SMILE: A Scale-aware Multiple Instance Learning Method for Multicenter STAS Lung Cancer Histopathology Diagnosis

Spread through air spaces (STAS) represents a newly identified aggressive pattern in lung cancer, which is known to be associated with adverse prognostic factors and complex pathological features. Pathologists currently rely on time-consuming manual assessments, which are highly subjective and prone to variation. This highlights the urgent need for automated and precise diagnostic solutions. 2,970 lung cancer tissue slides are comprised from multiple centers, re-diagnosed them, and constructed and publicly released three lung cancer STAS datasets: STAS-CSU (hospital), STAS-TCGA, and STAS-CPTAC. All STAS datasets provide corresponding pathological feature diagnoses and related clinical data. To address the bias, sparse and heterogeneous nature of STAS, we propose an scale-aware multiple instance learning(SMILE) method for STAS diagnosis of lung cancer. By introducing a scale-adaptive attention mechanism, the SMILE can adaptively adjust high-attention instances, reducing over-reliance on local regions and promoting consistent detection of STAS lesions. Extensive experiments show that SMILE achieved competitive diagnostic results on STAS-CSU, diagnosing 251 and 319 STAS samples in CPTAC and TCGA, respectively, surpassing clinical average AUC. The 11 open baseline results are the first to be established for STAS research, laying the foundation for the future expansion, interpretability, and clinical integration of computational pathology technologies. The datasets and code are available at https://github.com/panliangrui/IJCAI25.