Diagnostic Value of EBUS-TBNA in Various Lung Diseases (Lymphoma, Tuberculosis, Sarcoidosis) Sevda Sener Cömert, MD, FCCP. SBU, Kartal Dr.Lütfi Kırdar Training and Research Hospital Department of Pulmonary Medicine
EBUS-TBNA minimally invasive technique for sampling the hilar/ mediastinal lymph nodes improve the diagnostic yield by direct visualization of lymph node beyond the tracheobronchial wall allows real-time sampling of the lymph nodes
EBUS-TBNA the utility of CP EBUS-TBNA was reported first in sampling mediastinal nodes in 2003 the diagnostic yield of EBUS-TBNA has been enhanced rapid on-site cytological evaluation (ROSE) increasing the number of lymph nodes sampled increase in the number of aspirates taken per node use of a larger bore 21G needle
EBUS-TBNA primarily intended for minimally invasive staging of bronchogenic carcinoma its use has been extended in diagnosis of lymphoma and benign conditions like tuberculosis and sarcoidosis
Sarcoidosis Sarcoidosis is a multisystem granulomatous disorder of unknown etiology It commonly presents with bilateral hilar adenopathy, pulmonary infiltrates, ocular and skin lesions The diagnosis is established in presence of compatible clinicoradiographic findings and histologic evidence of noncaseating epithelioid cell granulomas Exclusion of other known causes for granulomatous inflammation is essential
Sarcoidosis lung and mediastinal lymph nodes are most often affected bronchoscopic techniques bronchoscopic lung biopsy endobronchial biopsy transbronchial needle aspiration demonstration of noncaseating granulomas
2004 to 2011 describing the diagnostic value of EBUSTBNA in patients with sarcoidosis The criteria for conclusive diagnosis by EBUS-TBNA in sarcoidosis was lymph node aspirates showing epithelioid, noncaseating granulomas without necrosis OR epithelioid and giant cells AND absence of identifiable malignancy, lymphoma, or infection (i.e. tuberculosis or fungal disease)
15 studies finally met the inclusion criteria 9 prospective, 6 retrospective 553 confirmed patients of sarcoidosis 8 studies included stage I and II patients 2 studies included all stages of sarcoidosis the stage was not reported in five studies 12 studies under conscious sedation wo any artificial airway 2 studies used conscious sedation with endotracheal tube/ laryngeal mask 1 study used general anesthesia with laryngeal mask
paratracheal, subcarinal, hilar and interlobar nodes lower paratracheal and subcarinal lymph nodes (stations 4 and 7) were the most frequently accessed with a very low rate of complications all the studies had used the 22G dedicated EBUS-TBNA needle
the diagnostic yield of EBUS-TBNA surpasses every other bronchoscopic investigation in isolation
The diagnostic yield of EBUS-TBNA in sarcoidosis ranged from 54 to 93% with the pooled accuracy being 79% (95% CI, 71e86%) by the random effects model The yield was not statistically different in studies employing on-site cytological evaluation (165/206; 80.1%) vs. those without (282/347; 81.3%). 5 minor complications minimal pneumothorax, minor bleeding, airway edema/hypoxemia (n=2) prolonged cough
good quality studies involving more than 550 confirmed predominantly stage I and II patients of sarcoidosis excellent overall diagnostic yield (79%) of EBUS-TBNA in sarcoidosis suggesting that this technique should be routinely employed in diagnosis of sarcoidosis wherever available
meta-analysis has certain limitations presence of significant clinical and statistical heterogeneity in the studies evaluated studies from various centers with operators having differing levels of expertise in performing EBUS-TBNA
Tuberculosis Tuberculosis remains a major global problem Global TB control remains a challenge diagnosis drug resistance treatment smear microscopy usually misses half of all cases The progress in TB control is hindered by the lack of rapid and accurate diagnostic assays
Tuberculosis The conclusive diagnosis of TB is still difficult. The standard procedures still play a key role smear for acid-fast bacilli microbiological culture pathologic examination
Tuberculosis Pulmonary TB is often accompanied by intra thoracic tuberculous LAP The lack of a specific clinical or radiologic presentation leads to diagnostic challenges for intrathoracic tuberculous LAP EBUS- TBNA provides a new sampling technique for intrathoracic lymph nodes and peribronchial tissues
assess the effectiveness and safety of EBUS-TBNA for intrathoracic TB studies up to March 2014 Inclusion criteria: Articles in English, stuides on human patients All trials tested the diagnostic value of EBUS-TBNA in intrathoracic TB all studies included more than 5 cases of intrathoracic TB studies provided enough data to calculate the sensitivity of EBUS-TBNA J Ultrasound Med 2015; 34:1645 1650
From 383 relevant articles a total of 8 studies were included in the metaanalysis J Ultrasound Med 2015; 34:1645 1650
meta-analysis included 809 patients most studies did not report any information about HIV infection status 2 articles did not enroll HIV-positive patients only 1 study included 17 HIV-positive patients Half of the trials were performed prospectively The most common needle size was 22 gauge Most of the studies did not use rapid on-site evaluation J Ultrasound Med 2015; 34:1645 1650
