Original papers
DOI: 10.11152/mu.2013.2066.173.nkiAbstract
Aims: Patients with suspected tuberculosis without pulmonary lesions and with intrathoracic lymphadenopathy often pose a diagnostic challenge. The aim of this study was to describe the diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with isolated intrathoracic lymphadenopathy due to tuberculosis (TB). Materials and methods: Cases with tuberculous lymphadenitis (TBLA) as the final diagnosis were analysed among patients in whom EBUS-TBNA had been performed. All patients underwent routine clinical assessment and a CT scan prior to EBUS-TBNA. Demographic data, pathological findings, and microbiological results were recorded. All patients received 6-month antituberculous treatment, followed-up regularly and recovered both on clinical and radiological basis. Results:
Fourty-four patients were included. EBUS-TBNA diagnosed TB intrathoracic lympadenopathy in 42 (95.4%) patients. In 2 patients, EBUS-TBNA was not able to confirm a diagnosis and additional procedures were required. Cytopathological findings alone revealed TB in 32 (72.7%) patients. One of the patients (2.2%) was smear positive while microbiological investigations provided a positive culture of TB in 22 (50%) patients. TB culture was positive in 10 of 12 patients in whom cytopathologic evaluation was not able to diagnose. Addition of mycobacterium culture to cytopathologic investigation has improved the diagnostic yield from 72.7% to 95.4%. Conclusion: EBUS-TBNA is a safe and effective first line investigation for evaluat- ing isolated intrathoracic tuberculous lympadenopathy. Addition of mycobacterium culture to cytopathologic investigation improves the sensitivity of EBUS-TBNA.
Keywords: bronchoscopy, endobronchial ultrasound, transbronchial needle aspiration, lymphadenopathy, tuberculosis
Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing intrathoracic tuberculous lymphadenitis.
Nesrin Kiral
1, Benan Caglayan
1, Banu Salepci
1, Elif Torun Parmaksiz
1, Ali Fidan
1, Sevda Sener Comert
1, Dilek Yavuzer
2, Mualla Partal
31Dr. Lutfi Kirdar Kartal Training and Research Hospital Department of Chest Diseases, 2Dr. Lutfi Kirdar Kartal Train- ing and Research Hospital Department of Pathology, 3Sureyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Microbiology, Istanbul, Turkey
Received 24.03.2015 Accepted 20.06.2015 Med Ultrason
2015, Vol. 17, No 3, 333-338
Corresponding author: Nesrin Kiral, M.D
Kozyatagi Mah. Kocayol cad. Atilim Sitesi A Blok 39/30, 34742 Kadikoy, Istanbul, TURKEY Phone: + 90 216 416 49 88
Gsm: +90 535 596 90 85, Fax: + 90 216 442 18 84 E-mail: [email protected]
Introduction
Tuberculous (TB) is a major health problem with a high mortality rate in developing countries. Tuberculous lymphadenopathy (TBLA) is the most common form of extrapulmonary TB. The intrathoracic lymph nodes are frequently involved in endemic areas. The diagnosis may be difficult in the absence of accompanying parenchy-
mal involvement, the vast majority of such cases hav- ing negative sputum smear and cultures. Tomographical appearance of an adenopathy with a low-density center and peripheral rim enhancement does not confirm the di- agnosis. Moreover, fungal infections or malignancy can also produce similar radiological abnormality. Mediasti- noscopy, thoracotomy, or video-assisted thoracic surgery (VATS) may be warranted for definite diagnosis [1-3].
Being a simple, safe, and repeatable method, fine nee- dle aspiration (FNA) is becoming increasingly popular in the diagnosis of extrapulmonary tuberculosis [4,5].The diagnostic value of computed tomographic (CT) guided fine needle aspiration biopsies (FNAB) in mediastinal tu- berculosis is 66% [6]. Gulati et al had seven culture posi- tive cases out of 26 TB patients diagnosed by ultrasound (US) guided FNAB [2].
