Barber, Philip V.

Booton, Richard

Crosbie, Philip

Evison, Matthew

Martin, Julie

English

The University of Manchester - Institutional Repository

The University of Manchester ResearchImproved negative predictive value of EBUS-TBNA inisolated mediastinal / hilar lymphadenopathy:Link to publication record in Manchester Research ExplorerCitation for published version (APA):Evison, M., Crosbie, P., Martin, J., Barber, P. V., & Booton, R. (2013). Improved negative predictive value ofEBUS-TBNA in isolated mediastinal / hilar lymphadenopathy: Why and what it means for patients?. Poster sessionpresented at European Respiratory Society Congress 2013, Barcelona, Spain.Citing this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact uml.scholarlycommunications@manchester.ac.uk providingrelevant details, so we can investigate your claim.Download date:09. Jun. 2022Matthew Evison1*, Philip A J Crosbie1,2, Julie Martin1, Philip V Barber1, Richard Booton1,21: North West Lung Centre, University Hospital of South Manchester, Southmoor Road, Wythenshawe, M23 9LT, UK;2: The Institute of Inflammation and Repair, The University of Manchester, M13 9PL, UK.Introduction Results ConclusionsReferences1. Navani N, Lawrence DR, Kolvekar S. Endobronchial ultrasound-guided transbronchial needle aspiration prevents mediastinoscopies in the diagnosis of isolated mediastinal lymphadenopathy: a prospective trial. Am J Respir Crit Care Med 2012;186(3):255-260 2. Kirchner J, Kirchner EM, Goltz JP et al. Prevalence of enlarged mediastinal lymph nodes in heavy smokers – a comparative study. European Radiology 2011;21(8):1594-15993. Kirchner J, Kirchner EM, Goltz JP et al. Enlarged hilar and mediastinal lymph nodes in chronic obstructive pulmonary disease. J Med Imaging Radiat Oncol 2010;54(4):333-3384. Bergin C, Castellino RA. Mediastinal lymph node enlargement on CT scans in patients with usual interstitial pneumonitis. AJR 1990;154:251-2545. Souza CA, Muller NL, Lee KS et al. Idiopathic interstitial pneumonias: prevalence of mediastinal lymph node enlargement in 206 patients. AJR 2006;186:995-9996. Thomas RD, Blacquiere RM. Reactive mediastinal lymphadenopathy in bronchiectasis assessed by CT. Acta Radiol 1993;34(5):489-4917. Moua T, Levin DL, Carmond EM et al. Frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension. Chest 2013;143(2):344-3488. Chabbert V, Canevet G, Baixas C et al. Mediastinal lymphadenopathy in congestive cardiac failure: a sequential CT evaluation with clinical and echocardiographic correlations. Eur Radiol 2004;14(5):881-8899. Pastis NJ, Van Bakel AB, Brand JM et al. Mediastinal lymphadenopathy in patients undergoing cardiac transplant evaluation. Chest 2011;139(6):1451-145710. Martinez FJ, Karlinsky JB, Gale ME et al. Intrathoracic lymphadenopathy. A rare manifestation of rheumatoid pulmonary disease. Chest 1990;97(4):1010-1012The traditional differential diagnosis of isolated mediastinal and hilar lymphadenopathy includes benign granulomatous disorders e.g. sarcoidosis and tuberculosis and malignant conditions such as lymphoma and carcinoma. Each of these diagnoses requires pathological confirmation to ensure appropriate treatment. Lymphadenopathy in which such causes have been excluded has been termed “reactive lymphadenopathy”, and is considered benign.In a prospective trial of 77 patients with isolated mediastinal lymphadenopathy EBUS-TBNA prevented mediastinoscopy in 87% of patients and demonstrated a sensitivity of 92%1. EBUS-TBNA is therefore recommended as a first line investigation in such patients. However the negative predictive value was 40% suggesting in cases of negative  EBUS-TBNA further sampling, such as mediastinoscopy, is required. Of note, only 4 patients in this study were ultimately diagnosed with ‘reactive lymphadenopathy’.There is increasing evidence that common chronic diseases, both respiratory and non-respiratory, are associated with mediastinal and hilar lymphadenopathy. This includes: emphysema and chronic bronchitis, interstitial lung disease, bronchiectasis, pulmonary hypertension, heart failure and rheumatoid arthritis2-10. Lymphadenopathy in this scenario would fall under the term “reactive lymph nodes” following pathological sampling. Could this lead to a higher prevalence of reactive lymphadenopathy in the isolated lymphadenopathy