Peripheral Lung Adenocarcinoma Research Articles

Early detection and early treatment of lung cancer: risks and benefits.

The paper by Zhu and colleagues (1) on the clinical characteristics of primary peripheral lung adenocarcinomas is notable for showing that lesions up to 1 cm in diameter have different clinical characteristics to, and better survival than, lesions 1.1–2.0 cm. The authors coined the term “micro-sized” to describe these adenocarcinomas up to 1 cm, and suggested they might be adequately treated by sublobar resection without mediastinal lymph node dissection.

Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung.

BackgroundThe detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA.MethodsThe tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed.ResultsThe concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03).ConclusionThe tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas.

Radiomic Features Are Associated With EGFR Mutation Status in Lung Adenocarcinomas

BackgroundIn this study we retrospectively evaluated the capability of computed tomography (CT)-based radiomic features to predict epidermal growth factor receptor (EGFR) mutation status in surgically-resected peripheral lung adenocarcinomas in an Asian cohort of patients. Patients and MethodsTwo hundred ninety-eight patients with surgically resected peripheral lung adenocarcinomas were investigated in this institutional review board-approved retrospective study with requirement waived to obtain informed consent. Two hundred nineteen quantitative 3-D features were extracted from segmented volumes of each tumor, and 59 of these, which were considered independent features, were included in the analysis. Clinical and pathological information was obtained from the institutional database. ResultsMutant EGFR was significantly associated with female sex (P = .0005); never smoker status (P < .0001), lepidic predominant adenocarcinomas (P = .017), and low or intermediate pathologic grade (P = .0002). Statistically significant differences were found in 11 radiomic features between EGFR mutant and wild type groups in univariate analysis. Mutant EGFR status could be predicted by a set of 5 radiomic features that fell into 3 broad groups: CT attenuation energy, tumor main direction, and texture defined according to wavelets and Laws (area under the curve [AUC], 0.647). A multiple logistic regression model showed that adding radiomic features to a clinical model resulted in a significant improvement of predicting power, because the AUC increased from 0.667 to 0.709 (P < .0001). ConclusionComputed tomography-based radiomic features of peripheral lung adenocarcinomas can capture useful information regarding tumor phenotype, and the model we built can be useful to predict the presence of EGFR mutations in peripheral lung adenocarcinoma in Asian patients when mutational profiling is not available or possible.

Value of Ki-67 and computed tomography in the assessment of peripheral lung adenocarcinoma

Purpose: This study was designed to determine whether proliferation antigen Ki-67 and/or a computed tomography (CT) value could be used to evaluate the clinical-pathological features of peripheral lung adenocarcinoma.Materials and methods: A total of 116 eligible lung cancer patients were enrolled. Nodule size, lymph node metastasis, differentiation, Ki-67 expression and CT findings were assessed. The relationship between clinic parameters and the CT feature was analysed statistically.Results: The percentage of lesions that had ground-glass opacity or localised air bronchogram was significantly greater in low CT value group (<30, p < 0.05). No significant association was observed between CT value and size in the subgroup with CT value > 0 (p = 0.66). As a proliferative marker of lung cancer, Ki-67 was present in a total of 115 (99.9%) of the 116 evaluable primary lung cancers. There was a statistically significant correlation between the Ki-67 index and CT value (p < 0.05). Compared to CT value, Ki-67 index possessed higher sensitivity to predict the differentiation and lymph node metastasis of peripheral lung adenocarcinoma, adding of CT value would enhance its specificity.Conclusion: Combination of Ki-67 expression and CT value determination was useful for the classification of differentiation and metastatic or proliferative potential of peripheral lung adenocarcinoma.

Precise Diagnosis of Intraoperative Frozen Section Is an Effective Method to Guide Resection Strategy for Peripheral Small-Sized Lung Adenocarcinoma.