US has been increasingly incorporated into diagnos- tic and therapeutic modalities. US technology may be employed via a probe inserted through the working chan- nel [radial probe endobronchial US (EBUS)] or incor- porated into the distal end of the bronchoscope (convex probe EBUS), the latter allowing real-time biopsy. The convex probe EBUS bronchoscope, utilizes a fixed array of transducers aligned in a curvilinear pattern. This gen- erates a 50° image parallel to the long axis of the bron- choscope. The use of a 7.5-MHz frequency transducer allows deeper tissue penetration. Using the water-filled balloon the image quality can be improved (fig 1). Power Doppler US differentiates the tissue from the vascular structure. US and the white-light bronchoscopic images can be display simultaneously [7,8].
Recently, development of EBUS has increased the validity of transbronchial needle aspiration (TBNA).
Convex probe endobronchial ultrasound-guided trans- bronchial needle aspiration (EBUS-TBNA) has a high sensitivity and diagnostic value in lung cancer and sar- coidosis; however, its utility in TB lymphadenitis has not been reported [7,9]. We undertook this study to assess the diagnostic yield of EBUS-TBNA in the evaluation of TBLA.
Material and methods Patients
Between February 2009 and July 2013, 780 patients had undergone EBUS-TBNA in our Department for the study of radiographically detected hilar/mediastinal lym- phadenopathy (adenopathy larger than 1 cm in short axis on CT). Out of 780 EBUS-TBNA cases, 736 were diag- nosed with diseases other than tuberculosis by EBUS- TBNA itself or by additional diagnostic procedures. The records of 44 patients who were diagnosed as TBLA were retrospectively analysed. All the patents signed an informed consent before endoscopic procedure. Demo-
graphical data and results of cytopathological and micro- biological analyses were recorded. The detection of case- ating granulomatous reaction and/or direct identification of Mycobacterium tuberculosis by Ziehl-Neelson stain and/or growth in MGIT (Mycobacteria Growth Indicator Tube) system were considered as TBLA. Mediastinosco- py or other invasive procedures undertaken in the case of non-diagnostic EBUS-TBNA were recorded. Treatment results of all cases were also recorded.
Convex probe EBUS-guided TBNA
The bronchoscopy procedure was performed via oral route with the patient in supine position under lo- cal anesthesia and conscious sedation using intravenous midazolam. A 7.5-MHz BF-UC160F convex-probe bronchoscope and EU-C2000 processor (Olympus Op- tical Co, Tokyo, Japan) were used. The lymph nodes were classified according to the Mountain’s regional lymph node classification system [10]. The dimensions of the lymph nodes seen on the convex probe-EBUS were recorded from archived US images. Although lymph nodes with a short axis greater than 1 cm at CT were included in the study, in presence of any lymph node with a short axis greater than 0.5 cm measured by EBUS, EBUS-guided TBNA was performed with real- time imaging (fig 2).TBNA was performed by using 22-gauge Olympus NA-201SX-4022 needle and power Doppler mode to avoid vascular injury. During the pro- cess, for every detected lymph node short and long axis diameters, station of the lymph node, and number of passes per patient and per lymph node were recorded in each patient.
The specimens obtained were immediately smeared on slides and fixed in 95% ethanol and flushed in 0.9%
normal saline for pathological and microbiological as- sessment, respectively. There was not a pathologist on- site and the Ziehl-Neelsen smear reading was done in the microbiology laboratory after the bronchoscopy finished, Fig 1. Distal tip of dedicated bronchoscope with the curved
array transducer covered with a saline inflated baloon (a) and echogenic needle pushed out of the bronchoscope (b)
Fig 2. a) Right lower paratracheal lymph node. The tip of the needle is shown with an arrow. The echogenic view under the tip of the needle is an internal echo of the lymph node; b) The correlative CT image of the right lower paratracheal lymph node. LN – lymph node, VCS – vena cava superior
but on the same day. The specimens were stained with Ziehl-Neelsen stain and cultured MGIT media. The re- maining aspirates were also expelled in alcohol for cell block analysis. Cytopathological findings revealing ca- seating granulomatous reaction or detection of acid-fast bacilli on smear or growth of mycobaterium tuberculosis in the MGIT system were considered to be TBLA. When EBUS-TBNA findings were non-diagnostic, the patients were submitted to mediastinoscopy.
