Significance of nonmucinous lepidic component with mild nuclear atypia in the discrimination of multiple primary lung cancers from intrapulmonary metastases.

The distinguishing of intrapulmonary metastases from multiple primaries is of great clinical importance. Although comprehensive histological assessment (CHA) was recommended for addressing this problem, the limitations of CHA have been addressed. We hypothesized that a nonmucinous lepidic component with mild nuclear atypia (NLCMA) may be one of the important sign suggesting primary lesions. In this study, we measured the value of NLCMA in distinguishing multiple primaries from intrapulmonary metastases. We retrospectively analyzed a cohort of 54 patients with 116 lesions (70 comparisons). Intrapulmonary metastases and multiple primaries were differentiated on the basis of CHA (Method I) and CHA combined with the assessment of NLCMA (Method II), respectively. Then, the results of two methods were compared with survival analysis. 33 cases were defined as multiple primaries and 21 cases as metastases by Method I, while 41 cases as multiple primaries and 13 cases as metastases by Method II. On univariate analysis, there was a better DFS in patients with a tumor ≤ 3 cm (P=0.012), female gender (P=0.011), highest N0 (P=0.002), absent micropapillary (P=0.013), multiple primaries (P=0.008 by method I, P < 0.001 by method II). A multivariate analysis adjusting for gender, tumor size, micropapillary and multiple primaries/metastases (by methodI and method II, respectively) indicated that multiple primaries (by method II) was an independent predictors for DFS. The presence of NLCMA may indicate that a lesion should be defined as primary in multifocal adenocarcinoma.