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Mediastinal Lymphadenopathy in Lung Cancer Screening: A Red Flag

2021; Radiological Society of North America; Volume: 302; Issue: 3 Linguagem: Inglês

10.1148/radiol.212501

1527-1315

Mario Mascalchi, Maurizio Zompatori,

Lymphoma Diagnosis and Treatment

HomeRadiologyVol. 302, No. 3 PreviousNext Reviews and CommentaryFree AccessEditorialMediastinal Lymphadenopathy in Lung Cancer Screening: A Red FlagMario Mascalchi , Maurizio ZompatoriMario Mascalchi , Maurizio ZompatoriAuthor AffiliationsFrom the Clinical Epidemiology and Clinical Governance Support Unit, Oncological Network, Prevention and Research Institute (ISPRO), via Cosimo il Vecchio 2, Florence, 50139, Italy (M.M.); Department of Clinical and Experimental Biomedical Sciences “Mario Serio,” University of Florence, Florence, Italy (M.M.); and Department of Radiology, S. Giuseppe Hospital, Multimedica IRCCS, Milan, Italy (M.Z.).Address correspondence to M.M. (e-mail: [email protected]).Mario Mascalchi Maurizio ZompatoriPublished Online:Nov 23 2021https://doi.org/10.1148/radiol.212501MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Chalian et al and the editorial by McLoud in this issue.Dr Mario Mascalchi is a full professor of translational technical and medical sciences at the University of Florence, Italy. He is radiology coordinator for the lung cancer screening programs at the Oncological Network, Prevention and Research Institute (ISPRO), Florence, Italy. His research interests focus on lung and colorectal cancer screening with CT and on neuroimaging.Download as PowerPointOpen in Image Viewer Dr Maurizio Zompatori is full professor and former chairman of radiology at the University of Bologna and director of the radiology services at the S. Orsola-Malpighi Bologna University Hospital, Italy. He was formerly director and chairman at Parma University Hospital. Since 2017, he has been senior consultant of radiology at S. Giuseppe Hospital, Multimedica IRCCS, Milan, Italy. His main clinical and research interests are in the areas of thoracic and cardiac diseases.Download as PowerPointOpen in Image Viewer Low-dose CT (LDCT) lung cancer screening allows detection of surgically treatable early lung cancer in smokers and former smokers. Treatment of patients with enlarged mediastinal lymph nodes at LDCT screening is not considered in current standards, and evidence-based guidelines are lacking.In this issue of Radiology, Chalian et al (1) reported a retrospective analysis of National Lung Screening Trial (NLST) data. Enlarged mediastinal lymph nodes were defined as greater than or equal to 1.0 cm in the short-axis dimension. In the NLST, 1.6% of study participants with enlarged noncalcified lymph nodes at baseline LDCT had an approximately fourfold greater likelihood of being diagnosed with lung cancer over the next 7 years than those without enlarged nodes (17.1% vs 3.9%, respectively). Moreover, mediastinal lymphadenopathy was significantly associated with earlier lung cancer diagnosis, higher stage at presentation, and increased overall and lung cancer mortality. Finally, greater size of the abnormal mediastinal nodes was associated with worse patient survival. The study confirms that (a) mediastinal lymphadenopathy is uncommon in smokers and former smokers undergoing LDCT screening (2) and (b) more important, abnormally enlarged mediastinal lymph nodes are associated with a higher frequency of lung cancer and hence should be regarded as a red flag. This study raises important questions about the management of mediastinal lymphadenopathy in patients undergoing lung cancer screening.Thoracic lymphadenopathies are not rare in general radiologic practice and can have benign or malignant causes. Most often, we assume the nodes are reactive and have few clinical implications (3,4). The American College of Radiology recommends reporting “incidental” lymphadenopathy at chest CT performed with or without intravenous contrast media when lymph nodes have a short-axis diameter greater than 1.5 cm (5). However, in the context of LDCT screening, two opposing modifying factors must be considered. Smokers and former smokers have a higher incidence of lung cancer than the general population. Thus, enlarged nodes have the potential to indicate metastatic disease in advanced lung cancer. However, smokers may also have clinical or subclinical conditions that can be associated