This study investigated the accuracy of intraoperative frozen section (FS) diagnosis for predicting the final pathology (FP) of peripheral small-sized lung adenocarcinoma and evaluated its usefulness in sublobar resection. The records of 803 patients with clinical stage I peripheral lung adenocarcinoma who underwent sublobar resection for FS diagnosis to guide surgical strategy were reviewed. The surgical extension was mainly based on FS. The FS were stratified into atypical adenomatous hyperplasia, adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma. The diagnostic accuracy of FS, the reasons for the discrepancy between FS and FP, and the clinical influence of the FS errors were evaluated. To assess the survival of patients with different subtypes after surgery, 301 patients were identified for prognosis evaluation. The total concordance rate between FS and FP was 84.4%. When atypical adenomatous hyperplasia, AIS, and MIA were classified together as a low-risk group, the concordance rate was 95.9%. Most discrepant cases were the underestimation of AIS and MIA. The diagnostic accuracy of FS for tumors ≤ 1 cm and larger than 1 cm in diameter was 79.6% and 90.8%, respectively (P < .01). The FS errors had significant clinical impact on 0.9% of the 803 patients due to insufficient resection. The 5-year recurrence-free survival rate (100%) was significantly better for the patients with AIS/MIA than for patients with invasive adenocarcinoma (74.1%, P < .01). Frozen pathology has a high concordance rate with FP. Precise diagnosis by intraoperative FS is an effective method to guide resection strategy for peripheral small-sized lung adenocarcinoma.

Expression and prognostic value of GalNAc-T3 in patients with completely resected small (≤2 cm) peripheral lung adenocarcinoma after IASLC/ATS/ERS classification.

BackgroundGalNAc-T3 catalyzes initial glycosylation of mucin-type O-linked protein involved in proliferation, adhesion, and migration of tumor cells. This study was performed to explore the relationships of the expression of GalNAc-T3 in small peripheral lung adenocarcinoma, especially as an indicator of prognosis.Materials and methodsA retrospective analysis of the patients with small peripheral lung lesions, including 106 adenocarcinoma and two precancerous lesions (atypical adenomatous hyperplasia and adenocarcinoma in situ) after complete surgical resection, was launched. Expression of GalNAc-T3 was examined using immunohistochemistry staining on primary tumor specimens, and the tumors were reclassified in light of the IASLC/ATS/ERS (International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society) adenocarcinoma classifications followed by grading and scoring. Moreover, reverse transcription polymerase chain reaction and Western blot were used to study the expression of GalNAc-T3 in vivo.ResultsThe low expression of GalNAc-T3 was found in the cytoplasm of tumor cells in 56 of 108 patients (51.9%) and was associated with IASLC/ATS/ERS classification of high risk groups (P=0.007), high Sica score (P=0.036), poorly differentiated tumor (P=0.023), poor tumor-node-metastasis (TNM) stage (P=0.007), pleural invasion (P=0.007), and vascular invasion (P<0.001) by Pearson’s chi-squared test, but not with sex, age, smoking status, concentration of carcinoembryonic antigen, and lymph node metastasis. In logistic regression analysis, low GalNAc-T3 expression was only correlated with high-ranking TNM stage (odds ratio [OR] =8.975, 95% confidence interval [CI]: 1.797–44.661), vascular invasion (OR =5.668, 95% CI: 1.827–17.578), and the higher risk grade (low risk grade: OR =0.141, 95% CI: 0.027–0.719; moderate risk grade: OR =0.122, 95% CI: 0.017–40.871). The low expression of the GalNAc-T3 usually in adenocarcinoma cell lines was compared with normal bronchial epithelium cell line. Based on the univariate and multivariate analysis, poor TNM stage (P<0.001), pleural invasion (hazard ratio [HR]: 7.958, P=0.021), vascular invasion (HR: 2.403, P=0.040), and low GalNAc-T3 expression (HR: 3.317, P=0.016) were shown to be independently associated with an unfavorable prognosis. However, IASLC/ATS/ERS classification of risk groups and Sica score (P=0.034 and P=0.032, respectively) was correlated with overall survival on Kaplan–Meier method but not Cox regression model.ConclusionGalNAc-T3 expression was correlated with the IASLC/ATS/ERS classification and also associated with prognosis of patients with completely resected small (≤2 cm) peripheral lung adenocarcinoma.

Clinical characteristics and advantages of primary peripheral micro-sized lung adenocarcinoma over small-sized lung adenocarcinoma.

