Introduction:: As there is little information on the histologic characteristics of adenocarcinoma in smokers, we histologically examined the effect of smoking on the carcinogenesis and progression of peripheral small lung adenocarcinomas. Methods:: Two hundred thirty-six consecutive patients with peripheral adenocarcinoma of the lung 30 mm or less in diameter were studied. Prognosis, histology, and location of the adenocarcinoma were compared among patients with a Brinkman index (B.I.) of 0, 1 to 500, and more than 500. Results:: The ratio of smokers to nonsmokers was 1.4:1. The rate of carcinogenesis in the upper region of the lung (S1-3) was 1.4 times as high that in the lower region (S4-10) in smokers, but almost equal in the two regions in nonsmokers. Outcome tended to be worse in patients with a B.I. of more than 500 than in those with a B.I. of less than or equal to 500 for adenocarcinomas 30 mm or less in diameter (p = 0.0855), and was significantly worse for adenocarcinomas 20 mm or less in diameter (p = 0.0359). Patients with a high B.I. tended to have invasive adenocarcinoma (IAC) without a bronchioloalveolar carcinoma (BAC) component (IAC- BAC) or IAC with a BAC component (IAC + BAC) rather than noninvasive adenocarcinoma. For adenocarcinomas as a whole, B.I. was correlated with several pathologic prognostic factors, including pathologic stage, lymphatic permeation, vascular invasion, presence of a solid component, necrosis, and modified scar grade, particularly in the upper region. Specifically, in IAC + BAC, B.I. was correlated with modified scar grade and the presence of a solid component. In IAC- BAC, B.I. was correlated with the presence of a solid component and necrosis. Conclusions:: Small adenocarcinoma in smokers seems to occur frequently in the upper region of the lung, shows invasive features more frequently, and shows greater progression and dedifferentiation than that in nonsmokers. Tobacco-smoking may have an effect on the carcinogenesis and multistep progression of peripheral lung adenocarcinoma 30 mm or less in diameter.
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