Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy

L. Eickhoff; H. Golpon; P. Zardo; H. Suhling; T. Welte; D. Jonigk; J. Gottlieb; T. Fuehner

doi:10.1055/a-0583-0265

Pneumologie, Table of Contents

Pneumologie 2018; 72(08): 559-567
DOI: 10.1055/a-0583-0265

Original Paper

Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy

Endobronchialer Ultraschall bei nicht maligner mediastinaler Lymphadenopathie

Authors

L. Eickhoff

¹Department of Respiratory Medicine, Medical School Hannover, Germany
H. Golpon

¹Department of Respiratory Medicine, Medical School Hannover, Germany

⁴Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Germany
P. Zardo

²Department of Cardiothoracic, Transplant and Vascular Surgery, Medical School Hannover, Germany
H. Suhling

¹Department of Respiratory Medicine, Medical School Hannover, Germany
T. Welte

¹Department of Respiratory Medicine, Medical School Hannover, Germany

⁴Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Germany
D. Jonigk

³Institute of Pathology, Hannover Medical School, Germany

⁴Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Germany
J. Gottlieb

¹Department of Respiratory Medicine, Medical School Hannover, Germany

⁴Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Germany
T. Fuehner

¹Department of Respiratory Medicine, Medical School Hannover, Germany

⁴Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Germany

Abstract

Background Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non-malignant diseases.

Methods A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications.

Results During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35 %) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15 mm [IQR10 – 19]). Preferred station for TBNA was lymph node station 7 (38 %). Cytopathological findings revealed non-specific inflammation (n = 81; 70 %), carcinoma (n = 7; 6 %), epithelioid cell granulomas (n = 20; 17 %). 7 samples (6 %) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [n = 2] and Nocardia nova [n = 1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8 %) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76 % and specificity 96 %.

Conclusions EBUS-TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one-third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA.

Zusammenfassung

Einführung Die endobronchiale ultraschallgestützte transbronchiale Nadelaspiration (EBUS-TBNA) ist eine gängige Methode zum mediastinalen Lymphknotenstaging bei Patienten mit Lungenkarzinom und gewinnt an Stellenwert in der Untersuchung von gutartigen Lungenerkrankungen. Das Ziel der Studie war es, den Stellenwert der EBUS-TBNA bei nicht maligner mediastinaler Lymphadenopathie zu prüfen.

Methodik Wir führten eine retrospektive, monozentrische Beobachtungsanalyse von EBUS-TBNA-Prozeduren in einem Universitätsklinikum zwischen März 2013 und Juli 2015 durch. Alle Patienten mit vermeintlich nicht maligner mediastinaler Lymphadenopathie wurden eingeschlossen. Zytopathologische und mikrobiologische Ergebnisse der EBUS-TBNA Proben wurden 6 Monate nach der Untersuchung mit der klinischen Diagnose und malignen Indikationen verglichen.

Ergebnisse Während des Untersuchungszeitraumes wurden 333 EBUS-Bronchoskopien an 315 Patienten mit mediastinaler Lymphadenopathie durchgeführt. 111 von 315 (35 %) Patienten hatten weder primäre Zeichen noch eine Anamnese für eine Tumorerkrankung. Die Patienten wurden kategorisiert als Patienten mit vermeintlich nicht maligner Erkrankung. 245 Lymphknoten wurden punktiert (mediane Größe 15 mm [IQR 10 – 19]). Die bevorzugte Position für TBNA war Lymphknotenstation 7 (38 %). Zytopathologische Befunde ergaben unspezifische Entzündung (n = 81; 70 %), Karzinom (n = 7; 6 %), epitheloidzellige Granulome (n = 20; 17 %). 7 Proben (6 %) waren nicht repräsentativ. Die mikrobiologische Untersuchung der Lymphknotenpunktate wiesen 3 behandelbare Infektionen (Mycobacterium tuberculosis [n = 2] und Nocardia nova [n = 1]) nach. Leichtgradige Komplikationen wurden bei 9 von 115 (8 %) Patienten beobachtet. Die Sensitivität der EBUS-TBNA Untersuchung bei vermeintlich nicht maligner Lymphadenopathie lag bei 76 %, bei einer Spezifität bei 96 %.

Zusammenfassung In einem Drittel der Fälle ergab die EBUS-TBNA spezifische Ursachen für vermeintlich nicht maligne Lymphadenopathie. Häufigster Nachweis waren Granulome, gefolgt von Tumorerkrankung. Bei 3 Patienten konnten Erreger aus dem TBNA-Material isoliert werden.

