Carcinoid of the ampulla of Vater

Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.     

The expression of carcinoma-associated antigens and blood-group-related antigens in rectal carcinoids

The immunohistochemical expression of blood-group substances and carcinoma-associated antigens were compared in rectal carcinoids and adenocarcinomas. Rectal carcinoid tumors, in contrast to rectal carcinomas, were consistently negative for CEA, gastrointestinal cancer antigen GICA (or CA 19-9), and carcinoma-associated antigen CA-50 (except in one case where less than 10 percent of the cells expressed CA-50). The carcinoids and rectal carcinomas extensively expressed blood-group substance A, B, and H, Lewis B antigen, and difucosylated carbohydrate antigens (DFCA). Thus, rectal carcinoids and adenocarcinomas possess both similar and different tumor antigen profiles. The occurrence of discrepant antigen determinants may be used in the differential diagnosis of these two types of tumors. The coexpression of blood-group substance A, B, and H, Lewis B antigen, and DFCA is consistent with the opinion that both rectal carcinomas and carcinoids have a common entoderm origin, but carcinoids are considered to rise from the endocrine-differentiated and the adenocarcinomas from the nonendocrine-differentiated enterocytes.     

The diffuse endocrine system and the carcinoids of the alimentary tract. Part I: Orthological aspects and common morphological features of the carcinoids (author's transl)

Carcinoids arise from the so-called system of diffuse clear cells. Because of common histochemical properties it was proposed in the APUD-concept that these endocrine cells are of neural crest origin. As for the gastrointestinal tract endocrine cells this embryological derivation is disputed. Modern methods have led to the identification of about 18 distinct cell types. - According to the different localization of these cells in the alimentary canal the carcinoids show various histological structures i.e., a solid, trabecular, adenoid, undifferentiated and mixed growth. According to the reactivity to silver salts one can distinguish argentaffin, argyrophil and argyrophobe carcinoids. Biochemically and immunohistochemically some carcinoids are multihormonal, while others show paraendocrine hormone production. Small cell anaplastic carcinomas with endocrine granules are highly malignant variants of the carcinoids. There may be a mixed endo- and exocrine (amphicrine) differentiation in normal cells and in the so-called mucicarcinoids.     

Phase II trial of etoposide in APUD tumors

Thirty-three patients with advanced, metastatic APUD tumors (islet cell, carcinoid, or medullary carcinomas of the thyroid) were treated with etoposide as a single agent. Of 29 evaluable patients, four (14%) had partial responses (95% confidence limits, 1%-26%). Toxic effects seen were those previously reported for etoposide as a single agent. Etoposide has activity in APUD tumors; further studies with this agent are indicated.     

Small-granule (neuro)endocrine cells in the infracardiac lobe of a hamster lung. Number, subtypes, and distribution

Small-granule APUD (amine precursor uptake and decarboxylation) endocrine cells were surveyed in 600 3 microns glycol methacrylate-embedded, periodic acid-Schiff (PAS)-lead hematoxylin-stained serial sections comprising 95% of the infracardiac lobe of a hamster lung. Results were confirmed by less systematic study of other hamster lungs. Positions of endocrine cells were marked on cardboard profiles of bronchi and bronchioles for assembly into a 70 X enlarged three-dimensional model from which size and branching of the airway were determined. Records were made for computer analysis of the number and staining patterns of endocrine cells, the nature of contiguous epithelial cells, and the presence of underlying smooth muscle and blood and lymph vessels. APUD cells occurred in 95% of all airways, at a mean density of six solitary cells and 10 cell clusters (neuroepithelial bodies) per millimeter of airway length, measured along the bronchial-bronchiolar long axis. Nineteen percent of endocrine cell loci (29% of all cells) were found at bronchioloalveolar portals in all regions of peripheral lung. Twenty percent of loci (28% of all cells) occurred about the origins of lateral airway branches; these included 4% of loci on carinal points of bifurcation. Two groups of APUD cells had distinctive anatomic relationships: 1) 13% of loci (20% of cells) were related to pulmonary capillaries and venules, mainly at bronchioloalveolar portals; and 2) 39% of loci (53% of cells) overlaid peribronchial muscle, mainly in larger airways where changes in diameter might affect ventilation. In this lobe, APUD cells were not related to goblet or mast cells; 74% of loci abutted Clara and/or ciliated cells, 17% great alveolar cells. Few loci were associated with pulmonary arteries and veins. Five APUD cell types were identified by PAS-lead hematoxylin staining. Types I, II, and V, with granules approximately 0.2 micron in diameter, made up 38%, 45%, and 2% of cells, respectively. Types III and IV, 10% and 5% of cells, respectively, had larger granules. Types I, II, III, and V occurred as solitary cells as well as in neuroepithelial bodies. One-third of the neuroepithelial bodies contained a single cell type; the rest were mixed. Type IV cells, with coarse lead hematoxylin-positive granules, usually were found in large neuroepithelial bodies containing two to four cell types and were never seen occurring alone. We conclude that 1) hamster lungs contain different kinds of APUD cells; 2) those likely have a variety of functions; 3) distinctions merely between solitary and clustered cells may not be significant; 4) the histophysiology of many neuroepithelial bodies probably is more complex than previously suspected; and 5) PAS-lead hematoxylin is superior to argyrophilia and amine fluorescence for light microscopic counting and analysis of pulmonary APUD cells in this species.     

