Eosinophil exocytosis in a poorly differentiated tubular gastric adenocarcinoma: case report.

A case of poorly differentiated tubular gastric adenocarcinoma with tumor-associated tissue eosinophilia (TATE) is studied by light and electron microscopy, focusing on membrane interactions between eosinophils and tumor cells. 29.2% of the eosinophils in contact with tumor cells showed intact granules, 28.3% exhibited piecemeal degranulation (PMD), 40% were characterized by coexistence of PMD and compound exocytosis in the same granulocyte, whereas classical exocytosis was found in 2.5% of the eosinophils with PMD. Eosinophil Sombrero Vesicles (EoSVs), important tubulovesicular carriers for delivery of cytotoxic proteins from the specific granules during PMD, were also studied at the ultrastructural level. In activated eosinophils, EoSVs and specific granules with ultrastructural signs of degranulation were polarized toward tumor cells. Ultrastructural changes in paraptosis-like cell death, such as mitochondrial swelling, dilation of the nuclear envelope, cytoplasmic vacuoles, and nuclear chromatin condensation, but without margination of the chromatin, were observed in these tumor cells. Our data support the notion that eosinophils may exert an antitumoral role in gastric cancer. Finally, the case reported provides, for the first time, ultrastructural evidence of classical and compound exocytosis of eosinophils in the tumor stroma of human adenocarcinoma.

Autophagy in advanced low- and high-grade tubular adenocarcinomas of the stomach: An ultrastructural investigation.

Autophagy represents a catabolic process in which cellular protein and organelles are engulfed into autophagosomes, digested in lysosomes and reutilized for the cellular metabolism. In neoplastic conditions, autophagy may act either as a tumour suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumour growth. Although enhanced autophagy has been reported in hypoxic areas of solid tumors, there are only few ultrastructural reports concerning the relationships between autophagy and tumor grade. In the present study, we have performed an ultrastructural investigation aimed to document autophagy in a cohort of advanced gastric carcinomas of tubular type, correlating the observed findings with low and high tumor grade. Among 71 surgically resected cases of advanced gastric carcinomas, we have selected twelve low-grade and thirteen high-grade tubular adenocarcinomas. Autophagic vacuoles (AV) were only occasionally found in low-grade tubular carcinomas, while they constituted a frequent finding in high-grade ones (p < 0.01). Moreover, in high-grade tubular adenocarcinomas, our data revealed a morphologic association between autophagy and nuclear changes, such as multinucleation, micronucleation and nuclear buds, largely considered as ultrastructural aspects of mitotic instability. However, an increased autophagy was associated with organelle-poor cytoplasm or a senescent phenotype, characterized by lipofuscin granules and cytoplasmic vacuoles. In the light of our observations, it may be suggested that autophagy should be considered a phenomenon mainly related to the cellular differentiation and tumor progression.

Pleomorphic Carcinoma of the Colon: Morphological and Immunohistochemical Findings.

Pleomorphic carcinoma is an aggressive neoplasm defined by the World Health Organization (WHO) as a poorly differentiated (squamous cell carcinoma or adenocarcinoma) or undifferentiated carcinoma in which at least 10% spindle and/or giant cells are identified, or as a carcinoma constituted purely of spindle and giant cells. Although this entity has initially been shown in the lung, it has been described also in extrapulmonary locations, with only one report for a colonic site. A 65-year-old woman developed a caecal tumour. Gross examination revealed an endophytic/ulcerative mass 7 cm in length. Microscopically, the tumour was a poorly differentiated adenocarcinoma with a pleomorphic component that occupied more than 10% of the specimen. The tumour shared these histopathological findings with pulmonary giant cell carcinoma but differed in other clinicopathological features such as a pushing growth pattern, stage pT3N1, and an uneventful outcome 24 months after operation. The pleomorphic component showed morphological and immunohistochemical features compatible with mitotic catastrophe, a non-apoptotic cell death occurring in cycling cells after aberrant mitosis. These features included multinucleation, micronucleation, atypical mitoses, foci of geographic necrosis, as well as immunohistochemical overexpression of p53 and Ki-67. The interpretation of the pleomorphic component as morphological expression of mitotic catastrophe may be useful in comprehending the pathogenesis of this rare neoplasm, and it may have practical implications as a potential cancer therapeutic target.

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.

A rare case of male breast cavernous-type angioleiomyoma.

Cutaneous leiomyomas of the breast are extremely rare, particularly in men. Leiomyomas are categorized into three groups: angioleiomyomas, pilar leiomyomas and genital leiomyomas. Angioleiomyomas, or vascular leiomyomas, are benign tumors arising from smooth muscle cells of arterial or venous walls. We report the case of a 70-year-old man who was admitted to the surgery unit because of a painful lump in the left periareolar region. Ultrasound investigation showed a well-delimited, hyperechogenic, inhomogeneous nodular lesion. The final diagnosis was made after surgical excision and pathological evaluation of the mass. The histological features and immunohistochemical profile, characterized by positive expression of the spindle-shaped tumor cells for desmin and smooth muscle actin and by positive expression of the endothelial cells of the vascular channels for pan-endothelial markers CD34 and CD31, confirmed the diagnosis of a cavernous-type angioleiomyoma.

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.

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.