Epithelial malignancies frequently metastasize to the serous cavities and result in symptomatic effusions. Cytology has high specificity but moderate sensitivity for the diagnosis of a malignant effusion. We developed and validated a simple, rapid, 3-color flow cytometric panel using the adhesion molecule Ber-EP4 to detect epithelial cells in effusions. One hundred ninety-five consecutive benign and malignant effusions received for routine cytologic examination were analyzed. Eighty-three fluid specimens were benign and 76 were malignant as judged by follow-up data. Ber-EP4-positive cells were detected with flow cytometry in 89.3% of malignant effusions. The sensitivity and specificity of flow cytometry was 88.15% and 97.64% compared with 73.68% and 100% on cytologic examination alone for the presence of a malignant effusion. Flow cytometry is a useful adjunct to cytology for the diagnosis of a malignant effusion and is particularly useful if the cytologic diagnosis is atypical/suspicious or if the cytologic preparations are hypocellular or hemorrhagic.
[Show abstract][Hide abstract] ABSTRACT: Some patients with epithelial-cell cancers develop leptomeningeal carcinomatosis (LC), a severe complication difficult to diagnose and with an adverse prognosis. This study explores the contribution of flow cytometry immunophenotyping (FCI) to the diagnosis and prognosis of LC. Cerebrospinal fluid (CSF) samples from patients diagnosed with LC were studied using FCI. Expression of the epithelial-cell adhesion molecule (EpCAM) was the criterion used to identify the epithelial cells. To test the diagnostic precision, 144 patients (94 diagnosed with LC) were included. The prognostic value of FCI was evaluated in 72 patients diagnosed with LC and eligible for therapy. Compared with cytology, FCI showed greater sensitivity and negative predictive value (79.79 vs. 50 %; 68.85 vs. 51.55 %, respectively), but lower specificity and positive predictive value (84 vs. 100 %; 90.36 vs. 100 %, respectively). The multivariate analysis revealed that the percentage of CSF EpCAM+ cells predicted an increased risk of death (HR: 1.012, 95 % CI 1.000-1.023; p = 0.041). A cut-off value of 8 % EpCAM+ cells in the CSF distinguished two groups of patients with statistically significant differences in overall survival (OS) (p = 0.018). This cut-off value kept its statistical significance regardless of the absolute CSF cell-count. The FCI study of the CSF improved the sensitivity for diagnosing LC, but refinement of the technique is needed to improve specificity. Furthermore, quantification of CSF EpCAM+ cells was revealed to be an independent prognostic factor for OS in patients with LC eligible for therapy. An 8 % cut-off value contributed to predicting clinical evolution before initiation of therapy.
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