The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the Classification of Residual Tumor After Resection for the Forthcoming (Ninth) Edition of the TNM Classification of Lung Cancer.

INTRODUCTION: The goal of surgical resection is to completely remove a cancer; it is useful to have a system to describe how well this was accomplished. This is captured by the residual tumor (R) classification, which is separate from the TNM classification that describes the anatomic extent of a cancer independent of treatment. The traditional R-classification designates as R0 a complete resection, as R1 a macroscopically complete resection but with microscopic tumor at the surgical margin, and as R2 a resection that leaves gross tumor behind. For lung cancer, an additional category encompasses situations in which the presence of residual tumor is uncertain. METHODS: This paper represents a comprehensive review of evidence regarding these R categories and the descriptors thereof, focusing on studies published after the year 2000 and with adjustment for potential confounders. RESULTS: Consistent discrimination between complete, uncertain, and incomplete resection is revealed with respect to overall survival. Evidence regarding specific descriptors is generally somewhat limited and only partially consistent; nevertheless, the data suggest retaining all descriptors but with clarifications to address ambiguities. CONCLUSION: On the basis of this review, the R-classification for the ninth edition of stage classification of lung cancer is proposed to retain the same overall framework and descriptors, with more precise definitions of descriptors. These refinements should facilitate application and further research.

Guidelines for Pathologic Diagnosis of Mesothelioma.

CONTEXT.­: Mesothelioma is an uncommon tumor that can be difficult to diagnose. OBJECTIVE.­: To provide updated, practical guidelines for the pathologic diagnosis of mesothelioma. DATA SOURCES.­: Pathologists involved in the International Mesothelioma Interest Group and others with expertise in mesothelioma contributed to this update. Reference material includes peer-reviewed publications and textbooks. CONCLUSIONS.­: There was consensus opinion regarding guidelines for (1) histomorphologic diagnosis of mesothelial tumors, including distinction of epithelioid, biphasic, and sarcomatoid mesothelioma; recognition of morphologic variants and patterns; and recognition of common morphologic pitfalls; (2) molecular pathogenesis of mesothelioma; (3) application of immunohistochemical markers to establish mesothelial lineage and distinguish mesothelioma from common morphologic differentials; (4) application of ancillary studies to distinguish benign from malignant mesothelial proliferations, including BAP1 and MTAP immunostains; novel immunomarkers such as Merlin and p53; fluorescence in situ hybridization (FISH) for homozygous deletion of CDKN2A; and novel molecular assays; (5) practical recommendations for routine reporting of mesothelioma, including grading epithelioid mesothelioma and other prognostic parameters; (6) diagnosis of mesothelioma in situ; (7) cytologic diagnosis of mesothelioma, including use of immunostains and molecular assays; and (8) features of nonmalignant peritoneal mesothelial lesions.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groups in the Forthcoming (Ninth) Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: The TNM classification of lung cancer is periodically revised. The International Association for the Study of Lung Cancer collected and analyzed a new database to inform the forthcoming ninth edition of the TNM classification. The results are herewith presented. METHODS: After exclusions, 76,518 patients from a total of 124,581 registered patients were available for analyses: 58,193 with clinical stage, 39,192 with pathologic stage, and 62,611 with best stage NSCLC. The proposed new N2 subcategories (N2a, involvement of single ipsilateral mediastinal or subcarinal nodal station, and N2b, involvement of multiple ipsilateral mediastinal nodal stations with or without involvement of the subcarinal nodal station) and the new M1c subcategories (M1c1, multiple extrathoracic metastases in one organ system, and M1c2, multiple extrathoracic metastases in multiple organ systems) were considered in the survival analyses. Several potential stage groupings were evaluated, using multiple analyses, including recursive partitioning, assessment of homogeneity within and discrimination between potential groups, clinical and statistical significance of survival differences, multivariable regression, and broad assessment of generalizability. RESULTS: T1N1, T1N2a, and T3N2a subgroups are assigned to IIA, IIB, and IIIA stage groups, respectively. T2aN2b and T2bN2b subgroups are assigned to IIIB. M1c1 and M1c2 remain in stage group IVB. Analyses reveal consistent ordering, discrimination of prognosis, and broad generalizability of the proposed ninth edition stage classification of lung cancer. CONCLUSIONS: The proposed stages for the ninth edition TNM improve the granularity of nomenclature about anatomic extent that has benefits as treatment approaches become increasingly differentiated and complex.

