Small tumor invasion of metastatic lymph node can develop extranodal extension in oral cancer

Objective: Extranodal extension (ENE) of lymph node metastasis in oral cancer has been well demonstrated to reflect tumor aggressiveness. However, there are few studies to show the association between ENE and tumor invasion status of metastatic lymph node. The purpose of this study is therefore to investigate pathological nodal factors including tumor invasion status of ENE-positive lymph node and its association with clinical outcomes in oral cavity squamous cell carcinoma (OSCC) patients. Methods: We identified OSCC patients with at least one pathologically ENE-positive node and measured area of metastasis within lymph node (inside metastasis), and area of metastatic lymph node. We defined tumor invasion ratio (TIR) as the ratio of inside metastasis area to metastatic lymph node area. Results: We observed that the value of TIR had a wide variation and that metastatic lymph nodes with small TIR can develop ENE. In addition, we demonstrated that tumors with smaller TIR had significantly worse DFS (HR 3.94, [1.21–12.83]; p = 0.014), OS (HR 5.38, [1.45–19.93]; p = 0.005), and more DM (HR 10.01, [1.17–86.0]; p = 0.001) than those with larger TIR. Conclusion: This is the first study to evaluate the detailed tumor invasion status of lymph node with ENE and showed that smaller TIR can develop ENE which was associated with clinical outcomes.