Cytologic re-evaluation of negative effusions from patients with malignant mesothelioma

Cytology is a controversial means of diagnosing malignant mesothelioma due to the high rates of negative samples. The aim of the present study was to review effusions originally reported as "negative" in patients with histologically-proven mesothelioma to evaluate possible pitfalls.

We reviewed the cytologic slides of 25 specimens that refer to 15 epithelioid, 5 biphasic, 4 sarcomatoid and 1 well-differentiated papillary mesotheliomas. For comparison, we also reviewed 23 specimens from non-neoplastic conditions. For each effusion, we evaluated the background and calculated a score considering the following items: amount of mesothelial cells, architectural pattern and atypical features, and a revised diagnosis was rendered.

More than half of the effusions initially called "negative" (but mesothelioma by histology) were considered atypical/ suspicious (false-negative diagnosis); the remaining cases were true-negative or inadequate. Almost all effusions initially called "negative" (but non-neoplastic by histology) were considered negative. The only item that seems to discriminate between the two groups is atypia of mesothelial cells.

The present study has highlighted the following pitfalls: (i) to report effusions devoid of mesothelial cells as negative that instead should be reported as inadequate/non-diagnostic; (ii) to underestimate low cellular effusions containing atypical mesothelial cells or high cellular effusions containing bland mesothelial cells with a morular pattern; (iii) to consider that an inflammatory background may obscure a scant number of mesothelial cells. A categorized system (inadequate (M1), negative (M2), atypical (M3) and suspicious (M4)) for reporting effusion cytology may be of help in the diagnostic work-up of patients with effusions suspicious for mesothelioma.