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C Capella

Publications and source records attributed to C Capella.

At least 19 recordsLinked to original sources

Differential diagnostic patterns of lung neuroendocrine tumours. A clinico-pathological and immunohistochemical study of 122 cases.

A series of 3 tumourlets (TLs), 81 typical carcinoids (TCs), 14 atypical carcinoids (ACs) (well-differentiated neuroendocrine carcinomas, WDNCs) and 24 small cell-intermediate cell carcinomas (SCC-ICCs) of the lung were studied. Histopathological features were correlated with amine and peptide hormone immunoreactivity and with clinical data. All types of tumours expressed general neuroendocrine (NE) markers: Grimelius positivity and chromogranins were detected more frequently in well-differentiated (TLs, TCs) than in less well differentiated tumours [ACs (WDNCs) and SCC-ICCs] whereas neuron specific enolase (NSE) was prominent in the latter tumours. TLs and peripheral TCs were benign, often showing a paraganglioid pattern and frequently expressing gastrin-releasing peptide (GRP), which is present in the peripheral airways of normal lung. Central TCs were associated with lymph node metastases in 8.5% of the cases, frequently had a trabecular architecture, often associated with human milk fat globule 2 (HMFG2)-positive acinar and rosette-like structures, and were mainly immunostained for the alpha-subunit of human chorionic gonadotrophin (alpha-hCG) and serotonin. ACs (WDNCs) were associated with intrathoracic and/or extrathoracic metastases in 57.1% of the cases with a mortality rate of 35.7%. Their histological and cytological features were intermediate between those of TCs and SCC-ICCs. ACs (WDNCs) expressed serotonin and alpha-hCG less frequently than TCs. All SCC-ICCs were surgically treated and displayed a mortality rate of 91.6% with a mean survival of 10.2 months after operation. These tumours were characterized by high expression of HMFG2 and NSE, while the expression of both orthotopic (serotonin, GRP) and ectopic (ACTH) specific NE substances was very low. Since all TCs (either central or peripheral) had a favourable outcome, while about 36% of ACs (WDNCs) were fatal, the latter seem more appropriately designated "well-differentiated NE carcinomas". The differential diagnosis between different NE tumours of the lung is important and is mainly based on morphology. Both panendocrine and specific immunohistochemical markers are helpful in distinguishing the less aggressive, mostly benign varieties from the more malignant varieties.

Adult

Neuroendocrine carcinoma within lymph nodes in the absence of a primary tumor, with special reference to Merkel cell carcinoma.

We report eight cases of neuroendocrine carcinomas found within inguinal (five cases), axillary (two cases), and submandibular (one case) lymph nodes. The patients underwent extensive investigations, but no primary tumor was found in any case. Although the existence of an occult or regressed primary cannot be ruled out, the possibility of a lymph node origin should be considered on the basis of epithelial inclusions or anomalous carcinomatous differentiation of stem cells of the lymphoreticular system.

Adult

Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia.

Immunohistological analysis of the expression of lactase protein in adults with hypolactasia has been carried out using monoclonal antibodies. Eight different antibodies that recognize at least three distinct epitopes on the lactase protein each gave the same result. Strong brush border staining was observed in all the lactase-persistent adults. No staining at all was detected in 9 of the hypolactasic subjects. In the remaining 12 individuals a mosaic pattern of expression was observed: small patches of enterocytes stained strongly, whereas the surrounding areas showed no staining at all. Sucrase-isomaltase, in contrast, showed no such mosaicism in these or in any of the other individuals. The mosaicism observed in the 12 hypolactasic individuals suggests that the differentiation of the columnar cells along the villus is not homogeneous. Furthermore, the existence of two patterns of expression of the lactase protein in the lactase-deficient individuals (i.e., absence of protein and mosaicism), if characteristic of the entire length of the intestine of the individuals tested, would suggest the existence of two phenotypes of adult-type hypolactasia in the population studied.

Antibodies, Monoclonal

Morphology and pathogenesis of endocrine hyperplasias, precarcinoid lesions, and carcinoids arising in chronic atrophic gastritis.

