cGAS-STING PATHWAY LIMITS SARS-CoV-2 REPLICATION IN ACE2+ AIRWAY CELL LINES

Background: We previously screened 10 human lung and upper airway cell lines expressing variable levels of endogenous ACE2/TMPRSS2. We found that H522 human lung adenocarcinoma cells supported SARS-CoV-2 replication independent of ACE2, whereas the ACE2 positive cell lines were not permissive to infection. Type I/III interferons (IFNs) potently restrict SARS-CoV-2 replication through the actions of hundreds of interferon-stimulated genes (ISGs) that are upregulated upon IFN signaling. Here we report that a number of ACE2 positive airway cell lines are unable to support SARS-CoV-2 replication due to basal activation of the cGAS-STING DNA sensing pathway and subsequent upregulation of IFNs and ISGs which restrict SARS-CoV-2 replication. Method(s): SARS-CoV-2 WT strain 2019-nCoV/USA-WA1/2020 viral replication was detected through analysis of cell associated RNA. RNA sequencing was used to study the basal level of genes in the type-I IFN pathway in the 10 cell lines, which was further validated by western blotting and qRT-PCR. A panel of 5 cell lines, with varying expression levels of ACE2 and TMPRSS2, were pre-treated with Ruxolitinib, a JAK1/2 inhibitor. A siRNA-mediated screen was used to determine the molecular basis of basally high expression of ISGs in cell lines. CRISPR knockout of IFN-alpha receptor and cGAS-STING pathway components was conducted in parallel Results: Here we show that higher basal levels of IFN pathway activity underlie the inability of ACE2+ cell lines to support virus replication. Importantly, this IFN-induced block can be overcome by chemical inhibition and genetic disruption of the IFN signaling pathway or by ACE2 overexpression, suggesting that one or more saturable ISGs underlie the lack of permissivity of these cells. Ruxolitinib treatment increased SARS-CoV-2 RNA levels by nearly 3 logs in OE21 and SCC25. Furthermore, the baseline activation of the STING-cGAS pathway accounts for the high ISG levels and genetic disruption of the cGAS-STING pathway enhances levels by nearly 2 and 3 logs of virus replication in the two separate ACE2+ cell line models respectively. Conclusion(s): Our findings demonstrate that cGAS-STING-dependent activation of IFN-mediated innate immunity underlies the inability of ACE2+ airway cell lines to support SARS-CoV-2 replication. Our study highlights that in addition to ACE2, basal activation of cGAS-STING pathway, IFNs and ISGs may play a key role in defining SARS-CoV-2 cellular tropism and may explain the complex SARS-CoV- 2 pathogenesis in vivo.

EBUS audit: assessing the diagnostic performance of the service at UHL

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an important diagnostic procedure in the lung cancer pathway. False-negative or inadequate sampling can lead to inaccurate staging or delay in diagnosis. This study was conducted to assess the performance of the Cancer EBUS service at a tertiary hospital. Method(s): We conducted a retrospective analysis of patients who underwent EBUS-TBNA for suspected cancer between 1st June 2021 to 31st May 2022. Request forms, CT reports, EBUS reports and pathology reports were reviewed for analysis. Result(s): 205 EBUS-TBNA procedures were performed. All patients had an appropriate staging CT prior to procedure. The mean time to test was 10.5 days (7.4). 77 (38%) had tests within 7 days of request. 293 lymph nodes and 10 mass lesions were sampled. The mean time to pathological results being received was 2.9 days (1.8). Final histology showed 39 (19%) cases of lung adenocarcinomas, 3 (1%) lung non-small cell carcinomas, 25 (12%) lung squamous cell carcinomas, 25 (12%) small cell cancers, 4 (2%) lung NOS, 3 (1%) pulmonary carcinoid, 2 (1%) lymphoma, 12 (6%) other cancers, 12 granulomata and 1 thyroid tissue (6%). 43 (21%) cases showed lymphoid tissue and 28 (14%) were reported as inadequate. No samples were taken in 8 cases (4%). Adequate tissue for predictive marker testing was available in 93% (66) of cases of non-small cell lung cancer (NSCLC). Complications were encountered in 9 cases (4%). Only 3 cases (1.5%) required any form of intervention. [Figure presented] Conclusion(s): Our data provides assurance of safety while also highlighting specific areas for attention regarding performance and time to test that can be addressed and our sensitivity was comparable to national standards. The increased waiting times may be partly related to COVID-19 precautions and will require reauditing at a later date. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.