Micro-sized lung adenocarcinoma with a tumour of 1.0 cm or less could help identify the patients who would undergo the surgery treatment with limited resection; however, its clinical characteristics and survival rates remain unclear and are to be tested further. Histology, lymphatic metastasis, surgical procedure and survival rates of 366 lung adenocarcinoma patients (from January 2007 to December 2013) with a tumour of 2.0 cm or less were analysed retrospectively. Among these patients, 175 had a primary tumour with a diameter of 1.0 cm or less and 191 had a tumour of 1.1-2.0 cm. The survival of 366 patients was evaluated by the restricted mean survival time (RMST) test, and the risk factors were assessed by multivariable analysis. Larger lesion had a significant relation to old age, male sex, preoperatively carcinoembryonic antigen (CEA) positive, invasive adenocarcinoma (IAC) and advanced-stage disease (P < 0.0001, P = 0.001, P = 0.001, P < 0.0001 and P < 0.0001, respectively). Patients with adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma obtained a better prognosis than those with IAC (5-year overall survival rate: 98.5 vs 84.3%, P = 0.001; disease-related survival rate: 98.5 versus 85.2%, P = 0.001). The 5-year overall survival rates of patients with a tumour less than 1.0 cm in comparison with 1.1-2.0 cm were 100.0 and 88.4% (P < 0.001), whereas the 5-year lung adenocarcinoma-specific survival rates were 100.0 and 89.0% (P < 0.001), respectively. Multivariable analysis for prognosis of lung adenocarcinoma patients with a tumour 2.0 cm or less in diameter revealed that histology, lymphatic metastasis and advanced pathological stage affected the 5-year overall and disease-related survival rates unfavourably (P < 0.0001, 0.002, 0.001; and P < 0.0001, 0.005, 0.001, respectively), whereas tumour size did not have an obvious influence on survival. Micro-sized lung adenocarcinoma (1.0 cm or less) had specific clinical characteristics and more favourable survival rates. These tumours and a subtype of AIS evaluated by computed tomography images or intraoperative frozen section may be appropriate candidates for a limited resection without mediastinal lymph node dissection.

P0122 The unique pathological characteristics and prognostic significance of primary lung adenocarcinoma of 1 cm or less in size

Background Diagnosis and treatment of lung cancer at an early stage improves the prognosis of the patients. This study assessed prognosis in peripheral lung cancer according to tumour size (dimensions of 2.0 cm or less). Methods A retrospective analysis was done to analyse the clinical pathological features and CT signs in 429 patients with peripheral lung cancer with different tumour sizes (0.5–1.0 cm, 1.1–1.5 cm, and 1.6–2.0 cm). Findings The main subtype of peripheral lung cancer with tumour size of 2 cm or less was adenocarcinoma. Different tumour sizes of peripheral lung adenocarcinoma had significant differences in clinical pathological stage, serum level of carcinoembryonic antigen (CEA), CT signs and tumour subtypes (p Interpretation Different tumour sizes (2.0 cm or less) in lung adenocarcinoma have different clinical pathological characteristics. Overall survival and 5-year survival for lung adenocarcinoma of 1.0 cm or less was higher than in larger tumours, thus early diagnosis and treatment of micro-sized lung cancer is clinically important.

Correlation of thin-section CT morphologic features and pathological vascular invasion in the clinical stage IA peripheral lung adenocarcinoma

