The changes of the stromal elastotic framework in the growth of peripheral lung adenocarcinomas

Abstract

Most peripheral lung adenocarcinomas form a characteristic central fibrosis; however, the mechanism of formation has not yet been clarified. The stromal elastosis of 176 patients with peripheral lung adenocarcinomas was studied histologically, morphometrically, radiographically, and clinicopathologically. The tumors were classified into two types, according to the histomorphological pattern of the stromal elastosis: (1) a preserved framework composed of a uniformly thick stroma (Type 1; 20 patients) and (2) a disrupted framework in the central fibrosis in which many air spaces were collagenized or collapsed (Type 2; 156 patients). Around the central fibrosis in the Type 2 tumors, replacement growth took the form of a thin-walled, elastic framework. Image analysis disclosed that the elastotic framework had an increased elastic fiber volume (approximately three- to nine-fold, compared with the normal alveolar wall), especially in Type 1 tumors, related to the contraction of the pre-existing alveolar wall. In Type 2 replacement growth, the amount of elastic fibers was slightly increased, which suggested mild reaction of the pre-existing alveolar wall. Radiographically, Type 1 tumors were characterized by a gradual increase of the density without enlargement, while the Type 2 tumors often enlarged within a short period. Recurrence was seen in 54% of the patients with Type 2 tumors, but in none of those with Type 1 tumors. In the early development of peripheral adenocarcinoma, there is preservation of the elastotic framework (Type 1) of the stroma due to contraction and thickening of the alveolar walls. As the tumors grow, the elastotic framework is disrupted (Type 2), indicating stromal invasion. Based on the clinicopathologic findings and the outcome, Type 1 tumors may be in situ peripheral lung adenocarcinomas.