Pulmonary artery resection and reconstruction in locally advanced lung cancer with moderate hemoptysis

Lobectomy with pulmonary artery (PA) angioplasty in locally advanced lung cancer is an alternative to pneumonectomy. It is feasible, oncologically effective and the procedure of choice in patients with recurrent hemoptysis and limited pulmonary reserves. We present a case of a successful left upper lobectomy with PA resection and reconstruction by an autologous pericardial patch.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Immunohistochemical profile of cell cycle control, proliferation and differentiation proteins of the pulmonary atypical alveolar epithelium with COVID-19-induced diffuse alveolar damage as compared to pulmonary [lepidic-growth] adenocarcinoma.

We aim aim to compare immunophenotypic charac-teritics of atypical epithelium (AE) with COVID-19-induced diffuse alveolar damage (DAD) and pulmonary lepidic-growth adenocarcinoma, accounting for cell cycle control, proliferation and differentiation]. Methods. We examined pulmonary tissue specimens from twenty-four fatal cases of CO VID-19-induced acute respiratory damage syndrome confirmed by autopsy (Group 1) and four cases of pulmonary lepidic-growth adenocarcinoma (Group 2). Perpendicular dimensions of 10 nuclei were measured on the H&E slides, means of their sums of products (SPNM) were calculated. We have used p53, Ki67, pi6, p63 antibodies for immunohistochemical staining in each case. We evaluate colour intensity, rate of stained cells of AE and the product of these parameters. We evaluated separately Nuclear and cyto-plasmic staining (couple) and only cytoplasmic staining (cyt) for pi6 expression. We measured proliferative index only at KI-67 stained slides. U-test and Spearman rank correlation test were used for statistical analysis. Results. Expression of p63 was higher in group 1 (p=0.001), while pi6 was more frequently expressed in group 2 (p=0.002). We have found no statistically significant differences (p>0.1) in the p53 and Ki67 expression. Group 1 showed There was negative correlation between the number of days from onset of symptoms and the following variables: Ki67 (r=M).587, p=0.003);SPNM (r 0.406, p=0.049). Conclusion. The present study has shown heterogeneity in levels of cell cycle control expression, proliferation and differentiation of atypical epithelium in the pulmonary lep-idic-growth adenocarcinoma and CO VID-19-induced diffuse alveolar damage.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy!

Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion(s): These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN.Copyright © The Author(s) 2022.

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

Immunohistochemical profile of cell cycle control, proliferation and differentiation proteins of the pulmonary atypical alveolar epithelium with COVID-19-induced diffuse alveolar damage as compared to pulmonary [lepidic-growth] adenocarcinoma

We aim aim to compare immunophenotypic charac-teritics of atypical epithelium (AE) with COVID-19-induced diffuse alveolar damage (DAD) and pulmonary lepidic-growth adenocarcinoma, accounting for cell cycle control, proliferation and differentiation]. Methods. We examined pulmonary tissue specimens from twenty-four fatal cases of CO VID-19-induced acute respiratory damage syndrome confirmed by autopsy (Group 1) and four cases of pulmonary lepidic-growth adenocarcinoma (Group 2). Perpendicular dimensions of 10 nuclei were measured on the H&E slides, means of their sums of products (SPNM) were calculated. We have used p53, Ki67, pi6, p63 antibodies for immunohistochemical staining in each case. We evaluate co¬lour intensity, rate of stained cells of AE and the product of these parameters. We evaluated separately Nuclear and cyto-plasmic staining (couple) and only cytoplasmic staining (cyt) for pi6 expression. We measured proliferative index only at KI-67 stained slides. U-test and Spearman rank correlation test were used for statistical analysis. Results. Expression of p63 was higher in group 1 (p=0.001), while pi6 was more frequently expressed in group 2 (p=0.002). We have found no statistically significant differences (p>0.1) in the p53 and Ki67 expression. Group 1 showed There was negative correlation between the number of days from onset of symptoms and the following variables: Ki67 (r=M).587, p=0.003);SPNM (r 0.406, p=0.049). Conclusion. The present study has shown heterogeneity in levels of cell cycle control expression, proliferation and differentiation of atypical epithelium in the pulmonary lep-idic-growth adenocarcinoma and CO VID-19-induced diffuse alveolar damage.

An unusual presentation of malignant Invasive Mucinous Adenocarcinoma of Lung mimicking Pulmonary Renal syndrome

Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.

Concurrent lung adenocarcinoma hidden among multiple shadows of COVID-19 pneumonia: A rare and instructive case report.

