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

Abstract

<b>BACKGROUND.</b> Pure ground-glass nodules (pGGNs) may represent a diverse range of histologic entities of varying aggressiveness. <b>OBJECTIVE.</b> 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. <b>METHODS.</b> 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. <b>RESULTS.</b> 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; <i>p</i> = .001) but was not a significant independent predictor of MIA or IAC. <b>CONCLUSION.</b> 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. <b>CLINICAL IMPACT.</b> Those pGGNs that show the reticulation sign should be strongly suspected to represent IAC; this suspicion may guide risk assessments and follow-up recommendations.