Mixed Ground-glass Opacity Research Articles

Ground-glass Opacity Nodules

Ground-glass opacity (GGO) nodules noted at thin-section computed tomography (CT) scan have been shown to have a histopathologic relationship with atypical adenomatous hyperplasia, bronchioloalveolar carcinoma (BAC, or adenocarcinoma in situ), and adenocarcinoma with a predominant BAC component (minimally invasive adenocarcinoma). Patients harboring GGO nodules of BAC or adenocarcinoma with a predominant BAC component demonstrate negative results for malignancy at positron emission tomography. In peripheral adenocarcinoma of a part-solid (mixed GGO and solid attenuation) nodular nature, both the degree of disappearance of GGO area, when the lung window is changed to a mediastinal window image at CT scanning, and the maximum standardized uptake value at positron emission tomography correlate well with histopathologic BAC and non-BAC ratios. However, a high non-BAC ratio appears to be the only independent prognosis-determining factor. Epidermal growth factor receptor mutations are positively correlated with the GGO ratio at a thin-section CT scan in lung adenocarcinomas. As patients with a GGO nodule of BAC or adenocarcinoma with a predominant BAC component have a good prognosis, a wedge resection is recommended as a treatment option, in preference to lobectomy. Even for multiple malignant pure GGO nodules, minimally invasive surgery (including multiple resections) with the preservation of lung volume and adequate imaging follow-up studies are the recommended diagnostic and therapeutic measures.

Volume-Doubling Time of Pulmonary Nodules with Ground Glass Opacity at Multidetector CT: Assessment with Computer-Aided Three-Dimensional Volumetry

To investigate the volume-doubling time (VDT) of histologically proved pulmonary nodules showing ground glass opacity (GGO) at multidetector CT (MDCT) using computer-aided three-dimensional volumetry. We retrospectively evaluated 47 GGO nodules (mixed n = 28, pure n = 19) that had been examined by thin-section helical CT more than once. They were histologically confirmed as atypical adenomatous hyperplasia (AAH, n = 13), bronchioloalveolar carcinoma (BAC, n = 22), and adenocarcinoma (AC, n = 12). Using computer-aided three-dimensional volumetry software, two radiologists independently performed volumetry of GGO nodules and calculated the VDT using data acquired from the initial and final CT study. We compared VDT among the three pathologies and also compared the VDT of mixed and pure GGO nodules. The mean VDT of all GGO nodules was 486.4 ± 368.6 days (range 89.0-1583.0 days). The mean VDT for AAH, BAC, and AC was 859.2 ± 428.9, 421.2 ± 228.4, and 202.1 ± 84.3 days, respectively; there were statistically significant differences for all comparative combinations of AAH, BAC, and AC (Steel-Dwass test, P < .01). The mean VDT for pure and mixed GGO nodules was 628.5 ± 404.2 and 276.9 ± 155.9 days, respectively; it was significantly shorter for mixed than pure GGO nodules (Mann-Whitney U-test, P < .01). The evaluation of VDT using computer-aided volumetry may be helpful in assessing the histological entities of GGO nodules.

Possible Delayed Cut-End Recurrence After Limited Resection for Ground-Glass Opacity Adenocarcinoma, Intraoperatively Diagnosed as Noguchi Type B, in Three Patients

In our limited resection trial of pulmonary peripheral ground-glass opacity (GGO) lesions from 1998 to 2002, limited resection of Noguchi type A and B carcinomas seemed to have a positive outcome. However, recently three of the 24 patients, with mixed GGO lesions intraoperatively diagnosed as type B, developed a solid lesion at the cut-end scar. Medical records and radiology and pathology findings of the three patients were reviewed. We also analyzed epidermal growth factor receptor gene mutations when possible. Radiologically, these three second tumors were clearly cut-end scar area recurrences. However, other pathologic and mutation findings suggest metachronous primary cancers developed in Case 1, cut-end recurrence in Case 2, and needle biopsy implantation in Case 3. It is difficult to definitively conclude whether the second tumors were recurrences or metachronous primaries. These second tumors have convinced us that our initial caution in concluding GGO lesions can be cured by limited resection was very appropriate. The recurrences definitely indicate that continuing follow-up attention for more than 5 years is needed after limited resection even for GGO bronchioloalveolar carcinomas.