A 40-year-old man was admitted with a diagnosis of COVID-19 pneumonia. Although most of multiple ground-glass opacities and consolidations on computed tomography improved, a round ground-glass opacity with consolidation remained unchanged and was suspected to be a part-solid nodule of lung adenocarcinoma. Pathologic diagnosis of resected tumor was papillary adenocarcinoma.

MTOR hypermethylation may associate with the susceptibility and survival of SARS-CoV-2 infections to lung adenocarcinoma patients based on multi-omics data and machine learning

Recent studies have shown that lung adenocarcinoma (LUAD) patients have a higher risk and worse prognosis of COVID-19 caused by SARS-CoV-2 compared to normal samples. Whereas, in addition to the receptor for SARS-CoV-2, other genes also deserve attention. In our study, we identified 19 differentially methylated genes (DMGs) that were co-upregulated in LUAD and COVID-19 samples. These 19 DMGs mainly regulated the immune-related and multiple viral infection signaling pathways. Gene Ontology and pathway enrichment analysis were applied with these genes. Then, 6 key DMGs (MTOR, ACE, IGF1, PTPRC, C3, and PTGS2) were identified by constructing and analyzing the protein-protein interaction (PPI) network. Besides, MTOR was significantly associated with 5 prognostic markers (CDO1, NEURL4, SMAP1, NPEPPS, IQCK) identified by survival analysis based on machine learning. In total, MTOR hypermethylation may be related to the susceptibility of LUAD patients to SARS-CoV-2 and the prognosis of LUAD patients suffering from COVID-19. © 2022 IEEE.

Mechanistic studies of MALAT1 in respiratory diseases.

Background: The incidence of respiratory diseases and the respiratory disease mortality rate have increased in recent years. Recent studies have shown that long non-coding RNA (lncRNA) MALAT1 is involved in various respiratory diseases. In vascular endothelial and cancer cells, MALAT1 expression triggers various changes such as proinflammatory cytokine expression, cancer cell proliferation and metastasis, and increased endothelial cell permeability. Methods: In this review, we performed a relative concentration index (RCI) analysis of the lncRNA database to assess differences in MALAT1 expression in different cell lines and at different locations in the same cell, and summarize the molecular mechanisms of MALAT1 in the pathophysiology of respiratory diseases and its potential therapeutic application in these conditions. Results: MALAT1 plays an important regulatory role in lncRNA with a wide range of effects in respiratory diseases. The available evidence shows that MALAT1 plays an important role in the regulation of multiple respiratory diseases. Conclusion: MALAT1 is an important regulatory biomarker for respiratory disease. Targeting the regulation MALAT1 could have important applications for the future treatment of respiratory diseases.

Network Pharmacology and Bioinformatics Analysis Identifies Potential Therapeutic Targets of Paxlovid Against LUAD/COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic in many countries around the world. The virus is highly contagious and has a high fatality rate. Lung adenocarcinoma (LUAD) patients may have higher susceptibility and mortality to COVID-19. While Paxlovid is the first oral drug approved by the U.S. Food and Drug Administration (FDA) for COVID-19, its specific drug mechanism for lung cancer patients infected with COVID-19 remains to be further studied. Methods: COVID-19 related genes were obtained from NCBI, GeneCards, and KEGG, and then the transcriptome data for LUAD was downloaded from TCGA. The drug targets of Paxlovid were revealed through BATMAN-TCM, DrugBank, SwissTargetPrediction, and TargetNet. The genes related to susceptibility to COVID-19 in LUAD patients were obtained through differential analysis. The interaction of LUAD/COVID-19 related genes was evaluated and displayed by STRING, and a COX risk regression model was established to screen and evaluate the correlation between genes and clinical characteristics. The Venn diagram was drawn to select the candidate targets of Paxlovid against LUAD/COVID-19, and the functional analysis of the target genes was performed using KEGG and GO enrichment analysis. Finally, Cytoscape was used to screen and visualize the Hub Gene, and Autodock was used for molecular docking between the drug and the target. Result: Bioinformatics analysis was performed by combining COVID-19-related genes with the gene expression and clinical data of LUAD, including analysis of prognosis-related genes, survival rate, and hub genes screened out by the prognosis model. The key targets of Paxlovid against LUAD/COVID-19 were obtained through network pharmacology, the most important targets include IL6, IL12B, LBP. Furthermore, pathway analysis showed that Paxlovid modulates the IL-17 signaling pathway, the cytokine-cytokine receptor interaction, during LUAD/COVID-19 treatment. Conclusions: Based on bioinformatics and network pharmacology, the prognostic signature of LUAD/COVID-19 patients was screened. And identified the potential therapeutic targets and molecular pathways of Paxlovid Paxlovid in the treatment of LUAD/COVID. As promising features, prognostic signatures and therapeutic targets shed light on improving the personalized management of patients with LUAD.

