Molecular Testing of Non-Small Cell Lung Carcinoma Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Fine-Needle Aspiration: The Cleveland Clinic Experience

Abstract

Context.—: Given the increasing demand for molecular testing of non-small cell lung carcinoma specimens to guide therapeutic decision-making and the trend toward minimally invasive techniques for obtaining diagnostic tissue, cytopathology laboratories must devise strategies to maximize DNA yield for necessary molecular testing.

Objective.—: To describe our experience at Cleveland Clinic with epidermal growth factor receptor (EGFR) mutation testing by next-generation sequencing and anaplastic lymphoma kinase (ALK) gene rearrangement testing by fluorescence in situ hybridization of non-small cell lung carcinomas diagnosed by cytology, with an emphasis on specimens obtained by endobronchial ultrasound-guided transbronchial fine-needle aspiration.

Data sources.—: Data sources include a review of the current literature, including published articles from our institution.

Conclusions.—: At our institution, liquid-based cytology specimens are the primary resource used for molecular testing of non-small cell lung carcinomas; in most instances, adequate DNA can be extracted from the residual cell pellet for next-generation sequencing, and ThinPrep slides can be used reliably for fluorescence in situ hybridization testing for ALK gene rearrangements. In occasional cases where the cell pellet material is not adequate for molecular testing, cell blocks and/or surgical pathology specimens are secondary options. The cytopathologist's role in specimen handling and triage is essential to ensure that molecular testing can be carried out successfully.