Perivascular mast cells in advanced gastric adenocarcinomas: an electron microscopic study.

Mast cells are frequently found in close proximity to blood vessels and have been implicated in tumour angiogenesis. The aim of the present ultrastructural study was to characterize, in detail, the mutual association between mast cells and microvasculature in 9 cases of advanced gastric carcinoma. Perivascular mast cells were ultrastructurally identified as T mast cells and exhibited piecemeal degranulation, indicative of a slow release of granule-stored contents. In two cases they were adjacent to endothelial cells showing vesiculo-vacuolar organelles, a newly-defined endothelial cell permeability structure. Collagen fibres and dispersed fibrous long-spacing collagen were found near T mast cells in one case, suggesting their role in perivascular collagen degradation and/or turnover. Mast cells were associated with microvascular basal lamina changes including irregular thickness, multiple layers and loose association with endothelial cells and pericytes, reminiscent of degenerating or regenerating blood vessels. In conclusion, our ultrastructural study suggests that mast cells contribute to the remodelling of existing vessels by a slow release of granule-stored contents in advanced gastric adenocarcinomas.

Morphological evidence of neutrophil-tumor cell phagocytosis (cannibalism) in human gastric adenocarcinomas.

The phenomenon of neutrophil-tumor cell emperipolesis or phagocytosis has been documented by light microscopy in various human carcinomas, but little is known about the cellular pathological processes and the morphological changes involved. In an attempt to clarify the nature of this phenomenon, the authors' ultrastructural studies on the relationships among neutrophils and tumor cells in human gastric carcinomas are reviewed and analyzed. At the electron microscopy level, apoptotic neutrophils were found within vacuoles of adenocarcinoma cells in 2 cases. They showed either early apoptotic morphology with perinuclear chromatin aggregation but cytoplasm integrity or late apoptotic morphology with uniform, collapsed nucleus and tightly packed cytoplasmic granules. A light microscopy review of 200 cases of resected gastric carcinomas identified 22 cases (11%) that were characterized by neutrophil-tumor cell phagocytosis (cannibalism). TUNEL staining confirmed the presence of apoptotic neutrophils within the cytoplasm of the tumor cells. This study provides light and electron microscopic evidence of apoptotic neutrophils phagocytosed by gastric adenocarcinoma cells. The morphological features of neutrophil-tumor cell phagocytosis (cannibalism) would suggest a particular mechanism of tumor-immune escape in human gastric carcinoma.

Eosinophil-tumor cell interaction in advanced gastric carcinoma: an electron microscopic approach.

BACKGROUND: Tumor-associated tissue eosinophils have been observed in human tumors and experimental tumor models, but their function is poorly understood. MATERIALS AND METHODS: One case of intestinal-type adenocarcinoma of the stomach, mainly infiltrated by eosinophils, is studied by light and electron microscopy, focusing on the relationships between eosinophils and tumor cells and on the nature of tumor cell death. RESULTS: Using light microscopy, eosinophils, single or in clusters, were present both in the stroma and within neoplastic glands. With electron microscopy, tumor cells in intimate contact with eosinophils revealed changes consistent with autophagic cell death such as chromatin condensation in small masses into the nucleus, dilation of the nuclear envelope, and numerous cytoplasmic vacuoles. The adenocarcinoma cells, not contacted by neutrophils, remained morphologically well preserved. CONCLUSIONS: Our ultrastructural study suggests the hypothesis of a direct relationship between eosinophil infiltration and induction of autophagic cell death in gastric adenocarcinoma cells.

Ultrastructural observations on the microvasculature in advanced gastric carcinomas.

