Interest in measuring the exact size of the solid component of lung adenocarcinoma on CT has increased because of the close relationship to prognosis [2–4, 8–10], and several studies have established standardized methods to evaluate solid components with different windows. The present study focused on the differences in solidity categorization between observers and which components and windows should be used to determine clinical T staging of ADC.
Surprisingly enough, when categorizing the solidity of lesions, approximately 25% were atypical cases that caused discordant results among observers. Given that interobserver agreement has been reportedly low when classifying lesion types (pure-GGN, part-solid, or solid) in lung window–based assessment in several studies [7, 11], our results showed a generally good, but not exceptionally high, agreement among observers.
According to our analysis, three different radiologic situations made categorization difficult. First, subjective interpretation of borderline attenuating lesions in the lung window was the main cause of the discordancy (Fig. 2A). Because borderline attenuated lesions were more dense than usual GGOs, they caused confusion as to whether they should be classified as pure-GGN or part-solid nodules. In the Fleischner glossary, the solid component of a part-solid nodule should fulfill the criteria of consolidation. Fleischner recommendations advised mediastinal windows for evaluation of solid components, which usually exceed − 160 HU [12, 13]. However, a study by Lee et al. suggested that a lower density range of − 261 to − 160 HU is more appropriate to describe an invasive tumor component [4]. There is therefore a question of whether these borderline attenuated lesions should be considered solid, and further discussion is warranted. Although they constitute relatively small portions, other lesions such as entirely heterogeneous lesions or lesions with smoothly transitional margins also caused inconsistencies among observers (Figs. 2B and 2C). All three types described above caused inconsistencies among observers, creating a considerable number (25%) of discordant atypical cases. As inaccurate solidity categorization may affect the accuracy of measurements, visual assessment alone limits accuracy and consistent categorization.
Many groups have reported the possibility of using histograms and texture analysis to distinguish invasive ADC from pre-invasive ADC or MIA and to predict tumor metabolism or stages [14–17]. Ikeda et al. reported that the 75th percentile CT number of GGO lesions was the optimal CT number for differentiating atypical adenomatous hyperplasia and other histology using a CT number histogram [15]. Similarly, in categorizing borderline attenuated lesions or lesions with smoothly transitional margins, a histogram analysis may supply a more objective method for differentiating between pure-GGN and part-solid nodules. Also, texture analysis that includes entropy and uniformity could help categorize entirely heterogeneous attenuated lesions.
As to which components should be measured to predict invasive components and patient prognoses in part-solid nodules, recent studies have shown that solid components are more useful than total components [2, 8–10]. However, our study demonstrated that the total size measurement is no worse than solid component measurements at predicting invasive components. This is likely because we included a variety of lesions that contained relatively large solid components, while most previous studies targeted small tumors (≤ 3 cm) that had a substantial ground-glass or lepidic component. Further study is needed to determine which component should be measured in the case of larger tumors or tumors composed predominantly of invasive components with a minor ground-glass component.
In terms of the reproducibility of the measurement, we compared interobserver agreements among radiologists and pulmonologists with respect to the total and solid component measurements between lung and mediastinal windows. We found no significant differences in interobserver agreement for both solid and total size measurements at different windows. We also found a very good degree of interobserver agreement between the radiologist and pulmonologists and between residents versus fellow. Lee et al. reported that both windows could be applied to solid component measurement without a significant difference in the case of MIA [5]. Yoo et al. reported no significant difference in interobserver agreement among five readers for solid component measurements between two windows in the case of subsolid nodules with solid components smaller than 8 mm [18]. Our results are consistent with these previous studies. However, unlike previous studies that targeted only patients with solid components smaller than 8 mm, our study targeted various sizes of ADC and included more patients, similar to a real clinical setting. Our results reconfirmed and strengthened the previous findings by larger number and a wide range of lesions. We also confirmed that a pulmonologist can measure as well as a radiologist.
In terms of accuracy of size measurement, the lung window demonstrated greater accuracy compared with mediastinal window, especially in the case of part-solid nodules. The absolute difference value was significantly high in mediastinal windows, which means less similarity to pathologic size. The ICC values between CT and pathological measurement also tended to be higher with narrower 95% CIs in a lung window than those in mediastinal window. These results indicate the lung window is better than mediastinal window at predicting pathologic invasive component size [6, 18]. A recent study by Yanagawa et al. suggested that the solid proportion in the lung window is more appropriate than using mediastinal window, because nodules with a larger solid proportion using the lung window tended to have greater malignant potential [19]. In addition, mediastinal windows tended to underestimate the size of pathologic invasive components compared with lung windows. This result is inevitable owing to various CT morphologies of invasive components, ranging from ground-glass to solid density. Invasive components manifesting as complete GGO to intermediate density on a CT scan may not appear on a mediastinal windows and lead to an underestimate [6, 18].
In addition to the inherent characteristics of invasive components being underestimated, we found that several characteristics of the lesions produce a greater difference in size measurements on mediastinal windows. A lesion with multiple scattered solid components and internal air densities was difficult to measure and showed increased interobserver variability on the mediastinal window compared with the lung window (Fig. 3). Also, multiplicity of solid components caused increased interobserver variability, especially in the mediastinal window (Fig. 4). Current IASLC guidelines recommend measuring the long axis of the largest solid component in the case of part-solid lesions with several solid components [1]. Although we measured and added all the solid components in order to measure as closely as possible the pathologic invasive components, we still encountered underestimates. Kim et al. reported substantial interobserver and intraobserver variability in determining the multiplicity and size of the solid components, and that the multiplicity of the solid component was not a significant risk factor of tumor recurrence [20]. Our study also demonstrated that the sum of multiple solid components is prone to observer variability and could be inaccurate.
Our study had several limitations. First, it was retrospective; therefore, CT protocols and section thickness were not uniform. Second, the pathological assessment we used as a reference standard may be inaccurate inadequately inflated lung tissue after resection with tissue processing.