Lepidic Predominant Adenocarcinoma Research Articles

Lepidic-predominant adenocarcinoma of the lung in an elderly cat with kidney failure

A long-haired, male, neutered domestic cat was referred to a veterinary clinic for the first time at 13 years of age due to anorexia, vomiting, dehydration, and depression. Blood biochemistry revealed renal azotemia. The cat was only given food for animals with kidney failure, and no treatment was given. Three weeks before its death at 16 years of age, the clinical signs returned, becoming more frequent and intense. The cat was referred to the veterinary clinic again, and also severe hypertension and mild dyspnea as the unique respiratory signs were detected. Blood biochemistry again revealed renal azotemia. At necropsy, the lungs exhibited a nodule in the right caudal lobe with a 3-cm-long axis and another nodule in the left caudal lobe with a 2-cm long axis, which histologically corresponded to a lepidic-predominant adenocarcinoma. The bronchioalveolar origin of the neoplasms was corroborated by immunohistochemistry with specific biomarkers, namely Thyroid Transcription Factor-1 (TTF-1), Napsin A, Surfactant Protein B (SP-B), Pancytokeratin and Vimentin, with the neoplastic tissue testing positive for all biomarkers. Both kidneys presented macroscopic and microscopic lesions consistent with nephritis and severe fibrosis, which was deemed to be the cause of death. Primary lung neoplasms in cats are rare and difficult to detect clinically due to clinic signs that may be nonspecific.

Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageⅠA lung cancer

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach

To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

Prognostic impact of noninvasive areas in resected pathological stage IA lung adenocarcinoma.

In non-small-cell lung cancer, ground-glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma. We analyzed 402 patients with pathological stage (p-Stage) IA lung adenocarcinoma who underwent surgery in 2013-2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity-score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p-T), p-Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non-LPA), the prognostic impact of NIAs was evaluated. Patients were divided into NIA-present (N = 231) and NIA-absent (N = 171) groups. Multivariable analysis showed that NIA-present was strongly associated with earlier p-T, earlier p-Stage, LPA, and epidermal growth factor receptor mutation. Kaplan-Meier survival analysis showed that the NIA-present group displayed a better prognosis than the NIA-absent group in disease-free survival (DFS) and overall survival (OS) (5-year DFS 94.6% vs. 87.2%, 5-year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA-present and NIA-absent groups (5-year DFS 92.4% vs 89.6%, 5-year OS 95.6% vs 94.3%). Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors.

Selective Mediastinal Lymph Node Dissection Strategy for Clinical T1N0 Invasive Lung Cancer: A Prospective, Multicenter, Clinical Trial

IntroductionWe aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC. MethodsThis is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10–12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an “inaccurate” case. ResultsA total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11–20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status. ConclusionsThis is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.

Clinicopathological features of patients with RET fusion-positive non-small cell lung cancer

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.

Radiomics for identifying lung adenocarcinomas with predominant lepidic growth manifesting as large pure ground-glass nodules on CT images.

PurposeTo explore the value of radiomics in the identification of lung adenocarcinomas with predominant lepidic growth in pure ground-glass nodules (pGGNs) larger than 10 mm.MethodsWe retrospectively analyzed CT images of 204 patients with large pGGNs (≥ 10 mm) pathologically diagnosed as minimally invasive adenocarcinomas (MIAs), lepidic predominant adenocarcinomas (LPAs), and non-lepidic predominant adenocarcinomas (NLPAs). All pGGNs in the two groups (MIA/LPA and NLPA) were randomly divided into training and test cohorts. Forty-seven patients from another center formed the external validation cohort. Baseline features, including clinical data and CT morphological and quantitative parameters, were collected to establish a baseline model. The radiomics model was built with the optimal radiomics features. The combined model was developed using the rad_score and independent baseline predictors. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. The differential diagnosis performance of the models was compared with three radiologists (with 20+, 10+, and 3 years of experience) in the test cohort.ResultsThe radiomics (training AUC: 0.833; test AUC: 0.804; and external validation AUC: 0.792) and combined (AUC: 0.849, 0.820, and 0.775, respectively) models performed better for discriminating than the baseline model (AUC: 0.756, 0.762, and 0.725, respectively) developed by tumor location and mean CT value of the whole nodule. The DeLong test showed that the AUCs of the combined and radiomics models were significantly increased in the training cohort. The highest AUC value of the radiologists was 0.600.ConclusionThe application of CT radiomics improved the identification performance of lung adenocarcinomas with predominant lepidic growth appearing as pGGNs larger than 10 mm.

