature.

Primary gastrin cell hyperfunction of the gastric antrum as a clinical syndrome consists of basal hypergastrinemia, an exaggerated gastrin response to feeding, the absence of any ectopic source of gastrin secretion, and peptic ulcer disease. The number of G-cells were quantitated in the gastric antrum of five patients with clinically diagnosed primary G-cell hyperfunction, and the results were compared to controls with a variety of gastric diseases. Patients with the clinical diagnosis of primary G-cell hyperfunction had a significantly increased number of antral G-cells (p less than 0.05). The clinical syndrome of primary G-cell hyperplasia appears to be associated with hyperplasia of G-cells rather than with the hypersecretion of gastrin by a normal number of G-cells.

Brain-stem and adrenal abnormalities in the sudden-infant-death syndrome.

Fourteen of 28 sudden-infant-death syndrome (SIDS) victims had an abnormal proliferation of astroglial fibers in their brain stems and an enlarged mass of chromaffin cells in their adrenal medullas. Both of these abnormalities were associated with greater than normal muscle in the small pulmonary arteries, abnormal brown fat retention, and retained extramedullary erythropoiesis. These latter three findings are probably evidences of chronic alveolar hypoventilation and hypoxemia. The brain stem and adrenal abnormalities are probably also secondary to chronic hypoxemia.

Incidence and significance of argentaffin and paneth cells in some tumours of the large intestine.

The incidence of argentaffin and Paneth cells in epithelial tumours of the large intestine was investigated. Argentaffin cells were found in adenomatous polyps, villus adenomas, polyposis coli, Peutz-Jehgers' polyps, juvenile polyposis, and adenocarcinomas. Paneth cells were not found in metaplastic or juvenile polyps. The crypt unit was destroyed in neoplasia and argentaffin and Paneth cells occurred either as a result of sequestration or were taking part in the neoplastic process. The crypt unit was retained in the disorders of epithelial growth. The identification of argentaffin and Paneth cells enabled the crypt to be defined and thus provided a useful, practical aid in the differentiation between neoplasms and disorders of epithelial growth.

Argyrophil cells in normal, hyperplastic, and neoplastic endometrium.

Scanty argyrophil cells are present in a substantial proportion of normal endometria, particularly during the secretory stage of the cycle. Argyrophil cells are also present in the various types of hyperplastic endometria and are found in more than half of endometrial adenocarcinomas. In some endometrial neoplasms they are present in abundance, but tumours rich in such cells do not have any features suggestive of a carcinoid tumour and are morphologically identical to adenocarcinomas of similar grade which are devoid of argyrophil cells. Endometrial adenocarcinomas containing argyrophil cells tend to be well differentiated and tend not to invade deeply into the myometrium. It is suggested that Müllerian epithelial stem cells possess a potentiality for differentiation into APUD cells.

Ultrastructure of malignant paraganglioma of organ of Zuckerkandl.

Electron microscopic study of a malignant paraganglioma of the organ of Zuckerkandl revealed similarities between the tumor and the normal paraganglia. The well-differentiated portion of the tumor recapitulated the structure of the basic functional units of the paraganglion. In addition there signs of anaplasia both at the histologic and ultrastructural level. Large neurosecretory granules were noted in some of the tumor cells, but most of the cells were agranular. Crystaloids resembling those seen in alveolar soft part sarcoma were also noted. The study supports the theory on the common origin and histogenesis of paragangliomas and alveolar soft part sarcomas.

Effect of repeated immobilization stress on the uptake of exogenous [3H]dopamine in adrenal chromaffin cells of mice.

Uptake of [3H]dopamine in adrenal chromaffin cells of the mouse during repeated immobilization was examined by autoradiography. Repeated daily immobilization of mice resulted in an increased uptake of [3H]dopamine to the level of denervated chromaffin cells. The increase was observed only in adrenaline-storing (A) cells, not in noradrenaline-storing (NA) cells. The results indicate that sympathetic outflow to the adrenal gland, especially to A cells, is ceased or blocked during the adaptation to stress.

NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells.

Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.

Histopathology, cytology and cytochemistry of pheochromocytomas and paragangliomas including chemodectomas.