Atypical Cells on Transbronchial Biopsies of Peripheral Pulmonary Lesions: How Should We Interpret the Result?

SESSION TITLE: Lung Nodule Biopsy: Yield and Accuracy SESSION TYPE: Original Investigations PRESENTED ON: 10/16/2022 10:30 am - 11:30 am PURPOSE: Atypia is common on biopsy specimens of peripheral pulmonary lesions (PPLs) and may result from inflammation or inadequate sampling of a malignancy. The significance of atypical cells on PPLs biopsies has not been well described. In addition, recent studies of navigational bronchoscopy have variably considered atypia on biopsies as diagnostic. METHOD(S): We analyzed a prospective database of consecutive PPLs sampled via navigational bronchoscopy at our institution (IRB: 212187). Search terms "atypia" and "atypical" were applied to pathology reports generated by these procedures. Manual inspection ensured atypia was present in the PPL itself. Definitive PPL diagnosis was established during a two-year routine clinical follow-up. Bronchoscopy diagnostic yield was defined as histopathological findings which readily explained a nodule (malignancy, organizing pneumonia, frank purulence, granulomatous inflammation) and permitted management of the patient without an immediate additional diagnostic intervention. Atypia was considered nonspecific and, therefore, nondiagnostic. RESULT(S): From 11/2017 to 4/2019, 461 biopsied PPLs were identified. Eleven cases, none exhibited atypia, lacked complete two-year follow-up, and were excluded. Ultimately, 274 of 450 (61%) analyzed PPLs were malignant. Diagnostic biopsies were obtained in 331 (73.5%) cases. Atypical cells were present in 33 PPLs (7% of overall cohort, 28% of the 119 nondiagnostic cases). Two-thirds (22 of 33) were eventually determined to be malignant. Lung adenocarcinoma was the most common ultimate malignant diagnosis (10 cases). Most benign PPLs with atypia regressed on follow-up imaging without further pathological data (5 cases). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of atypia for an eventual diagnosis of malignancy among the 223 PPLs not diagnosed as malignant at index bronchoscopy were 46% (95% CI 31-61%), 94% (89-97%), 92% (85-96%), and 53% (46-60%), respectively, with positive likelihood ratio (+LR) of 7.3 (3.8-14). CONCLUSION(S): The presence of atypical cells was a common finding, found in 28% of PPLs without a specific diagnosis after bronchoscopy. Two-thirds of PPLs with atypia were ultimately malignant, with a high PPV (92%) for malignant diagnosis in this cohort with an overall prevalence of malignancy of 61%. CLINICAL IMPLICATIONS: Atypia not diagnostic of malignancy in bronchoscopic biopsy specimens is a nonspecific finding, which may be due to inadequate sampling of a malignant PPL or inflammation. However, the high PPV and +LR of atypia for ultimate malignant PPL diagnosis suggest that in populations with a similar prevalence of malignancy and/or in the clinical context of a high pre-test probability of malignancy, atypical findings might prompt repeat biopsy or definitive PPL management (resection or ablation). DISCLOSURES: No relevant relationships by Robert Lentz No relevant relationships by Kaele Leonard No relevant relationships by See-Wei Low PI ofan investigator-initiated study relationship with Medtronic Please note: >$100000 by Fabien Maldonado, value=Grant/Research Support PI on investigator-initiated relationship with Erbe Please note: $5001 - $20000 by Fabien Maldonado, value=Grant/Research Support Consulting relationship with Medtronic Please note: $5001 - $20000 by Fabien Maldonado, value=Honoraria co-I industry-sponsored trial relationship with Lung Therapeutics Please note: $5001 - $20000 by Fabien Maldonado, value=Grant/Research Support Board of director member relationship with AABIP Please note: $1-$1000 by Fabien Maldonado, value=Travel Consultant relationship with Medtronic/Covidien Please note: $1001 - $5000 by Otis Rickman, value=Consulting fee No relevant relationships by Briana Swanner Copyright © 2022 American College of Chest Physicians

