Neutrophil-rich gastric carcinoma in the integrated cancer registry of eastern Sicily, Italy.

BACKGROUND/AIM: Neutrophil-rich carcinoma is a variant of gastric carcinoma that has not been well-studied or characterized. The purpose of the present study was to reveal the incidence and clinicopathological findings compared to ordinary gastric carcinoma. PATIENTS AND METHODS: A population-based series of 430 gastric cancers, identified between 2003 and 2006 from the province of Messina (insular Italy; population, 662,450), was used. The number of tumor-infiltrating neutrophils was assessed in a semi-quantitative manner using the mean value of 20 non-overlapping high-power fields (magnification, 400; 0.08 mm(2)). Tumors with >10 neutrophils per 20 high-power fields were arbitrarily considered as neutrophil-rich gastric carcinomas. Moreover, MUC1 immunohistochemical expression was investigated to show possible correlation with neutrophil infiltration in gastric carcinomas. RESULTS: Among 193 gastric cancers resected for curative purposes, 30 (15.54%) were represented by neutrophil-rich gastric carcinomas. These tumors occurred more frequently in patients aged more than 72 years (p<0.05), showing an inverse correlation with mucinous subtype according to the WHO classification (p<0.001) and expressed MUC1. However, intensity and distribution of MUC1 was heterogeneous, and independent of neutrophil infiltration within the tumor stroma. CONCLUSION: Neutrophil-rich carcinoma seems to represent a distinctive morphological variant of gastric carcinoma, although the true mechanism for the infiltration of neutrophils is still unclear.

Mechanisms of coagulative necrosis in malignant epithelial tumors (Review).

Histological tumor necrosis (TN) has been reported to indicate a poor prognosis for different human cancers. It is generally accepted that TN results from chronic ischemic injury due to rapid tumor growth. However, whether insufficient tumor vascularization and inadequate tumor cell oxygenation are the only factors causing TN remains controversial. Mitotic catastrophe is considered to occur as a result of dysregulated/failed mitosis, leading to cell death. We hypothesize that mitotic catastrophe, induced by hypoxic stress, may lead to the TN which is observed in high grade carcinomas. The current review describes the morphological features of TN in malignant epithelial tumors. In addition, evidence regarding the involvement of mitotic catastrophe in the induction of TN in human carcinomas is discussed.

Gastric adenocarcinoma incidence in the province of Messina (Insular Italy): A cancer registry study.

The incidence of cancer by age, gender and tumor type at a population-based level is infrequently investigated. The aim of the present study was to describe the burden and outcome of gastric carcinomas (excluding cancers of the esophagogastric junction) experienced by the elderly, particularly for patients aged ≥81 years. A population-based series of 322 patients exhibiting gastric cancer, diagnosed between 2003 and 2005 and from the province of Messina (insular Italy; population, 662,450) was used. The median age of patients at the time of diagnosis was 72 years. The patients were categorized into three age groups according to interquartile range values, <64, 65-80 and >81 years. The cancer-specific survival rate at five years was lowest in the very elderly (P<0.001). Patients aged ≥81 years were less likely to receive surgery than younger patients (44 vs. 55 vs. 22% for the <64, 65-80 and >81 years age groups, respectively; P<0.01). In the resected cases, very elderly patients (age, >81 years) were more likely than younger patients to exhibit advanced stage pathological tumor-node-metastasis (P<0.05). It was concluded that patients aged ≥81 years accounted for 25% of total gastric carcinomas, were less likely to receive surgery and experienced worse outcomes when compared with younger patients.

Apoptotic-like tumor cells and apoptotic neutrophils in mitochondrion-rich gastric adenocarcinomas: a comparative study with light and electron microscopy between these two forms of cell death.

Mitochondrion-rich adenocarcinomas represent a rare variant of gastric adenocarcinomas composed predominantly of columnar adenocarcinoma cells with eosinophilic cytoplasm, a strong supranuclear immunoreactivity for antimitochondrial antibody, and a marked neutrophil infiltration associated to tumor cell death. The purpose of this work is to investigate, using correlated light and electron microscopy, mitochondrion-rich gastric adenocarcinomas focusing on the nature of the death in neoplastic cells and in infiltrating neutrophils. Adenocarcinoma cells, single or in small clusters, showed convoluted nuclei, irregularly condensed chromatin, loss of microvilli, and nuclear envelope dilatation. No nuclear fragmentation was observed in these dying cells and the plasma membrane did not show signs of disruption. These ultrastructural findings represent intermediate aspects between apoptosis and necrosis and are compatible with apoptosis-like programmed cell death. By contrast, some infiltrating neutrophils showed ultrastructural signs of classic apoptosis such as chromatin condensation into compact geometric (globular, crescentshaped) figures, tightly packed cytoplasmic granules and intact cell membrane. Our study provides ultrastructural evidence of apoptosislike tumour cell death in mitochondrion-rich gastric carcinomas and confirms that stereotyped outcome either as apoptosis or necrosis of tumor cells cannot always be expected in human neoplasms.

