Part-solid Ground-glass Nodules Research Articles

Morphological Predictors of Primary Lung Cancer among Part-Solid Ground-Grass Nodules on High-Resolution CT.

Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.

Long-term follow-up of persistent pulmonary subsolid nodules: Natural course of pure, heterogeneous, and real part-solid ground-glass nodules.

Previous studies have suggested the applicability of three classifications of subsolid nodules (SSNs). However, few studies have unraveled the natural history of the three types of SSNs. A retrospective study from two medical centers between November 2007 and November 2017 was conducted to explore the long-term follow-up results of three different types of SSNs, which were divided into pure ground-glass nodules (pGGNs), heterogeneous ground-glass nodules (hGGNs), and real part-solid nodules (rPSNs). A total of 306 consecutive patients, including 361 SSNs with long-term follow-up, were reviewed. The median growth times of pGGNs, hGGNs, and rPSNs were 7.7, 6.0, and 2.0 years, respectively. For pGGNs, the median period of development into rPSNs was 4.6 years, while that of hGGNs was 1.8 years, and the time from pGGNs to hGGNs was 3.1 years (p < 0.05). In SSNs with an initial lung window consolidation tumor ratio (LW-CTR) >0.5 and mediastinum window (MW)-CTR >0.2, all cases with growth were identified within 5 years. Meanwhile, in SSNs whose LW-CTR and MW-CTR were 0, it took over 5 years to detect nodular growth. Pathologically, 90.6% of initial SSNs with LW-CTR >0 were invasive carcinomas (invasive adenocarcinoma and micro-invasive adenocarcinoma). Among patients with rPSNs in the initial state, 100.0% of the final pathological results were invasive carcinoma. Cox regression showed that age (p=0.038), initial maximal diameter (p < 0.001), and LW-CTR (p=0.002) were independent risk factors for SSN growth. pGGNs, hGGNs, and rPSNs have significantly different natural histories. Age, initial nodule diameter, and LW-CTR are important risk factors for SSN growth.

Stepwise evolutionary genomics of early-stage lung adenocarcinoma manifesting as pure, heterogeneous and part-solid ground-glass nodules.

This study was designed to unravel the genomic landscape and evolution of early-stage subsolid lung adenocarcinomas (SSN-LUADs) manifesting as pure ground-glass nodules (pGGNs), heterogeneous ground-glass nodules (HGGNs) and part-solid nodules (PSNs). Samples subjected to either broad-panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were included. Clinicopathologic and genomic features were compared among pGGN, HGGN and PSN, while tumour evolutionary trajectories and mutational signatures were evaluated in the entire cohort. In total, 247 SSN-LUAD samples subjected to broad-panel NGS and 125 to WES were identified. Compared with PSNs, HGGNs had significantly lower tumour mutation count (P < 0.001), genomic alteration count (P < 0.001), and intra-tumour heterogeneity (P = 0.005). Statistically significant upward trends were observed in alterations involving driver mutations and oncogenic pathways from pGGNs to HGGNs to PSNs. EGFR mutation was proved to be a key early event in the progression of SSN-LUADs, with subsequently two evolutionary trajectories involving either RBM10 or TP53 mutation in the cancer-evolution models. This study provided evidence for unravelling the previously unknown genomic underpinnings associated with SSN-LUAD evolution from pGGN to HGGN to PSN, proving that HGGN was an intermediate SSN form between pGGN and PSN genetically.

Management of Ground-Glass Nodules: When and How to Operate?

