Tertiary lymphoid structures in lung adenocarcinoma: characteristics and related factors

Tertiary lymphoid structures (TLSs) are found in a variety of malignancies and affect the growth of tumors, but few studies have addressed their role in lung adenocarcinoma (LAC). We aimed to evaluate clinical features associated with TLSs in patients with LAC.

A collection of resected pulmonary nodules in patients with LAC was retrospectively analyzed. TLSs were quantified by their number per square millimeter tumor area (density) and by the degree of lymphocyte aggregation (maturity) in each case. The correlation between TLS density and maturity and clinical features was calculated.

A total of 243 patients were selected, of whom 219 exhibited TLSs. The occurrence of TLSs was correlated with computed tomography (CT) features as follows: pure ground-glass nodules (pGGNs) (n = 43) was associated with a lower occurrence rate than part-solid nodules (PSNs) (n = 112) and solid nodules (SNs) were (n = 88) (p = 0.037). TLS density was correlated with age and CT features. Poisson regression showed higher TLS density in PSNs and SNs than in pGGNs (incidence rate ratio [IRR]: 3.137; 95% confidence interval [CI]: 1.35-7.27; p = 0.008 and IRR: 2.44; 95% CI: 1.02-5.85; p = 0.046, respectively). In addition, TLS density was higher in patients aged under 60 years than in those aged over 60 years (IRR: 0.605; 95% CI: 0.4-0.92; p = 0.018). The maturity of TLSs was higher in patients with higher tumor stages (p = 0.026).

We demonstrated distinct profiles of TLSs in early LAC and their correlations with CT features, age, and tumor stages, which could help understand tumor progression and management.