The diagnoses of TB in most included studies were based on the combination of the following tools: acid-fast bacilli TB skin tests interferon γ release assays nucleic acid amplification tests cultures pathologic findings clinical responses to anti-tb treatment pathologic findings were used as the only reference standard for diagnosis of TB in 2 studies J Ultrasound Med 2015; 34:1645 1650
The sensitivity of EBUS-TBNA for diagnosis of intra thoracic TB ranged from 0.5 to 0.95, and the specificity ranged from 0.917 to 1.0. J Ultrasound Med 2015; 34:1645 1650
4 stuides from countries with a high incidence of TB The pooled sensitivity of EBUS-TBNA for diagnosis of intrathoracic TB was 0.80 (95% CI, 0.74 0.85), and the pooled specificity was 1.00 (95% CI, 0.99 1.00) no significant heterogeneity existed among the studies J Ultrasound Med 2015; 34:1645 1650
EBUS-TBNA is an effective and safe tool for diagnosis of intrathoracic TB, especially intrathoracic tuberculous lymphadenopathy Only 1 serious complication (sepsis) was reported J Ultrasound Med 2015; 34:1645 1650
In tuberculous lymphadenitis patients, Development of intrabronchial polypoid lesions at the puncture sites after EBUS-TBNA reported by Hata et al., Kim et.al and Gupta et.al. Von Bartheld et al. reported the occurrence of mediastinal-esophageal fistulae following transesophageal endoscopic ultrasound-guided FNA There is a possibility of aggravation caused by puncturing the bronchial mucosa. Excessive puncturing should therefore be avoided in patients with suspected tuberculous lymphadenitis. Intern Med 52:2553-2559,2013 Eur J Cancer 2009;45(8):1389-1396 Tuberc Respir Dis. 2015 Oct;78(4):419-22
Lymphoma lymphoproliferative malignancy common cause of mediastinal tumors cervical or supraclavicular LAP excisional lymph node biopsy primary mediastinal lymphoma rare in adults 10% of all mediastinal lymphomas
Lymphoma Mediastinal LAP biopsy is a challenge excisional biopsies thoracotomy, thoracoscopy or mediastinoscopy general anesthesia associated complications
Lymphoma EBUS-TBNA increasingly used when lymphoma is suspected Diagnostic accuracy of EBUS-TBNA in lymphoma is still debated Disadvantages of EBUS-TBNA lesser sampling of core tissue an inferior negative predictive value
Lymphoma The low-volume samples are important diagnosing marginal zone and follicular lymphoma high level of discordance between cytologic and histologic specimens the diagnostic accuracy of EBUS-TBNA for lymphoma is lower than that for lung cancer staging multidirectional analysis such cytology, immunophenotype, and histology to confirm the subtype of lymphoma
Lymphoma Surgical excision and core biopsy are the current preferred sampling techniques for diagnosing lymphoma less invasive endoscopic techniques with lower complication rates EBUS-TBNA, along with appropriate immunohistochemical, flow cytometric, cytogenetic, and molecular studies, can definitively diagnose lymphoma
Lymphoma EBUS-TBNA is not usually a clinically appropriate diagnostic tool if lymphoma is suspected samples of EBUS-TBNA can be adequate for flow cytometry and immunohistochemistry analysis EBUS-TBNA was successful in subclassifying lymphoma in 87% of cases ROSE of cytopathology has no addition in this regard in improving diagnostic yield
Retrospective study between January 2007 to March 2014 181 lymphoma suspected patients 111 (61.3%) suspected relaps, 70 (38.7%) suspected de novo 75 patients (41.5%) had lymphoma at final diagnosis 21 (28%) HL 54 (72%) NHL 36 low grade and 18 high grade
369 LNs and 19 mediastinal masses 2 lymph nodes per patient 5 needle passes per lymph node (3 19) no difference in the number of passes between patients with and without lymphoma (p= 0.27) EBUSTBNA could establish the diagnosis of lymphoma in 84% of cases and subclassify it in 77% of patients.
retrospective study September of 2010 and September of 2013 Patients with suspected lymphoma were included a history of lymphoma newly isolated mediastinal lymphadenopathy, identified using CT or PET-CT Pts with other likely causes of LAP lung cancer, extrathoracic malignancy or granulomatous diseases Pts with pulmonary lesions accompanying mediastinal LAP were excluded from the study Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
22-gauge needle min 3 needle passes/ln air-dried and alcohol-fixed glass slides cell block for histological evaluation and immunohistochemistry 35 (51.5%) male, 33 (48.5%) female total 68 patients median age was 50 years (20-80 years) 35 sarcoidosis 15 lymphoma 9 tuberculous lymphadenitis 6 reactive LAP 2 sarcoma 1 squamous cell Ca Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
135 LN sampled median number of needle passes 3 /LN (2-6) median size of LNs 15mm (5-50mm) 7 and 10R most frequently sampled 13/15 correctly diagnosed as lymphoma by EBUS-TBNA 2 false-negative cases diagnosed by thoracotomy and mediastinoscopy 10 Hodgkin s lymphoma, 3 follicular center cell lymphoma, 2 extranodal marginal zone B-cell lymphoma (MALTOMA) Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
EBUS-TBNA is an accurate and safe procedure for the evaluation of primary or recurrent lymphoma sensitivity of 86.7% and an accuracy of 97% EBUS-TBNA can be considered as an initial procedure for the diagnosis of mediastinal lymphadenopathies in patients with suspected lymphoma. Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
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