Simple SummaryAn increasing number of lung cancer screening programs have detected the frequent occurrence of small pulmonary ground-glass nodules (GGNs). If GGN is an incidental finding, it should be followed according to the guidelines. A multidisciplinary team discussion should be initiated if a new solid component develops or the solid portion grows on follow-up CT. Preoperative attempts to biopsy solid components in part-solid GGNs are often not feasible and not helpful. If malignancy is suspected, a surgical biopsy with the guidance of various localization methods is recommended. Once the GGN is confirmed to be malignant, sub-lobar resection may be reasonable in the majority of cases, and the extent of lung resection should be determined based on the CT finding or intraoperative frozen section examination using special inflation technique. Although rare, the recurrence in the remaining lobe can occur especially in patients with high risk histologic features, which currently cannot accurately diagnosed either pre- or intra-operatively.With the increased popularity of low-dose computed tomography (LDCT), many patients present with pulmonary ground-glass nodules (GGNs), and the appropriate diagnostic and management strategy of those lesions make physicians be on the horn of the clinical dilemma. As there is not enough data available to set universally acceptable guidelines, the management of GGNs may be different. If GGN is an incidental finding through LDCT, the lesion should be followed according to the current guidelines. We recommend a multidisciplinary team discussion to be initiated if a new solid component develops or the solid portion size grows on follow-up CT as the risk of malignancy is high. Attempts to preoperatively biopsy solid components in part-solid GGNs are often not feasible and not helpful in clinical settings. Currently, if malignancy is suspected, a surgical biopsy with the guidance of various localization methods is recommended. If malignancy is confirmed, sub-lobar resection may provide an excellent oncologic outcome.

Thoracoscopic segmentectomy and lobectomy assisted by three-dimensional computed-tomography bronchography and angiography for the treatment of primary lung cancer.

BACKGROUNDAnatomical segmentectomy has been proposed as a substitution for lobectomy for early-stage lung cancer. However, it requires technical meticulousness due to the complex anatomical variations of segmental vessels and bronchi.AIMTo assess the safety and feasibility of three-dimensional computed-tomography bronchography and angiography (3D-CTBA) in performing video-assisted thoracoscopic surgery (VATS) for lung cancers.METHODSIn this study, we enrolled 123 patients who consented to undergo thoracoscopic segmentectomy and lobectomy assisted by 3D-CTBA between May 2017 and June 2019. The image data of enhanced computed tomography (CT) scans was reconstructed three-dimensionally by the Mimics software. The results of preoperative 3D-CTBA, in combination with intraoperative navigation, guided the surgery.RESULTSA total of 59 women and 64 men were enrolled, of whom 57 (46.3%) underwent segmentectomy and 66 (53.7%) underwent lobectomy. The majority of tumor appearance on CT was part-solid ground-glass nodule (pGGN; 55.3%). The mean duration of chest tube placement was 3.5 ± 1.6 d, and the average length of postoperative hospital stay was 6.8 ± 1.8 d. Surgical complications included one case of pneumonia and four cases of prolonged air leak lasting > 5 d. Notably, there was no intraoperative massive hemorrhage, postoperative intensive-care unit stay, or 30-d mortality. Preoperative 3D-CTBA images can display clearly and vividly the targeted structure and the variations of vessels and bronchi. To reduce the risk of locoregional recurrence, the application of 3D-CTBA with a virtual 3D surgical margin help the VATS surgeon determine accurate distances and positional relations among the tumor, bronchial trees, and the intersegmental vessels. Three-dimensional navigation was performed to confirm the segmental structure, precisely cut off the targeted segment, and avoid intersegmental veins injury.CONCLUSIONVATS and 3D-CTBA worked in harmony in our study. This combination also provided a new pattern of transition from lesion-directed location of tumors to computer-aided surgery for the management of early lung cancer.

Percutaneous Electromagnetic Transthoracic Nodule Localization for Ground Glass Nodules.

BackgroundA recent increase in the incidental detection of ground glass nodules (GGNs) has created a need for improved diagnostic accuracy in screening for malignancies. However, surgical diagnosis remains challenging, especially via video-assisted thoracoscopic surgery (VATS). Herein, we present the efficacy of a novel electrical navigation system for perioperative percutaneous transthoracic nodule localization.MethodsEighteen patients with GGNs who underwent electromagnetic navigated percutaneous transthoracic needle localization (ETTNL), followed by 1-stage diagnostic wedge resections via VATS between January and December 2020, were included in the analysis. Data on patient characteristics, nodules, procedures, and pathological diagnoses were collected and retrospectively reviewed.ResultsOf the 18 nodules, 17 were successfully localized. Nine nodules were pure GGNs, and the remaining 9 were part-solid GGNs. The median nodule size was 9.0 mm (range, 4.0–20.0 mm); and the median depth from the visceral pleura was 5.2 mm (range, 0.0–14.4 mm). The median procedure time was 10 minutes (range, 7–20 minutes). The final pathologic results showed benign lesions in 3 cases and malignant lesions in 15 cases.ConclusionPerioperative ETTNL appears to be an effective method for the localization of GGNs, providing guidance for a 1-stage VATS procedure.