Quantitative studies of argyrophilic APUD cells in airways: II. The effects of transplacental diethylnitrosamine

The effects of transplacental administration of diethylnitrosamine (DEN) on the densities of epithelial and APUD cells in the large and small airways of developing hamsters have been studied quantitatively. The APUD cells are quantitated by relating them to the number of airway epithelial cells; APUD cells are present in similar densities in the large airways (0.12 APUD cells/100 cells) and small airways (0.14) of 2-day-old control hamsters. At 4 days an increase in the densities of APUD cells and an increase in epithelial cells is observed in the small airways, whereas those in the large airways decrease slightly. At later periods there is a progressive decline in the density of APUD cells in the control hamsters. Exposure in utero to DEN results in a generalized increase in APUD cells in 2-day-old hamsters, which is more pronounced in bronchioles (fivefold increase). The effect disappears in older animals. It also results in a transient increase in tracheal epithelial cell density in 7-day-old hamsters. Whether the selective and transient APUD cell hyperplasia induced by transplacental administration of DEN results from proliferation of these cells or from differentiation of other types of epithelial cells into APUD cells requires further study.     

Quantitative studies of argyrophilic APUD cells in airways and intestine: effects of hypothalamic injuries

A morphometric study of argyrophilic Amine Precursor Uptake and Decarboxylase (APUD) cells in airways and intestine of guinea pigs after hypothalamic lesions is reported. APUD cell densities are expressed as APUD cell number/mm of airway or gut perimeter length and as APUD cell/100 epithelial cells. The latter ratio is useful to distinguish generalized epithelial changes from specific alterations in APUD cell densities. Lesions to anterior hypothalamic areas are known to inhibit death due to anaphylactic shock in the guinea pig by a yet to be determined mechanism. It is also known that lesions placed in other hypothalamic nuclei located in the posterior hypothalamus do not interfere with lethal anaphylaxis. Recent quantitative studies of respiratory argyrophilic APUD cells have demonstrated changes in densities of these cells during sensitization and anaphylaxis in the guinea pig, suggesting that they participate in the complex events of anaphylaxis. The present study was performed to determine whether lesions in the anterior and posterior hypothalamus result in changes in APUD cell densities that would suggest a role of the neuroendocrine system in the modulation of lethal anaphylaxis in the guinea pig. The guinea pig has 0.53±2.44 APUD cells/100 nuclei in the larynx, 0.64±0.29 in the trachea, 0.39±0.18 in bronchi, 0.03±0.03 in bronchioles and 10.40±0.70 in the ileum. No significant changes were found in APUD cell densities in animals with hypothalamic lesions when compared to controls, suggesting that mechanisms other than APUD cell hyperplasia or hypoplasia are responsible for the effects of these lesions on lethal anaphylaxis in the guinea pig.     

Neuroendocrine gastric carcinoma. A case report and review of current management

Neuroendocrine or carcinoid tumors of the gastrointestinal tract considered previously extremely rare, are diagnosed at present with increased frequency due to the better capacity to identify neuroendocrine system cells in normal and pathologic conditions. Occasionally, these tumors secrete a great variety of vasoactive substances, producing the carcinoid syndrome. Gastric carcinoids are classified, according to their degree of differentiation into well differentiated and poorly differentiated tumors, also called neuroendocrine carcinomas. Neuroendocrine gastric carcinomas or poorly differentiated gastric carcinoids are seen in 5-15% of all gastric carcinoids, mainly in older male patients. Generally they are large, very aggressive tumors with extensive local infiltration. Due to poor differentiation, they are not frequently associated with an endocrine syndrome. They can be located in any part of the stomach but are mainly seen in antrum. These tumors have an aggressive behavior and must be treated in a radical manner; recurrences are not uncommon. We report the case of a patient with a neuroendocrine gastric carcinoma treated with an en bloc subtotal gastrectomy and colectomy.     

