(a) DNA was extracted from multiple AAH lesions collected from six patients on resection of primary lung adenocarcinoma. Samples from AIS and MIA tumours extracted from five patients each were collected from different zones of histologic progression within the same lesion. (b) AAH is the earliest form of glandular neoplasia of the lung, which characterized by the proliferation of slightly atypical epithelial cells lining the slightly thickened by intact septae. Size is a critical feature in distinguishing AAH from AIS, a scale bar (1.0 mm) was included to underscore the small size of the AAH (magnification × 4). AIS is characterized by atypical cells with enlarged hyperchromatic nuclei lining intact alveolated lung parenchyma (zone 1). With progression towards the centre of the tumour, the septae become increasingly thickened and the cytologic atypia becomes more pronounced (zone 2 and zone 3) (magnification × 40 for normal lung and all AIS panels). MIA exhibits increasing septal thickening and epithelial atypia with progression from the periphery of the lesion (zone 1) towards its centre (zone 2 and zone 3). In addition, there is a small focus (<0.5 cm) of invasion at the core of the lesion (zone 4) characterized by irregular acinar glands in a desmoplastic stroma (magnification × 10 for all MIA panels).