T1 invasive lung adenocarcinoma: Thin-section CT solid score and histological periostin expression predict tumor recurrence.

Adenocarcinoma is the most common histological type of non-small cell lung cancer (NSCLC), and various biomarkers for predicting its prognosis after surgical resection have been suggested, particularly in early-stage lung adenocarcinoma. Periostin (also referred to as POSTN, PN or osteoblast-specific factor) is an extracellular matrix protein, the expression of which is associated with tumor invasiveness in patients with NSCLC. In the present study, the novel approach, in which the thin-section CT findings prior to surgical resection and periostin expression of resected specimens were analyzed in combination, was undertaken to assess whether the findings could be a biomarker for predicting the outcomes following resection of T1 invasive lung adenocarcinoma. A total of 73 patients who underwent surgical resection between January 2000 and December 2009 were enrolled. A total of seven parameters were assessed in the thin-section CT scans: i) Contour; ii) part-solid ground-glass nodule or solid nodule; iii) percentage of solid component (the CT solid score); iv) presence of air-bronchogram and/or bubble-like lucencies; v) number of involved vessels; vi) shape linear strands between the nodule and the visceral pleura; and vii) number of linear strands between the nodule and the visceral pleura. Two chest radiologists independently assessed the parameters. Periostin expression was evaluated on the basis of the strength and extent of staining. Univariate and multivariate analyses were subsequently performed using the Cox proportional hazards model. There was a substantial to almost perfect agreement between the two observers with regard to classification of the seven thin-section CT parameters (κ=0.64-0.85). In the univariate analysis, a CT solid score >80%, pathological lymphatic invasion, tumor and lymph node status and high periostin expression were significantly associated with recurrence (all P<0.05). Multivariate analysis demonstrated that a CT solid score >80% and high periostin expression were risk factors for recurrence (P=0.002 and P=0.011, respectively). The cumulative recurrence rates among the three groups (both negative, CT solid score >80% or high periostin expression, or both positive) were significantly different (log-rank test, P<0.001). Although the solid component is already known to be a major predictor of outcome in lung adenocarcinomas according to previous studies, the combined analysis of CT solid score and periostin expression might predict the likelihood of tumor recurrence more precisely.

Differentiation of adenocarcinoma in situ with alveolar collapse from minimally invasive adenocarcinoma or invasive adenocarcinoma appearing as part-solid ground-glass nodules (≤ 2cm) using computed tomography.

To investigate the differentiating computed tomographic (CT) features between adenocarcinoma in situ (AIS) with alveolar collapse and minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IA) appearing as part-solid nodules. A total of 147 consecutive patients with 157 pathology-confirmed part-solid ground-glass nodules (GGNs) ≤ 20mm without other pathological condition such as inflammation and fibrosis who underwent chest CT were included. The 157 part-solid GGNs included 33 (21.02%) pathologically confirmed AISs with alveolar collapse. Multivariate analysis revealed that smaller lesion size (odds ratio [OR] 0.671), and well-defined border (OR 5.544), concentrated distribution (OR 7.994), and homogeneity of the solid portion (OR 4.365) were significant independent predictors for differentiating AIS with alveolar collapse from MIA (P < 0.05) with excellent accuracy (area under receiver operating characteristic [ROC] curve, 0.902). Multivariate analysis revealed that smaller lesion size (OR 0.782), and size (OR 0.821), well-defined border (OR 5.752), and homogeneity of solid portion (OR 6.182) were significant independent predictors differentiating AIS with alveolar collapse from IA (P < 0.05) with excellent accuracy (area under ROC curve 0.910). Among part-solid GGNs, AIS with alveolar collapse can be accurately differentiated from MIA on the basis of smaller lesion size, well-defined border, concentrated distribution, and homogeneity of solid portion, and from IA according to smaller lesion size, and smaller size, well-defined border, and homogeneity of solid portion.

