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Updated: May 19, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Molecular pathology of non-small cell lung cancer: a practical guide
Dara L Aisner1, Carrie B Marshall
1Department of Pathology, University of Colorado, Anschutz Medical Campus, 12801 East 17th Ave, Mail Stop 8104, Aurora, CO 80045, USA. dara.aisner@ucdenver.edu
Abstract:
The traditional distinction between small cell lung cancer and non-small cell lung cancer (NSCLC) is no longer sufficient for treatment planning. It is advised to handle small diagnostic specimens prudently because they are often the only specimen available for molecular analysis. Pathologists are experiencing pressure to subclassify lung carcinoma based on extremely small tumor samples, because NSCLC tumor subtyping is now essential to determine molecular testing strategies. Evaluation for EGFR mutations and ALK rearrangements are now considered to be the standard of care in advanced-stage pulmonary adenocarcinomas. Immunohistochemical stains can aid in subclassifying NSCLC, but performing these ancillary studies can significantly reduce the quantity of tissue available for molecular tests, requiring careful balancing of these 2 needs. The pathologist plays a pivotal role in facilitating clear and timely communication between the clinical oncology care team and the molecular laboratory to ensure that the appropriate tests are ordered and optimal material is submitted for testing.
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