Computer-Aided Diagnosis of Ground-Glass Opacity Nodules Using Open-Source Software for Quantifying Tumor Heterogeneity.

OBJECTIVE: The purposes of this study are to develop quantitative imaging biomarkers obtained from high-resolution CTs for classifying ground-glass nodules (GGNs) into atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC); to evaluate the utility of contrast enhancement for differential diagnosis; and to develop and validate a support vector machine (SVM) to predict the GGN type. MATERIALS AND METHODS: The heterogeneity of 248 GGNs was quantified using custom software. Statistical analysis with a univariate Kruskal-Wallis test was performed to evaluate metrics for significant differences among the four GGN groups. The heterogeneity metrics were used to train a SVM to learn and predict the lesion type. RESULTS: Fifty of 57 and 51 of 57 heterogeneity metrics showed statistically significant differences among the four GGN groups on unenhanced and contrast-enhanced CT scans, respectively. The SVM predicted lesion type with greater accuracy than did three expert radiologists. The accuracy of classifying the GGNs into the four groups on the basis of the SVM algorithm was 70.9%, whereas the accuracy of the radiologists was 39.6%. The accuracy of SVM in classifying the AIS and MIA nodules was 73.1%, and the accuracy of the radiologists was 35.7%. For indolent versus invasive lesions, the accuracy of the SVM was 88.1%, and the accuracy of the radiologists was 60.8%. We found that contrast enhancement does not significantly improve the differential diagnosis of GGNs. CONCLUSION: Compared with the GGN classification done by the three radiologists, the SVM trained regarding all the heterogeneity metrics showed significantly higher accuracy in classifying the lesions into the four groups, differentiating between AIS and MIA and between indolent and invasive lesions. Contrast enhancement did not improve the differential diagnosis of GGNs.

Lung Cancer Staging and Prognosis.

The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms.

Impact of the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology clinical practice guidelines for EGFR and ALK testing in lung cancer in Canada.

This paper summarizes the practical impact of the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology lung cancer biomarkers guidelines on the lung cancer approach in Canada, providing possible practical solutions for other similar health care systems in which scientific reality needs to be constantly balanced against economic reality.

Predictive scoring of high-grade histology among early-stage lung cancer patients: The MOSS score.

BACKGROUND: Poor prognosis associated with adenocarcinoma of International Association for the Study of Lung Cancer (IASLC) grade 3 has been recognized. In this study we aimed to develop a scoring system for predicting IASLC grade 3 based before surgery. METHODS: Two retrospective datasets with significant heterogeneity were used to develop and evaluate a scoring system. The development set was comprised of patients with pathological stage I nonmucinous adenocarcinoma and they were randomly divided into training (n = 375) and validation (n = 125) datasets. Using multivariate logistic regression, a scoring system was developed and internally validated. Later, this new score was further tested in the testing set which was comprised of patients with clinical stage 0-I non-small cell lung cancer (NSCLC) (n = 281). RESULTS: Four factors that were related to IASLC grade 3 were used to develop the new scoring system the MOSS score; male (M, point 1), overweight (O, point 1), size>10 mm (S, point 1), and solid lesions (S, point 3). Predictability of IASLC grade 3 increased from 0.4% to 75.2% with scores from 0 to 6. The area under the curve (AUC) of the MOSS was 0.889 and 0.765 for the training and validation datasets, respectively. The MOSS score exhibited similar predictability in the testing set (AUC: 0.820). CONCLUSION: The MOSS score, which combines preoperative variables, can be used to identify high-risk early-stage NSCLC patients with aggressive histological features. It can support clinicians in determining a treatment plan and surgical extent. Further refinement of this scoring system with prospective validation is needed.

Comprehensive analysis of mutational profile and prognostic significance of complex glandular pattern in lung adenocarcinoma.