The ultrastructural features associated with vascular permeability in 9 cases of advanced gastric carcinomas were studied, and compared with that of control non-neoplastic mucosa. Tumour microvasculature showed features in common with those of control mucosa, including complete basal lamina, well-developed interendothelial junctions, fenestrations and caveolae. Some tumour blood vessels showed endothelial cell swelling accompained by luminal narrowing and perivascular fibrosis. In 2 out of 9 cases, there were endothelial attenuation with numerous fenestrations and vesiculo-vacuolar organelles. The vesiculo-vacuolar organelle is a recently described cytoplasmic structure found in the endothelial cells lining tumour microvessels and normal venules and which provides an important pathway for extravasation of circulating macromolecules. Our ultrastructural data suggest that advanced gastric carcinomas share with experimental tumour models in vivo only some morphologic features associated with hyperpermeability including fenestration, endothelial attenuation and vesiculo-vacuolar organelles. The implications of perivascular fibrosis on the delivery of immune cells to gastric carcinomas are discussed.

Small early gastric cancer with special reference to macrophage infiltration.

The authors investigate the tumor-infiltrating cells in small early gastric cancer (EGC) (<10 mm) and describe the ultrastructural features and interactions of macrophages with tumor cells and other inflammatory cells. Sections from 20 small EGCs were stained by immunohistochemical methods for CD20, UCHL1, CD4, CD8, and CD68 (electron microscopic examination was used in 6 of the 20). In all of the tumors, CD68-positive macrophages accounted for most tumor-infiltrating cells, with UCHL1-positive T lymphocytes, eosinophils, and neutrophils being the next most frequent. We found only a few CD20-positive B lymphocytes. Electron microscopic analysis revealed macrophages with many phagocytic vesicles, cellular debris, and apoptotic bodies. These morphologic data show that macrophages are actively phagocytic. The tumor cells in contact with macrophages showed no cytopathic changes. These data do not support a macrophage-mediated cancer lysis like the ones reported in some systems in vitro. Contacts among macrophages and other inflammatory cells formed a recurrent ultrastructural hallmark and suggest a communication among varying inflammatory cell types during the precocious host response to gastric neoplasia.

Clinicopathological features of early gastric cancer in younger versus older patients in a high incidence area of northern Italy.

AIMS: The relationship between the clinicopathological features of early gastric cancer and age were analysed in a retrospective study of 168 patients. METHODS: 168 patients, residents of the Region of Cremona, who had undergone surgery in the period 1978 to 1990 for early gastric cancer, were divided into two groups by age and compared. Group I (n = 89) consisted of patients less than 65 years of age and Group II (n = 79) of patients between 66 and 85 years of age. RESULTS: There were no significant differences between the two groups with respect to the sex ratio, tumour size, depth of tumour invasion, and 5-year survival rate. Group I patients showed more lymph node involvement (p < 0.01), cancer of the diffuse histological type (p < 0.01), and cancers located in the gastric body (p < 0.05). Conversely, Group II exhibited more cancers of the protruded (p < 0.05) and intestinal histological type (p < 0.01), and more adenomatous residue (p < 0.01). CONCLUSIONS: Our findings suggest that early gastric cancer may present differently in different age groups; persons 65 years of age and older are more likely to have early gastric cancer of the slow-growing type than middle-aged patients.

Mast cell interaction with tumor cells in small early gastric cancer: ultrastructural observations.

The authors studied the mast cells by light and electron microscopy in four small intramucosal early gastric cancers (EGC). Mast cells were found in the tumor stroma and among neoplastic cells of adenocarcinoma glands. Stromal and adenocarcinoma-infiltrating mast cells were ultrastructurally identified as T mast cells, and exhibited anaphylactic or piecemeal degranulation. Tumor cells in intimate contact with mast cells showed no cytopathic changes. These data do not support a mast cell-mediated cancer lysis, such as that reported in some systems in vitro. The interepithelial localization of T mast cell in adenocarcinoma glands is similar to that observed in some disease states, including interstitial cystitis, fibrotic lung disorders, and mucosal allergic reaction. The findings suggest that T mast cells may be involved in the pathophysiology of the host reaction to small intramucosal EGC.

