Case of pulmonary Langerhans cell histiocytosis presenting as ground-glass opacity in the lower lung.

Nodules and cysts with upper lobe predominance on chest computed tomography (CT) are highly suggestive of pulmonary Langerhans cell histiocytosis (PLCH). Herein, we describe a case of PLCH that presented with the unusual CT findings of subpleural ground-glass opacity (GGO) and traction bronchiectasis mostly in both lower lungs. No nodules or cysts were observed in the upper or middle lung areas. Video-assisted thoracoscopic biopsies were performed at the right lower lobe. Biopsy specimens showed findings consistent with those of scarred PLCH. To the best of our knowledge, this is the first case of PLCH presenting as GGO in the lower lungs.

Resected lung adenocarcinoma with lymph node metastasis: is ground glass opacity component a prognostic factor?

Background: Ground glass opacity (GGO)-featured lung adenocarcinoma generally has excellent prognosis, and here is rarely the occurrence of lymph node metastasis. We conducted a retrospective cohort study to explore the prognostic impact of GGO component in node-positive lung adenocarcinomas. Methods: A total of 669 patients with pathologic N1/N2 lung adenocarcinoma receiving R0 resection and systemic lymph node dissection from 2008 to 2015 were reviewed, including 635 solid and 34 part-solid lesions. Propensity score matching (PSM) was performed to compare survival outcomes of solid and part-solid lesions, in order to determine the prognostic value of GGO component. Cox proportional hazard model was performed to identify significant prognostic factors for resected node positive lung adenocarcinoma. Results: About 5.1% (34 of 669) of resected node-positive lung adenocarcinoma presented as part-solid nodules on computed tomography (CT) images in this cohort. The median nodule size on CT of the 34 part-solid lesions was 31 mm (range, 15-68 mm), median solid component size on CT was 24 mm (range, 12-62 mm), and median consolidation/tumor ratio was 0.8 (range, 0.64-0.95). After 1:4 PSM, 136 patients and 34 patients were matched from the solid and part-solid groups. No significant difference in either recurrence-free survival (RFS) (P=0.71) or overall survival (OS) (P=0.82) was found between the solid and part-solid groups. Multivariable Cox regression showed that pN stage was the strongest prognostic factor for RFS and OS. GGO component was not an independent prognostic factor toward for RFS [P=0.75; hazard ratio (HR) =0.93; 95% confidence interval (CI): 0.59-1.46] or OS (P=0.53; HR =1.19; 95% CI: 0.69-2.05). Conclusions: A minority of resected node-positive lung adenocarcinoma presents as GGO component on CT. The presence of GGO component does not predict better prognosis in node-positive lung adenocarcinoma.

Imaging diagnostics of pulmonary ground-glass nodules: a narrative review with current status and future directions.

Background and Objective: The incidence rate of lung cancer, which also has the highest mortality rates for both men and women worldwide, is increasing globally. Due to advancements in imaging technology and the growing inclination of individuals to undergo screening, the detection rate of ground-glass nodules (GGNs) has surged rapidly. Currently, artificial intelligence (AI) methods for data analysis and interpretation, image processing, illness diagnosis, and lesion prediction offer a novel perspective on the diagnosis of GGNs. This article aimed to examine how to detect malignant lesions as early as possible and improve clinical diagnostic and treatment decisions by identifying benign and malignant lesions using imaging data. It also aimed to describe the use of computed tomography (CT)-guided biopsies and highlight developments in AI techniques in this area. Methods: We used PubMed, Elsevier ScienceDirect, Springer Database, and Google Scholar to search for information relevant to the article's topic. We gathered, examined, and interpreted relevant imaging resources from the Second Affiliated Hospital of Nanchang University's Imaging Center. Additionally, we used Adobe Illustrator 2020 to process all the figures. Key Content and Findings: We examined the common signs of GGNs, elucidated the relationship between these signs and the identification of benign and malignant lesions, and then described the application of AI in image segmentation, automatic classification, and the invasiveness prediction of GGNs over the last three years, including its limitations and outlook. We also discussed the necessity of conducting biopsies of persistent pure GGNs. Conclusions: A variety of imaging features can be combined to improve the diagnosis of benign and malignant GGNs. The use of CT-guided puncture biopsy to clarify the nature of lesions should be considered with caution. The development of new AI tools brings new possibilities and hope to improving the ability of imaging physicians to analyze GGN images and achieving accurate diagnosis.