Background: Complex glandular pattern (CGP) was included as high-grade pattern in the new grading system proposed by The International Association for the Study of Lung Cancer. We aimed to investigate the mutational profile and validate the prognostic significance and proper cut-off value to distinguish the aggressive behavior of CGP. Methods: CGP was defined as nests of tumor cells with sieve-like perforation, fused glands with irregular borders or back-to-back glands without intervening stroma. Patients were categorized into four groups according to the percentage of CGP component (0%, 1-19%, 20-49%, 50-100%). Cox's proportional hazards model was applied to analyze recurrence free survival (RFS) and overall survival (OS). Results: A total of 950 patients with resected lung adenocarcinoma was enrolled. The most frequent driver mutation in this cohort was EGFR and was detected in 624 (65.7%) patients. EGFR mutation was more frequently observed in patients with <20% CGP than in patients with ≥20% CGP (73.6% vs. 60.2%), while KRAS mutation and ALK rearrangement was significantly associated with ≥20% CGP. Patients with 20% or greater CGP exhibited significant worse RFS (P<0.001) and OS (P<0.001) than their counterparts. Moreover, the multivariate Cox regression analysis confirmed that CGP (≥20%) was a risk factor for a worse RFS (P=0.001) and OS (P<0.001) independent of staging and gene mutation. Smaller portion of CGP (<20%) were comparable in RFS and OS to those without CGP (0%). There was also no significant difference in RFS and OS between the 20-49% and ≥50% group. Conclusions: Our study provided mutational profile of patients with different CGP, validated CGP as a negative prognostic factor and provided extra evidences for the optimal cut-off value of CGP percentage.

Visualization of patterns of lymph node metastases in non-small cell lung cancer using network analysis.

Objective: We aimed to visualize complicated patterns of lymph node metastases in surgically resected non-small cell lung cancer by applying a data mining technique. Methods: In this retrospective study, 783 patients underwent lobectomy or pneumonectomy with systematic mediastinal lymph node dissection for non-small cell lung cancer between January 2010 and December 2018. Surgically resected lymph nodes were classified according to the International Association for the Study of Lung Cancer lymph node map. Network analysis generated patterns of lymph node metastases from stations 1 to 14, and the degree of connection between 2 lymph node stations was assessed. Results: The median number of lymph nodes examined per patient was 20, and the pathological N category was pN0 in 428 cases, pN1 in 132, pN2 in 221, and pN3 in 2. N1 lymph node stations had strong associations with superior mediastinal lymph node stations for patients with primary tumors in the upper lobes and with station 7 for the lower lobes. There was also a connection from the N1 lymph node stations to superior mediastinal lymph node stations in the lower lobes. In the right middle lobe, an even distribution from station 12m toward stations 2R, 4R, and 7 was noted. We released an interactive web application to visualize these data: http://www.canexapp.com. Conclusions: Lymph node metastasis patterns differed according to the lobe bearing the tumor. Our results support the need for clinical trials to further investigate selective mediastinal lymph node dissection.

Bronchial carcinoid tumor in the era of covid-19 pandemic: A case report.

INTRODUCTION: Bronchial carcinoid tumors are rare, slow growing, malignant neuroendocrine tumors which arise from Enterochromaffin (Kulchitsky) cells. Early diagnosis is extremely important as the main stay of treatment is surgical excision. PRESENTATION OF CASE: We present a rare case of bronchial typical carcinoid tumor in a 27-year-old male who presented with a complaint of intermittent dry cough of 2 weeks' duration associated with shortness of breath and low grade fever. He was initially misdiagnosed as covid-19 pneumonia and was admitted to covid-19 treatment center. Right lung bi-lobectomy with regional lymph node resection was done and he was discharged home in good condition. DISCUSSION: Majority of typical carcinoids are located in the central airways leading to bronchial obstruction with recurrent pneumonia, chest pain and wheezing. In the era of covid-19 pandemic, lung cancer patients are at higher risk of being affected by covid-19 and, early identification and differential diagnosis is extremely difficult in the absence of comprehensive evaluation and work up as the clinical and imaging findings of covid-19 may resemble lung cancer. Although hilar and mediastinal lymph nodes are the most common metastatic sites for typical carcinoids most lymphadenopathies are caused by a reactive inflammatory reaction. CONCLUSION: Bronchial carcinoids are rare, malignant neuroendocrine tumors with complete surgical resection being the only curative management. During the Covid-19 pandemic crisis, diagnosing rare lung diseases like carcinoid tumor is real challenge especially in resource limited set up and needs high index of suspicion with meticulous diagnostic work up. The outcome of typical carcinoids with lymph node metastasis is excellent with complete resection.