The International Association for the Study of Lung Cancer (IASLC) Staging Project for Lung Cancer: Recommendation to Introduce Spread Through Air Spaces as a Histologic Descriptor in the Ninth Edition of the TNM Classification of Lung Cancer. Analysis of 4061 Pathologic Stage I NSCLC.

INTRODUCTION: Spread through air spaces (STAS) consists of lung cancer tumor cells that are identified beyond the edge of the main tumor in the surrounding alveolar parenchyma. It has been reported by meta-analyses to be an independent prognostic factor in the major histologic types of lung cancer, but its role in lung cancer staging is not established. METHODS: To assess the clinical importance of STAS in lung cancer staging, we evaluated 4061 surgically resected pathologic stage I R0 NSCLC collected from around the world in the International Association for the Study of Lung Cancer database. We focused on whether STAS could be a useful additional histologic descriptor to supplement the existing ones of visceral pleural invasion (VPI) and lymphovascular invasion (LVI). RESULTS: STAS was found in 930 of 4061 of the pathologic stage I NSCLC (22.9%). Patients with tumors exhibiting STAS had a significantly worse recurrence-free and overall survival in both univariate and multivariable analyses involving cohorts consisting of all NSCLC, specific histologic types (adenocarcinoma and other NSCLC), and extent of resection (lobar and sublobar). Interestingly, STAS was independent of VPI in all of these analyses. CONCLUSIONS: These data support our recommendation to include STAS as a histologic descriptor for the Ninth Edition of the TNM Classification of Lung Cancer. Hopefully, gathering these data in the coming years will facilitate a thorough analysis to better understand the relative impact of STAS, LVI, and VPI on lung cancer staging for the Tenth Edition TNM Stage Classification.

International reproducibility study of thymic epithelial tumors staging: pT stage is an issue. proposals for improvement. A RYTHMIC/ITMIG study.

INTRODUCTION: Pathologists are staging thymic epithelial tumors (TET) according to the 8th UICC/AJCC TNM system. Within the French RYTHMIC network, dedicated to TET, agreement on pathologic tumor stage (pT) among the pathology panelists was difficult. The aim of our study was to determine the interobserver reproducibility of pT at an international level, to explore the source of discrepancies and potential interventions to address these. METHODS: An international panel of pathologists was recruited through the International Thymic Malignancy Interest Group (ITMIG). The study focused on invasion of mediastinal pleura, pericardium, and lung. From a cohort of cases identified as challenging within the RYTHMIC network, we chose a series of test and validation cases (n = 5 and 10, respectively). RESULTS: Reproducibility of the pT stage was also challenging at an international level as none of the 15 cases was classified as the same pT stage by all ITMIG pathologists. The agreement rose from slight (κ = 0.13) to moderate (κ = 0.48) between test and validation series. Discussion among the expert pathologists pinpointed two major reasons underlying discrepancies: 1) Thymomas growing with their "capsule" and adhering to the pleurae, pericardium, or lung were often misinterpreted as invading these structures. 2) Recognition of the mediastinal pleura was identified as challenging. CONCLUSION: Our study underlines that the evaluation of the pT stage of TET is problematic and needs to be addressed in more detail in an upcoming TNM classification. The publication of histopathologic images of landmarks, including ancillary tests could improve reproducibility for future TNM classifications.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

BACKGROUND AND OBJECTIVE: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. METHODS: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. RESULTS: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. CONCLUSION: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Overnight desaturation in interstitial lung diseases: links to pulmonary vasculopathy and mortality.