Full Text

References

References
1 Ye T, Hu H, Luo X. et al. The role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for qualitative diagnosis of mediastinal and hilar lymphadenopathy: a prospective analysis. BMC Cancer 2011; 11
2 Tournoy KG, Govaerts E, Malfait T. et al. Endobronchial ultrasound-guided transbronchial needle biopsy for M1 staging of extrathoracic malignancies. Ann Oncol 2011 22: 127-131
3 Sun J, Bao L, Teng J. et al. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Diagnosis of Intrathoracic Metastasis from Extrapulmonary Malignancy. Zhongguo Fei Ai Za Zhi 2015; 18: 295-300
4 Ortakoylu MG, Iliaz S, Bahadir A. et al. Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in various lung diseases. J Bras Pneumol 2015; 41: 410-414
5 Caglayan B, Salepci B, Dogusoy I. et al. The role of convex probe endobronchial ultrasound guided transbronchial needle aspiration in the diagnosis of malignant mediastinal and hilar lymph nodes. Iran J Radiol 2012; 9: 183-189
6 Ribeiro C, Oliveira A, Neves S. et al. Diagnosis of sarcoidosis in the endobronchial ultrasound-guided transbronchial needle aspiration era. Rev Port Pneumol 2014; 20: 237-241
7 Low SY, Koh MS, Ong TH. et al. Use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of granulomatous mediastinal lymphadenopathy. Ann Acad Med Singapore 2014; 43: 250-254
8 Kiral N, Caglayan B, Salepci B. et al. Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing intrathoracic tuberculous lymphadenitis. Med Ultrason 2015 17: 333-338
9 Geake J, Hammerschlag G, Nguyen P. et al. Utility of EBUS-TBNA for diagnosis of mediastinal tuberculous lymphadenitis: a multicentre Australian experience. J Thorac Dis 2015; 7: 439-448
10 Alsharif M, Andrade RS, Groth SS. et al. Endobronchial ultrasound-guided transbronchial fine-needle aspiration: the University of Minnesota experience, with emphasis on usefulness, adequacy assessment, and diagnostic difficulties. Am J Clin Pathol 2008; 130: 434-443
11 Kuo CH, Chen HC, Chung FT. et al. Diagnostic Value of EBUS-TBNA for Lung Cancer with Non-Enlarged Lymph Nodes: A Study in a Tuberculosis-Endemic Country. PLoS One 2011; 6
12 Yarmus LB, Akulian J, Lechtzin N. et al. Comparison of 21-gauge and 22-gauge aspiration needle in endobronchial ultrasound-guided transbronchial needle aspiration: results of the American College of Chest Physicians Quality Improvement Registry, Education, and Evaluation Registry. Chest 2013; 143: 1036-1043
13 Gnass M, Szlubowski A, Soja J. et al. Comaparison of conventional and ultrasound-guided needle biopsy techniques in the diagnosis of sarcoidosis: a randomized trial. Pol Arch Med Wewn 2015; 125: 321-328
14 Moonim MT, Breen R, Fields PA. et al. Diagnosis and Subtyping of De Novo and Relapsed Mediastinal Lymphomas by Endobronchial Ultrasound Needle Aspiration. Am J Respir Crit Care Med 2013; 188: 1216-1223
15 Harris RM, Arnaout R, Koziel H. et al. Utility of microbiological testing of thoracic lymph nodes sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with mediastinal lymphadenopathy. Diagn Microbiol Infect Dis 2016; 84: 170-174
16 Naidich DP, Bankier AA, MacMahon H. et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013; 266: 304-317
17 MacMahon H. Compliance with Fleischner Society guidelines for management of lung nodules: lessons and opportunities. Radiology 2010; 255: 14-15
18 Bhora FY, Chen DJ, Detterbeck FC. et al. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol 2014; 9 (Suppl. 02) S88-96
19 Bechade D, Chomy F. Role of endoscopic ultrasound (EUS) and endobronchial ultrasound (EBUS) for the evaluation of mediastinal adenopathy. Bull Cancer 2012; 99: 761-770
20 VanderLaan PA, Wang HH, Majid A. et al. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): an overview and update for the cytopathologist. Cancer Cytopathol 2014; 122: 561-576
21 Kossakowski CA, Morresi-Hauf A, Schnabel PA. et al. Preparation of cell blocks for lung cancer diagnosis and prediction: protocol and experience of a high-volume center. Respiration 2014; 87: 432-438
22 Martinez TomasR, Menendez VillanuevaR, Reyes CalzadaS. et al. Pulmonary nocardiosis: risk factors and outcomes. Respirology 2007; 12: 394-400
23 Yasufuku K, Pierre A, Darling G. et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg 2011; 142: 1393-400.e1
24 Jhun BW, Park HY, Jeon K. et al. Nodal stations and diagnostic performances of endobronchial ultrasound-guided transbronchial needle aspiration in patients with non-small cell lung cancer. J Korean Med Sci 2012; 27: 46-51