Recommended changes for the 8th edition of the TNM classification for lung cancer-the findings of a single-institution evaluation.

BACKGROUND: To evaluate the efficacy of the nodal descriptors and subgroups proposed by International Association for the Study of Lung Cancer (IASLC) in the 8th edition of the TNM classification system and to provide references for future editions. METHODS: A total of 3,177 patients with non-small cell lung cancer at the Beijing Cancer Hospital were classified based on the following three methods: (I) the N descriptors in the 8th edition of the TNM classification system: N0, N1, N2, and N3; (II) the IASLC-proposed N subgroups: N1a, N1b, N2a1, N2a2, and N2b; (III) our more extensive division method: N1a, N1b, N1c, N2a1, N2a2, N2b1, N2b2, N2c, N3a, and N3b. Five-year survival analysis was performed using the Kaplan-Meier method, and differences between subgroups were evaluated using the log-rank test. RESULTS: (I) A significant survival difference was found between each adjacent N descriptor; (II) the difference between each adjacent subgroup N descriptor was significant, but the difference between N1b and N2a1 was not; (III) in our proposed method, a significant difference was found between all the subgroups apart from N2a2 and N2b1, N2b1 and N2b2, N2c and N3a, and N3a and N3b. CONCLUSIONS: The N descriptors in the 8th edition of the tumor, node, and metastasis (TNM) classification system are consistent with our data. Although our more extensive division method could distinguish between patients at different stages, its implementation is complicated; thus, we recommend the implementation of the IASLC-proposed subgroups with the addition of the N1b and N2a1 groups.

Postoperative radiotherapy option based on mediastinal lymph node reclassification for patients with pN2 non-small-cell lung cancer.

Background: In this research, we used the mediastinal lymph node reclassification proposed by the International Association for the Study of Lung Cancer (iaslc) to screen for patients with pathologic N2 (pN2) non-small-cell lung cancer (nsclc) who might benefit from postoperative radiotherapy (port). Methods: The study enrolled 440 patients with pN2 nsclc who received complete surgical resection and allocated them to one of three groups: N2a1 (single-station skip mediastinal lymph node metastasis), N2a2 (single-station non-skip mediastinal lymph node metastasis), and N2b (multi-station mediastinal lymph node metastasis). Rates of local recurrence at first recurrence in patients receiving and not receiving port were compared using the chi-square test. Overall (os) and disease-free survival (dfs) were then compared using Kaplan-Meier survival analysis with log-rank test. In addition, the factors potentially influencing os and dfs were analyzed using univariate and multivariate Cox regression. Results: The rate of local recurrence for the N2a2 and N2b groups was significantly lower in patients receiving port (p = 0.044 and p = 0.043 respectively). The log-rank test revealed that, for the N2a1 group, differences in os and dfs were not statistically significant between the patients who did and did not receive port (p = 0.304 and p = 0.197 respectively). For the N2a2 group, os and dfs were markedly superior in patients who received port compared with those who did not (p = 0.001 and p = 0.014 respectively). For the N2b group, os was evidently better in patients who received port compared with those who did not (p = 0.025), but no statistically significant difference in dfs was observed (p = 0.134). Multivariate regression analysis revealed that, in the N2a1 group, port was significantly associated with poor os [hazard ratio (hr): 2.618; 95% confidence interval (ci): 1.185 to 5.785; p = 0.017]; in the N2a2 group, port was associated with improved os (hr: 0.481; 95% ci: 0.314 to 0.736; p = 0.001) and dfs (hr: 0.685; 95% ci: 0.479 to 0.980; p = 0.039). Conclusions: For patients with pN2 nsclc who receive complete resection, port might be beneficial only for patients with single-station non-skip metastasis (N2a2). Patients with single-station skip metastasis (N2a1) and multi-station metastasis (N2b) might not currently benefit from port.

