High-grade histological patterns in metastatic lymph nodes associated with poor prognosis in resected lung adenocarcinoma: a multicentre retrospective cohort study.

We aimed to investigate the prognostic value of high-grade patterns (HGPs) in lymph node metastasis in lung adenocarcinoma (LUAD). We retrospectively analysed patients (n=345; 2016-2018) with pathological stage IIB-IIIB LUAD who underwent lobectomy. We evaluated the overall survival (OS) and recurrence-free survival (RFS) of patients with and without a micropapillary/solid pattern in the primary tumour and lymph node metastases. Among the patients, the median age was 61.0 years, 54.2% (n=187) were female and 36.5% (n=126) had a history of smoking. Among the involved lymph nodes, 70.4% (n=243) were in pN2 stage and 29.6% (n=102) were in pN1 stage. Of the patients, 32.8% (n=113) had only one lymph node metastasis at the N2 station, whereas 37.7% (n=130) had multiple lymph node metastases at the N2 station. Patients with vascular invasion (p=0.003), pN2 stage (p<0.001), and a predominantly solid histological pattern in the primary tumour (p<0.001) were more likely to have metastatic lymph nodes of the solid subtype. Using a cut-off value of 10% rather than 20%, HGPs were more significant in evaluating RFS (p<0.001 vs p=0.22) and OS (p=0.009 vs p=0.46). Compared to patients without HGPs in lymph node metastases, the presence of a solid component [hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.27-3.38; p=0.004], micropapillary component (HR 3.20, 95% CI 1.81-5.68; p<0.001), and both solid and micropapillary components (HR 2.60, 95% CI 1.54-4.40; p<0.001) in lymph node metastasis were all significantly associated with poorer OS. Patients with only micropapillary components (HR 1.96, 95% CI 1.19-3.22; p=0.008) or both micropapillary and solid components (HR 1.75, 95% CI 1.12-2.71; p=0.013) in lymph node metastasis had significantly poorer RFS. For surgically resected LUAD patients with lymph node metastasis, those with high-grade histological patterns in metastatic lymph nodes had a poorer prognosis, and the histological patterns of metastatic lymph nodes can be used to stratify such patients.