with an increased incidence of benign lymphadenopathies. These conditions include infections (associated with exacerbation of chronic obstructive pulmonary disease), inflammatory changes associated with pulmonary fibrosis or granulomatous diseases (eg, tuberculosis and sarcoidosis), and congestive heart failure (5). On the other hand, LDCT performed without the use of iodine contrast material underestimates the true prevalence of enlarged thoracic lymph nodes, since some enlarged hilar lymph nodes may not be distinguished from adjacent vessels. In fact, the mediastinal node stations 4R (right lower paratracheal), 7 (subcarinal), and 4L (left lower paratracheal) were the ones more frequently involved in the NLST. Thus, the apparent prevalence of mediastinal or hilar lymphadenopathy in patients undergoing LDCT for lung cancer screening may be different from routine contrast-enhanced chest CT performed for clinical reasons; recommendations for management may therefore vary accordingly.In the current American College of Radiology Lung CT Screening Reporting and Data System (Lung-RADS) version 1.1 classification system used for lung cancer screening (6), lymphadenopathy is labeled as either the “X” modifier for category 3 or 4 lung nodules, noting an increased risk of nodule malignancy, or “S” for its observation for 0–4 category coding, namely including patients with no nodule or with benign lung nodules. However, prognostic implications of mediastinal lymphadenopathy have remained uncertain, and Lung-RADS 1.1 does not provide specific recommendations for their management.We envision three scenarios when encountering enlarged mediastinal noncalcified lymphadenopathy at LDCT. In the first scenario, mediastinal lymphadenopathy is associated with at least one lung nodule. This occurred in 143 (34%) of the 422 participants with mediastinal lymphadenopathy in the NLST, of whom 58 of 72 (80%) were ultimately cancer-positive and 85 of 350 (24%) were cancer-negative at follow-up (1). Moreover, lung nodules were present in 98% of participants with mediastinal lymphadenopathy at initial LDCT with final diagnosis of lung cancer. In this scenario, according to Lung-RADS 1.1, the management is nodule-oriented with follow-up LDCT, fluorine 18 (18F) fluorodeoxyglucose PET, and, ultimately, invasive diagnostic procedures on the nodule, such as CT-guided fine-needle aspiration or core biopsy, video-assisted thoracoscopic surgery, or surgery.The second scenario is mediastinal lymphadenopathy in association with benign lung conditions (eg, infectious, inflammatory, fibrotic, granulomatous, or other changes) or congestive heart failure (5). In this case, the probability of malignant lymphadenopathy is likely low, and conservative management is advised (follow-up LDCT sometime after antibiotic therapy). The third scenario is mediastinal lymphadenopathy not associated with any pulmonary or cardiac abnormality. In this scenario, the possibility must be entertained that the lymphadenopathy points to a lung cancer that is otherwise undetected at LDCT. The abnormal lymph nodes may also represent lymphoproliferative disease or even correspond to a metastasis from extrapulmonary malignancy. Extrapulmonary malignancy occurred in 0.5% of 5201 patients undergoing a 5-year lung cancer screening program in Italy (7). However, only one of these patients presented with mediastinal (and axillary) lymphadenopathy due to lymphoma.We agree with the suggestion from Chalian et al that follow-up LDCT or whole-body PET/CT should be performed within 3 months in patients with mediastinal lymphadenopathy at lung cancer screening, especially before targeted invasive procedures (1). We recommend that the radiologist carefully scrutinize the follow-up LDCT scans beyond the enlarged lymph nodes according to the three scenarios outlined earlier.As recognized by Chalian and colleagues, the NLST study raises several questions. The study by Chalian et al is a secondary, unplanned analysis of prospectively collected data. Therefore, considerations for use of 18F fluorodeoxyglucose PET/CT for follow-up for patients with mediastinal lymphadenopathy are not data-driven. Moreover, the authors used a single-dimensional threshold for node abnormality, not taking into account that the size of normal mediastinal lymph nodes is influenced by the nodal station (8,9). No evaluation of the node shape was considered. Finally, correspondence