Predictors of relapse of polymyositis/dermatomyositis associated interstitial lung disease.

Background: Polymyositis/dermatomyositis (PM/DM) patients often develop interstitial lung disease (ILD), which can lead to relapse despite anti-inflammatory treatments. This study aims to elucidate the clinical characteristics of relapses in PM/DM-associated ILD patients. Methods: We gathered clinical data, including laboratory results, pulmonary function tests, chest high-resolution computed tomography findings from patients treated at Okinawa Chubu Hospital between January 1, 2010 and December 31, 2018. Results: We identified a total of 74 patients, comprising 21 men and 53 women. Among them, 38 patients remained relapse-free with maintenance therapy, while 36 experienced relapses despite immunosuppressive management. We followed these patients until June 30, 2023, and 13 patients died. The median survival period was 51.4 months (range, 0.3-214 months). When comparing clinical variables, relapsed patients tended to be younger (49.9 vs. 64.1 years), reported myalgia and rash more frequently (63.9% vs. 28.9% and 61.15% vs. 21.1%, respectively). In terms of laboratory findings, lactate dehydrogenase (LDH) levels were higher in relapsed patients (613±464 vs. 381±203 U/L). Radiological findings showed that ground glass opacity (GGO) was more prevalent in relapsed patients (58.3% vs. 16.7%). A Cox-proportional hazards model for relapse demonstrated that serum LDH [hazard ratio (HR) 1.005, 95% confidence interval (CI): 1.000-1.009, P=0.02] and GGO (HR 1.863, 95% CI: 1.103-3.147, P=0.02) were valuable predictors of relapse. Receiver operating characteristic curve analysis of serum LDH indicated that a threshold of 450 correctly classified relapse in PM/DM-associated ILD patients. Conclusions: Serum LDH and GGO may serve as predictors of relapse in PM/DM-associated ILD patients.

Protocol for a single-arm, multicenter, prospective, confirmatory phase III trial of wedge resection for invasive ground glass opacity-featured lung cancer with a size ≤2 cm and a consolidation tumor ratio between 0.25 and 0.5 (ECTOP-1020 study).

Background: Segmentectomy is the current standard treatment for ground glass opacity (GGO)-featured lung cancer patients with a tumor size ≤2 cm and a consolidation tumor ratio (CTR) between 0.25 and 0.5. However, compared with wedge resection, segmentectomy destroys the patient's hilar structure and consumes more lung parenchyma. A recent study demonstrated that wedge resection could yield comparable results for this group of patients. Methods: This study aimed to confirm the noninferiority of wedge resection over standard surgery in invasive GGO-featured lung cancer patients with a size ≤2 cm and a CTR between 0.25 and 0.5, as measured by 5-year overall survival (OS). The primary endpoint is 5-year OS. The secondary endpoints are 5-year recurrence-free survival (RFS), the R0 resection rate, pulmonary function, recurrence and metastasis sites, and adverse events after surgery. During the trial period, 286 patients are enrolled from six Chinese institutions. Discussion: The primary results of this study will be actively disseminated through manuscript publications and conference presentations. This prospective study will evaluate the surgical efficacy and safety of wedge resection for small (tumor size ≤2 cm with a CTR between 0.25 and 0.5) invasive GGO-featured lung cancer and will support the standardization of this surgical strategy. Trial Registration: This trial has been registered on ClinicalTrial.gov (No. NCT06102161).

Different clinicopathological features between young and older patients with pulmonary adenocarcinoma and ground-glass opacity.

