The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed.All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of .5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed.EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma.Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.

BackgroundConventional smears of samples obtained by endobronchial ultrasound with real-time transbronchial needle aspiration (EBUS-TBNA) have proven useful in lung cancer staging, but the value of additional information from cell-block processing of EBUS-TBNA samples has only been marginally investigated. This study focussed on the contribution of cell block analysis to the diagnostic yield in lung cancer.MethodsPatients referred for lung cancer diagnosis and/or staging by means of EBUS-TBNA were enrolled, the adequacy of the obtained samples for preparing cell blocks was assessed, and the additional pathologic or genetic information provided from cell block analysis was examined.ResultsIn 270 lung cancer patients referred for EBUS-TBNA (mean age, 63.3 SD 10.4 years) 697 aspirations were performed. Cell blocks could be obtained from 334 aspirates (47.9%) and contained diagnostic material in 262 (37.6%) aspirates, providing information that was additional to conventional smears in 50 of the 189 samples with smears that were non-diagnostic, corresponding 21 of these blocks to malignant nodes, and allowing lung cancer subtyping of 4 samples. Overall, cell blocks improved the pathologic diagnosis attained with conventional smears in 54 of the 697 samples obtained with EBUS-TBNA (7.7%). Cell blocks obtained during EBUS-TBNA also made epithelial growth factor receptor mutation analysis possible in 39 of the 64 patients with TBNA samples showing metastatic adenocarcinoma (60.1%). Overall, cell blocks provided clinically significant information for 83 of the 270 patients participating in the study (30.7%).ConclusionsCell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma.

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Intrathoracic lymph node enlargement is a common finding in patients with extrathoracic malignancies. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is commonly used for lung cancer diagnosis and staging but that has not been widely investigated for the diagnosis of enlarged mediastinal and lobar lymph nodes in patients with extrathoracic malignancies. We conducted a retrospective study of 117 patients with extrathoracic malignancies who underwent EBUS-TBNA for diagnosis of intrathoracic lymph node enlargement from October 2005 to December 2009 and compared the EBUS-TBNA findings with the final diagnoses. EBUS-TBNA diagnosed mediastinal metastases in 51 of the 117 (43.6 %) cases and gave an alternate diagnosis or ruled out the presence of malignancy in 35 (56.4 %). Fourteen of these 35 patients underwent further surgical investigation, while the remaining 21 had clinical and radiological follow-up for 18 months. No false negatives were found in the surgery group. In the follow-up group, 13 patients had stable or regressive lymphadenopathy, and eight developed clinicoradiological progression and were assumed to have been false negatives by EBUS-TBNA. The sensitivity and negative predictive value of EBUS-TBNA were 86.4 and 75 %, respectively. Immunohistochemical staining (IHC) was performed in 80.4 % of the samples obtained by EBUS-TBNA. In samples obtained from ten patients with metastatic breast cancer, estrogen receptor expression was successfully assessed in eight patients and progesterone receptor and human epidermal growth factor receptor 2 in four. EBUS-TBNA is an accurate procedure for the diagnosis of thoracic lymph node metastases in patients with extrathoracic malignancies and should be an initial diagnostic tool in these patients. Furthermore, EBUS-TBNA can obtain high-quality specimens from metastatic lymph nodes for use in molecular analyses.