Objective To evaluate the correlation between thin-section CT morphologic features and pathological vascular invasion in the clinical stage IA peripheral lung adenocarcinoma. Methods The preoperative thin-section CT images, clinical and pathological characteristics of 102 nodules in 98 patients were retrospectively analyzed and divided into two groups according to pathological vascular invasion. Variables including the diameter of tumor(T) and consolidation part (C) in the mix ground glass nodule(mGGN), C/T ratio, morphology and pathological classification were analyzed by two-independent samples Mann-Whitney U test or t test and χ2 test or Fisher exact probability test. Variables with significant difference in the univariate analyses were entered into multivariate analysis to explore predictors for vascular invasion.The correlation between these measurements and vascular invasion was evaluated by a ROC analysis. Results All of 102 nodules,36 had pathological vascular invasion and 66 without.The numbers of two groups with speculation, air bronchogram,abnormal vein,vascular convergence, pleural indentation were 30,30;26,26;35,3;35,39;32,39 and the mediandiameter of tumors were 2.1(1.0–3.0), 1.2(0.5–3.0) cm respectively. By univariateanalysis,spiculation, air bronchogram, abnormal vein, vascular convergence, pleural indentation, and diameter of tumor were significantly associated with pathological vascularinvasion(P<0.01).By multivariate logistic analysis, the statistically significant difference were found in speculation and abnormal vein(OR=33.867,8 161.063,P<0.05).The ROC analysis showed the area under curve, cut-off value, sensitivity and specificity ofthe diameter of tumor and consolidation part of mGGN and C/T ratio were 0.784, 2.05 cm, 66.7%, 78.8%; 0.886,1.08 cm, 82.4%, 90.0% and 0.861, 0.65, 79.4%, 85.0% respectively in differentiating tumors with pathological vascular invasion. Conclusion The spiculation sign and abnormal vein are independent predictors for vascular invasion in stage IA peripheral lung adenocarcinoma. Key words: Lung neoplasms; Adenocarcinoma; Tomography, X-ray computed

The revised lung adenocarcinoma classification-an imaging guide.

Advances in our understanding of the pathology, radiology and clinical behaviour of peripheral lung adenocarcinomas facilitated a more robust terminology and classification of these lesions. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification introduced new terminology to better reflect this heterogeneous group of adenocarcinomas formerly known as bronchoalveolar cell carcinoma (BAC). There is now a clear distinction between pre-invasive, minimally invasive and frankly invasive lesions. The radiographic appearance of these ranges from pure ground glass nodules to solid mass lesions. Radiologists must be aware of the new classification in order to work alongside multidisciplinary colleagues to allow accurate staging and treatment. This article reviews the new classification of lung adenocarcinomas. Management options of these lesions with particular focus on radiological implications of the new classification will be reviewed.

A preliminary study on prognosis of polypeptide-N-acetylgalactosaminyl transferase 3 to forecast patients with small peripheral lung adenocarcinoma

Objective To explore the expression of UDP-N-acetyl-alpha-D-Galactosamine:polypeptide-N-acetylgalactosaminyl transferase 3 (GalNAc-T3) and prognosis factors in small peripheral lung adenocarcinoma (＜ 2 cm).Methods The clinical data of 108 patients with lung adenocarcinoma who underwent complete surgical resection were collected between January 2006 and June 2009,and had detailed clinical follow-up information.The GalNAc-T3 expression in the primary lung adenocarcinoma specimens was detected by using immunohistochemistry (IHC).The clinical characteristics and outcomes in patients were analysed.Results The rate of low expression of GalNAc-T3 was 40.7％,and its was associated with poorly differentiated tumour (P ＜ 0.05),pleural invasion (P ＜ 0.05),lymphatic invasion (P =0.05),vascular invasion (P ＜ 0.01) and Noguchi' s subtypes (P ＜ 0.01),but not with gender,ages,concentration of carcinoembryonic antigen(CEA) and pTNM (P ＞ 0.05).Univariate survival ananlysis revealed aht Noguchi' s subtypes (x2 =4.845,P ＜ 0.05),pleural invasion (x2 =15.975,P ＜ 0.01),and low expression of GalNAc-T3 (x2 =8.830,P ＜ 0.01) were correlated with prognosis.In addition,the low expression of GalNAc-T3 [relative risk (RR) =4.030,95％ confidence interval (CI):1.284-12.647) and pleural invasion (RR =0.187,95％ CI:0.063-0.550) were significant independent prognosis factors in small peripheral adenocarcinomas patients.Conclusion The low expression of GalNAc-T3 was associated with poorly differentiated tumour,pleural invasion,lymphatic invasion,vascular invasion and Noguchi's subtypes,and may be a useful marker for predicting prognosis in small peripheral adenocarcinomas patients. Key words: Polypeptide-N-acetylgalactosaminyl transferase 3; Lung adenocarcinoma; Prognosis

Recommendations for the Management of Subsolid Pulmonary Nodules Detected at CT: A Statement from the Fleischner Society