Quantitative studies of argyrophilic APUD cells in airways. III. The effects of sensitization and anaphylactic shock

A morphometric study of argyrophilic APUD cells in airways and intestine of guinea pigs during sensitization with ovalbumin and anaphylactic shock is reported. The APUD cell densities are expressed as APUD cell number/mm of airway or gut perimeter length and as APUD cell/100 epithelial cells. The latter ratio is useful to distinguish specific changes in APUD cells from generalized epithelial changes. Control guinea pigs have greater densities of APUD cells in the larynx (0.075 +/- 0.021 APUD/100 nuclei) than in more distal airways: trachea (0.025 +/- 0.007), bronchi (0.013 +/- 0.003), and bronchioles (0.003 +/- 0.002). In the ileal mucosa APUD cells are present in greatest density: 10.0 +/- 3.0 APUD/100 nuclei. Immunization with ovalbumin followed by sham challenge with saline results in 2- to 10-fold increases in APUD cell densities in all airway sectors as compared to control subjects. These differences are statistically significant in the trachea and bronchioles when ratios of APUD cells/mm are compared to control subjects but only in bronchioles when the ratios of APUD cells/100 nuclei are calculated. Immunization with ovalbumin followed by challenge with this antigen results in similar changes in large airways. However, bronchiolar APUD cells exhibit a 30-fold decrease in density when compared to immunized-sham challenged animals within the limits of our ability to quantitate them. Our findings suggest that argyrophilic APUD cells participate in the complex physiologic events that take place in the lung during sensitization and anaphylaxis.     

Quantitative studies of APUD cells in airways of rats. The effects of diethylnitrosamine and NO2

A method of quantitating the airways amine precursor uptake decarboxylase (APUD) cells is proposed that relates these cells to total airway epithelial cells or airway length. In control rats, these values were 0.13 APUD cells/100 epithelial cells in the trachea, 0.03 in the large airways, and 0.02 in the small airways. In order to evaluate the ability of this method to determine changes in number of APUD cells, rats were exposed to diethylnitrosamine (DEN) and nitrogen dioxide (NO2), which have been reported to increase the number of airways APUD cells. The NO2 exposure was associated with a twofold increase in APUD cells of the trachea only without associated epithelial hyperplasia; DEN produced marked epithelial hyperplasia in the trachea and bronchi with a disproportionate increase in APUD cells in the bronchial epithelium only. The basis of this differential effect requires further study.     

Endocrine-related biochemistry in the spectrum of human lung carcinoma

The association of hormonal syndrome and APUD (amine precursor uptake, decarboxylase) features with small cell carcinoma of the lung (SCC) has suggested that SCC has a separate cell origin from other major forms of lung cancer. Recently, however, both SCC and non-SCC lung cancers have been found to contain small polypeptide hormones and APUD enzymes. The present study quantitates, in 50 samples of human lung cancer tissue, relationships among the 4 major types of lung cancer and endocrine-related properties. Among 4 parameters measured (dopa decarboxylase, histaminase, beta-endorphin, and calcitonin), no single marker clearly separated SCC from non-SCC lung cancer. The high activity of dopa decarboxylase (the "D" in "APUD") best separated SCC from non-SCC, but significant overlap existed even for this critical APUD property. In fact, 2 adenocarcinomas had among the highest concentrations of dopa decarboxylase, histaminase, and calcitonin of any tumor tissue studied. The simultaneous appearance of high levels of 2 or more markers favored SCC. This was quantitated by deriving an index unit based upon the product of the values for the 4 markers in each lesion. This index separated all SCC from all non-SCC lung carcinomas, with the exception of the above 2 adenocarcinomas. Endocrine-related properties thus occur throughout the spectrum of human lung cancer. Biochemical differences between the major histopathological types are quantitative rather than qualitative and probably reflect the fact that the major forms of lung cancer represent a continuum of differentiation within a common cell lineage which includes both SCC and non-SCC lung tumors.     