Predictors of Invasiveness in Adenocarcinoma of Lung with Lepidic Growth Pattern.

Lung adenocarcinoma with lepidic growth pattern (LPA) is characterized by tumor cell proliferation along intact alveolar walls, and further classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (iLPA). Accurate diagnosis of lepidic lesions is critical for appropriate prognostication and management as five-year survival in patients with iLPA is lower than in those with AIS and MIA. We aimed to evaluate the accuracy of CT-guided core needle lung biopsy classifying LPA lesions and identify clinical and radiologic predictors of invasive disease in biopsied lesions. Thirty-four cases of adenocarcinoma with non-invasive lepidic growth pattern on core biopsy pathology that subsequently were resected between 2011 and 2018 were identified. Invasive LPA vs. non-invasive LPA (AIS or MIA) was defined based on explant pathology. Histopathology of core biopsy and resected tumor specimens was compared for concordance, and clinical, radiologic and pathologic variables were analyzed to assess for correlation with invasive disease. The majority of explanted tumors (70.6%) revealed invasive disease. Asian race (p = 0.03), history of extrathoracic malignancy (p = 0.02) and absence of smoking history (p = 0.03) were associated with invasive disease. CT-measured tumor size was not associated with invasiveness (p = 0.15). CT appearance of density (p = 0.61), shape (p = 0.78), and margin (p = 0.24) did not demonstrate a significant difference between the two subgroups. Invasiveness of tumors with lepidic growth patterns can be underestimated on transthoracic core needle biopsies. Asian race, absence of smoking, and history of extrathoracic malignancy were associated with invasive disease.

COUGH, FEVER, AND BILATERAL INFILTRATES ON IMAGING: WHAT CAN IT BE?

TYPE: Case Report TOPIC: Lung Cancer INTRODUCTION: Lepidic-predominant adenocarcinoma (LPA), is a subtype of invasive adenocarcinoma, histologically characterized by bland pneumocytic-type neoplastic cells with growth along with normal structures. Radiologic pattern is variable; most typical appearance being part-solid nodule or mass. However, it can also present as segmental or lobar consolidation, with a multifocal or diffuse pattern. We present a case of LPA which was being treated as recurrent pneumonia due to its clinical and radiologic presentation. CASE PRESENTATION: 67-year-old non-smoker male, without medical comorbidities presented with worsening cough, wheezing, shortness of breath that initially started a year ago. He stated having intermittent episodes of low-grade fever with night sweats. Patient was treated with multiple courses of antibiotics and steroids throughout the year which would provide intermittent symptomatic relief. He denied hemoptysis, leg swelling or any other associated symptoms. Patient used to work in cotton fields and denied having birds or pets. Computed tomographic imaging of chest showed bilateral infiltrates with air bronchograms, consolidations with minimal ground glass opacities and nodular infiltrates with some showing evidence of cavitation. Laboratory data and bronchoscopic cultures were non-diagnostic. Open lung biopsy revealed lepidic-predominant adenocarcinoma. DISCUSSION: Diagnosing LPA might be challenging due to its varied and non-specific symptomatology. Suspicion should be high in patients with recurrent, ongoing symptoms that fail to resolve with multiple courses of antibiotics and steroids. Timely diagnosis is the key to successful therapy and thereby, early biopsy should be considered. CONCLUSIONS: LPA may mimic pneumonia radiologically and symptomatically. Early biopsy is the key to establish timely diagnosis in such patients. DISCLOSURE: Nothing to declare. KEYWORD: Lepidic-predominant adenocarcinoma