This report is to complement the original Fleischner Society recommendations for incidentally detected solid nodules by proposing a set of recommendations specifically aimed at subsolid nodules. The development of a standardized approach to the interpretation and management of subsolid nodules remains critically important given that peripheral adenocarcinomas represent the most common type of lung cancer, with evidence of increasing frequency. Following an initial consideration of appropriate terminology to describe subsolid nodules and a brief review of the new classification system for peripheral lung adenocarcinomas sponsored by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), six specific recommendations were made, three with regard to solitary subsolid nodules and three with regard to multiple subsolid nodules. Each recommendation is followed first by the rationales underlying the recommendation and then by specific pertinent remarks. Finally, issues for which future research is needed are discussed. The recommendations are the result of careful review of the literature now available regarding subsolid nodules. Given the complexity of these lesions, the current recommendations are more varied than the original Fleischner Society guidelines for solid nodules. It cannot be overemphasized that these guidelines must be interpreted in light of an individual's clinical history. Given the frequency with which subsolid nodules are encountered in daily clinical practice, and notwithstanding continuing controversy on many of these issues, it is anticipated that further refinements and modifications to these recommendations will be forthcoming as information continues to emerge from ongoing research.

Adenocarcinomas with Predominant Ground-Glass Opacity: Correlation of Morphology and Molecular Biomarkers

To retrospectively identify successive changes in peripheral lung adenocarcinoma that feature dominant ground-glass opacity (GGO) at computed tomography (CT) and correlate with biomolecular markers. The institutional review board approved this retrospective study, and all 25 patients provided informed consent. Patients with lung adenocarcinomas smaller than 3 cm in diameter in whom tumor growth could be evaluated with CT before surgery were included. Two thoracic radiologists evaluated tumor growth by analyzing GGO type (pure or mixed) and size increases. Immunohistochemistry of the p53 protein and molecular analysis of the epidermal growth factor receptor (EGFR) and K-ras genes were performed. The Fisher exact test was used to assess statistical significance. Tumor size increased in 19 of 25 patients (76%) during the observation period. The CT changes in 19 patients were classified into four patterns: persistent pure GGO (n = 8), change from pure to mixed GGO (n = 3), mixed GGO with growth of solid component (n = 4), and mixed GGO with growth of GGO component (n = 4). The remaining six patients (24%) had pure GGO without any interval changes. Staining for p53 was negative in all 14 patients with pure GGO and positive in six of 11 patients (55%) with mixed GGO (P < .01). In these six patients appearance or growth of the solid component was seen. EGFR mutations were found in both pure (36%) and mixed (45%) GGO lesions (P = .70). Lung adenocarcinomas with a dominant GGO often possess EGFR mutations. Interval changes in the solid component may be related to p53 inactivation.

Small peripheral lung adenocarcinoma: CT and histopathologic characteristics and prognostic implications.

Since the introduction of computed tomography (CT), detection of small lung cancer, especially small peripheral adenocarcinoma, is common. Recently, the morphological characteristics, including thin-section CT and pathologic findings, and prognosis of small peripheral lung adenocarcinomas have been studied extensively. The radiologic and microscopic findings correlate well with each other and are closely associated with tumour prognosis. Most importantly, some subtypes of small lung adenocarcinomas with specific CT or pathologic features are curable. Therefore, all defining characteristics (CT, pathologic and prognostic) of this kind of tumour should be integrated to improve our understanding, provide guidelines for management and accurately assess its prognosis.

DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in situ, and lung adenocarcinoma.

BackgroundAberrant DNA methylation is common in lung adenocarcinoma, but its timing in the phases of tumor development is largely unknown. Delineating when abnormal DNA methylation arises may provide insight into the natural history of lung adenocarcinoma and the role that DNA methylation alterations play in tumor formation.Methodology/Principal FindingsWe used MethyLight, a sensitive real-time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG islands that are frequently methylated in lung adenocarcinoma and that we had flagged as potential markers for non-invasive detection. We also used two repeat probes as indicators of global DNA hypomethylation. We examined DNA methylation in 249 tissue samples from 93 subjects, spanning the putative spectrum of peripheral lung adenocarcinoma development: histologically normal adjacent non-tumor lung, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS, formerly known as bronchioloalveolar carcinoma), and invasive lung adenocarcinoma. Comparison of DNA methylation levels between the lesion types suggests that DNA hypermethylation of distinct loci occurs at different time points during the development of lung adenocarcinoma. DNA methylation at CDKN2A ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at 2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML, RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present predominantly in invasive cancer.Conclusions/SignificanceThe gradual increase in DNA methylation seen for numerous loci in progressively more transformed lesions supports the model in which AAH and AIS are sequential stages in the development of lung adenocarcinoma. The demarcation of DNA methylation changes characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible roadmap for aberrant DNA methylation events in tumor development. In addition, it identifies which DNA methylation changes might be used as molecular markers for the detection of preinvasive lesions.

