Extracting Histologic Features to Distinguish Primary and Metastatic Squamous Cell Carcinoma of the Lung

Lung is a common site of metastasis for squamous cell carcinoma (SqCC), and distinguishing primary lung SqCC from pulmonary metastatic SqCC is critical for clinical decision-making, including treatment planning. However, no practical histological criteria have been established for routine diagnosis. This study aimed to develop histopathological criteria to differentiate lung SqCC and pulmonary metastatic SqCC. A total of 85 surgical cases (48 primary and 37 metastatic) were collected with clinical background data. Seven histological features were evaluated. Six [morphological heterogeneity, dilated airway, interstitial fibrosis (IF), squamous dysplasia (SD), emphysema, RB macrophage] were presented as primary-associated features, while stromal infarction was proposed as metastatic. Seven pathologists scored these features. Primary-associated findings showed significantly higher score in primary cases. Tumor size (size) was significantly larger in the primary group (median: primary, 30 mm; metastatic, 14 mm; p < 0.001). A multivariate analysis incorporating size produced the "pathological primary formula" based on parameter estimates: 0.70・IF + 0.36・SD + 0.09・size, with an AUC of 0.86, sensitivity of 89.5%, and specificity of 70.2%. These results suggest that the extracted histologic features may provide reproducible criteria for distinguishing primary lung SqCC from pulmonary metastatic SqCC, offering insight into potential diagnostic applications.