population and do these patients require further surgical biopsy following a negative EBUS-TBNA?A total of 100 patients underwent EBUS-TBNA for isolated mediastinal / hilar lymphadenopathy during the study period (Table 1) and the final diagnosis is demonstrated in Figure 1. Reactive lymphadenopathyReactive lymphadenopathy was the most common cause of isolated lymphadenopathy. There was a higher prevalence of co-morbidities compared to the other diagnosis groups (Table 2). There was only 1 patient in which no co-morbidity was present to account for the lymphadenopathy. Figure 2 demonstrates the co-morbidities present in those patients with reactive lymphadenopathy.False negative EBUS-TBNAThere were 9 false negative EBUS-TBNA (sarcoidosis 4, lymphoma 4, tuberculosis 1).In each case there was a high pre-test probability of a diagnosis other than reactive lymphadenopathy, based on pre-procedure radiology and clinical history.Granulomatous disordersSarcoidosis accounted for 20% of the final diagnoses.The sensitivity of EBUS-TBNA was 80% (16/20 correctly diagnosed). Patients with sarcoidosis had a higher total number of enlarged lymph node stations compared with the other diagnoses and mediastinal lymphadenopathy always occurred with hilar lymphadenopathy and the lymphadenopathy was almost always symmetrical (table 2). In 45% (9/20) of patients there were lung parenchymal abnormalities suggestive of sarcoidosis (nodularity with upper zone predominance). One patient had associated erythema nodosum.Tuberculosis accounted for 18% of the final diagnoses.EBUS-TBNA correctly diagnosed 17/18 patients (sensitivity 94.4%). All patients diagnosed with tuberculosis in this cohort were of non-Caucasian ethnicity (table 2). In addition, patients frequently had isolated mediastinal lymphadenopathy without hilar lymphadenopathy (67% of cases). The lymphadenopathy was frequently asymmetrical. Five patients had known TB contact and 1 patient had cavitating upper lobe consolidation in association with the lymphadenopathy.Malignant diagnosesLymphoma accounted for 6% of the diagnoses.EBUS-TBNA correctly diagnosed 2/6 patients (sensitivity 33.3%). 67% (4/6) of patients had extra-thoracic lymphadenopathy (sites included: abdominal 3, axillary 2, neck 1, inguinal 1). One patient had previously undergone a liver transplant was therefore heavily immunosuppressed.Carcinoma accounted for 7% of diagnoses (small cell lung cancer 4, squamous cell carcinoma 1, non-small cell lung cancer “not otherwise specified” 1, mesothelioma 1), all were correctly diagnosed with EBUS-TBNA (n=7/7; sensitivity 100%). Two patients (29%) had anterior mediastinal lymphadenopathy.The overall diagnostic performance ofEBUS –TBNA in this cohort was:  Sensitivity 82.4%,  Negative predictive value 84.5%, Diagnostic accuracy 91%.Materials and MethodsThe study was a prospective observational cohort of all patients undergoing EBUS-TBNA for investigation of isolated mediastinal and/or hilar lymphadenopathy, between March 2010 and November 2012, at the Bronchoscopy Unit of the University Hospital of South Manchester, UK.Patients were included if they had enlarged hilar or mediastinal lymph nodes(≥10mm in short axis diameter) without evidence of an intra-pulmonary mass and no evidence of extra-thoracic malignancy. The final diagnosis for each patient was based on EBUS-TBNA results, any subsequent pathological sampling and clinical- radiological follow-up, which was undertaken for a period of six months after the procedure.Diagnoses were classified as one of: sarcoidosis, tuberculosis, lymphoma, carcinoma or reactive lymphadenopathy. A lymph node was only classified as reactive if the EBUS-TBNA, any subsequent pathological sampling and 6 months of clinical- radiological follow up failed to demonstrate any evidence of the other diagnoses.ObjectivesThe primary objective of this study was to determine the prevalence of reactive lymphadenopathy in patients undergoing EBUS-TBNA for isolated lymphadenopathy at a tertiary centre. Secondary aims were to determine the presence of respiratory and non-respiratory disease that may explain the lymphadenopathy in this group and to investigate for potential clinical and radiological characteristics that could identify which patients may need further invasive sampling and which may undergo surveillance