Pathology Research International of FNAB sample preparation methods is needed to preserve biomolecular integrity to enable seamless integration into molecular testing. At present, there are few studies that rigorously compare the cellular composition of FNA samples with the quantity and quality of the desired analyte (DNA, mRNA, or protein) or the robustness of the biomarker test utilizing the sample. Schuurbiers et al. in their study conclude that molecular testing of EGFR and KRAS on cytologic material obtained by endobronchial ultrasound-guided transbronchial FNAB is feasible and could be performed on 77% of their specimens [34]. Another study by Smouse et al. showed that 67% of cytology specimens were adequate for molecular testing with some of the samples having as little as 25% tumor cellularity [35]. We have found that in a large screen of various cytologic specimens (FNABs, eﬀusions, and exfoliative specimens) submitted for EGFR or KRAS mutational testing, 98% of samples were suitable for analysis. We concluded that testing is feasible and that with rare exception all cell blocks subjec- tively interpreted as “adequate” for diagnosis by a pathologist yielded suﬃcient quantity and quality of DNA for mutational analysis. This ﬁnding is in agreement with several other studies [18]. In a study of consecutive specimens from our institution, it was found that 79% of cytology specimens and 89% of small biopsy specimens submitted for molecular testing were suﬃciently cellular [36]. The rate of EGFR and KRAS mutations detected in cytologic specimens in the study was comparable to the rate detected in surgical specimens. 7. Use of FNAB for Prognostic Markers The reported incidence of local or distant recurrence following surgical resection of early-stage NSCLC is around 36% [37]. The risk of recurrence is clearly linked to clinical stage but further biomarkers predictive of tumor recurrence are needed. A histological grading system based on the predominant histological patterns seen in pulmonary ade- nocarcinoma has been described recently [38]. In that study, patients with stage 1 pulmonary adenocarcinoma could be accurately stratiﬁed according to risk of recurrence of death of the disease into 3 tiers representing low, intermediate and high risk, thus indicating that an objective system of tumor grade had prognostic signiﬁcance. In cytological material however, there was no reliable corresponding pattern of cellular aggregates to predict a histological pattern for the same tumor [39], therefore a grading system based on nuclear features has been developed and evaluated in FNAB of pulmonary adenocarcinoma. The cytology grading system is based on the nuclear size of neoplastic cells; pattern of chromatin distribution; and nuclear contour and it separates stage 1 pulmonary adenocarcinomas into two groups. Tumors with low nuclear scores show a lower risk of recurrence or death of the disease in contrast to tumors with high nuclear scores [40]. In conclusion, FNAB can provide signiﬁcant prognostic information to clinicians managing patients with pulmonary adenocarcinoma. EGFR mutations are the best predictor of response to EGFR kinase inhibitors in pulmonary adenocarcinoma. 5 Recently, two antibodies that detect speciﬁcally mutated EGFR proteins have become commercially available. A recent study from our institution demonstrated that these antibod- ies show sensitivity of 95% for the detection of EGFR L858R mutation, and sensitivity of 85% for the detection of exon 19 deletions. They concluded that immunohistochemistry for mutated EGFR could be used as a screen method to identify candidates for therapy with EGFR tyrosine-kinase inhibitors [41]. An antibody that correlates with ALK gene rearrange- ment in NSCLC has also been reported recently with promi- sing results [42, 43] however this antibody is not yet com- mercially available. The use of these antibodies in cytological material has not yet been validated, but they may oﬀer an invaluable tool for screening patients with lung cancer where cytological material is the only specimen available. 8. New Sampling Methods in Lung FNAB (EBUS and ENB) A couple of new minimally invasive procedures have been recently developed as an alternative to standard approaches. One of them, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has recently emerged as a valid minimally invasive method for mediasti- nal staging of lung cancers and diagnostic workup of cen- trally located masses [44]. When used to sample mediastinal lymph nodes, at least a moderate number of lymphocytes must be present to ensure the adequacy of the specimen and avoid a false negative result. A large retrospective study performed at our institution found that EBUS-TBNA had 89% sensitivity and 100% speciﬁcity for malignant disease, revealing no major discrepancies between tumor subtypes rendered by EBUS-TBNA cytology and histology [45]. A study by Turnoy et al. showed that in patients with NSCLC without extrathoracic metastasis, EBUS-TBNA reduces the need for surgical staging by 68% with lower incidence of complications and no diﬀerence in diagnostic performance, thus establishing the procedure as a valid alternative to mediastinoscopy [46]. The two major limitations of standard ﬂexible bron- choscopy are its inability to reach peripheral segments of the lung and the limited diagnostic yield from lesions less than 3 cm in diameter. The alternative to bronchoscopy is CT-guided percutaneous biopsy where the possible compli- cations include hemorrhage and pneumothorax. Recently developed technology that is emerging in clinical practice essentially combines these two methods. Electromagnetic navigation is a localization device that assists in placing endobronchial accessories (e.g., forceps, brush, and needle) in the desired areas of the lung. The system uses low frequency electromagnetic waves and real-time 3D digital reconstruction of the previously obtained CT scan of the bronchial tree. Electromagnetic navigational bronchoscopy (ENB) systems were recently cleared by the US Food and Drug Administration to aid the physician in guid- ing endoscopic tools in the respiratory tract. This novel technical advance localizes and samples lesions in the lung