One-dimensional mean computed tomography value evaluation of ground-glass opacity on high-resolution images

GGO is defined as a shadow completely occupied by a hazy increased attenuation of the lung, with reservation of the bronchial and vascular margins in the lesion on HRCT. Although GGO is a nonspecific finding that may be caused by various disorders, including inflammatory disease, fibrosis, and neoplastic disease [6], the pathologic diagnoses of GGO in this study, adenocarcinoma in 47 patients (90 %) and AAH in 4 patients (8 %), were shown to be neoplastic lesions, and all patients with adenocarcinoma had T1N0M0 disease. These results suggest that persistent focal GGO is a significant sign of early-stage adenocarcinoma.

Many radiologic studies of small lung adenocarcinomas have demonstrated a strong correlation between CT findings and pathologic features. Several authors have classified small lung lesions into nonsolid (pure) GGO type, partly solid (mixed) GGO type, and solid type, and have suggested that pure type and mixed type with small solid components are almost always non-invasive carcinomas [7‐10]. However, it is sometimes difficult to differentiate between pure and mixed GGO, and between high-density GGO and solid tumor. Suzuki et al. [11] classified homogeneous (so-called “pure”) GGO into pure GGO and semiconsolidation to evaluate the differences in density within the tumor, and stated that pathologically, semiconsolidation tends to be adenocarcinoma with invasive foci. Although the differentiation between pure GGO and semiconsolidation is unclear in their report, density within homogeneous GGO appears to be an important factor for predicting tumor invasiveness.

Some authors have used quantitative densitometric methodologies to evaluate GGO lesions [12‐15]. Ikeda et al. reported that the 75th percentile CT value analyzed by three-dimensional computerized quantification of GGO lesions was the optimal CT value for differentiating between AAH, BAC and adenocarcinoma. These investigators noted that CT cutoff value of −584 HU was optimal for differentiation between AAH and BAC, and −472 HU was optimal for differentiation between BAC and adenocarcinoma [13]. Nomori et al. used histograms of CT pixel numbers for AAH and nonmucinous adenocarcinoma to quantify peaks and mean numbers of CT pixels, and found the mean value of mean CT values to be −697 ± 56 HU for AAH lesions and −541 ± 73 for BAC lesions. These investigators noted that the peak CT value on the histogram is the most frequent value observed in the tumor, and that the effect of vessels and bronchi within the tumor can be ignored [14]. Although the one-dimensional quantitative m-CT value can be slightly affected by the densities of vessels or bronchi within the tumor, this calculation method is straightforward, and can similarly estimate pure GGO and mixed GGO. The present study demonstrates that an m-CT value of −600 HU may represent a cutoff value demarcating AAH versus invasive lesions. We believe that this finding could significantly impact the selection of therapeutic strategies for GGO lesions.

Kushihashi et al. [16] reported CT findings of AAH as bronchioloalveolar adenoma in 1994. Although AAH is usually discovered incidentally during microscopic examination of surgically resected lung specimens, a recent increase in the detection of AAH as pure GGO has occurred. Pathologically, AAH was classified as a premalignant lesion in the 1999 World Health Organization classification. Thus, while the clinical and pathological features of AAH have become clearer, therapeutic strategy for AAH lesions have not. AAH is considered to be a precursor of BAC or adenocarcinoma [17‐19]; however, no reports of progression of AAH to BAC or adenocarcinoma have been published. We believe that at time, pure GGO lesions that are suspected to be AAH based on m-CT values are now possible to follow-up.

Whether GGO lesions that are suspected to be BAC should be resected or followed up also remains controversial. Recently, several researchers reported that for noninvasive lesions identified on HRCT, careful observation without surgical intervention represents a valid treatment options [20‐22]. According to the interim guidelines suggested by Godoy and Nadich [23], isolated lesions with pure GGO that are ≤5 mm do not necessarily require CT follow-up, since they almost always represent foci of AAH, but for lesions between 5 and 10 mm, follow-up is requisite pending better definition of their true nature; lesions >1 cm should be assumed to be BAC or invasive adenocarcinoma, but surgery should be considered particularly if the nodule is growing or if an increase in attenuation or development of a solid component is observed.

Diligent long-term follow-up is the natural history of pure GGO, and should be conducted to determine whether surgical intervention is acceptable or unnecessary [24]. However, we believe that early detection and early therapy of some primary lung cancers with GGO is important for improving individual prognoses for the following reasons. First, pure GGO lesions are not all histologically pre-invasive lesions, as some have an invasive adenocarcinoma component, such as Noguchi’s Type C. Second, some researchers have reported the concept of a multi-step progression from AAH through localized BAC (type A and B) to advanced adenocarcinoma with a replacement growth pattern (Type C) [17‐19]. Third, patients with Noguchi’s type C lesions have a worse 5-year survival rate (75 %) than patients with type A or B lesions (100 %).

GGO lesions with a maximum diameter >1 cm and m-CT value >−600 HU are absolute indication of operation, because those lesions were highly diagnosed as invasive lesions. GGO lesions with a maximum diameter ≤1 cm and m-CT ≤−600 HU should be observed, because all seven lesions were preinvasive lesions. Although, GGO lesions with a maximum diameter >1 cm or m-CT value >−600 HU are possible to be observed, we think these lesions should be resected because it is more important to avoid observation for invasive lesions than resection for preinvasive lesions.

It is noteworthy that pure GGO are not all preinvasive lesions, and specificity of pure GGO correlated between invasiveness and maximum diameter and m-CT value is significantly higher than that of mixed GGO. Evaluation of m-CT value is useful for determining “follow up or resection” for GGO, especially pure type.

The usefulness of m-CT value for benign GGO including inflammatory disease, fibrosis, and so on is unclear, because 98 % of removed GGO in this study is malignant neoplasm including AAH.

We think persistent GGO is almost all neoplasms, so differentiating benign and malignant is more important solid lesions than GGO lesions.