Spread through air spaces—novel pattern of cancer progression

Despite the proliferation of antismoking campaigns and lung cancer screening by computed tomography, lung cancer remains the leading cause of cancer death worldwide. Because of the anatomical features of the lung, the growth patterns of lung malignancies differ from malignancies of other sites. The patterns of lung cancer progression are cancer spread via vascular, lymphatic, or alveolar spaces (1). These are related to the biological behavior of the lung tumor. Regarding lung cancer prognosis, histopathological findings that include grade of differentiation (2), pleural invasion (3,4), and lymphovascular invasion (5,6) have been reported to be prognostic factors. The spread of lung cancer to the alveolar spaces was recently reported as a novel pattern of cancer progression, and reports on lung adenocarcinoma have shown that cancer spread through the air spaces (STAS) is a significant risk factor for recurrence and a poor prognostic factor for overall survival (1,7-15) (Table 1). As an aggressive manifestation of lung cancer, STAS was introduced as a new concept for lung adenocarcinoma in the 2015 World Health Organization (WHO) classification (16). WHO classification defined STAS as “micropapillary clusters, solid nests, or single cells spreading within air spaces beyond the edge of the main tumor” (16)