Unusual presentation of lepidic adenocarcinoma in a healthy female

BackgroundLepidic adenocarcinoma represents a histologic pattern of non-small cell lung cancer that characteristically arises in the lung periphery with tracking alongside pre-existing alveolar walls. Noninvasive and invasive variants of lepidic adenocarcinoma are dependent on parenchymal destruction, vascular, or pleural invasion. The lepidic-predominant lung malignancies are collectively recognized as slow growing with rare metastasis and excellent prognosis. The World Health Organization classification of lung malignancies depends on molecular and histopathological findings. CT findings most commonly include ground-glass characteristics, commonly mistaken for inflammatory or infectious etiology. These tumors are generally surgically resectable and associated with better survival given infrequent nodal and extrathoracic involvement. Rarely these tumors present with diffuse pneumonic-type involvement associated with worse outcomes despite lack of nodal and distant metastases.Case presentationA 63-year-old Caucasian athletic immunocompetent female presented with 2 months of progressive shortness of breath, fatigue, loss of appetite and 15 pound weight loss. History was only notable for well controlled essential hypertension and hypothyroidism. Contrast computed tomography angiogram and positron emission tomography revealed diffuse hypermetabolic interstitial and airspace abnormalities of the lungs without lymphadenopathy (or distant involvement) in addition to right hydropneumothorax and left pleural effusion. Baseline laboratory testing was unremarkable, and extensive bacterial and fungal testing returned negative. Bronchoscopy and video-assisted thoracoscopic surgery was subsequently performed with pleural fluid cytology, lung and pleural biopsies returning positive for lepidic adenocarcinoma with 2% programmed death ligand 1 expression and genomic testing positive for PTEN gene deletion. Prior to treatment, the patient perished on day 15 of admission.ConclusionWe present a rare case of lepidic predominant adenocarcinoma with extensive bilateral aerogenous spread in the context of no lymphovascular invasion in a healthy, low risk patient. This case presentation may add to the body of knowledge regarding the different behavior patterns of lepidic predominant adenocarcinomas.

Serum tumor markers level and their predictive values for solid and micropapillary components in lung adenocarcinoma.

BackgroundThis study aims to reveal the serum tumor marker (STM) levels in lung adenocarcinoma (LUAD) histological subtypes and evaluate their values in predicting the solid and micropapillary components (SMC).MethodsWe retrospectively analyzed 3100 invasive LUAD patients between January 2017 and December 2020. Associations between preoperative STMs (CEA, CYFRA21‐1, CA199, CA724, NSE, AFP) and LUAD subtypes were evaluated. Multivariate regression analyses were used to determine the independent predictors. Predictive models for SMC were constructed and AUC (area under the curve) was calculated.ResultsCEA and CYFRA21‐1 levels differed across the LUAD histological subtypes, with the SPA (solid‐predominant adenocarcinoma) having the highest level and the LPA (lepidic‐predominant adenocarcinoma) harboring the lowest level (p <0.001). Tumors with SMC also had higher CEA and CYFRA21‐1 levels than those absence of SMC. Gender, tumor size, CEA, Ki‐67, EGFR mutation (solid components only), and tumor differentiation were significantly independently associated with the containing of SMC. Patients were split into two data sets (training set: 2017–2019 and validation set: 2020). The model with gender and tumor size yielded an AUC of 0.723 (training set) and 0.704 (validation set) for the solid component. Combination of CEA, gender, and tumor size led to a significant increase in the predictive accuracy (training set: 0.771, p = 0.009; validation set: 0.747, p = 0.034). The AUC of the model for micropapillary component with only gender and tumor size was 0.699 and 0.711 in the training set and validation set, respectively. Integration of CEA with gender and tumor size significantly improved the predictive performance with an AUC of 0.746 (training set, p = 0.045) and 0.753 (validation set, p <0.001).ConclusionSerum CEA and CYFRA21‐1 varied considerably according to LUAD histological subtypes. The combination of serum CEA and other factors showed prominent values in predicting the SMC.