After the recommendation of computed tomography as a routine procedure for lung cancer screening, an increasing number of young adults have been diagnosed with pulmonary ground-glass opacity (GGO). Up to 63% of pulmonary nodules with a GGO component can be malignant. Since young cancer patients have limited exposure to environmental mutagens, they have special characteristics and needs. This study sought to compare the clinicopathological characteristics of young and old patients with GGO-associated lung adenocarcinoma (GGO-LUAD). Clinicopathological data from 203 patients who underwent video-assisted thoracoscopic surgery between January 2018 and April 2020 for pulmonary GGO component nodules were reviewed. Lung nonmucinous adenocarcinoma patients younger than 40 years old and older than 40 years old were enrolled: 103 patients ≤ 40 years old and 100 patients > 40 years old. The relevant clinicopathological features, including sex, smoking status, tumor size, pathological characteristics, radiographic features and prognosis of pulmonary nodules, were evaluated. Univariate analyses were applied for comparisons between groups. The differences in baseline characteristics (sex, smoking status, tumor location) between the different age groups were not significant. Young patients were more likely to have tumors < 1 cm in size, while older patients predominantly had tumors > 2 cm in size. The mean percentage of invasive adenocarcinoma was greater in the elderly group. Young and older patients seemed to have similar subtypes of adenocarcinoma (p > 0.05) but had different degrees of differentiation (p < 0.001). The 3-year overall survival (OS) and recurrence-free survival (RFS) of the young group were 100% and 99.03%, respectively, while the 3-years OS and RFS of the older group were 99% and 98%, respectively. Our work revealed that young patients with malignant pulmonary nodules and GGOs have distinct pathological subtypes. Patients with GGOs of different ages have different clinicopathological characteristics. The 3-year prognosis of young patients with malignant pulmonary nodules with GGOs is satisfactory.

Segmentectomy versus lobectomy for ground-glass opacity dominant cT1N0 invasive lung adenocarcinoma.

Background: The Japan Clinical Oncology Group (JCOG) 1211 suggested that segmentectomy should be considered as standard treatment for clinical T1N0 (cT1N0) ground glass opacity (GGO). However, over half of patients in JCOG1211 had pre-/minimal invasive adenocarcinoma. This study aims to retrospectively investigate the long-term survival of GGO featured cT1N0 invasive lung adenocarcinoma undergoing segmentectomy or lobectomy. Methods: This study screened patients with primary cT1N0 lung adenocarcinoma who received segmentectomy or lobectomy from 2010-2020. Prior computed tomography (CT) scans before surgery of all patients were reviewed and the inclusion was confirmed according to tumor diameter and consolidation tumor ratio (CTR). GGO nodules between 2-3 cm with CTR ≤0.5 or ≤2 cm with CTR between 0.25-0.5 were finally included. Patients with pathologically diagnosed pre-/minimally invasive lung adenocarcinoma were excluded. Long-term survivals between segmentectomy group and lobectomy group were compared after propensity score matching (PSM). Recurrence and postoperative complication events were also analyzed. Results: In total, 617 patients were enrolled, 159 received segmentectomy and 458 received lobectomy. Clinicopathological characteristics were well distributed between two groups. With a median follow-up time of 61.1 months (IQR: 42.3-71.7 months), after PSM, the 5-year overall survival rate was 98.8% (97.9-99.6%) for lobectomy and 99.3% (98.2-99.8%) for segmentectomy (P=0.42), the 5-year relapse-free survival rate was 95.3% (92.2-97.6%) for lobectomy and 95.2% for segmentectomy (92.3-98.7%) (P=0.81). The proportion of recurrence was 4.1% for lobectomy and 4.4% for segmentectomy (P=0.89). The proportion of grade 2 and above early postoperative complications was 9.6% for lobectomy and 8.8% for segmentectomy (P=0.86). Conclusions: For cT1N0 GGO featured invasive lung adenocarcinoma (2 cm < tumor diameter ≤3 cm, CTR ≤0.5 or tumor diameter ≤2 cm, 0.25< CTR ≤0.5), postoperative outcomes between segmentectomy group and lobectomy group were comparable. Concerning minimally invasive surgical strategy, segmentectomy should be confirmed as the standard surgical approach.

Uncommon Causes of Interlobular Septal Thickening on CT Images and Their Distinguishing Features.

Interlobular septa thickening (ILST) is a common and easily recognized feature on computed tomography (CT) images in many lung disorders. ILST thickening can be smooth (most common), nodular, or irregular. Smooth ILST can be seen in pulmonary edema, pulmonary alveolar proteinosis, and lymphangitic spread of tumors. Nodular ILST can be seen in the lymphangitic spread of tumors, sarcoidosis, and silicosis. Irregular ILST is a finding suggestive of interstitial fibrosis, which is a common finding in fibrotic lung diseases, including sarcoidosis and usual interstitial pneumonia. Pulmonary edema and lymphangitic spread of tumors are the commonly encountered causes of ILST. It is important to narrow down the differential diagnosis as much as possible by assessing the appearance and distribution of ILST, as well as other pulmonary and extrapulmonary findings. This review will focus on the CT characterization of the secondary pulmonary lobule and ILST. Various uncommon causes of ILST will be discussed, including infections, interstitial pneumonia, depositional/infiltrative conditions, inhalational disorders, malignancies, congenital/inherited conditions, and iatrogenic causes. Awareness of the imaging appearance and various causes of ILST allows for a systematic approach, which is important for a timely diagnosis. This study highlights the importance of a structured approach to CT scan analysis that considers ILST characteristics, associated findings, and differential diagnostic considerations to facilitate accurate diagnoses.