A Prospective Radiological Study of Thin-Section Computed Tomography to Predict Pathological Noninvasiveness in Peripheral Clinical IA Lung Cancer (Japan Clinical Oncology Group 0201)

Pathological noninvasiveness needs to be precisely predicted in preoperative radiological examinations of patients with early lung cancer for the application of limited surgery. Patients with clinical T1N0M0 peripheral lung cancer were recruited. Radiological findings of the main tumor were evaluated as to ground-glass opacity with thin-section computed tomography. The primary end point was specificity, i.e., the proportion of patients with radiologically diagnosed invasive lung cancer to patients with pathologically diagnosed invasive lung cancer. The precision-based planned sample size was 450. We expected that the lower limit of the 95% confidence interval (CI) for specificity should be satisfied in ≥97% of patients. We enrolled 811 patients from 31 institutions between December 2002 and May 2004. The primary end point was evaluated in 545 patients. The specificity and sensitivity for the diagnosis of pathologically diagnosed invasive cancer were 96.4% (161/167, 95% CI: 92.3-98.7%) and 30.4% (115/378, 95% CI: 25.8-35.3%), respectively, i.e., a negative result. Nevertheless, the specificity for lung adenocarcinoma ≤2.0 cm with ≤0.25 consolidation to the maximum tumor diameter was 98.7% (95% CI: 93.2-100.0%), and this criterion could be used to radiologically define early adenocarcinoma of the lung. Although our predetermined criterion for specificity was not statistically confirmed, radiological diagnosis of noninvasive lung cancer with a thin-section computed tomography scan corresponded well with pathological invasiveness. Radiological noninvasive peripheral lung adenocarcinoma could be defined as an adenocarcinoma ≤2.0 cm with ≤0.25 consolidation.

Lung Adenocarcinoma, Mixed Subtype

"Adenocarcinoma, mixed subtype" is the most common histologic subtype of lung adenocarcinomas in the World Health Organization classification of 2004. For small peripheral adenocarcinomas, for example, those measuring 2 cm or less in greatest diameter, invasive areas can present various histologic patterns. The purpose of this study is to present the radiologic features of small peripheral lung adenocarcinomas with or without a bronchioloalveolar component and with or without invasive areas, in comparison with histopathologic findings. For this purpose, a detailed evaluation of the characteristics of solid regions in ground-glass opacity on high-resolution computerized tomographic images of lung adenocarcinoma is useful.

A Diagnostic Assay Based on MicroRNA Expression Accurately Identifies Malignant Pleural Mesothelioma

The definitive identification of malignant pleural mesothelioma (MPM) has significant clinical implications, yet other malignancies often involve the lung pleura, confounding the diagnosis of MPM. In the absence of accurate markers, MPM can be difficult to distinguish from peripheral lung adenocarcinoma and metastatic epithelial cancers. MicroRNA expression is tissue-specific and highly informative for identifying tumor origin. We identified microRNA biomarkers for the differential diagnosis of MPM and developed a standardized microRNA-based assay. Formalin-fixed, paraffin-embedded samples of 33 MPM and 210 carcinomas were used for assay development. Using microarrays, we identified microRNAs differentially expressed between MPM and various carcinomas. Hsa-miR-193-3p was overexpressed in MPM, while hsa-miR-200c and hsa-miR-192 were overexpressed in peripheral lung adenocarcinoma and carcinomas that frequently metastasize to lung pleura. We developed a standardized diagnostic assay based on the expression of these microRNAs. The assay reached a sensitivity of 100% and a specificity of 94% in a blinded validation set of 68 samples from the lung and pleura. This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura.

