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

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).

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.

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_MIP+S) > 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_MIP+S ≤ 5 %. Moreover, multivariable Cox analysis showed LML (vs. SML) was independently associated with worse prognosis for patients with PHC_MIP+S > 5 % (RFS, HR = 2.143, P < 0.001; OS, HR=1.963, P < 0.001), but not for those with PHC_MIP+S ≤ 5 % (RFS, P = 0.398; OS, P = 0.298). The sensitivity and specificity of frozen section to intraoperatively identify PHC_MIP+S ≤ 5 % were 97.6 % and 84.2 %, respectively.

PHC_MIP+S 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.