A simple and safe surgical technique for nonpalpable lung tumors: One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH).

When performing thoracoscopic partial resections of nonpalpable lung tumors such as ground-glass opacities (GGOs) and small tumors, detecting the location of the lesion and assessing the resection margins can be challenging. We have developed a novel method to ease this difficulty, the One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH), which uses a hybrid operating room wherein the operating table is seamlessly integrated with cone-beam computed tomography (CBCT). We performed the OS-MRCH method on 62 nodules including primary lung cancer presenting with GGO. Identification of the lesion and confirmation of the margin were performed in 58 of the cases, while nodules were detected in all. The frequency of computed tomography (CT) scans performed prior to resection was one time in 51 cases, two times in eight cases, and ≥3 times in three cases. Additional resection was performed in two cases. The median operative time was 85.0 minutes, and the median pathological margin was 11.0 mm. The key advantages of this method are that all surgical processes can be completed in a single session, specialized skill sets are not required, and it is feasible to perform in any facility equipped with a hybrid operating room. To overcome its disadvantages, such as longer operating time and limited patient positioning, we devised various methods for positioning patients and for CT imaging of the resected specimens. OS-MRCH is a simple, useful, and practical method for performing thoracoscopic partial resection of nonpalpable lung tumors.

The presence of micropapillary and/or solid subtypes is an independent prognostic factor for patients undergoing curative resection for stage I lung adenocarcinoma with ground-glass opacity.

Background: Non-predominant or even minimal micropapillary and/or solid (MP/S) subtypes have been reported to exert an unfavorable prognostic influence on surgically resected lung adenocarcinoma (ADC). Currently, there is a lack of evidence to demonstrate that high-grade pathological subtypes, including MP/S components, impact the prognosis of patients with surgically resected lung ADCs with ground-glass opacity (GGO). In this investigation, we explored the prognostic implications of minimal MP/S components in lung ADCs with GGO. Methods: A retrospective cohort study was conducted on 1,004 consecutive patients undergoing curative resection for pathologic stage (p-stage) I lung ADCs featuring GGO on computed tomography (CT) scans between January 2014 and December 2016. Tumors were categorized into MP/S positive (MP/S+) group and MP/S negative (MP/S-) group. MP/S+ tumors were defined when MP/S subtypes constituted ≥1% of the entire tumor. The prognostic impact of MP/S subtypes was evaluated using Kaplan-Meier analysis, Cox proportional hazard model and restricted cubic spine (RCS) model. Results: A total of 86 (8.6%) cases with MP/S+ tumors and 918 (91.4%) cases with MP/S- tumors were identified. The solid component tumor diameter and pathological invasive tumor size of MP/S+ tumors were both significantly larger than that of MP/S- tumors (13.0 vs. 4.0 mm, P<0.001, and 18.0 vs. 10.0 mm, P<0.001, respectively). After a median follow-up of 7.3 years, the presence of MP/S components was significantly associated with decreased RFS (5-year RFS, MP/S+ 88.3% vs. MP/S- 97.4%; P<0.001; HR =1.02). The presence of a histologic lepidic (Lep) component demonstrated a prognostic advantage in both MP/S- (5-year RFS, MP/S-Lep+ 98.0% vs. MP/S-Lep- 95.3%; P=0.01; HR =0.89) and MP/S+ subgroups (5-year RFS, MP/S+Lep+ 93.4% vs. MP/S+Lep- 83.2%; P=0.10; HR =0.84). MP/S+ components ≥5% were the only tumor-related factor that independently affected RFS [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.07-2.94] according to multivariate analysis. There was a progressively negative impact of the proportion of MP/S subtypes on RFS as illustrated by RCS model. Conclusions: The presence of MP/S patterns in stage I GGO-featured lung ADCs exhibit significant prognostic value and may have implications for tailored postoperative treatment and surveillance strategies, especially when the proportion exceeds 5% of the entire tumor.

Genetic characteristics of lung adenocarcinoma with ground-glass opacity component.