The Impact of Extended Delayed Surgery for Indolent Lung Cancer or Part-Solid Ground Glass Nodules

BackgroundDuring the COVID-19 pandemic, patients with lung cancer may experience treatment delays. The objective of this study was to evaluate the impact of extended treatment delays on survival among patients with stage I typical bronchopulmonary carcinoid (BC), lepidic predominant adenocarcinoma (LPA) or invasive adenocarcinoma with a lepidic component (ADL). MethodsUsing National Cancer Database data (2004-2015), multivariable Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage I BC, LPA, and ADL. Propensity score–matched analyses compared the overall survival of patients who received “early” vs “delayed” surgery (ie, 0-30 vs 90-120 days after diagnosis) across the different histologic subtypes. ResultsDuring the study period, patients with stage I BC (n = 4947), LPA (n = 5340), and ADL (n = 6816) underwent surgery. Cox regression analysis of these cohorts showed a gradual steady increase in the hazard ratio the longer treatment is delayed. However, in propensity score–matched analyses that created cohorts of patients who underwent early and delayed surgery that were well-balanced in patient characteristics, no significant differences in 5-year survival were found between early and delayed surgery for stage I BC (87% [95% CI:77%-93%] vs 89% [95% CI: 80%-94%]), stage I LPA (73% [95% CI: 64%-80%] vs 77% [95% CI: 68%-83%]), and stage I ADL (71% [95% CI: 64%-76%] vs 69% [95% CI: 60%-76%]). ConclusionsDuring the COVID-19 pandemic, for early-stage indolent lung tumors and part-solid ground glass lung nodules, a delay of surgery by 3-4 months after diagnosis can be considered.

Natural Progression of Ground-glass Nodules after Curative Resection for Non-small Cell Lung Cancer.

BackgroundThis retrospective study investigated the natural course of synchronous ground-glass nodules (GGNs) that remained after curative resection for non-small-cell lung cancer (NSCLC).MethodsProspectively collected retrospective data were reviewed concerning 2,276 patients who underwent curative resection for NSCLC between 2008 and 2017. High-resolution computed tomography or thin-section computed tomography data of 82 patients were included in the study. Growth in size was considered the most valuable outcome, and patients were grouped according to GGN size change. Patient demographic data (e.g., age, sex, and smoking history), perioperative data (e.g., GGN characteristics, histopathology and pathological stage of the resected tumours), and other medical history were evaluated in a risk factor analysis concerning GGN size change.ResultsThe median duration of follow-up was 36.0 months (interquartile range, 23.0–59.3 months). GGN size decreased in 6 patients (7.3%), was stationary in 43 patients (52.4%), and increased in 33 patients (40.2%). In univariate analysis, male sex, the GGN size on initial CT, part-solid GGN and smoking history (≥ 10 pack-years) were significant risk factors. Among them, multivariate analysis revealed that lager GGN size, part-solid GGN and smoking history were independent risk factors.ConclusionDuring follow-up, 40.2% of GGNs increased in size, emphasising that patients with larger GGNs, part-solid GGN or with a smoking history should be observed.

Cause determination of missed lung nodules and impact of reader training and education: Simulation study with nodule insertion software.