Opacités pulmonaires localisées partiellement ou totalement en verre dépoli

Localized ground-glass opacities (GGOs) have been recently individualized and account for between 2.9% and 19% of all pulmonary nodules detected in high-risk patients included in CT screening series for lung cancer. These opacities, nodular, lobular or flat, correspond to benign lesions (localised infectious and inflammatory diseases, focal interstitial fibrosis, and atypical alveolar hyperplasia) or malignant lesions (bronchioloalveolar carcinoma, early-stage adenocarcinoma and sometimes metastases). Localized GGOs are more likely to be malignant than solid nodules and prognosis is related to the percentage of the ground-glass component. However, doubling time of pure localized malignant GGOs is longer than mixed localized malignant GGOs and even longer than the doubling time of solid malignant nodules. Therefore, localized GGOs warrant a dedicated diagnostic workup.

Intraoperative ultrasonographic localization of pulmonary ground-glass opacities

Ground-glass opacities are typically difficult to inspect and to palpate during video-assisted thoracic surgery. We therefore examined whether ultrasonographic assessments could localize ground-glass opacities and help to achieve adequate resection margins. An intraoperative ultrasonographic procedure was prospectively performed on 44 patients harboring ground-glass opacities of less than 20 mm in diameter to localize these lesions and to achieve adequate margins. We also examined whether there were any complications resulting from the intraoperative ultrasonogram, such as lung injury, heart injury, or arrhythmia. We excluded patients with both asthma and chronic obstructive pulmonary disease from this study inasmuch as the intraoperative ultrasonographic procedure is more difficult to interpret when residual air is present in the lung. A total of 53 ground-glass opacities were successfully identified by intraoperative ultrasonography without any complications. Of the 20 mixed ground-glass opacities that we examined, 15 were found on palpation. However, only 4 (12.1%) of the 33 pure ground-glass opacities could be palpated. In all instances in which complete collapse of the lung was achieved (30/53 of these cases), high-quality echo images were obtained. Additionally, a strong correlation was found between the resection margins measured by ultrasonogram and the margins determined by histologic examination in the resected lung specimens (r(2) = 0.954, P < .001). Intraoperative ultrasonography can both safely and effectively localize pulmonary ground-glass opacities in a completely deflated lung. This procedure is also useful for the evaluation of surgical margins in a resected lung. Hence, ultrasonography may assist surgeons to perform minimally invasive lung resections with clear surgical margins during the treatment of solitary lung ground-glass opacity.

Diagnostic Accuracy of CT Fluoroscopy–Guided Needle Aspiration Biopsy of Ground-Glass Opacity Pulmonary Lesions

The purpose of this study was to evaluate the diagnostic performance of CT fluoroscopy-guided percutaneous needle aspiration biopsy of ground-glass opacity (GGO) pulmonary lesions. Twenty-eight patients with GGO lesions who underwent CT fluoroscopy-guided needle aspiration biopsy were enrolled in this study. GGO lesions were divided into three groups according to their size: group 1, lesions < or = 10 mm (n = 10); group 2, lesions 11-20 mm (n = 10); and group 3, lesions > 20 mm (n = 8). Sensitivity, specificity, and diagnostic accuracy were calculated on the basis of 28 needle aspiration biopsy results and were compared among the three groups using Fisher's exact test. Diagnostic accuracy was also compared according to length of needle path (< 5 cm vs 5-9 cm vs > 9 cm) and GGO component (50-90% vs > 90%). Each case was reviewed for complications, which included pneumothorax, thoracostomy tube insertion, and hemoptysis. There were 17 (61%) malignant and 11 (39%) benign lesions. Three (10%) biopsy results were nondiagnostic, all of which were confirmed as benign. The sensitivity, specificity, and accuracy of CT fluoroscopy-guided needle aspiration biopsy for diagnosing GGO were 67%, 100%, and 80% in group 1; 71%, 100%, and 80% in group 2; and 75%, 100%, and 88% in group 3. The diagnostic accuracy of CT fluoroscopy-guided needle aspiration biopsy for diagnosing GGO was not significantly different among the three groups (p > 0.05). The diagnostic accuracy was not significantly different according to the length of the needle path (p > 0.05). However, diagnostic accuracy was significantly more accurate in mixed GGO lesions than in pure GGO lesions (p = 0.046). Five patients (18%) developed a pneumothorax, two of whom (7%) required placement of a thoracostomy tube. Mild hemoptysis occurred in three patients (11%). CT fluoroscopy-guided needle aspiration biopsy is a useful diagnostic technique for GGO pulmonary lesions and has an acceptable complication rate, even for small and deeply located lesions. The diagnostic accuracy is influenced by the GGO component.

