Invited review The cytology of malignant mesothelioma

Whitaker, Darrel

doi:10.1046/j.1365-2303.2000.00247.x

Cited by 127 publications

(92 citation statements)

References 51 publications

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“…In serous effusions, MPM cell aggregates show a diversity of structures; some display a true papillary structure, whereas others exhibit structures of pseudoacinar formation or randomly coiled cords of cells. 4 In our model of pluricellular aggregates, two MPM cell lines displayed micropapillary-like structures, whereas the other displayed less typical structures. Moreover, MPM cell aggregates presented some features described in cells in epithelial effusion, showing Adh junctions, basal lamina, microvilli and intermediate filaments adjacent to the nuclear envelope, which are diagnostic criteria for mesothelioma.…”

Section: Discussionmentioning

confidence: 70%

“…The cytological analysis of the pleural fluids generally reveals the presence of free spheroidal aggregates of MPM cells, which are strongly linked to malignancy. 3,4 These observations suggest that free aggregates of MPM cells have a propensity to survive in the pleural fluid; yet, there has been very little research to date into the mechanisms allowing them to do so.…”

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confidence: 99%

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Malignant pleural mesothelioma cells resist anoikis as quiescent pluricellular aggregates

et al. 2009

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Pleural fluid accumulation is a frequent clinical observation in diffuse malignant pleural mesothelioma (MPM). The cytological analysis of pleural fluid often reveals the presence of free spheroid aggregates of malignant cells, giving rise to the question of the ability of non-adherent tumor cells to resist the loss of anchorage-induced apoptosis (termed as anoikis), and to develop new tumor foci in the pleural cavity. Here, we show that MPM cells cultured under non-adherent conditions form well-organized aggregates composed of viable cells, which progressively enter in G 0 . Although the PI3K/Akt, ERK and SAPK/JNK signaling pathways are activated in adherent MPM cells, loss of anchorage results in the inactivation of these pathways. By comparison, we show that the non-tumoral mesothelial cells MeT-5A enter anoikis in an SAPK/JNK-, Bim-and caspase-9-dependent pathway. The survival of MPM cells can be reversed by activating SAPK/JNK with anisomycin, according to a Bim-dependent mitochondrial pathway. Finally, our findings show that impairment of cell aggregation activates SAPK/JNK and Bim and induces anoikis. Our results underline the importance of intercellular contacts in the anoikis resistance of MPM cells.

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Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 99%

Malignant pleural mesothelioma cells resist anoikis as quiescent pluricellular aggregates

et al. 2009

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“…Even though the cytologic features of MM were described more than 50 years ago and have been further refined in numerous subsequent articles, there is still doubt as to the ability of the cytopathologic modality to establish a definitive diagnosis of malignant mesothelioma. 12,13 The published sensitivity of cytologic diagnosis of mesothelioma ranges between 32% and 76%. This broad range of sensitivity (high false-negative rate) is probably related to sampling rather than interpretation, though one has to accept that there is a broad morphologic overlap between reactive mesothelial cells and malignant cells of mesothelioma.…”

Section: Cytologic Diagnosis Of Malignantmentioning

confidence: 99%

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

Husain

Colby

Ordóñez

et al. 2013

Archives of Pathology & Laboratory Medicine

479

559

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“…Cytopathological features of mesothelioma are characterized by mesothelial cells with nuclear atypia, multinucleation, cell-in-cell engulfment, and mirror ball-like cell cluster formation, which are useful in discrimination from other diseases. [4][5][6][7] Effusion cytology for differential diagnosis of malignant pleural mesothelioma and adenocarcinoma uses immunostaining panels with mesothelial markers, such as calretinin, podoplanin (D2-40), Wilms' tumor 1 protein, and cytokeratin 5/6, and carcinoma markers, such as epithelialrelated antigen (MOC-31) and carcinoembryonic antigen. 8,9 On the other hand, distinction of malignant pleural mesothelioma from reactive mesothelium is challenging, because of the similarity of morphology and the lack of reliable discriminating markers in effusion cytology.…”

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confidence: 99%

Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium

et al. 2010

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Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.

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Invited review The cytology of malignant mesothelioma

Cited by 127 publications

References 51 publications

Malignant pleural mesothelioma cells resist anoikis as quiescent pluricellular aggregates

Malignant pleural mesothelioma cells resist anoikis as quiescent pluricellular aggregates

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium

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