631 results found
Lindsay CR, Shaw EC, Moore DA, et al., 2021, Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists., Br J Cancer
Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.
Cookson W, Nastase A, Mandal A, et al., 2021, Integrated genomics point to immune vulnerabilities in pleural mesothelioma, Scientific Reports, ISSN: 2045-2322
Ravaglia C, Nicholson AG, 2021, Biopsy in interstitial lung disease: specific diagnosis and the identification of the progressive fibrotic phenotype, CURRENT OPINION IN PULMONARY MEDICINE, Vol: 27, Pages: 355-362, ISSN: 1070-5287
Bui LT, Winters NI, Chung M-I, et al., 2021, Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723
Willis-Owen S, Domingo Sabugo C, Starren E, et al., 2021, Y disruption, autosomal hypomethylation and poor male lung cancer survival, Scientific Reports, Vol: 11, ISSN: 2045-2322
Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40–10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.
Klebe S, Nakatani Y, Dobra K, et al., 2021, The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis, PATHOLOGY, Vol: 53, Pages: 446-453, ISSN: 0031-3025
Schulte JJ, Chapel DB, Attanoos R, et al., 2021, Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma., Am J Clin Pathol
OBJECTIVES: Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM. METHODS: Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions. RESULTS: Histologic subtype was concordant in 81% of cases (κ = 0.58). When compared with resection specimens, epithelioid morphology at biopsy had a positive predictive value (PPV) of 78.9% and a negative predictive value (NPV) of 93.5%; sarcomatoid morphology showed high PPV (92.9%) and NPV (99.3%), and biphasic morphology PPV was 89.7% and NPV was 79.7%. Agreement of the percentage of epithelioid morphology was fair (κ = 0.27). Nuclear grade and necrosis were concordant in 75% (κ = 0.59) and 81% (κ = 0.53) of cases, respectively. Nuclear grade showed moderate (κ = 0.53) and substantial (κ = 0.67) agreement from patients with and without neoadjuvant therapy, respectively, and necrosis showed moderate (κ = 0.47 and κ = 0.60) agreement, respectively, in the same subsets of paired specimens. CONCLUSIONS: Paired biopsy-resection specimens from pleural MM show overall moderate agreement in pathologic parameters. These findings may help guide postbiopsy management and triage of patients with MM.
Abdelhady SG, Fouda EM, Shaheen MA, et al., 2021, Spectrum of childhood interstitial and diffuse lung diseases at a tertiary hospital in Egypt, ERJ OPEN RESEARCH, Vol: 7
Mino-Kenudson M, Le Stang N, Daigneault JB, et al., 2021, The International Association for the Study of Lung Cancer Global Survey on Programmed Death-Ligand 1 Testing for NSCLC, JOURNAL OF THORACIC ONCOLOGY, Vol: 16, Pages: 686-696, ISSN: 1556-0864
Devaney R, Simpson T, Bush A, et al., 2021, Fructose 1,6-bisphosphatase deficiency as a cause of childhood interstitial lung disease, PEDIATRIC PULMONOLOGY, Vol: 56, Pages: 2362-2365, ISSN: 8755-6863
Johkoh T, Lee KS, Nishino M, et al., 2021, Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper from the Fleischner Society, RADIOLOGY, Vol: 298, Pages: 550-566, ISSN: 0033-8419
Johkoh T, Lee KS, Nishino M, et al., 2021, Chest CT Diagnosis and Clinical Management of Drug-Related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors A Position Paper From the Fleischner Society, CHEST, Vol: 159, Pages: 1107-1125, ISSN: 0012-3692
Salguero FJ, White AD, Slack GS, et al., 2021, Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723
Invernizzi R, Wu BG, Barnett J, et al., 2021, The respiratory microbiome in chronic hypersensitivity pneumonitis is distinct from that of idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 339-347, ISSN: 1073-449X
RATIONALE: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises following repeated exposure and sensitisation to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease but to date, no study has investigated the composition of microbial communities in the lower airways in CHP. OBJECTIVE: To characterise and compare the airway microbiome in subjects with CHP, idiopathic pulmonary fibrosis (IPF) and controls. METHODS: We prospectively recruited individuals diagnosed with CHP (n=110), IPF (n=45) and controls (n=28). Subjects underwent bronchoalveolar lavage and bacterial DNA was isolated, quantified by qPCR and the 16S rRNA gene was sequenced to characterise the bacterial communities in the lower airways. MAIN MEASUREMENTS AND RESULTS: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both IPF and CHP subjects included Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. However, in IPF, Firmicutes dominated while the percentage of reads assigned to Proteobacteria in the same group was significantly lower compared to CHP subjects. At the genus level, Staphylococcus was increased in CHP and Actinomyces and Veillonella in IPF. The lower airway bacterial burden in CHP subjects was higher than controls but lower than those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP. CONCLUSIONS: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF and, notably, bacterial burden in individuals with CHP fails to predict survival.