Complete Lymphadenectomy for Clinical Stage I Lepidic Adenocarcinoma of the Lung: Is it justified?

The role of a systematic lymphadenectomy in patients undergoing surgery for clinical stage I lung lepidic adenocarcinoma is still unclear. In the last years, some authors have advocated the possibility to avoid a complete lymph-node dissection in this setting. Results of patients who received systematic hilar-mediastinal nodal dissection for this oncologic condition are here reported. Between 2012 and March 2019, 135 consecutive patients underwent lung resection for clinical stage I lepidic adenocarcinoma, at our institution. Only patients (n = 98) undergoing lobectomy or sublobar resection associated with systematic hilar-mediastinal nodal dissection were retrospectively enrolled in the study. Patients' mean age was 67.8 ± 8.7 years (range 37-84). Three were 52 females and 46 males. Resection was lobectomy in 77.6% (n = 76) and sublobar in 22.4% (n = 22). All the resections were complete (R0). Histology was lepidic predominant adenocarcinoma in 85 cases and minimally invasive adenocarcinoma in 13 cases. At pathologic examination, N0 was confirmed in 78 patients (79.6%), while N+ was found in 20 cases (20.4%), (N1 in 12, 12.2% and N2 in 8, 8.2%). No mortality occurred. Complication rate was 8.2%. At a median follow-up of 45.5 months, recurrence rate was 26.5%. Disease-free 5-year survival was 98.6% for stage I, 75% for stage II and 45% for stage III, p < 0.001. A complete nodal dissection can reveal occult nodal metastases in lepidic adenocarcinoma patients and can increase the accuracy of pathologic staging. N1/N2 disease is a negative prognostic factor for this histology. A systematic lymph-node dissection should be considered even in this setting.

HRCT features between lepidic-predominant type and other pathological subtypes in early-stage invasive pulmonary adenocarcinoma appearing as a ground-glass nodule

BackgroundDifferent pathological subtypes of invasive pulmonary adenocarcinoma (IPA) have different surgical methods and heterogeneous prognosis. It is essential to clarify IPA subtypes before operation and high-resolution computed tomography (HRCT) plays a very important role in this regard. We aimed to investigate the HRCT features of lepidic-predominant type and other pathological subtypes of early-stage (T1N0M0) IPA appearing as a ground-glass nodule (GGN).MethodsWe performed a retrospective analysis on clinical data and HRCT features of 630 lesions in 589 patients with pathologically confirmed IPA (invasive foci > 5 mm) appearing as pure GGN (pGGN) and mixed GGN (mGGN) with consolidation-to-tumor ratio (CTR) ≤0.5 from January to December 2019. All GGNs were classified as lepidic-predominant adenocarcinoma (LPA) and nonlepidic-predominant adenocarcinoma (n-LPA) groups. Univariate analysis was performed to analyze the differences of clinical data and HRCT features between the LPA and n-LPA groups. Multivariate analysis was conducted to determine the variables to distinguish the LPA from n-LPA group independently. The diagnostic performance of different parameters was compared using receiver operating characteristic curves.ResultsIn total, 367 GGNs in the LPA group and 263 GGNs in the n-LPA group were identified. In the univariate analysis, the CTR, mean CT values, and mean diameters as well as mixed GGN, deep lobulation, spiculation, vascular change, bronchial change, and tumor–lung interface were smaller in the LPA group than in the n-LPA group (P < 0.05). Logistic regression model was reconstructed including the mean CT value, CTR, deep lobulation, spiculation, vascular change, and bronchial change (P < 0.05). Area under the curve of the logistic regression model for differentiating LPA and n-LPA was 0.840 (76.4% sensitivity, 78.7% specificity), which was significantly higher than that of the mean CT value or CTR.ConclusionsDeep lobulation, spiculation, vascular change, and bronchial change, CT value > − 472.5 HU and CTR > 27.4% may indicate nonlepidic predominant invasive pulmonary adenocarcinoma in GGNs.

A radiomics model can distinguish solitary pulmonary capillary haemangioma from lung adenocarcinoma.