Computer-aided diagnosis of lung cancer: definition and detection of ground-glass opacity type of nodules by high-resolution computed tomography

The ground-glass opacity (GGO) of lung cancer is identified only subjectively on computed tomography (CT) images as no quantitative characteristic has been defined for GGOs. We sought to define GGOs quantitatively and to differentiate between GGOs and solid-type lung cancers semiautomatically with a computer-aided diagnosis (CAD). High-resolution CT images of 100 pulmonary nodules (all peripheral lung cancers) were collected from our clinical records. Two radiologists traced the contours of nodules and distinguished GGOs from solid areas. The CT attenuation value of each area was measured. Differentiation between cancer types was assessed by a receiver-operating characteristic (ROC) analysis. The mean CT attenuation of the GGO areas was -618.4 +/- 212.2 HU, whereas that of solid areas was -68.1 +/- 230.3 HU. CAD differentiated between solidand GGO-type lung cancers with a sensitivity of 86.0% and specificity of 96.5% when the threshold value was -370 HU. Four nodules of mixed GGOs were incorrectly classified as the solid type. CAD detected 96.3% of GGO areas when the threshold between GGO and solid areas was 194 HU. Objective definition of GGO area by CT attenuation is feasible. This method is useful for semiautomatic differentiation between GGOs and solid types of lung cancer.

Evaluation of lesions corresponding to ground-glass opacities that were resected after computed tomography follow-up examination

Background Ground-glass opacity (GGO), which is closely related with bronchioloalveolar carcinoma (BAC), is being detected more frequently. BAC is considered to be a relatively less aggressive tumor, and immediate resection at the time of detection might not be necessary. Therefore, when GGO is detected, a CT follow-up examination is often performed. If growth is detected during the follow-up CT examination, resection is usually considered. However, the possible treatment delay caused by the scheduling of a CT follow-up examination is an issue that must be clarified. Since the cancer might progress during the follow-up period, such follow-up periods might have a negative influence on the patient's prognosis. This study attempted to clarify whether CT follow-up causes treatment delay. Methods A total of 113 lung cancer patients with pure or mixed GGO findings who underwent a resection after a CT follow-up examination between 1999 and 2005 were retrospectively examined. The CT findings at the initial detection, the changes in the CT findings during the CT follow-up period, the histology, the pathological stage and the outcomes after resection were reviewed and evaluated. Results The CT finding at the time of the initial detection showed pure GGO in 63 patients and mixed GGO in 50 patients. Histology revealed that adenocarcinoma was found in all 113 patients; squamous cell carcinoma was not found in any of the patients. One-hundred twelve patients were diagnosed as having Stage IA, and a singe patient with visceral pleura invasion was diagnosed as having Stage IB. Complete resections were performed in all the patients. The median postoperative follow-up period was 45.0 months. No recurrences or deaths were observed during the study period. Conclusions No treatment delays or negative influences on patient outcome resulted from the CT follow-up period. A future prospective study should be conducted to establish the optimal CT follow-up program.