Microsatellite instability in early gastric cancer.

Microsatellite replication errors (RERs), consisting in random tumour-associated allele contractions or expansions, represent a frequent genetic alteration in gastric cancer and appear to be associated with important clinicopathologic parameters. To verify the role of microsatellite instability in the initial phases of gastric carcinogenesis, we analysed the status of II microsatellites in paired microdissected samples of tumour and unaffected mucosa from 30 cases of early gastric carcinoma. Fifteen tumours (50%) demonstrated RERs: these included 7 cases with RERs at one locus and 8 cases with RERs at 2 or more loci. Cases with 2 or more RERs were more frequent among intramucosal tumours, compared to tumours with submucosal spread (43% vs. 12%) and among tumours staged T1NOMx, compared to tumours staged T1N1Mx (35% vs. 0%). RER-positive microsatellite typings were statistically more frequent among tumours with intramucosal extension, lower stage (T1NOMx) and excavated growth pattern (macroscopic type III), compared to tumours with submucosal extension, higher stage (T1N1Mx) and elevated, flat or depressed growth patterns (macroscopic types IIa-IIb-IIc respectively). The above findings indicate that microsatellite instability occurs early in the progression of sporadic gastric cancer and tends to be associated with good prognostic indicators.

Report of an intrapulmonary solitary fibrous tumor: fine-needle aspiration cytologic findings, clinicopathological, and immunohistochemical features.

The authors describe a rare case of intrapulmonary solitary fibrous tumor (SFT). Morphologically, the tumor showed a disorganized or "patternless" arrangement of plump to spindle cells in a collagenous stroma. Tumor cells were immunoreactive for vimentin, but not for keratin, carcinoembryonic antigen, epithelial membrane antigen, factor-VIII related antigen, S-100 protein, desmin, and actin. These immunohistochemical findings suggested fibroblastic differentiation, in keeping with the putative submesothelial origin of the tumor. The problems concerning the fine-needle aspiration (FNA) preoperative diagnosis of SFT are briefly discussed.

Ultrastructural study of the vascular response in small early gastric cancer.

The microvasculature of the stroma of four cases of small early gastric cancer (EGC) was investigated by conventional electron microscopy. Severe damage to small and large fenestrated capillaries was observed around endothelium-adherent, partially degranulated neutrophils. The findings suggest the existence of neutrophil-mediated injury of endothelial cells during the development of inflammatory responses in small EGC. The severely injured microvessels exhibited increase in vasopermeability, microhaemorrhage, and platelet aggregates. Other microvascular changes included endothelial cell and pericyte activation as well as basal lamina replications, indicative of repeated episodes of endothelial injury, necrosis and regeneration. This new capillary growth within the old basal laminas shared morphological features with a peculiar angiogenic process described in man and animals.

Neutrophil interaction with tumour cells in small early gastric cancer: ultrastructural observations.

The authors studied the neutrophil inflammatory reaction by light and electron microscopy in 4 small early gastric cancers (three tubular adenocarcinomas and one adenocarcinoma with signet-ring cell component), selected for the absence of coagulative necrosis and ulceration. Neutrophils showed ultrastructural signs of activation such as aggregation, adhesion and lipid bodies. Some neutrophils were found to be in intimate contact with the intact tumour cells and with those that displayed a varying degree of damage. In particular, relatively early damage, such as disorganization of the intermediate filaments and dilatation of the rough endoplasmic reticulum, occurred at the contact regions. In spite of the severe damage to the tumour cells, the neutrophils themselves were intact. These findings are discussed in relationship to a number of recent studies of the neutrophil-mediated tumour cell injury, in man and animals.

Minute and small early gastric carcinoma with special reference to eosinophil infiltration.