The results of histopathological, histochemical and ultrastructural investigations on pheochromocytomas and paragangliomas have been reported. These results allowed the functional identification of the cell types composing many of such tumours. Moreover, comparison of these data with clinico-pathologic findings outlined the advantages and limits of cytologic studies for understanding the natural history of pheochromocytomas and paragangliomas and improving our diagnostic and prognostic criteria.

Lysosomes in Brenner's tumor simulating secretory argentaffin granules.

Argentaffin cells were searched for in the epithelial nests of 30 Brenner's tumors, with the Fontana-Masson stain for the screening. Although these cells were found in five tumors, ultrastructural examination of one case, in which the argentaffin cells were multiple, identified the cytoplasmic granules as lysosomes and not as amine precursor uptake and decarboxylation (APUD)-type granules. We conclude that the epithelial component of Brenner's tumors consists of urothelium only and does not include the cells containing argentaffin APUD-type granules.

Fine-needle aspiration cytology of pheochromocytoma-ganglioneuroma of the organ of Zuckerkandl.

Fine-needle aspiration (FNA) cytologic and immunocytochemical findings of a rare combined pheochromocytoma-ganglioneuroma developing in a 48-yr-old Japanese man in the organ of Zuckerkandl are described. This is the first report of a combined pheochromocytoma-ganglioneuroma of the organ of Zuckerkandl. FNA cytology showed typical cytologic findings of these two components similar to those described individually in fine-needle aspirates of these neoplasms. The neoplastic cells showed positive reactions for vasoactive intestinal polypeptide, neuron-specific enolase, and S-100.

[Histological analysis of the gastric mucosa, enterochromaffin cells and gastrin-producing cells in endoscopic biopsies of patients with achlorhydria]. / Análise histológica da mucosa gástrica, das células enterocromafins e das produtoras de gastrina em biopsias endoscópicas de pacientes com acloridria.

Twenty achlorhydric patients and five controls were submitted to gastric endoscopic biopsies in order to study the histological pattern of the gastric mucosa and the number of enterochromaffin (EC) and gastrin (G) cells of the antral mucosa. The histological changes of the oxyntic mucosa of achlorhydric patients were variable being the predominant pattern the severe chronic atrophic gastritis. The antral mucosa was normal in appearance or revealed mild degree of gastritis. In the most achlorhydric patients the antral EC cell number was decreased when compared to the controls and the G cell number were relatively numerous. The results of the present work are suggestive of an increased G:EC cell ratio in achlorhydric patients.

[Changes in the dimensions of cells and their nuclei in the adrenal medullary substance of white rats during acute overheating]. / Izmenenie razmerov kletok i ikh iader v mozgovom veshchestve nadpochechnikov belykh krys pri ikh ostrom peregrevanii.

It has been shown for the first time that the size of adrenocytes and of their nuclei does not change in the adrenal medulla on the state of motor excitation, and decreases at the heat stroke under conditions of acute overheating. According to Bennighoff (1950), the decrease of nuclear volume suggests the weakness of the adrenocyte secretory activity. But in reality the specific activity of adrenocytes may increase at hyperthermy, which contradicts to the hypothesis in question. Such a contradiction may be explained by the fact of adrenocyte dehydration under the influence of the external heat. It may result in a decrease in the nuclear volume irrespective of the functional state of the nuclei. The secretory activity of adrenocytes can be evaluated on the basis of the changed relation in the nuclear number of varying volume corresponding to different steps of the secretory cycle.

[Diagnosis and etiology of Barrett esophagus. Presence of gastrin secreting cells (G cells)]. / Diagnóstico y etiología del esofago de Barrett. Presencia de células secretoras de gastrina (G).

We present the patterns for the diagnosis, checking the clinical, radiological, endoscopical and histological data of 35 patients suffering from Barrett's Esophagus (BE) (columnar metaplasia lining the lower esophagus). The clinical characteristics are those of a severe esophagitis of long evolution, although metaplasia itself is asymptomatic, and its features depend on the inflammation degree. Radiology can bring out some data as GE reflux, hiatal hernia, ulcers or stricture, and perhaps double contrast may show any sign by means of which endobrachyesophagus (EBE) can be suspected. Endoscopy provides us with accurate data about EBE, ulcers, stricture and inflammation. Histology reveals the type of columnar metaplasia (junctional or cardial, gastric fundic, intestinal or specialized, or composite). Acquired or congenital etiology can be clarified by an immunohistochemical method, Peroxidase anti-Peroxidase (PAP), showing the presence of gastrin secretory cells (G cells) in the congenital cases.