There are "blind spots" on chest computed tomography (CT) where pulmonary nodules can easily be overlooked. The number of missed pulmonary nodules can be minimized by instituting a training program with particular focus on the depiction of nodules at blind spots. The purpose of this study was to assess the variation in lung nodule detection in chest CT based on location, attenuation characteristics, and reader experience. We selected 18 noncalcified lung nodules (6-8 mm) suspicious of primary and metastatic lung cancer with solid (n = 7), pure ground-glass (6), and part-solid ground-glass (5) attenuation from 12 chest CT scans. These nodules were randomly inserted in chest CT of 34 patients in lung hila, 1st costochondral junction, branching vessels, paramediastinal lungs, lung apices, juxta-diaphragm, and middle and outer thirds of the lungs. Two residents and two chest imaging clinical fellows evaluated the CT images twice, over a 4-month interval. Before the second reading session, the readers were trained and made aware of the potential blind spots. Chi-square test was used to assess statistical significance. Pretraining session: Fellows detected significantly more part-solid ground-glass nodules compared to residents (P = 0.008). A substantial number of nodules adjacent to branching vessels and posterior mediastinum were missed. Posttraining session: There was a significant increase in detectability independent of attenuation and location of nodules for all readers (P < 0.0008). Dedicated chest CT training improves detection of lung nodules, especially the part-solid ground-glass nodules. Detection of nodules adjacent to branching vessels and the posterior mediastinal lungs is difficult even for fellowship-trained radiologists.

Three-dimensional mean CT attenuation value of pure and part-solid ground-glass lung nodules may predict invasiveness in early adenocarcinoma

This study evaluated the relationship between three-dimensional (3D) mean computed tomography (CT) attenuation values of ground-glass nodules (GGN) and pathological invasiveness in early lung adenocarcinoma. The diagnostic accuracy of 3D CT attenuation values was compared with that of two-dimensional (2D) CT attenuation values and standardised uptake value on positron-emission tomography (PET). Surgical and radiological data from 96 pure or part-solid GGNs of <20 mm were analysed retrospectively. Mean 2D and 3D CT attenuation values of the tumours were obtained with semi-automated volumetric software. Pathological invasiveness was diagnosed according to the International Association for the Study of Lung Cancer (IASLC))/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. Pre-invasive lesions and minimally invasive adenocarcinomas were classified as non-invasive adenocarcinoma. Univariate and multivariate analyses determined relationships between pathological invasiveness and clinical/radiological findings. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for detecting invasive adenocarcinoma. A total of 66 non-invasive and 30 invasive adenocarcinoma cases between 2010 and 2016 were analysed. Univariate analysis revealed four tumour invasiveness-associated predictors: maximum diameter, SUVmax, mean 2D CT attenuation value, and mean 3D CT attenuation value (p<0.05). Multivariate analysis revealed that the maximum diameter, SUVmax, and mean 3D CT attenuation value were significant predictors of pathological invasiveness (p=0.023, 0.022, 0.004). The area under the ROC curve to predict invasive adenocarcinoma for mean 3D CT attenuation value was 0.838 and the cut-off value was -489 HU. The mean 3D CT attenuation value could distinguish pre-invasive lesions and minimally invasive adenocarcinoma from invasive adenocarcinoma.

A radiomics model for determining the invasiveness of solitary pulmonary nodules that manifest as part-solid nodules

A nomogram model was developed to predict the histological subtypes of lung invasive adenocarcinomas (IAs) and minimally invasive adenocarcinomas (MIAs) that manifest as part-solid ground-glass nodules (GGNs). This retrospective study enrolled 119 patients with histopathologically confirmed part-solid GGNs assigned to the training (n=83) or testing cohorts (n=36). Radiomic features were extracted based on the unenhanced computed tomography (CT) images. R software was applied to process the qualitative and quantitative data. The CT features model, radiomic signature model, and combined prediction model were constructed and compared. A total of 396 radiomic features were extracted from the preoperative CT images, four features including MaxIntensity, RMS, ZonePercentage, and LongRunEmphasis_angle0_offset7 were indicated to be the best discriminators to establish the radiomic signature model. The performance of the model was satisfactory in both the training and testing set with areas under the curve (AUCs) of 0.854 (95% confidence interval [CI]: 0.774 to 0.934) and 0.813 (95% CI: 0.670 to 0.955), respectively. The CT morphology of the lesion shape and diameter of the solid component were confirmed to be a significant feature for building the CT features model, which had an AUC of 0.755 (95% CI: 0.648 to 0.843). A nomogram that integrated lesion shape and radiomic signature was constructed, which contributed an AUC of 0.888 (95% CI: 0.82 to 0.955). The radiomic signature could provide an important reference for differentiating IAs from MIAs, and could be significantly enhanced by the addition of CT morphology. The nomogram may be highly informative for making clinical decisions.