OBJECTIVESSolitary pulmonary capillary haemangioma (SPCH) is a benign lung tumour that presents as ground-glass nodules on computed tomography (CT) images and mimics lepidic-predominant adenocarcinoma. This study aimed to establish a discriminant model using a radiomic feature analysis to distinguish SPCH from lepidic-predominant adenocarcinoma.METHODSIn the adenocarcinoma group, all tumours were of the lepidic-predominant subtype with high purity (>70%). A classification model was proposed based on a two-level decision tree and 26 radiomic features extracted from each segmented lesion. For comparison, a baseline model was built with the same 26 features using a support vector machine as the classifier. Both models were assessed by the leave-one-out cross-validation method.RESULTSThis study included 13 and 49 patients who underwent complete resection for SPCH and adenocarcinoma, respectively. Two sets of features were identified for discrimination between the 2 different histology types. The first set included 2 principal components corresponding to the 2 largest eigenvalues for the root node of the two-level decision tree. The second set comprised 4 selected radiomic features. The area under the receiver operating characteristic curve, accuracy, sensitivity, specificity were 0.954, 91.9%, 92.3% and 91.8% in the proposed classification model, and were 0.805, 85.5%, 61.5% and 91.8% in the baseline model, respectively. The proposed classification model significantly outperformed the baseline model (P < 0.05).CONCLUSIONSThe proposed model could differentiate the 2 different histology types on CT images, and this may help surgeons to preoperatively discriminate SPCH from adenocarcinoma.

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.

Value of PET/CT Combined with CT Three-dimensional Reconstruction in Distinguishing Different Pathological Subtypes of Early Lung Adenocarcinoma

背景与目的早期肺腺癌中病理亚型以贴壁为主型的浸润性腺癌（lepidic predominant invasive adenocarcinoma, LPA）与原位腺癌（adenocarcinoma in situ, AIS）、微浸润性腺癌（microinvasive adenocarcinoma, MIA）的良好预后相似，临床上也迫切需要能够区分LPA与非LPA型浸润性腺癌（non-lepidic predominant invasive adenocarcinoma, non-LPA）的手段，本研究拟通过正电子发射型计算机断层显像（positron emission computed tomography, PET）/计算机断层扫描（computed tomography, CT）的最大标准化摄取值（maximal standard uptake value, SUVmax）和CT三维重建后参数探讨术前影像学表现为部分实性结节（part-solid nodules, PSNs）的早期肺腺癌不同病理亚型间的关系。方法回顾性分析2016年1月-2019年1月于江苏省苏北人民医院胸外科行解剖性肺切除术且影像学表现为PSNs的早期肺腺癌患者资料，所有患者胸部增强CT和PET/CT资料完整可获取，利用Mimics软件行三维重建，获取肿瘤体积、肿瘤三维平均CT值（3-dimensional mean-CT value, 3Dm-CT）、SUVmax等数据，采用SPSS 25.0进行统计分析，GraphPad Prism 8.3.0绘制受试者工作曲线（receiver operating curve, ROC），P < 0.05为差异有统计学意义。结果最终共计67例患者纳入本研究，按病理亚型不同将所有患者分为两组，AIS、MIA及浸润性腺癌（invasive adenocarcinoma, IAC）中的LPA归为低危组28例（41.8%），其余non-LPA如腺泡型（acinar pattern-predominant adeno-carcinoma, APA）、乳头型（papillary pattern-predominant adenocarcinoma, PPA）、微乳头型（micropapillary pattern-predominant adeno-carcinoma, MPA）归为高危组39例（58.2%），两组间SUVmax（t=3.153, P=0.002）、肿瘤体积（t=3.331, P=0.001)、实性/磨玻璃成分体积（t=2.74, P=0.006) /（t=3.127, P=0.002）、实性/磨玻璃成分3Dm-CT（t=3.655, P < 0.001) /（t=7.082, P < 0.001) 均具有显著统计学意义。ROC曲线提示：SUVmax[曲线下面积（area under curve, AUC）=0.727]、肿瘤体积（AUC=0.740）、磨玻璃成分体积（AUC=0.725）、实性成分3Dm-CT（AUC=0.763）、磨玻璃成分3Dm-CT（AUC=0.756）预测效能最佳。将上述AUC > 0.7的协变量纳入多因素ROC曲线分析，获得联合预测因子（AUC=0.835）具有中等以上预测价值。结论PET/CT中SUVmax和CT三维重建参数与影像学表现为PSNs的早期肺腺癌的不同病理亚型具有显著相关性，联合SUVmax、肿瘤体积、磨玻璃成分体积和实性/磨玻璃成分3Dm-CT对鉴别表现为PSNs的早期肺腺癌的病理亚型具有一定价值。