Background: Increasing evidence suggests that ground-glass opacity featured lung adenocarcinoma (GGO-LUAD) and pure solid-LUAD have significantly different tumor biological behaviors; the former is usually indolent. Genetic variations fundamentally contribute to this distinct tumor behaviors. This study aims to investigate and compare the gene mutations using next-generation sequencing (NGS) technology in these two subtypes of LUAD. Methods: The clinical data and gene testing results of 46 patients suffering from LUAD with a histologically invasive subtype ≤3 cm and operated in the Thoracic Surgery Department of Beijing Tsinghua Changgung Hospital from May 2019 to December 2022 were retrospectively analyzed; a case-control study was performed to compare the pathological and genetic differences between LUAD with a GGO component and pure solid-LUAD. Results: Notable differences existed in vascular invasion, tumor spread through air spaces (STAS) and high-risk histological subtypes (micropapillary or solid subtypes) between the two types of LUAD with similar histologically invasive size. No significant difference was found in the mutation frequency of EGFR and KRAS. However, gene mutations were more prevalent in the cell cycle and TP53 signaling pathway for solid-LUAD. A significant difference was found in the mutation frequency of the tumor suppressor genes TP53 and CDKN2A between the two types. Conclusions: The wild-type TP53 and CDKN2A genes could potentially be used as molecular indicators for indolent LUAD characterized by GGO-featured.

Impact of extended mediastinal lymph node dissection for stage I ground-glass opacity lesions.

Background: Mediastinal lymph node dissection (MLND) is a critical component in lung cancer surgery. With the increasing number of patients with ground-glass opacity (GGO) lesions, the clinical impact of MLND has not been sufficiently assessed, particularly for part-solid lesions. This study aimed to evaluate the impact of extended N2 MLND in patients with GGO lesions with a consolidation tumor ratio (CTR) of 0.3-0.7. Methods: Among patients diagnosed with stage I adenocarcinoma between 2013 and 2019, we retrospectively reviewed 138 patients with a CTR of 0.3-0.7. They were divided into the following two groups by MLND: limited N2 MLND (<3 N2 stations; n=100) and extended N2 MLND (≥3 N2 stations; n=38). Kaplan-Meier curves were used to compare oncologic outcomes and logistic regression was used to identify the predictive factors for postoperative complications (PoCs). Propensity-score matching regarding tumor characteristics and surgical extent were also performed to compare these two MLND assessments in clinical outcome. Results: The extended N2 MLND group had larger solid components (9.5 vs. 7.0 mm, P=0.002) and more patients underwent lobectomy (P=0.008). Kaplan-Meier survival curves revealed no significant difference in clinical outcomes. After propensity score matching, the difference between two MLND strategies was also non-significant in clinical outcome. However, extended N2 MLND was found to be a significant factor in the development of PoC [odds ratio (OR), 4.57; 95% confidence interval (CI): 1.26-16.6; P=0.021]. Conclusions: For GGO lesions with a CTR of 0.3-0.7, the extended MLND strategy may not be optimal in terms of clinical outcome. It could lead to more frequent early complications with no oncologic benefits. Due to the limited number of cases in this study, further prospective research on MLND for part-solid lesions is required.

Pathological and radiological T descriptors in invasive lung adenocarcinoma: from correlations to prognostic significance.

Background: The eighth T classification excluded lepidic and ground-glass opacity (GGO) components. Current studies demonstrated lepidic and GGO components showed independent prognostic significances. This study elucidated the correlations and prognostic impacts of pathological and radiological T descriptors in invasive lung adenocarcinoma. Methods: A total of 1,490 patients with invasive lung adenocarcinoma were retrospectively reviewed. Correlation between pathological invasive size (PIS) and radiological solid size (RSS), and lepidic ratio and GGO ratio were comprehensively evaluated. Impacts of these pathological and radiological T descriptors on recurrence-free survival (RFS) were comparatively analyzed. Results: Clinical (c)T-stage was more frequently downstaged than upstaged comparing with the pathological (p)T-stage (28.4% vs. 18.2%). The correlation between PIS and RSS in solid nodule was stronger than that in part-solid nodule (solid: R2=0.750 vs. part-solid: R2=0.355). Some pathological invasive components except solid component were featured as GGO. Among T1 patients, lepidic absent GGO showed better RFS than lepidic present solid nodule (pT1: P=0.001; cT1: P=0.021). Multivariable analysis revealed GGO ratio was an independent prognostic factor for RFS in T1 invasive lung adenocarcinoma, whereas lepidic ratio was not. Conclusions: Among T1 invasive lung adenocarcinoma, GGO ratio showed independent prognostic value for RFS, regardless of RSS. Meanwhile, lepidic ratio was not an independent RFS factor. GGO component rather than lepidic component should be considered as an additional T descriptor.