PRIMARY PULMONARY CAVITATING ADENOCARCINOMA IN A PATIENT PRESENTING WITH COVID-19 PNEUMONIA: A CASE REPORT

SESSION TITLE: Lung Cancer Imaging Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: SARS-CoV-2 pneumonia typically presents with ground-glass and consolidative pulmonary opacities, atypically small cavities may be seen in severe cases. In patients with cavities persisting beyond 12 weeks, an underlying malignancy is a worrisome concern. We present a case of a 39-year old female without significant risk factors for pulmonary malignancy who was found, surprisingly, to have a cavitating adenocarcinoma in the setting of COVID-19 Pneumonia. CASE PRESENTATION: A 39 year old obese African American female, never smoker, with co-existing metabolic syndrome presented to our institution with a four day history of productive cough (without hemoptysis), body aches, fever and fatigue. She denied weight loss or loss of appetite. No known family history of malignancy. She tested positive for SARS-CoV-2. She was clinically stable, hence discharged home with recommendations for quarantine and supportive care. She returned the following day with worsening dyspnea. Her chest radiograph noted a supra-hilar opacity with central lucency, Chest CT revealed wedge-shaped ground-glass and consolidative density in the right lower lobe and a 3.8 x 4.1 cm cavitary right upper lobe mass with mediastinal lymphadenopathy. She received parenteral antibiotic therapy and underwent infectious and autoimmune workup, which was negative. Repeat CT imaging, approximately three months post discharge, revealed persisting cavitary lesion and enlarging mediastinal lymphadenopathy. She underwent Electromagnetic Navigational Bronchoscopy with biopsy and fine needle aspiration of mediastinal lymph nodes (stations 7 and 4R) via endobronchial ultrasound. Biopsy results and fine needle aspiration of lymph nodes revealed adenocarcinoma with tumor cells being positive for TTF-1 and negative for CK20, CDX2, GATA3, PAX8 and Synaptophysin. Next generation sequencing reported several variants including EGFR and Tp53, there was also noted amplification of CDK4 and MDM2. PDL-1 was negative. DISCUSSION: A cavity is a gas-filled space, seen as a lucency or low-attenuation area, within a nodule, mass, or area of parenchymal consolidation. Underlying etiologies are typically classified as infectious, autoimmune and malignant. Cavities are atypical findings on CT imaging in patients with viral pneumonias, including SARS-CoV-2. Those cavities persisting beyond 12 weeks are typically classified as being chronic, with malignancy a key concern in these patients. The most common type of primary cavitary lung cancer is squamous cell carcinoma, in fact Primary Pulmonary Adenocarcinomas are unlikely to cavitate. Treatment options, depending on the presence of targetable mutations, include concurrent chemoradiation, chemoimmunotherapy or oral targeted agent. CONCLUSIONS: Though an atypical presentation, Pulmonary Adenocarcinoma may present as a cavitary lesion, particularly in the presence of persisting or enlarging lymphadenopathy. Reference #1: Gafoor K, Patel S, Girvin F, Gupta N, Naidich D, Machnicki S, Brown KK, Mehta A, Husta B, Ryu JH, Sarosi GA, Franquet T, Verschakelen J, Johkoh T, Travis W, Raoof S. Cavitary Lung Diseases: A Clinical-Radiologic Algorithmic Approach. Chest. 2018 Jun;153(6):1443-1465. doi: 10.1016/j.chest.2018.02.026. Epub 2018 Mar 6. PMID: 29518379. Reference #2: Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to COVID-19: Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA Scott Simpson, Fernando U. Kay, Suhny Abbara, Sanjeev Bhalla, Jonathan H. Chung, Michael Chung, Travis S. Henry, Jeffrey P. Kanne, Seth Kligerman, Jane P. Ko, and Harold Litt Radiology: Cardiothoracic Imaging 2020 2:2 DISCLOSURES: No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No releva t relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Sulaiman Tijani

