MALIGNANT MESOTHELIOMA PATHOLOGY

MALIGNANT MESOTHELIOMA PATHOLOGY
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A common symptom of mesothelioma is represented by recurrent pleural effusions, which are routinely submitted for cytological examination (smears and/or cell blocks). Since on cytology it is impossible to assess invasion by neoplastic mesothelial cells into sub-pleural tissue or lung parenchyma, establishing a definitive diagnosis of MPM by cytological examination alone remains controversial, especially in the light of the medico-legal implications correlated with the diagnosis of MPM. However, in selected cases in which more invasive procedures are contraindicated, the cytological diagnosis of MPM, which relies on a different set of both cellular and architectural features and is supported by ancillary techniques, can be performed, although its sensitivity is low compared to histology. In fact, the published sensitivity of cytology for the diagnosis of mesothelioma ranges from 30% to 75%. Moreover, in the cases in which histology is not available, a close correlation with clinical and imaging findings is essential for a definitive diagnosis.

Not all MPMs exfoliate tumor cells in the pleural cavity; particularly, the malignant cells in sarcomatoid mesothelioma tend not to be shed into the effusion fluid. Thus, the effusion could only contain reactive epithelioid mesothelial cells, and these cells may mislead the pathologist. In these cases, a core biopsy (or larger specimens) is necessary to establish a definitive diagnosis, particularly when surgery is considered, because the presence of a sarcomatoid component may influence therapeutic management.

There are several cytological features in pleural effusions that raise varying levels of suspicion for MPM, such as the extent of mesothelial proliferation, the presence of papillary structures, scalloped borders of cell clumps, intercellular windows, variation of cytoplasmic staining and its density, and low nuclear-to-cytoplasmic ratios. However, some of the cytomorphological findings of MPM are shared between reactive and malignant epithelioid mesothelial cells. Therefore, the differential diagnosis of mesothelial proliferations may be very difficult or even impossible in cytological specimens, underscoring the importance of ancillary techniques to clarify diagnosis.

The application of immunocytochemistry (ICC) and molecular methods, such as fluorescent in situ hybridization (FISH) performed preferentially on cell blocks, increases the diagnostic accuracy of cytology. The differential diagnosis of MPM and the use of ICC and molecular markers in cytological samples are the same as in histological specimens. Several ICC markers, such as desmin, p53, epithelial membrane antigen (EMA), glucose transporter protein 1 (GLUT-1), insulin-like growth factor 2 messenger RNA-binding protein 3 (IMP-3), and CD146, have been proposed to assist in uncertain cases. Nevertheless, none of these markers, alone or in combination, appeared to be useful with sufficient confidence in the routine diagnosis of MPM.

Among new ancillary tests, FISH that shows the homozygous deletion of p16 (CDKN2A) and the loss of BRCA1-associated protein 1 (BAP1) expression by immunocytochemistry are particularly useful to differentiate mesothelial hyperplasia (MH) from MPM. These two markers were shown to be highly specific for MPM; however, their low sensitivity limits their clinical utility.

The cytological distinction between mesothelioma and secondary carcinoma is less problematic now than in earlier decades; overall, the sample is adequate for cell block preparation for various immunohistochemical studies. Because of the frequent litigation of cases of MPM and the availability of many mesothelial and adenocarcinoma markers, the guidelines strongly recommend that all cases should be confirmed with ICC/IHC.

MPM is a heterogeneous tumor, including three main histological subtypes: epithelioid (60–80%), sarcomatoid (10%), biphasic/mixed (10–15%), and other less common ones. The recognition of the various histopathologic patterns facilitates differential diagnosis and subsequent ancillary tests. The invasion of the chest wall soft tissue or underlying lung parenchyma is still the most reliable indicator of malignancy.

MALIGNANT MESOTHELIOMA PATHOLOGY
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🔗 https://www.ncbi.nlm.nih.gov/p....mc/articles/PMC58305

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  Mesothelioma