Neutrophil-rich gastric carcinomas: light and electron microscopic study of 9 cases with particular reference to neutrophil apoptosis.

The authors report 9 cases of gastric carcinomas characterized by a prominent neutrophilic infiltration of the stroma. These tumors (8 of intestinal type, 1 of diffuse type) showed a pushing growth pattern. Metastatic involvement of regional lymph nodes was seen in 5 cases. The metastatic foci were associated with heavy neutrophilia as well. There was no histologic evidence of Helicobacter pylori infection, whereas various degrees of multifocal intestinal metaplasia were present in the background mucosa. Based on histologic and histochemical results, there were no apparent causes due to other infectious agents responsible for the neutrophil-rich gastric carcinomas. Some of intraepithelial and stromal neutrophils exhibited apoptotic changes, such as chromatin condensation and cell shrinkage, and were TUNEL-positive. Electron microscopy disclosed apoptotic neutrophils in cytoplasmic vacuoles of tumor cells, a finding suggestive of neutrophil-tumor cell phagocytosis (cannibalism). Different stages of neutrophil apoptosis were also shown by electron microscopy and the ultrastructural findings were compared to those described in experimental models, both in vivo and in vitro.

Ultrastructural descriptions of pericyte/endothelium peg-socket interdigitations in the microvasculature of human gastric carcinomas.

BACKGROUND: Angiogenesis requires complex multistep signalling pathways and a high degree of spatial and temporal coordination among endothelial cells and pericytes. The two cell types exhibit numerous contacts in vivo and in vitro, including the occurrence of peg-socket junctions. MATERIALS AND METHODS: Ultrastructural findings in 9 cases of advanced gastric carcinomas were reviewed with special emphasis on endothelium/pericyte peg-socket junctions. RESULTS: The incidence of peg-socket junctions was approximately 8% in 5 out of 9 cases. The remaining 4 cases showed a very low rate, including two cases in whom interactions were totally absent. Peg-socket junctions consisted of cytoplasmic projection from the pericyte protruding into the endothelial indentation. The endothelial cells interacting with pericytes showed ultrastructural signs of partial stabilization such as continuous endothelial lining, regularly constructed interendothelial junctions, more or less integrated pericytes, and multilayered basement membrane. CONCLUSION: Our ultrastructural study confirms previous reports regarding pericyte/endothelial peg-socket interdigitations in murine and human granulation tissues and extends these findings to the microvasculature of human gastric carcinomas.

Granulomatous inflammatory reaction in human gastric adenocarcinomas: a light and electron microscopy study.

Granuloma is a focal, compact collection of inflammatory cells in which mononuclear phagocytes predominate. The authors report 9 cases of papillary-tubular gastric adenocarcinomas characterized by mature granulomas associated with recent microhemorrhages. Mature granulomas were composed of foamy, CD68-positive histiocytes with occasional giant cells. Hemosiderin-containing macrophages were present in the tumor stroma, suggesting phagocytosis of erythrocytes. Under electron microscopy, mature (nonepithelioid) granulomas and clusters containing 1 macrophage and 1-3 eosinophils were found. This study provides morphological examples of skewed type II macrophage infiltration in gastric adenocarcinomas that is involved in scavenging activity, particularly erythrophagocytosis, formation of mature (nonepithelioid granulomas), and heterotypic aggregation with eosinophils.

Krukenberg tumour of the ovary: a case report with light microscopy, immunohistochemistry and electron microscopy study.

A rare case of a 46-year-old woman with bilateral Krukenberg tumours is reported. Histologically, oedematous ovarian stroma was infiltrated by signet-ring cells arranged singly, in cords or in nests. Immunoreactivity for cytokeratin-7, carcinoembryonic antigen as well as histochemical positivity for mucins demonstrated the epithelial nature of the tumour. The gastric primary site was suggested by the cytoplasmic immunoreactivity for MUC-5AC and by ultrastructural evidence of gastric differentiation in signet-ring cells such as mucous granules with eccentric dense cores and intracellular microcysts, lined by sparse microvilli. Gastric biopsy, performed after pathological diagnosis, revealed a signet-ring cell carcinoma similar to that in the ovaries, confirming the gastric origin of the Krukenberg tumour. Because none of the individual immunohistochemical markers used for tissue identification is both site specific and site sensitive, electron microscopy in combination with immunohistochemistry is a valuable tool for the pathologist in the diagnosis of the tissue origin of a Krukenberg tumour.

