Foamy cell aggregation in duodenal diverticula

We have investigated 44 cases of duodenal diverticulum to delineate the pathological features. Foamy cell aggregations were observed in 24 (54.5%) of the cases. The foamy cells were located within the submucosa in all 24 cases and were found around the deepest portion of the diverticula in 14. There were no statistically significant differences between the depth of the diverticulum and the presence or degree of foamy cell aggregation. Lymphoid aggregates, focal thickening of the muscularis mucosae, submucosal fibrosis, intimal thickening of submucosal vessels and submucosal haemorrhage were also detected, but statistical analysis showed no significant associations between these pathological findings and the presence of foamy cell aggregates. We conclude that the foamy cell aggregates are a non-specific but frequent pathological finding in duodenal diverticula and which have not been described in previous studies.     

Foamy cell syndrome associated with repeated platelet transfusions

Variable numbers of foamy cells (macrophages with foamy cytoplasm) were noted in generalized organs from four patients who received repeated were noted in generalized organs from four patients who received repeated platelet transfusions. The underlying disease in three cases was aplastic anemia, and the remaining case was chronic myelocytic leukemia. In two patients (aplastic anemia and chronic myelocytic leukemia) bone marrow transplantation (BMT) was done. Opportunistic infection was noted in three out of four cases. The foamy cells were stained black with Sudan black B. Variable amounts of materials immunoreactive with antihuman platelet antibody were demonstrated in most of the foamy cells. Ultrastructurally, the foamy cells contained myelin-like materials. The foamy cells described here resembled those demonstrable in the spleen from patients with idiopathic thrombocytopenic purpura. We suggest that the foamy appearance of the macrophage results from incomplete intracellular degradation of phagocytosed platelets.     

Foamy cell (hibernoma-like) change is a rare histopathological feature in renal cell carcinoma

We report nine patients (seven males and two females, median age 64 years (range 51–79 years)) with a renal cell carcinoma, each of which contained a significant component of neoplastic epithelial cells with a striking microvacuolated (hibernoma-like) cytoplasmic appearance. Tumor sizes ranged from 1.5 to 8.0 cm (mean 4.2 cm, median 4.3 cm). The basic architecture of the tumors was solid-alveolar in two cases (classified as renal cell carcinoma-not otherwise specified (NOS)) and papillary in seven cases (classified as papillary renal cell carcinoma NOS). The nuclear grade according to the Fuhrman grading system was three in all cases. By immunohistochemistry, the cells with microvacuolated cytopasm and significantly expressed adipophilin and anti-mitochondrial antigen in a similar cytoplasmic pattern. On ultrastructural examination, the cytoplasm of the neoplastic epithelial cells was packed with distended mitochondria, most of which displayed lamellated cristae. Numerous microvesicles were dispersed between the mitochondria. No mutations in the succinate dehydrogenase B gene were identified. Based on our findings, we propose that the mechanism behind this phenomenon is an abnormal intracellular processing of lipids. No aggressive behavior was observed in six out of nine patients with available follow-up information.     

Adiponectin pathway attenuates malignant mesothelioma cell growth

Malignant mesothelioma (MM) is caused by exposure to asbestos. Because MM has a latency period, short survival time, and has a poor response to current therapeutic regimes, long-term preventive strategies are required to suppress the advance of pathological states after asbestos exposure. Accumulating evidence suggests that adiponectin plays a crucial role in the regulation of energy metabolism by increasing AMP-activated protein kinase (AMPK) activation. Several studies have indicated that the activation of AMPK decreases cyclooxygenase (COX)-2 expression. Because high COX-2 levels correlated with a worse prognosis and survival rate in MM, we examined whether the adiponectin pathway suppresses MM cell growth through the AMPK/COX-2 pathway. In vivo, dietary fish oil (a potential promoter of adiponectin) decreased the growth rate of MM, which was accompanied by an increase in adiponectin and phospho-AMPK levels, and a decrease in COX-2 level. In vitro, adiponectin significantly impaired the cell proliferation rate of MM cell lines. These effects partly involved induction of growth arrest and apoptosis to MM cells. MM cells expressed both adiponectin receptors 1 and 2 (AdipoR1 and -R2) at mRNA and proteins levels. These receptors were functional, because adiponectin activated AMPK. Adiponectin treatment also significantly down-regulated protein levels of COX-2 and its downstream prostaglandin E(2). Finally, inhibitory analysis of AdipoR1/R2 by small interfering RNA knockdown suggests that adiponectin enhances AMPK activity and impairs the cell proliferation rate of MM cells, mainly via AdipoR1. These findings suggest that the induction or supplementation of adiponectin is an important tactic for developing therapeutic strategies against MM.     

