The morphological diversity of small lung adenocarcinoma with mixed subtypes is associated with local invasiveness and prognosis

Abstract

Under the current World Health Organization (WHO) classification, 'lung adenocarcinoma with mixed subtypes' is the most frequent type, even in small lung adenocarcinoma, with a diameter of 3 cm or less. For this type of lung adenocarcinoma, it has been reported that the high ratio of the peripheral bronchioloalveolar carcinoma (BAC)/lepidic growth (LG) component was a favorable prognostic factor. On the other hand, the central solid components of lung adenocarcinoma with mixed subtypes have not been focused on in the past. In this study, we took note of the histological features in central solid components of lung adenocarcinoma with mixed subtypes and evaluated whether the morphological diversity of these tumors is associated with local invasiveness and prognostic implication. A total of 103 surgically resected peripheral lung adenocarcinomas were reviewed. All the tumors were 3 cm or less in diameter and histologically diagnosed as lung adenocarcinoma with mixed subtypes, containing a BAC/LG component at the peripheral lesion of the tumor. The tumors were classified into two groups, according to the number of histological subtypes in the tumor, using the modified WHO classification (including the micropapillary subtype); group A (n = 76) has two or three histological subtypes, and group B (n = 27) has four or five subtypes in the tumor, respectively. Then, we evaluated the differences in clinicopathological factors and prognosis between these two groups. Group B was significantly associated with positive lymphatic and vascular invasion, lymph node metastasis, and advanced pathological stage, compared with group A. The 5-year survival rates of all patients were 91.4% for group A and 43.3% for group B, respectively, with a significant difference (p < 0.01). Multivariate analysis showed that the group classification by the number of histological subtypes was an independent prognostic factor in stage IA patients (p < 0.01). The morphological diversity of small lung adenocarcinoma with mixed subtypes is an independent prognostic factor and is associated with tumors' local invasiveness and patients' prognosis.