Background: Overnight desaturation predicts poor prognosis across interstitial lung diseases (ILDs). The aim of the present study was to investigate whether nocturnal desaturation is associated with pulmonary vasculopathy and mortality. Methods: A retrospective single centre study of 397 new ILD patients was carried out including patients with idiopathic pulmonary fibrosis (IPF) (n=107) and patients with non-IPF fibrotic ILD (n=290). This is the largest study to date of the effect of significant nocturnal desaturation (SND) (≥10% of total sleep time with oxygen saturation ≤90% measured by pulse oximetry). Results: The prevalence of SND was 28/107 (26.2%) in IPF and 80/290 (27.6%) in non-IPF ILD. The prevalence of SND was higher in non-IPF ILDs than in IPF (p=0.025) in multivariate analysis. SND was associated with noninvasive markers of pulmonary hypertension (PH): tricuspid regurgitation velocity (TRV) (p<0.0001), brain natriuretic peptide (p<0.007), carbon monoxide transfer coefficient (p<0.0001), A-a gradient (p<0.0001), desaturation >4% in 6-min walking test (p<0.03) and pulmonary artery diameter (p<0.005). SND was independently associated with high echocardiographic PH probability in the entire cohort (OR 2.865, 95% CI 1.486-5.522, p<0.002) and in non-IPF fibrotic ILD (OR 3.492, 95% CI 1.597-7.636, p<0.002) in multivariate analysis. In multivariate analysis, SND was associated with mortality in the entire cohort (OR 1.734, 95% CI 1.202-2.499, p=0.003) and in IPF (OR 1.908, 95% CI 1.120-3.251, p=0.017) and non-IPF fibrotic ILD (OR 1.663, 95% CI 1.000-2.819, p=0.041). Separate models with exclusion of each one of the diagnostic subgroups showed that no subgroup was responsible for this finding in non-IPF ILDs. SND was a stronger marker of 5-year mortality than markers of PH. Conclusion: SND was associated with high echocardiographic probability and mortality and was a stronger predictor of mortality in IPF and non-IPF ILDs grouped together to power the study.

A 74-Year-Old Man With Waldenström Macroglobulinemia and Progressive Dyspnea.

CASE PRESENTATION: A 74-year-old man presented to our department with progressive dyspnea on exertion over the last year. The patient did not report any other symptoms. He had previously smoked with a 60 pack-year history. He worked in an office and did not report any environmental, occupational, or domestic exposures. His history included asymptomatic Waldenström's macroglobulinemia that was diagnosed 18 months before respiratory symptoms. He was not receiving any treatment and was monitored regularly by the hematology department.

Diagnosis of cystic lung diseases: a position statement from the UK Cystic Lung Disease Rare Disease Collaborative Network.

BACKGROUND: Rare cystic lung diseases are increasingly recognised due the wider application of CT scanning making cystic lung disease management a growing part of respiratory care. Cystic lung diseases tend to have extrapulmonary features that can both be diagnostic but also require surveillance and treatment in their own right. As some of these diseases now have specific treatments, making a precise diagnosis is crucial. While Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia and lymphangioleiomyomatosis are becoming relatively well-known diseases to respiratory physicians, a targeted and thorough workup improves diagnostic accuracy and may suggest other ultrarare diseases such as light chain deposition disease, cystic pulmonary amyloidosis, low-grade metastatic neoplasms or infections. In many cases, diagnostic information is overlooked leaving uncertainty over the disease course and treatments. AIMS: This position statement from the Rare Disease Collaborative Network for cystic lung diseases will review how clinical, radiological and physiological features can be used to differentiate between these diseases. NARRATIVE: We highlight that in many cases a multidisciplinary diagnosis can be made without the need for lung biopsy and discuss where tissue sampling is necessary when non-invasive methods leave diagnostic doubt. We suggest an initial workup focusing on points in the history which identify key disease features, underlying systemic and familial diseases and a clinical examination to search for connective tissue disease and features of genetic causes of lung cysts. All patients should have a CT of the thorax and abdomen to characterise the pattern and burden of lung cysts and extrapulmonary features and also spirometry, gas transfer and a 6 min walk test. Discussion with a rare cystic lung disease centre is suggested before a surgical biopsy is undertaken. CONCLUSIONS: We suggest that this focused workup should be performed in all people with multiple lung cysts and would streamline referral pathways, help guide early treatment, management decisions, improve patient experience and reduce overall care costs. It could also potentially catalyse a national research database to describe these less well-understood and unidentified diseases, categorise disease phenotypes and outcomes, potentially leading to better prognostic data and generating a stronger platform to understand specific disease biology.