Small cell lung cancer, endocrine cells of the fetal bronchus, and other neuroendocrine cells express the Leu-7 antigenic determinant present on natural killer cells

Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of normal and malignant neural and neuroendocrine cell types. We have found intense anti-Leu-7 binding to a large number of small cell lung cancers, while other lung cancer types were negative or showed only weak and focal binding. Other antigens expressed by natural killer cells, lymphocytes, and monocytes were never or less often expressed on small cell lung cancer cells. In addition, we report for the first time anti-Leu-7 binding by carcinoids, carotid body tumors, pheochromocytomas, endocrine cells of the fetal bronchus and the adult intestine, and select pancreatic islet cells. Anti-Leu-7 binding by small cell lung cancer is consistent with a derivation from pulmonary precursor cells, and anti-Leu-7 staining is clinically useful for the identification of human neuroendocrine tumors of the amine precursor uptake and decarboxylation ("APUD") type.     

Endocrine cell proliferation in the rat lung following asbestos inhalation

Endocrine cells occur rarely in the adult lung. When they do, they occur mainly in the tracheobronchial lining. These particular cells are thought to be implicated in the development of bronchial carcinoids and oat cell carcinomas. However, there are few reports of abnormal proliferations in animals. Endocrine cells have been found in SPF rats following either chrysotile or crocidolite inhalation for 6 months to 2 years. Attempts to differentiate these cells by conventional light microscopical techniques were unsuccessful. However, the cells were characterised at the ultrastructural level by the presence of dense cored vesicles typical of endocrine cells. The cells were found in several locations in the respiratory portion of the lung. The abundance and various locations of these cells was unexpected.     

Feasibility of the new WHO classification of pulmonary neuroendocrine tumours

Primary pulmonary neuroendocrine tumours present a heterogeneous group of tumours causing problems in diagnosis and treatment. The new WHO classification of lung tumours was published in 1999 in order to improve this situation by combining morphology, immunohistochemistry and clinical background for diagnosis. The aim of our study was to evaluate the feasibility of this classification and to discuss the consequences of modified diagnostic criteria. 50 cases of neuroendocrine tumours and 50 poorly differentiated lung tumours diagnosed in the years 1981-1994 were independently evaluated by three pathologists. The diagnosis of all 27 typical carcinoids (TC) was given by all authors, however, no unanimous agreement was achieved in one of three atypical carcinoids (AC) and two of four large cell neuroendocrine carcinomas (LCNEC). While typical and atypical carcinoids can be distinguished by the number of mitoses or presence of necrosis it was found that the most difficult diagnostic factor for large cell neuroendocrine carcinoma is the recognition of its light-microscopic neuroendocrine features. In consequence it must be distinguished not only from atypical carcinoid or small cell lung carcinoma (SCLC), but also from poorly differentiated carcinoma. Immunohistochemistry is important for the diagnosis of this entity but also for nonsmall cell lung carcinoma with neuroendocrine differentiation (of which 1 case was detected in our series) There was agreement on the diagnosis of small cell carcinomas in all but one case. The results indicate the excellent reproducibility of the WHO classification.     

Management of early gastrointestinal neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) of the stomach, duo- denum, appendix or rectum that are small (≤ 1 cm) and well differentiated can be considered "early" tumors, since they generally have a (very) good prognosis. In the new WHO classification of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs), grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted incidence in the U.S.A. by about 700 % in the last 35 years. Improved early detection seems to be the main reason for these epidemiological changes. Both the better generalavailability of endoscopy, and imaging techniques, have led to a shift in the discovery of smaller-sized (≤ 10-20 mm) intestinal NETs/carcinoids and earlier tumor stages at diagnosis. Endoscopic screening is therefore effective in the early diagnosis, not only of colorectal adenocarcinomas, but also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic surveillance is the treatment of choice in NETs/carcinoids of the stomach, duodenum and rectum that are ≤ 10 mm in size, have a low proliferative activity (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the other intestinal NENs, optimal treatment generally needs surgery and/or medical therapy depending on type, biology and stage of the tumor, as well as the individual situation of the patient.     

Antiulcer Drugs and Gastric Cancer

Inhibitors of gastric acid secretion are efficient drugs in the treatment of acid-related diseases. However, by reducing gastric acidity, hypergastrinemia develops. Gastrin regulates its target cell, the enterochromaffin (ECL) cell, both functionally and trophically. Long-term hypergastrinemia in whatever species studied, has been shown to induce tumors originating from the ECL cell. In man, at least 10 years of hypergastrinemia, accompanied by high or reduced gastric acidity is necessary to induce ECL cell carcinoids. There are reports indicating development of ECL cell carcinoids after long-term treatment with proton pump inhibitors. Moreover, the ECL cell may give rise to gastric carcinomas of diffuse type, which have increased during the last decades. Furthermore, most of the carcinomas developing in patients with long-lasting hypergastrinemia are of ECL cell origin. Therefore, long-lasting iatrogenic hypergastrinemia induced by potent inhibitors of acid secretion may be expected to increase the occurrence of gastric carcinomas in the future.     