Reactive mesothelial cell and mesothelioma of the pleura

Summary The results of a light and electron microscopic study and enzyme histochemistry of reactive mesothelial cells and diffuse and localized (solitary) pleural mesotheliomas were compared, in order to establish a diagnosis and elucidate the cell of origin of the mesotheliomas. The reactive mesothelial cells were usually regular in appearance but could be cuboidal or columnar, or even peg-shaped with large nuclei and prominent nucleoli. Colloidal iron and alcian blue staining were positive in the plasma membrane, microvilli and in parts of the cytoplasm of mesothelial cells. These stains were mostly negative following testicular hyaluronidase treatment. The neoplastic cells of diffuse pleural mesothelioma had some epithelial characteristics such as microvilli, desmosomes, and a prominent basement membrane and were similar to reactive mesothelial cells with regard to cellular form and staining for acid mucopolysaccharides. In this study the colloidal iron and PAS stains appeared to be more intense in mesothelioma cells than in reactive mesothelial cells.In enzyme histochemistry, naphthol AS-D acetate esterase and -naphthyl acetate esterase activity were demonstrated strongly in neoplastic cells. The nuclear-cytoplasmic ratio, the numbers of microvilli and mitochondria and the amount of glycogen were greater in the neoplastic cells when studied by electron microscopy. Electron lucent intracytoplasmic fibrils appeared wider and more distinct in mesothelioma cells.Localized mesotheliomas, thought to be an entirely different entity from reactive mesothelial cells, showed little characteristic morphology in light microscopic pictures, few cytoplasmic organelles were seen ultrastructurally.     

The histology and immunohistochemistry of small cell mesothelioma

The object of this study was to describe the histology and immunohistochemistry of 13 small cell mesotheliomas, concentrating on reliable distinctions between them and small cell carcinoma. All 13 tumours showed regions of more typical mesothelioma if multiple blocks were examined. No tumours showed the streams, ribbons, rosettes, or haematoxyphilic blood vessels that are typical of small cell carcinoma. Mitotic figures were relatively scarce and the nuclei had a particularly characteristic open appearance with prominent nucleoli and delicate chromatin. Nuclear moulding was not seen. No tumour produced neutral mucin. Immunohistochemical positivity for neuron-specific enolase (NSE) was found in 11/13, cytokeratin in 9/13 and Leu-7 in 4/13 but none was positive for chromogranin A, carcino-embryonic antigen (CEA) or leucocyte common antigen (LCA). We conclude that the accurate diagnosis of small cell mesothelioma is possible, provided that the clinical presentation is known, the tumour is adequately sampled and the microscopy carefully assessed. In small biopsy specimens, where the diagnosis is less straightforward, immunohistochemistry for CEA, and perhaps LCA and chromogranin A may be helpful. NSE and Leu-7 positivity is common in these tumours and might be misleading if interpreted as reliable evidence of neuroendocrine differentiation.     

Signet ring cell mesothelioma; A diagnostic challenge

Signet ring cell mesothelioma is a rare variant of epithelioid mesothelioma with limited cases published. It has a male predilection and most commonly occurs on pleura; it can also arise in the peritoneal cavity. The signet ring cell morphology can pose a challenge leading to a potential diagnostic error. A variety of benign and malignant diseases, including reactive histiocytic hyperplasia, adenocarcinoma, melanoma, and lymphoma with signet ring cell morphology should be considered in the differential diagnosis. In signet ring cell mesothelioma work up, mucin stains are of limited value. Even though immunohistochemistry is routinely used in mesothelioma diagnosis, there is no sole specific mesothelial marker. Hence, a panel of mesothelial and epithelial markers are used; these should be interpreted with caution especially in this variant. Electron microscopy and genetic testing can be very helpful in distinguishing signet ring cell mesothelioma from its mimickers.     

Unusual clear cell variant of epithelioid mesothelioma.

Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.     

Characterization of three human malignant mesothelioma cell lines

Three human malignant mesothelioma cell lines, designated Mero-14, Mero-25, and Mero-41, have been isolated from effusions and from autopsy material of confirmed cases of malignant mesothelioma. Light and electron microscopy, cytogenetics, growth requirements, and intermediate filament expression of these cell lines were studied and, where possible, compared with the original tumor material of the patient. Cytologic and ultrastructural morphology was consistent with the mesothelial nature of the cells. All cell lines displayed a hyperdiploid karyotype similar to that of the tumor cells obtained directly from the patient. All three malignant mesothelioma cell lines had marker chromosomes 1, 3, 9, and 22, as well as other markers that were occasionally present in these cell lines and in other malignant mesotheliomas studied. Growth kinetic studies in medium supplemented with epidermal growth factor (EGF) showed increased proliferation and a decreased proliferation in medium supplemented with hydrocortisone (HC) or EGF plus HC. The three malignant mesothelioma cell lines were positive for the cytokeratins 7, 8, 18, and 19 based on immunofluorescence and immunoblotting tests with chain-specific monoclonal antibodies. The characteristics of these cell lines support the assumption that Mero-14, Mero-25 and Mero-41 are derived from malignant mesotheliomas and have retained their original character.     

