Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to 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 (MIP), solid (SOL), or both patterns in lymph node (LN) metastases has prognostic value. Methods Patients who underwent lobectomy for pathologic stages II to 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 MIP and SOL 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 MIP or SOL in the primary tumor (p < 0.0001), shorter OS (5-y OS, 40% [95% confidence interval or CI: 29%–56%] versus 63% [48%–83%] for no MIP/SOL in LNs, p = 0.03), higher LC-CID (5-y, 43% [29%–56%] versus 14% [4%–29%], p = 0.013), and higher CIR (5-y, 65% [50%–77%] versus 43% [25%–60%], p = 0.057). MIP and SOL 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). Conclusions MIP/SOL histologic patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stages II to III lung ADC. MIP/SOL histologic patterns in LN metastases can stratify patients with high-risk stages II to III lung ADC.