Domenica Paparo

Mitotic Catastrophe in Malignant Epithelial Tumors: The Pathologist’s Viewpoint

Mitotic catastrophe is a common phenomenon occurring in tumor cells with impaired p53 function exposed to various cytotoxic and genotoxic agents. The defective p53 checkpoint causes improper segregation of chromosomes, resulting in aberrant mitosis, multiple micronuclei, multinucleate giant cells, and eventual necrosis-like death and centrosome aberration. Although various descriptions explaining mitotic catastrophe exist, there is still no generally accepted definition of this phenomenon. However, the syndrome of mitotic catastrophe may be a unifying morphological concept of particular interest to cancer research, as it integrally links cell death to checkpoints of the cell cycle. Morphological findings compatible with mitotic catastrophe may be found in pleomorphic, giant cell carcinomas—neoplasms characterized by a poor prognosis. The inclusion of mitotic catastrophe as part of the microscopic evaluation of tumors will add further insight to the pathobiology of tumor progression and in novel therapeutic designs. Finally, the possibility of assimilating mitotic catastrophe into a prognostic score is discussed.

Ultrastructural Descriptions of Heterotypic Aggregation between Eosinophils and Tumor Cells in Human Gastric Carcinomas

A histological variant of gastric adenocarcinoma, characterized by an intense tumor-associated tissue eosinophilia (TATE), has been occasionally reported in the literature. The purpose of this ultrastructural study was to determine the interactions between frequently occurring eosinophils and tumor cells in gastric carcinoma characterized by TATE. Fresh tumor tissue of 92 gastric carcinomas was processed for both light and electron microscopic examination. Intense TATE was found in 7 out of 92 (7.6%) gastric carcinomas (6 of intestinal-type and 1 of diffuse-type). Electron microscopy, selectively performed in 7 cases with intense TATE, revealed eosinophils, singly or in groups, in contact with damaged or necrotic tumor cells. Activated eosinophils showing piecemeal degranulation were also found in intimate contact with viable tumor cells, characterized by plasma membrane caveolar invaginations. The authors regard this close morphological relationship as in vivo evidence for possible cross-talk between eosinophil and viable tumor cell, a conclusion that has already been drawn from experimental studies, but until now inadequately supported by ultrastructural observations in a human tumor.

Abnormal nuclear structures (micronuclei, nuclear blebs, strings, and pockets) in a case of anaplastic giant cell carcinoma of the thyroid: an immunohistochemical and ultrastructural study.

The authors report a case of a 70-year-old woman with an anaplastic giant cell thyroid carcinoma, along with immunohistochemical and electron microscopic findings. Histologically, the tumor is characterized by mononucleated and multinucleated giant cells, lack of architectural cohesion, atypical mitoses, and extensive areas of coagulative necrosis. Tumor cells showed AE1/AE3 positivity as well as nuclear overexpression of p53 and ki-67. Semithin sections revealed multiple nuclei with heterogeneous size ranging from micronuclei to large-size (giant) nuclei. Micronuclei were confirmed by electron microscopy that disclosed also the presence of nuclear blebs, strings, and pockets. Morphological findings of these abnormal nuclear structures in conjunction with p53 and Ki-67 nuclear overexpression suggested a faulty mitotic checkpoint/mitotic catastrophe in the progression of anaplastic giant cell thyroid carcinoma.

Neutrophil-rich Gastric Carcinomas: Light and Electron Microscopic Study of 9 Cases with Particular Reference to Neutrophil Apoptosis

Abstract 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.

Chronic Allergic-like Inflammation in the Tumor Stroma of Human Gastric Carcinomas: An Ultrastructural Study

Inflammatory cell infiltration around the sites of carcinoma invasion is believed to play important roles in tumor biological behavior. The status of inflammatory cell infiltration at the sites of frank invasion in 92 cases of gastric carcinomas was examined, with special emphasis on tumor-associated tissue eosinophilia (TATE). TATE was found in 7 out of 92 (7.6%) gastric carcinomas (6 of intestinal-type and 1 of diffuse-type). Electron microscopy, selectively performed in the 7 cases of gastric carcinomas with TATE, showed that eosinophils participated in the stromal reaction by interacting with tumor cells, mast cells, and each other. Most of the tumor-infiltrating mast cells exhibited anaphylactic or piecemeal degranulation, indicating that the mast cells had been activated in situ. Some mast cells were noted in close contact to viable tumor cells, suggesting the existence of direct cell-to-cell interactions. There was also extracellular deposition of free eosinophil granules and Charcot-Leyden crystals. These morphologic findings are similar to that described in late/chronic-phase allergic reaction in both human and experimental animals, where angiogenesis and fibrosis/tissue repair are also present. In conclusion, TATE may indicate a chronic allergic-like Th2 host–tumor reaction, and understanding these pathways should create tools to enhance defence and contrast neoplastic disease.

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

ABSTRACT 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.