Low diacylglycerol values in colonic adenomas and colorectal cancer.

The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis.     

Changes in intestinal mucosa above lymph follicles during carcinogenesis in rats

Summary p Changes in the intestinal mucosa during carcinogenesis were investigated in 36 rats after weekly s.c. injection of 20 mg dimethylhydrazine/kg body-weight. More changes were seen in the large than in the small intestine. In the first week, 60% of colonic lymphoid plaques displayed various crypt abscesses and glandular regenerations. These mucosal changes correspond to the glands covering the lymph follicles, in direct contact with lymphoid cells. Beginning in week 8, dysplastic glands developed in these mucosal areas above the lymph follicles. The number of lymphoid plaques with dysplastic glands in the large intestine increased week by week, attaining 75% in week 20. At the end of week 12 the first adenocarcinoma was detected in the cecum by light microscopy, and classified as a poorly differentiated adenocarcinoma with signet ring cells infiltrating the lymph follicles which contained endocrine cells. The majority of adenocarcinomas (10 cases) occurred in week 20. of these, 7 were localized above the lymphatic plaques in the intestine.Endocrine cells were found in varying numbers in 6 of 10 adenocarcinomas. Three endocrine cell carcinomas, corresponding to human adenocarcinoids or goblet cell carcinoids, developed within the intestinal mucosa; all were identified as poorly differentiated intestinal adenocarcinomas, two of them situated above lymph follicles. These suprafollicular tumors developing from the glandular base, were composed of mucoid cells, endocrine cells, and undifferentiated cells. Microcarcinomas are considered as initial stages of endocrine cell carcinoma.The trend of tumor development above colonic lymph follicles, and the histogenesis of endocrine cell carcinomas and de novo carcinomas is discussed.Dedicated to Professor E. Grundmann on the occasion of his 65th birthday, September 28, 1986Supported by A. v. Humboldt-Stiftung and Ministerium für Wissenschaft und Forschung NRW, grant IV B5-FA 9843Fellow of the Alexander-von-Humboldt-Stiftung     

Zinc in total parenteral nutrition: requirements and metabolic effects.

Rat gastric oxyntic glands contain argyrophil "enterochromaffin-like" endocrine cells that synthesize and store histamine and also have APUD ability--they can take up exogenous L-5-hydroxytryptophan (5-HTP), can decarboxylate it to 5-hydroxytryptamine (5-HT, serotonin) by the enzyme DOPA-decarboxylase, and can store the amine. Previous cytochemical studies suggested that these cells correspond to both the ECL and A-like cells, the two predominant endocrine cells identified by electron microscopy (EM) in rat oxyntic glands. In a recent study, however, we demonstrated that the ECL but not the A-like cell exhibited APUD ability when rat gastric mucosa was incubated with H3-5-HTP and studied by EM radioautography. The purpose of the present study was to identify by EM radioautography the histamine-synthesizing endocrine cells in the rat stomach. Pieces of rat (male Sprague-Dawley) gastric mucosa were incubated in organ culture with L-H3-histidine (50 muCi, 1.8 x 10(-5) M) with and without inhibitors and were processed for LM and EM radioautography. H3-histidine labeled the ECL cells heavily but the A-like and other endocrine cells only lightly. The labeling of ECL cells was only modestly reduced by cycloheximide, an inhibitor of protein synthesis, whereas the labeling of A-like and other endocrine cells was almost abolished. In contrast, the labeling of ECL cells was markedly reduced by 4-bromo-3-hydroxybenzyloxyamine (NSD-1055), an inhibitor of histidine decarboxylase and DOPA decarboxylase, but was not appreciably affected by carbidopa, an inhibitor of only the DOPA decarboxylase. Incubations with H3-histamine (50 muCi, 0.9 x 10(-5) M) failed to label endocrine cells. Thus, this study demonstrates that the ECL but not the A-like cell is the histamine-synthesizing endocrine cell of the rat stomach.     

Apudomas of the lung from the cytochemical and electron microscopic viewpoint

12 small cell anaplastic carcinomas and two bronchial carcinoids have been analysed by light and electron microscopy. Using cytological smears from tumor materials (imprints) silver stainings were applied for detection of argyrophilic and argentaffin nature of APUDoma (Fontana-Masson, Grimelius). The results were compared with ultrastructural findings of neurosecretory granules.