Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients with Stage II-III Lung Adenocarcinoma.

INTRODUCTION: High-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary and/or solid patterns (MIP/SOL) in lymph node (LN) metastases has prognostic value.

METHODS: Patients who underwent lobectomy for pathologic stage II-III lung ADC with N1 or N2 LN metastases (n=360; 2000-2012) were analyzed. We assessed overall survival (OS), lung cancer-specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases. Multivariable Cox regression analysis was used to quantify the association between MIP/SOL patterns and outcomes.

RESULTS: Micropapillary and solid patterns in LN metastases were associated with a higher incidence of smoking history (p=0.004), tumor necrosis (p=0.013), and spread of tumor through air spaces (p<0.0001), a higher prevalence of micropapillary or solid pattern in the primary tumor (p<0.0001), shorter OS (5-year OS, 40% [95% CI, 29%-56%] vs. 63% [48-83%) for no MIP/SOL in LNs; p=0.03), higher LC-CID (5-year, 43% [29%-56%] vs. 14% (4-29%); p=0.013), and higher CIR (5-year, 65% [50%-77%] vs. 43% (25-60%); p=0.057). Micropapillary and solid patterns in LN metastases were independently associated with poor outcomes: OS (hazard ratio [HR], 1.81 [95% CI, 1.00-3.29]; p=0.05), LC-CID (HR, 3.10 [1.30-7.37]; p=0.01), and CIR (HR, 2.06 [1.09-3.90]; p=0.026).

CONCLUSION: MIP/SOL histological patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stage II-III lung ADC. MIP/SOL histological patterns in LN metastases can stratify patients with high-risk stage II-III lung ADC.