This study showed a similar distribution of SLCNs in the different groups categorized based on nodule size. Lung cancers are generally believed to be mainly distributed in the upper lobes [29-31]. Regarding nodule location, most nodules, particularly the smaller ones, were not found to be connected with the adjacent pleura. It appeared that the space between the tumor and pleura subsists until the nodules grow large enough to occupy it [32]. It is possible that a SLCN is typically derived from the distal bronchus, and a gap exists between the lesion and the pleura. These findings show that smaller nodules clinging to the pleura, which are usually detected on chest CT scan, are less likely to be lung cancer.
In this study, the CT features of smaller lesions (≤ 1 cm) were usually different from those of the bigger ones (> 1 cm). As nodule size increased, the lesions acquired a more regular shape and the margins and surrounding features also gradually increased. It may be because a nodule becomes more regular with an increase in size, and the limitation of the surrounding structure becomes more obvious. Lobulation, spiculation, pleural retraction, and vascular convergence are considered common signs of malignancy in lung cancer [6, 20-25]. However, for smaller nodules, traction and invasion of surrounding blood vessels and tissues, as well as tumor and peritumoral fibrosis were not obvious. As nodules size increased, the invasion of the surrounding tissue also increased, and more surrounding signs were evident.
Siegelman et al. [33] reported that the incidence of coarse tumor–lung interface was significantly higher in lung cancers than in benign lesions. In this study, tumor–lung interface in each group was mainly coarse. Additionally, the incidence of coarse interface increased with the increasing size of the nodule. This may be because tumor cells locally infiltrate the peripheral tissue, particularly the bigger nodules. However, the smaller the nodules, the higher the incidence of unclear interface, which may be related to the relatively sparse tumor cells in the peripheral areas of those nodules. Therefore, for smaller solid nodules with unclear interface, the possibility of lung cancer cannot be completely excluded and follow-up is recommended in such cases to avoid an erroneous diagnosis.
The growth of solid lung cancer is a gradual process. The tumor cells gradually accumulate, and the lesion size continuously increases. Theoretically, tumor density is more homogeneous on plain CT scan with an increase in the lesion size. In the present study, small nodules, particularly those with diameter < 1 cm, had a higher incidence of heterogeneous density. However, the incidence of internal calcification, vacuole sign, or cavity was low in each group, as previously reported [34, 35]. Therefore, small solid nodules with heterogeneous density can be selectively observed, and lung cancer should be highly suspected once their density increases and becomes homogeneous.
Beam-shaped opacity is banded ground glass opacity, which is located on the side of the tumor close to the pleura in different directions. It is common in adenocarcinoma and highly significant in the diagnosis of lung cancer [36]. This sign may be related to the traction of the surrounding lung tissue. In this study, the incidence of beam-shaped opacity was higher in the group D, but it was significantly lower in the group A. This implicates that small nodules do not cause significant changes in surrounding structures.
Halo sign is a nonspecific sign around solid pulmonary nodules, and its border is usually clear in lung cancer lesions [37]. In this study, a well-defined halo sign was mainly located on one side of the nodule, and its incidence was slightly higher in smaller lesions. Therefore, small solid nodules not presenting with other features but well-defined halo sign should be suspected for lung cancer.
Overall, regarding the small pulmonary nodules, follow-up seems to be an effective way to discriminate their nature based on changes in CT features. A recent study has confirmed that quantitative image features (“radiomics”) can also help discriminate benign from malignant pulmonary nodules [38]. Additionally, quantitative radiomic signatures have shown the potential to reveal and predict the tumor growth rate, and they can help identify the indolent from aggressive lung cancer [39]. Thus, radiomics may provide a new way for evaluating and managing indeterminate pulmonary nodules in the future.
This study had several limitations. The evaluation of changing regularity of CT features for SLCNs was performed by comparing grouped nodules with different sizes rather than following only one group of lesions. Thus, results obtained here should be confirmed in clinical practice. Additionally, the pathological types of SLCNs varied but showed no significant differences among different groups. Therefore, present results seem to represent a general, rather than a specific tumor type. It should be noted that some tumor types within smaller samples may not conform to the general morphological development.