Focal interstitial fibrosis manifesting as nodular ground-glass opacity: thin-section CT findings

The purpose of this study was to describe the thin-section computed tomographic (CT) features of focal interstitial fibrosis manifesting as nodular ground-glass opacity (GGO) and its changes during follow-up. The thin-section CT findings of pathologically proven focal interstitial fibrosis manifesting as nodular GGO were retrospectively evaluated in nine patients (five women and four men; mean age, 59.3 years; age range, 34-81 years). The thin-section CT findings of each lesion were analyzed for multiplicity, location, shape, margin characteristics, pleural retraction or vascular convergence, size and internal attenuation, lesion internal features and lesion changes on follow-up CT scans (mean 90 days, range 5 to 215 days). All lesions manifested as a solitary nodular GGO (100%), and seven of the nine lesions (77.8%) were located in the upper lobe. Focal interstitial fibrosis was round or oval in shape in five cases (55.6%), complex in shape in three cases (33.3%) and polygonal in one case (11.1%). Lesion margins were smooth in five patients (55.6%), irregular in three (33.3%) and spiculated in one (11.1%). Pleural retraction or vascular convergence was present in two patients (22.2%). Lesions measured 4.8 mm to 25.5 mm (mean, 11.5 mm) and had attenuations ranging from -151 to -699 HU (mean, -514.7 HU). Eight (88.9%) manifested as pure nodular GGOs and one as mixed GGO with a spiculated margin. In all patients, no lesion changes were observed in follow-up CT scans. Focal interstitial fibrosis manifesting as nodular GGO usually presents as a solitary nodule with pure GGO on thin-section CT, which does not change significantly during follow-up.

Nodular Ground-Glass Opacities on Thin-section CT: Size Change during Follow-up and Pathological Results

ObjectiveTo evaluate the inter-group differences in growth and the pathological results of nodular ground-glass opacities (GGOs) according to their size and focal solid portions.Materials and MethodsNinety-six nodular GGOs in 55 individuals followed by CT for at least one month from an initial chest CT were included. Forty nodular GGOs in 30 individuals were pathologically confirmed to be: adenocarcinoma (n = 15), bronchioloalveolar carcinoma (BAC) (n = 11), atypical adenomatous hyperplasia (AAH) (n = 8), focal interstitial fibrosis (n = 5) and aspergillosis (n = 1). Lesions were categorized based on high-resolution CT findings: pure nodular GGO (PNGGO) ≤ 10 mm, PNGGO > 10 mm, mixed nodular GGO (MNGGO)≤ 10 mm, and MNGGO > 10 mm. In each group, the change in size during the follow-up period, the pathological results and the rate of malignancy were evaluated.ResultsThree MNGGO lesions, and none of the PNGGO, grew during the follow-up period. Resected PNGGOs ≤ 10 mm were AAH (n = 6), BAC (n = 5), and focal interstitial fibrosis (n = 1). Resected PNGGOs > 10 mm were focal interstitial fibrosis (n = 4), AAH (n = 2), BAC (n = 2), and adenocarcinoma (n = 2). Resected MNGGOs ≤ 10 mm were adenocarcinoma (n = 2), and BAC (n = 1). Resected MNGGOs > 10 mm were adenocarcinoma (n = 11), BAC (n = 3), and aspergillosis (n = 1).ConclusionMixed nodular GGOs (MNGGOs) had the potential for growth; most were pathologically adenocarcinoma or BAC. By contrast, PNGGOs were stable for several months to years; most were AAH, BAC, or focal interstitial fibrosis.

Pathologic and Biological Assessment of Lung Tumors Showing Ground-Glass Opacity

We evaluated the pathologic and biological aspects of lung tumors 3.0 cm or less in diameter with the appearance of ground-glass opacity (GGO). Of 988 patients with non-small cell lung cancer who underwent operations at our institute between January 1994 and December 2004, 87 resected lung tumor specimens that showed GGO appearance on helical computed tomography were obtained from 81 patients. Forty-four lesions were pure GGO with no solid component in the tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a solid component. Together with histological features, MIB1 and nm23 expression within tumors were examined immunohistochemically. The mean tumor size in the pure GGO group was significantly smaller than that in the mixed GGO group. The composition of pathologic subtypes and biological characteristics were clearly different between the two groups. Although atypical adenomatous hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B were the predominant pathologic subtypes and nm23 negativity was rare in the pure GGO group, a high score for expression of MIB1 was often found in pure GGO tumors even though the tumors were less than 10 mm in diameter. If the tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems to be low in pure GGO tumors. However, the proliferation ability of these tumors suggests the necessity of a careful follow-up schedule if the tumor is greater than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of observation is justified.