between the nodal station and tumor location was not evaluated. Lymphatic drainage from a lung nodule to its corresponding nodal station is associated with metastatic lymphadenopathy due to lung cancer (10).In conclusion, results of this study nested in NLST data deserve our attention—a red flag to those radiologists engaged in interpretation of LDCT studies. Ultimately, additional data (eg, from other lung cancer screening studies) may help provide evidence-based guidelines for the treatment of patients with mediastinal lymphadenopathy at lung cancer screening.Disclosures of conflicts of interest: M.M. No relevant relationships. M.Z. No relevant relationships.References1. Chalian H, McAdams HP, Lee Y, et al. Mediastinal lymphadenopathy in the National Lung Screening Trial (NLST) is associated with interval lung cancer. Radiology 2022;302(3):684–692. Abstract, Google Scholar2. Jacobs PCA, Mali WPTM, Grobbee DE, van der Graaf Y. Prevalence of incidental findings in computed tomographic screening of the chest: a systematic review. J Comput Assist Tomogr 2008;32(2):214–221. Crossref, Medline, Google Scholar3. Stigt JA, Boers JE, Oostdijk AH, van den Berg JWK, Groen HJM. Mediastinal incidentalomas. J Thorac Oncol 2011;6(8):1345–1349. Crossref, Medline, Google Scholar4. Evison M, Crosbie PAJ, Morris J, Martin J, Barber PV, Booton R. A study of patients with isolated mediastinal and hilar lymphadenopathy undergoing EBUS-TBNA. BMJ Open Respir Res 2014;1(1):e000040. Crossref, Medline, Google Scholar5. Munden RF, Carter BW, Chiles C, et al. Managing incidental findings on thoracic CT: mediastinal and cardiovascular findings. A white paper of the ACR Incidental Findings Committee. J Am Coll Radiol 2018;15(8):1087–1096. Crossref, Medline, Google Scholar6. American College of Radiology. Lung-Screening Reporting and Data System (Lung-RADS) Version 1.1. https://www.acr.org/-/media/ACR/Files/RADS/Lung-RADS/LungRADSAssessmentCategoriesv1-1.pdf?la=en. Published 2019. Accessed September 21, 2021. Google Scholar7. Rampinelli C, Preda L, Maniglio M, et al. Extrapulmonary malignancies detected at lung cancer screening. Radiology 2011;261(1):293–299. Link, Google Scholar8. Kiyono K, Sone S, Sakai F, et al. The number and size of normal mediastinal lymph nodes: a postmortem study. AJR Am J Roentgenol 1988;150(4):771–776. Crossref, Medline, Google Scholar9. Glazer GM, Gross BH, Quint LE, Francis IR, Bookstein FL, Orringer MB. Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping. AJR Am J Roentgenol 1985;144(2):261–265. Crossref, Medline, Google Scholar10. Volterrani L, Mazzei MA, Banchi B, et al. MSCT multi-criteria: a novel approach in assessment of mediastinal lymph node metastases in non-small cell lung cancer. Eur J Radiol 2011;79(3):459–466. Crossref, Medline, Google ScholarArticle HistoryReceived: Oct 4 2021Revision requested: Oct 15 2021Revision received: Oct 16 2021Accepted: Oct 22 2021Published online: Nov 23 2021Published in print: Mar 2022 FiguresReferencesRelatedDetailsAccompanying This ArticleMediastinal Lymphadenopathy in the National Lung Screening Trial (NLST) Is Associated with Interval Lung CancerNov 23 2021RadiologyRecommended Articles Mediastinal Lymphadenopathy in the National Lung Screening Trial (NLST) Is Associated with Interval Lung CancerRadiology2021Volume: 302Issue: 3pp. 684-692Incidental Lymphadenopathy at CT Lung Cancer ScreeningRadiology2021Volume: 302Issue: 3pp. 693-694Low-Dose CT Screening for Lung Cancer: Evidence from 2 Decades of StudyRadiology: Imaging Cancer2020Volume: 2Issue: 2Lung Nodule Risk Calculator and Cost-Effectiveness of Different Lung Cancer Screening AlgorithmsRadiology: Cardiothoracic Imaging2021Volume: 3Issue: 2Low-Dose Chest CT to Predict Disease-Free Survival for Early-Stage Node-Negative Centrally Located Lung AdenocarcinomaRadiology2021Volume: 299Issue: 2pp. 448-449See More RSNA Education Exhibits Unraveling the maze - Patterns of lung cancer lymphatic disseminationDigital Posters2022Management of Solitary Pulmonary Nodules: Pushing the Limits Beyond the GuidelinesDigital Posters2019Role Of Radiology In Addressing The Challenge Of Lung Cancer After Lung Transplantation.Digital Posters2021 RSNA Case Collection Post vaccination axillary adenopathyRSNA Case Collection2021Chronic silicosisRSNA Case Collection2020Granulomatous lymphocytic interstitial lung disease RSNA Case Collection2021 Vol. 302, No. 3 Metrics Altmetric Score PDF download