The new 8th TNM staging system of lung cancer and its potential imaging interpretation pitfalls and limitations with CT image demonstrations.

The tumor, node, metastasis (TNM) staging system approved by International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC) to stage lung cancer was recently revised. The latest revision is the 8th edition published in January, 2017. This new edition made some important changes to the previous edition, including modification of the T classification based on 1 cm increment, downstage of T descriptor including endobronchial tumor disregarding its distance from carina (T2), merging total and partial atelectasis/pneumonitis into the same T category (T2), upstage diaphragmatic invasion to T4, new classification concept of adenocarcinoma in situ and minimally invasive adenocarcinoma for pure and part-solid ground-glass nodules, and further division of extrathoracic metastasis into M1b and M1c based on the number and sites of extrathoracic metastases. Consensus is reached for debating situations not covered in the previous edition of staging system, such as the classification of pancoast tumor based on its invasion depth and staging tumors that extend directly across the fissure as T2a. Classification of multiple sites of pulmonary involvement, including multiple primary lung cancer, separate lung cancer nodules, multiple ground-glass or lepidic lesions, and consolidation, is also discussed. Even though the 8th edition of the TNM lung staging system provides us with more precise classification based on prognostic analysis of each TNM descriptors, there are still some potential limitations and clinical situations that have not yet been clarified in terms of clinical staging by imaging. It is important for radiologists to understand the major changes introduced in the 8th edition of TNM staging and to recognize the potential pitfalls and limitations of imaging interpretation to precisely classify the clinical stage of lung cancer.

Radiomic features from computed tomography to differentiate invasive pulmonary adenocarcinomas from non-invasive pulmonary adenocarcinomas appearing as part-solid ground-glass nodules.

ObjectiveWe aim to investigate radiomic imaging features extracted in computed tomography (CT) images to differentiate invasive pulmonary adenocarcinomas (IPAs) from non-IPAs appearing as part-solid ground-glass nodules (GGNs), and to incorporate significant radiomic features with other clinically-assessed features to develop a diagnostic nomogram model for IPAs.MethodsThis retrospective study was performed, with Institutional Review Board approval, on 88 patients with a total of 100 part-solid nodules (56 IPAs and 44 non-IPAs) that were surgically confirmed between February 2014 and November 2016 in the First Affiliated Hospital of China Medical University. Quantitative radiomic features were computed automatically on 3D nodule volume segmented from arterial-phase contrast-enhanced CT images. A set of regular risk factors and visually-assessed qualitative CT imaging features were compared with the radiomic features using logistic regression analysis. Three diagnostic models, i.e., a basis model using the clinical factors and qualitative CT features, a radiomics model using significant radiomic features, and a nomogram model combining all significant features, were built and compared in terms of receiver operating characteristic (ROC) curves. Decision curve analysis was performed for the nomogram model to explore its potential clinical benefit.ResultsIn addition to three visually-assessed qualitative imaging features, another three quantitative features selected from hundreds of radiomic features were found to be significantly (all P<0.05) associated with IPAs. The diagnostic nomogram model showed a significantly higher performance [area under the ROC curve (AUC) =0.903] in differentiating IPAs from non-IPAs than either the basis model (AUC=0.853, P=0.0009) or the radiomics model (AUC=0.769, P<0.0001). Decision curve analysis indicates a potential benefit of using such a nomogram model in clinical diagnosis.ConclusionsQuantitative radiomic features provide additional information over clinically-assessed qualitative features for differentiating IPAs from non-IPAs appearing as GGNs, and a diagnostic nomogram model including all these significant features may be clinically useful in preoperative strategy planning.