Foamy cells associated with phagocytosis of glutaraldehyde-treated red blood cells and red cell membranes

In order to clarify the mechanism for the formation of foamy cells (macrophages with foamy appearance) associated with increased erythrophagocytosis, we tried to reproduce these cells in mice by subcutaneous injection of intact red blood cells (RBCs), OsO4-treated RBCs (Os-RBCs), glutaraldehyde-treated RBCs (G-RBCs), or isolated red cell membranes, and time-course observation was done by light and electron microscopy. Foamy cells were induced by the latter two methods. Within the macrophages, G-RBCs were fragmented into spherules by newly formed small vacuoles, and with time these spherules lost their hemoglobin content transforming into small vacuoles with translucent matrix. In most of these vacuoles, red cell membrane structure was discernible adjacent to the phagocytic vacuole. Such macrophages containing abundant small vacuoles appear foamy in light microscopy. Foamy cells induced by injection of red blood cell membranes were positive for lipid stains and contained abundant laminated membrane structures in electron microscopy. These results suggest that the foamy cells related with increased erythrophagocytosis are heterogeneous with respect to their pathogenesis and cellular inclusions, and proteinaceous constituents resistant to intracellular digestion are also responsible for the occurrence of foamy cells.     

Clear cell mesothelioma presenting as an incarcerated abdominal hernia

A clear cell mesothelioma presenting as an incarcerated ventral abdominal hernia in a 67-year-old man who had no history of asbestos exposure is described. The cause of the cytoplasmic clearing was the presence of large amounts of glycogen. Although uncommon, this variant of mesothelioma is important to recognize because it can be easily confused with other clear cell tumors involving the serosal membranes. Significant recent advances in the immunohistochemistry of epithelioid mesothelioma are briefly reviewed because immunohistochemical studies can be helpful in establishing the correct diagnosis.     

Foamy gland microcarcinoma in needle prostatic biopsy

Foamy gland carcinoma is an uncommon variant of prostatic carcinoma. Foamy microcarcinoma of the prostate has not been studied in detail in needle biopsy. We describe here useful criteria for the diagnosis of foamy gland microcarcinoma of the prostate in needle biopsy. We reviewed 6 cases of foamy gland microcarcinoma. All tumors measured less than 1 mm and involved less than 5% of the biopsied tissue. A range of 4 to 40 foamy neoplastic glands were found in the 6 tumors. The original diagnosis of foamy gland microcarcinoma was made in 3 cases. They were composed of 21 to 40 glands lined by cuboidal to columnar cells with abundant foamy cytoplasm and small picnotic nuclei. Infiltrating and nodular patterns were readily identified, and absence of basal cells was shown by cytokeratin stains. The remaining 3 cases were designated as atypical foamy glands and consisted of similar but fewer glands (4-20). The diagnosis of foamy gland microcarcinoma was not made because of lack of nucleomegaly and prominent nucleoli and because an infiltrating pattern was less apparent. Subsequent biopsies confirm the diagnosis of microcarcinoma. The number of glands lined by voluminous foamy cells with hyperchromatic nuclei, an infiltrating pattern, and the absence of basal cells with high-molecular-weight cytokeratin were the most useful features in the diagnosis of foamy microcarcinoma. The presence of few atypical foamy glands in needle biopsy requires detailed analysis because they may represent foamy gland microcarcinoma.     

Foamy cells associated with platelet phagocytosis.

In order to gain an insight into the mechanism for the formation of foamy cells (macrophages with foamy cytoplasm) frequently seen in spleens affected by idiopathic thrombocytopenic purpura (ITP), these cells were experimentally induced in mice by subcutaneous injection of platelets with or without accompanied administration of corticosteroid. The light- and electron-microscopic features of experimentally reproduced foamy cells were essentially similar to those seen in the spleens of ITP patients. Corticosteroid had no significant effect on the formation of foamy cells. Most macrophages with foamy cytoplasm contained various amounts of phospholipids, which were derived from platelet membranes. By electron microscopy, myelinlike materials were frequently demonstrated in the cytoplasm of foamy cells. Although lysosomal enzyme activity was revealed in the macrophages that contained morphologically recognizable platelets, there was no demonstrable activity in the cells that contained myelinlike materials. From these results, the following conclusion has been suggested as the mechanism for the formation of foamy cells. Under the state of accelerated phagocytosis of platelets by the macrophages, such as in ITP, the amount of ingested platelet membranes is beyond the capacity of lysosomal digestion. Thus, the incompletely degraded membrane constituents, especially membrane-derived phospholipids, remain in the macrophages, and they are most responsible for the foamy appearance of these macrophages.     

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.