The spectrum of endocrine cell changes occurring in 80 cases of body-fundus chronic atrophic gastritis (CAG), mostly type A or multifocal, including various types of hyperplasia, precarcinoid lesions (20 cases), and neoplasia (carcinoid, 24 cases) have been analyzed histologically, histochemically, and ultrastructurally. Changes associated with gland atrophy, pyloric- or intestinal-type metaplasia, regenerative hyperplasia, and hypergastrinemia have been identified and their neoplastic potential evaluated in the light of their proliferative capacity (bromodeoxyuridine incorporation) and clinicopathologic behavior. A close link between disseminated precarcinoid lesions of non-tumor mucosa and multiple carcinoids (carcinoidosis) arising in hypergastrinemic type-A CAG is suggested. Hyperplastic changes, including endocrine cell clusters, seem to have no or only minimal neoplastic potential.

Carcinoid Tumor

Calcitonin free oat-cell carcinoma of the thyroid gland.

Two cases of primary oat-cell carcinoma of thyroid, in a 63-year-old woman and a 73-year-old man, are described. Case 1 was a compound tumour with the oat-cell component merging with a papillary component. Both tumours, in addition to histological features consistent with oat-cell carcinoma, showed immunohistochemical positivity with anti-chromagranin A and anti-synaptophysin antisera. Negative results were obtained when anti-calcitonin and anti-thyroglobulin antisera were employed. Using in situ hybridization, chromogranin A and B messenger RNAs were localized with biotinylated oligonucleotide probes. In contrast, with in situ hybridization, no localization for calcitonin messenger RNA was seen using radioactive and biotinylated probes. It is concluded that these calcitonin-free, small-cell carcinomas should be considered separately from medullary thyroid carcinomas and be regarded as a distinct entity, probably the thyroid equivalent of oat-cell carcinomas of the lung.

Aged

Ultrastructural identification of human secretin cells by the immunogold technique. Their costorage of chromogranin A and serotonin.

We have localized secretin in a morphologically distinctive endocrine cell scattered in the epithelium covering the villi and uppermost crypts of the human duodenum and jejunum. The human secretin cell was characterized by relatively large (mean diameter 299 nm +/- 69 SD), fairly irregular granules, the majority of which showed homogeneous distribution of secretin and chromogranin A immunolabelling in a structurally homogeneous core. Other granules had a targetoid pattern due to an inner, argyrophobe, secretin-immunoreactive body surrounded by an argyrophil, chromogranin A immunoreactive mantle. These targetoid granules represent a distinctive ultrastructural marker of the secretin cell. Secretin cell granules have been shown to react with chromogranin A antibodies and Grimelius' silver, while lacking chromogranin B immunoreactivity. About 1/3 of secretin cells also showed serotonin immunostaining.

APUD Cells

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells.

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.

Antibodies, Monoclonal

The foveolar cell component of gastric cancer.

M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines.

Antibodies

Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia. A newly recognized association.

We report four cases of gastric argyrophil carcinoidosis arising in the oxyntic mucosa of patients with Zollinger-Ellison syndrome as part of type 1 multiple endocrine neoplasia (MEN) syndrome. Multiple mucosal and submucosal carcinoids were seen in combination with innumerable hyperplastic and dysplastic growths of argyrophil endocrine cells disseminated in the entire acidopeptic mucosa. Histochemical and ultrastructural investigation indicated that the argyrophil enterochromaffin-like (ECL) cell, a type of endocrine cell normally restricted to the oxyntic mucosa and very sensitive to gastrin stimulation, was a major component of the carcinoidosis. Five similar cases were found in the literature. Because argyrophil ECL cell carcinoid or carcinoidosis is unusual in patients who have the Zollinger-Ellison syndrome but do not have MEN, we believe that the genetic trait of the MEN syndrome has an important permissive role in the promotion of gastric carcinoids through the hypergastrinemia inherent to Zollinger-Ellison syndrome.

Adult

Classification and histogenesis of gastroenteropancreatic endocrine tumours.