Staging Lung Cancer: Regional Lymph Node Classification.

This article reviews regional lymph node assessment in lung cancer. In the absence of a distant metastasis, the absence or location of lung cancer spread to a regional mediastinal lymph node affects treatment options and prognosis. Regional lymph node maps have been created to standardize assessment of the N descriptor. The International Association for the Study of Lung Cancer lymph node map is used for the standardization of N descriptor assessment. CT, PET/CT with fluorodeoxyglucose, endobronchial ultrasound-guided and/or esophageal ultrasound-guided biopsy, and mediastinoscopy are common modalities used to determine the N descriptor.

Correlation between epidermal growth factor receptor mutation and histologic subtypes or characteristics of computed tomography findings in patients with resected pulmonary adenocarcinoma.

OBJECTIVE: To investigate the correlation between epidermal growth factor receptor (EGFR) mutation and the histologic subtypes features or computed tomography (CT) findings in patients with resected pulmonary adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed 153 patients underwent surgical resected pulmonary adenocarcinoma. EGFR mutations were detected using the amplification refractory mutation system. Histologic subtype was classified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society pulmonary adenocarcinoma classification. Characteristics of CT in the tumor were retrospectively analyzed, and compared to mutation-negative cohort. RESULTS: EGFR mutations were found in 67 (43.79%) cases. The prevalent histologic subtypes of invasive adenocarcinoma were acinar predominant adenocarcinoma (33.99%), papillary predominant adenocarcinoma (24.18%), micropapillary predominant adenocarcinoma (MPA; 18.95%), solid predominant adenocarcinoma (11.76%), and lepidic predominant adenocarcinoma (LPA; 11.11%). EGFR mutations were correlated with the MPA and LPA subtypes (P = 0.009 and P = 0.018) and was correlated with the air bronchograms (P = 0.008). EGFR mutations were independently associated with other CT characteristics including ground-glass opacity/tumor ratio (P = 0.054). CONCLUSIONS: Correlation exists between EGFR mutations and histologic subtypes of invasive adenocarcinoma or air bronchograms on CT images, which could use to predict EGFR mutation status in patients with pulmonary adenocarcinoma.

Pulmonologist's Road Map to Mediastinal Lymph Node Imaging.

Mediastinal lymph node station maps are intended to facilitate nodal staging in patients with non-small cell lung cancer. These maps have been revised over time and the International Association for Study of Lung Cancer (IASLC) map is the latest rendition. This article illustrates the imaging appearance of each of the IASLC map mediastinal lymph node stations, overviews some of the mediastinal lymph node sampling techniques, and discusses common pitfalls of the IASLC map. It also reviews mediastinal anatomic variants and pathologic features that may simulate lymphadenopathy.

Tumor heterogeneity assessed by texture analysis on contrast-enhanced CT in lung adenocarcinoma: association with pathologic grade.

