Cytopathological Diagnosis of Non Small Cell Lung Cancer: Recent Advances Including Rapid On-Site Evaluation, Novel Endoscopic Techniques and Molecular Tests

Abstract

Important advances in non small cell lung cancer (NSCLC) diagnosis, staging and treatment have been made over the last decade. Minimally-invasive endoscopic techniques including endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) and navigational bronchoscopy have emerged as valid alternatives to transthoracic and/or surgical approaches, providing aspiration cytology material instead of histological material for diagnosis and staging of mediastinal and lung lesions. Several drugs designed to target molecular pathways involved in cancer-cell growth and survival have been shown to be effective in a selected fraction of NSCLC patients, mostly with adenocarcinoma (targeted therapy). Somatic activating mutations in several genes involved in those pathways (EGFR/KRAS) can predict patients’ responses to targeted therapies (individualized therapy). Those mutations are commonly detected in histopathological samples (core-needle biopsy/surgical resection). However, when histological tissues are not available, molecular testing can be performed on cytological specimens. This scenario is increasing in frequency, due to the use of less invasive procedure for diagnosis and staging such EBUS-TBNA and/or patients in advanced stage of disease who are not candidates for surgery. Several strategies exist and may be combined to ensure that the less abundant material that results from minimally invasive techniques can be used efficiently for molecular analyses. These include Rapid On-Site Evaluation (ROSE) of EBUS-TBNA cytological material, to ensure optimal sampling and triage of the material (e.g. cell-block preparation), and microdissection techniques, to select an adequate population of tumor cells. Major issues raised by cytological diagnosis of NSCLC and molecular testing on cytological specimen are discussed in this article.