Pneumoconiosis: Comparison of Imaging and Pathologic Findings

Pneumoconiosis may be classified as either fibrotic or nonfibrotic, according to the presence or absence of fibrosis. Silicosis, coal worker pneumoconiosis, asbestosis, berylliosis, and talcosis are examples of fibrotic pneumoconiosis. Siderosis, stannosis, and baritosis are nonfibrotic forms of pneumoconiosis that result from inhalation of iron oxide, tin oxide, and barium sulfate particles, respectively. In an individual who has a history of exposure to silica or coal dust, a finding of nodular or reticulonodular lesions at chest radiography or small nodules with a perilymphatic distribution at thin-section computed tomography (CT), with or without eggshell calcifications, is suggestive of silicosis or coal worker pneumoconiosis. Magnetic resonance imaging is helpful for distinguishing between progressive massive fibrosis and lung cancer. CT and histopathologic findings in asbestosis are similar to those in idiopathic pulmonary fibrosis, but the presence of asbestos bodies in histopathologic specimens is specific for the diagnosis of asbestosis. Giant cell interstitial pneumonia due to exposure to hard metals is classified as a fibrotic form of pneumoconiosis and appears on CT images as mixed ground-glass opacities and reticulation. Berylliosis simulates pulmonary sarcoidosis on CT images. CT findings in talcosis include small centrilobular and subpleural nodules or heterogeneous conglomerate masses that contain foci of high attenuation indicating talc deposition. Siderosis is nonfibrotic and is indicated by a CT finding of poorly defined centrilobular nodules or ground-glass opacities.

Radiologists' Performance for Differentiating Benign from Malignant Lung Nodules on High-Resolution CT Using Computer-Estimated Likelihood of Malignancy

The purpose of our study was to evaluate whether a computer-aided diagnosis (CAD) scheme can assist radiologists in distinguishing small benign from malignant lung nodules on high-resolution CT (HRCT). We developed an automated computerized scheme for determining the likelihood of malignancy of lung nodules on multiple HRCT slices; the likelihood estimate was obtained from various objective features of the nodules using linear discriminant analysis. The data set used in this observer study consisted of 28 primary lung cancers (6-20 mm) and 28 benign nodules. Cancer cases included nodules with pure ground-glass opacity, mixed ground-glass opacity, and solid opacity. Benign nodules were selected by matching their size and pattern to the malignant nodules. Consecutive region-of-interest images for each nodule on HRCT were displayed for interpretation in stacked mode on a cathode ray tube monitor. The images were presented to 16 radiologists-first without and then with the computer output-who were asked to indicate their confidence level regarding the malignancy of a nodule. Performance was evaluated by receiver operating characteristic (ROC) analysis. The area under the ROC curve (Az value) of the CAD scheme alone was 0.831 for distinguishing benign from malignant nodules. The average Az value for radiologists was improved with the aid of the CAD scheme from 0.785 to 0.853 by a statistically significant level (p = 0.016). The radiologists' diagnostic performance with the CAD scheme was more accurate than that of the CAD scheme alone (p < 0.05) and also that of radiologists alone. CAD has the potential to improve radiologists' diagnostic accuracy in distinguishing small benign nodules from malignant ones on HRCT.