The authors examined 25 minute early gastric cancers (EGC) and 13 small EGC in order to investigate the incidence and possible causes for the infiltration of eosinophils. The degree of eosinophil infiltration was higher in tumour stroma than in adjacent normal-appearing mucosa; this correlation was statistically significant (P < 0.001). Tumour-associated tissue eosinophilia (TATE) was not correlated with size, histological type, necrosis of the tumour nor gastritis activity in adjacent non-tumoral mucosa. Electron microscopy, performed in 4 cases of small EGC, showed tumour stromal eosinophils with morphological evidence of activation similar to those described for tissue eosinophils in various disorders. Some tumour cells in intimate contact with activated eosinophils exhibited focal cytopathic changes. TATE represents local inflammation probably leading to tumour cell damage. The immunological role of the eosinophils against tumour cells in vivo deserves further investigation.

Immunocytochemical detection of lactoferrin in human gastric carcinomas and adenomas.

In gastric carcinomas, including 20 cases of intestinal type and 10 cases of diffuse type, in adenomas with mild to severe dysplasia (20 cases), and in hyperplastic polyps (10 cases), the presence of lactoferrin was investigated by immunohistochemistry. Incomplete or complete intestinal metaplasia or both and normal gastric mucosa were also tested. Preoperative hematocrit and serum iron levels (18 patients) were recorded. An evident reactivity for lactoferrin was encountered in intestinal type carcinomas, adenomas, and incomplete intestinal metaplasia, whereas diffuse-type carcinomas, hyperplastic polyps, and complete intestinal metaplasia were always unstained; mucous neck cells of the antrum and body were also positive for lactoferrin. The results are discussed in relation to the increased requirement of iron by neoplastic cells, although in gastric carcinomas serum iron levels appear to be unrelated to the immunohistochemical presence of lactoferrin.

Morphological demonstration of non-heme iron and iron-binding proteins in placentas from cases of congenital nephrotic syndrome of Finnish type.

Two placentas (gestational age 36 and 39 weeks respectively), obtained from Congenital Nephrotic Syndrome of Finnish type (CNF) cases, have been studied by histochemistry in relation to the presence of non-heme iron and iron-binding proteins (ferritin, transferrin and lactoferrin). Ten control placentas of gestational age ranging from 35 to 40 weeks have been also examined. Employing the Prussian Blue ferrocyanide method, an intense positive reaction of the trophoblastic basament membrane (TBM) was observed only in cases of CNF. By immunoperoxidase techniques, ferritin was demonstrated in the villous stroma whereas lactoferrin was identified only in the cytoplasm of polymorphonuclear neutrophils within fetal stem vessels; a clear positivity for transferrin was encountered on the apical site of the syncytial trophoblast. All these immunohistochemical findings were similar in CNF cases and in control placentas. Ultrastructural observations of terminal villi revealed the presence of osmiophilic granulo-filamentous hemosiderin-like bodies in TBM of placentas from CNF. Although the role of iron-binding proteins in the iron transport through the placenta seems to be unaltered in CNF, the presence of non-heme iron in TBM could represent a histochemical approach for placental diagnosis in this type of nephrotic syndrome.

Vascular changes in placentae from cases of materno-fetal rhesus incompatibility.

Three placentae from cases of materno-fetal Rhesus incompatibility have been studied electron microscopically. An abnormal villous vascular arrangement with dilated capillaries and newly formed vessels and stromal edema were the most characteristic findings. Syncytiotrophoblastic trophic changes and focal thickening of the trophoblast basement membrane were also found. It is suggested that placental changes observed in Rh incompatibility could be related to endothelial cell damage.

Persistent neonatal normoinsulinaemic hypoglycaemia.

A case is recorded of persistent neonatal hypoglycaemia characterized by early onset, normoinsulinaemia and improvement following glucagon therapy. The pancreatic A cell were very few in number and were mainly degranulated. There was a slight increase of B cells, but changes in cells producing somatostatin and human pancreatic polypeptide were not encountered. The differential diagnosis is discussed with the conclusion that the most probable causative factor was the deficiency of A cells.