Molecular Alterations in Patients with Pulmonary Adenocarcinoma Presenting with Malignant Pleural Effusion at the First Diagnosis

Abstract

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.

The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients’ Demographics

“…This has been expanded, primarily due to the availability of IHC/immunocytochemistry, and, more recently, by performing other ancillary techniques such as molecular studies and identifying specific biomarkers such as PD-L1 on cytologic material [3, 12, 16-18]. However, obtaining adequate material to perform all the studies necessary to diagnose and guide therapy is still a challenge.…”

“…The mean age of presentation is approximately 65 years and most patients are symptomatic. MPE can be the initial presentation of a malignant process, e.g., up to 15% of lung carcinomas present with MPE [3]. …”

“…In the current era of precision medicine, molecular tests can be successfully performed on MPEs, which are easily accessible [3, 11-13]. However, adequacy for molecular studies can be challenging on cytology specimens.…”

Novel insights into the systemic treatment of lung cancer malignant pleural effusion

“…Only small series are available. In the series published, the most common genetic aberrations identified were EGFR, KRAS mutations and ALK translocation . A Chinese study analysed the clinical and prognostic implications of RET rearrangements in metastatic lung adenocarcinoma patients with MPE.…”

Not like breast cancer, but like breast cancer: micrometastasis and micropapillary structure in lung cancer

“…STAS as originally described as micropapillary subtypes (16) STAS might represent the aggressive nature as invasion to alveolar spaces. It is of note that micropapillary structure is always overrepresented in pleural effusion (17).…”