Evolving concepts in lung cancer pathology and its impact on thoracic oncology practice

Lung cancer is the commonest cause of death worldwide but unfortunately, most patients present in an advanced stage of the disease. The classification of lung cancer has evolved since the first WHO publication in 1981, and the present edition was published in March 2015. A major change in 2015 was the introduction of the new terms adenocarcinoma in situ and minimally invasive adenocarcinoma to describe early adenocarcinoma of lung and abolition of the previous term bronchioloalveolar carcinoma. Tumors with micropapillary pattern and those showing spread through alveolar spaces have significant clinical implications with an increased propensity for recurrence. Tissue specimens require proper fixation in 10% buffered formalin which is an essential but an often neglected basic step; proper fixation is a prerequisite for good immunohistochemistry (IHC) and molecular test outcomes. Needle core biopsies should be handled judiciously to ensure that sufficient material is prioritized for molecular studies which are needed to guide personalized treatment. The WHO 2015 classification recommends the use of a single squamous cell marker (p40, or CK5/6) and a single adenocarcinoma marker (TTF1, or napsin) to distinguish squamous cell carcinoma and adenocarcinoma in difficult biopsies. The non-committal designation of non-small cell lung carcinoma (NSCLC) is discouraged. The exciting ongoing research findings on molecular biology of lung cancer necessitate constant expansion of laboratory test menu. Testing and treating lung cancer patients with epidermal growth factor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene fusion is now a standard of care, and ROS1 has been approved recently. The updated guidelines from the College of American Pathologists (CAP) and approval notifications from the Federal Drug Authority (FDA) are invaluable to justify initiation of new tests by pathology laboratories. Recently, FDA has approved testing for programmed death ligand (PDL1) with 22C3 antibody by IHC and EGFR testing on plasma by a non-invasive liquid biopsy test approach. To conclude, a comprehensive pathology report is vital for staging, comparing outcomes, and developing better strategies for patient care in the future.