in cases of negative EBUS-TBNA.In patients undergoing EBUS-TBNA at our centre for isolated mediastinal and /or hilar lymphadenopathy, nearly half had reactive lymphadenopathy rather than one of the traditional diagnoses in this setting (sarcoidosis, tuberculosis, lymphoma, carcinoma).The most common chronic diseases that could be responsible for this reactive lymphadenopathy are emphysema, chronic bronchitis and heart failure.Clinical and radiological features that suggest a high probability of a diagnosis other than reactive lymphadenopathy and indicate the need for further sampling in cases of negative EBUS-TBNA include:• ≥5 lymph stations enlarged with symmetrical mediastinal and hilar lymphadenopathy (suggestive of sarcoidosis),• lung parenchymal abnormalities (upper lobe cavitating consolidation in tuberculosis and upper zone nodularity in sarcoidosis),• non-Caucasian ethnicity (suggestive of tuberculosis),• anterior mediastinal lymphadenopathy (suggestive of lymphoma or carcinoma),• extra-thoracic lymphadenopathy (suggestive of sarcoidosis or lymphoma),• splenomegaly (suggestive of sarcoidosis or lymphoma), • absence of diseases associated with lymphadenopathy.With the increasing use of CT, an ageing population and an increasing prevalence of chronic diseases the detection of isolated hilar and mediastinal lymphadenopathy is increasing and reactive lymphadenopathy is representing a higher proportion of these cases.The negative predictive value of EBUS-TBNA may be significantly higher than previously reported due to this subgroup of patients. This may allow a period of surveillance rather than requiring further invasive sampling with mediastinoscopy in carefully selected patients.Improved negative predictive value of EBUS-TBNA in isolated mediastinal / hilar lymphadenopathy:Why and what it means for patients?Figure 1:  Final Diagnosis (n=100)Figure 2:  Co-morbiditiesTable 1:  Patients’ Characteristics (n=100)Table 2:  Patient characteristics stratified into diagnosis groupsTable 3:  Sensitivities forEBUS-TBNA in this studySarcoidosis0 5 10Number of patients15 20 25TuberculosisCarcinomaLymphomaReactiveMediastinal cystPatient characteristics n=100Age (mean ± SD) 58.7 ±15.6Gender (male) 63 Ethnicity:Caucasian 70Asian 24African 6Symptoms: Cough 64Dyspnoea 52Weight loss 27Fever or night sweats 18Chest pain 9Asymptomatic 1448%20%18%7%6%1%Chronic bronchitisEmphysemaHeart failureBronchiectasisPulmonary hypertensionMitral valve diseaseAortic valve diseaseILDRAABPALiver cirrhosisPneumoniaAnkylosing spondylitisRecent radiotherapy for breast caChronic bowel obstructionChronic cervical discitisKey: Isolated M = isolated mediastinal lymphadenopathy, without hilar lymphadenopathy Isolated H = isolated hilar lymphadenopathy, without mediastinal lymphadenopathy Symmetrical M = symmetrical (bilateral) mediastinal lymphadenopathy Symmetrical H = symmetrical (bilateral) hilar lymphadenopathy Sarcoidosis Tuberculosis Lymphoma Carcinoma Reactive LN n=20 n=18 n=6 n=7 n=48Age (mean ± SD) 50.6 ± 13.8 41.2 ± 13.3 66.3 ± 13.2 70.9 ± 5.3 68.0 ± 11.1Ethnicity:Caucasian 15 (75%) 0 6 (100%) 7 (100%) 41 (85%)Asian     3 (15%)  16 (89%) 0 0   5 (11%)African    2 (10%)   2 (11%) 0 0 2 (4%)Co-morbidities:     Emphysema   2 (10%) 0 0 3 (43%) 13 (27%)Ch bronchitis 1 (5%) 1 (5%) 0 0 20 (42%)ILD  0  0 0 1 (14%) 4 (8%)Bronchiectasis 0 0 1 (17%) 1 (14%)    8 (17%)Pul HTN 0 0 0 0    8 (17%)HF 0 0 0 0 13 (27%)MVD 0 0 0 0   6 (12%)AVD 0 0 0 0   6 (12%)CTD 0 0 0 1 (14%) 1 (2%)LN Stations:     0-2 0 14 (78%) 1 (17%) 2 (29%) 20 (42%)3-4   5 (25%)   3 (17%) 3 (50%) 4 (57%) 24 (50%)≥5 15 (75%) 1 (5%) 2 (33%) 1 (14%) 4 (8%)Isolated M 0 12 (67%) 2 (33%) 4 (57%) 16 (33%)Isolated H 0   2 (11%) 1 (17%) 0 4 (8%)Symmetrical M  15 (75%) 1 (5%) 2 (33%) 3 (43%) 10 (21%)Symmetrical H 18 (90%)   2 (11%) 2 (33%) 0 10 (21%)North WestLung Centre SensitivitySarcoidosis (n=20)    80%Tuberculosis (n=18) 94.4%Lymphoma (n=6) 33.3%Carcinoma (n=7)  100%Overall 82.4%

Improved negative predictive value of EBUS-TBNA in isolated mediastinal / hilar lymphadenopathy::Why and what it means for patients?

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Improved negative predictive value of EBUS-TBNA in isolated mediastinal / hilar lymphadenopathy::Why and what it means for patients?

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