COVID-19 VACCINATION-ASSOCIATED LYMPHADENOPATHY: A DIAGNOSTIC CONUNDRUM IN LUNG CANCER STAGING

SESSION TITLE: Lung Cancer Imaging Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic affected millions of people globally, prompting the emergent need for an effective vaccine. Lymphadenopathy associated with COVID-19 vaccine is a recognized phenomenon that can present a diagnostic dilemma for staging thoracic malignancies. We present a case of post COVID-19 vaccination axillary lymphadenopathy complicating the staging process for a patient with newly diagnosed lung adenocarcinoma. CASE PRESENTATION: A 64-year-old-male with chronic obstructive pulmonary disease, former smoker with a 20-pack-year smoking history was found to have a 1.7 cm solid nodule in the left upper lobe with irregular margins on low dose computed tomography (CT) scan of the chest for lung cancer screening. Fine needle aspiration of the nodule was done, and histopathology results were consistent with the diagnosis of adenocarcinoma. Patient then underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) scan that showed a 16 mm nodule in the left upper pulmonary lobe with maximum standardized uptake value (SUVmax) of 5.3 and left axillary nodes measuring up to 8 mm with SUVmax of 4.4 concerning for metastatic disease. On further history, patient had received the Pfizer mRNA vaccination booster three days prior to undergoing the FDG-PET scan. Patient was evaluated by oncology and decision was made to treat with a 7-day course of prednisone 20 mg daily and to repeat FDG-PET scan. FDG-PET scan done four weeks later showed resolution of axillary lymphadenopathy. Patient was clinically staged as T1bN0M0 stage 1A and underwent robotic left upper lobe lingular-sparing lobectomy. DISCUSSION: In patients with thoracic malignancies, lymphadenopathy related to COVID-19 vaccination with avid FDG uptake on PET scan was reported in 29% of patients (2). The presentation of FDG avid lymphadenopathy creates a clinical challenge by confounding accurate cancer staging and leading to unnecessary workup (3). More importantly, detection of lymphadenopathy while staging lung cancer has crucial implications in the process of triaging patients to oncologic management in terms of candidacy for surgical resection (3). Currently, no consensus is available to guide management for incidental lymphadenopathy associated with COVID-19 vaccination in lung cancer patients. For this patient, we chose to treat with steroids and to obtain repeat imaging within 4 weeks of the original FDG-PET to not delay treatment planning. Repeat imaging showed resolution of the axillary lymphadenopathy and patient was able to undergo definitive treatment promptly. CONCLUSIONS: This case highlights the diagnostic challenge posed by COVID-19 lymphadenopathy in patients with newly diagnosed lung cancer and delineates our approach to navigating this challenge to avoid malignancy up-staging and treatment delay. Reference #1: Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577 Reference #2: Nishino M, Hatabu H, Ricciuti B, Vaz V, Michael K, Awad MM. Axillary Lymphadenopathy After Coronavirus Disease 2019 Vaccinations in Patients with Thoracic Malignancy: Incidence, Predisposing Factors, and Imaging Characteristics. J Thorac Oncol. 2022;17(1):154-159. doi:10.1016/j.jthoCH.2021.08.761 Reference #3: Lehman CD, D'Alessandro HA, Mendoza DP, Succi MD, Kambadakone A, Lamb LR. Unilateral Lymphadenopathy After COVID-19 Vaccination: A Practical Management Plan for Radiologists Across Specialties. J Am Coll Radiol. 2021;18(6):843-852. doi: 10.1016/j.jacr.2021.03.001 DISCLOSURES: No relevant relationships by Hadya Elshakh No relevant relationships by Stephen Karbowitz No relevant relationships by Gina Villani

POST-COVID-19 CHANGES MASKED A MALIGNANCY: INVASIVE MUCINOUS ADENOCARCINOMA

SESSION TITLE: Challenges in Lung Tumors SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Patients can have a variety of post Coronovirus induced disease (COVID) associated interstitial lung diseases (ILD) ranging from cystic lung disease to fibrinous organizing pneumonia. However, very little is known about malignancies that have been overshadowed by post COVID associated pulmonary changes. We present one such case of insidious invasive mucinous adenocarcinoma of the lung that was masked by post COVID related changes. CASE PRESENTATION: A 70 year old female with COPD, systolic heart failure and significant tobacco use disorder presented with progressively worsening hypoxemic respiratory failure. She has had 4 hospitalizations in past year all for acute on chronic hypoxemic respiratory failure following COVID. She has been on Supplemental Oxygen 3L/min since her infection with SARS-COV2. Patient was found to have worsening bibasilar ground glass opacities (GGO) on CT of chest over the past 1 year since having COVID. She was treated with several rounds of steroids without any relief. Patient had a PET scan that showed a very avid left upper lobe consolidation. Given these worsening abnormalities and symptoms, she underwent bronchoscopy with transbronchial biopsy guided by the positive PET scan and fluoroscopy. However, during bronchoscopy she had copious secretions which were therapeutically cleared helping relieve some of patient's hypoxemia. All her cultures and Fungitell assay on bronchoalveolar lavage were negative. However, post biopsy pathology came back positive for Invasive Mucinous Adenocarcinoma. Patient was treated with chemo and radiation therapy with good response against her malignancy and significant relief in her hypoxemia. DISCUSSION: COVID associated pneumonia is well known to cause chronic hypoxemic respiratory failure. Post COVID related pulmonary changes range from organizing pneumonia to fungal pneumonia. However, patients should start to recover with time as inflammatory changes resolve on CT scan with adequate steroids or anti-fungals. If patients continue to deteriorate then a prompt work-up that rules out other infections and even malignancies is warranted as seen in our patient. This case brings forth an important consideration for aggressively pursuing an adequate work-up in the face of worsening GGO on the CT and patient's continual deterioration due to her hypoxemic respiratory failure. Our patient was able to be adequately diagnosed with malignancy and was then started on chemotherapy that allowed for adequate control of her hypoxemic respiratory failure and helped improve her quality of life. CONCLUSIONS: Post COVID related pulmonary changes can be from a variety of ILD and infections. However, clinician should be vigilant in considering malignancy as a possible etiology of post COVID related changes and initiate an adequate work-up to help evaluate for cancer that can be masked amongst post COVID related ILD. Reference #1: Beck KS, Sung YE, Lee KY, Han DH. Invasive mucinous adenocarcinoma of the lung: Serial CT findings, clinical features, and treatment and survival outcomes. Thorac Cancer. 2020 Dec;11(12):3463-3472. doi: 10.1111/1759-7714.13674. Epub 2020 Oct 5. Reference #2: Matsui T, Sakakura N, Koyama S, Nakanishi K, Sasaki E, Kato S, Hosoda W, Murakami Y, Kuroda H, Yatabe Y. Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma. Ann Thorac Surg. 2020 Nov 24:S0003-4975(20)32001-4. doi: 10.1016/j.athoracsur.2020.09.042. Epub ahead of print. Reference #3: Lee MA, Kang J, Lee HY, Kim W, Shon I, Hwang NY, Kim HK, Choi YS, Kim J, Zo JI, Shim YM. Spread through air spaces (STAS) in invasive mucinous adenocarcinoma of the lung: Incidence, prognostic impact, and prediction based on clinicoradiologic factors. Thorac Cancer. 2020 Nov;11(11):3145-3154. doi: 10.1111/1759-7714.13632. Epub 2020 Sep 25. DISCLOSURES: No relevant relationships by Danya Ahmed No relevant relationships by David Chambers No rele ant relationships by Jalal Damani No relevant relationships by Deon Ford No relevant relationships by Rachaita Lakra

