Clinicopathological Significance of Spread Through Air Spaces in Lung Cancer

Although it has been known for over 40 years that lung cancer can progress by spreading through alveolar spaces, the WHO formally published the term "spread through air spaces" (STAS) only 10 years ago, in 2015. Numerous studies have proven that STAS is a poor prognostic factor in all histological types of lung cancer and affects surgical procedure selection and stage classification. While it is clear that STAS should be reported in the routine diagnosis of lung cancer, diagnosis can sometimes be challenging, and pathologists need to be aware of the diagnostic and exclusion criteria. Clinicians also need to recognize the importance of STAS and cooperate in improving diagnosis using frozen sections, which has become a topic of discussion in recent years. In this review, we summarize the current status of research on STAS from various perspectives, including clinical, morphological, genetic, molecular, and tumor immune microenvironmental properties, and discuss future prospects.