Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical resection: a radiological, histological, and immunohistochemical study

Purpose: Bronchioloalveolar carcinoma (BAC) is a subtype of lung adenocarcinoma whose incidence is raising. Bronchioloalveolar carcinoma has a tendency to involve diffusely the lung. No agreement exists about whether diffuse bronchioloalveolar carcinoma has a multicentric or unicentric origin. The purpose of this work is to evaluate the correlation between intrapulmonary spread of bronchioloalveolar carcinoma and its histologic and immunohistochemical characteristics. Design: Surgical specimens of 20 bronchioloalveolar carcinomas with radiologically proved evolution from focal to diffuse disease were retrieved and reviewed. Patterns of pulmonary spread were defined on the basis of CT and MR imaging examinations. Immunohistochemical studies were performed to investigate the expression of gelatinase A and α2-integrin. Correlation between immunohistochemical results and patterns of pulmonary spread was evaluated. Statistical evaluation was performed by using Fisher Exact Test. Results: Three histological subtypes of bronchioloalveolar carcinoma were found: mucinous (11 cases), non-mucinous (3 cases), and mixed adenocarcinoma with prominent bronchioloalveolar pattern (6 cases). Three patterns of pulmonary spread were depicted radiologically: parenchymal opacification (11 cases), multiple nodules (7 cases) and mixed pattern (2 cases). Eleven out of 12 mucin-producing versus none out of 8 non-mucin producing cancers developed parenchymal opacification. The difference was statistically significant (P<0.028). A statistically significant difference was also found between the development of parenchymal opacification and the level of α2-integrin: 11 out of 13 tumors with negative α2-integrin versus none out of 7 with positive α2-integrin immunoreactivity (P<0.033). Conclusions: Diffuse bronchioloalveolar carcinoma may develop from a prior focal cancer. Mucinous subtype is the most prone to develop diffuse disease with parenchymal opacification, probably representing aerogenous spread. Low levels of α2-integrin receptors were found in bronchioloalveolar carcinoma which developed parenchymal opacification.