PRIMARY LUNG MALIGNANCY PRESENTING AS RARE CUTANEOUS METASTASIS TO EYELID

SESSION TITLE: Unusual Cancer Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Cutaneous lesions may present as a clue to an internal malignancy and provide an easily accessible site for tissue confirmation. We present a case of an eyelid metastatic lesion presenting as an initial sign of primary pulmonary malignancy. CASE PRESENTATION: A 67-year-old woman with past medical history of SARS-COVID-2 pneumonia six months ago and reformed smoker (26 pack year) who quit 27 years ago, presented to the primary care physician's office with a chief complaint of a small right upper eyelid margin (base of eyelashes) lesion (Figure 1A), and ongoing nonproductive cough and fatigue since diagnosis of SARS-COVID-2 pneumonia. The eyelid lesion appeared two weeks prior and had quickly grown in size. The lesion was associated with mild itching, but without any associated pain, discharge, or bleeding. She also complained of left elbow and foot pain but denied fever, chills, rigors, hemoptysis, pleurisy, and weight loss. Physical examination was negative for lymphadenopathy. Chest x-ray revealed a hazy left upper lobe opacity. Urine antigen for blastomycoses and histoplasma were negative. Rheumatoid factor, erythrocyte sedimentation rate, C reactive protein, QuantiFERON TB gold and anti-nuclear and cyclic citrullinated peptide antibodies were negative. Computed tomography of chest revealed a left upper lobe 3.7 x 5.4 x 5.6 cm mass, numerous bilateral ground glass opacities, and scattered (less than 5 mm) nodules (Figure 1B). Simultaneously, the patient was evaluated by an ophthalmologist for excision of the eyelid lesion. Histopathological evaluation revealed malignancy compatible with metastatic lung adenocarcinoma (Figure 1C) DISCUSSION: While an uncommon presentation, this case highlights the importance of a through history and examination in a patient presenting with pulmonary symptoms with risk factors for a lung malignancy. While she did have imaging that demonstrated lung masses, the diagnosis of lung cancer came not from invasive sampling of these masses, but rather from excision and histopathological evaluation of an eyelid soft tissue mass. Lung cancer is prone to metastasis, however cutaneous manifestations of lung cancer are relatively rare and are more common in the advanced stages of disease, making cutaneous metastasis a poor prognostic factor. In terms of cutaneous metastases, ocular metastases are one of the rarest locations making this a unique presentation. In a patient presenting with pulmonary masses, any concurrent development of new and/or growing skin lesions should be evaluated to rule out metastasis and potentially yield diagnosis. CONCLUSIONS: In patients presenting with concern for a malignant lung process, a skin exam should be completed, and suspicious skin lesions should be biopsied. Although rare, lung malignancies do metastasize to ocular cutaneous tissues and are a marker of more advanced stage of the malignancy. Reference #1: Hidaka T, Ishii Y, Kitamura S. Clinical features of skin metastasis from lung cancer. Intern Med. 1996;35:459-462. Reference #2: Marcoval J, Penin RM, Llatjos R, Martinez-Ballarin, I. Cutaneous metastasis from lung cancer: retrospective analysis of 30 patients. Australas J Dermatol. 2012;53(4):288-290. Reference #3: Abdeen Y, Amireh S, Patel A, Al-Halawani M, Shaaban H, Miller R. Cutaneous metastasis as a first presentation for lung adenocarcinoma. N Am J Med Sci. 2016;8(5): 222-225. DISCLOSURES: No relevant relationships by Gregory Griepentrog No relevant relationships by Chinmay Jani No relevant relationships by Bailey Ray No relevant relationships by Harpreet Singh No relevant relationships by Amit Taneja No relevant relationships by Kara Young