25 Fernandez-Bussy S, Labarca G, Canals S. et al. Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal staging in lung cancer. J Bras Pneumol 2015; 41: 219-224
26 Parmaksiz ET, Caglayan B, Salepci B. et al. The utility of endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal or hilar lymph node evaluation in extrathoracic malignancy: Benign or malignant?. Ann Thorac Med 2012; 7: 210-214
27 Karunamurthy A, Cai G, Dacic S. et al. Evaluation of endobronchial ultrasound-guided fine-needle aspirations (EBUS-FNA): correlation with adequacy and histologic follow-up. Cancer Cytopathol 2014; 122: 23-32
28 Dziedzic DA, Peryt A, Orlowski T. The role of EBUS-TBNA and standard bronchoscopic modalities in the diagnosis of sarcoidosis. Clin Respir J 2017; 11: 56-63
29 Nakajima T, Yasufuku K, Kurosu K. et al. The role of EBUS-TBNA for the diagnosis of sarcoidosis--comparisons with other bronchoscopic diagnostic modalities. Respir Med 2009; 103: 1796-1800
30 Agarwal R, Srinivasan A, Aggarwal AN. et al. Efficacy and safety of convex probe EBUS-TBNA in sarcoidosis: a systematic review and meta-analysis. Respir Med 2012 106: 883-892
31 von Bartheld MB, Dekkers OM, Szlubowski A. et al. Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial. JAMA 2013; 309: 2457-2464
32 Caglayan B, Salepci B, Fidan A. et al. Sensitivity of convex probe endobronchial sonographically guided transbronchial needle aspiration in the diagnosis of granulomatous mediastinal lymphadenitis. J Ultrasound Med 2011; 30: 1683-1689
33 Navani N, Molyneaux PL, Breen RA. et al. Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study. Thorax 2011; 66: 889-893
34 Sun J, Teng J, Yang H. et al. Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing intrathoracic tuberculosis. Ann Thorac Surg 2013; 96: 2021-2027
35 Wilson JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc 2012; 87: 403-407
36 Fujikura Y, Kouzaki Y, Ohta S. et al. A case of Nocardia asteroides infection in a patient with HIV/AIDS diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Intern Med 2012; 51: 1413-1417
37 Aragaki-Nakahodo A, Benzaquen S, Kirschner M. Coinfection by Nocardia beijingensis and Nocardia arthritidis in an immunocompromised patient diagnosed by endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). Respir Med Case Rep 2014; 12: 22-23
38 Dabrowska M, Durlik M, Maskey-Warzechowska M. et al. Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration as a New Diagnostic Tool for Invasive Pulmonary Mycoses. Exp Clin Transplant 2016;
39 Nakajima T, Yasufuku K, Shibuya K. et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the treatment of central airway stenosis caused by a mediastinal cyst. Eur J Cardiothorac Surg 2007; 32: 538-540
40 Onuki T, Kuramochi M, Inagaki M. Mediastinitis of bronchogenic cyst caused by endobronchial ultrasound-guided transbronchial needle aspiration. Respirol Case Rep 2014; 2: 73-75
41 Hong G, Song J, Lee KJ. et al. Bronchogenic cyst rupture and pneumonia after endobronchial ultrasound-guided transbronchial needle aspiration: a case report. Tuberc Respir Dis (Seoul) 2013; 74: 177-180
42 Gilbert S, Wilson DO, Christie NA. et al. Endobronchial ultrasound as a diagnostic tool in patients with mediastinal lymphadenopathy. Ann Thorac Surg 2009; 88: 896-900; discussion 901-2
43 Lange TJ, Kunzendorf F, Pfeifer M. et al. Endobronchial ultrasound-guided transbronchial needle aspiration in routine care – plenty of benign results and follow-up tests. Int J Clin Pract 2012; 66: 438-445
44 Haponik EF, Shure D. Underutilization of transbronchial needle aspiration: experiences of current pulmonary fellows. Chest 1997; 112: 251-253
45 Mallya V, Kumar SP, Meganathan P. et al. The utility of ROSE (rapid on-site evaluation) in endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA): Is the picture rosy?. J Cytol 2015; 32: 230-233
46 Wahidi MM, Herth F, Yasufuku K. et al. Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: CHEST Guideline and Expert Panel Report. Chest 2016; 149: 816-835
47 Kang HJ, Hwangbo B. Technical aspects of endobronchial ultrasound-guided transbronchial needle aspiration. Tuberc Respir Dis (Seoul) 2013; 75: 135-139
48 Herth FJ, Morgan RK, Eberhardt R. et al. Endobronchial ultrasound-guided miniforceps biopsy in the biopsy of subcarinal masses in patients with low likelihood of non-small cell lung cancer. Ann Thorac Surg 2008; 85: 1874-1878
49 Shiu KK, Eberhardt R, Herth FJ. Comparison of 22-gauge and 19-gauge needles in endobronchial ultrasound (ebus) transbronchial needle aspiration (tbna) in mediastinum lymph node assessment. Chest 2007; 132: 465b-465