Mast cell and eosinophil interaction in gastric carcinomas: ultrastructural observations.

BACKGROUND: An increase in the number of mastocytes has been described in some human neoplasms, mainly in gastric and colorectal cancer. MATERIALS AND METHODS: A case of diffuse-type gastric carcinoma, mainly infiltrated by eosinophils and mast cells, was studied using light and electron microscopy. RESULTS: Using light microscopy, cell clusters containing one mast cell and one to three eosinophils were found in the tumour stroma. Electron microscopy of this unusual stromal element revealed that mast cells established areas of junctions with eosinophils. Moreover, focal polarized exocytosis of mast cell granules was found in the areas of junctions with eosinophils. Eosinophils in contact with mast cells showed signs of important in situ activation, such as alterations in the size and number of granules, cytoplasmic vacuoles, and scattered extracellular granules. CONCLUSION: Our ultrastructural study provides morphological evidence of cross-talk between activated mast cells and eosinophils that may play an important role in the enhancement of host immunity against cancer cells.

Gastric hepatoid adenocarcinoma with autophagy-related necrosis-like tumor cell death: report of a case.

A case of hepatoid adenocarcinoma of the stomach is presented. The characteristic features of the tumor are summarized on the basis of the authors' experience and the literature. Ultrastructural examination revealed patchy condensations of chromatin throughout the nucleus suggestive of necrosis-like programmed cell death (PCD). These nuclear alterations were associated with the occurrence of vacuoles and lipofuscins, conferring an autophagic phenotype to this PCD. Thus, the case reported here provides an example of autophagic-related necrosis-like PCD. Alternative PCDs are reviewed and their morphologic distinction is discussed.

Synthesis, characterization, antibacterial activity and cytotoxicity of hollow TiO2-coated CeO2 nanocontainers encapsulating silver nanoparticles for controlled silver release.

Biomaterials as implants are being applied more extensively in medicine due to their on-going development and associated improvements, and the increase in human life expectancy. Nonetheless, biomaterial-related infections, as well as propagating bacterial resistance, remain significant issues. Therefore, there is a growing interest for silver-based drugs because of their efficient and broad-range antimicrobial activity and low toxicity to humans. Most newly-developed silver-based drugs have an extremely fast silver-ion release, increasing adverse biological impact to the surrounding tissue and achieving only short-term antimicrobial activity. Nanoencapsulation of these drugs is hypothesized as beneficial for controlling silver release, and thus is the aim of the present study. Initially, an amorphous or crystalline (anatase) titania (TiO2) coating was synthesized around silver nanoparticle-containing (AgNP) ceria (CeO2) nanocontainers using a sonication method forming AgNP/CeO2/TiO2 nanocontainers. These nanocontainers were characterized by high-resolution transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, gas sorption experiments and energy-dispersive X-ray spectroscopy. Silver release, monitored by using inductively coupled plasma optical emission spectroscopy, showed that these containers prevented silver release in water at neutral pH, and released the silver in concentrated nitric acid solution (pH = 1.1). The AgNP/CeO2/TiO2 nanocontainers showed an antibacterial activity against E. coli, however a concentration-dependent cytotoxicity towards a model epithelial barrier cell type (A549 cells) was observed. These nanocontainers offer the concept of potentially controlling silver delivery for the prevention of implant-associated infections.

HER2 Status in Premalignant, Early, and Advanced Neoplastic Lesions of the Stomach.

OBJECTIVES: HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC. RESULTS: HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases. CONCLUSIONS: HER2 overexpression in premalignant gastric lesions suggests its potential involvement in the early steps of gastric carcinogenesis. The assessment of HER2 status in EGC may be helpful for the identification of patients who are at low risk for developing nodal metastases. Finally, the possible discordance in HER2 status between primary GC and its synchronous metastases support routine assessment of HER2 both in the primary GC and in its metastatic lesions.

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.

Acinar cell carcinoma of the pancreas. A histologic, immunocytochemical and ultrastructural study.

A rare case of acinar cell carcinoma of the pancreas is presented. Because of its unusual solid growth pattern, correct diagnosis required electron microscopic analysis and the demonstration of intracellular amylase by immunohistochemical stains. The presence of pleomorphic electron-dense cytoplasmic granules containing fibrillary internal structures is confirmed in this ultrastructural study. The differential diagnosis of acinar cell carcinoma from other neoplasms involving the pancreas, including neuroendocrine tumours, poorly-differentiated adenocarcinomas and neoplasms of putative acinar cell derivation, is discussed.