IDENTIFYING A NOVEL SURFACTANT PROTEIN MUTATION IN A FAMILY WITH PULMONARY FIBROSIS

SESSION TITLE: Rare Genetic Mutations and Anatomical Variants SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fatal disease affecting older adults that results in progressive scarring of the lung parenchyma. Familial IPF (FPF), defined by disease in two or more first-degree relatives, is estimated to occur in 2–20% of all IPF cases and can present with varying phenotypes which may be difficult to diagnose. Inherited gene variation as well as environmental factors predispose a patient to disease development. Additionally, rare genetic variants in the genes encoding surfactant A (SFTPA1, and SFTPA2) that affect alveolar stability and endoplasmic reticulum stress have been reported in less than 1% of FPF cases. Understanding these genetic variants is essential in the diagnosis and management of patients with FPF. CASE PRESENTATION: A 47-year-old Hispanic male with a history of COVID-19 one year ago (not requiring hospitalization) presented to the hospital for a two-day history of subjective fever and shortness of breath. He was hypoxic requiring oxygen via high flow nasal cannula. He was admitted four months ago for shortness of breath and treated for pneumonia. Since then, he has had chronic dyspnea with exertion. Computed tomography of the chest showed extensive ground glass opacities, worse in the right lung, with basilar and upper lobe honeycombing, and air bronchograms in the bilateral lower lobes. Family history was significant for a mother, maternal aunt, maternal grandfather, and maternal cousin who all died from pulmonary fibrosis. His maternal cousin was treated at our facility, in which genetic sequencing revealed a mutation in SFTPA2, c.697T>C. Our patient was found to have the same genetic mutation. DISCUSSION: The genetic basis of IPF remains poorly understood. Prior studies suggest only 20-30% of FPF cases harbor an identifiable causative genetic variant. Rare variants in two biologic pathways contribute to the known heritability of FPF including pathologic variants in surfactant related genes which cause improper protein trafficking leading to endoplasmic reticulum stress, defects in autophagy, and type II alveolar cell toxicity. SFTPA1 and SFTPA2 variants have been associated with FPF and lung adenocarcinoma in a small number of families and there are few reported cases. While currently the SFTPA2, c.697T>C mutation, previously reported by our group in 2016, is considered a variant of unknown significance, its occurrence in two relatives with serious progressive interstitial lung diseases suggests that it is indeed pathogenic. CONCLUSIONS: Gene sequencing should be considered for all patients with a family history of pulmonary fibrosis as identification of a rare genetic variant may offer guidance to diagnosis, prognostication, and risk stratification when considering lung transplantation as well as identify additional relatives who may be affected by IPF. Reference #1: Kropski JA, Young LR, Cogan JD, et al. Genetic Evaluation and Testing of Patients and Families with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017;195(11):1423-1428. doi:10.1164/rccm.201609-1820PP Reference #2: Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009 Jan;84(1):52-9. doi: 10.1016/j.ajhg.2008.11.010. Epub 2008 Dec 18. PMID: 19100526;PMCID: PMC2668050. Reference #3: Pulmonary Fibrosis Due to a Novel Surfactant Protein Mutation R.A. Arciniegas Flores, I.A. Vital, K. Medepalli, D. DeMarzo, M.K. Glassberg Csete, R.A. Alvarez. https://doi.org/10.1164/ajrccm-conference.2019.199.1_Meetings.A5437 DISCLOSURES: No relevant relationships by Roger Alvarez No relevant relationships by Eduardo Lopez Gonzalez No relevant relationships by Anita Singh