Low papillary structure in lepidic growth component of lung adenocarcinoma: a unique histologic hallmark of aggressive behavior.

Small-sized lung adenocarcinomas often contain a lepidic growth component in part. The term lepidic growth has recently been used to represent a growth pattern of neoplastic cells along preexisting alveolar structures. We reviewed 91 small-sized (≤3 cm) invasive lung adenocarcinomas with a lepidic component to study the histopathologic and clinicopathologic characteristics. In the lepidic component of invasive adenocarcinoma, we have identified a morphologically unique structure characterized by proliferation of low papillae, consisting of neoplastic cells piling up toward the alveolar space, and we defined this architecture as "low papillary structure." There were 18 cases with the low papillary structure in the lepidic components, whereas 73 cases did not have the structure. In the lepidic component, the cases with the low papillary structure had higher Ki-67 labeling index (15.7%) and more frequent p53 overexpression (50.0%) than did those without the structure (9.4% and 16.4%, respectively). Based on clinicopathologic findings, the presence of low papillary structure was significantly associated with lymphatic invasion (P = .023) and lymph node metastasis (P = .001). Furthermore, the patients with the low papillary structure in the lepidic components demonstrated significantly shorter disease-free and overall survival than did those without the structure (P = .001 and P = .010, respectively). We conclude that the low papillary structure is a significant histologic feature in a lepidic component and is associated with aggressive cancer behavior in lung adenocarcinoma.