Reticulation Sign on Thin-Section CT: Utility for Predicting Invasiveness of Pure Ground-Glass Nodules

BACKGROUND. Pure ground-glass nodules (pGGNs) may represent a diverse range of histologic entities of varying aggressiveness. OBJECTIVE. The purpose of this study was to evaluate the use of the reticulation sign on thin-section CT images for predicting the invasiveness of pGGNs. METHODS. This retrospective study included 795 patients (mean age, 53.4 ± 11.1 [SD] years; 254 men, 541 women) with a total of 876 pGGNs on thin-section CT that underwent resection between January 2015 and April 2022. Two fellowship-trained thoracic radiologists independently reviewed unenhanced CT images to assess the pGGNs for a range of features, including diameter, attenuation, location, shape, air bronchogram, bubble lucency, vascular change, lobulation, spiculation, margins, pleural indentation, and the reticulation sign (defined as multiple small linear opacities resembling a mesh or a net); differences were resolved by consensus. The relationship between the reticulation sign and lesion invasiveness on pathologic assessment was evaluated. RESULTS. On pathologic assessment, the 876 pGGNs included 163 nonneoplastic and 713 neoplastic pGGNs (323 atypical adenomatous hyperplasias [AAHs] or adenocarcinomas in situ [AISs], 250 minimally invasive adenocarcinomas [MIAs], and 140 invasive adenocarcinomas [IACs]). Interobserver agreement for the reticulation sign, expressed as kappa, was 0.870. The reticulation sign was detected in 0.0% of nonneoplastic lesions, 0.0% of AAHs/AISs, 6.8% of MIAs, and 54.3% of IACs. The reticulation sign had sensitivity of 24.0% and specificity of 100.0% for a diagnosis of MIA or IAC and sensitivity of 54.3% and specificity of 97.7% for a diagnosis of IAC. In multivariable regression analyses including all of the assessed CT features, the reticulation sign was a significant independent predictor of IAC (OR, 3.64; p = .001) but was not a significant independent predictor of MIA or IAC. CONCLUSION. The reticulation sign, when observed in a pGGN on thin-section CT, has high specificity (albeit low sensitivity) for invasiveness and is an independent predictor of IAC. CLINICAL IMPACT. Those pGGNs that show the reticulation sign should be strongly suspected to represent IAC; this suspicion may guide risk assessments and follow-up recommendations.