Distinctive clinicopathological features of adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung: A retrospective study

ObjectivesThe aim of this study was to investigate distinguishing clinicopathological features, in addition to histological invasiveness, in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) of the lung. Materials and methodsPatients with lung adenocarcinoma who underwent surgery at our hospital between 2007 and 2014 were reviewed, focusing on computed tomography (CT) images, operative procedures and clinical outcomes, histopathology, Ki-67 immunostaining, and EGFR-mutation status. EGFR mutations were examined using a peptide nucleic acid–locked nucleic acid PCR clamp method. Group comparisons were investigated by Mann–Whitney U or Fisher’s exact tests. ResultsOf 629 patients with lung adenocarcinoma who underwent surgery, 91 (14%) of 103 AIS (n = 34) or MIA (n = 69) tumors were reviewed. The ratio of male to female patients with MIA compared to AIS was significantly higher (p < 0.02). Of 103 tumors, 99 (96%) were non-mucinous. By CT, 74% of AIS appeared as pure ground-glass nodules and 75% of MIAs as part-solid ground-glass nodules. Pathological tumor diameters and Ki-67 labeling index (LI) values were significantly greater for MIAs compared to AIS (p < 0.001 for both). A Ki-67 LI of ≥2.8% indicated the presence of an MIA rather than an AIS. EGFR mutations were more frequently detected in MIAs (33/69, 48%) than AIS (9/34, 26%; p = 0.055). The ratio of exon 19 deletions to exon 21 missense mutations in MIAs tended to be higher than those in AIS (p = 0.06). Patients did not experience a local recurrence or metastasis after AIS and MIAs were removed by wedge resection, segmentectomy or lobectomy. Five-year recurrence-free survival rates were 100%. ConclusionDespite similar surgical outcomes for AIS and MIAs, we found differences in terms of gender, tumor diameters, CT findings, Ki-67 LI and a subset of EGFR mutations, highlighting the validity of classifying the two subtypes.

Applying CT texture analysis to determine the prognostic value of subsolid nodules detected during low-dose CT screening

To analyse subsolid nodules (SSNs) detected during low-dose (LD) computed tomography (CT) screening and investigated whether CT texture analysis parameters can predict the malignancy and growth trends of GGNs. In this retrospective study, 89 SSNs were detected in 86 LDCT screening participants, including 42 pure ground-glass nodules (GGNs) and 47 part-solid GGNs. In these participants, 28 SSNs were diagnosed as lung cancer at histopathology, and 61 SSNs from participants who underwent at least two LDCT imaging studies. All nodules were divided into three groups: cancer group, growth group, and non-growth group. The nodule size, volume, attenuation, volume doubling time (VDT), and texture parameters (mean value, uniformity, entropy and energy) were assessed, respectively. The entropy of the cancer group was significantly higher than that of the growth and non-growth groups (pure GGNs: p=0.009, 0.001; part-solid GGNs: p=0.012, 0.004). The energy of the cancer group was significantly lower than that of the other groups (pure GGNs: p=0.043, 0.021; part-solid GGNs: p=0.001, 0.002). A good positive correlation was found between uniformity and VDT (p=0.022). Different CT texture parameters show good predictive value for SSNs detected at LDCT screening: the entropy and energy differences between malignant pulmonary nodules and others could be a helpful quantitative index to predict the malignancy of SSNs. Uniformity could be used to predict the growth probability of pure GGNs at baseline to pay more attention to these nodules. Moreover, the follow-up and treatment plan could be more targeted.

Solitary pulmonary capillary hemangioma: An under-recognized pulmonary lesion mimicking early lung cancer on computed tomography images

