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Context: - Traditional methods for storing histologic and cytologic specimens for future use in molecular assays have consisted of either snap-freezing with cryopreservation or formalin-fixing, paraffin-embedding the samples. Although snap-freezing with cryopreservation is recommended for better preservation of nucleic acids, the infrastructure and space required for archiving impose challenges for high-volume pathology laboratories. Cost-effective, long-term storage at room temperature; relatively easy shipment; and standardized handling can be achieved with formalin-fixed, paraffin-embedded samples, but formalin fixation induces fragmentation and chemical modification of nucleic acids. Advances in next-generation sequencing platforms, coupled with an increase in diagnostic, prognostic, and predictive molecular biomarkers have created a demand for high-quality nucleic acids. To address issues of the quality of nucleic acid and logistics in sample acquisition, alternatives for specimen preservation and long-term storage have been described and include novel universal tissue fixatives, stabilizers, and technologies., Objective: - To collect, retrieve, and review information from studies describing the use of nucleic acids recovered from cytologic/tissue specimens stored on Flinders Technology Associates (FTA, GE Whatman, Maidstone, Kent, United Kingdom) cards for downstream molecular applications., Data Sources: - An electronic literature search in the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database allowed the selection of manuscripts addressing the use of FTA cards for storage of cytologic samples for molecular analysis. Only articles published in English were retrieved., Conclusions: - The use of FTA cards is a versatile method for fostering multicenter, international collaborations and clinical trials that require centralized testing, long-distance shipment, and high-quality nucleic acids for molecular techniques. Studies with controlled temperature are required to test the quality of recovered RNA after long-term storage.

Context: - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer., Objective: - To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer., Data Sources: - An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review., Conclusions: - Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.

The advent of targeted therapy in lung cancer has heralded a paradigm shift in the practice of cytopathology with the need for accurately subtyping lung carcinoma, as well as providing adequate material for molecular studies, to help guide clinical and therapeutic decisions. The variety and versatility of cytologic-specimen preparations offer significant advantages to molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is critical, not only from a lung cancer diagnosis standpoint but also for the myriad ancillary studies that are necessary to provide appropriate clinical management. A large fraction of lung cancers are diagnosed by aspiration or exfoliative cytology specimens, and thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. This review focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era.