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.

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.

Lysozyme and mucins in gastric adenomas.

A method for the simultaneous demonstration of lysozyme and mucins in 39 cases of gastric adenomas differentiated two intermediate cell types. The first was similar to a columnar cell comprising a single cell population which covered extensive areas of the adenomas. This cell type often showed supranuclear lysozyme reactivity and apical neutral mucins, sialomucins, and sulphomucins in variable amounts. The second cell type was found in 11 adenomas, located mainly in the fundal area. It seemed to be a transitional form between the goblet cell and the Paneth cell. This cell type was scattered among columnar cells, occasional Paneth-like cells, and small goblet cells. These two types of intermediate cells may be regarded as abnormally differentiated integral elements of gastric adenomas. They may be associated with the neck stem cells in the cytogenesis of gastric adenomas.

Prognostic significance of standardized AgNOR analysis in early and advanced gastric carcinomas.

To assess the prognostic significance of silver-stained nucleolar organizer region (AgNOR) proteins, a standardized AgNOR analysis was performed on 78 patients affected by early (EGC, n=24) or advanced (AGC, n=54) gastric carcinomas. The histopathological diagnosis, grading and staging were done according to WHO and UICC recommendations; the mean follow-up time was 56.9 months. Visualization and quantification of AgNORs were made in formalin-fixed, paraffin-embedded sections as specified in the guidelines of the Committee on AgNOR Quantification (1995). Statistical analysis was performed on the mean AgNOR area values (NORA). Highly significant differences (P<0.001) were found in NORA values between EGC and AGC, between low- and high-grade gastric carcinomas and between patients dead from gastric cancer and living patients. In addition, significant P values were found on comparison of NORA values relating to pT status, pN status and stage. Comparison of Kaplan-Meier survival curves revealed that patients affected by gastric carcinomas with higher NORA values (>5.213 microm2) had a worse prognosis. Finally, using Cox multiple regression analysis, the AgNOR quantity emerged as a useful independent prognostic variable to predict the final outcome of patients affected by EGC or AGC.

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.

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.

Mitochondrial DNA mutation at np 3243 in a family with maternally inherited diabetes mellitus.

Mitochondrial DNA (mtDNA) gene defects may play a role in the development of maternally inherited diabetes mellitus and deafness (MIDD). A family from Southern Italy who showed maternal transmission of type 2 diabetes mellitus with three individuals affected is described. A 10.4 kb deletion and mutations at nucleotide positions (np) 3243, 7445 and 11778 in the mtDNA of six relatives were sought. The mitochondrial np 3243 mutation of the tRNA Leu (UUR) gene was identified in a boy affected by optic atrophy and mental retardation, as well as in his diabetic mother. No other mutations or deletions were found. Our study points out the variable phenotypic expression of the np 3243 mtDNA mutation. This may suggest the presence of other mitochondrial or nuclear mutations required to modulate the phenotype. A clinical and metabolic follow-up of all family members was necessary to understand the role of the np 3243 mutation, especially in one child affected by optic atrophy and mental retardation. Further studies will be aimed at investigating the prevalence of mutations and deletions of mtDNA in type 2 diabetes mellitus.

Photodegradation of SiO2-coated CdS nanoparticles within silica gels.

A comparative study of the photodegradation of CdS nanoparticles coated with silica shells dispersed in water and embedded in two silica gels with different pore size is presented. Although encapsulation of the quantum dots in a silica shell previously was proven to provide a basically permanent protection against light-induced surface oxidation (photodegradation), this protection is not always maintained when the coated particles are incorporated within different silica gels. Degradation of the CdS occurs when the coated particles are incorporated within silica gels with an open structure, which suggests that the shells somehow crack due to tension in the gel structure. This behavior is analyzed by absorption and luminescence spectroscopies, electron microscopy, and nitrogen sorption.

Neoplastic Paneth cells in adenocarcinoma of the stomach: a case report.

A case of well-differentiated (intestinal type) adenocarcinoma of the stomach in a 73-year-old man is reported. The tumor contained Paneth-like cells as an integrated part, and their identity at the light microscopic level was confirmed by histochemical stains including an immunohistochemical stain for lysozyme. This case is unusual, since neoplastic Paneth cells occur only rarely in adenocarcinomas of the stomach.