Histological Features of Lung Squamous Cell Carcinoma According to Radiological Early-Phase Progression Patterns

We have previously reported radiological patterns of precursor lesions of lung squamous cell carcinoma (SqCCs) using computed tomography. SqCCs were found to develop from five unique precursor patterns. We histologically analyzed 61 cases from the previous cohort to evaluate whether these precursor patterns reflect possible developmental pathways. Of the precursor patterns, the endobronchial group demonstrated involvement of large bronchi in the hilar region. In the subsolid nodule pattern group, which exhibited ground-glass opacities radiologically, the tumors showed intra-alveolar wall infiltration, nuclear inclusion/vacuoles, low mitotic count, and absent atypical mitosis. In two of the seven cases in this group, lepidic growth, corresponding to ground-glass opacity, occurred at the tumor periphery. In the cyst wall thickening group, the tumors were located subpleurally, characterized by papillary growth structures. In the multiple-nodule group, all tumors displayed elastofibrous collapse and intra-alveolar wall infiltration. Overall and recurrence-free survival varied across the progression patterns. The radiological progression patterns were reflected in the histological features, highlighting the unique characteristics of subsolid and multiple nodule groups corresponding to peripheral-type SqCC. This study represented a new approach to the assessment of tumor evolutional pathways with histological features in combination with temporal radiographic changes.