[Cytologic mechanisms of postnatal growth of adrenal chromaffin tissue]. / Tsitologicheskie mekhanizmy postnatal'nogo rosta khromaffinnoi tkani nadpochechnika.

We have studied the contribution of proliferation and hypertrophy of glandular cells to the ontogenetic growth of adrenal chromaffin tissue using several methods (organometry, cytometry, cytophotometric quantitation of DNA in the nuclei, radioautographic analysis of 3H-thymidine incorporation, calculation of the mitotic index and proportion of binuclear cells, as well as stereological analysis). Mitotic division of diploid glandular cells is the main cellular mechanism of postnatal growth of chromaffinocytes. It is most prominent during the first 2 weeks of life and is maintained at a rather high level throughout the life of animals (the daily proliferative pool in 6-month-old and 30-month-old rats equals 0.3%). Development of cellular hypertrophy has been noted during the first 6 months after birth. The population of chromaffinocytes throughout life is practically diploid; the proportion of tetraploid (binuclear) cells does not exceed 1-1.5%. The growth of adrenal chromaffin tissue during the first month of life is generally supported by hyperplasia and hypertrophy of norepinephrocytes and later of epinephrocytes. The contribution of cell proliferation and hypertrophy to postnatal growth of each subpopulation appears to be equal.

G-cells and gastrinaemia in chronic nonspecific bulbitis.

Chronic nonspecific bulbitis (CNB), the number of G-cells in the antrum and the level of serum gastrin were unrelated in a group of 24 patients. Gastrin may be produced by cells outside the antrum or by a few but hyperactive antral G-cells.

The distribution of duodenal G cells in duodenal ulcer patients.

The number of G cells is evaluated in biopsy specimens of fundic, antral and duodenal mucosa from the bulb, second and third parts in 10 patients with duodenal ulcer, and compared with that observed in 6 normal controls. G cells are absent in fundic mucosa but in the antrum their number in duodenal ulcer patients does not differ from that of controls and is strictly related to the histological pattern of the mucosa. In the second and third duodenum of duodenal ulcer patients the number of G cells is significantly higher in comparison with controls, while in the bulb the two groups do not differ significantly. Moreover, when different duodenal portions are compared no differences in the number of G cells are observed in the duodenal ulcer group; while in controls the bulbar number of G cells is higher in comparison with second and third duodenum.

[Endocrine cells in cancer of the ampulla of Vater]. / Endokrinnye kletki v rake faterova soska.

Histochemical examinations of 28 cancers of Vater's papilla detected argirophilic cells in 7 (25%) and argentaffinic cells in 3 (10.8%) tumors. Neoplastic endocrine cells occurred most frequently in structures of the highly differentiated papillary and tubular adenocarcinoma. The analysis of the qualitative composition of mucus produced by these tumors showed the likelihood of detection of endocrine cells in cancer of Vater's papilla to increase with higher secretion of acid mucopolysaccharides and to decrease with a higher portion of sulphomucines in them. The occurrence of impregnated endocrine cells and non-sulphated acid mucopolysaccharides in cancers of Vater's papilla appears to indicate the differentiation of the tumor tissue in the direction of the intestinal epithelium. The regular participation of argentaffinic and argirophilic cells in the development of intestinal tumors, in particular, cancer of Vater's papilla is in favour of the entodermal origin of endocrine cells of the gastrointestinal tract.

[Dynamics of changes in enterochromaffin cells during tumor growth]. / Dinamika izmenenii énterokhromaffinnykh kletok pri opukholevom roste

A distinct correlation was found between changes in enterochromaffin cells producing highly active chemical substances--melatonin and serotonin, and stages of the neoplastic process. In early stages of tumor development a marked hyperplasia of enterochromaffin cells was noted, that was associated with enhancement of their histochemical properties. In advanced forms of cancer and chronic leucosis the number of cells is markedly reduced with simultaneous diminishing of their staining by specific histochemical methods. Such kinetics of changes of enterochromaffin cells appears to be related with definite antiblastic properties inherent to them and their products (melatonin and serotonin).