The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma.

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposals for the N and the M Components for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: Stage classification is an important underpinning of management in patients with cancer and rests on a combination of three components-T for tumor extent, N for nodal involvement, and M for distant metastases. This article details the revision of the N and the M components of thymic epithelial tumors for the ninth edition of the TNM classification of malignant tumors proposed by the Thymic Domain of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee. METHODS: The N and M components of the eighth edition staging system were verified by a large international collaborative data source through a data-driven analysis. A total of 9147 cases were included for analysis, including 7662 thymomas, 1345 thymic carcinomas, and 140 neuroendocrine thymic tumors. RESULTS: Lymph node involvement rates were 1.5% in thymomas and 17.6% and 27.7% in thymic carcinomas and neuroendocrine thymic tumors, respectively. Rates of lymph node metastasis were increasingly higher in tumors with higher T stage and higher-grade histologic type. Survival analysis validated the differences in the N and M categories proposed in the eighth edition staging system. Good discrimination in overall survival was detected among pathologic (p)N and pM categories in patients with thymoma and thymic carcinoma. CONCLUSIONS: No changes are proposed from the eighth edition for the N and M components. The proposed stage classification will provide a useful tool for management of the disease among the global thymic community.

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers. METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading. CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).

Pulmonary invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA) is a relatively rare subtype of lung adenocarcinoma, composed of goblet and/or columnar tumour cells containing abundant intracytoplasmic mucin vacuoles. While a majority of IMAs are driven by KRAS mutations, recent studies have identified distinct genomic alterations, such as NRG1 and ERBB2 fusions. IMAs also more frequently present as a pneumonic-like pattern with multifocal and multilobar involvement, and comparative genomic profiling predominantly shows a clonal relationship, suggesting intrapulmonary metastases rather than synchronous primary tumours. Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.

Radiomics-based decision support tool assists radiologists in small lung nodule classification and improves lung cancer early diagnosis.

BACKGROUND: Methods to improve stratification of small (≤15 mm) lung nodules are needed. We aimed to develop a radiomics model to assist lung cancer diagnosis. METHODS: Patients were retrospectively identified using health records from January 2007 to December 2018. The external test set was obtained from the national LIBRA study and a prospective Lung Cancer Screening programme. Radiomics features were extracted from multi-region CT segmentations using TexLab2.0. LASSO regression generated the 5-feature small nodule radiomics-predictive-vector (SN-RPV). K-means clustering was used to split patients into risk groups according to SN-RPV. Model performance was compared to 6 thoracic radiologists. SN-RPV and radiologist risk groups were combined to generate "Safety-Net" and "Early Diagnosis" decision-support tools. RESULTS: In total, 810 patients with 990 nodules were included. The AUC for malignancy prediction was 0.85 (95% CI: 0.82-0.87), 0.78 (95% CI: 0.70-0.85) and 0.78 (95% CI: 0.59-0.92) for the training, test and external test datasets, respectively. The test set accuracy was 73% (95% CI: 65-81%) and resulted in 66.67% improvements in potentially missed [8/12] or delayed [6/9] cancers, compared to the radiologist with performance closest to the mean of six readers. CONCLUSIONS: SN-RPV may provide net-benefit in terms of earlier cancer diagnosis.

Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis.

