Does oncogenic mutation status influence tumor spread in resectable lung cancer?

Skip N2 metastasis of lung cancer is known to involve the mediastinum, but not the hilar lymph nodes. This phenomenon itself is not especially rare, as the incidence in resected pN2 disease is reported to range from 17.6% to 40.4% (Table 1) (1-13). Prognosis after resection is favorable for skip N2 cases compared with that of pN2 cases accompanied with hilar disease. Based on data from the International Association for the Study of Lung Cancer, Asamura et al. (15) documented no significant survival differences between the skip N2 phenotype and multistation pN1 disease, and thus recommend that physicians record N categories using new descriptors for further testing. With regard to factors predictive of skip N2 metastasis, several authors suggested that the histological type and tumor-containing lobe are predictive of skip pN2. An investigation on resected non-small-cell lung cancer cases conducted by Misthos et al. (3) reported that skip N2 occurred more frequently in squamous cell carcinoma than in adenocarcinoma. Li et al. (13) documented that acinar adenocarcinoma was more frequently associated with skip N2 metastasis in pN2 cases. In terms of the tumor-containing lobe, Riquet et al. (5) actually revealed a higher incidence of skip N2 metastasis involving tumors of the upper lobe and suggested potential contributions of lymph drainage patterns and visceral pleural invasion (VPI) to the spread patterns. In a study of 422 cases of cStage IA adenocarcinoma, Gorai et al. (12) identified 21 instances of skip N2 in 52 pN2 cases and found a significant association between skip pN2 and VPI and concluded that lymph node dissection was essential in cN0 VPI cases.