Objectives To investigate whether texture features on contrast-enhanced computed tomography (CECT) images of lung adenocarcinoma have association with pathologic grade. Methods A cohort of 148 patients with surgically operated adenocarcinoma was retrospectively reviewed. Fifty-four CT features of the primary lung tumor were extracted from CECT images using open-source 3D Slicer software; meanwhile, enhancement homogeneity was evaluated by two radiologists using visual assessment. Multivariate logistic regression analysis was performed to determine significant image indicator of pathologic grade. Results Tumors of intermediate grade were more likely to be never smokers (P=0.020). Enhancement heterogeneity by visual assessment showed no statistical difference between intermediate grade and high grade (P=0.671). Among those 54 features, 29 of them were significantly associated with pathologic grade. Multivariate logistic regression analyses identified F33 (Homogeneity 1) (P=0.005) and F38 (Inverse Variance) (P=0.032) as unique independent image indicators of pathologic grade, and the AUC calculated from this model (AUC=0.834) was higher than clinical model (AUC=0.615) (P=0.0001). Conclusions Our study revealed that texture analysis on CECT images could be helpful in predicting pathologic grade of lung adenocarcinoma.

Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification.

The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.

Cytopathology of pulmonary adenocarcinoma with a single histological pattern using the proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification.

BACKGROUND: Guidelines for histological subtyping in patients with surgically resected lung adenocarcinoma (ADC) were recently proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. The objective of the current study was to investigate the cytomorphology of these subtypes of ADC in cases with matched histology specimens demonstrating a single pure subtype. METHODS: The authors reviewed their database for patients with histological diagnoses of primary lung ADC with a single histological pattern observed on surgical resection and investigated the cytological findings in 18 matched cytology specimens to eliminate sampling issues in cases of mixed ADC. RESULTS: Resections were classified as acinar (7 specimens), solid (6 specimens), lepidic (2 specimens), mucinous (2 specimens), and papillary (1 specimen). Cytology specimens demonstrating a solid pattern had a predominance of 3-dimensional clusters (5 of 6 vs 0 of 12 specimens) (P = .0007, Fisher exact test), necrotic background (3 of 6 vs 0 of 12 specimens) (P = .02), pleomorphic nuclei (6 of 6 vs 1 of 12 specimens) (P = .0004), irregular nuclear contours (6 of 6 vs 3 of 12 specimens) (P = .009), and nuclear enlargement (5 of 6 vs 2 of 12 specimens) (P = .01) compared with the nonsolid patterns. Nuclear pseudoinclusions were present only in nonsolid patterns (5 of 12 specimens), although this finding was not statistically significant (P = .05) CONCLUSIONS: Cytological features of lung ADC subtypes proposed by the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification overlap. However, architectural and nuclear features may be helpful, particularly in distinguishing the prognostically adverse solid pattern from other patterns.

The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects.

The new the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) pathologic classification of lung cancer has markedly changed the pathologic diagnosis of lung adenocarcinoma. This classification deals with many aspects that directly affect clinical practice, and opens new gateways for future research. By means of a multidisciplinary approach, it differs significantly from the former 2004 the World Health Organization (WHO) classification, which was mainly written by pathologist. The present review, in line with the consensus article, is divided in two components: the diagnosis and classification of lung adenocarcinoma in resection specimens and the diagnosis of lung cancer in small biopsies and cytology. Resection specimens are currently classified according to the predominant histologic pattern after comprehensive subtyping in 5% increments. This approach has led to the addition of new pathologic subtypes [adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and micropapillary predominant adenocarcinoma)] and to the discontinuation of some heterogeneous entities included in the former 2004 WHO classification (mixed subtype adenocarcinoma and bronchioloalveolar carcinoma). Overall, these changes have resulted in a better stratification of lung adenocarcinoma tumors in more homogeneous morphologic, clinical and biological subgroups. Pathologic subtyping has demonstrated prognostic utility in resected stage I-III patients, and recent data support their predictive role for the benefit of adjuvant chemotherapy. Moreover, comprehensive pathologic subtyping may potentially affect TNM staging and surgical management or early-stage tumors. On the other hand, for the first time, the novel pathologic classification provides standardized terminology and diagnostic criteria of small biopsies and cytology. Criteria are proposed not only for adenocarcinoma but also for other histologies, but special emphasis was put on the distinction between adenocarcinoma and squamous-cell carcinoma due to its major clinical implications. This review outlines the main issues of the new lung adenocarcinoma classification from a clinical perspective. We describe the different pathologic subtypes in resection specimens, with their most relevant clinical implications. Further on, we address the new terminology and diagnostic criteria for lung adenocarcinomas in small specimens, oriented to their importance for the management and treatment of metastatic lung cancer patients. Finally, we discuss some unanswered questions and relevant issues for the near future.

