Exploring the key clinical and computed tomography features for distinguishing high-grade lung cancers from morphologically similar benign tumors: a two-center case-control study

Some high-grade lung cancers (HGLCs) and pulmonary benign tumors (PBTs) exhibit similar computed tomography (CT) features. This study aims to determine the key clinical and CT features for identifying HGLCs. From 2011 to 2025, 102 HGLCs presenting as regular solid nodules (SNs) and 102 size-matched PBTs were retrospectively enrolled. Clinical data and qualitative and quantitative CT indicators of lesions were analyzed and compared. Firth’s penalized logistic regression was used to identify independent predictors, and model performance was evaluated using 5-fold cross-validation. Compared to patients with PBTs, those with HGLCs were more likely to be male, older, and symptomatic individuals and smokers, with greater smoking amount (all P < 0.05). HGLCs also demonstrated higher rates of mediastinal/hilar lymph node enlargement, vascular encasement, and bronchial obstruction, while calcification was absent (all P < 0.001). The male (odds ratio [OR], 42.340; 95% confidence interval [CI], 2.283 -785.149; P = 0.012), high pack-years (> 27.6) (OR, 1.161; 95%CI, 1.022–1.321; P = 0.022), mediastinal/hilar lymph node enlargement (OR, 208.631; 95% CI, 6.477–6720.607; P = 0.003), bronchial obstruction (OR, 34.375; 95% CI, 2.314–196.064; P = 0.010), and vascular encasement (OR, 39.650; 95% CI, 9.089–67.752; P = 0.002) were revealed as independent predictors of HGLCs. In male heavy smokers, SNs with morphological features of PBTs but exhibiting vascular encasement, bronchial obstruction, or mediastinal/hilar lymph node enlargement warrant closer monitoring or further evaluation.