Popat S, Sharma B, MacMahon S, et al., 2021, Durable Response to Vismodegib in PTCH1 F1147fs Mutant Relapsed Malignant Pleural Mesothelioma: Implications for Mesothelioma Drug Treatment, JCO PRECISION ONCOLOGY, Vol: 5, Pages: 39-43
Bui LT, Winters NI, Chung M-I, et al., 2021, Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity., bioRxiv
Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD epithelial cells expressed higher levels of genes linked directly to the efficiency of viral replication and innate immune response. Additionally, we identified basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
Barnett J, Pulzato I, Javed M, et al., 2021, Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy, CLINICAL RADIOLOGY, Vol: 76, ISSN: 0009-9260
Raghu G, Remy-Jardin M, Ryerson CJ, et al., 2021, Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline (vol 202, pg e36, 2020), AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 203, Pages: 150-151, ISSN: 1073-449X
Cui W, Yousaf N, Bhosle J, et al., 2020, Real-world outcomes in thoracic cancer patients with severe Acute respiratory syndrome Coronavirus 2 (COVID-19): Single UK institution experience, Cancer Treatment and Research Communications, Vol: 25, Pages: 100261-100261, ISSN: 2468-2942
BACKGROUND: UK COVID-19 mortality rates are amongst the highest globally. Controversy exists on the vulnerability of thoracic cancer patients. We describe the characteristics and sequelae of patients with thoracic cancer treated at a UK cancer centre infected with COVID-19. METHODS: Patients undergoing care for thoracic cancer diagnosed with COVID-19 (RT-PCR/radiology/clinically) between March-June 2020 were included. Data were extracted from patient records. RESULTS: Thirty-two patients were included: 14 (43%) diagnosed by RT-PCR, 18 (57%) by radiology and/or convincing symptoms. 88% had advanced thoracic malignancies. Eleven of 14 (79%) patients diagnosed by RT-PCR and 12 of 18 (56%) patients diagnosed by radiology/clinically were hospitalised, of which four (29%) and 2 (11%) patients required high-dependency/intensive care respectively. Three (21%) patients diagnosed by RT-PCR and 2 (11%) patients diagnosed by radiology/clinically required non-invasive ventilation; none were intubated. Complications included pneumonia and sepsis (43% and 14% respectively in patients diagnosed by RT-PCR; 17% and 11% respectively in patients diagnosed by radiology/clinically). In patients receiving active cancer treatment, therapy was delayed/ceased in 10/12 (83%) and 7/11 (64%) patients diagnosed by RT-PCR and radiology/clinically respectively. Nine (28%) patients died; all were smokers. Median time from symptom onset to death was 7 days (range 3-37). CONCLUSIONS: The immediate morbidity from COVID-19 is high in thoracic cancer patients. Hospitalisation and treatment interruption rates were high. Improved risk-stratification models for UK cancer patients are urgently needed to guide safe cancer-care delivery without compromising efficacy.