All TB cases recieved anti-TB treatment and fol- lowed for at least 6 months.
Statistical analysis
The accuracy of EBUS-TBNA in the diagnosis of TBLA and contribution of smear and culture to the di- agnosis were evaluated. Sensitivity of EBUS-TBNA and diagnostic values of cytopathological and micobiological tests were calculated using descriptive data.
Results
The mean age of study group (29 female and 15 male) was 50.55±2.65 years (range between 11-82 years). The mean diameter of the short axis of lymph nodes based on EBUS was 2.01±0.09cm. The majority of aspirations were from subcarinal lymph nodes (station number 7).
A total of 83 lymph nodes were sampled in 44 patients and 181 aspirations were applied. The number of aspira- tions was 2.2 per lymph node and 4.1 per patient (table I, fig 3).
Fourty-two patients (95.4%) were diagnosed as TBLA by EBUS-TBNA via cytopathological (fig 4) and/or microbiological analysis. For two cases who had nondiagnostic EBUS-TBNA results, diagnosis of TB was reached by mediastinoscopy. No complications due to EBUS were seen. TB was diagnosed in 32 pa- tients (72.7%) based on cytopathology. One of the cas- es had positive smears of the EBUS-guided aspirates.
Mycobacterium tuberculosis was isolated in 22 cases (50%). Out of 12 cases with nondiagnostic cytopatho-
logical analysis, 10 had positive TB cultures. One pa- tient was TBNA material smear positive and was also cytopathologically diagnosed as TBLA. Considering culture results in addition to cytopathological analysis the diagnostic value of EBUS-TBNA increased from 72.7% to 95.4%. Consequently, the culture of TBNA material improved the diagnostic utility of EBUS- TBNA as much as 22.7%. The cytopathological and microbiological findings of lymph node stations are shown in Table II.
All patients recieved six-month antituberculous treat- ment, followed-up regularly and recovered both on a clinical and radiological basis.
Fig 3. a) Right lower paratracheal lymph node (number 4R).
The tip of the needle and internal echo of the lymph node are shown. b) Right lower paratracheal lymph node (num- ber 4R). Bronchoscopic image (arrow shows the location of TBNA).
Fig 4. a) HEx200. Cell block, necrotizing granuloma at the centre (arrow shows the necrosis); b) MGGX200. EBUS-TB- NA smear showing epitheloid granuloma (HE:Hematoxylin eozin) (MGG: May Grünwald Giemsa)
Table I. Location, diameter and aspiration frequency of sampled lymph nodes
Lymph node station Number of lymph nodes Mean diameter (cm) Mean passes per lymph node
2R 3 1.68 ± 0.70 2
2L - - -
4R 25 1.83 ± 0.14 2.4
4L 4 0.93 ± 0.25 2
7 33 2.38 ± 0.15 2.3
10R 3 2.67 ± 0.33 1.3
10L - - -
11R 8 1.69 ± 0.25 1.8
11L 7 1.71 ± 0.14 1.7
Total 83 2.01 ± 0.09 2.2
Discussions
The current study demonstrates a diagnostic value of 95.4% for EBUS-TBNA in intrathoracic TBLA. No com- plications were observed. Twenty two patients (50%) had positive cultures for Mycobacterium tuberculosis. Incor- porating culture to cytopathological analysis the diagnos- tic rate increased from 72.7% to 95.4%.
TB is still a common universal health problem.
TBLA accounts for about 30-40% of the cases and is one of the most frequent causes of lymphadenopathy [11].
Fine needle aspiration is a simple, non-invasive alterna- tive to excisional biopsy [5]. The diagnosis is confirmed by the recognition of epitheloid histiocyte granulomas with or without multinucleate giant cells and caseation necrosis [11]. Acid fast staining of the aspirates seem to increase the diagnostic rate [12]. The prevalance of acid resistant bacilli in smears prepared using the Zie- hl-Neelsen technique has been reported to vary from 0 to76.4% [11,13]. Nataraj et al found that culture posi- tivity was significantly higher than smear positivity [4].