Diagnostic sensitivity of solid volume measurement for pathological invasion in non-solid lung adenocarcinoma.

Background: In the current tumor-node-metastasis (TNM) classification, the clinical T descriptor is defined by solid size (SS) on a computed tomography (CT) slice and the pathological one is done by invasive size (IS) in microscopic evaluations. We sometimes experience discrepancies in diagnosis of both descriptors. A volume analyzing application enables semi-automatic measurement of three-dimensional (3D) parameters in cases where there are discrepancies in diagnosing tumors' solid size and IS. In this study, we aimed to evaluate the association between 3D parameters and pathological invasion in non-solid small-sized lung adenocarcinomas. Methods: We enrolled 246 consecutive patients who underwent pulmonary resection at Shizuoka Cancer Center. Patients with lung adenocarcinomas that were radiologically non-solid, node-negative and sized ≤3 cm were eligible. We used a volume analyzing application to retrospectively measure 3D parameters of max and mean Hounsfield units (HUs) and solid volume (SV). The cut-off value of these parameters for diagnosing invasive adenocarcinoma (IAD) was set by describing receiver operating characteristic (ROC) curves. The correlation of IAD with these parameters was compared to its correlation with the SS. This study was not registered. Results: Of 246 patients with adenocarcinoma, 183 (74.4%) had IADs. In multivariate analyses, the total size (TS) and SS were significantly associated with IAD (P=0.006, 0.001, respectively), whereas 3D parameters including SV were not (P=0.80). In radiological adenocarcinoma (2.1-3.0 cm), SV >300 mm3 diagnosed IAD with a higher sensitivity than that of the SS (0.93 and 0.83, respectively). Conclusions: TS >20 mm and SS >5 mm were well-correlated with IAD. SV measurement may complement the current computed tomographic diagnosis of IAD based on the SS (2.1-3.0 cm).

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.

Prognostic effect of ground-glass opacity in subcentimeter invasive lung adenocarcinoma.

Background: Although subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group. Methods: Patients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses. Results: A total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules. Conclusions: The radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.

A narrative review of the clinical approach to subsolid pulmonary nodules.

Background and Objective: The widespread use of chest computed tomography (CT) for lung cancer screening has led to increased detection of subsolid pulmonary nodules. The management of subsolid nodules (SSNs) is challenging since they are likely to grow slowly and a long-term follow-up is needed. In this review, we discuss the characteristics, natural history, genetic features, surveillance, and management of SSNs. Methods: PubMed and Google Scholar were searched to identify relevant articles published in English between January 1998 and December 2022 using the following keywords: "subsolid nodule", "ground-glass nodule (GGN)", and "part-solid nodule (PSN)". Key Content and Findings: The differential diagnosis of SSNs includes transient inflammatory lesions, focal fibrosis, and premalignant or malignant lesions. Long-term CT surveillance follow-up is needed to manage SSNs that persist for >3 months. Although most SSNs have an indolent clinical course, PSNs may have a more aggressive clinical course than pure GGNs. The proportion of growth and the time to grow is higher and shorter in PSN than pure GGN. In lung adenocarcinoma manifesting as SSNs, EGFR mutations were the major driver mutations. Guidelines are available for the management of incidentally detected and screening-detected SSNs. The size, solidity, location, and number of SSNs are important factors in determining the need for surveillance and surgical resection, as well as the interval of follow-up. Positron emission tomography/CT and brain magnetic resonance imaging (MRI) are not recommended for the diagnosis of SSNs, especially for pure GGNs. Periodic CT surveillance and lung-sparing surgery are the main strategies for the management of persistent SSNs. Nonsurgical treatment options for persistent SSNs include stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA). For multifocal SSNs, the timing of repeated CT scans and the need for surgical treatment are decided based on the most dominant SSN(s). Conclusions: The SSN is a heterogeneous disease and a personalized medicine approach is required in the future. Future studies of SSNs should focus on their natural history, optimal follow-up duration, genetic features, and surgical and nonsurgical treatments to improve the corresponding clinical management. All these efforts will lead to the personalized medicine approach for the SSNs.