The morphological diversity of small lung adenocarcinoma with mixed subtypes is associated with local invasiveness and prognosis

Under the current World Health Organization (WHO) classification, 'lung adenocarcinoma with mixed subtypes' is the most frequent type, even in small lung adenocarcinoma, with a diameter of 3 cm or less. For this type of lung adenocarcinoma, it has been reported that the high ratio of the peripheral bronchioloalveolar carcinoma (BAC)/lepidic growth (LG) component was a favorable prognostic factor. On the other hand, the central solid components of lung adenocarcinoma with mixed subtypes have not been focused on in the past. In this study, we took note of the histological features in central solid components of lung adenocarcinoma with mixed subtypes and evaluated whether the morphological diversity of these tumors is associated with local invasiveness and prognostic implication. A total of 103 surgically resected peripheral lung adenocarcinomas were reviewed. All the tumors were 3 cm or less in diameter and histologically diagnosed as lung adenocarcinoma with mixed subtypes, containing a BAC/LG component at the peripheral lesion of the tumor. The tumors were classified into two groups, according to the number of histological subtypes in the tumor, using the modified WHO classification (including the micropapillary subtype); group A (n = 76) has two or three histological subtypes, and group B (n = 27) has four or five subtypes in the tumor, respectively. Then, we evaluated the differences in clinicopathological factors and prognosis between these two groups. Group B was significantly associated with positive lymphatic and vascular invasion, lymph node metastasis, and advanced pathological stage, compared with group A. The 5-year survival rates of all patients were 91.4% for group A and 43.3% for group B, respectively, with a significant difference (p < 0.01). Multivariate analysis showed that the group classification by the number of histological subtypes was an independent prognostic factor in stage IA patients (p < 0.01). The morphological diversity of small lung adenocarcinoma with mixed subtypes is an independent prognostic factor and is associated with tumors' local invasiveness and patients' prognosis.

The clinical application value of PET/CT in adenocarcinoma with bronchioloalveolar carcinoma features

The goal of our study was to demonstrate the clinical usefulness of positron emission tomography/computed tomography (PET/CT) for adenocarcinoma with bronchioloalveolar carcinoma (BAC) features, through evaluating the relationship between the intrathoracic lymph node metastases and maximum standardized uptake value (SUVmax), tumor size of the primary tumor and the ratio of BAC component and analysing the correlation of SUVmax, tumor size and the ratio of BAC component. This was a retrospective study. Forty-five patients with focal peripheral lung adenocarcinoma with BAC features were included in this study and underwent the PET/CT scan. Twenty-one patients were women and 24 were men. None of the patients had insulin-dependent diabetes and the serum glucose levels in all patients just before (18)F-FDG was injected were less than 120 mg/dl. The diagnosis of the lesion was made by surgical histopathology. All patients underwent successful surgery, and pathologic examination confirmed that 34 of 118 excised nodal groups in 18 patients were proved to be positive for malignancy. Univariate analysis revealed 3 potential factors related to intrathoracic lymph node metastases: SUVmax (P = 0.002); the ratio of BAC component (P = 0.002); maximum dimension of a tumor on mediastinal window setting images (mDmax, P = 0.025). The maximum dimension of a tumor on pulmonary window setting images (pDmax, P = 0.373) had no significance. A receiver operating characteristic (ROC) curve based on SUVmax, mDmax and the ratio of BAC component was constructed, the area under curve (AUC) was 85.2, 70.3 and 81.5% separately. There was no statistical significance between AUC of SUVmax and AUC of the ratio of BAC component (Z = 0.901, P = 0.368). The AUC of SUVmax and AUC of the ratio of BAC component were significantly higher than AUC of mDmax (Z = 2.112, P = 0.035; Z = 2.016, P = 0.042).The SUVmax and the ratio of BAC component had significant inverse correlation (r = -0.85, P < 0.01). The mDmax and the ratio of BAC component had significant inverse correlation (r = -0.69, P < 0.01). The SUVmax and mDmax had significant correlation (r = 0.60, P < 0.01). PET/CT would be clinically useful for adenocarcinoma with BAC features, because SUVmax obtained by PET/CT can predict the incidence of intrathoracic lymph node metastases at preoperative stages and even for inoperable patients.