Molecular Pathology of Lung Cancer Cytology Specimens: A Concise Review

Abstract

Context.— There has been a paradigm shift in the understanding of molecular pathogenesis of lung cancer. A number of oncogenic drivers have been identified in non–small cell lung carcinoma, such as the epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement. Because of the clinical presentation at an advanced stage of disease in non-small cell lung carcinoma patients, the use of minimally invasive techniques is preferred to obtain a tumor sample for diagnosis. These techniques include image-guided biopsies and fine-needle aspirations, and frequently the cytology specimen may be the only tissue sample available for the diagnosis and molecular testing for these patients. Objective.— To review the current literature and evaluate the role of cytology specimens in lung cancer mutation testing. We reviewed the types of specimens received in the laboratory, specimen processing, the effect of preanalytic factors on downstream molecular studies, and the commonly used molecular techniques for biomarker testing in lung cancer. Data Sources.— PubMed and Google search engines were used to review the published literature on the topic. Conclusions.— Mutation testing is feasible on a variety of cytologic specimen types and preparations. However, a thorough understanding of the cytology workflow for the processing of samples and appropriate background knowledge of the molecular tests are necessary for triaging, and optimum use of these specimens is necessary to guide patient management.