Mitochondrion-rich differentiated adenocarcinomas of the stomach: clinicopathological, immunohistochemical and electron microscopy study of nine cases.

Pathologic and prognostic data of nine patients with mitochondrion-rich carcinomas (MRC) were compared retrospectively to data of 101 patients with conventional gastric adenocarcinomas. MRC was defined as a tumour composed predominantly, or entirely, of columnar adenocarcinoma cells with eosinophilic cytoplasm and a strong supranuclear immunoreactivity for antimitochondrial antibody. Electron microscopy confirmed supranuclear distribution of mitochondria in MRC while immunostaining pattern was irregular or absent in the remaining 101 cases. MRC exhibited a tubulopapillary or cribriform growth pattern with focal infiltration of neutrophils in the tumour stroma. Prominent necrosis was present including segmental and intraluminal "dirty necrosis", while mitotic and ki-67 proliferative rates were low. MRC showed immunohistochemical findings compatible with gastric differentiation (CK7+/CK20-/CDX-) When MRC were compared with non-MRC carcinomas, tumour size (< 4 cm vs >4 cm, P < 0.01) , frequency of lymph node metastases (11% vs. 80%, P < 0.01), low stage (I, II) at diagnosis (100% vs. 56%, P < 0.01), Goseki's group I (100% vs. 6%, P < 0.01), and better survival (0% vs. 70%, P < 0.01) differed significantly. Our results suggest that MRC of the stomach may be considered a low-grade malignancy with an excellent prognosis.

Histological heterogeneity and somatic mtDNA mutations in gastric intraepithelial neoplasia.

Somatic mutations of mitochondrial DNA (mtDNA) are associated with various types of human cancer. To elucidate their role in gastric carcinogenesis, we analyzed mutations in the displacement loop region of mtDNA in 24 paraffin-embedded gastric intraepithelial neoplasias (formerly dysplasia) from a high gastric cancer risk area in northern Italy. Helicobacter pylori infection was assessed by histological examination (Giemsa staining). Gastritis was classified according to the guidelines of the Updated Sydney System. The mtDNA displacement loop region was amplified and sequenced from gastric intraepithelial neoplasia samples and adjacent non-neoplastic gastric mucosa. The gastric intraepithelial neoplasias were divided into two groups by their association with H. pylori gastritis. Group A with lesions arising on a background of H. pylori-positive gastritis contained 7 patients, and group B with lesions associated with H. pylori-negative gastritis contained 17 patients. Group A had a larger proportion of high-grade lesions than group B and showed a foveolar phenotype (type II dysplasia). Group B had a larger proportion of cases with mtDNA displacement loop region mutations than group A (P=0.004, Fisher's exact test) and exhibited an intestinal phenotype. No evidence of heteroplasmic variants in the mtDNA displacement loop, suggestive of mutations, was detected in gastric biopsies from 25 H. pylori-negative subjects and 60 cancer-unaffected H. pylori-positive patients. These results provide further evidence for the morphologic and mtDNA biomolecular differences of gastric intraepithelial neoplasias, and suggest the existence of two distinct pathways to gastric cancer--corpus-dominant H. pylori gastritis and the atrophy-metaplasia pathway.

A case of gastric adenocarcinoma associated with giant-cell phlebitis.

A 60-year-old male patient with advanced gastric adenocarcinoma was treated by subtotal gastrectomy with dissection of the regional lymph nodes. Microscopic examination of the tumour revealed tubular adenocarcinoma which invaded the muscularis propria. There was no evidence of metastatic carcinoma in the dissected lymph nodes (pT2N0Mx). Granulomatous reaction comprising epithelioid cells and giant cells involved subserosal muscular veins, adjacent to the carcinoma tissue. Fibrinoid necrosis, with or without infiltration of eosinophils, was noted within the lumen of some veins. The acid-fast and fungal stains were negative. Remnants of parasites were not identified in serial sections of the paraffin blocks. No pulmonary disease was evident on radiographic or pulmonary examination. The presence of granulomatous destruction of muscular veins with sparing of arteries suggested the diagnosis of giant-cell phlebitis. To our knowledge, there have been no previous reports regarding an association between giant-cell phlebitis and advanced gastric adenocarcinoma.