A series of 267 gastroenteropancreatic endocrine tumours has been revised from the point of view of histopathologic diagnosis, hormonal profile and clinical behaviour. Results of this investigation, together with revised concepts on the histogenesis of gastroenteropancreatic endocrine growths, allowed to develop detailed classification systems which proved useful for precise tumour diagnosis and for clinicopathologic correlation, with special reference to tumour function, prognosis and therapy. Among 132 pancreatic growths, various types of islet cell tumours (61 cases), with (45 cases) or without (16 cases) hyperfunctional syndrome, were separated from different types of gut-related (38 cases) and 'ectopic' (three cases) tumours, as well as from 25 non-functioning, locally symptomatic tumours, three small cell carcinomas and two mixed endocrine-exocrine tumours. Among 97 intestinal tumours, 39 argentaffin EC cell carcinoids, mostly from the appendix and ileum, were separated from 23 hindgut-type carcinoids, mostly from the rectum, 22 gastrin cell tumours, mainly from the duodenal bulb, five somatostatin cell tumours, mostly from the periampullary region of the duodenum, and two gangliocytic paragangliomas. Among 38 gastric tumours, five small cell 'neuroendocrine' carcinomas were separated from three gastrin cell tumours and 30 argyrophil carcinoids, 27 of which arose in the body fundus, 16 associated with chronic atrophic gastritis and four with combined Zollinger Ellison/Multiple Endocrine Neoplasia Syndrome.

Biomarkers, Tumor

Endocrine tumors of the duodenum and upper jejunum. A study of 33 cases with clinico-pathological characteristics and hormone content.

Thirty duodenal and three upper-jejunal endocrine tumors are reported. Clinical manifestations included: a) the Zollinger-Ellison syndrome (10 cases); b) peptic ulcer disease in which hypergastrinemia was not documented (3 cases); c) cholestasis or cholelithiasis (4 cases); d) abdominal pain (4 cases); e) gastro-intestinal bleeding (1 case); f) celiac sprue (1 case). Ten further tumors were discovered incidentally, at autopsy or in pathological specimens after gastrectomy or duodenopan-createctomy. Histological pattern was trabecular in 19 cases, insular in 2 and mixed in ten cases. Two cases were typical ganglioneuromatous paragangliomas. All tumors were examined immunohistochemically. Twelve tumors contained gastrin, four somatostatin, six both of these peptides, one serotonin, two both gastrin and serotonin, and two tumors contained gastrin, serotonin and somatostatin. Ganglioneuromatous paragangliomas combined somatostatin and/or pancreatic polypeptide containing endocrine cells with protein-S100-positive Schwann cells. In four tumors no peptide or amine was demonstrated. Gastrin cell tumors (63.6% of our cases), both functionally active (gastrinomas) and clinically silent, predominated in the proximal duodenum, while somatostatin cell tumors (15.1%) and paragangliomas were mostly found in the periampullary region. Two tumors were classified as malignant on the basis of lymph node metastases, and both were jejunal gastrinomas associated with Zollinger-Ellison syndrome. Two somatostatin cell tumors had manifestations of von Recklinghausen's disease.

Adenoma, Islet Cell

Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases.

A group of human breast carcinomas shows morphologic and histochemical evidence of neuroendocrine (NE) differentiation. This study presents a structural, immunologic, and electron microscopic analysis of 51 cases in order to establish positive criteria for identification of these tumors, their incidence, variants, and biological behavior. Argyrophilia (by the Grimelius procedure), presence of chromogranin A and/or B, and of synaptophysin are the most reliable histochemical features, correlating with the ultrastructural demonstration of dense-core secretory granules and of clear vesicles of the synaptic type. Structural features alone may be suggestive, but do not prove NE differentiation, which has to be established by additional techniques. Seven histologic types were identified, but those herein described as types A, B, and C, which show cohesive, mucoid, and mixed patterns, respectively, comprise the vast majority of the tumors. Rare NE carcinomas of the breast show structural similarities to Merkel cell and oat cell carcinomas, and behave as highly aggressive tumors. Type B (mucinous) tumors proved to be relatively indolent, while the most frequent types of endocrine tumors (types A and C) have an intermediate grade of malignancy. The analysis of a consecutive series of 100 cases of breast cancer indicates that about 8% of breast carcinomas display some degree of NE differentiation.