ObjectivesSolitary pulmonary capillary hemangioma (SPCH) is a rare lung tumor typically presenting as pure or part-solid ground-glass nodules (GGNs) on computed tomography (CT), which clinically resembles early lung cancer. Materials and MethodsIn addition to 10 recently diagnosed patients with SPCH, 71 benign lung nodules that were surgically resected between January 2013 and December 2017 were reviewed by thoracic pathologists to identify any previously unrecognized SPCH cases. Finally, 6 tumors (8.5%; 6/71) were determined to be SPCH. Elastic fiber stain (orcein stain) as well as immunohistochemistry for cytokeratin, CD31, and thyroid transcription factor 1 were performed for confirmation. Clinical and radiological data were analyzed. ResultsAll 16 SPCH lesions were unrecognized or misdiagnosed by general pathologists. The SPCH ranged in size from 3 to 15 mm, and a predominance among women (68.8%; 11/16) was noted. Pathologically, all SPCH lesions were nodular with a higher vascular density than the adjacent lung tissue. Decreased cytokeratin staining and disrupted elastic fibers were clearly observed in all SPCH lesions. ConclusionsSPCH lesions mimic early lung cancer on CT; they are largely unrecognized by general pathologists and are diagnosed as other nonspecific benign lesions. With careful histologic examination, SPCH can be successfully diagnosed using cytokeratin/CD31 immunohistochemistry and elastic fiber staining.

Ground-glass nodules of the lung in never-smokers and smokers: clinical and genetic insights.

Pulmonary ground-glass nodules (GGNs) are hazy radiological findings on computed tomography (CT). GGNs are detected more often in never-smokers. Retrospective and prospective studies have revealed that approximately 20% of pure GGNs and 40% of part-solid GGNs gradually grow or increase their solid components, whereas others remain stable for years. Most persistent or growing GGNs are lung adenocarcinomas or their preinvasive lesions. To distinguish GGNs with growth from those without growth, GGNs should be followed for at least 5 years. Lesion size and smoking history are predictors of GGN growth. Genetic analyses of resected GGNs have suggested that EGFR mutations are also predictors for growth but a subset of KRAS- or BRAF-mutated GGNs may undergo spontaneous regression because the frequencies of KRAS or BRAF mutations decrease with the advance of pathological invasiveness. Although lobectomy is the standard surgical procedure for lung cancer, limited surgery such as wedge resection or segmentectomy for lung cancers ≤2 cm with consolidation/tumor ratio ≤0.25 can be a viable alternative based on the recent clinical trial. Further genetic analyses and clinical trials can contribute to elucidation of the biological aspects of preinvasive adenocarcinoma and the development of less invasive management strategies for patients with GGNs.

Statistical analysis of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ground-glass nodule findings.

18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT) is important in lung cancer diagnosis; false negatives are often caused by ground-glass nodules (GGNs). PET/CT utility in GGN diagnosis is unknown. The associations between GGN CT findings (size, properties), the pathological diagnosis and maximum standardized uptake value (SUVmax) were explored. Sixty-six patients with pathological stage IA1-IIA lung adenocarcinoma underwent surgical resection and PET/CT between January 2010 and December 2014. Clinical characteristics, CT findings, pathological diagnoses and PET/CT findings were retrospectively examined. The age range was 47-86 years (median, 69 years), the female/male ratio was 38:28 and the pathological stage was IA1, IA2, IA3, IB and IIA in 5, 30, 21, 9 and 1, respectively. Total and solid-part lesion diameters ranged from 7.00-41.13 mm (median, 19.43 mm) and 0.00-23.23 mm (median, 4.55 mm), respectively; the solid-part ratio (solid-part diameter/total diameter) was 0-77% (median, 20%). SUVmax ranged from a value too low for evaluation to 3.9 (median, 1.0). Pathological diagnoses were adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), lepidic-predominant adenocarcinoma (LPA) and papillary predominant adenocarcinoma (PPA) in 17, 15, 32 and 2, respectively. Correlation coefficients for each factor and SUVmax for total and solid-part diameters were 0.513 (p<0.0001) and 0.461 (p<0.0001), respectively. All pure GGNs showed clinically unimportant SUVmax<2.5, even though some large GGNs were included (maximum, 40.0 mm). A total diameter ≥20 mm was significantly associated with FDG uptake (p<0.0001). SUVmax were <2.5 when the solid-part diameter was <4.55 mm. The AIS-MIA group showed significantly lower SUVmax than the LPA-PPA group (p=0.0008). There was no clinically important SUVmax with diagnostic value for pure or small part-solid GGNs. There were medium correlations for GGN total diameter, solid-part diameter, and SUVmax. We should note PET/CT's limitations in GGN diagnosis.