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.