Adult

The gastroenteropancreatic endocrine system and related tumors.

Up to 16 types of endocrine cells have been characterized morphologically (and most of them also functionally) in the gastroenteropancreatic area. Four main groups of pancreatic endocrine tumors (with several subtypes) have been identified: islet cell, ectopic, nonfunctioning, and poorly differentiated tumors. A detailed classification system that combines cytologic and clinicopathologic patterns has been developed for the study of 132 pancreatic tumors. Among a large series (more than 120 cases) of endocrine tumors arising in the gastrointestinal tract, serotonin-producing argentaffin carcinoids have been separated from hindgut trabecular carcinoids, producing glucagon- and pancreatic polypeptide-related peptides, paragangliomas, somatostatin cell tumors, gastrinomas, and argyrophil ECL cell carcinoids. The clinicopathologic profile of the various pancreatic and gastrointestinal tumor entities has been delineated and involvement in the multiple endocrine neoplasia syndrome has been analyzed in detail.

Adenoma, Islet Cell

Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases.

We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II-positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed-type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II-negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II-reactive cells were found significantly more often in advanced than in early diffuse cancers (P less than 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P less than 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P less than 0.01), advanced glandular-type cancer alone (P less than 0.01), advanced glandular- and diffuse- type cancers together (P less than 0.001), and early diffuse-type cancer (P less than 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy.

Humans

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.

Adrenal Gland Neoplasms

The morphology and neuroendocrine profile of pancreatic epithelial VIPomas and extrapancreatic, VIP-producing, neurogenic tumors.

The histology, histochemistry, and ultrastructure of 43 VIP-producing tumors (34 from the pancreas, one jejunal, six retroperitoneal and two mediastinic), 37 of which were associated with the WDHA syndrome, have been investigated on paraffin sections of primary or metastatic tumor tissue. The pancreatic and jejunal tumors showed all structural and secretory patterns of epithelial endocrine tumors, including expression of cytokeratin, neuroendocrine markers like neuron-specific enolase, chromogranins and synaptophysin, peptides like VIP, PHM, GRH, PP, insulin, neurotensin, glucagon, somatostatin and enkephalin, secretory granules, small clear vesicles, peculiar osmiophilic bodies, and occasional formation of tubules or microacini with specialized luminal surfaces. All the remaining tumors were neurogenic, showing either neurons and nerve fibers together with Schwann cells (ganglioneuromas and ganglioneuroblastomas) or endocrine cells (pheochromocytomas) reacting with VIP, PHM, NPY, enkephalin, somatostatin, neuron-specific enolase, synaptophysin, and MAP2 (but not cytokeratin, PP, or GRH) antibodies. A possible origin of pancreatic VIPomas from transformed pancreatic PP cells or ductular stem cells partially committed to differentiation along the PP cell line is suggested.

Adenoma, Islet Cell

Widespread expression of intestinal markers in gastric carcinoma: a light and electron microscopic study using BD-5 monoclonal antibody.

BD-5 monoclonal antibody reacted with tumour cells in 262 of 316 cases of gastric cancers, including 121 of 134 early, 141 of 182 advanced tumours (p less than 0.01), and 113 of 146 glandular, 72 of 83 diffuse, 22 of 25 mucoid, and 55 of 59 mixed tumours. No difference in reactivity was observed between metastatic and non-metastatic advanced tumours. Immunocytochemical techniques applied to light and electron microscopical specimens of colorectal mucosa and gastric cancer showed that BD-5 immunoreactive material occurred in the Golgi complex, in small clear, to dense cored, cytoplasmic vesicles, and in the glycocalix of the luminal and lateral membranes of normal and neoplastic cells in the glands, as well as in the peripheral membrane of dispersed neoplastic cells. Mucin granules stored in the cytoplasm of goblet cells were unreactive or poorly reactive. Ultrastructural features consistent with colorectal type differentiation were observed in many reactive tumours. Unreactive tumours showing ultrastructural patterns consistent with intestinal differentiation, especially of small bowel type, were also observed. Signs of intestinal differentiation, including BD-5 immunoreactivity, often occur in gastric cancer, irrespective of histological type and stage of disease.

Adult