Invasive adenocarcinoma manifesting as pure ground glass nodule with different size: radiological characteristics differ while prognosis remains the same.

BackgroundInvasive adenocarcinoma (IA) manifesting as pure ground-glass nodule is rare and not been well studied. Meanwhile, tumor size is considered as a predictor of invasiveness in lung adenocarcinoma. The present study aimed to investigate the radiological and pathological characteristics as well as prognosis of IA manifesting as pure ground-glass nodule with different sizes.MethodsPatients with solitary pure ground glass nodule (GGN) who underwent resection and were pathologically diagnosed as IA between July 2013 and July 2015 were included. Nodules were divided into four groups according to size: A, B, C, and D, corresponding to “≤1 cm,” “1–2 cm,” “2–3 cm,” and “>3 cm,” respectively. The correlations and differences in radiological and pathological characteristics as well as prognosis among these groups were analyzed.ResultsThe amounts of nodules in groups A, B, C, and D are 17, 148, 78, and 30, respectively. The average diameter of these 273 nodules is 1.9 (1.5–2.4) cm. A large tumor is likely to have low computed tomography (CT) value (P<0.001), irregular shape (P=0.001), spiculation appearance (P<0.001) and exhibit pleural indentation (P<0.001) and air bronchogram (P<0.001). The proportion of lepidic predominant adenocarcinoma (LPA) (n=239, 87.5%) is much higher than that of other subtypes (n=34, 12.5%). Currently, there is no case with lymphatic, pleural, or vessel invasion and lymph node involvement, and none died of recurrence or metastasis within 5 years after resection.ConclusionsFor IA manifesting as pure ground-glass nodule, size is correlated to invasiveness, and large tumors tend to have lower CT value, an irregular shape, lobulation and spiculation appearance and exhibit pleural indentation and air bronchogram. Nevertheless, the prognosis is excellent with 100% 5-year disease-free survival regardless of the size and pathological subtype.

Assessment of relationships among clinicopathological characteristics, morphological computer tomography features, and tumor cell proliferation in stage I lung adenocarcinoma.

BackgroundSurgically resected stage I lung adenocarcinoma (ADC) has wide variation in prognosis. It is significant to identify high-risk patients and optimize therapeutic strategy. This study aimed to investigate the relationships among histological grade, serum tumor marker index (TMI), morphological computer tomography (CT) features, and a well-established prognosticator cell proliferation (Ki-67) in stage I ADC.MethodsPreoperative CT was performed in 182 patients with stage I ADC confirmed by pathology. The Ki-67 expression was acquired by immunohistochemistry. TMI was the square root of standardized serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) values. Tumor shadow disappearance rate (TDR) and other morphological CT features were interpreted by two radiologists. Histological grade, TMI, CT features were statistically evaluated to explore the associations with Ki-67 expression.ResultsIn univariate analysis, gender, smoking history, pack-year, histological grade, TNM stage (IA and IB), serum CEA and CYFRA 21-1 status, TMI status, as well as TDR, long-axis diameter, short-axis diameter, lobulation, spiculation, attenuation types, vacuolation, vascular invasion, vascular convergence, thickened bronchovascular bundles, pleural attachment and peripheral fibrosis were significantly associated with Ki-67 expression (all P<0.05). Solid-predominant ADC had the highest Ki-67 expression, followed by micropapillary, papillary and acinar-predominant ADC, while lepidic-predominant ADC had the lowest Ki-67 expression (P<0.001). TDR was negatively correlated with Ki-67 (r =−0.478, P<0.001). Multivariate logistic regression analysis revealed that gender, histological grade, TDR and attenuation types were independent factors associated with Ki-67 expression.ConclusionsKi-67 expression differed distinctly according to ADC histological subtypes. High Ki-67 expression is independently associated with male patients of stage I ADC with worse differentiation, lower TDR and solid tumors, which might be of prognostic value for poor prognosis in stage I ADC.

