Impact of histological components on selecting limited lymphadenectomy for lung adenocarcinoma ≤ 2 cm.

Objectives: There is still some dispute regarding the performance of limited mediastinal lymphadenectomy (LML) even for lung adenocarcinoma ≤ 2 cm. We aimed to recognize the potential candidates who can benefit from LML based on the percentage of histological components (PHC).

Methods: We analyzed 1160 surgical patients with invasive lung adenocarcinoma ≤ 2 cm from seven institutions between January 2012 and December 2015. All histological subtypes were listed in 5% increments by pathological slices. To test the accuracy of frozen section in judging PHC, frozen section slides from 140 cases were reviewed by three pathologists.

Results: There were 882 patients with systematic mediastinal lymphadenectomy (SML) and 278 with LML. Multivariable analysis indicated that, the total percentage of micropapillary and solid components (PHC) > 5 % was the independent predictor of N2 metastasis (P < 0.001). Overall, recurrence-free survival (RFS) and overall survival (OS) favored SML compared with LML, but the subgroup analysis revealed LML and SML had similar prognosis in the group of PHC ≤ 5 %. Moreover, multivariable Cox analysis showed LML (vs. SML) was independently associated with worse prognosis for patients with PHC > 5 % (RFS, HR = 2.143, P < 0.001; OS, HR=1.963, P < 0.001), but not for those with PHC ≤ 5 % (RFS, P = 0.398; OS, P = 0.298). The sensitivity and specificity of frozen section to intraoperatively identify PHC ≤ 5 % were 97.6 % and 84.2 %, respectively.

Conclusions: PHC showed the predictive value for N2 metastasis and procedure-specific outcome (LML vs. SML). It may serve as a feasible indicator for identifying proper candidates of LML by using intraoperative frozen section.