Aberrant expansion of KRT5+ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+ cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+ cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5+ cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+ cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification. METHODS: A central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world. RESULTS: A total of 11,347 patients were collected. Submitting organizations were the following: Japanese Association for Research in the Thymus, European Society of Thoracic Surgeons, Chinese Alliance for Research in Thymoma, Korean Association for Research in the Thymus, International Thymic Malignancy Interest Group, and Réseau tumeurs THYMiques et Cancer. Additional contributions came from centers in the United States, United Kingdom, Turkey, Australia, Spain, and Italy. A total of 9147 cases were eligible for analysis. Eligible cases for analysis came from Asia and Australia (5628 cases, 61.5%), Europe (3113 cases, 34.0%), and North America (406 cases, 4.4%). CONCLUSIONS: This report provides an overview of the database that has informed the proposals for the updated T, N, and M components and the stage groups for the ninth TNM of malignant tumors.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: A Re-Assessment of the International Thymic Malignancy Interest Group/International Association for the Study of Lung Cancer Lymph Node Map for Thymic Epithelial Tumors for the Forthcoming Ninth Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: A lymph node map is the pillar on which accurate assignment and documentation of nodal classification stands. The International Thymic Malignancy Interest Group created the first map for thymic epithelial malignancies in conjunction with the eighth edition of the TNM classification, representing the first official TNM classification of thymic epithelial malignancies. The map was based on clinical experience and published studies, but it was largely empirical because of limited available data. Dissemination of the map and implementation of a standard thymic stage classification across the world in 2017 have provided more consistent and granular data. METHODS: More than twice as many cases of node involvement are available for analysis in the current database compared with that of the eighth edition database, allowing validation of many aspects of the eighth edition map. This article details the process and considerations for refinement of the thymic map for the ninth TNM used by the Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer. The committee evaluated a large international collaborative data set, published anatomical and clinical studies pertaining to lymph node spread from thymic epithelial tumors, in conjunction with the analysis underlying refinements of the TNM components for the ninth edition TNM classification. RESULTS: The node map boundaries of the N1 and N2 categories remain unchanged. Visual clarifications have been added to the nomenclature of nodal stations within these regions. CONCLUSIONS: On the basis of the recommendation to keep the N component unchanged for the ninth edition TNM classification, the lymph node map remains unchanged as well; however, clarifications have been added to facilitate clinical use.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the ninth edition. This article outlines the proposed definitions for the T, the N, and the M components and their combination into stage groups. METHODS: A large central database of 11,347 patients with thymic epithelial tumors was assembled thanks to the contribution of the major thymic organizations worldwide and analyses were carried out for the T, the N, and the M components and the stage groups. Overall survival was the outcome measure for patients with completely and incompletely resected tumors, and recurrence for those with complete resection. When the number of patients was sufficient, analyses were performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors. RESULTS: Tumor size is included in the T1 category as T1a (≤5cm) and T1b (>5 cm); the mediastinal pleura is dropped as a T descriptor; invasion of the lung or phrenic nerve is reclassified as T2 (instead of T3). No changes are proposed for the N and the M components from the eighth edition. The stage groups remain the same. CONCLUSIONS: The proposed changes for the ninth edition of the TNM classification set the stage for further progress in the future for these rare tumors.

Combination of BAL and Computed Tomography Differentiates Progressive and Non-progressive Fibrotic Lung Diseases.

Rationale: Identifying patients with pulmonary fibrosis (PF) at risk of progression can guide management. Objectives: To explore the utility of combining baseline BAL and computed tomography (CT) in differentiating progressive and nonprogressive PF. Methods: The derivation cohort consisted of incident cases of PF for which BAL was performed as part of a diagnostic workup. A validation cohort was prospectively recruited with identical inclusion criteria. Baseline thoracic CT scans were scored for the extent of fibrosis and usual interstitial pneumonia (UIP) pattern. The BAL lymphocyte proportion was recorded. Annualized FVC decrease of >10% or death within 1 year was used to define disease progression. Multivariable logistic regression identified the determinants of the outcome. The optimum binary thresholds (maximal Wilcoxon rank statistic) at which the extent of fibrosis on CT and the BAL lymphocyte proportion could distinguish disease progression were identified. Measurements and Main Results: BAL lymphocyte proportion, UIP pattern, and fibrosis extent were significantly and independently associated with disease progression in the derivation cohort (n = 240). Binary thresholds for increased BAL lymphocyte proportion and extensive fibrosis were identified as 25% and 20%, respectively. An increased BAL lymphocyte proportion was rare in patients with a UIP pattern (8 of 135; 5.9%) or with extensive fibrosis (7 of 144; 4.9%). In the validation cohort (n = 290), an increased BAL lymphocyte proportion was associated with a significantly lower probability of disease progression in patients with nonextensive fibrosis or a non-UIP pattern. Conclusions: BAL lymphocytosis is rare in patients with extensive fibrosis or a UIP pattern on CT. In patients without a UIP pattern or with limited fibrosis, a BAL lymphocyte proportion of ⩾25% was associated with a lower likelihood of progression.