Prognostic significance of a histologic subtype in small adenocarcinoma of the lung: The impact of nonbronchioloalveolar carcinoma components

Background. We tried to clarify whether the histologic subtypes and the size of the solid component of an adenocarcinoma are more important predictive factors for invasiveness or prognosis than is total tumor size, even in lung adenocarcinomas that were 2 cm or smaller. Methods. Between 1996 and December 2005, after standard surgical treatment, 82 patients were diagnosed as having adenocarcinoma with a maximum diameter of 2 cm or less. The group comprised 37 females and 45 males, with ages ranging from 41 to 80 years (median, 64). The clinicopathologic records of the patients were examined with regard to age, sex, nodal status, tumor size (largest diameter of the total tumor as well as the largest diameter without the bronchioloalveolar carcinoma [BAC] component [solid component]), serum carcinoembryonic antigen level, and histologic type. These variables were analyzed as risk factors for vascular or lymphatic invasion, lymph node metastasis, and prognosis. Histologic subtype was classified into two groups: mixed BAC (mixed adenocarcinoma with BAC) and minimal or non-BAC (tumors with little or no BAC component). Results. Histologic subtype was a significant predictive factor both for invasiveness (vascular or lymph vessels) and lymph node metastasis, in both univariate and multivariate analysis. Tumor diameter was not a significant factor in either univariate or multivariate analysis (p = 0.28, 0.15, respectively). However, diameter excluding the BAC component was a significant factor for invasiveness in mixed BAC type (p = 0.035), whereas total diameter was not significant (p = 0.28). Finally, histologic subtype and lymph node metastasis were significant prognostic factors for survival in both univariate (p = 0.03, 0.05, respectively) and multivariate (p = 0.04, 0.05, respectively) analyses. The 5-year survival rate was 94.4% (94.1% for pN0) for the mixed BAC type and 71.4% (78.7% for pN0) for the minimal or non-BAC type (p = 0.009; p = 0.04 for pN0 nodes). Conclusions. Small adenocarcinomas can be classified into two categories. The first category is a minimal or non-BAC adenocarcinoma that shows aggressive biological behavior. The second category is a mixed BAC, which demonstrates less invasive or aggressive biological behavior than the minimal or non-BAC type, with the degree of invasiveness being associated with the size of the non-BAC component.