Background: Imaging studies provide essential clinical information for lung cancer diagnosis, treatment and management. Features such as ground glass opacity (GGO) or internal air bronchogram (IAB), while commonly seen in early stage lung cancer, have minimal clinical implication. By examining a cohort at a single institution, we explored the hypothesis that radiographic characteristics correlates with the molecular signatures. Methods: Since 2009, our institution has prospectively characterized the EGFR status of all non-squamous lung carcinomas. Our inclusion criteria included tumor size < 3 cm and positive EGFR mutation. We randomly selected wild type (WT) patients matched by age and tumor size. The CT imaging of these patients was evaluated by a single radiologist (EO). Results: Imaging features were extracted from 20 WT and 19 EGFR-mutated tumors. Of the EGFR-mutated tumors, 7 had the exon 21 L858R point mutation and 12 had in-frame exon 19 deletion. There were 68% (13) solid nodules in EGFR-mutated and 90% (18) in WT tumors. While solid nodule was the primary feature seen in both WT and EGFR-mutated tumors, exon 21 mutation was associated with mixed ground glass/solid nodule (MGGS) (p = 0.005). This tendency, however, is not present in the exon 19 mutated tumors. No pure GGO was identified in either EGFR or WT group. IAB was present in 62% (24), pleural attachment (PA) in 87% (34), and spiculated (SP) as opposed to lobulated (LO) nodules in 90% (34) of the tumors, which do not differ significantly among groups. Conclusions: Early stage lung adenocarcinomas show a spectrum of imaging features that can be correlated with tumor’s genetic mutations. MGGS is a distinct imaging characteristic differentiating exon 19 and exon 21 EGFR-mutated tumors.

* WT and exon 19; ^# WT and exon 21; ^& WT and exon 19&21; ^≠ p value comparing exon 19 and exon 21.