Objectives: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. Study Design: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression. Results: We identified 18 patients (9 males and 9 females). Micropapillary and/or solid adenocarcinoma type features predominated among cytologic specimens (n = 15), while acinar patterns predominated in controls. Survival was not significantly different from that of the control group (mean 13.8 vs. 13.9 months, respectively; p = 0.61). Ten (55%) cases had mutations in EGFR (n = 6; 60%), KRAS (n = 3; 30%), or ALK translocation (n = 1; 10%). No mutations were identified in BRAF, AKT, ERBB2, NRAS, or PIK3CA (tested in 7 patients). Patients positive for the tested mutations had a better overall survival than patients negative for the mutations (mean survival 16.2 vs. 6.05 months, respectively; p = 0.006, log-rank test). Ten (84%) control patients were positive for mutations in EGFR (n = 5; 42%), KRAS (n = 4; 34%), or ALK translocation (n = 1; 8.4%). Conclusion: In our series, a micropapillary-like and solid-like morphology, common in cytologic specimens, and alterations in EGFR were the most frequent identifiable molecular changes.

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