Date Published: October 18, 2018
Publisher: Public Library of Science
Author(s): Jae Ho Lee, Tae Hoon Kim, Sungsoo Lee, Kyunghwa Han, Min Kwang Byun, Yoon Soo Chang, Hyung Jung Kim, Geun Dong Lee, Chul Hwan Park, Aamir Ahmad.
To evaluate and compare the diagnostic accuracy of high versus low attenuation thresholds for determining the solid component of ground-glass opacity nodules (GGNs) for the differential diagnosis of adenocarcinoma in situ (AIS) from minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA).
Eighty-six pathologically confirmed GGNs < 3 cm observed in 86 patients (27 male, 59 female; mean age, 59.3 ± 11.0 years) between January 2013 and December 2015 were retrospectively included. The solid component of each GGN was defined using two different attenuation thresholds: high (-160 Hounsfield units [HU]) and low (-400 HU). According to the presence or absence of solid portions, each GGN was categorized as a pure GGN or part-solid GGN. Solid components were regarded as indicators of invasive foci, suggesting MIA or IA. Among the 86 GGNs, there were 57 cases of IA, 19 of MIA, and 10 of AIS. Using the high attenuation threshold, 44 were categorized as pure GGNs and 42 as part-solid GGNs. Using the low attenuation threshold, 13 were categorized as pure GGNs and 73 as part-solid GGNs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the invasive focus were 55.2%, 100%, 100%, 22.7%, and 60.4%, respectively, for the high attenuation threshold, and 93.4%, 80%, 97.2%, 61.5%, and 91.8%, respectively, for the low attenuation threshold. The low attenuation threshold was better than the conventional high attenuation threshold for determining the solid components of GGNs, which indicate invasive foci.
According to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classifications, adenocarcinoma is pathologically classified as a pre-invasive lesion (atypical adenomatous hyperplasia, adenocarcinoma in situ [AIS]), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA) according to the presence and size of the invasive foci . Currently, adenocarcinoma is the most common histological type of lung cancer and often appears as ground-glass opacity nodules (GGNs) on computed tomography (CT) imaging .
The present study received approval from the institutional review board of Gangnam Severance Hospital (3-2016-0324). Clinical data were reviewed from medical records. Given the retrospective nature of the study and the use of anonymized data, requirements for informed consent were waived.
A total of 86 GGNs in 86 patients (27 male, 59 female; mean age 59.3 ± 11.0 years) were evaluated in this study. The mean size of the tumors was 15.0 ± 7.5 mm. Detailed demographic patient data are summarized in Table 1.
This study demonstrated that the low attenuation threshold (-400 HU) was better than the high attenuation threshold (-160 HU) in determining the solid component of GGNs, which indicates an invasive focus. GGNs can be divided into part-solid and pure according to morphology on CT imaging. Although the solid portions of GGNs have a tendency to represent invasive foci, they do not directly correspond with invasive foci . Visual assessment with qualitative analysis for differential diagnosis of GGNs has well-known limitations, including inter-/intra-observer variations [11,16,17]. To overcome the drawbacks of visual assessments, various types of quantitative analysis of GGNs have recently been reported. The sizes of GGNs correlate with the invasion foci and pathologic results . Lim et al.  reported that a difference in mean attenuation value could be observed between invasive and non-invasive adenocarcinomas. Lee et al.  suggested -472 HU as the cut-off of mean attenuation value in the evaluation of tumor invasiveness. However, with these methods, it is difficult to define the invasive focus of a GGN directly, although identifying the invasive focus is the easiest way to differentiate AIS from MIA and IA. Furthermore, in the 8th TNM guidelines the T staging of lung cancer depends on the size of the solid portion . For these reasons, direct measurement of the solid portion of a GGN, which indicates an invasive focus, is crucial, and the absolute attenuation threshold to define invasive foci has been applied because CT attenuation is related to the density of the tissue . Matsuguma et al.  attempted to define the solid portion of a GGN using a threshold of -160 HU. Ko et al.  set the threshold at -188 HU and regarded the part of the nodule that exhibited higher values as the solid component. Recently, Cohen et al  used -350 HU, as the threshold when measuring GGNs, because the invasive foci and solid component of the GGN demonstrated the highest agreement for that threshold. Therefore, the optimal threshold for identifying the solid portion of GGNs has not been established. In this study, we attempted to obtain better thresholds for defining the solid portion of GGNs. We used -400 HU as a representative low threshold and -160 HU as a representative high threshold. The high threshold categorized all AIS cases as pure GGNs, but 44.8% of MIA and IA cases were also categorized as pure GGNs. In contrast, with the low threshold, 93.4% of MIA and IA cases were categorized as part-solid GGNs. These findings suggest that with the use of a high threshold, invasive foci may be missed, and a low threshold might be better at distinguishing MIA and IA, which are observed as part-solid GGNs, from AIS, which are observed as pure GGNs.