Biomarker testing of cytology specimens in personalized medicine for lung cancer patients

Every patient with advanced non-small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrange-ments that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candi-dates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic chang-es with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of pro-grammed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cyto-logic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are neces-sary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical compo-nent of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for bio-marker testing of lung cancer and the role of cytopathology in the molecular era.