Domingo-Sabugo C, Starren E, Mandal A, et al., 2020, Distinct Landscapes of Genomic Alterations between Lung Carcinoids and Non-Small Cell Lung Cancers, Publisher: SPRINGERNATURE, Pages: 528-528, ISSN: 1018-4813
Chang W-C, Zhang YZ, Wolf JL, et al., 2020, Mucinous adenocarcinoma arising in congenital pulmonary airway malformation: clinicopathological analysis of 37 cases, 108th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP) - Unlocking Your Ingenuity, Publisher: WILEY, Pages: 434-444, ISSN: 0309-0167
Dean C, Taylor B, Rice A, et al., 2020, Mechanism of lung development in the aetiology of adult congenital pulmonary airway malformations, Thorax, Vol: 75, Pages: 1001-1003, ISSN: 0040-6376
Congenital pulmonary airway malformations (CPAMs) are rare lung abnormalities that result in cyst formation and are associated with respiratory distress in infants and malignant potential in adults. The pathogenesis of CPAMs remains unknown but data suggest disruption of the normal proximo-distal programme of airway branching and differentiation. Here, we demonstrate that adult human CPAM are lined with epithelium that retains SOX-2 and thyroid transcription factor-1 immunohistochemical markers, characteristic of the developing lung. However, RALDH-1, another key marker, is absent. This suggests a more complex aetiology for CPAM than complete focal arrest of lung development and may provide insight to the associated risk of malignancy.
Moreira AL, Ocampo PSS, Xia Y, et al., 2020, A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee, JOURNAL OF THORACIC ONCOLOGY, Vol: 15, Pages: 1599-1610, ISSN: 1556-0864
Bartlett EC, Kemp S, Ridge CA, et al., 2020, Baseline Results of the West London lung cancer screening pilot study - Impact of mobile scanners and dual risk model utilisation, LUNG CANCER, Vol: 148, Pages: 12-19, ISSN: 0169-5002
Tokaca N, Cui W, Hazell S, et al., 2020, Squamous Non-Small-Cell Lung Cancer Molecularly Reclassified as Transdifferentiated Prostate Cancer Due to Identification of TMPRSS2-ERG Translocation With SOX2 Amplification, JCO ONCOLOGY PRACTICE, Vol: 16, Pages: 695-+, ISSN: 2688-1527
Hanley B, Naresh KN, Roufosse C, et al., 2020, Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study, The Lancet Microbe, Vol: 1, Pages: e245-e253, ISSN: 2666-5247
BackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of
Wolf JL, van Nederveen F, Blaauwgeers H, et al., 2020, Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel, Publisher: WILEY, Pages: 734-741, ISSN: 0309-0167
Stock CJ, Conti C, Montero-Fernandez Á, et al., 2020, Interaction between the promoter MUC5B polymorphism and mucin expression: is there a difference according to ILD subtype?, Thorax, Vol: 75, Pages: 901-903, ISSN: 0040-6376
The MUC5B promoter variant rs35705950 is associated with idiopathic pulmonary fibrosis (IPF). MUC5B glycoprotein is overexpressed in IPF lungs. We examined immunohistochemical expression of MUC5B in different interstitial lung disease patterns according to rs35705950 T-allele carriage. We observed increased expression of MUC5B in T-allele carriers in both distal airways and honeycomb cysts in patients with IPF (n=23), but no difference in MUC5B expression according to T-carrier status in the distal airways of patients with idiopathic non-specific interstitial pneumonitis (n=17), in scleroderma-associated non-specific interstitial pneumonitis (n=15) or in control lungs (n=20), suggesting that tissue overexpression in MUC5B rs35705950 T-carriers is specific to IPF.
Feary J, Parfrey H, Burge S, et al., 2020, Interstitial Lung Disease (ILD) in aluminium welders, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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