Pathological features and prognostic implications of ground-glass opacity components on computed tomography for clinical stage I lung adenocarcinoma.

To investigate the prognostic implications and pathological features of clinical stage I lung adenocarcinoma with ground-glass opacity (GGO) on computed tomography (CT). The subjects of this retrospective study were 1228 patients with lung adenocarcinoma classified as clinical stage I, who underwent complete resection by lobectomy. The patients were divided into four groups based on the presence and proportion of GGO according to the consolidation-to-tumor ratio (CTR); A, CTR ≤ 0.5; B, 0.5 < CTR ≤ 0.75; C, 0.75 < CTR ≤ 1.0 with GGO; D, without GGO (pure-solid). We compared overall survival, pathological findings (N/ly/v/STAS), and histological subtypes within each clinical stage among the four groups. We found no significant differences among tumors with GGO (groups A, B and C) for prognosis or pathological findings in all the clinical stages. The prognoses of groups A, B and C were significantly better than that of group D for patients with clinical stages IA2-IB disease. Tumors without GGO on CT had a significantly larger number of positive N, ly, v and STAS in almost all stages than tumors with GGO on CT. Tumors without GGO on CT had significantly more solid predominant and less lepidic predominant adenocarcinoma. Not the proportion of GGO, but its presence on CT, as well as the size of the solid component, were correlated significantly with pathological characteristics and survival.

Tumor cell proliferation (Ki-67) expression and its prognostic significance in histological subtypes of lung adenocarcinoma

ObjectivesKi-67 is a key molecular marker to indicate the proliferative activity of tumor cells in lung cancer. However, Ki-67 expression and its prognostic significance in histological subtypes of lung adenocarcinoma (LUAD) remain unclear. Materials and MethodsWe retrospectively analyzed 1028 invasive LUAD patients who underwent surgery treatment between January 2012 and April 2020 in our department. Associations between Ki-67 expression and histological subtypes of LUAD, as well as other clinicopathological characteristics, were evaluated. The prognostic role of Ki-67 in LUAD subtypes was further assessed using log-rank test and univariate/multivariate Cox proportional hazards regression analyses. ResultsKi-67 expression differed across LUAD histological subtypes. The solid-predominant adenocarcinoma (SPA, 46.31 ± 24.72) had the highest expression level of Ki-67, followed by micropapillary (MPA, 31.71 ± 18.14), papillary (PPA, 22.09 ± 19.61), acinar (APA, 19.73 ± 18.71) and lepidic-predominant adenocarcinoma (LPA, 9.86 ± 8.10, P < 0.001). Tumors with solid or micropapillary components also had a higher Ki-67 expression than those without solid or micropapillary components. Besides, males, smokers, larger tumor size, lymph node metastasis and EGFR wild type were correlated with elevated Ki-67 expression. Univariate analysis indicated that increased Ki-67 expression and MPA/SPA subtypes were significantly associated with a poorer prognosis. Notably, the survival differences between LUAD subtypes vanished after adjusting for tumor size and Ki-67 expression in multivariate analysis, while Ki-67 was an independent prognostic factor of LUAD. Patients with MPA/SPA had non-inferior overall and disease-free survival than LPA/APA/PPA patients with a Ki-67 expression comparable to MPA/SPA subjects. ConclusionKi-67 expression varied considerably according to the predominant histological subtypes of LUAD. Ki-67 expression level and tumor size contributed to the survival differences between LUAD histological subtypes.