Fig. 1

a Schematic representation of the morphological characteristics of C1 versus C2 tumors. C1 tumors show sporadic appearance of a high-grade invasive focus from a low-grade precursor and are often asymmetrical. As such the typical C1 is lepidic predominant with a minor invasive component, although tumors with any residual lower grade, nonsymmetrical lepidic component would similarly be classified as C1 by our scoring. C2 tumors represent high-grade invasive carcinomas with peripheral lepidic spread (outgrowth) of invasive tumor cells. As C2 tumors are expanding from a central invasive region, they show more symmetry, often with a marked constant-thickness ‘penumbra’ of in situ disease due to lepidic outgrowth. b Histology of representative C1 and C2 tumors. Low-power views show tumor architecture alongside high power regions from the in situ and invasive component of both tumors. c Lymph node positivity at resection by subtype. C2 tumors are more likely to show nodal metastasis than C1 tumors (p < 0.01). c Kaplan–Meier plot of 5 year overall survival of early lung adenocarcinoma patients in the LATTICe-A cohort – Noguchi A and B (biologically in situ), Noguchi C1, Noguchi C2, and a combined group of fully invasive subtypes (d)