Radiographic ground-glass nodules: Features and immune profiles in early-stage lung adenocarcinoma and its precursors—Insights into early detection and cancer prevention.

e20022 Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis. Enhanced computed tomography (CT) screening has led to increased detection of indeterminate pulmonary nodules (IPNs), which include preneoplasia, preinvasive lesions and early-stage LUAD. Ground-glass nodules (GGNs), a subset of IPNs, are often associated with early-stage LUAD and its precursors. However, their clinical and pathological implications remain incompletely understood. Methods: This retrospective study evaluated clinical, radiographic, pathological, and immune data from 174 patients with resected IPNs. The lesions included atypical adenomatous hyperplasia (AAH, N=19), adenocarcinoma in situ (AIS, N=50), minimally invasive adenocarcinoma (MIA, N=40), and stage I invasive adenocarcinoma (ADC, N=65). Radiographic patterns were categorized as GGNs, part-solid nodules, or solid nodules. Immune profiling was conducted using CD4/CD8 immunohistochemical staining. Results: Among 174 resected pulmonary nodules, GGNs were most prevalent in early lesions, including atypical adenomatous hyperplasia (AAH, 86.0%), adenocarcinoma in situ (AIS, 72.5%), and minimally invasive adenocarcinoma (MIA, 52.6%), compared to invasive adenocarcinoma (ADC, 20.0%; p<0.01). GGNs were associated with fewer aggressive features, including lower rates of pleural traction (4.0%) and lymphovascular invasion (2.9%). Immune profiling revealed a progressive decline in CD8+ cytotoxic T cells and increasing CD4/CD8 ratios from AAH to invasive ADC, suggesting impaired immune responses with disease progression. GGNs exhibited higher CD4 and CD8 levels compared to non-GGNs, indicating a more robust immune environment. Poorly differentiated ADC tumors, predominantly presenting as solid nodules, showed increased pleural traction (45.5%) and lymphovascular invasion (18.2%), underscoring their aggressive nature comparing to well and moderately differentiated ADCs (p<0.05; p<0.05). Conclusions: Radiographic GGNs are associated with less aggressive features and a favorable immune environment in early-stage LUAD and its precursors, serving as potential biomarkers for indolent disease. Poorly differentiated early-stage ADC tumors, predominantly solid nodules, exhibit increased aggressiveness, highlighting the importance of radiologic and histologic integration for risk stratification. These findings highlight the importance of integrating radiologic and histologic characteristics for effective risk stratification. GGNs may play a pivotal role in early detection and cancer prevention efforts, guiding tailored surveillance and intervention strategies.