Usefulness of computerized scheme for differentiating benign from malignant lung nodules on high-resolution CT

A computer-aided diagnosis (CAD) scheme for determination of the likelihood of malignancy of 244 nodules on high-resolution CT (HRCT) was developed. The performance ( A z) for 16 radiologists was improved from 0.785 to 0.853 ( P=0.02) with the aid of the CAD scheme by use of 56 nodules, including 28 cancerous and 28 benign nodules which were matched in size and pattern to the cancers. Our purpose in this study was to investigate further whether a CAD scheme can assist radiologists in distinguishing benign from malignant nodules in different groups. The results indicated that A z values for radiologists without and with the CAD scheme were improved from 0.770 to 0.855 for general radiologists ( P=0.01) and from 0.805 to 0.850 for chest radiologists ( P=0.12); from 0.717 to 0.821 for nodules at 6–10 mm ( P=0.04) and from 0.837 to 0.901 for nodules at 11–20 mm ( P=0.04); and from 0.812 to 0.892 for nodules with pure ground-glass opacity (GGO) ( P=0.149), from 0.819 to 0.863 for nodules with mixed GGO ( P=0.196), and from 0.784 to 0.844 for solid nodules ( P=0.334). CAD has the potential to improve the diagnostic accuracy in distinguishing benign nodules from malignant ones in different groups on HRCT.

Low-dose computed tomography screening for lung cancer in a general population: characteristics of cancer in non-smokers versus smokers 1

Rationale and Objectives. To report the detection rate for lung cancers in computed tomography (CT) screening in Japanese adults, and to analyze differences in the appearance of the cancers in non-smokers versus smokers. Materials and Methods. Subjects consisted of 7,847 Japanese adults who received low-dose CT screening at least once in a 3-year period. The detection rate of lung cancers and the correlation of imaging, clinical, and pathologic findings of cancers in non-smokers versus smokers were examined. Results. The detection rate for lung cancer was 1.1% for both non-smokers (45 of 4,251) and smokers (39 of 3,596). The prevalence of well-differentiated adenocarcinomas was greater in non-smokers (88%; 22 of 25) than in smokers (29%; 4 of 14) ( P < .001). The prevalence and incidence of pathologic stage IA disease were greater in non-smokers than in smokers (92%; [22 of 24] vs 58% [7 of 12], and 100% [19 of 19] vs 70% [14 of 20]) (both P < .05). The mean size of the tumors in the non-smokers (12.4 mm) was smaller than that in smokers (18.2 mm) ( P < .001). The percentage of cancers categorized as pure or mixed ground-glass opacity (86%; 38 of 44) on CT was greater in non-smokers than in smokers (46%; 16 of 35) ( P < .001). Conclusion. Most of the lung cancers in non-smokers were slow-growing adenocarcinomas appearing as faint ground-glass opacities on CT, whereas rapidly growing cancers appearing as solid nodules were more commonly seen in smokers.

Prospective study of thoracoscopic limited resection for ground-glass opacity selected by computed tomography

Background With recent advances in low-dose helical computed tomography (CT), detection of ground-glass opacity (GGO) has increased. The aim of this study was to correlate high-resolution CT (HRCT) findings with pathologic features and to evaluate the efficacy of thoracoscopic limited resection for focal GGO, which were selected based on HRCT findings. Methods Focal GGO lesions were classified into two subtypes based on HRCT findings: pure type and mixed type. Ninety-six patients with persistent GGO 2 cm or less in diameter underwent pulmonary resection from January 1997 to December 2001. Among these, thoracoscopic wedge resection was performed prospectively between June 2000 and December 2001 in 33 patients with pure GGO lesions that were 1 cm or less. Results Thoracoscopic wedge resection was completed with complete safety. The histologic diagnoses of these 33 lesions were adenocarcinoma in 1, bronchioloalveolar carcinoma (BAC) in 23, and atypical adenomatous hyperplasia (AAH) in 9. No patients have had any evidence of tumor recurrence to date. Of the total 96 GGO lesions, 93.0% (53/57) of pure GGO 1 cm or less were BAC or AAH, whereas 38.5% (15/39) of pure GGO larger than 1 cm or mixed GGO were adenocarcinoma. Conclusions Pure GGO 1 cm or less was characteristic of noninvasive lesions. Thoracoscopic limited resection for small GGO lesions selected by HRCT was valid.