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Wednesday, January 22, 2014

Cytological features of malignant mesothelioma

The majority opinion among surgical pathologists is that an essential condition for
definitive histological diagnosis of pleural mesothelioma is the demonstration of
neoplastic invasion – such as infiltration into underlying fat, skeletal muscle, rib or lung –
as opposed to benign entrapment of mesothelium
Effusion fluid cytology in isolation does not allow assessment of invasion, although a
2007 Update Statement on Mesothelioma from the British Thoracic Society (BTS)
stated that cytological examination of pleural effusion fluid from patients may be
sufficient for diagnosis in some patients, when correlated with imaging studies – that is,
using imaging studies as a surrogate for the histological demonstration of invasion
For example, the combination of the following may allow a diagnosis of mesothelioma
at a high level of confidence: florid atypical mesothelial proliferation on pleural effusion
fluid cytology supported by immunohistochemical studies on cell-block sections and
with no evidence of any infective process on microbiological investigation, plus confluent
pleural thickening with nodularity on imaging studies (with/without evidence of chest
wall invasion), plus absence from imaging studies of any intrapulmonary mass lesion or
extrathoracic tumour with the capacity for spread to the pleura.

Cytology-only diagnosis based on effusion fluids remains controversial  Although
several cytological findings raise varying levels of suspicion of malignant pleural
mesothelioma (58) – such as the extent of the mesothelial proliferation, the presence of
papillary structures (especially in the pleura), cytological atypia, frequent cytoplasmic
vacuoles and focal necrosis – there is some overlap in the cytological appearances
between reactive mesothelial hyperplasia and malignant mesothelioma
The most useful cytological features of malignant mesothelioma include the presence
of numerous relatively large (>50 cell) balls of cells with berry-like external contours
comprising cells that are much larger (with enlarged cytoplasm, nucleus and nucleolus)
than most benign mesothelial cells; the presence of macronucleoli – although prominent
nucleoli can be present in reactive mesothelial cells and not all malignant mesothelioma
cells have macronucleoli; and nuclear atypia.
Many cytological features of malignant mesothelioma – such as scalloped borders of cell
clumps, intercellular windows, variation in cytoplasmic staining and its ‘density’, and low
nuclear-to-cytoplasmic ratios – are shared between reactive and malignant epithelioid
mesothelial cells .
Reported sensitivities for a clear cytodiagnosis of mesothelioma on effusion fluids have
ranged widely. One 1997 study reported a low sensitivity of 32% ). In another study
26
of 162 cases , effusion fluid cytology showed high specificity (~99%) when all criteria
specified for mesothelioma were fulfilled, but the sensitivity was only 47.5% when
not all criteria were met. This sensitivity was improved by interpreting the cytological
findings together with effusion fluid hyaluronic acid concentrations. Some centres with
specialised interest and experience in the cytodiagnosis of mesothelioma from effusion
fluid (58) have found a high positive predictive value for diagnosis. Such results may
not be obtainable for other centres with less experience in cytological assessment of
mesothelial proliferations.

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