Cultures of fine needle aspirates are thought to be a more specific additional tool to increase sensitivity in TBLA evaluation [14]. Our findings suggest that using cultures as an adjunct to cytopathological analysis the diagnostic rate increase from 72.7% to 95.4%. Bronchoscopy and sputum culture have a limited role in diagnosing isolated intrathoracic TBLA. Bilaçeroğlu et al found the diagnos- tic yield of cultures of conventional TBFNA to be 27 % (17/63) [1]. Mediastinoscopy may be employed; how- ever, it is more invasive, requires general anesthesia and carries 1-2% morbidity [3,15]. Another disadvantage is that posterior subcarinal and hilar lymph nodes cannot be accessed. Anterior mediastinoscopy or thoracotomy may be required to establish their diagnosis [3]. Farrow et al obtained 14/24 culture positivity by mediastinos- copy [16].
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has recently emerged as an important tool in diagnosing TBLA. The diagnostic yield was found to be 90-93% [17,18]. Songür et al sampled celiac lymph nodes by EUS-FNA and detected acid-fast bacilli [19].
EUS-FNA cannot reach right paratracheal or hilar lymph nodes, which are commonly involved in TB. In a study, Mycobacterium tuberculosis culture positivity was found to be 21% by EUS [18].
Currently, EBUS-TBNA is an important alternative of mediastinoscopy in diagnosis of granulomatous in- thrathoracic lymphadenopathy. It is well-tolerated out- patient procedure, providing access to intrathoracic and hilar lymph nodes as well as enabling bronchial wash- ing [7,20]. It allows higher smear and culture positivity compared to conventional TBNA [21]. The isolation of the agent allows susceptibility testing [20]. Due to the novelty of this method, there are limited studies on this subject.
EBUS samples that demonstrate necrotic granulomas or necrosis are more likely to have positive TB cultures [20,22]. Navani et al observed 47% culture positivity through EBUS-TBNA and concluded that the bacillary load was higher in necrotising lesions, thereby increas- ing culture positivity in these lymph nodes [20]. Accord- ing to another study, the cultures for mycobacterium TB were positive in 49% and maximum positivity was seen in necrotic material [22]. In our study, necrosis was found in 18.1% of cases with culture positivity.
It is well documented that EBUS-TBNA is an im- portant tool in staging lung cancer [9,23]. The com- plications reported are no more than few case reports.
Symptomatic bacteremia was observed in one patient [20], and a case with mediastinal-esophageal fistulae following EUS-FNA of subcarinal lymph node with a 22 gauge needle was described [24]. A non-small cell lung cancer patient who had experienced mediastinitis Table II. Distribution of lymph nodes diagnosed with cytopathology and/or tuberculous culture
Lymph node
station Lymph nodes diagnosed
cytopathologically (n) Lymph nodes with positive TB
culture (n) Lymph nodes with positive TB culture and nondiagnostic cytopathology (n)
2R 3 2 1
2L – – –
4R 18 14 4
4L 2 3 1
7 20 19 8
10R 2 2 1
10L – – –
11R 5 5 1
11L 3 3 2
Total 53 48 18
n-number
following EUS guided aspiration of a necrotic subcari- nal lymph node has been reported in another study [25].
The fact that no major complications were encountered in our study supports the idea that EBUS-TBNA is a safe procedure.
One limitation of our study is that the analysis is ret- rospective and the patient population is small. Prospec- tive studies conducted in larger populations evaluating microbiological and cytological results of EBUS-TBNA are required.
Conclusions
EBUS-TBNA is a safe and reliable method with a high accuracy in diagnosing TBLA. The diagnostic yield may be increased by the addition of mycobacterium cul- tures as a routine laboratory examination. Therefore, we emphasize the need for incorporating mycobacterium cultures in the evaluation of intrathoracic lymph nodes with EBUS-TBNA.
Conflict of interest: none
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