Tumor invasiveness as defined by the newly proposed IASLC/ATS/ERS classification has prognostic significance for pathologic stage IA lung adenocarcinoma and can be predicted by radiologic parameters.

OBJECTIVES: The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) have collaborated to propose a new pathologic classification of lung adenocarcinoma. In this classification, noninvasiveness and invasiveness have been newly defined for lung adenocarcinoma. The aims of this study were to validate the prognostic significance of tumor invasiveness as defined by the new IASLC/ATS/ERS classification and to assess the relationship between pathologic invasiveness and radiologic findings in pathologic stage IA lung adenocarcinoma. METHODS: We retrospectively reviewed 123 consecutive patients with pathologic stage IA lung adenocarcinoma. Pathologic data were classified according to the new IASLC/ATS/ERS classification. The following radiologic parameters were assessed using thin-section computed tomography: the ground-glass opacity ratio, tumor disappearance rate, and consolidation diameter. RESULTS: There were 54 noninvasive and 69 invasive adenocarcinomas. Five-year overall survival rates for noninvasive adenocarcinoma and invasive adenocarcinoma were 100% and 78.4%, respectively; this difference was statistically significant (P < .01), indicating the prognostic value of this classification. Receiver operating characteristic curves of the ground-glass opacity ratio, tumor disappearance rate, and consolidation diameter identified the optimal cut-off values for predicting the presence of invasive tumors as 50%, 75%, and 10 mm, respectively. CONCLUSIONS: We found that by using the new IASLC/ATS/ERS classification, histologic subtypes of pathologic stage IA lung adenocarcinoma with prognostic value could be identified. Tumor invasiveness of lung adenocarcinoma as defined by this classification can be predicted by evaluating the ground-glass opacity ratio, tumor disappearance rate, and consolidation diameter on thin-section computed tomography.

Cytologic subtyping of lung adenocarcinoma by using the proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) adenocarcinoma classification.

BACKGROUND: The significance of histologic subtyping of surgically resected lung adenocarcinoma (ADC) was recently proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. Approximately 70% of lung cancer patients present with advanced disease, and small biopsies or cytology specimens are frequently the only available diagnostic material. It is uncertain whether proposed morphologic subtyping of ADC can be applied to small specimens. The objective of this study was to assess the applicability of morphologic subtyping of ADC on cytologic specimens. METHODS: Consecutive, newly diagnosed primary lung ADC specimens from patients with matched surgical resection and cytology specimens (n = 66) were selected for the study. The dominant morphologic pattern was determined according to the IASLC/ATS/ERS classification. The number and percentage of malignant cells in cytology specimens were also evaluated. RESULTS: Concordant subtyping of ADC between the dominant pattern on resection and cytology specimens was observed in 26 cases (40%), and was discordant in 32 cases (48%). Concordance increased in specimens that had >200 cells and when correlating with the primary or secondary histologic pattern. The acinar pattern was the most common in concordant cases, whereas discordant cases had a predominantly solid pattern. CONCLUSIONS: Application of the IASLC/ATS/ERS ADC classification to cytologic specimens is challenging and depends on the sufficient cellularity of cytologic preparations. The identification of solid and micropapillary patterns is prognostically important but may be unreliable and difficult on cytology specimens. Future studies are needed to establish reproducible cytologic criteria for the precise subtyping of lung ADC on small specimens.